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Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer
Abstract
Although many biochemical markers have been examined in pancreatic cancer none are definitive for pre-operative diagnosis. This systematic review examines studies using biochemical markers for the diagnosis of pancreatic cancer in order to appraise their role in contemporary management algorithms.
A search of the MEDLINE database was undertaken using the key words pancreatic neoplasm and serum tumour marker. Only studies providing original data on sensitivity and specificity are included and data are presented on diagnostic accuracy, effect of cholestasis and the relation of tumour stage to blood levels of markers.
CA 19-9 is the most extensively evaluated with pooled data from 2283 patients. The median sensitivity of CA 19-9 for diagnosis is 79 (70-90%) and median specificity 82 (68-91%). CA 19-9 elevation in non-malignant jaundice results in a fall in specificity. Combination with other markers improves accuracy.
As the most extensively evaluated marker, CA 19-9 should be used in contemporary algorithms for the diagnosis of pancreatic cancer. Elevated values should be repeated after relief of jaundice.
... CA19-9 is the most broadly investigated and validated biomarker regarding diagnostic, prognostic, and surveillance capacity (38). Hence, it is the only FDA-approved biomarker tool for monitoring and diagnosis of PDAC (39). A thorough meta-analysis of 2283 individuals demonstrated a median specificity of 82% and a median sensitivity of 79% for the diagnosis of PDAC in symptomatic patients (39). ...
... Hence, it is the only FDA-approved biomarker tool for monitoring and diagnosis of PDAC (39). A thorough meta-analysis of 2283 individuals demonstrated a median specificity of 82% and a median sensitivity of 79% for the diagnosis of PDAC in symptomatic patients (39). These observations have been confirmed in subsequent investigations on the use of CA19-9 in the diagnosis of PDAC (40)(41)(42). ...
... However, some limitations of CA 19-9 reduce its utility as a biomarker. To begin with, due to Lewis antigen dependency, around 5-10% of the Caucasian population has significantly decreased CA19-9 production (39). As a result, current research is focusing on defining distinct kinds of CA19-9 secretions based on the patient's Lewis antigen status and other characteristics (43,44). ...
Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.
... Another well-known serum tumor biomarker is CA19-9, also known as sialyl-Lewis a, which can occur in both glycoproteins and glycosphingolipids; its expression, exposure, and secretion are altered in oncogenic cellular transformation [19][20][21][22] . The CA19-9 epitope can also be present in the normal biliary tree and in acute and chronic biliary tract disease, such as biliary tract obstruction, cholangitis, inflammatory bowel disease, and pancreatitis. ...
... Additionally, CA19-9 is the sialylated version of the Lewis blood group antigen Lea, but approximately 5-20% of the human population is Lea-negative 48 , depending on the ethnic group, as their inherited fucosyltransferase (FUT3) lacks activity. In individuals that are Lea-positive, however, elevated serum CA19-9 levels have been observed in late-stage PDAC 20,31,49 . By contrast, CD175 is widely expressed in many types of human carcinomas, particularly ~ 90% of patients with PDAC consistent with our studies here, and ~ 70% in precursor lesions, but not in normal tissues, as assessed with a variety of anti-Tn/ anti-CD175 reagents 8 . ...
Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients.
... Moreover, several limitations regarding CA19-9 have to be taken into account. First, its secretion is connected to Lewis antigen and, thus, CA19-9 cannot be produced in 10-15% of patients (5-10% in Caucasians) [13]. Second, several nonmalignant conditions (e.g., chronic pancreatitis, liver cirrhosis, cholangitis or jaundice which is especially common in patients with pancreatic head tumors [the most common tumor location]) can lead to false elevated CA19-9 levels hampering exact diagnosis [13]. ...
... First, its secretion is connected to Lewis antigen and, thus, CA19-9 cannot be produced in 10-15% of patients (5-10% in Caucasians) [13]. Second, several nonmalignant conditions (e.g., chronic pancreatitis, liver cirrhosis, cholangitis or jaundice which is especially common in patients with pancreatic head tumors [the most common tumor location]) can lead to false elevated CA19-9 levels hampering exact diagnosis [13]. This is especially alarming when considering CA19-9 as the only biomarker in pancreatic cancer care used for neoadjuvant chemotherapy recommendation when < 500 U/ml acknowledged by NCCN (National Comprehensive Cancer Network) [14,15]. ...
Pancreatic cancer still has dismal survival rates and high rates of early recurrence despite improvements of multimodal treatment options and more and more aggressive surgical approaches in recent years. Thus, precise and personalized management strategies to improve patient outcomes are needed. Circulating tumor DNA (ctDNA), a component of cell-free DNA (cfDNA) in body fluids, harbors genetic and epigenetic signatures of tumors and can be detected noninvasively for example through simple blood collections or peritoneal fluid during staging laparoscopy (liquid biopsies). This biomarker provides real-time insights into systemic tumor burden, heterogeneity, and genetic profile and has been proven to be of significant prognostic relevance for several gastrointestinal malignancies. Furthermore, the testing of ctDNA has emerged as a pivotal prognostic biomarker to indicate patients with high biological risk for recurrence and worse overall survival. Especially in pancreatic cancer, it has been shown that preoperative ctDNA detectability in peripheral blood is associated with systemic tumor burden (even volumetric). This indicates potential micrometastatic or subclinical disseminated disease, suggesting a benefit from neoadjuvant chemotherapy to address the systemic component of the disease prior to surgery. Furthermore, dynamic changes in ctDNA during systemic treatment can predict therapeutic response and guide adjustments in treatment regimens. Postoperatively, ctDNA presence could assist in detecting minimal residual disease which also predicts early relapse, facilitating timely intervention (or immediate adjuvant chemotherapy as already shown in colorectal cancer, e.g., Dynamic trial). Therefore, perioperative ctDNA detection has the potential to refine the management of pancreatic cancer, enhancing decision-making processes and optimizing personalized treatment approaches in serving as an additional highly sensitive biomarker for guiding treatment decisions between upfront surgery and neoadjuvant chemotherapy in patients with resectable pancreatic cancer. The first ever personalized change of treatment decision from upfront surgery (by current gold standard staging) to neoadjuvant chemotherapy based on additional liquid biopsy results was documented in March 2024 (Linz, Austria).
... Increased levels of CA19-9 have been reported in PDAC patients compared with healthy individuals [13,14]. The concentration of CA19-9 and its sensitivity as a diagnostic marker increase with increasing PDAC stage [15,16], with the most pronounced increase detected between AJCC/UICC stage II and stage III. However, especially in early stages (e.g., stage I [17]), the level of CA19-9 is similar to that in various benign conditions, precancerous lesions, and other malignancies (e.g., colorectal cancer, gastric cancer, hepatocellular carcinoma), resulting in low specificity [14,15]. ...
... The concentration of CA19-9 and its sensitivity as a diagnostic marker increase with increasing PDAC stage [15,16], with the most pronounced increase detected between AJCC/UICC stage II and stage III. However, especially in early stages (e.g., stage I [17]), the level of CA19-9 is similar to that in various benign conditions, precancerous lesions, and other malignancies (e.g., colorectal cancer, gastric cancer, hepatocellular carcinoma), resulting in low specificity [14,15]. With respect to its use for diagnostic purposes, it is important to consider that 6% of Caucasians and 22% of non-Caucasians who lack Lewis antigen A cannot produce CA19-9, subsequently leading to false-negative results [18]. ...
Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.
... • The new marker of neoadjuvant therapy. efficacy for malignancy degree and predictive accuracy for chemotherapy response [12][13][14] . Consequently, there is an urgent need for novel detection approaches to stratify patients with pancreatic adenocarcinoma and identify biomarkers predicting chemotherapy response. ...
... In consideration of pancreatic specific anatomical site, the difficulty and low specificity of tumor tissue acquisition leaded to a variety of limitations [11] . The conventional serum biomarkers CEA and CA 19-9 provided the single diagnosis efficacy for the degree of malignancy [12][13][14] . There were lack of effective methods of the identification of high risk group with poor response for therapy. ...
Pancreatic adenocarcinoma characterized by a mere 10% five-year survival rate, poses a formidable challenge due to its specific anatomical location, making tumor tissue acquisition difficult. This limitation underscores the critical need for novel biomarkers to stratify this patient population. Accordingly, this study aimed to construct a prognosis prediction model centered on S100 family members. Leveraging six S100 genes and their corresponding coefficients, an S100 score was calculated to predict survival outcomes. The present study provided comprehensive internal and external validation along with power evaluation results, substantiating the efficacy of the proposed model. Additionally, the study explored the S100-driven potential mechanisms underlying malignant progression. By comparing immune cell infiltration proportions in distinct patient groups with varying prognoses, the research identified differences driven by S100 expression. Furthermore, the analysis explored significant ligand-receptor pairs between malignant cells and immune cells influenced by S100 genes, uncovering crucial insights. Notably, the study identified a novel biomarker capable of predicting the sensitivity of neoadjuvant chemotherapy, offering promising avenues for further research and clinical application.
... The potential efficacy of this marker in the diagnosis of pancreatic cancer has been extensively studied (2,3). Furthermore, the sensitivity and specificity in symptomatic patients with pancreatic cancer has been reported to range from 70-79% and 68-91%, respectively (4,5). This marker is also commonly employed in the management of biliary tract cancers such as cholangiocarcinoma and gallbladder cancer. ...
Serum levels of the tumor marker CA 19–9 are widely utilized in the diagnosis and monitoring pancreatic and biliary malignancies. However, serum levels of CA 19–9 have also been reportedly elevated in non-malignant conditions. Here, we present the rare case of a 65-year-old woman with a history of gallbladder malignancy who was found to have a new hepatic lesion on surveillance CT with an associated elevation in CA 19–9 to 5,866 U/mL. Drainage of the lesion and treatment with antibiotics resulted in a rapid decline in CA 19–9 levels, indicating that the elevation in CA 19–9 was due to a benign hepatic lesion. We review eight similar reported cases of CA 19–9 elevations due to benign hepatic abscesses, thereby highlighting a need to interpret the tumor marker with caution.
... Our pilot study with 30 healthy controls and 30 PDAC patients found that AHNAK2 expression in plasma achieved a sensitivity and specificity of 86.67% and 83.33% with an AUC of 0.903. This outperformance over CA19-9 needs to be validated in a large sample size, controlling for other variables such as non-secretion of CA19-9 in Lewis genotype negative 50,51 , as well as co-morbidities, lifestyle factors, ethnicity and other unknown confounders. Our limited analysis has shown that neither age, tumoral AHNAK2 expression or tumour stage influence AHNAK2 levels in plasma. ...
Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker. At a plasma level of 421.47 ng/ml, AHNAK2 could potentially diagnose PDAC with a specificity and sensitivity of 83.33% and 86.67%. In vitro analysis suggests that in cell lines with diffuse cytoplasmic distribution of AHNAK2, there was colocalization of AHNAK2 with Cortactin in filipodia. This colocalization increased when cells were cultured on substrates such as Fibronectin and Collagen, as well as in hypoxia, and resulted in an augmented invasion of cancer cells. However, in cell lines with a vesicular AHNAK2 staining, such changes were not observed. Our study posits AHNAK2 as a valuable diagnostic biomarker in PDAC, now demanding prospective validation. Determination of mechanisms regulating AHNAK2 subcellular localisation may help explain its biological role.
... Ключевые слова: билирубин, механическая желтуха, углеводный антиген 19-9 (CA19-9), злокачественные новообразования поджелудочной железы и желчных путей CA19-9 -опухолевый маркёр, широко используемый при заболеваниях желчевыводящих путей и поджелудочной железы для дифференциальной диагностики доброкачественных и злокачественных поражений, оценки резектабельности опухоли, ответа на специфическое лечение и оценки прогноза выживаемости пациентов [1]. Тем не менее, результат измерения может фактически не отражать истинный уровень CA19-9, так как он повышается при холангите, желчнокаменной болезни или других доброкачественных состояниях, включая кисту яичников, сер-дечную недостаточность, тиреоидит Хашимото и системных заболеваниях. ...
... Both cancers likely originate from precursor lesions in ductal and acinar cells (PDAC) or the bile duct lining (dCCA). Serum carbohydrate antigen 19-9 (CA 19-9) is the only FDA-approved biomarker for both cancers, though its accuracy is limited due to its elevation in benign conditions [87][88][89]. Emerging technologies like artificial intelligence and machine learning show promise in improving diagnostic accuracy by analyzing clinicopathological features and imaging data. The standard treatment for both cancers involves pancreaticoduodenectomy with regional lymph node dissection, but chemotherapy regimens differ, with PDAC commonly treated with FOL-FIRINOX or gemcitabine-based therapies, while dCCA is treated with cisplatin and gemcitabine [90][91][92]. ...
Cholangiocarcinoma (CCA) is the second most common primary malignancy of the hepatobiliary system and presents as a heterogeneous disease with three distinct morphological subtypes: mass-forming, periductal-infiltrating, and intraductal-growing, each characterized by distinguishing imaging features. Accurate diagnosis of CCA is challenging due to the overlap of imaging findings with a broad range of benign and malignant conditions. Therefore, it is essential for radiologists to recognize these mimickers and offer a reasonable differential diagnosis, as this has a significant impact on patient management. Although histopathological confirmation is often required for a definitive diagnosis, understanding specific imaging characteristics that differentiate CCA from its mimickers is crucial. This article highlights a variety of benign and malignant conditions that resemble CCA on imaging, emphasizing features that enhance diagnostic accuracy in clinical practice.
... The sensitivity of CA19-9 for PC is reported to be in the range of 70% to 95% with a specificity between 72% and 90%. Moreover, several studies demonstrated a good potential for CA 19-9 in detecting early-stage PC with a median sensitivity of 76.1% (AUC 0.89) and a median specificity of 82%, with increased sensitivity up to 80.1% when considering all stages of PC [41,42]. ...
Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine.
... The ability to detect biochemical markers is important in industrial testing, environmental science, food safety, and clinical medicine, as such detection methods can be used to monitor the presence and concentrations of biochemical markers and, in some cases, prevent fatal diseases and lifethreatening situations [1][2][3][4] . For example, in clinical medicine, certain biochemical markers (e.g., carbohydrate antigen 19-9 (CA19-9), cancer embryonic antigen (CEA), and alphafetoprotein (AFP)) are used for the early diagnosis of cancer and monitoring the effectiveness of treatment 5,6 , whereas myocardial injury markers (such as troponin and CK-MB) are used for the diagnosis of heart disease and evaluation of acute myocardial infarction 7 . In environmental science, biochemical markers of heavy metals and organic pollutants in environmental samples (such as water and soil) are used to assess and control environmental pollution, and biomarkers (such as changes in liver enzyme activity) in fish are used to assess the impact of environmental pollution on ecosystems 8 . ...
Ultrasonic biochemical detection is important for biomarker detection, drug monitoring, and medical diagnosis, as it can predict disease progression and enable effective measures to be taken in a timely manner. However, the ultrasonic technology currently used for biochemical marker detection is directly modified on the surface of the device. The associated test methods are costly and unreliable while having poor repeatability; therefore, they cannot achieve low-cost rapid testing. In this study, a detection mechanism based on the Rayleigh scattering of acoustic waves caused by nanoparticles, which causes changes in the received sound pressure, was developed for the first time. The modification of antibodies on an insertable substrate decouples the functionalization step from the sensor surface and facilitates the application of capacitive micromachined ultrasonic transducers (CMUTs) in conjunction with Au nanoparticles (AuNPs) for CA19-9 cancer antigen detection. A corresponding detection theory was established, and the relevant parameters of the theoretical formula were verified using different nanoparticles. Using our fabricated CMUT chip with a resonant frequency of 1 MHz, the concentrations and substances of the CA19-9 antigen markers were successfully measured. In the concentration range of 0.1–1000 U/mL, the receiving voltage decreased with increasing concentration. Further investigations revealed that the influence of other interfering markers in the human body can be ignored, demonstrating the feasibility and robustness of biochemical detection based on CMUTs combined with nanoparticles.
... Patients with pancreatic cancer were defined as individuals who met the diagnostic criteria for pancreatic cancer and had a confirmed diagnosis at West China Hospital. The diagnostic criteria included clinical symptoms (such as abdominal pain and jaundice), radiological assessments (CT and MRI), histopathological examination, and blood tests (serum CA19-9>39 U/mL) (Chan et al., 2014;Goonetilleke and Siriwardena, 2007;Ni et al., 2005). These factors were analyzed comprehensively to establish the diagnosis by the doctor. ...
Objectives
This study aimed to identify the risk factors for pancreatic cancer through machine learning.
Methods
We investigated the relationships between different risk factors and pancreatic cancer using a real-world retrospective cohort study conducted at West China Hospital of Sichuan University. Multivariable logistic regression, with pancreatic cancer as the outcome, was used to identify covariates associated with pancreatic cancer. The machine learning model extreme gradient boosting (XGBoost) was adopted as the final model for its high performance. Shapley additive explanations (SHAPs) were utilized to visualize the relationships between these potential risk factors and pancreatic cancer.
Results
The cohort included 1,982 patients. The median ages for pancreatic cancer and nonpancreatic cancer groups were 58.1 years (IQR: 51.3–64.4) and 57.5 years (IQR: 49.5–64.9), respectively. Multivariable logistic regression indicated that kirsten rats arcomaviral oncogene homolog (KRAS) gene mutation, hyperlipidaemia, pancreatitis, and pancreatic cysts are significantly correlated with an increased risk of pancreatic cancer. The five most highly ranked features in the XGBoost model were KRAS gene mutation status, age, alcohol consumption status, pancreatitis status, and hyperlipidaemia status.
Conclusion
Machine learning algorithms confirmed that KRAS gene mutation, hyperlipidaemia, and pancreatitis are potential risk factors for pancreatic cancer. Additionally, the coexistence of KRAS gene mutation and pancreatitis, as well as KRAS gene mutation and pancreatic cysts, is associated with an increased risk of pancreatic cancer. Our findings offered valuable implications for public health strategies targeting the prevention and early detection of pancreatic cancer.
... Additionally, it also had some limitations of clinical application, such as unstable detection value and no expression in Lewis blood-group negative patients. [18][19][20][21] In 2021, Immunovia launched IMMray PanCan-d diagnostic kit used for pancreatic cancer diagnosis, which was an 8-plex biomarker signature with CA19-9 to detect serum samples for early screening of pancreatic cancer. It has a sensitivity of 85% and a specificity of 99% for the diagnosis of stage I-II PDAC, which has a good market application prospect. ...
Background
COL10A1 expression was up-regulated and could promote tumor development in pancreatic cancer. As a secreted protein, plasma COL10A1 level was proven to have certain diagnostic efficacy in gastric cancer, breast cancer, and colorectal cancer. It is still unknown whether it has a biomarker role for pancreatic cancer.
Aim
To explore and analyze the diagnostic and prognostic value of plasma COL10A1 level in pancreatic ductal adenocarcinoma (PDAC).
Method
The RNA-seq dataset of PDAC from The Cancer Genome Atlas (TCGA) and six expression profiling microarray datasets from Gene Expression Omnibus (GEO) were downloaded to analyze the expression of COL10A1 in tissues. Thirty-six patients with PDAC and eighteen healthy volunteers were enrolled to measure COL10A1 levels in tissues and plasmas, and the relationship between clinical characteristics and the COL10A1 levels was analyzed. The diagnostic and prognostic efficacy of plasma COL10A1 levels were calculated.
Results
Aspects of COL10A1 expression level in tissues, COL10A1 expression was significantly higher in PDAC tissue than adjacent normal tissue. The expression of COL10A1 was correlated with T, M, and AJCC stages. Patients with high COL10A1 expression had worse recurrence-free survival (RFS) and overall survival (OS) than those with low expression. Aspects of COL10A1 expression levels in plasma, its diagnostic area under the curve (AUC) for PDAC was 0.926 (95% CI 0.853–0.999), diagnostic sensitivity was 81% (95% CI 64–92%), and specificity was 100% (95% CI 81–100%). The time-dependent AUCs at 1-year and 3-year were 0.71 (95% CI 0.51–0.90) and 0.74 (95% CI 0.48–1.00), respectively.
Conclusion
In PDAC, plasma COL10A1 levels showed certain diagnostic and prognostic efficacy. COL10A1 may be a diagnostic and prognostic biomarker for PDAC and play a role in liquid biopsy of this disease.
... This suggests that these scores could be combined with other highly sensitive prognostic factors to predict early recurrence in a stepwise approach, nomograms, or multimarker panels, possibly resulting in satisfactory prognostic accuracy. Ca 19-9, as the most extensively evaluated biomarker with a reported sensitivity of 79% [43], could be a logical candidate. Furthermore, Ca 19-9 has been shown to relate to early recurrence. ...
Background
Disease recurrence after surgical resection for pancreatic ductal adenocarcinoma can affect more than 50% of patients in the first 12 months after resection. The goal of this current systematic review and meta‐analysis is to assess the ability of preoperative inflammatory scores to predict early recurrence after resection and to identify the best candidates for surgical resection.
Methods
Medline and Web of Science databases were searched for studies reporting inflammatory scores and oncological outcomes in patients with PDAC after curative‐intent resection. The systematic review revealed that the most common scores were modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI), platelet‐to‐lymphocyte ratio (PLR), neutrophil‐to‐lymphocyte ratio (NLR), and Systemic Immune‐Inflammation Index (SII). After, a meta‐analysis was performed to determine the prognostic value of these scores in early recurrence (12 months) after resection. A subgroup analysis was also carried out in patients who had upfront surgery and in those who underwent neoadjuvant chemotherapy. The ROBINS‐I tool was used to assess the risk of bias.
Results
The literature search retrieved 1864 articles, 16 of which were eligible for analysis. The included studies comprised 4460 patients. Nine studies reported outcomes for mGPS, four studies for PNI, seven studies for PLR, eight studies for NLR, and two studies for SII. In the meta‐analysis, mGPS, NLR, and PLR showed significantly higher rates of early recurrence in the high‐score groups compared to the low‐score groups. Analyzing the sensitivity and specificity of these scores showed no significant difference in their diagnostic accuracy (mGPS area under the curve [AUC] = 0.534; NLR AUC = 0.628, and PLR AUC = 0.607). High and low PNI and SII scores demonstrated similar rates of early recurrence.
Conclusion
mGPS, PNI, PLR, NLR, and SII scores did not show a suitable diagnostic accuracy to predict PDAC recurrence in the first 12 months after resection. Therefore, these inflammatory scores should not be used to select the best candidates or to preclude a possible surgical indication.
... Combining tumor markers and imaging methods may be the best choice for early PC screening, with studies showing increased sensitivity and specificity with CA19-9 and CA125, and potentially more diagnostic than separate detection [11]. ...
This comprehensive literature review is to summarize the most recent findings regarding the causes, diagnosis, and treatments of pancreatic cancer and to encourage additional investigation into this under-researched malignant tumor. Pancreatic cancer is a significant public health issue in China, with annual mortality rates almost equal to incidence rates. The disease is more prevalent in rural areas and has a poor prognosis. The data was collected from the following databases: Pub Med, Cross ref, Science Direct, Scopus, and Google Scholar we reviewed published articles from 2018 to 2023 on the annual incidence of pancreatic cancer in China is 5.1%, with only 5-7% of patients completely cured. The prognosis is extremely poor, with a 1-year survival rate of 8% and a 5-year survival rate of 3%. Pancreatic cancer has no specific clinical manifestations or tumor markers, and its characteristics are not typical of high-risk factors including smoking, alcohol, chronic pancreatitis, abnormal microorganism metabolism, blood type, and glucose and lipid levels. For increased detection and survival rates, pancreatic cancer must be diagnosed as early as possible. However, the low specificity of tumor markers calls for more study. Future treatment strategies could include immunotherapy and a microbiology-free system, and it's anticipated that they'll offer intriguing clinical applications for extending patients' lives with pancreatic cancer. Finally, we suggest measures to improve the health outcomes of pancreatic cancer patients in China. Introduction Pancreatic cancer (PC) has become more common over the past several years. It contributes to 5% of cancer-related deaths and around 2% of all cancers. Most patients have no overt symptoms until the disease progresses to advanced pancreatic metastasis when tumor cells are very invasive. It has become one of the most fatal malignant tumors, and early diagnosis is challenging [1]. Pancreatic cancer represents a substantial public health challenge in China, where its incidence and mortality rates rival those of malignant tumors. This alarming trend underscores the severity of the disease and its significant impact on the population's health. With a high incidence rate, a considerable number of new cases are diagnosed annually, placing a burden on healthcare resources, and necessitating urgent attention from policymakers and healthcare providers. Furthermore, the mortality rate associated with pancreatic cancer is equally concerning, indicating the dire need for improved prevention, early detection, and treatment strategies to mitigate its devastating effects on individuals and families across the country. In the UK, it accounts for 5.6% and 5.3% of cancer-related deaths, ranking fifth. China's rapid urbanization, lifestyle changes, and aging environment have led to a 9% increase in pancreatic cancer-related deaths in the past decade. Despite improvements in diagnosis and treatment, the survival rate remains below 8%, making it a major issue faced by medical circles both domestically and internationally [2]. Advancements in pancreatic cancer diagnosis and treatment have improved accuracy and sensitivity, with new diagnostic modalities like MRI scanners becoming routine in high-volume centers. Chemotherapeutic agents like gemcitabine and 5-fluorouracil are moderately effective but not significant in terms of survival. A prospective study in China collected medical records, pathological reports, and imaging reports for subject eligibility evaluation [3]. However, at present, there are no standard programs in the world to screen patients with a high risk of PC. To improve the prognosis of pancreatic cancer patients, we reviewed recent advances in risk factors, diagnosis, and treatment of PC.
... It is overexpressed in a wide range of benign diseases such as cholestasis and malignant diseases, mainly in pancreatic ductal adenocarcinoma (PDAC) (4,5). It has been used as a useful biomarker in diagnosis, assessment of resectability, monitoring response to treatment, prognosis, and surveillance in pancreatic cancer (6)(7)(8)(9). It reflects biological aggressiveness and is a predictor of hematogenous dissemination, micrometastatic, and metastatic disease since this biomarker plays a role in malignant cell-adhesion to endothelial cells and transmigration (10,11). ...
Background
Traditionally, serum carbohydrate antigen 19-9 (CA 19-9) has been used as a key biomarker for pancreatic cancer and recently other biomarkers which reflect the systemic immune and inflammatory responses also have been explored as potential prognostic factors. The study aims to evaluate the significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and serum CA 19-9 as prognostic factor in pancreatic cancer patients.
Methods
A retrospective analysis was conducted in 153 consecutive patients with pancreatic cancer in Instituto Nacional de Cancerología from 2013 to 2018. Pretreatment NLR and serum CA 19-9 values were recorded as well as survivals.
Results
The cut-off value determined for NLR was 2.4 and for serum CA 19-9 was 553 U/mL. Survival analysis showed that the 5-year overall survival (OS) was 9% in patients with low-NLR compared with 2% for patients with high-NLR (P=0.008), and 5-year progression-free survival (PFS) was 5.7% in patients with low-NLR compared with 1.3% in patients with high-NLR (P=0.007). For patients with low-CA 19.9, 5-year OS was 8.5% compared with 0% for patients with high-CA 19-9 (P=0.002), and 5-year PFS was 4.1% in patients with low-CA 19-9 compared with 0% in patients with high-CA 19-9 (P=0.005). Classification groups created showed that 5-year OS in Group 1 (low-NLR and low-CA 19-9) was 11.8% compared with 1.9% for patients in Group 2 (either one or both high-NLR or CA 19-9) (P<0.001), and 5-year PFS was 8.6% in Group 1 and 0% in Group 2 (P=0.001).
Conclusions
High-NLR and high-CA 19-9 values used separately are both independently associated with worse OS and PFS in patients with pancreatic cancer. The classification groups created combining both biomarkers showed better prognostic significance than when used separately as demonstrated by survival analysis and multivariate analysis.
... CA19-9 is the most thoroughly evaluated marker for pancreatic cancer (22). CA19-9 concentration before surgery was reported as a prognosis maker, where various cut-off values were proposed, such as 37 (23), 50 (24), and 338 (25) U/mL. ...
Background
Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear.
Methods
Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas.
Results and Conclusions
Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.
... Research on SMAD4 emphasizes its regulatory role in the development of CRC, particularly with respect to the tumor microenvironment and the interactions between tumor cells and their environment. 57 CA19-9 is the most commonly used serologic marker in clinical practice for disease monitoring 78 and assessment recurrence risk in CRC. 79 However, the sensitivity and specificity of CA19-9 are limited, especially in early CRC diagnosis and screening. ...
Colorectal Cancer (CRC) is the third most common cancer worldwide, and the occurrence and development of CRC are influenced by the molecular biology characteristics of CRC, especially alterations in key signaling pathways. The transforming growth factor-β (TGF-β) plays a crucial role in cellular growth, differentiation, migration, and apoptosis, with SMAD4 protein serving as a key transcription factor in the TGF-β signaling pathway, thus playing a significant role in the onset and progression of CRC. CRC is one of the malignancies with a high mortality rate worldwide. Despite significant research progress in recent years, especially regarding the role of SMAD4, its dual role in the early and late stages of tumor progression has promoted further discussion on its complexity as a therapeutic target, highlighting the urgent need for a deeper analysis of its role in CRC. This review aims to explore the function of SMAD4 protein in CRC and its potential as a therapeutic target.
... 95 Other researchers have shown through meta-analysis that the CA19-9 and CA242 combination, or CA19-9 and K-RAS gene mutation or endoscopic retrograde cholangiopancreatography and EUS may be more diagnostic than separate detection. [96][97][98][99] There is also evidence that the combination of microRNAs and CA19-9 is more accurate. 100,101 In recent years, advances in cytology and genomics have been used in conjunction with serum tumor markers for early diagnosis of PC. ...
This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied malignant tumor. At present, we urgently need to identify high-risk patients with precancerous diseases through screening approaches, so that medical professionals and the general public may better understand prevention strategies or early detection measures. Pancreatic cancer is a highly invasive malignant tumor with a fatal risk, mainly seen in men and older adults (60-85 years old). Pancreatic cancer is now increasingly observed in young patients. Because the disease has no early symptoms and can quickly invade surrounding tissues and organs, it is one of the deadliest cancers. With a view to identify the important factors for the development of pancreatic cancer, previous studies have found that smoking, alcohol, and chronic pancreatitis are considered high-risk factors. Recent studies have shown that abnormal metabolism of human microorganisms, blood type, and glucose and lipid levels are also important factors in the development of pancreatic cancer. Identifying early diagnosis options is an important way to improve detection and survival rates of pancreatic cancer. None of the many tumor markers associated with pancreatic cancer are highly specific, which also indicates further research is required to improve the early detection rate. Future directions in terms of treatment evaluating the relationship between the microbiology-free system and immunotherapy will bring a major breakthrough and is expected to bring exciting clinical applications in improving the life-cycle of pancreatic cancer patients.
... CA can be used to assess response to chemotherapy, to identify patients with poor prognosis, and to guide treatment decision [1]. However, it is not recommended for screening, and its value as an early diagnostic tool remains controversial [5][6][7]. Indeed, CA 19-9 is undetectable or normal in the 5-10% of the population with the Lewis antigennegative phenotype [8,9], and it can also elevate in conditions such as chronic pancreatitis, biliary obstructions, and other gastrointestinal (GI) tumors [10]. It is well known that CA 19-9 is influenced by serum bilirubin [11,12]. ...
Serum carbohydrate antigen 19-9 (Ca19-9) is the only approved biomarker approved for the screening and diagnosis of pancreatic cancer (PC), but its value remains controversial. The aim of our study is to evaluate the role of CA 19-9 in the management of PC patients in jaundiced patients staged by both Computed Tomography (CT) and Endoscopic Ultrasound (EUS). Additionally, we evaluated traditional cholestasis marker behavior. Medical records of 73 patients have been retrospectively reviewed. We considered tumor size, tumor stage, CA 19-9, cytolysis, and cholestasis biomarkers. All patients underwent CT scan for staging. EUS +/− fine-needle biopsy (FNB) was performed in doubtful cases. Median alkaline phosphatase (ALP) and y-glutamyltransferase (GGT) levels were significantly lower compared to baseline after the biliary drainage (204 vs. 465 U/L, p < 0.0001, 204. U/L vs. 608.5, p < 0.0001, respectively), whilst no differences were observed for CA 19-9 levels. CA 19-9 showed significant association with the tumor stage in the pre-drainage setting. CT and EUS showed a low agreement in estimating tumor size (mean difference 4.8 mm 95% LoA −10.82–20.38). We did not find any significant correlation between CA 19-9 and bilirubin levels (r = −0.05, p = 0.7). In our cohort, survival rate was lower in patients with higher CA 19-9 levels (log rank p = 0.007). CA 19-9 has some limitations as a biomarker in the PC setting, thus it cannot address the treatment strategy alone. Nonetheless, it provides valuable information, and is not replaceable for the time being.
... CA19-9 is the most routinely used and best-validated biomarker for PC, with a median specificity of 82% and a median sensitivity of 79%. 22 In addition to the diagnostic performance for PC, CA19-9 response is also a strong predictor of the outcome of various treatments. 23 Boone et al found that a CA19-9 decrease of >50% resulted in improved OS and increased R0 resection rate among patients with pancreatic ductal adenocarcinoma in neoadjuvant setting. ...
Background
Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC).
Methods
In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS).
Results
Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group.
Conclusion
The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).
... There is currently only one FDA approved biomarker used clinically for PDAC diagnosis, carbohydrate antigen 19-9 (CA19-9) [137]. This biomarker, however, lacks both specificity and sensitivity [138,139]. With improved isolation techniques of body fluids, sncRNAs in blood-bound exosomes or other extracellular vesicles (EVs) will surpass the usefulness of CA19-9 in the diagnosis of PDAC. ...
... are increasingly being recognized. However, these markers have important limitations, especially in terms of sensitivity and specificity (4,7). Therefore, circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) can be used to detect the dynamic and genomic alterations associated with pancreatic malignancies (5,6). ...
Background
The diagnostic and prognostic clinical value of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in pancreatic malignancies are unclear. Herein, we aimed to perform a meta-analysis to evaluate ctDNA and cfDNA as potential diagnostic and prognostic biomarkers.
Methods
PRISMA reporting guidelines were followed closely for conducting the current meta-analysis. The PubMed/Medline, Scopus, and Web of Science (WoS) databases were scanned in detail to identify eligible papers for the study. A quality assessment was performed in accordance with the REMARK criteria. The risk ratios (RRs) of the diagnostic accuracy of ctDNA compared to that of carbohydrate antigen 19.9 (CA 19.9) in all disease stages and the hazard ratios (HRs) of the prognostic role of ctDNA in overall survival (OS) were calculated with 95% confidence intervals (CIs).
Results
A total of 18 papers were evaluated to assess the diagnostic accuracy and prognostic value of biomarkers related to pancreatic malignancies. The pooled analysis indicated that CA19.9 provides greater diagnostic accuracy across all disease stages than ctDNA or cfDNA (RR = 0.64, 95% CI: 0.50–0.82, p < 0.001). Additionally, in a secondary analysis focusing on prognosis, patients who were ctDNA-positive were found to have significantly worse OS (HR = 2.00, 95% CI: 1.51–2.66, p < 0.001).
Conclusion
The findings of this meta-analysis demonstrated that CA19-9 still has greater diagnostic accuracy across all disease stages than KRAS mutations in ctDNA or cfDNA. Nonetheless, the presence of detectable levels of ctDNA was associated with worse patient outcomes regarding OS. There is a growing need for further research on this topic.
Systematic review registration
https://doi.org/10.37766/inplasy2023.12.0092, identifier INPLASY2023120092.
... In fact, some serum glycoproteins/ glycans have been clinically employed in diagnosing and monitor-ing various types of cancer. For instance, glycoproteins such as prostate-specific antigen (PSA), α-fetoprotein (AFP), cancer antigen 125 (CA125), CA15-3, and β-HCG (β-human chorionic gonadotropin) are employed as biomarkers for prostate, liver, ovarian, breast, and female reproductive system cancers, respectively [109][110][111][112][113]. CA19-9, a versatile tumor biomarker in the digestive system, stands out as the sole fully glycol-composed marker and is also known as sialyl Lewis A glycotope (sLeA) [114]. However, the sensitivity and specificity of these cancer-associated glycoforms are relatively limited. ...
N-glycans play important roles in a variety of biological processes. In recent years, analytical technologies with high resolution and sensitivity have advanced exponentially, enabling analysts to investigate N-glycomic changes in different states. Specific glycan and glycosylation signatures have been identified in multiple diseases, including cancer, autoimmune diseases, nervous system disorders, and metabolic and cardiovascular diseases. These glycans demonstrate comparable or superior indicating capability in disease diagnosis and prognosis over routine biomarkers. Moreover, synchronous glycan alterations concurrent with disease initiation and progression provide novel insights into pathogenetic mechanisms and potential treatment targets. This review elucidates the biological significance of N-glycans, compares the existing glycomic technologies, and delineates the clinical performance of N-glycans across a range of diseases.
... CA199 refers to a carbohydrate structure originally characterized by monoclonal antibody 1116-NS19-9 [116] that is present on glycoproteins such as mucin [117]. It is predominantly expressed in biliary tract and pancreatic cancers, but also present in other cancers such as ovarian. ...
Cancer is still one of the most arduous challenges in the human society, even though humans have found many ways to try to conquer it. With our incremental understandings on the impact of sugar on human health, the clinical relevance of glycosylation has attracted our attention. The fact that altered glycosylation profiles reflect and define different health statuses provide novel opportunities for cancer diagnosis and therapeutics. By reviewing the mechanisms and critical enzymes involved in protein, lipid and glycosylation, as well as current use of glycosylation for cancer diagnosis and therapeutics, we identify the pivotal connection between glycosylation and cellular redox status and, correspondingly, propose the use of redox modulatory tools such as cold atmospheric plasma (CAP) in cancer control via glycosylation editing. This paper interrogates the clinical relevance of glycosylation on cancer and has the promise to provide new ideas for laboratory practice of cold atmospheric plasma (CAP) and precision oncology therapy.
... sensitivity and 0.70-0.75 specificity for distinguishing PDAC from non-cancer conditions [4,5]. Such performance is insufficient for surveillance for PDAC [3,6]. ...
A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.
... The most common biomarker is CA 19.9 which has a sensitivity of 79% and specificity of 82% in symptomatic patients (46). CA 19.9 is not tumor-type specific and can be raised in other malignancies or benign diseases (47). ...
... It is wellknown that Lewis and Secretor status can affect CA19-9 biosynthesis. CA19-9 has limitations for its clinical use for diagnosis and screening, including false positive elevation in patients with benign biliary, pancreatic and gastrointestinal disease, false negative results in patients with Lewis (a−b−) genotype, and its poor positive predictive value (72.3%) (30,31). These limitations make CA19-9 not a good cancer-specific biomarker. ...
Background and objective:
Pancreatic cancer is an aggressive malignancy with high mortality. At the time of diagnosis, majority of patients (80-90%) present with either locally advanced unresectable disease or metastatic disease. Even after curative resection, the recurrence rate remains quite high. This article aimed at reviewing the updated management of pancreatic cancer.
Methods:
We identified literature by searching Medline and PubMed from January 2010 to June 2023 using the keywords.
Key content and findings:
A multidisciplinary approach is essential to optimize the outcomes for both curable and advanced diseases. Management of pancreatic cancer divided into resectable, borderline resectable, locally advanced, and metastatic diseases. Surgery and adjuvant chemotherapy is a standard treatment approach for resectable pancreatic cancer. The recommended adjuvant chemotherapy regimen for patients with good functional status is modified FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan, and oxaliplatin). The recommended adjuvant chemotherapy regimen for patients with suboptimal functional status is gemcitabine plus capecitabine or monotherapy gemcitabine. The optimal treatment strategy for borderline resectable pancreatic cancer is still uncertain. Traditionally, upfront surgery is the choice of treatment. There is increasing evidence showing benefits of neoadjuvant therapy in borderline resectable pancreatic cancer. However, the optimal neoadjuvant treatment regimen was not certain yet. Advancement of chemotherapy has a positive impact for the survival of advanced disease. For patients with good functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is combination chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nabpaclitaxel. For patients with suboptimal functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is gemcitabine plus capecitabine or monotherapy gemcitabine. Recently, more researches showed promising results in the use of nanoliposomal irinotecan, targeted agents such as a poly [adenosine diphosphate (ADB)-ribose] polymerase inhibitor, tyrosine receptor kinase (TRK) inhibitors, and immune checkpoint-inhibitors.
Conclusions:
Pancreatic cancer is a challenging disease for management. Radical surgery itself is not enough for prolong survival. The improvement of chemotherapy, target agents and immunotherapy with multidisciplinary approach will be the only solution for improvement of survival outcome and quality of life for patients with pancreatic cancer.
... Meanwhile, it should be noted that there was no significant difference in cancer scores between early and late clinical stages among the three cancer types, suggesting that these models have similar performance in detecting both early-and late-stage biliopancreatic cancers. Since CA19-9 is a commonly used biomarker for biliopancreatic patients in clinical practice [27], we then examined the performance of cancer score from the Stacked model and CA19-9 in detecting cancer samples. The positive rates of CA19-9 (> 39 U/mL) in the training and validation cohort were 69.0% and 78.7% for all patients, 50.0% and 74.4% for CCA patients, 78.6% and 75.0% for GBC patients, and 75.0% and 85.3% for PAC patients (Table 1). ...
Background:
Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection.
Methods:
One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19-9 (CA19-9) was explored to improve model performance.
Results:
The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved.
Conclusions:
Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.
... As its expression is increased by oncogenesis in the gallbladder, biliary ducts, and pancreas [6], CA19-9 is a useful marker for malignancies in these organs [1]. Moreover, its expression has been observed in various solid malignancies, such as hepatocellular carcinoma, gastric cancer, colorectal cancer, ovarian cancer, and endometrial cancer [8][9][10][11]. ...
Background
CA19-9 is a tumor marker for gastrointestinal and biliary-pancreatic adenocarcinomas; however, its association with thyroid cancer is unknown. Here, we report a case of CA19-9 producing locally advanced papillary thyroid carcinoma (PTC).
Case presentation
A 66-year-old woman who was identified with a thyroid tumor after a close examination of an elevated serum CA19-9 level, which was detected at health screening, was referred to our hospital. Ultrasonography revealed a 34 × 31 mm hypoechoic lesion in the lower pole of the left thyroid lobe. Computed tomography revealed a solid thyroid tumor with tracheal invasion without any distant metastases. Bronchoscopy revealed tumor exposure into the tracheal lumen on the left side of the trachea. Fine-needle aspiration cytology led to a diagnosis of papillary thyroid carcinoma (PTC). The patient underwent a total thyroidectomy, tracheal sleeve resection with end-to-end anastomosis, and lymph node dissection in the left cervical and superior mediastinal regions (D3c) with a reversed T-shaped upper sternotomy down to the third intercostal level. Histopathological analysis confirmed the diagnosis of PTC with tracheal invasion and no lymph node metastases (pT4a Ex2 N0). Immunohistochemical staining showed the expression of CA19-9 in cancer cells. Postoperatively, the serum CA19-9 level of the patient decreased to within the normal range.
Conclusions
Some PTCs produce CA19-9, although less frequently. When elevated serum CA19-9 levels are observed, PTC should be included in the differential diagnosis for further investigation.
... For the diagnosis of PDAC in symptomatic patients, serum carbohydrate antigen 19-9 (CA19-9) exhibits a sensitivity of approximately 80% and a specificity of 80% to 90%. 37,38 There is also robust evidence suggesting that normal or decreased levels can predict resectability and improved survival. Carbohydrate antigen 19-9 levels <100 U/mL suggest resectability, whereas levels ≥100 U/mL suggest unresectability or metastatic disease. ...
This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.
... However, given the frequency of elevation in benign pathologies, some have suggested using a higher cutoff [6]. With the cutoff of 37 kU/l, the mean sensitivity and mean specificity were found to be 79% and 82%, respectively, as was seen in a systematic review done by Goonetilleke et al. [7]. It has been proposed to increase the cutoff to 100 kU/l or even 1000 kU/l; however, that would inversely increase the specificity and decrease the sensitivity [4,6]. ...
Carbohydrate antigen 19-9 (CA 19-9) is widely recognized as a tumor marker primarily associated with pancreatic cancer. However, its elevation in benign pancreaticobiliary conditions complicates its diagnostic utility. We present the case of a 39-year-old male with no significant medical history who presented with symptoms of abdominal pain, nausea, vomiting, and diarrhea. The initial diagnosis suggested viral enteritis, but the subsequent worsening of symptoms led to further investigation. Elevated white blood cell counts, bilirubin levels, and liver function tests prompted magnetic resonance cholangiopancreatography (MRCP), which revealed dilated bile ducts and acute cholecystitis. Following endoscopic retrograde cholangiopancreatography (ERCP), significant hemobilia was observed, raising suspicions of cholangiocarcinoma. Despite extensive investigations, including CT angiography, MRCP, and repeat ERCPs, no malignancy was detected. Remarkably, the CA 19-9 level was elevated to 904 U/mL after the initial ERCP and uptrended to 7380 U/mL. These levels, however, normalized to 13 U/mL within two weeks of discharge. While CA 19-9 is a valuable marker in the diagnosis of pancreatic cancer, its elevation in benign pancreaticobiliary conditions necessitates cautious interpretation. In our case, choledocolithasis, cholangitis, and biliary manipulation appeared to have contributed to a transiently elevated CA 19-9. Clinicians must consider the entire clinical context when evaluating elevated CA 19-9 levels to avoid misdiagnosis and ensure appropriate patient management.
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response to chemotherapy, aggressive tumor biology, and high rates of tumor recurrence. Therefore, the development of a non-invasive and effective method for early detection of PDAC is crucial to improving patient outcomes. Continued research and exploration in this area are essential to enhance early detection methods and ultimately improve the prognosis for individuals with PDAC. In this study, we examined 37 exosomal surface proteins through a multiplex flow cytometry test on peripheral plasma samples from a group of 51 clinical control individuals (including healthy volunteers and non-cancer patients (Cholecystectomy, Hernia, healthy volunteers)), 21 pancreatitis, and 48 patients diagnosed with PDAC. Our research findings revealed that the level of exosomal CD40 expression is significantly lower in patients with PDAC and pancreatitis compared to non-cancer patients (p < 0.0001). Additionally, pancreatitis patients exhibited higher levels of exosomal CD25 expression than PDAC patients (p = 0.0104). PDAC patients with higher exo-CD40 had worse survival than patients with lower exo-CD40 (p = 0.0035). Similarly, PDAC patients with higher exo-CD25 showed worse survival in comparison to patients with lower exo- CD25 (p = 0.04). Statistical analysis revealed that exosomal CD40 achieved an AUC of 0.827 in distinguishing PDAC from clinical controls. Combining exo-CD40 along with exo-CD25 and CA19-9 discriminated PDAC patients from clinical controls with an AUC of 0.92. Exo-CD40 and exo-CD25 proteins found in exosomes isolated from plasma can serve as excellent non-invasive biomarkers for the early diagnosis of PDAC. Further larger scale studies are needed to validate combined exo-CD40 and exo-CD25 as a diagnostic tool for the identification of PDAC patients through non-invasive liquid biopsy.
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response to chemotherapy, aggressive tumor biology, and high rates of tumor recurrence. Therefore, the development of a non-invasive and effective method for early detection of PDAC is crucial to improving patient outcomes. Continued research and exploration in this area are essential to enhance early detection methods and ultimately improve the prognosis for individuals with PDAC. In this study, we examined 37 exosomal surface proteins through a multiplex flow cytometry test on peripheral plasma samples from a group of 51 clinical control individuals (including healthy volunteers and non-cancer patients (Cholecystectomy, Hernia, healthy volunteers)), 21 pancreatitis, and 48 patients diagnosed with PDAC. Our research findings revealed that the level of exosomal CD40 expression is significantly lower in patients with PDAC and pancreatitis compared to non-cancer patients (p < 0.0001). Additionally, pancreatitis patients exhibited higher levels of exosomal CD25 expression than PDAC patients (p = 0.0104). PDAC patients with higher exo-CD40 had worse survival than patients with lower exo-CD40 (p = 0.0035). Similarly, PDAC patients with higher exo-CD25 showed worse survival in comparison to patients with lower exo-CD25 (p = 0.04). Statistical analysis revealed that exosomal CD40 achieved an AUC of 0.827 in distinguishing PDAC from clinical controls. Combining exo-CD40 along with exo-CD25 and CA19-9 discriminated PDAC patients from clinical controls with an AUC of 0.92. Exo-CD40 and exo-CD25 proteins found in exosomes isolated from plasma can serve as excellent non-invasive biomarkers for the early diagnosis of PDAC. Further larger scale studies are needed to validate combined exo-CD40 and exo-CD25 as a diagnostic tool for the identification of PDAC patients through non-invasive liquid biopsy.
Background/aim:
For patients with unresectable locally advanced pancreatic cancer (LAPC), carbon-ion radiotherapy (C-ion RT) can safely deliver higher doses than conventional photon therapy, increasing the potential for long-term survival. However, achieving meaningful improvements in survival rates requires reliable prognostic biomarkers to identify patients likely to benefit from treatment.
Patients and methods:
In this study, we measured plasma levels of soluble interleukin-6 receptor (sIL-6R) before C-ion RT and examined their association with the risk of distant metastasis (DM), local recurrence (LR), and overall survival (OS).
Results:
Results showed that patients with higher plasma sIL-6R levels had a lower risk of DM [hazard ratio (HR)=0.53; p=0.033] and improved OS (HR=0.55; p=0.037). No significant association was observed between LR and plasma sIL-6R levels (HR=1.47; p=0.273).
Conclusion:
These findings suggest that pretreatment plasma sIL-6R levels may serve as a prognostic marker for C-ion RT in LAPC.
Integrating OMICS-based platforms and analytical tools for diagnosis and management of pancreatic cancer.
Colorectal cancer (CRC) stands as a major contributor to cancer-related deaths worldwide. Notably, approximately half of all individuals diagnosed with CRC will develop metastatic disease, which significantly worsens the prognosis. CRC represents around 10% of all cancer diagnoses and related deaths globally each year. It is the most frequently diagnosed cancer in women after breast cancer and the third most common in men. Factors like genetics, lifestyle, obesity, and environmental influences are thought to be linked to this trend, but the exact causes remain partly unclear. Clinical/translational research advancements have effectively doubled the overall survival rate for advanced CRC to approximately three-years, and the outcomes remain most favorable for patients without metastatic disease. Pancreatic cancer occurs when abnormal DNA mutations in the pancreas cause pancreatic cells to uncontrollably grow and divide, forming tumors. It predominantly manifests as pancreatic ductal adenocarcinoma (PDAC), originating from the ductal epithelium, and accounts for more than 90% of pancreatic cancers. Due to relatively poor survival outcomes, PDAC is the seventh leading cause of global cancer death despite being the 10th most common cancer. Despite advancements in medical technology that have improved outcomes for many cancers, pancreatic cancer continues to exhibit a staggeringly low five-year survival rate, hovering between 2% and 9%. Recent clinical and basic science research has yielded promising developments in identifying biomarkers that delineate the subtypes and stages of pancreatic cancer, potentially paving the way for personalized treatment strategies. In this chapter, we outline the importance risk factors, genetics, epidemiological factors associated with colon and pancreatic cancers. We also discuss the diagnosis modalities for both the diseases.
Introduction: Gallbladder cancer (GBC) has been documented since the 17th century, with increasing incidence over time. Despite advancements, GBC remains highly fatal due to its asymptomatic progression and limited understanding of its origins. Gallbladder cancer is the 25th most common cancer globally, with significant gender and regional variations. In India, the incidence is notably higher in the north compared to the south. Risk factors identified by the Indian Council of Medical Research (ICMR) include age, gender, ethnicity, gallstones, chronic inflammation, genetics, and lifestyle. Improved imaging and tumor markers like CEA and CA19-9 are crucial for better diagnosis and prognosis. Objective: To investigate the epidemiology and clinical presentation of gallbladder carcinoma, to assess the levels of tumor markers CA19.9 and CEAin relation to different stages of gallbladder carcinoma and to examine the relationship between tumor markers CA19.9 and CEAin predicting the prognosis of patients with gallbladder carcinoma who have undergone resection. Methods: This prospective study was conducted at GSVM Medical College, Kanpur, from January 1, 2023, to June 30, 2024, on patients suspected or diagnosed with gallbladder carcinoma or mass lesions. Patients aged between 18 to 70 years, patients suspected or diagnosed with gallbladder carcinoma or mass lesions, and patients who provided informed consent. Results: Predominantly in patients under 60 years (43.3%), with a higher prevalence in females (73.3%). The most common symptoms were a lump abdomen (80%) and pain abdomen (55%). The body of the gallbladder was the most common site (65%), with dilated CBD in 30% of cases. Adenocarcinoma was the most common subtype (90%). Raised CA19-9 and CEAlevels were effective in diagnosing gallbladder carcinoma with sensitivities of 63.6% and 54.5%, respectively. CA19-9 was superior in predicting tumour burden and recurrence. Significant reductions in CA19-9 levels were observed one-week post-surgery, while CEA levels significantly decreased one-month post-surgery. Conclusion: Raised CA19-9 and CEAlevels are useful for initial screening and prognostication of gallbladder carcinoma. CA19-9 is particularly effective in predicting tumor burden and recurrence. Tumor resection significantly reduces these markers, indicating a positive response to surgery. These markers, combined with cytohistology, can enhance diagnostic accuracy and patient outcomes.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.
A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.
Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.
CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
Tumor biomarkers, the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.
To study the pattern of serum CA19-9 in adnexal masses and its accuracy in diagnosing malignancy.
A cross-sectional study of 267 women with an adnexal mass, who underwent CA 19-9 testing prior to surgery. Descriptive statistics and diagnostic test characteristics were used.
There were 115 benign, 13 borderline and 139 malignant cases. CA 19-9 was elevated in 68 patients (25.5%) when a cut-off of 33 IU/ml was considered. Among the benign, borderline and malignant tumours, 26, 38.5 and 23.7%, respectively, had elevated CA 19-9. Among patients with benign tumours, CA 19-9 was elevated in 48% of the dermoids, 29.6% of the mucinous tumours and 15.9% of the others. There were 131 epithelial (34 mucinous, 97 non-mucinous types), 18 non-epithelial tumours and three metastatic to the ovaries. CA19-9 was raised in 30 (26.1%) of benign, five (38.5%) borderline and 33 (23.7%) of malignant tumours. Elevated CA 19-9 was seen in 15 (34.1%) of the mucinous type, 32 (23.5%) of the non-mucinous type and 21 (27.3%) of the non-epithelial tumours.
CA 19-9 is most likely to be raised in ovarian mucinous tumours and dermoid cysts. It is not a good test for malignant ovarian tumours.
Background and Objective
Five-year survival in pancreatic adenocarcinoma is less than 20%. While previous studies have postulated that a carbohydrate antigen 19-9 (CA19-9) threshold could predict outcome of resection, the role for CA19-9 in decision-making remains unclear. This study aims to assess whether CA19-9 levels combined with tumor size improve prediction of post-resection survival.
Method
A retrospective analysis was conducted on 109 patients with pancreatic adenocarcinoma who underwent perioperative chemotherapy followed by resection. The primary outcome of mortality was, divided into short (<1 year) or prolonged (>2 years). Univariate and multivariable analyses compared the tumor size-adjusted CA19-9 between the outcome groups.
Results
Twenty-seven (24.78%) and eighty-two (75.23%) patients were in the short survival and prolonged-survival groups, respectively. The mean CA19-9 was significantly greater in the short vs prolonged group ( P < .001). Analyzing CA19-9 level by tumor size, the association of high CA19-9 and short survival was significant for small (≤2 cm) and large tumor (>4 cm), but not for intermediate-size tumors (2-4 cm). Adjusting for preoperative variable did not change this association.
Conclusion
CA 19-9 in combination with tumor size better identifies patients with prolonged post-resection survival. This prediction is most accurate in patients with either small (≤2 cms) or large (>4 cms) tumors compared to intermediate-size tumors.
In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, “Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition” was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of “Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition” as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.
The aim of this study was to evaluate the new monoclonal tumour marker CA 242 in the diagnosis of pancreatic carcinoma and to compare it with the established markers CA 50 and CEA. Serum concentrations were determined in 113 patients with jaundice, in 20 patients with laboratory values suggesting cholestasis, and in 60 patients with a suspicion to have chronic pancreatitis. Twenty-four of these 193 patients had pancreatic carcinoma and two patients had carcinoma of papilla of Vater. The sensitivities of CA 242, CA 50 and CEA were 80.7%, 96.1%, and 92.3%, respectively. The specificities were 79.0%, 58.0%, and 59.2%. The sensitivities of combinations of CA 50 and CEA with CA 242 did not exceed the sensitivity of CA 50 alone. The specificity of CA 242 was improved by combining it with CEA (92.2%). The serum marker CA 242 seems to be less sensitive than CEA and CA 50 in the detection of pancreatic carcinoma, but it may prove useful because of its high specificity.
After a pancreatic endocrine tumor has been diagnosed on the basis of clinical signs and the results of laboratory tests, localization of the tumor by the usual imaging procedures fails in as many as 40 to 60 percent of patients. Endoscopic ultrasonography, a sensitive test for small carcinomas of the pancreas, might also be useful in patients with endocrine tumors of the pancreas that cannot be localized by conventional methods.
We studied 37 patients later shown to have 39 endocrine tumors of the pancreas who had negative results on transabdominal ultrasonography and CT. All the patients underwent endoscopic ultrasonography, and 22 also underwent selective angiography. All the tumors were confirmed by surgical excision and immunohistologic examination; they consisted of 31 insulinomas, 7 gastrinomas, and 1 glucagonoma, 0.5 to 2.5 cm (mean, 1.4 cm) in diameter. All but one of the patients were cured of their disease, as ascertained by at least six months of clinical and laboratory follow-up.
Using endoscopic ultrasonography, we were able to localize 32 of the 39 tumors (sensitivity, 82 percent); no tumor was incorrectly localized. The size of the tumors was very similar (within 2 mm) to that predicted by endoscopic ultrasonography. Among the 22 patients who underwent both angiography and endoscopic ultrasonography, ultrasonography was significantly more sensitive than angiography for tumor localization (sensitivity, 82 percent vs. 27 percent). Among 19 control patients without pancreatic endocrine tumors, endoscopic ultrasonography was negative in 18 (specificity, 95 percent).
Endoscopic ultrasonography is a highly sensitive and specific procedure for the localization of pancreatic endocrine tumors. It should be considered for the preoperative localization of such tumors once the clinical and laboratory diagnosis has been established.
A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer.
The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and biliary cancers (68%). The sensitivity was somewhat lower than that of CA 19-9 (76%) and CA 50 (73%). On the other hand, in benign pancreatic and biliary tract diseases the CA 242 level was less frequently elevated than the CA 19-9 and CA 50 levels. The serum CA 242 concentration was increased in 55% of patients with colorectal cancer. CA 242 detected more Dukes A-B carcinomas (47%) than CEA (32%), whereas CEA was more often elevated (71% vs 59%) in Dukes C-D carcinomas. CA 242 was slightly elevated (ad 41 U ml-1) in 10% of patients with benign colorectal diseases. CA 50 and CA 19-9 had lower sensitivities than CA 242 using the recommended cut-off values. When cut-off levels based on relevant benign colorectal diseases were used, the sensitivities of these markers were similar and somewhat higher than that of CEA. Less than half of patients with gastric cancer (44%) had an elevated CA 242 serum level. CA 242 is a promising new tumour marker, that may be of additional value in the diagnosis of pancreatic and biliary, as well as colorectal cancer, and may be useful in monitoring cancer patients after radical surgery.
Seventy-eight patients were evaluated to ascertain the usefulness of markers CA 19-9 and CA 50 in diagnosing pancreatic cancer, using a less specific marker (CEA) as reference. Three groups were considered: a) 36 controls; b) 22 patients with benign obstructive jaundice; c) 20 patients with pancreatic cancer. Preoperative blood samples were obtained to ascertain CEA (E.I.A.), CA 19-9 (R.I.A.) and CA 50 (T.R.-F.I.A.). Serum concentrations of the various markers were significantly higher for patients with pancreatic cancer in comparison with the other groups, at cut-offs of 10 ng/ml (CEA), 100 ng/ml (CA 19-9) and 170 U/ml (CA 50). The sensitivity of CA 19-9 (94%) and CA 50 (88%) was much greater than that of CEA (30%). The specificity of the three markers in patients with pancreatic cancer, with respect to the control group, was 100% and this figure is reduced with respect to the group suffering from benign obstructive jaundice (CEA: 90%; CA 19-9: 88% and CA 50: 87%). Diagnostic results (sensitivity, specificity, positive predictive value (P.P.V.) and negative predictive value (N.P.V.] did not significantly increase with respect to CA 19-9 and CA 50 when considered individually. It is concluded that the serum concentrations of CA 19-9 and CA 50 showed high sensitivity and specificity as markers of pancreatic cancer with respect to the other groups, pointing towards clinical routine clinical use of both markers. In addition, a comparative study of the literature has been made and prospects for short-term development and concrete applications for early and reliable diagnosis have been highlighted.
Monoclonal antibody 19-9, produced by a hybridoma prepared from spleen cells of a mouse immunized with a human colon carcinoma cell line, detects an antigen in the serum from most patients with gastrointestinal and pancreatic cancer (M. Herlyn, H.F. Sears, Z. Steplewski, and H. Koprowski, J. Clin. Immunol., 2: 135-140, 1982). The epitope of this antibody is a carbohydrate with the sugar sequence (formula; see text) in which NeuNAc is N-acetylneuraminic acid, Gal is galactose, GlcNAc is N-acetylglucosamine, and Fuc is fucose. In the colon carcinoma cell line and many gastrointestinal and pancreatic cancers, this sequence occurs in a monosialoganglioside containing a sialylated Lea-active pentasaccharide (sialylated lacto-N-fucopentaose II, IV3-alpha-NeuNAc-III4-alpha-Fuc-LcOse4, in which LcOse4 is Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc) (J. L. Magnani et al. J. Biol. Chem., 257: 14365-14369, 1982). However, the antigen in the sera of patients occurs mainly as a mucin, not a ganglioside, based on the following evidence. Little antigen is extracted by organic solvents from sera, and that which is extracted remains at the origin under conditions of thin-layer chromatography where the ganglioside antigen migrates up the plate. Upon gel filtration of serum on Sephacryl S-400, the antigen is eluted in the void volume, indicating a molecular weight of greater than or equal to 5 X 10(6). Incubation for 5 hr at 37 degrees in 0.1 N NaOH destroys the serum antigen but does not affect the ganglioside antigen. The density of the serum antigen as determined in a CsCl gradient is 1.50 g/ml, while in 4 M guanidine. HCl its density is 1.43 g/ml. Finally, antigen affinity purified by antibody 19-9 from the serum of a cancer patient belonging to the Le(a-b+) blood group contains Leb antigen, consistent with the multiple antigenic specificities exhibited by mucins.
The serum expression of a novel tumour marker, CA 242, defined by monoclonal antibody C 242, was studied in 179 patients with pancreatic cancer. The results were compared with CA 19-9, CA 50 and CEA. CA 242 is a carbohydrate closely related, but not identical, to CA 19-9 and CA 50. The overall sensitivity of the CA 242 assay was 74%: 55% in stage I, 83% in stage II-III and 78% in stage IV disease. The specificity calculated from 112 patients with benign diseases was 91%. CA 19-9 had a higher sensitivity of 83%, but the specificity was only 81%. When comparing the markers by receiver operating characteristic analysis, the sensitivities were almost identical at all specificity levels. The CA 242 level was elevated in 7%, 15% and 7% of patients with benign pancreatic, biliary and liver disease respectively. The corresponding figures for CA 19-9 were 19%, 28% and 15% respectively. The sensitivity of CA 242 was higher than that of CA 50 and CEA at all specificity levels. In conclusion, tumour marker CA 242 seems to be a useful diagnostic tool for the diagnosis of pancreatic cancer, and is an alternative to CA 19-9. The advantage of CA 242 over CA 19-9 is its higher specificity when using the recommended cut-off levels of the assays.
A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.
CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus glycoprotein with high specificity for intestinal mucus, particularly in the colon, small intestine, biliary tract and pancreas. We investigated the expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM 17.1 was weakly expressed on normal ductal cells and chronic pancreatitis, whereas it was overexpressed in pancreatic cancer. Serum analysis using a new enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P > 0.05).
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Figure 2
This study was performed in order to ascertain the role of an extra-hepatic cholestasis per se in increasing serum markers of pancreatic malignancy, in the absence of a malignant growth. In 14 patients with a benign obstruction of the main bile duct (12 stones and 2 stenoses) circulating CA 19-9, TPA and CEA were determined. Serum markers, cholestasis indices (total bilirubin, alkaline-phosphatase, gamma-glutamyltransferase) and aspartate-amino-transferase were evaluated at admission (time A) and after regression or resolution of cholestasis (time B). A significant decrease of TPA and CA 19-9 was detected at time B as compared to A. CEA did not show any variation. The differences of CA 19-9 and TPA serum levels between times A and B correlated with the corresponding variations of liver function tests. No correlation was detected between CEA and the above indices. We can conclude that CA 19-9 and TPA but not CEA increase in patients with a benign extra-hepatic cholestasis in relation to the degree of hepato-biliary impairment. Therefore caution should be taken in evaluating CA 19-9 and TPA in a jaundiced patient.
OBJECTIVE: Clinicians might be misled in interpreting an elevated CA19-9 when differentiating pancreaticobiliary cancer from benign clinical conditions such as acute cholangitis or cholestasis, because in these conditions, the concentration of CA19-9 may also be elevated. The aims of our study were to calculate new individual cutoff values for CA19-9 according to clinical situations using a receiver operating characteristic (ROC) curve and to define a new strategy for interpreting CA19-9 in pancreaticobiliary cancer.
Mucus glycoproteins are often present in the sera of patients with pancreatic cancer, and their detection and quantification can be used in serologic diagnosis.
A novel enzyme-linked "sandwich" assay (CAM 17.1/WGA) has been developed in which a lectin, wheat germ agglutinin (WGA), is bound to the solid phase to capture serum glycoproteins, and after addition of test sera, a monoclonal antimucin antibody (CAM 17.1) and peroxidase-tagged second antibody are used as a detection system.
The test has been applied to sera from 79 patients with pancreatic cancer and 120 controls. The CAM 17.1/WGA assay alone had a sensitivity of 78% and specificity of 76% in the diagnosis of pancreatic cancer. Combination of the CAM 17.1/WGA test with a previously described peanut lectin binding assay (PNA/ELLA) provided a sensitivity of 92% and specificity of 70%, whereas combination of the CAM 17.1/WGA assay with the CA 19-9 radioimmunoassay had a sensitivity of 85% and specificity of 76%. Combination of all three tests had a sensitivity of 94% and specificity of 66%. In nonjaundiced patients, the combination of CAM 17.1/WGA and PNA/ELLA had a sensitivity of 93% and specificity of 79% in the diagnosis of pancreatic cancer.
This new test adds significantly to the armamentarium of serologic tests for pancreatic cancer. These tests are particularly effective when used in combination to detect different mucin-borne carbohydrate antigens. They deserve more widespread use, particularly in examining nonjaundiced patients with unexplained abdominal pain or weight loss.
The clinical diagnostic utility of CA-50 (time-resolved fluoroimmunoassay) and Span-1 was compared with that of CA19-9 by measuring their levels in sera from patients with pancreatic cancer and other diseases. In pancreatic cancer CA-50, Span-1, and CA19-9 showed similar positive rates (84%, 82%, and 81%, respectively). With regard to the ability to distinguish pancreatic cancer from chronic pancreatitis, however, the specificity of CA-50 and Span-1 was higher than that of CA19-9 (85%, 85%, and 79%, respectively). Despite the similar positive rates of CA-50 and Span-1 in pancreatic cancer, the correlation between these two markers was low. Thus, used in combination, they compensated for each other in the diagnosis of pancreatic cancer. In chronic liver diseases, serum levels of both CA-50 and Span-1 were correlated with that of biliary tract enzymes, alkaline phosphatase, and r-glutamyl transpeptidase. And these two markers were more affected by the biliary system than CA19-9, resulting in the significantly higher positive rates. In these diseases immunohistochemical study showed that all three markers were localized in the epithelial cells of the bile duct, with CA-50 and Span-1 showing a similar tissue distribution.
BACKGROUND
The value of serum tissue polypeptide specific antigen (TPS) as a complement to CA 19-9 in the detection of pancreatic carcinoma was determined prospectively. TPS and CA 19-9 levels obtained at the time of diagnosis in patients suspected of having chronic pancreatitis or pancreatic carcinoma were evaluated in receiver operating characteristic (ROC) curve analysis.METHODS
Serum TPS and CA 19-9 levels were measured by immunoassays in 122 subjects, 48 with pancreatic carcinoma and 74 with chronic pancreatitis.RESULTSElevated levels of CA 19-9 were detected preoperatively in 70% of pancreatic carcinoma patients and in 19% of chronic pancreatitis patients. Elevated levels of TPS were detected in 100% of patients with pancreatic carcinoma and in 22% of patients with chronic pancreatitis. The median levels of TPS and CA 19-9 for pancreatic carcinoma were significantly higher than those for chronic pancreatitis (P < 0.0001). Increasing the upper reference value of TPS allowed for better discrimination between chronic pancreatitis and pancreatic carcinoma. ROC curve analysis showed that the introduction of 200 U/L as a decision criterion for TPS did not reduce its sensitivity but significantly improved its specificity. At a specificity of 98% for TPS, discrimination between pancreatic carcinoma and chronic pancreatitis was found to be 97%. Increasing the upper reference level for CA 19-9 to attain a specificity of 98% decreased its sensitivity from 70% to 33%.CONCLUSIONS
At an elevated cut-off level for TPS (200 U/L), almost complete discrimination between pancreatic carcinoma and chronic pancreatitis was obtained. TPS will be more useful than CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis. Cancer 2000;89:83–8. © 2000 American Cancer Society.
In 59 patients with ductal pancreatic cancer the monoclonal antibody (MAb) BW 494, which detects the CA 494 glycoprotein antigen, was analyzed in comparison with the reference tumor markers CA 19-9 and CEA. Eighty-one patients with non-pancreatic malignancies of the gastraintestinal (GI) tract, 95 with chronic pancreatitis, 124 with benign non-pancreatic GI diseases, 30 with diabetes mellitus (type I or type II) and I14 healthy blood donors served as controls. The sensitivity of pancreatic cancer was 90%, 44% and 90% for CA 19-9, CEA and CA 494, respectively. In chronic pancreatitis, as the most important control population for pancreatic cancer, the specificity was 85%, 72% and 94% for CA 19-9, CEA and CA 494, respectively.
The accuracy of computed tomography (CT) in predicting resectability of pancreatic malignancy has been questioned recently and alternative methods have been recommended.
To determine the accuracy of CT for predicting resectability and its influence on survival, a standard protocol for performing CT and reporting the results was developed and then compared retrospectively with the ability of one surgeon to perform a resection during 1989-1994. Postoperative survival was determined.
Of 88 consecutive patients 35 (40 per cent) had CT-resectable disease and 53 (60 per cent) had CT-irresectable disease. Twenty-one patients were excluded because of advanced disease or poor performance status. Of the remaining 67 patients, 47 (70 per cent) had pancreatic ductal adenocarcinoma and 20 (30 per cent) had ampullary adenocarcinoma, of whom 32 had a resection, 32 had a palliative bypass and three had only a staging laparoscopy. The sensitivity and specificity for computed tomographic prediction of resectability were 72 and 80 per cent respectively. The positive predictive value was 77 per cent and the negative predictive value 76 per cent. There were seven false-positive and nine false-negative findings. Survival was more dependent on whether or not resection was performed than on computed tomographic predictability of resection.
CT was reasonably accurate in predicting resectability but cannot be relied on entirely, requiring an improvement in staging methods for pancreatic malignancy.
This study was performed in order to assess the relative role of cholestasis in increasing some serum glycoproteic markers of malignancy (CA 19-9, TPA, CEA). 30 Patients with benign and 16 with malignant extra-hepatic cholestasis were studied on admission (stage A) and after the operative or spontaneous resolution of the cholestatic picture (stage B). CA 19-9 and TPA were found to be lower in stage B than in stage A benign diseases. A similar behaviour was found in malignant diseases, although findings were significant only for CA 19-9. In neither of the patient groups was CEA found to present a significant trend. Extra-hepatic cholestasis appears able to increase per se serum glycoproteic markers in benign diseases, with variations proportional to the severity of the clinical picture. The same considerations can apply to malignancies, even if in these situations the production of tumour markers by the neoplastic growth should also be considered. We should therefore be cautious in assessing the diagnostic usefulness of new tumour markers when cholestasis is present.
In view of the increasing number of new imaging techniques and serum tumor markers, it is not well established which combination or which order of tests may provide the most information for diagnosis of pancreatic carcinoma. This review determines the diagnostic value of the various tests and evaluates which combination of tests may provide the most information and what may be considered to be a current rational approach to the diagnosis of pancreatic carcinoma. In the present analysis endoscopic retrograde cholangiopancreatography (ERCP) provided a 92% sensitivity that exceeded the 83% and 74% sensitivities calculated for computed tomography (CT) and ultrasound, respectively. The specificity of all three imaging techniques exceeded 90%. Serum determination of CA 19-9 yielded an 83% sensitivity, which was considerably higher than sensitivities of carcinoembryonic antigen and various other tumor markers. The combination of CA 19-9 and ultrasound improved the sensitivity of each test performed alone by 10-15%. Fine-needle biopsy allows diagnosis of pancreatic carcinoma with a sensitivity of 83% and an almost perfect specificity of 99%. On the basis of these data, the combination of ultrasound and determination of CA 19-9 is recommended as the initial tests when pancreatic carcinoma is suspected. CT also must be performed if ultrasound is indeterminant or inconsistent with the clinical evaluation, as well as in patients with negative ultrasound but abnormal CA 19-9. Negative results of CT, ultrasound, and CA 19-9 will exclude pancreatic carcinoma in most patients. A positive ultrasound or CT result usually leads to fine-needle biopsy, which helps avoid most diagnostic laparotomies. ERCP must be performed in patients where ultrasound, CT, and fine-needle biopsy do not clarify the diagnosis. In the majority of patients with pancreatic carcinoma, noninvasive imaging techniques such as ultrasound and CT also allow adequate staging. In some patients, however, laparoscopy and angiography may need to be performed for strategic planning of further therapy. Although modern imaging techniques and serum tumor markers allow diagnosis of pancreatic carcinomas as small as 2-3 cm and help avoid most diagnostic laparotomies, this improvement in diagnostic capability has as yet not significantly improved the prognosis.
The diagnostic accuracy of the serum CA 19-9 determination was prospectively evaluated in patients selected for the presence of signs or symptoms highly suggestive for pancreatic cancer. Of 110 patients included in the study, 54 had a final diagnosis of pancreatic adenocarcinoma (49% prevalence). CA 19-9 values were higher than 40 U/ml in 45 patients with pancreatic carcinoma and in 18 of the 56 patients with other final diagnosis (sensitivity, 0.83; specificity, 0.68; positive predictive value [PPV], 0.71; negative predictive value [NPV], 0.81). The serum CA 19-9 determination was not capable of shortening the diagnostic workup of patients with strong clinical suspicion of pancreatic cancer since adequate imaging of the pancreas was required to confirm or exclude the diagnosis. However, values above 120 U/ml were strongly suggestive for pancreatic carcinoma in the overall population (PPV, 0.85) and they were diagnostic (PPV, 1.0) in the anicteric portion. Combined with pancreatic imaging, the CA 19-9 was an excellent confirmatory test; a normal value in a patient with negative imaging ruled out pancreatic carcinoma as the cause of symptoms (NPV, 1.0), whereas a pathological result in the presence of positive or equivocal pancreatic radiology was highly suggestive for the presence of the disease (PPV, 0.93).
To investigate the possibility of detecting carcinomas of the pancreas at an early stage by mass screening of persons without symptoms or by screening the outpatients with gastrointestinal complaints or jaundice, we performed a multicentral study of the mass screening of 10,162 persons at five local areas and of the outpatient screening of 4506 at 17 hospitals for pancreatic cancer in Japan for two years from 1984 to 1985, using serum CA19-9 and elastase-1 determinations or ultrasonography. Mass screening of 10,162 persons over 40 years old found only four (0.04%) cases of pancreatic cancer, including one case that was curatively treated. According to the screening of 4506 outpatients with gastrointestinal complaints or icterus, 85 (1.9%) patients were found to have pancreatic cancer. Of these 85 patients, 28 could undergo curative treatment. In addition to them, 73 (1.6%) patients with other digestive organ cancer were found. Our results suggest that the mass screening of persons without symptoms is not worthwhile in the early detection of pancreatic cancer, but outpatient screening is useful for detecting curative cancers of the pancreas.
The clinical diagnostic utility of CA-50 (time-resolved fluoroimmunoassay) and Span-1 was compared with that of CA19-9 by measuring their levels in sera from patients with pancreatic cancer and other diseases. In pancreatic cancer CA-50, Span-1, and CA19-9 showed similar positive rates (84%, 82%, and 81%, respectively). With regard to the ability to distinguish pancreatic cancer from chronic pancreatitis, however, the specificity of CA-50 and Span-1 was higher than that of CA19-9 (85%, 85%, and 79%, respectively). Despite the similar positive rates of CA-50 and Span-1 in pancreatic cancer, the correlation between these two markers was low. Thus, used in combination, they compensated for each other in the diagnosis of pancreatic cancer. In chronic liver diseases, serum levels of both CA-50 and Span-1 were correlated with that of biliary tract enzymes, alkaline phosphatase, and r-glutamyl transpeptidase. And these two markers were more affected by the biliary system than CA19-9, resulting in the significantly higher positive rates. In these diseases immunohistochemical study showed that all three markers were localized in the epithelial cells of the bile duct, with CA-50 and Span-1 showing a similar tissue distribution.
The levels of DU-PAN-2 antigen, carcinoembryonic antigen, and CA19-9 in serum and bile of patients with pancreatic and biliary tract diseases were measured. The sensitivities (true positive) of DU-PAN-2 in serum to pancreatic carcinoma (64%) and to biliary tract carcinoma (62%) were similar to those of CA19-9 in serum (69% and 72%, respectively). Nine of 18 (50%) patients with CA19-9-negative pancreatic carcinoma tested positive for DU-PAN-2. The sensitivities of CEA to pancreatic carcinoma (56%) and to biliary tract carcinoma (52%) were lowest. The measurement of these antigens in bile seemed to be of little diagnostic value in differentiating between malignant and benign diseases. False positives of these three assays occurred frequently in patients with benign pancreatic or biliary tract disease coupled with obstructive jaundice. After percutaneous transhepatic biliary drainage, serum DU-PAN-2 and CA19-9 levels returned to normal ranges in patients with benign diseases, but not in patients with carcinoma of the pancreas or of the biliary tract. Serum CA19-9 and DU-PAN-2 antigens are useful tumor markers for pancreatic and biliary tract carcinomas. Longitudinal assays of these antigens may be useful for the differential diagnosis of patients with obstructive jaundice.
Levels of serum Span-1, a new tumor marker for pancreatic cancer, were assayed in 64 patients with pancreatic cancer, 90 with nonpancreatic cancer, and 254 with nonmalignancies, involving 55 healthy controls. Furthermore, Span-1 was compared with other tumor markers (CA19-9, carcinoembryonic antigen [CEA], and DU-PAN-2). Frequency of elevated Span-1 levels was 81.3% in pancreatic cancer. False-positive elevations of serum Span-1 levels were rather common in liver cirrhosis (53.8%) and chronic hepatitis (26.3%). The sensitivity, specificity, and efficiency of this assay for pancreatic cancer, was 81.3%, 75.6%, and 76.5% against all subjects without pancreatic cancer, respectively. In comparison with other markers, sensitivity of Span-1 tended to be highest with similar specificity to those of CA19-9 and CEA. The Span-1 assay has a high sensitivity and specificity for pancreatic cancer. It is almost equivalent to CA19-9 assay. However, this assay is not specific for chronic liver diseases.
For the quantitative measurement of pancreatic oncofetal antigen (POA), an enzyme immunoassay for POA has been developed, and is based on the sandwich method using antibody-coupled glass beads and enzyme (peroxidase)-labelled antibody. Serum POA concentrations were increased significantly in patients with pancreatic cancer, but not in those with chronic pancreatitis or other miscellaneous diseases, or in normal subjects. It is concluded that the enzyme immunoassay could be used for the assay of POA and our results show that the determination of serum POA would be useful in the diagnosis of pancreatic cancer.
In 403 patients suspected of having pancreatic cancer, we prospectively studied a combination assay of various serum tumor markers: CA19-9, DUPAN2, tissue polypeptide antigen, elastase 1, gamma-glutamyltranspeptidase, lactate dehydrogenase, lipase, amylase, and alkaline phosphatase. The diagnostic value of each marker was compared with a multivariate analysis (computer-aided multivariate and pattern analysis system for pancreatic cancer examine-1: CAMPAS-PX1). Pancreatic cancer was subsequently identified in 47 patients. CAMPAS-PX1 had higher negative in health and positive predictability than those of each marker used alone in the diagnosis of pancreatic cancer. CAMPAS-PX1 proved the most effective marker for diagnosing pancreatic cancer, but in terms of its cost/benefit ration CAMPAS-PX1 was not superior to CA19-9 used alone. In this prospective trial, we experienced poor generalizability in the statistical models (CAMPAS-PX1). We believe that selection bias was present in samples used for model building. Based on this study a new model has been designed.
The carbohydrate antigen 19-9 (CA19-9) and radioimmunoassay have been shown to offer new hope for improving the diagnosis of pancreatic cancer, and various tumor markers (including SPan-1, DUPAN-2, and CA50) have been established. While clinical studies of these markers have found satisfactory sensitivities, only a few studies have compared these tumor markers on the same blood samples. We therefore evaluated the clinical efficacy of SPan-1, CA19-9, DUPAN-2, CA50, carcino-embryonic antigen, and Elastase 1 in detecting pancreatic cancer in identical blood samples.
A prospective, blinded study of CA19-9 in 2,467 patients having abdominal surgery yielded 356 patients with pancreatic, gallbladder, and biliary disease who submitted coded preoperative serum specimens. In this group, there were 84 patients with pancreatic cancer and 24 patients with gallbladder-biliary cancer; the remainder had benign lesions. The recorded imaging data and marker results were merged with the patients' demographic, clinical, and surgical data and tissue diagnoses for analysis. Receiver operator character calculation suggested that a reference value of 100 U/ml for CA19-9 was appropriate rather than the 37-40 U/ml value most frequently employed and yielded a specificity of 97% in the 467 operated patients with a sensitivity of 8.3% for all nonpancreatic-biliary cancers and 62% overall for these lesions. In the more diagnostically challenging nonicteric patients, CA19-9 sensitivity was 55%, specificity was > 99%, positive predictive value (PPV) was 97%, and negative predictive value (NPV) was 88%. When CA19-9 results were combined with those from endoscopic retrograde cholangiopancreatography, ultrasound (US), or computed tomography (CT), the PPV, and especially the NPV were increased. The addition of carcinoembryonic antigen results did not affect overall results. The addition of CA19-9 results to ambiguous or indeterminant imaging interpretation clearly improved the combined specificity, sensitivity, and PPV, but the change was less impressive, albeit positive, for NPV. The combination of CA19-9 and CT (or US) is a reasonable, cost-effective, noninvasive approach to establishing the diagnosis of pancreatic, cholangitic, or biliary cancer in nonicteric patients. Although no single procedure or combination of procedures was found to detect early, small lesions, CA19-9 is clearly a clinically useful adjunct to imaging in nonjaundiced patients suspected of having these malignancies.
Although the prognosis for pancreatic cancer is generally poor, the Japanese Pancreatic Cancer Register reported in 1992 that the survival rate for resected pancreatic cancer was much higher than that for more conservative treatment. T1 and T2 pancreatic tumors are much more frequently resectable than are T3 and T4 tumors, and the 5-year survival rate for unresected T2, T3, and T4 cases is 0%. These findings emphasize the importance of early diagnosis of resectable pancreatic cancer. CA19-9 has shown satisfactory sensitivity in detecting advanced pancreatic cancer; we sought to determine the effectiveness of CA19-9 as part of a screening program for early cancer. Using elastase 1, CA19-9, and ultrasonography, we developed and tested a program of mass screening on persons presenting with and without abdominal complaints.
A 50 year old man is described with hepatic dysfunction and chronic pancreatitis in whom greatly increased concentrations of the pancreatic tumour marker CA 19-9 combined with an abnormal appearance at endoscopic retrograde cholangiopancreatography lead to the false suspicion of pancreatic carcinoma. CA 19-9 concentrations should be interpreted with caution in patients with intrinsic liver disease or biliary obstruction.
The tumour markers CA 50 and CA 242 were determined in serum from 70 cholestatic patients--35 with pancreatic cancer and 35 with benign biliopancreatic diseases. Both markers correlated (r = 0.37) with serum bilirubin in all patients. When the patients were subdivided into groups, the only correlation apparent was between CA 50 and bilirubin in patients with benign diseases (r = 0.40). The serum concentrations of both markers were much higher in patients with pancreatic cancer. Serial sampling before and after decompression of the cholestasis showed reduction of CA 50 and CA 242 concurrently with bilirubin and alkaline phosphatases in nine patients with benign disease but unchanged levels in six cancer patients. When the two markers were compared, sensitivity was superior for CA 50 (94% versus 73%), whereas specificity was better for CA 242 (65% versus 34%), as was positive prediction (76% versus 59%), whereas negative prediction was higher for CA 50 (86% versus 61%). Higher cut-off levels yielded better specificity for CA 50 but not for CA 242. Both markers indicate pancreatic cancer irrespective of cholestasis, but moderate elevations occur in some patients with benign disorders.
There has been extensive use of serum tumor markers in diagnosing pancreatic adenocarcinoma. There is no tumor marker, however, that alone has sufficient diagnostic accuracy. It is necessary to know which combination of tumor markers should be used to detect pancreatic cancer, with respect to clinical usefulness and cost effectiveness.
Serum levels of 17 kinds of tumor markers were determined in 145 patients and 40 healthy volunteers. Thirty-five patients with proven pancreatic adenocarcinoma, and 32 with benign pancreatobiliary disease (14 chronic pancreatitis and 18 biliary stones) were selected. For analysis of the usefulness of each tumor marker to differentiate these two groups, scatterplot and relative operating characteristic (ROC) analyses were used. A multivariate discriminant system to differentiate these two groups was developed using stepwise discriminant analysis by backward elimination selection.
The significance of each tumor marker varied according to the tumor volume. By ROC analysis, the markers were divided into four subgroups according to their usefulness in discriminating pancreatic adenocarcinoma from benign pancreatobiliary disease. A discriminant system consisting of two different discriminant functions using nine tumor markers (CA 19-9, DUPAN-2, TPA, elastase-1, lipase, amylase, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactate dehydrogenase) was developed and designated CAMPAS-P; it could differentiate between all 35 cases of pancreatic adenocarcinoma and 32 cases of benign pancreatobiliary disease. On the other hand, CAMPAS-P showed a low positive rate in pancreatic tumors of unusual histologic type, and poor organ-specific diagnostic ability in various digestive organ malignancies.
CAMPAS-P may be very useful for differential diagnosis between pancreatic adenocarcinoma and benign pancreatobiliary disease.
The tremendous progress in imaging techniques over the past few years has not resulted in an earlier diagnosis of pancreatic cancer (PC). The search for a noninvasive diagnostic tool, capable of early diagnosis, led to the development of a series of tumor markers. This article discusses the evaluation of the latest one--CA 242--and its comparison with established markers such as CA 19.9, CA 50, and carcinoembryonic antigen (CEA).
The markers were tested in preoperative serum samples collected from 300 patients and 30 healthy controls between April 1986 and May 1991. There were 68 patients with ductal carcinoma of the pancreas, 24 with other pancreatic tumors, 57 with acute pancreatitis, 29 with chronic pancreatitis (CP), 90 with benign disease of the upper gastrointestinal tract, and 32 with malignant disease. The test for CA 242 consisted of a DELFIA research kit (WALLAC OY, Turku, Finland) with a cutoff level of 20 U/ml. The other markers were tested with commercially available kits.
Sensitivities for PC in this population, with other malignant neoplasms accounting for 16% of the group, were 66.2%, 70.6%, and 70.6% for CA 242, CA 19.9, and CA 50, respectively (90% specificity level). The best results were achieved with the combination of CA 242 and CA 50, reaching a sensitivity of 75.0%. The differential diagnosis between PC and CP could be made with a sensitivity of 64.7%, 79.4%, and 77.9%, respectively, for the three markers.
The authors conclude that, on its own, CA 242 does not improve the sensitivities reached with CA 19.9 and CA 50, but the combination does achieve both a higher sensitivity and specificity.
We compared the recently proposed tumor markers CA195, CA242, and CAM43 with a widely used antigen, CA19.9, and a circulating marker of cellular proliferation, TPS, to define their specificity, sensitivity, and cost-benefit ratio. The tumor markers were measured in 41 pancreatic carcinoma patients and in two control groups, the first comprising 19 patients with benign pancreatic diseases, the second comprising 41 healthy blood donors. Sensitivities were 79% for CA19.9, 57% for CA242, 60% for CAM43, 76% for CA195, and 98% for TPS. Specificities calculated for the group with pancreatic diseases were 60% for CA19.9, 84% for CA242, 95% for CAM43, 53% for CA195, and 22% for TPS. Specificities for the blood donor group were 100% for CA19.9, 93% for CA242, 98% for CAM43, 85% for CA195, and 88% for TPS. Positive values for the tumor markers appeared from second stage (Hermreck classification). Metastases, invasion of lymph nodes, and coupling of cancer-associated antigens did not significantly modify marker sensitivity. In pancreatic carcinoma, CA19.9 showed good sensitivity (79%) and high specificity (60-100%). In view of their own advantages (e.g., high specificity of CAM43, high sensitivity of TPS in recurrences) and limits (e.g., low sensitivity of CAM43, very low sensitivity of TPS), the other markers could be used alone or with CA19.9. Two pairs of tumor markers showed high similarity in our study: CA19.9 and CA195, and CAM43 and CA242.
Serum expression of the cancer-associated antigens CA 19-9 and CA 50 and their relation to Lewis blood cell status were studied in 26 patients with pancreatic duct carcinoma and 26 patients with pancreatitis. The discriminating capacity between benign and malignant disease was high for both tumor markers. The correspondence between serum levels of CA 19-9 and CA 50 was close irrespective of the Lewis phenotype of the patient. All cancer patients with normal levels of CA 19-9 and CA 50 were of the phenotype Le(a-b-). Knowledge of the Lewis phenotype may therefore add vital information when tumor marker assays are used for diagnosis and monitoring of malignant pancreatic disease.
High-quality preoperative radiographic evaluation is crucial in selecting patients with periampullary carcinomas who are candidates for surgical exploration and tumor resection while minimizing the rate of unnecessary laparotomy.
Twenty-one consecutive patients were prospectively investigated using helical computed tomography (CT) scanning, endoscopic ultrasonography (EUS), and selective visceral angiography (SVA) to determine tumor resectability. All patients were explored and resectability determined.
Helical CT had a sensitivity of 63%, a specificity of 100%, and an overall accuracy of 86%. EUS had a sensitivity of 75%, a specificity of 77%, and an overall accuracy of 76%. SVA had a sensitivity of 38%, a specificity of 92%, and an overall accuracy of 71%.
Helical CT scanning is the best preoperative imaging test to determine tumor resectability. EUS is more sensitive than CT for tumor detection, but underestimates resectability. SVA is no longer helpful in the preoperative evaluation of these malignancies.
The monoclonal antibody pyruvate kinase type tumor M2 (TUM2-PK) has been shown to have a high binding capacity to pancreatic cancer. In present study TUM2-PK serum levels were measured in pancreatic cancer and compared with the reference tumor markers CA19-9, CA50, CA72-4 and CEA. Overall 100 patients were included in this study, 64 patients had a histologically confirmed pancreatic carcinoma, 36 patients gastrointestinal cancer (stomach, colon), 666 healthy volunteers served as controls. Measurements were done by enzymimmunoassay. For the healthy blood donors a cut-off value of 22.5 U/ml was evaluated, which corresponds to 95% specificity. In patients with pancreatic cancer the sensitivities of TUM2-PK, CA19-9, CEA, CA72-4 and CA50 were 71%; 68%, 37%, 49% and 63.4% respectively. Linear regression analysis indicated that there was a positive correlation (r = 0.79). According to the results of our study TUM2-PK has comparable sensitivity but higher specificity than the reference tumor marker CA19-9.
Recent studies have shown evaluation of the small peripancreatic veins to have potential in improving pancreatic cancer staging. This study was performed to determine the effectiveness of thin-section pancreatic phase helical CT images in visualizing these veins.
Seventy-two patients (30 with pancreatic adenocarcinoma and 42 with no pancreatic disease) underwent dual-phase helical CT with thin-section pancreatic phase acquisition (40-70 sec after i.v. contrast initiation at 3 ml/sec) and hepatic phase acquisition (70-100 sec). Visualization (with diameter measurement) or nonvisualization of the posterior superior pancreaticoduodenal vein (PSPDV), anterior superior pancreaticoduodenal vein (ASPDV), and gastrocolic trunk was recorded for both acquisitions. We also correlated surgical tumor resectability with the status of the small peripancreatic veins.
Visualization of peripancreatic veins was significantly better on pancreatic phase images than on hepatic phase images for both healthy individuals (PSPDV, 88% of the veins visualized on the pancreatic phase images versus 50% on the hepatic phase images; ASPDV, 93% on the pancreatic phase images versus 48% on the hepatic phase images; gastrocolic trunk, 98% on the pancreatic phase images versus 76% on the hepatic phase images) and for pancreatic cancer patients (PSPDV, 97% on the pancreatic phase images versus 57% on the hepatic phase images; ASPDV, 77% on the pancreatic phase images versus 43% on the hepatic phase images) (p < .05). The exception was the gastrocolic trunk in cancer patients (83% on the pancreatic phase images versus 77% on the hepatic phase images) (p > .05). In pancreatic cancer patients, 11 dilated peripancreatic veins were identified on the pancreatic phase images compared with six on the hepatic phase images. However, only one of the 11 dilated peripancreatic veins was in a patient with surgically resectable disease.
In a dual-phase helical CT protocol, thin-section pancreatic phase images provided visualization of the small peripancreatic veins that was superior to hepatic phase images, providing further support for the use of this protocol in pancreatic cancer evaluation.
To determine the efficacy of arterial phase helical computed tomography (CT) for the depiction of small pancreatic arteries.
Arterial phase helical CT (3-mm collimation, 1-mm reconstruction interval) was performed during power injection of 180 mL of ioversol at 5 mL/sec. Two radiologists reviewed 100 consecutive arterial phase helical CT scans of the pancreas in patients with normal glands and recorded the frequency of visualization of the major visceral (celiac, hepatic, splenic, gastroduodenal, superior mesenteric) and small pancreatic (dorsal pancreatic, right branch of the dorsal pancreatic, pancreaticomagna, caudal pancreatic, transverse pancreatic, anterior and posterior arcade, and inferior pancreaticoduodenal) arteries.
Scans in 87 patients were technically satisfactory and were included in the analysis. The major visceral arteries were seen in all patients. The following secondary pancreatic arteries were seen: dorsal pancreatic, 82 (94%) patients; pancreaticomagna, 45 (52%); caudal pancreatic, 34 (39%); transverse pancreatic, 36 (41%); right branch of the dorsal pancreatic, eight (9%); anterior arcade, 47 (54%); posterior arcade, 63 (72%); and inferior pancreaticoduodenal, 73 (84%).
Small pancreatic arteries can be delineated on arterial phase helical CT scans by using optimized techniques.
The expression CA195 in serum, defined by monoclonal antibody CC3C195 (IgM), was studied in 67 patients with pancreatic cancer and in 138 patients with biliary or pancreatic benign disease. The results were compared with carcinoembryonic antigen (CEA) expression. The overall sensitivity of the CA195 assay (> 12 U/ml) was higher than that for CEA (89.5% vs. 53.7%) (p < 0.001). Sensitivity was increased to 92.5% with the simultaneous use of the two antigens, but the difference was statistically significant only with CEA (p < 0.001). The specificity of CA195 calculated from all patients with benign diseases was lower than that of CEA (73.1% vs. 89.8%). However, using a cutoff value of 100 U/ml for CA195, the specificity of this antigen (82%) was higher than that of CEA. These results demonstrate that marked elevations of tumor antigen CA195 are relatively specific for pancreatic carcinoma, and that this antigen is superior to CEA for diagnosing pancreatic cancer by virtue of its higher sensitivity.
A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer.
No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other.
A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers.
Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA 19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.
The diagnostic value of the tumor marker pyruvate kinase type tumor M2 was evaluated in patients with benign, malignant and metastasizing pancreatic lesions and compared to the reference markers CA19-9 and CEA. This prospective study comprised 166 individuals; 66 patients had various pancreatic pathologies (38 histologically proven pancreatic cancer, 28 benign pancreatic lesions such as pseudotumorous pancreatitis, pseudocysts or pancreatic (cyst)adenoma) and 100 healthy blood donors served as controls. With a cut-off value of 28 U/ml (corresponding to a specificity of 90%) the sensitivity of TUM2-PK for pancreatic cancer (as related to the control group) was 79% (CA19-9: 65%, CEA: 22%). There was a good correlation between the TUM2-PK levels and tumor metastasis (p < 0.001 for no versus distant metastasis, p = n.s. for CA19-9 and CEA). However, TUM2-PK was also elevated in 64.3% of the patients with benign pancreatic pathologies. In our study TUM2-PK had good diagnostic qualities for pancreatic cancer and also showed better correlation to metastasis than CA 19-9 and CEA.
Clinicians might be misled in interpreting an elevated CA19-9 when differentiating pancreaticobiliary cancer from benign clinical conditions such as acute cholangitis or cholestasis, because in these conditions, the concentration of CA19-9 may also be elevated. The aims of our study were to calculate new individual cutoff values for CA19-9 according to clinical situations using a receiver operating characteristic (ROC) curve and to define a new strategy for interpreting CA19-9 in pancreaticobiliary cancer.
One hundred sixty patients with pancreatic diseases (cancer 90, benign disease 70), 322 patients with biliary tract diseases (biliary cancer 152, benign disease 170), and 20,035 asymptomatic controls were enrolled in the present study. An ROC curve was described by plotting the sensitivity on the y-axis against 1-specificity on the x-axis for each of several cutoff values.
The area under the ROC curve was significantly greater for pancreatic cancer than for biliary cancer (p < 0.05). For patients with pancreatic cancer, CA19-9 proved to be useful. At a cutoff value of 37 U/ml, sensitivity and specificity were 76.7% and 87.1%, respectively. For patients with biliary cancer, CA19-9 was not helpful. However, when patients with biliary disease were divided into two groups according to the presence of cholangitis or cholestasis, CA19-9 proved to be more useful for the group without cholangitis or cholestasis than for the group with cholangitis or cholestasis (p < 0.05). In the former group, the sensitivity and specificity of CA19-9 were 77.6% and 83%, respectively, at the cutoff value of 37 U/ml. For the latter group, the sensitivity and specificity of CA19-9 were 74% and 41.5% respectively, whereas the specificity reached 87% at 300 U/ml. CA19-9 in diagnosing pancreatic cancer was useful regardless of accompanying acute pancreatitis or cholestasis. The serum concentration of CA19-9 in asymptomatic individuals was 9.42 +/- 9.95 U/ml. Only 1 of 157 patients with a concentration of CA19-9 above 37 U/ml was found to have gallbladder cancer. The positive and negative predictive values were 0.65% and 0.78%, respectively.
The use of CA19-9 for the differentiation of pancreaticobiliary cancer should be applied individually, depending on the clinical situation.
The value of serum tissue polypeptide specific antigen (TPS) as a complement to CA 19-9 in the detection of pancreatic carcinoma was determined prospectively. TPS and CA 19-9 levels obtained at the time of diagnosis in patients suspected of having chronic pancreatitis or pancreatic carcinoma were evaluated in receiver operating characteristic (ROC) curve analysis.
Serum TPS and CA 19-9 levels were measured by immunoassays in 122 subjects, 48 with pancreatic carcinoma and 74 with chronic pancreatitis.
Elevated levels of CA 19-9 were detected preoperatively in 70% of pancreatic carcinoma patients and in 19% of chronic pancreatitis patients. Elevated levels of TPS were detected in 100% of patients with pancreatic carcinoma and in 22% of patients with chronic pancreatitis. The median levels of TPS and CA 19-9 for pancreatic carcinoma were significantly higher than those for chronic pancreatitis (P < 0.0001). Increasing the upper reference value of TPS allowed for better discrimination between chronic pancreatitis and pancreatic carcinoma. ROC curve analysis showed that the introduction of 200 U/L as a decision criterion for TPS did not reduce its sensitivity but significantly improved its specificity. At a specificity of 98% for TPS, discrimination between pancreatic carcinoma and chronic pancreatitis was found to be 97%. Increasing the upper reference level for CA 19-9 to attain a specificity of 98% decreased its sensitivity from 70% to 33%.
At an elevated cut-off level for TPS (200 U/L), almost complete discrimination between pancreatic carcinoma and chronic pancreatitis was obtained. TPS will be more useful than CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.
Preoperative diagnosis of pancreatic adenocarcinoma can be difficult. Computed tomography (CT) is the standard, noninvasive imaging method for evaluation of suspected pancreatic adenocarcinoma, but it has limited sensitivity for diagnosis, local staging, and metastases. Endoscopic ultrasound (EUS) and fluoro-deoxyglucose/positron emission tomography (FDG-PET) are imaging methods that may improve diagnostic accuracy.
Thirty-five patients with presumed resectable pancreatic adenocarcinoma were prospectively evaluated with helical CT, EUS, and FDG-PET.
Sensitivity for the detection of pancreatic cancer was higher for EUS (93%) and FDG-PET (87%) than for CT (53%). EUS was more sensitive than CT for local vascular invasion of the portal and superior mesenteric veins. EUS diagnosis of vascular invasion was associated with poor outcome after surgery. EUS-guided, fine-needle aspiration allowed tissue diagnosis in 14 of 21 attempts (67%). FDG-PET diagnosed 7 of 9 cases of proven metastatic disease, 4 of which were missed by CT. Two of three metastatic liver lesions suspected by CT were indeterminate for metastases. FDG-PET confirmed metastases.
EUS and PET improve diagnostic capability in pancreatic adenocarcinoma. EUS is useful in determining local vascular invasion and obtaining tissue diagnosis. FDG-PET is useful in identifying metastatic disease. Both techniques are more sensitive than helical CT for identification of the primary tumor. (Gastrointest Endosc 2000;52:367-71).
The tumour marker CA19-9 has been promoted as a reliable test for the detection of pancreatobiliary malignancy, yet its diagnostic role remains poorly defined. In this study the clinical interpretation of a raised serum CA19-9 level has been evaluated, with particular reference to obstructive jaundice.
One hundred and sixty-four patients with a CA19-9 level above 33 U/ml were studied. Serum CA19-9 was compared with clinical diagnosis and correlated with serum bilirubin level. In a subgroup of jaundiced patients (16 benign and 15 malignant cases), follow-up CA19-9 levels were determined 2 weeks after biliary drainage.
The median CA19-9 level was lower in benign cases (102 (IQR 50-264) U/ml) than those with pancreatobiliary tumours (910 (IQR 263-6170) U/ml; P<0.01), although the overlap was substantial. In benign jaundiced cases, a positive correlation was observed between bilirubin and CA19-9 elevation (R=0.41, P<0.01). Relief of jaundice was associated with a fall in CA19-9 level in all benign cases and in nine of the 15 with malignancy.
Confident discrimination between benign and malignant disease could not be made on the basis of a solitary elevated CA19-9 measurement. Hyperbilirubinaemia was associated with a further deterioration in specificity and caution is warranted when interpreting the results in jaundiced patients. Overall, only one half of patients with an elevated CA19-9 level ultimately proved to harbour a malignancy.
CA 19-9 and CEA were evaluated for their specificity and sensitivity in the early diagnosis of pancreatic carcinoma.
This prospective study included 40 patients with pancreatic carcinoma. A control group of 60 patients were divided into two subgroups as upper gastrointestinal system malignancies and benign pancreatic disorders. CEA and CA 19-9 levels were measured in all the patients.
When the reference value of CA 19-9 was accepted as 74 U/mL, the specificity was 100% when pancreatic carcinoma was compared with benign disorders of the pancreas, but it's specificity for upper gastrointestinal malignancies was 60-90%. When the reference value of CEA was increased, the sensitivity had been decreased but the specificity had been increased when compared with the control group. If the reference value of CEA was accepted as 5 ng/mL, the specificity was 100% when pancreatic carcinoma was compared with acute or chronic pancreatitis, but it is less specific for the differential diagnosis of pancreatic carcinoma from the upper gastrointestinal malignancies.
With the progression of the pancreatic carcinoma, serum CEA level and the specificity of CEA were elevated similar to that of CA 19-9. However, the elevation of CEA specificity when compared with the control group was lower than the specificity of the CA 19-9 and the sensitivity of CA 19-9 was superior to that of CEA for pancreatic carcinoma. The level of CA 19-9 was increased with the development of early pancreatic cancer and this elevation steadily continued with the progression of the cancer.
The diagnostic value of pyruvate-kinase type tumor M2 (Tumor M2-PK) has been investigated in different tumors, and showed interesting results in cases of renal cancer, pancreatic cancer, lung cancer and some cases of gastric cancer. In this study we investigated EDTA-plasma of 68 patients with gastrointestinal cancer, 22 patients with inflammatory bowel disease (IBD) and 60 healthy controls. Sensitivity of Tumor M2-PK was 70.6% for all GI-tumors, that of CA19-9 was 55.4% and that of CEA was 53.3%. In pancreatic cancer CA19-9 showed the best sensitivity. In oesophageal/gastric cancer Tumor M2-PK was most sensitive and in colorectal cancer CEA and Tumor M2-PK showed the best results. The specificity of Tumor M2-PK was 90-96, 7%. In IBD some individuals showed elevated Tumor M2-PK levels but there was no correlation to CRP or to the clinical activity score. The results indicated that Tumor M2-PK might be a valuable marker in gastrointestinal cancer.