Article

Analysis of mortality rates for gallbladder cancer across the world

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Abstract

Ethnic background and geographical location are important when measuring the incidence of gallbladder carcinoma leading to variable mortality rates across the world. Age standardized mortality rates [ASR(W)] were extracted separately for males and females from a database maintained by the International Agency for Research on Cancer for 50 countries across the world (Europe 32; the Americas 8; and Asia 10) for the period 1992-2002 and log-linear regression was performed to analyse trends in the last decade. In the period 1992-2002, declining trends in mortality for both sexes were observed in Germany, Sweden, Japan, USA, and Hungary (p<0.001), and in France, Canada, United Kingdom, The Netherlands, and Hong Kong (p<0.01). Austria, Czechoslovakia, Slovenia, Denmark, Spain, and Israel exhibited decreasing mortality trends more significant in women (p<0.01) than in men (p<0.05). Decreasing female mortality trends were seen in Finland, Italy, and Portugal (p<0.01) and in Georgia, Luxembourg, and Belgium (p<0.05). Iceland, Costa Rica, and Korea were the only countries with an increase in male mortality (p<0.05). Overall, there was a decline in ASR(W) for gallbladder cancer. Better diagnostic modalities resulting in appropriate staging of gallbladder/biliary cancers, as well as changes in the ICD classification and perhaps increased awareness, may have contributed to these trends.

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... Pancreatic cancer is the fourth most common cause of cancer death in the UK [1]. In the USA, this is predicted to become the second most common cause of cancer death by 2030, overtaking deaths from breast and prostate cancer [2]. ...
... Despite modern advances in medical imaging, improvements in operative techniques and molecular understanding of the disease pathophysiology, the overall survival rate is still very poor. Often the disease is spread outside the organ or locally advanced at the time of diagnosis, thereby preventing curative treatments or therapies [1]. Operative options are available to less than 15% of patients; these depend on the site of the cancer and can either lead to a pancreaticoduodenectomy or a distal pancreatectomy [5]. ...
... On the other hand, locally advanced pancreatic cancer patients have a median survival of 6-10 months [8]. The estimated survival of a patient with untreated metastatic disease, the commonest stage of the disease at diagnosis, is 3-5 months [1] chemotherapy. The key to improving patient outcomes and survival is research into earlier detection of this highly complex and heterogeneous disease, which requires novel, tailored treatment options for each patient [9]. ...
... Mortality rates from GBC have been decreasing in males from Colombia (1992Colombia ( -2002, Ecuador andMexico (1995-2007) but it has been increasing in Costa Rica (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002). In Chile mortality rates remained stable in both females and males (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) [13,18,19]. There are no clear reasons to explain the decrease in mortality, however better diagnostic tools, increase and standardization of gallstones surgery and changes in the international classification of diseases are thought to be responsible for the declines [18][19][20][21]. ...
... In Chile mortality rates remained stable in both females and males (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) [13,18,19]. There are no clear reasons to explain the decrease in mortality, however better diagnostic tools, increase and standardization of gallstones surgery and changes in the international classification of diseases are thought to be responsible for the declines [18][19][20][21]. Recent estimates indicate that the burden of GBC is expected to increase in the CSA region by more than 80% by the year 2030 (27,000 new cases and 24,000 deaths) due to demographic changes [11]. ...
... Stable incidence rates have also been described in other parts of the world [7]. Declines in female mortality rates of GBC have been reported in Mexico (1998Mexico ( -2004 and Venezuela (1970Venezuela ( -2004 [30] while in Colombia, Costa Rica and Ecuador mortality rates remained fairly constant during 1992-2002 [18]. Likewise, increases in male mortality rates have been reported in Mexico (1971Mexico ( -2004 and Costa Rica (1992Rica ( -2002; while in Ecuador (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002), Colombia (1992Colombia ( -2002 and Venezuela (1970Venezuela ( -2004 rates have declined [18,30]. ...
Article
Rationale and objective: Gallbladder carcinoma (GBC) is a rare neoplasm yet it is the most common malignancy of the biliary tract and its prognosis is poor. Incidence of GBC is high in some areas of Central and South America and the Caribbean. We described the current burden of GBC in Central and South America (CSA). Methods: We obtained GBC incidence data from 48 population-based cancer registries in 13 countries in CSA, and national level cancer death data from the WHO mortality data base for 18 countries. We estimated World population age-standardized incidence and mortality rates per 100,000 persons-years, including distribution and incidence rates by anatomic subsite. Results: GBC rates were the highest in countries located in the Andean region. In 2003-2007, Chile had the highest incidence and mortality rates in CSA (17.1 and 12.9 in females and 7.3 and 6.0 in males, respectively). Females had higher GBC rates than males. The most frequently diagnosed anatomic subsite was gallbladder (60%). Unspecified subsite represented 21% of all cases. Trends in incidence and mortality of GBC remained unchanged in Argentina, Brazil, Chile and Costa Rica in 1998-2008. Conclusion: GBC rates varied extensively across the CSA region reflecting, in part, differences in data quality, coverage and healthcare access. Chile had the highest GBC rates in CSA and the world. The large proportion of unspecified cases indicates low precision in diagnosis/registration and highlights the need to promote and improve cancer registration in the region to better understand the burden of GBC in CSA.
... This study was able to exclude the two main pathologyrelated factors implicated as sources of the survival differences reported for T2 GBC: (1) geographic differences in the application of pathologic T-staging criteria and (2) under-sampling phenomenon leading to under-staging. Accordingly, the differences in survival appear to be attributable to pathologic or biologic characteristics other than Tstage, such as different tumor characteristics, healthcare practices such as post-operative management, or regional differences in prognostic risk factors, and the pathogenesis of GBC [2,5,12,56,57]. ...
... Additionally, the frequency of gallstones in the general population as well as in patients with GBC has been reported to be much higher in Chile than in the Far East. Along those lines, the duration of biliary calculus disease and mutations in regulatory genes KRAS and TP53 have been shown to vary by populations, as reported in the literature [2,5,12,57]. Several other studies also demonstrate region-specific mutational profiles that may account for the geographic differences of GBC. ...
Article
Full-text available
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... Majority of gallbladder carcinoma are diagnosed in their advanced stages with histological subtype, grade, and stage of the tumor at the time of presentation contributing to its prognostic value [18]. As a consequence of its late diagnosis; the overall mean survival rate for patients with gallbladder carcinoma is 6 months, with a very poor 5-year survival rate of 5% [16,18]. ...
... Majority of gallbladder carcinoma are diagnosed in their advanced stages with histological subtype, grade, and stage of the tumor at the time of presentation contributing to its prognostic value [18]. As a consequence of its late diagnosis; the overall mean survival rate for patients with gallbladder carcinoma is 6 months, with a very poor 5-year survival rate of 5% [16,18]. ...
Article
Full-text available
Introduction The density of gallbladder carcinoma differs in different parts of the world. It is an aggressive tumor with poor prognosis presenting in advanced stages due to paucity of signs and symptoms. This research was conducted to analyze the frequency of incidental and clinically suspected gallbladder carcinoma with clinicopathological correlation. Methods This is a retrospective cohort study conducted in the Department of Pathology, Manipal College of Medical Sciences, Pokhara, Nepal from January 2005 to December 2020. Results The study included 35 cases of gallbladder carcinoma compiled over a period of 16 years. There were 11 males and 24 females with a male to female ratio of 1: 2.1. Age ranged from 29 to 75 years with a mean age of 56.51 ± 11.38 years. Incidental carcinoma was observed in 26 (74.28%) cases while clinically suspected carcinoma was identified in 9 (25.71%) cases. Gallstone was associated in 14 (40%) cases of incidental carcinoma. Tumor staging of both incidental and clinically suspected carcinomas showed 13 (37.14%) cases in T1 stage, 15 (42.85%) cases in T2 stage and 7(20%) cases in T3 stage. Conclusion Our analysis established prevalance of gallbladder carcinoma from 5th to 7th decades with female predominance and higher association of gallstones in incidental carcinoma. The principal histology in incidental carcinoma was well differentiated carcinoma while poorly differentiated carcinoma was encountered only in clinically suspected carcinoma.
... The risk factors for gallstones and gallbladder carcinoma include obesity, metabolic syndrome, and diabetes. There is a risk of malignancy in diabetes mellitus patients in the absence of concrements in the organ [23][24][25][26][27] . An anomalous junction of the pancreaticobiliary duct is a congenital malformation that is rare in Western countries; however, the malformation occurs frequently in Asian populations and especially Japan [28] . ...
... A prophylactic cholecystectomy is recommended for these patients. When considering the risk factors for gallbladder cancer, it is important to assess the management of gallbladder polyps that are present in up to 5% of adults and are more frequently diagnosed due to better imaging modalities [24,29] . Approximately 60% of gallbladder polyps are cholesterol polyps and 25% have an adenomyosis with hyperplastic mucosa. ...
Article
The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed "incidental or occult gallbladder carcinoma" (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stageadjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.
... 1,2 Several risk factors have been implicated in the development of GBC including female sex, gallstone disease, smoking, gallbladder polyps, obesity, diabetes mellitus, infection, and primary sclerosing cholangitis. [3][4][5] Despite the discovery of innovative surgical and chemotherapeutic treatments, GBC is still associated with high mortality and its incidence remains high in some geographical regions, such as Chile, India and populations, such as American Indians and Japanese. [6][7][8][9] Diagnosis is usually made in the noncurable advanced stage because of nonspecific clinical manifestations. ...
Article
Objectives: Primary gallbladder cancer (GBC) is the most common biliary tract cancer with poor survival despite aggressive treatment. This study aimed to investigate the trends of GBC incidence and incidence-based mortality (IBM) over the last 4 decades. Materials and methods: GBC cases diagnosed between 1973 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates, IBM rates, and annual percent changes (APCs) were calculated and stratified according to population and tumor characteristics. Results: The cohort consisted of 10,792 predominantly white (81%) and female (71%) GBC patients. The overall GBC incidence decreased by 1.65% (95% confidence interval [CI]: 1.45% to 1.84%) per year since 1973, but has plateaued since 2002. IBM decreased by 1.69% (95% CI: 1.22% to 2.16%) per year from 1980 to 2015; the rate of decrease in IBM rates was lower during 1997 to 2015 (APC: -1.19%, 95% CI: -1.68% to -0.71%) compared with 1980 to 1997 (APC: -3.13%, 95% CI: -3.68% to -2.58%). Conclusions: The incidence and IBM rates of GBC have been decreasing over the last 40 years, but the decrease plateaued over the last 2 decades. The effects of treatment modalities, including laparoscopic cholecystectomy, adjuvant chemotherapy, and radiation on the incidence and IBM of GBC need to be further investigated.
... 16 Population based data reveals that the incidences of these disease is very high in the northern cities (22 per 100,000) and low (0-0.7 per 100,000 women) in southern India. [17][18][19][20] The present institute caters the greatest number of cancer patients from the state of Bihar for the diagnosis and the treatment. ...
Preprint
Full-text available
Background In recent times Gallbladder cancer (GBC) incidences increased many folds in India. Majority of GBC cases are being reported from arsenic hotspots identified in Bihar. Methods In this prospective study volunteers were selected who underwent surgery in our cancer institute. There were 11 control benign gallbladder cases and 28 confirmed gallbladder cancer cases. Their biological samples such as blood, gallbladder tissue, gallbladder stone, bile and hair samples were collected for arsenic estimation. Moreover, n=512 gallbladder cancer patients blood samples were evaluated for the presence of arsenic to understand exposure level in the population. Results A significantly high arsenic concentration (p<0.05) was detected in the blood samples, gallbladder tissue, gallstones, bile and hair samples in comparison to the control group. Moreover, n=512 blood samples of GBC patients had significantly very high arsenic concentration. Conclusions The study shows very high arsenic concentration observed in the blood, gallbladder tissue, gallbladder stone, bile and hair samples in GBC cases in comparison to the benign control cases indicates the correlation between chronic arsenic exposure and gallbladder cancer incidences in eastern Indo-Gangetic plains region. The study also makes an attempt to establish the likely correlation/association between arsenic exposure and gallbladder cancer disease.
... Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm, and is highly aggressive and malignant with a very low survival rate. Nowadays, as a devastating disease, PDAC is the fourth most common disease-associated mortality worldwide (1,2). The 5-year survival rate is ~6%, and only 20% of patients present with resectable disease (3,4). ...
Article
Full-text available
The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present anti‑human immunodeficiency virus‑1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored. The cytotoxicity assay, apoptosis assay, western blotting, migration and invasion assay, and a PDAC cell (AsPC‑1, BxPC‑3 and PANC‑1) xenograft mice model were employed. The results demonstrated that treatment with cordifoliketones A: i) inhibited proliferation and promoted apoptosis of PDAC cells; ii) significantly induced apoptosis and altered expression of apoptosis‑associated proteins in a dose‑dependent manner; iii) suppressed migration and invasion of PDAC cells in a dose‑dependent manner; and iv) restrained the growth of PDAC neoplasm in nude mice. Furthermore, cordifoliketones A demonstrated non‑cytotoxic activity in a panel of normal human cells, including hTERT‑HPNE, 293, hepatocyte HL‑7702 and HL‑1 cells. Therefore, these data indicated that cordifoliketones A may be a potential candidate compound for the prevention of PDAC cell proliferation and metastasis, presumably by induction apoptosis and inhibiting viability, invasion and migration of PDAC cells.
... The majority of the world has decreasing mortality trends in gallbladder cancer but GBC frequency is constantly rising in Shanghai, China which is substantial cause of mortality [7] . Although Gallbladder cancer is more common in females still in some countries like Korea, Iceland and Costa Rica, higher mortality rate has been reported for males as compare to females [8] . The data from National Cancer Institute; SEER Program (http:// seer.cancer.gov/) ...
Article
Full-text available
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/ pubmed,https://scholar.google.co.in/, http://www. medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
... Por ejemplo, en las mujeres del norte de la India el CVB se manifiesta entre 2 a 6 veces más que los hombres (22). Un meta-análisis que incluyó 8 estudios de cohorte y 4 de caso-control confirman esta situación de mayor riesgo en las mujeres RR = 1,88 (IC 95%: 1,66-2,13) que los hombres RR = 1,35 (IC 95%: 1,09-1,68) (24). Las mujeres chilenas de la ciudad de Valdivia presentan la incidencia de CVB más alta del mundo, con una tasa ajustada por edad de 12,8 por cada 100.000 individuos (8). ...
Article
Full-text available
Gallbladder cancer is the most malign neoplasm of the biliary tract. Chile presents the third highest prevalence of gallbladder cancer in the Americas, being Chilean women from the city of Valdivia the ones with the highest prevalence. The main risk factors associated with gallbladder cancer are: sex, cholelithiasis, obesity, ethnicity, chronic inflammation, history of infection diseases such as Helicobacter pylori and Salmonella and family history of gallbladder cancer. In Chile gallbladder cancer mortality is close to prevalence level. This is related to the silent symptomatology of this cancer, as well as the lack of specific symptoms. The high prevalence of obesity and infectious diseases present in Chile are two of the main risk factors of gallbladder cancer and Chile has prevalence of obesity close to 30% The aim of this literary review is to inform and summarize the main risk factors of gallbladder cancer that are prevalent in Chile, in order to be able to focus preventive and management interventions of this risk factor for the reduction in prevalence and mortality of gallbladder cancer in Chile.
... Por ejemplo, en las mujeres del norte de la India el CVB se manifiesta entre 2 a 6 veces más que los hombres (22). Un meta-análisis que incluyó 8 estudios de cohorte y 4 de caso-control confirman esta situación de mayor riesgo en las mujeres RR = 1,88 (IC 95%: 1,66-2,13) que los hombres RR = 1,35 (IC 95%: 1,09-1,68) (24). Las mujeres chilenas de la ciudad de Valdivia presentan la incidencia de CVB más alta del mundo, con una tasa ajustada por edad de 12,8 por cada 100.000 individuos (8). ...
Article
Full-text available
El cáncer de vesícula biliar es la neoplasia maligna más común en el tracto biliar. Chile presenta la tercera prevalencia más alta de cáncer de vesícula en el continente americano, siendo las mujeres chilenas de la ciudad de Valdivia las que presentan la prevalencia más alta.Los principales factores que se han asociado al cáncer de vesícula son: ser mujer, colelitiasis, obesidad, etnia, inflamación crónica, historia de enfermedades infecciones, como H. pylori y Salmonella e historia familiar de cáncer.En Chile la mortalidad por cáncer de vesícula es cercana al nivel de prevalencia. Esto se debe en parte a que el cáncer de vesícula es una enfermedad silenciosa y sin síntomas específicos en primeras instancias.Presentar obesidad y ser portador de agentes infecciosos, como Helicobacter pylori, son dos de los factores de riesgo más importantes para desarrollar cáncer de vesícula en Chile, ya que existe y una prevalencia de obesidad cercana al 30%.El objetivo de esta revisión literaria es informar y resumir los factores de riesgo de cáncer de vesícula prevalentes en Chile, para así enfocarse en la prevención y cuidado de estos, con el propósito de reducir la prevalencia de esta letal enfermedad.
... AQ4 ds: pancreatic cancer, pancreatic biopsy, ' (Surg Laparosc Endosc Percutan Tech 2016;00:000-000) P ancreatic cancer is the fourth leading cause of cancerrelated deaths worldwide. 1 Ductal adenocarcinoma is the most common epithelial type, accounting for over 80% of malignant neoplasms. 2 It is an aggressive cancer and the majority of patients present late with unresectable disease and a median survival of between 3 and 10 months. ...
Article
Purpose: To determine the accuracy and safety of the percutaneous biopsy of pancreatic mass lesions. Materials and methods: Over a 12-year period clinical parameters, imaging, pathologic results, and complications were assessed in patients undergoing percutaneous biopsies pancreatic lesions. Results: One hundred fifty-three patients underwent pancreatic biopsy. The preferred modality for performing the biopsy was ultrasound (93%, n=143) followed by computerized tomography (7%, n=10). Histologic diagnosis was achieved in 147 patients, of which 3 (2%) were benign and 144 (94%) were malignant. Complications included a single death from overwhelming hemorrhage and 2 patients with morbidity (hematoma and cerebrovascular accident). The sensitivity and specificity of percutaneous biopsies was 90% and 95%, respectively. Conclusions: Ultrasound-guided and computerized tomographic-guided percutaneous biopsy of pancreatic lesions is an effective and safe method to confirm or refute malignancy in suspicious pancreatic lesions. Endoscopic ultrasound-guided Tru-Cut may have the added advantage of avoiding the risk of peritoneal soiling.
... Previous studies showed that obesity is a predisposition for the development of GBC [29]. The likelihood of developing the disease increases by 1.1 for men and 1.6 for women with every 5-point rise in BMI [30,31]. It is known that metabolic syndrome exacerbates serious co-morbidities, such as diabetes, in people with a BMI of > 30 kg/m 2 , and diabetes is a strong risk factor for the formation of gallstones [32]. ...
Article
Full-text available
Background: There is paucity in the literature regarding gallbladder cancer in Saudi Arabia, possibly because it is not among the top 10 cancers diagnosed nationwide according to the Saudi Cancer Registry. Moreover, national or regional data on gallbladder cancer in Saudi Arabia have not been analyzed. The purpose of this study was to describe the presentation, disease stage, histology, and survival rates for gallbladder cancer in Saudi patients at a single institution between January 1, 2010 and December 31, 2017. Materials and methods: This was a retrospective study of 76 patients who presented to our hospital between January 1, 2010 and December 31, 2017, with established diagnosis of gallbladder carcinoma. The diagnosis was made either histopathologically following simple laparoscopic cholecystectomy or biopsy from metastatic liver lesion in patients with gallbladder mass, or the high suspicion of gallbladder carcinoma based on incidental radiological findings. Presentation, disease stage, histology, and treatment modalities were analyzed using descriptive statistics and frequency distributions. Survival rates were analyzed and presented using Kaplan-Meier curves. Results: Based on initial analyses the disease was more frequent among women (62.0%) than men (39.0%). Surgical resection was attempted in 40.8% patients. The average age at presentation and diagnosis of gallbladder carcinoma was 62.4 years. The disease had two peaks, one at 51.0 years and the other between 66.0 and 70.0 years. The median survival time for the overall at-risk patients was only 1.0 year, while for stage IVB patients was 7.2 months. Adenocarcinoma not otherwise specified (NOS) was the most common histopathology type (75.0%), with most patients presenting with stage IVB disease (75.0%). Gallbladder carcinoma was incidentally detected in 42.1%, including three cases (3.9%) diagnosed at our hospital. Conclusions: Gallbladder cancer is a rare type of cancer in Saudi Arabia, and most patients are treated surgically, despite being mostly diagnosed at the advanced stage of the disease.
... Por ejemplo, en las mujeres del norte de la India el CVB se manifiesta entre 2 a 6 veces más que los hombres (22). Un meta-análisis que incluyó 8 estudios de cohorte y 4 de caso-control confirman esta situación de mayor riesgo en las mujeres RR = 1,88 (IC 95%: 1,66-2,13) que los hombres RR = 1,35 (IC 95%: 1,09-1,68) (24). Las mujeres chilenas de la ciudad de Valdivia presentan la incidencia de CVB más alta del mundo, con una tasa ajustada por edad de 12,8 por cada 100.000 individuos (8). ...
Article
Full-text available
Gallbladder cancer is the most malign neoplasm of the biliary tract. Chile presents the third highest prevalence of gallbladder cancer in the Americas, being Chilean women from the city of Valdivia the ones with the highest prevalence. The main risk factors associated with gallbladder cancer are: sex, cholelithiasis, obesity, ethnicity, chronic inflammation, history of infection diseases such as Helicobacter pyloriand Salmonellaand family history of gallbladder cancer. In Chile gallbladder cancer mortality is close to prevalence level. This is related to the silent symptomatology of this cancer, as well as the lack of specific symptoms. The high prevalence of obesity and infectious diseases present in Chile are two of the main risk factors of gallbladder cancer and Chile has prevalence of obesity close to 30%. The aim of this literary review is to inform and summarize the main risk factors of gallbladder cancer that are prevalent in Chile, in order to be able to focus preventive and management interventions of this risk factor for the reduction in prevalence and mortality of gallbladder cancer in Chile.
... Consequently, the median survival rate is only 3-6 mo. Even the most favorable patients who undergo resection with adjuvant therapy show 5-year survival rates < 29%; for patients with metastatic advanced pancreatic cancer, surgery offers no advantage over palliative treatment and the prognosis is poor [6] . Although the spread of pancreatic cancer cells can be controlled in part by chemotherapy, it is often administered too late to be of therapeutic benefit and the toxic side effects are severe, causing some patients to give up treatment. ...
Article
Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.
... By contrast, gallbladder cancer is rare in the western world (USA, UK, Canada, Australia, and New Zealand) with incidence rates of 0.4-0.8 in men and 0.6-1.4 in women per 100,000 [10]. In keeping with this, a retrospective review of the International Agency for Research on Cancer identified increasing rates of male gallbladder cancer mortality only in Iceland, Costa Rica, and Korea with declining rates in all other countries studied [11]. This geographic variability is most likely attributable to differences in environmental exposures and a regional intrinsic predisposition to carcinogenesis [7]. ...
Article
Full-text available
Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC.
... The incidence of GBC shows significant geographic and ethnic variations (Hariharan et al., 2008). The highest incidence of GBC has been reported for populations living in the western parts of the Andes, and in North-American Indians, Mexican Americans, and inhabitants of northern India (Lazcano-Ponce et al., 2001). ...
Article
Our previous study detected aflatoxins in red chili peppers from Chile, Bolivia, and Peru, each of which have a high incidence of gallbladder cancer (GBC). Since the aflatoxin B1 concentration was not so high in these peppers, it is important to clarify the presence of other mycotoxins. Here we attempted to determine any associations between the concentrations of aflatoxins and ochratoxin A (OTA) in red chili peppers, and the corresponding GBC incidences. We collected red chili peppers from three areas in Peru: Trujillo (a high GBC incidence area), Cusco (an intermediate GBC incidence area), and Lima (a low GBC incidence rate), and from Chile and Bolivia. Aflatoxins and OTA were extracted with organic solvents. The concentrations of aflatoxins B1, B2, G1, and G2, and OTA were measured by high-performance liquid chromatography. The values obtained were compared with the incidence of GBC in each area or country. All of the red chili peppers from the three areas showed contamination with aflatoxins below the Commission of the European Communities (EC) recommended limits (5 μg/kg), but the OTA contamination of two samples was above the EC recommended limit (15 μg/kg). The mean concentrations of OTA in the peppers from Chile (mean 355 μg/kg, range <5-1,059 μg/kg) and Bolivia (mean 207 μg/kg, range 0.8-628 μg/kg), which has a high incidence of GBC, were higher than that in Peru (14 μg/kg, range <5-47 μg/kg), which has an intermediate GBC incidence. The OTA contamination in the red chili peppers from Chile, Bolivia, and Peru was stronger than that of aflatoxins. Our data suggest that OTA in red chili peppers may be associated with the development of GBC.
... Various risk factors are reported to be associated with GBC, out of which gallstone is considered one of the primary factors. [5,6] There is high incidence of GBC in India. The major published data from Indian population demonstrates the highest prevalence in North and Eastern part of India. ...
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BACKGROUND: We have reported here the 5‑year incidence (2004–2008) of gallbladder cancer (GBC) in North Central India along with its descriptive epidemiology. This provides potential clues for better prevention. The present study has also evaluated the association of ABO blood groups with GBC. PATIENTS AND METHODS: The study comprised 742 GBC cases referred to the regional cancer hospital, Gwalior, during 2004–2008. The demographic statistics of Gwalior district was considered to calculate the relative risk and incidence rates. ABO blood group distribution amongst90,000 healthy subjects registered in the local blood bank during 2002–2007 was taken as controls to study the association of blood groups with GBC. RESULTS: The age‑standardized total incidence rate of GBC was calculated to be 7.16/1,00,000. The relative risk of females getting GBC was2.693 at 95% confidence interval of 2.304–3.151 (P < 0.0001). The females formed 69.5% of total cancer cases, with age‑standardized incidence rate of 10/1,00,000. The mean age of male and female GBC cases was found to be 55.4 years (SD = 13, SE = 0.77) and 51.5 years (SD = 12.3,SE = 0.50), respectively. The blood groups A ( P = 0.0022) and AB ( P < 0.0001) had a positive association with GBC with significant level of differences in comparison to controls. CONCLUSION: Our study provided an estimate of a 5‑year incidence of GBC in North Central India for the first time. With regard to the association of risk factors like obesity, age, and urban living with GBC, the findings of the present study are contradictory to the general opinion. Blood groups A and AB were found to be associated with GBC, which would be provisional for further investigations.
... In the last 30 years, GBC and PHC have shown a decreasing and an increasing trend, respectively, in mortality rates [37,38]. GBC, specifically, in the Mediterranean area, was originally more prevalent than PHC mainly in subjects with prior cholelithiasis [39]. ...
Article
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Purpose: Bile is a hepatobiliary lipid-rich sterile solution, and its colonization by microorganisms defines the condition of bactibilia. In this study, we aimed to assess the bile microbiological flora and its potential link with comorbidity in women. Methodology: We performed a microbiologic investigation on 53 female patients with biliopancreatic diseases who granted consent, and we analysed the data using a MATLAB platform. Results: We found that the most frequent disease associated with bactibilia was pancreas head carcinoma (PHC) (P=0.0015), while the least frequent disease was gall bladder carcinoma (GBC) (P=0.0002). The most common microorganisms were Pseudomonas spp. (P<0.0001) and Escherichia coli (P<0.0001). In particular Pseudomonas spp. and E. coli were negatively correlated to PHC presence and positively correlated to CCA by both univariate and multivariate analysis. Conclusions: Gram-negative bacteria have been linked to a tumour-associated inflammatory status. In the last 30 years, the analysis of mortality rate in Italy for PHC and GBC shows an increasing and a decreasing trend, respectively. Although this study targeted only 53 patients and does not reflect the frequency of diagnosis in a Southern Italian population, the decrease in GBC may raise the suggestion ofnon-adherence to a Mediterranean diet that may have become more prevalent in Southern Italy since the 1990s.
... The authors attribute this decline to the increased awareness of this disease and better diagnostic modalities resulting in appropriate staging of gallbladder and biliary cancers. 5 Another recent study that analyzed data from the Danish Cancer Registry reported a minor improvement observed in the 5-year relative survival from 6% to 9% to 13% to 16% in the past 15 years for all age groups except those aged 90+ years. 6 A previous published study conducted in our university revealed 33 GBC out of 4502 cholecystectomies performed over a period of 7 years. ...
Article
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Background and Study Aims The prevalence of gallbladder cancer (GBC) varies between different parts of the world. This study is a review of literature and an update of a previously published study conducted in our university and aims to reassess the incidence of GBC over the past 2 decades. Patients and Methods We conducted a retrospective study between 2002 and 2016. Data regarding demographics, clinical presentation, risk factors, histopathology, investigations, and treatments were obtained. A diagnosis of GBC established during surgery or primarily detected in the surgical specimen was classified as incidental. Results Of 11 391 cholecystectomies performed, 31 cases (0.27%) of GBC were found. The mean age of patients with GBC was 68 years (43-103 years), 74% were women. The annual incidence of GBC was 0.2/100 000 (men: 0.1/100 000; women: 0.3/100 000). Biliary colic and acute cholecystitis were the main presentations. Diagnosis of GBC was “incidental” in 67% of cases. About 75% of patients with GBC had gallstones, 13% had polyps, and 3% had porcelain gallbladder. Adenocarcinoma was the dominant (87%) histologic type. Conclusions The GBC rate in our region, similar to others parts of the world, is still low and has not changed over the past 2 decades. This study consolidates the previously published recommendations regarding the high index of suspicion of GBC in elderly with cholelithiasis.
... The prevalence of GBPs in the general population has been estimated to be approximately 5%. (18,20,21) Some studies have reported a higher prevalence of gallbladder cancer in patients with UC and to some extent patients with CD. (22,23) However, available data suggest this association is most likely secondary to concomitant PSC and not to IBD independently. (7) The findings of this study also suggest that GBPs in patients with PSC occur independent of the underlying IBD. ...
Article
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The prevalence polyps (GBPs) in the general population has been estimated to be approximately 5%, with up to 10% of these being dysplastic or malignant. Previous studies have suggested that patients with primary sclerosing cholangitis (PSC) have increased frequency of GBPs. However, data on the prevalence, risk factors, and outcome of GBPs in these patients are sparse. This case‐control study investigates the frequency, risk factors, and outcome of GBPs in patients with PSC. In this study, 363 patients with an established diagnosis of PSC based on magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or liver biopsy were identified. Patients with at least one abdominal imaging and no history of cholecystectomy before the first available abdominal imaging were included. The presence of GBPs was confirmed by abdominal computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. Patients with GBPs were compared to those without GBPs. Furthermore, patients with malignant/premalignant polyps were compared to those with benign polyps. The frequency of GBPs in patients with PSC was 10.6%. There was no significant difference in the frequency of inflammatory bowel disease (IBD) between the two groups. Of the 16 with GBPs who underwent cholecystectomy, 10 had malignant/premalignant lesions, of whom 6 had adenocarcinoma, and 4 had high‐grade dysplasia. Of the 6 patients with adenocarcinoma, 4 had lesions >10 mm, 1 had a lesion as small as 4 mm, and 1 had a 7‐mm lesion. Conclusion: GBPs may be frequently seen in patients with PSC. These lesions seem to occur independent of IBD. In patients with PSC, even small GBPs appear to have a risk of malignancy. These findings suggest that patients with PSC and GBPs may benefit from cholecystectomy, regardless of the size of the polyp.
... hepatomegaly, ascites or duodenal obstruction . Various risk factor are reported to be associated with gall bladder carcinoma ,out of which gall stone is considered on the [5] [6] primary factors Risk of gall bladder carcinoma increase in anomalous pancreatico-biliary duct junction, gall stone ,xantho-granulomatous cholecystitis ,calcified or porcelain gall bladder ,cholecystitis with typhoid carrier, gall bladder a d e n o m a , r e d m e a t c o n s u m p t i o n a n d t o b a c c o [7] uses. Radiological features in the form of gall bladder wall thickening are largely non specific and may masquerade as [8] chronic cholecystitis. ...
Article
BACKGROUND: Gall bladder carcinoma is most common malignancy of the biliary tract and seventh most common gastrointestinal malignancy. Histologically most gall bladder carcinoma are pancreaticobiliary type adenocarcinoma, showing variable degrees of differentiation.The determination of the histology type of tumour and differential diagnosis from gall bladder adenocarcinoma are often difficult. It has unique significant and striking gender, geographic and ethnic variation in the incidence worldwide. MATERIAL AND METHOD: It is retrospective record based study, performed in department of Pathology RIMS, Ranchi. Study population included all cases who were operated for different pathology of gall bladder,with some common clinical presentations of upper right quadrant abdominal pain, jaundice, nausea and vomiting, from January 2018-December 2019. RESULT: Among the spectrum of gall bladder diseases most common finding was chronic cholecystitis, incidence of gall bladder carcinoma is a rare entity. In our present study female preponderance has been noted and mostly incidence is among the age group above 30 years.
... Pancreatic ductal adenocarcinoma (PDAC) is a near universally fatal disease with a 5 year survival of 9% (1,2). While cancers such as melanoma, renal cell carcinoma and non-small cell lung cancer appear relatively sensitive to cytotoxic T-cell based checkpoint inhibition, PDAC has been resistant (3). ...
Article
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Background: The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) contains abundant immunosuppressive tumor-associated macrophages. High level of infiltration is associated with poor outcome and is thought to represent a major roadblock to lymphocyte-based immunotherapy. Efforts to block macrophage infiltration have been met with some success, but noninvasive means to track tumor-associated macrophagess in PDAC are lacking. Translocator protein (TSPO) is a mitochondrial membrane receptor which is upregulated in activated macrophages. We sought to identify if a radiotracer-labeled cognate ligand could track macrophages in PDAC. Materials and methods: A murine PDAC cell line was established from a transgenic mouse with pancreas-specific mutations in KRAS and p53. After confirming lack of endogenous TSPO expression, tumors were established in syngeneic mice. A radiolabeled TSPO-specific ligand ([11C] peripheral benzodiazepine receptor [PBR]28) was delivered intravenously, and tumor uptake was assessed by autoradiography, ex vivo, or micro-positron emission tomography imaging. Results: Resected tumors contained abundant macrophages as determined by immunohistochemistry and flow cytometry. Immunoblotting revealed murine macrophages expressed TSPO with increasing concentration on activation and polarization. Autoradiography of resected tumors confirmed [11C]PBR28 uptake, and whole mount sections demonstrated the ability to localize tumors. To confirm the findings were macrophage specific, experiments were repeated in CD11b-deficient mice, and the radiotracer uptake was diminished. Micro-positron emission tomography imaging validated radiotracer uptake and tumor localization in a clinically applicable manner. Conclusions: As new immunotherapeutics reshape the PDAC microenvironment, tools are needed to better measure and track immune cell subsets. We have demonstrated the potential to measure changes in macrophage infiltration in PDAC using [11C]PBR28.
... GBC incidence increases with advanced age, with a median age at diagnosis of 69 years [7]. Additional risk factors commonly implicated in the pathogenesis of GBC include cholelithiasis, chronic biliary tract infection (Salmonella typhi, Helicobacter species), tobacco use, prolonged fertility, obesity, primary sclerosing cholangitis, and exposure to metals and metalloids including arsenic [8][9][10][11][12][13][14]. ...
Article
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The scope of our study was to compare the predictive ability of American Joint Committee on Cancer (AJCC) 7th and 8th edition in gallbladder carcinoma (GBC) patients, investigate the effect of AJCC 8th nodal status on the survival, and identify risk factors associated with the survival after N reclassification using the National Cancer Database (NCDB) in the period 2005–2015. The cohort consisted of 7743 patients diagnosed with GBC; 202 patients met the criteria for reclassification and were denoted as stage ≥III by AJCC 7th and 8th edition criteria. Overall survival concordance indices were similar for patients when classified by AJCC 8th (OS c-index: 0.665) versus AJCC 7th edition (OS c-index: 0.663). Relative mortality was higher within strata of T1, T2, and T3 patients with N2 compared with N1 stage (T1 HR: 2.258, p < 0.001; T2 HR: 1.607, p < 0.001; Τ3 HR: 1.306, p < 0.001). The risk of death was higher in T1–T3 patients with Nx compared with N1 stage (T1 HR: 1.281, p = 0.043, T2 HR: 2.221, p < 0.001, T3 HR: 2.194, p < 0.001). In patients with AJCC 8th edition stage ≥IIIB GBC and an available grade, univariate analysis showed that higher stage, Charlson–Deyo score ≥ 2, higher tumor grade, and unknown nodal status were associated with an increased risk of death, while year of diagnosis after 2013, academic center, chemotherapy. and radiation therapy were associated with decreased risk of death. Chemotherapy and radiation therapy were associated with decreased risk of death in patients with T3–T4 and T2–T4 GBC, respectively. In conclusion, the updated AJCC 8th GBC staging system was comparable to the 7th edition, with the recently implemented changes in N classification assessment failing to improve the prognostic performance of the staging system. Further prospective studies are needed to validate the T2 stage subclassification as well as to clarify the association, if any is actually present, between advanced N staging and increased risk of death in patients of the same T stage.
... 11,19,20 Although GBC is more common in female patients, in some countries like Korea, Iceland, and Costa Rica, higher mortality rates have been reported for male patients. 21 When it comes to the genetic basis of GBC, like others neoplasia, this tumor is a multifactorial disorder involving multiple genetic alterations seen in several ethnicities. 7,8 Many studies were performed to understand how certain types of genetic alterations act in GBC. ...
Article
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Prognostic markers for cancer can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Gallbladder cancer (GBC) is a rare tumor that causes 165 087 deaths in the world annually. It is the most common cancer of the biliary tract and has a particularly high incidence in Chile, Japan, and northern India. Currently, there is no accurate diagnosis test or effective molecular markers for GBC identification. Several studies have focused on the discovery of genetic alterations in important genes associated with GBC to propose novel diagnosis pathways and to create prognostic profiles. To achieve this, we performed data-mining of GBC in public repositories, harboring 133 samples of GBC, allowing us to describe relevant somatic mutations in important genes and to propose a genetic alteration atlas for GBC. In our results, we reported the 14 most altered genes in GBC: arid1a, arid2, atm, ctnnb1, erbb2, erbb3, kmt2c, kmt2d, kras, pik3ca, smad4, tert, tp53, and znf521 in samples from Japan, the United States, Chile, and China. Missense mutations are common among these genes. The annotations of many mutations revealed their importance in cancer development. The observed annotations mentioned that several mutations found in this repository are probably oncogenic, with a putative loss-of-function. In addition, they are hotspot mutations and are probably linked to poor prognosis in other cancers. We identified another 11 genes, which presented a copy number alteration in gallbladder database samples, which are ccnd1, ccnd3, ccne1, cdk12, cdkn2a, cdkn2b, erbb2, erbb3, kras, mdm2, and myc. The findings reported here can help to detect GBC cancer through the development of systems based on genetic alterations, for example, the development of a mutation panel specifically for GBC diagnosis, as well as the creation of prognostic profiles to accomplish the development of GBC and its prevalence.
... 11,19,20 Although GBC is more common in female patients, in some countries like Korea, Iceland, and Costa Rica, higher mortality rates have been reported for male patients. 21 When it comes to the genetic basis of GBC, like others neoplasia, this tumor is a multifactorial disorder involving multiple genetic alterations seen in several ethnicities. 7,8 Many studies were performed to understand how certain types of genetic alterations act in GBC. ...
Article
Full-text available
Prognostic markers for cancer can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Gallbladder cancer (GBC) is a rare tumor that causes 165 087 deaths in the world annually. It is the most common cancer of the biliary tract and has a particularly high incidence in Chile, Japan, and northern India. Currently, there is no accurate diagnosis test or effective molecular markers for GBC identification. Several studies have focused on the discovery of genetic alterations in important genes associated with GBC to propose novel diagnosis pathways and to create prognostic profiles. To achieve this, we performed data-mining of GBC in public repositories, harboring 133 samples of GBC, allowing us to describe relevant somatic mutations in important genes and to propose a genetic alteration atlas for GBC. In our results, we reported the 14 most altered genes in GBC: arid1a, arid2, atm, ctnnb1, erbb2, erbb3, kmt2c, kmt2d, kras, pik3ca, smad4, tert, tp53, and znf521 in samples from Japan, the United States, Chile, and China. Missense mutations are common among these genes. The annotations of many mutations revealed their importance in cancer development. The observed annotations mentioned that several mutations found in this repository are probably oncogenic, with a putative loss-of-function. In addition, they are hotspot mutations and are probably linked to poor prognosis in other cancers. We identified another 11 genes, which presented a copy number alteration in gallbladder database samples, which are ccnd1, ccnd3, ccne1, cdk12, cdkn2a, cdkn2b, erbb2, erbb3, kras, mdm2, and myc. The findings reported here can help to detect GBC cancer through the development of systems based on genetic alterations, for example, the development of a mutation panel specifically for GBC diagnosis, as well as the creation of prognostic profiles to accomplish the development of GBC and its prevalence.
... Gallbladder cancer (GBC) is a multi-factorial disease with diverse risk factors including gallstones, obesity, reproductive factors, chronic infection, and environmental exposure to specific chemicals [1][2][3][4]. It is the fifth most common malignant neoplasm of the digestive tract and despite recent advances in the diagnosis and management of gastrointestinal cancers, this cancer presents with a dismal prognosis [5]. The frequency of this cancer increases with age and reaches peak value after fifth decade of life [6]. ...
Article
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Background: Chronic inflammation is considered as an emerging area of research interest because of its cognize association with different organ cancers. Recent advances in cancer research have substantiated that targeting cytokines have a strong therapeutic potential in reducing the mortality of inflammation-related cancers. Gallbladder cancer (GBC) has been consistently associated with inflammation mostly due to presence of gallstones which prelude inflammatory response. The Interleukin-1 (IL1) gene cluster serves an important function of immunomodulation, thereby regulating interplay between inflammation and cancer. Studies on the association of IL1 polymorphisms with GS and GBC have shown drastic variations in different populations. Since no such study has been carried out in ethnic Kashmiri population which is known for high incidence of GS disease, we aimed to evaluate the possible role of pro-inflammatory IL1 family in the pathogenesis of GBC and GS disease.
... Currently, approximately 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC), which are the most aggressive form and the fourth leading cause of cancer death with extremely poor prognosis [1]. Poor prognosis is primarily attributed to the late diagnosis of the disease when patients are no longer candidates for surgical resection [2]. ...
Chapter
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Currently, approximately 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC), which are the most aggressive form and the fourth leading cause of cancer death with extremely poor prognosis [1]. Poor prognosis is primarily attributed to the late diagnosis of the disease when patients are no longer candidates for surgical resection [2]. Cancer cells are dependent on the oncogenes that allow them to proliferate limitlessly. Thus, targeting the expression of known oncogenes in pancreatic cancer has been shown to lead to more effective treatment [3]. This chapter discusses the complexity of metabolic features in pancreatic cancers. In order to comprehend the heterogeneous nature of cancer metabolism fully, we need to take into account the close relationship between cancer metabolism and genetics. Gene expression varies tremendously, not only among different types of cancers but also within the same type of cancer among different patients. Cancer metabolism heterogeneity is often prompted and perpetuated not only by mutations in oncogenes and tumor-suppressor genes but also by the innate diversity of the tumor microenvironment. Much effort has been focused on elucidating the genetic alterations that correlate with disease progression and treatment response [4, 5]. However, the precise mechanisms by which tumor metabolism contributes to cancer growth, survival, mobility, and aggressiveness represent a functional readout of tumor progression (Fig. 1).
... The reasons behind our younger age patients are difficult to speculate, but demographic and ethnic factors might play a role. The key implication is that, in this region, health professionals need to have a higher index of suspicion for GC among younger patients, which calls for more proactive work-up among this age group to rule out GC. Another point is that younger GC patients have better survival, partly explained by the better performance status and better chemotherapy tolerance [25] and this again calls for more aggressive therapeutic interventions among these younger patients. ...
Article
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Background: Gallbladder cancer (GC) is a relatively rare disease. To date, there are no studies describing the epidemiology of this disease in Qatar. Objective: To study the epidemiology of Gallbladder Cancer in Qatar. Methods: A retrospective analysis of the cases of GC in Hamad General Hospital in Qatar from 2009 to 2016. Results: Thirty-five patients presented with GC during the study period, 10 females (28.6%) and 25 males (71.4%). Fourteen patients (40%) were diagnosed incidentally after laparoscopic cholecystectomy, 16 (48.6%) were diagnosed pathologically, and 4 (11.4%) were diagnosed radiologically. The median age at diagnosis was 54 years (31-78). 74.3% of the disease occurred in patients less than 60 years old. Metastatic disease was discovered in 25 patients (71.4%) versus no metastasis in 10 patients (28.6%). The most common sites for metastasis were the liver (42.9%), peritoneum (25.7%), and lymph nodes (25.7%). Curative central hepatic resection was done in 8 patients (22.9%). Pathology showed adenocarcinoma in 27 patients (77.1%), neuroendocrine tumor in 3 patients (8.6%) and high-grade dysplasia in 1 patient (2.9%). No histopathology was available for 4 patients (11.4%). Twenty-eight patients (80.0%) had regular follow up, with 22 (62.9%) still alive. Six patients (17.1%) died during follow up with survival after diagnosis ranging from 42 days to 6.8 years. Conclusions: In Qatar, due to the unique demographics, GC is more common in males and younger age groups. Most of the patients present late with metastasis, but curative resection is associated with long-term survival.
... Gallbladder cancer has been ranked as the fifth most common gastrointestinal malignancy throughout the world, and it has a very poor prognosis [23,24]. Most gallbladder cancer patients are diagnosed in advanced stages when the tumor is unresectable owing to the rapid growth and metastasis [25]. Despite the recent advances in medical treatment, several multicenter studies report that the median survival time of GBC is approximately 25 months [26][27][28]. ...
Article
Background: Melatonin is an indolic compound mainly secreted by the pineal gland and plays a vital role in the regulation of circadian rhythms and cancer therapy. However, the effects of melatonin in gallbladder cancer (GBC) and the related mechanism remain unknown. Methods: In this study, the antitumor activity of melatonin on gallbladder cancer was explored both in vitro and in vivo. After treatment with different concentrations of melatonin, the cell viability, migration, and invasion of gallbladder cancer cells (NOZ and GBC-SD cells) were evaluated by CCK-8 assay, wound healing, and Transwell assay. Results: The results showed that melatonin inhibited growth, migration, and invasion of gallbladder cancer cells. Subsequently, the assays suggested that melatonin significantly induced apoptosis in gallbladder cancer cells and altered the expression of the apoptotic proteins, including Bax, Bcl-2, cytochrome C, cleaved caspase-3, and PARP. Besides, the intracellular reactive oxygen species (ROS) was found to be upregulated after melatonin treatment in gallbladder cancer cells. Melatonin was found to suppress the PI3K/Akt/mTOR signaling pathway in a time-dependent manner by inhibiting the phosphorylation of PI3K, Akt, and mTOR. Treatment with N-acetyl-L-cysteine (NAC) or 740 Y-P remarkably attenuated the antitumor effects of melatonin in NOZ and GBC-SD cells. Finally, melatonin suppressed the growth of GBC-SD cells in an athymic nude mice xenograft model in vivo. Conclusions: Our study revealed that melatonin could induce apoptosis by suppressing the PI3K/Akt/mTOR signaling pathway. Therefore, melatonin might serve as a potential therapeutic drug in the future treatment of gallbladder cancer.
... In our study the maximum time period of symptoms attributed to pathology up to surgical procedure is 56 weeks and minimum is 3 weeks (table and figure 3) with More than 90% of patients in our study presented with abdominal pain followed by weight loss, jaundice and vomiting as shown in table and figure 4. Similar observations were encountered by Rani Kanthan et al. 12 and proposed that Right upper quadrant or epigastric pain is the most common symptom (54-83%), followed by jaundice (10-46%), nausea and vomiting (15-43%), anorexia (4-41%), and weight loss (10-39%) and the development of gallbladder cancer is proposed to occur over a span of 5-15 years, with tissue alterations including metaplasia, dysplasia, carcinoma in situ and invasive cancer. Socio-economic status of an individual in our study (Table and Figure 5) most of the patients were belongs to lower socio-economic status similar observations were encountered by Lazcano-Ponce EC 13 and explained that socioeconomic issues can delay access to cholecystectomy thus increasing gallbladder cancer rates. In our study the patients with incidental gallbladder malignancy the mean body mass index was 30.14 which suggest a strong correlation between increased BMI and gall bladder malignancy similar observations were made by Hariharan D 13 and proposed that For every 5-point increase in body mass index, the relative risk of developing gallbladder cancer increases by 1.09 for men and 1.59 for women. ...
Article
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BACKGROUND Carcinoma of gall bladder is not a common entity among the malignancies of gastro intestinal tract, with an overall incidence of 0.3-1.5. Definition of Incidental Gallbladder Cancer (IGBC) is defined as a malignancy detected only on histopathological examination without prior pre-operative or intra-operative suspicion of malignancy. MATERIALS AND METHODS This is retrospective study conducted in the department of general surgery of government medical college, Srinagar, where the most commonly performed operation is cholecystectomy mostly laparoscopically. Data of this study was collected from December 2014 to December 2018. Number of patients enrolled in this study was 869 (all electively operated no emergency cholecystectomy was included). RESULTS In our study of 869 patients of cholecystectomies, 14 patients were diagnosed with incidental gall bladder cancer on histopathological examination. Mean age of the patients in our study is 60.07 with male to female ratio of 1:2.5. More than 90% of patients in our study presented with abdominal pain followed by weight loss, jaundice and vomiting, mean BMI of 30.14, intraoperative findings of patients with incidental gall bladder malignancy suggests that about half of the patients were having shrunken fibrosed gall bladder and rest gross findings were polypoid mass, difficulty in dissection due to adhesions and thickened gall bladder wall. CONCLUSION Performing cholecystectomy should never be the only treatment of gall stones or any other pathology which demands cholecystectomy unless and until the histopathological examination of the specimen is ensured so as to diagnose incidental gall bladder malignancy which is usually missed during peri-operative period.
Article
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Gallbladder carcinoma (GBC) is a chronic malignancy of the gall bladder and intrahepatic and extrahepatic common bile ducts with a high mortality rate and forms the fifth common cancer of gastrointestinal tract globally. Women remain at higher risk than men and recent studies have reported the highest rate of incidence in women from Delhi, India. GBC treatment suffers from the disadvantage of lack of suitable biomarkers for early diagnosis of the disease. Different proteomic approaches including (i) 2D gel electrophoresis (ii) Mass spectroscopic studies (iii) Isobaric tags for relative and absolute quantization (iTRAQ) -based quantitativeproteomicsstudies are being employed for detection of biomarkers in order to undertake early diagnosis of the disease. In this review we focus on (i) risk factors in GBC, (ii) diagnosis and treatment, (iii) molecular markers, and (iv) proteomic studies in GBC. The future scope of this review lies in the identifying biomarkers of GBC, and may provide directions to unraveling future implications in disease treatment.
Article
We aimed to define the benefit of extended radical surgery for incidental gallbladder carcinoma (IGC), the most appropriate treatment for which remains controversial. We analyzed retrospectively the management strategies and prognoses of 28 patients with IGC treated in our hospital. After initial cholecystectomy, 10, 5, and 13 of the 28 patients were found to have T1a (m), T1b (mp), and T2 (ss) disease, respectively. The patients with T1a disease (T1a group) had a good prognosis; however, 9 of the 18 patients with T1b or T2 disease required additional S4a + 5 segmentectomy of the liver and bile duct resection (extended radical surgery; re-resected group), while 9 did not undergo additional treatment because of their poor general condition (no-treatment group). The re-resected group had a favorable prognosis, with an 88.9 % 5-year disease-specific survival (DSS) rate, which was significantly better than that of the non-treatment group (30.5 %, p = 0.015) and comparable to that of the T1a group (90.0 %, p = 0.97). Examination of the re-resected specimens revealed residual disease in 44 % (4/9). Additional extended radical surgery improved the prognosis of patients with IGC, suggesting that there is curative potential in most cases.
Article
Objectives There is a lack of comprehensive analysis of recent gallbladder cancer (GBC) mortality trends in China. This study aims to analyse trends in GBC mortality in China, with a specific focus on urban and rural area differences, and to determine possible risk factors. Study design This was a cross-sectional study. Methods Data were accessed through the Chinese Health Statistics Annual Report for 31 provinces from 2013 to 2019. Age-standardised mortality rate (ASMR) stratified by regions, gender and the years of diagnoses were analysed by Joinpoint regression analysis. Results The GBC ASMR was higher in females than in males and higher in urban areas than in rural areas. Mortality was primarily observed in individuals aged ≥65 years (in both sexes). A non-significant downward trend of GBC mortality was identified in urban areas from 2013 to 2019 (average annual percent change [AAPC] −1.50%; 95% confidence interval [CI]: −3.49, 0.53). However, in rural areas, the ASMR significantly increased with an AAPC of 2.64% (95% CI: 1.15, 4.15) in males and 3.85% (95% CI: 2.17, 5.56) in females. The GBC mortality rate was positively related to red meat consumption. Conclusions The burden of GBC mortality in rural China cannot be ignored, as results from this study show significantly increasing trends in both females and males from 2013 to 2019. In addition, red meat consumption may play a vital role in the increasing GBC mortality rate.
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Many clinical and preclinical studies demonstrated that measurements of liver hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose and predict liver metastases from primary colorectal cancer in a research setting. However, Doppler measurements have some serious limitations when applied to general population. Ultrasound is very operator-dependent, and requires skilled examiners. Also, many conditions may limit the use of Doppler ultrasound and ultrasound in general, such as the presence of air in digestive tract, cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore, in spite of the results from clinical studies, its value may be limited in everyday practice. On the contrary, scientific research of the DPI in detection of liver metastases is of great importance, since current research speaks strongly for the presence of systemic vasoactive substance responsible for observed hemodynamic changes. Identification of such a systemic vasoactive substance may lead to the development of a simple and reproducible laboratory test that may reliably identify the presence of occult liver metastases and therefore increase the success of adjuvant chemotherapy through better selection of patients. Further research in this subject is therefore of great importance.
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Aims: This case report aims to describe an unusual presentation of gallbladder cancer, masked by Mirizzi Syndrome. Case description: a woman complained of nausea, dark urine and acholic stools started two months earlier, and jaundice started later. An abdominal ultrasound showed dilatation of the bile duct with choledocholithiasis and cholelithiasis. A cholangiopancreatography showed obstruction in the middle third of the common bile duct, without visualization of gallstones. The initial diagnosis was Mirizzi Syndrome. A stent was inserted in the main bile duct, to plan surgery. During surgery macroscopic lesions were found in gallbladder and peritoneum, which indicated interruption of the surgery and sample collection for biopsy. Pathological examination revealed adenocarcinoma. The patient was discharged with oncological follow-up plan and chemotherapy. Conclusions: The coexistence of Mirizzi Syndrome with carcinoma of the gallbladder is extremely rare, because both diseases are uncommon. Anatomopathological examination of all surgical specimens is always imperative for the definitive diagnosis of gallbladder tumor.
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Gallbladder carcinoma (GBC) is a chronic malignancy of the gall bladder and intrahepatic and extrahepatic common bile ducts with a high mortality rate and forms the fifth common cancer of gastrointestinal tract globally. Women remain at higher risk than men and recent studies have reported the highest rate of incidence in women from Delhi, India. GBC treatment suffers from the disadvantage of lack of suitable biomarkers for early diagnosis of the disease. Different proteomic approaches including (i) 2D gel electrophoresis (ii) Mass spectroscopic studies (iii) Isobaric tags for relative and absolute quantization (iTRAQ) -based quantitativeproteomicsstudies are being employed for detection of biomarkers in order to undertake early diagnosis of the disease. In this review we focus on (i) risk factors in GBC, (ii) diagnosis and treatment, (iii) molecular markers, and (iv) proteomic studies in GBC. The future scope of this review lies in the identifying biomarkers of GBC, and may provide directions to unraveling future implications in disease treatment.
Chapter
Biliary tract disease, representing a major health burden, has quite a varied epidemiology that substantially depends upon geography and ethnicity. Gallstone disease is most common. Several risk factors for cholesterol gallstone formation, such as obesity and the metabolic syndrome, are modifiable, providing opportunities for primary prevention. Other risk factors are not modifiable such as ethnic background, increasing age, female gender, and family history or genetics. Black pigment stones are associated with chronic hemolysis and cirrhosis. In East Asia, brown pigment stones form in bile ducts, predominately associated with parasitic infestation. Gallbladder cancer may be rare in developed populations, but is endemic in others such as American Indians. Gallbladder cancer is uncommon in developed countries. In the United States, it accounts for only 0.5% of all gastrointestinal malignancies with ∼5,000 cases per year. Elsewhere, high incidence rates occur in American Indians and Asian countries, particularly in women. Additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, and congenital biliary abnormalities. Cholangiocarcinomas are uncommon in developed countries although their association with primary sclerosing cholangitis creates a complex clinical problem for surveillance. In Asia, they are more frequent, being associated with liver fluke infestations, hepatolithiasis, and chronic viral hepatitis. This edition first published 2014 © 2014 John Wiley & Sons, Ltd.
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Among the malignant neoplasms of the hepatobiliary zone, gallbladder cancer (GBC) is rare. The incidence of GBC is highest in patients over 65 years of age. In the early stages GBC rarely has clinical manifestations, and often occurs under the guise of other gastroenterological diseases, and is often an accidental finding. Since GBC tends to show high dissemination, at the time of diagnosis, almost every second patient has an advanced form of the disease that is not the subject to surgical treatment. Most authors tend to believe that the use of combined treatment of GBC (extended resection and adjuvant chemotherapy) significantly increases the survival rate of patients. Currently, about 1/3 of patients receive adjuvant chemotherapy in the treatment of GBC. This is due to a small number of prospective randomized trials. Today, most experts recognize that surgery is the only treatment that can be performed in patients with early stages of prostate cancer. At the same time, a reduction in the risk of complications and a large percentage of five- and ten-year survival are achieved. Traditional cholecystectomy can be used to treat stage 1a PCa, this is possible if PC is accidentally found during surgical treatment of GSD. Unfortunately, prostate cancer and bile ducts belongs to the group of malignant neoplasms, in which most patients are unable to perform radical surgical treatment due to for the rapid dissemination of the process. When determining the tactics of patient supervision, it is necessary to take into account the prognostic factors of overall survival in prostate cancer: the type of surgery, the patient's age and sex, the size of the tumor, the presence of metastases in the regional lymph nodes, the presence of adjuvant chemotherapy. There is still a dispute between specialists about the appointment of adjuvanted chemotherapy to patients after surgical treatment of prostate cancer. Many authors acknowledge that adjuvant chemotherapy plays a positive role in improving patient survival after surgery. RAD is recognized as a chemosensitive cancer. Several drugs are active in relation to RS, used for adjuvant chemotherapy: fluorouracil, gemcitabine, mitomycin, cisplatin, capecitabine, epirubicin, and oxaliplatin. This article provides an overview of current research that is aimed at studying the effectiveness of adjuvant chemotherapy in patients with verified GBC of various stages.
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Gallbladder carcinoma is the commonest malignancy of the hepatobiliary system. It is plagued by the dismal outcome in terms of 5-year survival and high recurrence rate. The varying presentation from an incidental surprise during routine laparoscopic cholecystectomy for gallstone disease to presentation in advance stage. Surgical resection remains the only curative alternative; however, it is only possible in few patients at the time of diagnosis. Although, radical cholecystectomy is said to be the standard of surgical care, yet the extent of liver resection, lymphadenectomy, bile duct resection, adjacent organ resection, and palliative surgical treatment needs to be elaborately discussed. The resection of tumor with R0 margin with appropriate lymphadenectomy is the only hope for long-term survival. Revision surgery should be considered in patients who underwent simple cholecystectomy with incidentally diagnosed gallbladder carcinoma that invaded muscularis propria or beyond. The advance lesions are treated non-operatively with palliative intension. This review discusses the current surgical treatment options in patients with gallbladder cancer depending on the stage of disease.
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Gallbladder carcinoma (GBC) is a chronic malignancy of the gall bladder and intrahepatic and extrahepatic common bile ducts with a high mortality rate and forms the fifth common cancer of gastrointestinal tract globally. Women remain at higher risk than men and recent studies have reported the highest rate of incidence in women from Delhi, India. GBC treatment suffers from the disadvantage of lack of suitable biomarkers for early diagnosis of the disease. Different proteomic approaches including (i) 2D gel electrophoresis (ii) Mass spectroscopic studies (iii) Isobaric tags for relative and absolute quantization (iTRAQ) -based quantitativeproteomicsstudies are being employed for detection of biomarkers in order to undertake early diagnosis of the disease. In this review we focus on (i) risk factors in GBC, (ii) diagnosis and treatment, (iii) molecular markers, and (iv) proteomic studies in GBC. The future scope of this review lies in the identifying biomarkers of GBC, and may provide directions to unraveling future implications in disease treatment.
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Introduction Cancer is the second cause of death in Argentina, Cuba and Uruguay during the last decade, cancer mortality has shown a decrease trend in developed countries. Objective To describe mortality trends over time by cancer site in Argentina, Cuba and Uruguay during 1990-2005. Methods For each cancer site, country and gender, age-group specific and standardised (overall) rates were calculated by direct method (using the world standard population). The jointpoint regression analysis was used to identify the best-fitting points were a statistically significant change in the trend occurred and annual percent change was also estimated. Results Total cancer mortality rates decline during the whole period excepting for Cuba. Lung: a negative tendency was observed in men in Argentina and Uruguay (annual percent change: -2.25 and -1.28 % respectively), and increased in women (annual percent change: 1,75, 2,83 and 3,02) in Argentina, Uruguay and Cuba respectively. Breast: Negative trends were observed in the three countries. Prostate: it is the second cause of mortality in men in Cuba and Uruguay , and third in Argentina. A negative change in the tendency was observed from 1993 (Cuba) and 1998 (Argentina). Colon/recto: Decreasing rates were shown in Argentina in both sexes whereas not changes were noted in Cuba and Uruguay. Esophagus: Negative trends were detected in Argentina and Uruguay. Uterus: in the three countries mortality for Uterus non-specified was similar to cervix, diminishing for Argentina and Uruguay, while increased in Cuba. Body of uterus mortality diminished in Argentina. Conclusions Mortality trends in Cuba indicate an increasing for the tobacco related-cancer. Enhancing quality of death certification could mask a negative tendency of the mortality for cervix cancer. Negative trends in prostate cancer might be view from the impact of advances in diagnosis and treatment.
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A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institutional Study from the U.S. Extrahepatic Biliary Malignancy Consorium (Ann Surg Oncol 2017;24:1343-1350)
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Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with increasing incidence worldwide. Accumulating evidence indicated that circular RNAs (circRNAs) behave as a novel class of transcription products during multiple cancer processes. Specifically, hsa_circ_0001649 has been reported to be down-regulated in several cancers. However, its clinical significance and functional roles in PDAC is still unknown. RT-qPCR was carried out to measure the expression of hsa_circ_0001649 in PDAC tissue samples and cell lines. Additionally, the correlation between hsa_circ_0001649 expression and clinicopathological features was analyzed. The prognostic role of hsa_circ_0001649 was explored by Cox regression analysis. The potential effects of hsa_circ_0001649 in PDAC cells were evaluated in vitro including cell proliferation, colony-forming ability and apoptosis. As a result, hsa_circ_0001649 was abnormally decreased in PDAC tissues and cells, and this down-regulation was correlated with tumor stage and differentiation grade in PDAC patients. Hsa_circ_0001649 could serve as an independent prognostic factor for PDAC patients after surgery. What's more, increased hsa_circ_0001649 caused tumor suppressive effects via reducing cell proliferation, colony-forming ability and promoting cell apoptosis in PANC1 and BxPC3 cells. Collectively, the results illustrated that hsa_circ_0001649 may play a tumor suppressor role in PDAC and offer a potential therapeutic target for treating this fatal disease.
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Background: Soft tissue mass in gall bladder (GB) is a radiologic finding commonly encountered in surgical practice. It needs proper evaluation as there is a fair chance that it can be a malignant lesion. Gall bladder cancer (GBC) is considered an incurable disease with an extremely poor prognosis. However, there is good chance of survival if it can be diagnosed in earlier stages (stage Ib, II, selective III). Methods: All consecutive cases of soft tissue mass lesions of GB found in ultrasonogram of abdomen and admitted in Hepato-Biliary-Pancreatic Surgery (HBPS) unit of BIRDEM hospital, from January 2009- September 2016, were included in this study. Detailed history and thorough clinical examination was done in all cases. Pre-operative evaluations were done by ultrasound, Tumor marker (CA19.9) & CT scan,. CT scan was a crucial investigation for all the patients, as depending on the findings, decision was made whether a patient is eligible for a possible curative surgery or not. On-table frozen section biopsy or imprint cytology was done for tissue diagnosis. Radical resection was done for the histology/ cytology proved malignancy of gallbladder (stage Ib, II, selective III). Post-cholecystectomy patients also underwent full thickness excision of the umbilical port. In benign cases only cholecystectomy was done. Advanced GBC cases underwent FNAC for tissue diagnosis followed by palliative chemotherapy. Some needed endoscopic or surgical palliation in the form of percutaneous external biliary drainage, endobiliary prosthesis, triple bypass, hepaticojejunostomy, left duct anastomosis, gastrojejunostomy, ileotransverse anastomosis, external biliary drainage etc before chemotherapy. All the GBC patients were regularly followed according to a schedule. Results: We are reporting 334 cases of soft tissue mass lesions of GB. Female 191 (57.2%) and male 143 (42.81%), M : F = 1 : 1.3 ,,between the ages of 32 and 88 years. Of these, 81 patients (24.2%) turned out to be benign; another 81 patients (24.2%) were in early stage (Ib, II selective III). The rest of 172 patients (51.5%) showed signs of advanced malignancy in USG & CT scan. Post-operative complications occurred in 27 cases (8.1%). During follow-up, 34 patients (42%) have crossed their 5 years of disease free survival after curative surgery. Rest of the patients (44 cases), after curative surgery, are still under follow-up. The 172 patients in Stage III & IV disease who underwent some sort of palliative procedure, had a mean survival of 7.2 months. Conclusion: Soft tissue mass in gall bladder picked up by imaging has a very high chance to be malignant. Among these malignant patients, a good number has a chance of curative resection if evaluated and managed properly. Bangladesh Crit Care J March 2019; 7(1): 29-34
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Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities-inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract.
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There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.
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BACKGROUND—The age standardised mortality rate per 100 000 population for all causes of liver tumours (International Classification of Disease 9 (ICD-9) 155) has almost doubled in England and Wales during the period 1979-1996. We further analysed the mortality statistics to determine which anatomical subcategories were involved. METHODS—Mortality statistics for liver tumours of ICD-9 155, 156, and subcategories, and for tumours of the pancreas (ICD-9 157), in England and Wales were investigated from the Office for National Statistics, London, from 1968 to 1996 inclusive. Data for 1997 and 1998 were also available on intrahepatic cholangiocarcinomas. RESULTS—There has been a marked rise in age standardised mortality rates for intrahepatic cholangiocarcinoma. Since 1993, it represents the commonest recorded cause of liver tumour related death in England and Wales. This is evident in age groups older than 45 years. In contrast, mortality trends from other primary liver tumours, including hepatocellular carcinoma, were unremarkable. CONCLUSIONS—The observed increase in mortality from intrahepatic cholangiocarcinoma may represent better case ascertainment and diagnosis due to improved diagnostic imaging, use of image guided biopsies, or increased use of ERCP. However, the trend started before ERCP was introduced nationally, mortality rates have continued to increase steadily thereafter, and there is no clear evidence that diagnostic transfers easily explains the findings. Alternatively, these observations may represent a true increase in intrahepatic bile duct tumours. Epidemiological studies are required to determine whether there is any geographical clustering of cases around the UK. Keywords: intrahepatic cholangiocarcinoma; age standardised mortality rates; age specific mortality rates
Article
Lowenfels A B (Department of Surgery, New York Medical College, Valhalla, New York 10595, USA), Walker A M, Althaus D P, Townsend G and Domellöf L. Gallstone growth, size and risk of gallbladder cancer: An interracial study. International Journal of Epidemiology 1989, 18: 50–54. To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7–2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (≥3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones ≥3 cm was 9.2 compared with subjects with stones <1 cm. (95% confidence interval: 2.3–37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (≥3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.
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In Reply.— Trevino and Carter appropriately emphasize the importance of identifying "Hispanics" by national origin. The determination of Hispanic ethnicity is a complex and difficult task.1 Data for this study were obtained from the review of hospital records. Ethnicity determination was based on a global assessment of information available in the chart, including descriptions of patient ethnicity by physicians and clerical staff as well as patient surname. Although this method of ethnicity assessment has not been validated, it appears to be largely accurate for the population living in south Texas. Furthermore, the 1980 census found that 92.6% of persons of "Spanish origin" in the San Antonio standard metropolitan statistical area were of Mexican descent.2 Hence, the designation of patients in this study as Mexican-American can be accepted with reasonable confidence.Of the 29 persons included in this study who were born in Latin America, 27 were born in
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Trends in mortality from cancer of the gall-bladder and bile ducts over the period 1965-1989 were analysed for 25 European countries on the basis of official death certifications from the World Health Organization databank. A high-mortality area--i.e. with overall death certification rates, world standard, around or over 2/100,000 men and 4/100,000 women in 1985-1989--was identified in Germany and the surrounding central European countries (Austria, Czechoslovakia, Hungary and Poland). The highest rates were in Hungary (3.9/100,000 men and 7.4/100,000 women). During the two decades considered, rates increased in Czechoslovakia and Hungary, remained stable in Poland and declined in Austria and Germany. Intermediate-mortality areas included Scandinavian countries (except Norway) and Switzerland: their rates in the late 1980s were between 1.5 and 2.5/100,000 men and between 2.2 and 4.2/100,000 women. Mortality increased in Finland and Sweden, declined in the Netherlands and Switzerland, and did not change consistently in Denmark. Low-mortality countries (i.e. with rates in 1985-1989 below 2.0/100,000 men and 2.5/100,000 women) included Belgium, France, Britain, Ireland, Norway, Bulgaria and Mediterranean countries. Over the last two decades, certification rates declined in Bulgaria and Great Britain, but increased in all other countries. The ratio between the countries with the highest and lowest gall-bladder cancer mortality rates declined from 21 to 12 in women, although they remained stable around 10 for men. The pattern was similar when analysis was restricted to truncated rates from patients aged between 35 and 64 years. These trends, and particularly the exceedingly high rates in central Europe, the low rates in Mediterranean countries and the low and declining rates in Britain and Ireland are discussed in terms of known (cholelithiasis) or potential (dietary) factors in gall-bladder cancer aetiology, and of trends in cholecystectomy rates.
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The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance Research reports its annual compilation of estimated cancer incidence, mortality, and survival data for the United States in the year 2000. After 70 years of increases, the recorded number of total cancer deaths among men in the US declined for the first time from 1996 to 1997. This decrease in overall male mortality is the result of recent down-turns in lung and bronchus cancer deaths, prostate cancer deaths, and colon and rectum cancer deaths. Despite decreasing numbers of deaths from female breast cancer and colon and rectum cancer, mortality associated with lung and bronchus cancer among women continues to increase. Lung cancer is expected to account for 25% of all female cancer deaths in 2000. This report also includes a summary of global cancer mortality rates using data from the World Health Organization.
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Primary carcinoma of the gallbladder is an uncommon, aggressive malignancy that affects women more frequently than men. Older age groups are most often affected, and coexisting gallstones are present in the vast majority of cases. The symptoms at presentation are vague and are most often related to adjacent organ invasion. Therefore, despite advances in cross-sectional imaging, early-stage tumors are not often encountered. Imaging studies may reveal a mass replacing the normal gallbladder, diffuse or focal thickening of the gallbladder wall, or a polypoid mass within the gallbladder lumen. Adjacent organ invasion, most commonly involving the liver, is typically present at diagnosis, as is biliary obstruction. Periportal and peripancreatic lymphadenopathy, hematogenous metastases, and peritoneal metastases may also be seen. The vast majority of gallbladder carcinomas are adenocarcinomas. Because most patients present with advanced disease, the prognosis is poor, with a reported 5-year survival rate of less than 5% in most large series. The radiologic differential diagnosis includes the more frequently encountered inflammatory conditions of the gallbladder, xanthogranulomatous cholecystitis, adenomyomatosis, other hepatobiliary malignancies, and metastatic disease.
Article
The age standardised mortality rate per 100 000 population for all causes of liver tumours (International Classification of Disease 9 (ICD-9) 155) has almost doubled in England and Wales during the period 1979-1996. We further analysed the mortality statistics to determine which anatomical subcategories were involved. Mortality statistics for liver tumours of ICD-9 155, 156, and subcategories, and for tumours of the pancreas (ICD-9 157), in England and Wales were investigated from the Office for National Statistics, London, from 1968 to 1996 inclusive. Data for 1997 and 1998 were also available on intrahepatic cholangiocarcinomas. There has been a marked rise in age standardised mortality rates for intrahepatic cholangiocarcinoma. Since 1993, it represents the commonest recorded cause of liver tumour related death in England and Wales. This is evident in age groups older than 45 years. In contrast, mortality trends from other primary liver tumours, including hepatocellular carcinoma, were unremarkable. The observed increase in mortality from intrahepatic cholangiocarcinoma may represent better case ascertainment and diagnosis due to improved diagnostic imaging, use of image guided biopsies, or increased use of ERCP. However, the trend started before ERCP was introduced nationally, mortality rates have continued to increase steadily thereafter, and there is no clear evidence that diagnostic transfers easily explains the findings. Alternatively, these observations may represent a true increase in intrahepatic bile duct tumours. Epidemiological studies are required to determine whether there is any geographical clustering of cases around the UK.
Article
Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma. Between 1973 and 1997, the incidence and mortality rates from intrahepatic cholangiocarcinoma markedly increased, with an estimated annual percent change (EAPC) of 9.11% (95% CI, 7.46 to 10.78) and 9.44% (95%, CI 8.46 to 10.41), respectively. The age-adjusted mortality rate per 100,000 persons for whites increased from 0.14 for the period 1975-1979 to 0.65 for the period 1993-1997, and that for blacks increased from 0.15 to 0.58 over the same period. The increase in mortality was similar across all age groups above age 45. The relative 1- and 2-year survival rates following diagnosis from 1989 to 1996 were 24.5% and 12.8%, respectively. In conclusion, there has been a marked increase in the incidence and mortality from intrahepatic cholangiocarcinoma in the United States in recent years. This tumor continues to be associated with a poor prognosis.
Article
Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis. We report here the worldwide geographical distribution of gallbladder cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5-15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans. The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high-risk populations. Secondary prevention of gallbladder cancer could be effective if supported by cost-effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high-risk areas.
Article
The incidence of adenocarcinoma of the oesophagus and gastric cardia has increased in many countries. To describe the trends in the subsite and morphology of oesophageal and gastric cancer using cancer registry data from 1971 to 1998. We calculated the overall age-standardised incidence in each year; the age-standardised incidence by subsite, by morphology and by subsite and morphology; and the ratio of the rates in men and women in 1971 and 1998. The incidence of oesophageal adenocarcinoma increased from 1.5 to 7.0 per 100,000 men and from 0.4 to 1.5 per 100,000 women. The incidence of cancer at the cardia also increased, from 2.0 to 5.4 per 100,000 men and from 0.6 to 1.4 per 100,000 women, but the incidence of gastric cancer without a specified subsite decreased markedly from 21.3 to 9.3 per 100,000 men and from 10.7 to 4.2 per 100,000 women. Although some of the increase in the incidence of adenocarcinoma of the gastric cardia is probably real, this interpretation is limited by the proportion of cancers without specified subsites or morphologies.
Article
The incidence of pancreatic cancer worldwide appears to correlate with increasing age, and it is slightly more common among men and Jewish people. There is evidence that the incidence rate is higher among blacks than among whites. The published literature was reviewed for preparation of an overview on epidemiology of pancreatic cancer. A possible role of diabetes in the etiology of pancreatic cancer has been suggested by different epidemiological studies. Several investigations indicate that a history of pancreatitis may increase the risk of pancreas cancer, and it appears that people with a history of pernicious anemia or partial gastrectomy for ulcer as well as cholecystectomy may be at higher risk. Individuals with familial adenomatous polyposis (FAP) also have a high risk of developing this cancer. Pancreatic cancer is seen in some breast cancer families with BRCA1 and BRCA2 mutations. Epidemiological studies have confirmed that relatives of individuals with pancreatic cancer have an increased risk of this malignancy. Affected family members of the familial atypical multiple-mole melanoma (FAMMM) as well as those with a positive family history of ataxia-telangiectasia (AT) have much higher risk of developing pancreatic cancer, compared with the general population. A positive association has been reported between pancreatic cancer risk and dietary intake such as fat and oil, meat, and dairy products, as well as with high intake of energy, fried foods, carbohydrates, cholesterol, and salt. The risk is found to decrease with increased consumption of fresh fruits and vegetables, fiber, natural foods, and Vitamin C. Cigarette smoking has shown the strongest positive association with risk of pancreatic cancer. Some diseases and medical conditions such as diabetes, chronic pancreatitis, AP, family aggregation of pancreatic cancer, FAMMM, AT, as well as nutrition and lifestyle factors, like smoking may play important role in the etiology of pancreatic cancer.
Article
The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Article
Together with thyroid cancer, cancer of the gallbladder is the only non-sex hormone-related cancer displaying a female preponderance, with incidence being 3-4 times more common among women. We carried out this study to evaluate the role of menstrual, reproductive and lifestyle factors in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of cholelithiasis was carried out. A detailed menstrual and reproductive history was illustrated beside detailed lifestyle history, in particular consumption of betel nut, tobacco and alcohol and smoking, odds ratio was calculated. Mean age of the patients with cancer was 51+/-1.2 years while it was 40.9+/-1.2 years for gallstones; 69% of cancer patients and 90% of gallstones patients were females. More than half of the cancer patients (53%) and 43% of the gallstone patients were illiterate. A past history of typhoid was present in 22% of cancer patients and 13% of gallstone patients, while 35% of cancer and 25% of gallstone patients were chewers, 18.1 and 9.9% were smokers, and 10% of cancer and 2% of gallstone patients consumed alcohol. Mean age of menarche was 13.4+/-1.2 years among female patients with cancer while it was 14.0+/-1.4 years for gallstone patients. Higher age at menarche (>13 years, OR 2.48, 95% confidence interval (CI) 1.16-5.3), higher number of childbirths(>3 births, OR 3.92; 95% CI 1.4-10.3), higher number of pregnancies (>3 pregnancies, OR 6.66, 95% CI 1.8-23.4), and higher age at last childbirth (>25 years, OR 2.97, 95% CI 1.04-8.5) were found to have significantly higher risk of developing gallbladder cancer. In conclusion, tobacco chewing and smoking are associated with increased odds of gallbladder cancer. Similarly early menarche, late menopause, multiple pregnancies and childbirth increased the risk of gallbladder cancer.
Article
The aim of this study was to describe the epidemiology of gallbladder cancer in Scotland during the last 30 years. A secondary aim was to describe trends in cholecystectomy rates because it has been suggested that changing rates of cholecystectomy for benign gallbladder disease may be influencing the epidemiology of gallbladder cancer. A retrospective analysis of cancer registration and mortality (gallbladder cancer) and hospital discharge (cholecystectomy) data from Scotland in 1968-1998 was carried out. In Scotland the incidence of, and mortality from, gallbladder cancer have been falling in women since at least 1968, and in men since the late 1980s. Whilst overall survival remains poor, survival in older patients may have improved recently, and survival is better in patients from affluent areas. Cholecystectomy rates increased until 1977 then fell until the introduction of laparoscopic surgery caused them to return to the rates previously observed. The current declining incidence of gallbladder cancer in Scotland is probably, in part, related to the increasing cholecystectomy rates seen prior to 1977. Further studies addressing changes in stage at diagnosis and treatment provided are required to investigate the recent apparent improvement in survival of elderly gallbladder cancer patients.
Article
The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size <5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975-1979 to 26.3% in 1995-1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size <5 cm, and microscopic confirmation suggest a true increase of ICC.
Article
Gallbladder cancer is a relatively rare neoplasm that shows, however, high incidence rates in certain world populations. The interplay of genetic susceptibility, lifestyle factors and infections in gallbladder carcinogenesis is still poorly understood. Age-adjusted rates were calculated by cancer registry-based data. Epidemiological studies on gallbladder cancer were selected through searches of literature, and relative risks were abstracted for major risk factors. The highest gallbladder cancer incidence rates worldwide were reported for women in Delhi, India (21.5/100,000), South Karachi, Pakistan (13.8/100,000) and Quito, Ecuador (12.9/100,000). High incidence was found in Korea and Japan and some central and eastern European countries. Female-to-male incidence ratios were generally around 3, but ranged from 1 in Far East Asia to over 5 in Spain and Colombia. History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3-7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4-17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1-8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations. Diagnosis of gallstones and removal of gallbladder currently represent the keystone to gallbladder cancer prevention, but interventions able to prevent obesity, cholecystitis and gallstone formation should be assessed.
Article
Each year, the American Cancer Society (ACS) estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. This report considers incidence data through 2003 and mortality data through 2004. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,444,920 new cancer cases and 559,650 deaths for cancers are projected to occur in the United States in 2007. Notable trends in cancer incidence and mortality rates include stabilization of the age-standardized, delay-adjusted incidence rates for all cancers combined in men from 1995 through 2003; a continuing increase in the incidence rate by 0.3% per year in women; and a 13.6% total decrease in age-standardized cancer death rates among men and women combined between 1991 and 2004. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. While the absolute number of cancer deaths decreased for the second consecutive year in the United States (by more than 3,000 from 2003 to 2004) and much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
sample'' registration system [12]. Data were thus available from 32 countries in Europe The Netherlands, Switzerland, and the United King-dom; East Europe: Estonia, Latvia, Lithuania, Mol-dova, Poland, and Romania Log-References
  • Belgium
  • France
  • Germany
  • Ireland
  • Luxembourg
only 29 have an ''ideal'' civil registration system, while countries such as China and India have only a ''sample'' registration system [12]. Data were thus available from 32 countries in Europe (West Europe: Belgium, France, Germany, Ireland, Luxembourg, The Netherlands, Switzerland, and the United King-dom; East Europe: Estonia, Latvia, Lithuania, Mol-dova, Poland, and Romania; North Europe: Denmark, Finland, Iceland, Norway, and Sweden; South Europe: Albania, Croatia, Greece, Italy, Macedonia, Malta, Portugal, Slovenia, and Spain; Central Europe: Austria, Czechoslovakia, Hungary, and Slovakia), 10 countries in Asia (South East Asia: Hong Kong, Philippines, Singapore, and Thailand; North East Asia: Japan, Korea; Middle East: Georgia, Israel, Kuwait, and Kyrgyzstan), and 8 countries across the Americas (North America: Canada and the United States of America; South America: Colombia, Costa Rica, Ecuador, Mexico, Uruguay, and Venezuela). Log-References
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Gallbladder cancer worldwide: geographical distribution and risk factors
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