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Cancer staging using the American Joint Committee on Cancer TNM System
... Initial staging was performed in line with international guidelines. Tumor staging was performed according to the TNM staging systems of the American Joint Committee on Cancer (AJCC) [26,27]. The diagnosis was established by biopsy. ...
Aim
Perineal defects following the resection of anorectal malignancies are a reconstructive challenge. Flaps based on the rectus abdominis muscle have several drawbacks. Regional perforator flaps may be a suitable alternative. We present our experience of using the gluteal fold flap (GFF) for reconstructing perineal and pelvic defects.
Methods
We used a retrospective chart review and follow-up examinations focusing on epidemiological, oncological (procedure and outcome), and therapy-related data. This included postoperative complications and their management, length of hospital stay, and time to heal.
Results
Twenty-two GFFs (unilateral n = 8; bilateral n = 7) were performed in 15 patients (nine women and six men; anal squamous cell carcinoma n = 8; rectal adenocarcinoma n = 7; mean age 65.5 + 8.2 years) with a mean follow-up time of 1 year. Of the cases, 73.3% were a recurrent disease. Microscopic tumor resection was achieved in all but one case (93.3%). Seven cases had no complications (46.7%). Surgical complications were classified according to the Clavien-Dindo system (grades I n = 2; II n = 2; IIIb n = 4). These were mainly wound healing disorders that did not affect mobilization or discharge. The time to discharge was 22 + 9.9 days. The oncological outcomes were as follows: 53.3% of the patients had no evidence of disease, 20% had metastatic disease, 20% had local recurrent disease, and one patient (6.7%) died of other causes.
Conclusions
The GFF is a robust, reliable flap suitable for perineal and pelvic reconstruction. It can be raised quickly and easily, has an acceptable complication rate and donor site morbidity, and does not affect the abdominal wall.
... Disease was staged according to the tumour-node-metastasis (TNM) classification system of the American Joint Committee on Cancer [21]. The World Health Organization classification was used for pathologic grading [22]. ...
Tryptase(+) mast cells (MCs), abundant in the invasive front of tumours, contribute to tissue remodelling. Indeed, protease-activated receptor-2 (PAR-2) activation by MC-tryptase is considered an oncogenic event in colorectal cancer (CRC). Recently, we have suggested NHERF1 as a potential new marker in CRC. In this study, we aimed to determine the distribution of tryptase(+) MCs and PAR-2 and to examine the relationship between PAR-2 and NHERF1, investigating their reputed usefulness as tumour markers. We studied a cohort of 115 CRC specimens including primary cancer (C) and adjacent normal mucosa (NM) by immunohistochemical double staining, analyzing the protein expression of MC-tryptase, PAR-2 and cytoplasmic NHERF1. MC density was higher in NM than in C. Tumours with high TNM stage and poor grade showed the highest MC density. A higher PAR-2 immunoreactivity characterized tumours most infiltrated by MCs compared with samples with low MC density. Furthermore, PAR-2 overexpression was associated with advanced TNM stage, poor grade and lymphovascular invasion (LVI). A positive correlation existed between tryptase(+) MC density and PAR-2 expression. Cytoplasmic NHERF1 was higher in C than in NM and overexpressing tumours resulted associated with nodal and distant metastases, poor grade and LVI. PAR-2 correlated with cytoplasmic NHERF1 and the PAR-2(+)/cytoplasmic NHERF1(+) expression immunophenotype identified tumours associated with unfavourable prognosis and aggressive clinical parameters. Our data indicate that the high density of tryptase(+) MCs at invasive margins of tumours was associated with advanced stages of CRC and was strongly correlated with PAR-2 expression.
... A total of 116 patients with CS was identified during this period. Based on clinical and radiologic findings, those patients who were believed to have disease confined to the uterus (American Joint Committee on Cancer/International Union Against Cancer T1NXM0) 3 and who underwent primary surgical assessment were included in the study. Sixty-two such patients were identified, representing the study population. ...
BACKGROUND
The purpose of this study was to determine clinicopathologic variables associated with extrauterine disease, recurrence, and survival in patients with carcinosarcoma (CS) of the uterus.METHODS
Patients believed to have disease confined to the uterine corpus who underwent primary surgical assessment were identified and data retrospectively reviewed.RESULTSOccult metastases were found in 38 (61%) of 62 patients. At last follow-up, 31 (50%) had had recurrence, with an extrapelvic component in 43%, and 53% had died. Depth of myometrial invasion and lymph-vascular space invasion (LVSI) were associated with extrauterine disease. Five-year survival for patients with disease confined to the corpus (74%) was significantly greater than for those with more advanced disease (24%, P = 0.0013). Factors associated with recurrence and survival included depth of myometrial invasion, LVSI, adnexal and serosal involvement, positive cytology, and lymph node metastases. Of 24 patients with uterine disease only, 11 received no adjuvant therapy, yet 8 (73%) were free of disease at last follow-up. Neither adjuvant radiotherapy nor chemotherapy was identified as an independent prognostic variable for recurrence or survival.CONCLUSIONS
More than half of patients with CS clinically confined to the uterine corpus harbor occult metastases in a pattern similar to that found with endometrial carcinoma. Survival is significantly diminished for this group. Although the benefit of adjuvant therapy cannot be demonstrated by this study, a number of early stage patients survive without adjuvant therapy. This argues for extending the International Federation of Gynecology and Obstetrics endometrial carcinoma surgical staging system to include CS, and also for conducting prospective trials to examine the benefits of adjuvant therapy for patients with early stage disease. Cancer 2000;88:2782–6. © 2000 American Cancer Society.
... After resection, the colonic specimens were extensively rinsed with sterile water after which the specimens were examined by an oncological pathologist. Disease was staged according to the Tumor-Node-Metastasis (TNM) classification [19]. From each colonic specimen, biopsies were taken from the tumor site (''on-tumor'', A on –F on ) and from adjacent non-malignant tissue (''offtumor'' , A off –F off ) on the luminal side of the colonic wall (distance about 5–10 cm). ...
Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.
... The sizes of the tumors resected during surgery ranged from 0.6 -7.2 cm, and the mean and median sizes were 2.9 and 2.8 cm, respectively. Clinical staging was performed according to the Postsurgical International Union against Cancer TNM classification system (19). Histological grade of the tumors was determined according to criteria reported by Bloom and Richardson (20) and was known for 224 patients. ...
Polyadenylate polymerase (PAP) is one of the enzymes involved in the formation of the polyadenylate tail of the 3' end of mRNA. High levels of PAP activity were associated with rapidly proliferating cells. Here we evaluate the prognostic value of PAP activity in breast cancer patients. PAP specific activity values were measured by a highly sensitive assay in the tumor cytosols of 228 women with primary breast cancer. The median follow-up period was 58 months. PAP specific activity values ranged from 2.1-39.4 units/mg protein in the breast tumor cytosols, and the activity was correlated with the level of expression of the antigen. An optimal cutoff value of 5.5 units/mg extracted protein was first defined by statistical analysis. PAP status was then compared with other established prognostic factors in terms of relapse-free survival (RFS) and overall survival (OS). PAP activity levels had a tendency to increase with tumor-node-metastasis (TNM) stage and were higher in node-positive patients. Evaluation of the prognostic value of PAP was performed using univariate and multivariate analyses. Univariate analysis showed that PAP-positive patients had a less favorable prognosis for both RFS (relative risk (RR) = 2.35; P < 0.001] and OS (RR = 3.15; P < 0.001). PAP significantly added to the prognostic power for RFS (RR = 2.51; P = 0.0012) and OS (RR = 4.21; P < 0.001) in multivariate analysis, whereas patient age, tumor size, and nodal and ER status remained independent factors for predicting survival. When only node-negative patients were examined, PAP was found to be an independent factor for predicting RFS (RR = 3.68; P = 0.0032) and OS (RR = 4.81; P < 0.001). PAP did not appear to have a prognostic significance for node-positive patients. PAP is a new prognostic factor for early recurrence and death in breast cancer patients. Our results suggest that PAP may be used as an independent unfavorable prognostic factor in node-negative breast cancer patients because there were no significant associations between PAP and the other prognostic indicators evaluated in this group of patients.
... All patients had a histologically confirmed diagnosis of primary breast cancer and received no treatment before surgery. Clinical staging was performed according to the Postsurgical International Union Against Cancer Tumor-Node-Metastasis (TNM) classification system (23). Histological grade of the tumors was determined according to crite- ria reported by Bloom and Richardson (24). ...
Apoptosis, a normal physiological form of cell death, is critically involved in the regulation of cellular homeostasis. If the delicate balance between cell death and cell proliferation is altered by a defect in the normal regulation of apoptosis signaling, a cell population is able to survive and accumulate, thereby favoring the acquisition of further genetic alterations and promoting tumorigenesis. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of breast cancer, as well as in the responses of tumors to therapeutic intervention. Overexpression of anti-apoptotic members of the Bcl-2 family such as Bcl-2 and Bcl-XL has been implicated in cancer chemoresistance, whereas high levels of pro-apoptotic proteins such as Bax promote apoptosis and sensitize tumor cells to various anticancer therapies. Recently, a new member of the Bcl-2 family, BCL2L12, was cloned. The BCL2L12 gene is constitutively expressed in many tissues, suggesting that the encoded protein serves an important function in different cell types. In the present study, the expression of BCL2L12 gene was analyzed by reverse transcription-PCR (PT-PCR) in 70 breast cancer tissues. Our results indicate that BCL2L12 positive breast tumors are mainly of lower stage (I/II) or grade (I/II) (p=0.02 or p=0.04 respectively). Cox regression analysis revealed that BCL2L12 expression is positively related to disease-free (DFS) and overall survival (OS) at both univariate and multivariate analysis (p=0.021, p=0.029, p=0.032, p=0.044 respectively). Kaplan-Meier survival curves also demonstrated that patients with BCL2L12-positive tumors have significantly longer DFS and OS (p=0.002 and p<0.001 respectively). BCL2L12 expression may be regarded as a new independent favorable prognostic marker for breast cancer.
... All patients had a histologically confirmed diagnosis of primary breast cancer and received no treatment before surgery. Clinical staging was performed according to the Postsurgical International Union against cancer Tumor-Node-Metastasis (TNM) classification system (12). Histological grade of the tumors was determined according to criteria reported by Bloom and Richardson (13). ...
Kallikreins are a subgroup of serine proteases that are involved in the post-translational processing of polypeptide precursors. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. Human kallikrein gene 7 (KLK7; HSCCE) is a new member of the human kallikrein gene family. KLK7 is expressed in normal breast tissue and is up-regulated in breast cancer cells by estrogens and glucocorticoids. In the present study, expression of the KLK7 gene in 92 breast cancer tissues was analyzed by reverse transcription-PCR (RT-PCR) and direct sequencing of several samples. The results were correlated with other clinicopathological variables and patient outcome. KLK7 gene expression was significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and patients with positive progesterone receptors (p = 0.022). Survival analysis showed that breast cancer patients with KLK7 positive tumors have relatively shorter disease-free survival (DFS) and overall survival (OS) than patients with KLK7 negative tumors. These data suggest that KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients.
... Based on conventional histopathological examination of paraffin sections, the pathological stage was determined according to the TNM classification. 19 Immunohistochemistry In all, 4 mm paraffin sections of normal colon, primary tumor and liver metastases were semiserially cut. ...
Adhesion of inflammatory cells to vascular endothelium is mediated by specific cell adhesion receptors on both leukocytes and endothelial cells. One of the adhesion molecules on the endothelium is P-selectin. Decreased vascular P-selectin expression has been associated with tumor progression in melanoma patients. We now report on the expression of endothelial P-selectin in colorectal cancer (CRC). We studied a colorectal tissue specimen series ranging from normal colorectal tissue via unmetastasized primary tumors to tumors with the same depth of invasion at the primary site but with liver metastases. Moreover, P-selectin expression levels in liver metastases were determined. The number of P-selectin positive vessels as a fraction of the total number of vessels, both intra- and peritumorally, was determined by staining for CD62P and CD34, respectively. Furthermore, by immunostaining for leukocytes (CD45) and macrophages (CD68), it was evaluated whether levels of P-selectin expression influenced infiltrate density and composition. The results showed that levels of peritumoral P-selectin expression were reciprocal to the degree of progression in CRC. This relation was even more pronounced intratumorally: in metastasized primary tumors and in the metastatic lesions, P-selectin expression was virtually absent. This distribution pattern was reflected in the numbers of leukocytes that accumulated in the various tissues, since in the primary tumors with metastases, and in the metastatic lesions, hardly any infiltrating cells were observed. In these lesions, leukocytes were present in the peritumoral zone, but seemed unable to enter the tumor tissue. In primary tumors without metastasis, the intratumoral leukocyte infiltration density was significantly higher. Recruitment levels of macrophages remained constant throughout the different tissues. We suggest that downregulation of endothelial P-selectin expression is a mechanism by which CRC lesions evade inflammatory regression and, thereby, progress to a more advanced stage of malignancy.
This project evaluated paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method was shown to control local tumor disease as well as assist in control of systemic metastasis. We established 5 human breast cancer cell lines within our laboratory. We elected purchase and implement a unique (luciferase) imaging system which allows in vivo imaging of tumor growth and metastasis (and subsequently decrease animal use). Tumor cell lines were transfected with the luciferase gene. In vitro testing of cell lines established paclitaxel sensitivity and showed a synergistic effect of delivering paclitaxel by the poloxamer polymer, especially for the chemotherapy resistant cell line, MCF-7-ADR. We completed the simultaneous evaluation of local and systemic toxicity, local, regional and systemic distribution and local and systemic efficacy of locally delivered paclitaxel chemotherapy following tumor removal using the MCF-7-ADR cell line in nude mice. Intracavitary administration of taxol in poloxamer was well tolerated (locally and systemically) afld resulted in significantly improved control of local tumor regrowth and comparable control of metastasis following marginal tumor removal as compared to intravenous paclitaxel (parent drug) . Sustained drug levels (from polymer delivery) were seen in plasma and liver tissue at 60 days.
Somatic mtDNA mutations have been reported in some human tumors, but their spectrum in different malignancies and their role in cancer development remain incompletely understood. Here, we describe the breadth of somatic and inherited mutations across the mitochondrial genome by sequence analyses of paired tumor and normal tissue samples from 226 individuals with five types of cancer using whole-genome data generated by The Cancer Genome Atlas Research Network. The frequencies of deleterious tumor-specific somatic mutations found in mtDNA varied across tumor types, ranging from 13% of glioblastomas to 63% of rectal adenocarcinomas. Compared with inherited mtDNA variants, somatic mtDNA mutations were enriched for nonsynonymous vs. synonymous changes (93 vs. 15; P < 2.2E-16) and were predicted to functionally impact the encoded protein. Somatic missense mutations in tumors were distributed uniformly among the mitochondrial protein genes, but 65% of somatic truncating mutations occurred in NADH dehydrogenase 5. Analysis of staging data in colon and rectal cancers revealed that the frequency of damaging mitochondrial mutations is the same in stages I and IV tumors. In summary, these data suggest that damaging somatic mtDNA mutations occur frequently (13-63%) in these five tumor types and likely confer a selective advantage in oncogenesis.
The association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy.
The effect of black race on disease-free and overall survival was evaluated using Cox proportional hazards models adjusted for multiple covariates in a clinical trial population that was treated with anthracycline- and taxane-containing chemotherapy. Categorical variables were compared using the Fisher exact test. All P values are two-sided.
Of 4817 eligible patients, 405 (8.4%) were black. Compared with nonblack patients, black patients had a higher rate of triple-negative disease (31.9% vs 17.2%; P < .001) and a higher body mass index (median: 31.7 vs 27.4 kg/m(2); P < .001). Black race was statistically significantly associated with worse disease-free survival (5-year disease-free survival, black vs nonblack: 76.7% vs 84.5%; hazard ratio of recurrence or death = 1.58, 95% confidence interval = 1.19 to 2.10, P = .0015) and overall survival (5-year overall survival, black vs nonblack: 87.6% vs 91.9%; hazard ratio of death = 1.49, 95% confidence interval = 1.05 to 2.12, P = .025) in patients with hormone receptor-positive HER2-negative disease but not in patients with triple-negative or HER2-positive disease. In a model that included black race, hormone receptor-positive HER2-negative disease vs other subtypes, and their interaction, the interaction term was statistically significant for disease-free survival (P = .027) but not for overall survival (P = .086).
Factors other than disparities in care or aggressive disease contribute to increased recurrence in black women with hormone receptor-positive breast cancer.
In animal models, explosive growth of metastases after removal of the primary tumor has been attributed to abolishment of angiogenesis inhibition. We investigated the influence of (removal of) the primary tumor on vascularization of liver metastases in human colorectal cancer patients. We analyzed vascular density in synchronous liver metastases from patients with the primary tumor in situ, in synchronous metastases from patients with the primary tumor resected and in metachronous metastases. In a limited number of cases, biopsies from metastases from the same patient before and within 3 months after resection were analyzed. In addition, vascular density in metastases was compared to the vascular density in the corresponding primary tumor. Peritumoral and intratumoral vascular density were determined by staining for endothelial antigens CD31 and CD34, respectively. Both peritumoral and intratumoral vascular density were elevated in synchronous metastases from patients with the primary tumor removed compared to synchronous metastases from patients with the primary tumor in situ. Comparable results were observed in patients with metachronous metastases. An increase in vascular density after resection of the colorectal malignancy was also observed in biopsies taken from the same patient before and after tumor resection. Remarkably, vascular density in the liver metastases was always lower than that in the corresponding primary tumor. Our data show for the first time in humans that the presence of a primary tumor is correlated with decreased vascularization of its distant metastases. Resection of the primary tumor results in an increased vascularization of metastatic lesions.
This is the third in a series of articles relating results from a line of research whose intent was to construct a complete history of patient interactions with the health care system using available data sources for all patients diagnosed in 1990 with a primary breast, colorectal, or lung tumour in Manitoba. This article presents details of the development and application of methods to produce TNM staging data on the roughly 2,000 patients in this population. The operational definitions constructed for this research can be adapted for other tumour sites and data sources. Findings include methods developed to overcome the sometimes ambiguous and inconsistent available documentation, which ultimately produced reliable TNM staging data. Survival data for this population by stage of disease are given.
Many members of BCL2 (Bcl-2) apoptosis-related genes were found to be differentially expressed in various malignancies and were proposed as prognostic cancer biomarkers. Recently, a new member of the BCL2 gene family, BCL2L12, was cloned and was found to be expressed in mammary gland. In the present study, 55 specimens from patients with, histologically confirmed, epithelial breast carcinoma were analyzed for BCL2 and BCL2L12 gene expression by RT-PCR. Increased expression of BCL2 gene was found in patients belonging to the age groups <45 or >55 years, as well as in estrogen receptors (ER)-positive patients and in BCL2L12-positive tumors. In addition, BCL2 or BCL2L12-positive patients were found to be almost four times less likely to relapse or die in comparison to BCL2 or BCL2L12-negative patients, respectively. Multivariate analysis revealed that BCL2 and BCL2L12 might be used as independent prognostic biomarkers in breast cancer.
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