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The anatomic location of pancreatic cancer is a prognostic factor for survival.

ABSTRACT: BACKGROUND: Pancreatic cancers of the body and tail (BT) appear to have poorer survival compared with head (HD) lesions. We hypothesized that potential disparities in outcome may be related to tumor location. Our objective was to examine the relationship between tumor location and survival. METHODS: The Surveillance, Epidemiology, and End Results registry identified 33,752 patients with pancreatic adenocarcinoma and 6443 patients who underwent cancer-directed surgery between 1988 and 2004. Differences in survival and relationships between tumor location and clinical factors were assessed. Multivariate analysis was performed to determine the prognostic significance of tumor location. RESULTS: Median survival for the entire cohort was five months and was significantly lower for BT compared to HD lesions (four vs. six months, p<0.001). Distant metastases (67% vs. 36%, p<0.001) were greater and cancer-directed surgery (16% vs. 30%, p<0.001) was lower for BT tumors. Of 6443 resected patients, HD patients (n=5118) were younger, had a greater number of harvested lymph nodes, were more likely to be lymph node-positive, and had a higher proportion of T3/T4 lesions. Significant univariate predictors of survival included age, T-stage, number of positive and harvested lymph nodes. On multivariate analysis, BT location was a significant prognostic factor for decreased survival (OR 1.11, 95% CI 1.00-1.23, p=0.05). DISCUSSION: Pancreatic BT cancers have a lower rate of resectability and poorer overall survival compared to HD lesions. Prospective large-cohort studies may definitively prove that tumor location is a prognostic factor for survival in patients with pancreatic cancer.

SUBMITTER: Artinyan A

PROVIDER: S-EPMC2575681 | biostudies-other | 2008

REPOSITORIES: biostudies-other

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Project description:The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670-0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens.

Project description:BackgroundSmall bowel cancer (SBC) is a very rare solid malignancy. Consequently, compared with other malignant gastrointestinal tumors, our knowledge regarding SBC, specifically its molecular attributes, remains limited. Herein, we aim to provide an overview of the gene characteristics of Chinese patients with SBC, We particularly focus on elucidating the genetic intricacies that differentiate SBC patients whose primary tumors originate in distinct anatomical regions within the small bowel.MethodsDuring the period ranging from February 2018 to December 2022, a total of 298 tumor samples were consecutively collected from Chinese patients diagnosed with small bowel cancer.. Next-generation sequencing (NGS) was performed to detect gene mutation, assess microsatellite instability (MSI), and evaluate tumor mutational burden (TMB). Additionally,, IHC was used to analyze the level of PD-L1 expression within the samples.ResultsThe outcomes of the next-generation sequencing (NGS) unveiled the predominant gene mutations observed in Chinese patients with small bowel cancer (SBC). The top ten gene mutations identified were as follows: TP53 (53%), KRAS (51%), APC (31%), SMAD4 (19%), VEGFA (15%), CDKN2A (15%), RAC1 (15%), LRP1B (14%), MGMT (14%, CD74 (13%). Subsequent analysis revealed disparities in the gene landscape between the cohort in this study and that of the Memorial Sloan Kettering Cancer Center (MSKCC), Notably, distinguishable mutational frequencies were identified in several genes, including ERBB2, FBXW7, PIK3CA, etc. which exhibited contrasting presence in both this cohort and the MSKCC cohort.. Furthermore, we noticed variations in the frequency of gene mutations among SBC patients depending on the specific anatomical site where the tumors originated within the small bowel. In addition, the distribution of patients with high microsatellite instability (MSI-H) and tumor mutational burden (TMB) levels varied among SBC patients with tumors originating from the duodenum, jejunum, and ileum.ConclusionChinese patients with small bowel cancer exhibited a distinct genetic profile in comparison to other populations, highlighting a unique genetic landscape. Furthermore, noticeable disparities in the genetic landscape were observed between patients with cancer situated in the duodenum and those with cancer affecting other regions of the small bowel, this suggests that these patients should be treated differently.

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The anatomic location of pancreatic cancer is a prognostic factor for survival.

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