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Background: Small bowel cancer is not a single entity. Population-based studies taking into account histological diversity are scarce. The aim of this study was to report on their trends in incidence by histology in France over the past 20 years., Methods: All patients with a small bowel cancer diagnosed in 15 French administrative areas covered by a registry from the network of French cancer registries (FRANCIM) were included. Age-standardized incidence rates were estimated using the world standard population. Incidence rates were calculated by gender, age group, histology, and 5-year period., Results: The overall age-standardized incidence rates were 1.46/100,000 inhabitants in men and 0.9/100,000 inhabitants in women. Adenocarcinoma was the most common histological type (38%), followed by neuroendocrine tumors (35%), lymphoma (15%) and sarcoma (12%). Age at diagnosis and tumor location differed between adenocarcinoma and neuroendocrine tumors. The incidence of all four tumor types increased significantly over the 20-year period, with the exception of lymphoma in men. The annual percentage change for neuroendocrine tumors was 3.89% in men and 3.61% in women; for sarcoma, it was 3.38% and 4.08%, respectively. The incidence of adenocarcinoma and lymphoma also increased in women with an annual percentage change of 3.05% and 3.32%, respectively., Conclusion: Small bowel cancer incidence has increased over time. This increase occurred with different amplitudes and patterns in the four major histological types. The improvement in imaging techniques could partly explain this increase. It is necessary to determine whether predisposing conditions may contribute to this change.

The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.

Assessment of the risk of lymph node invasion and tumour recurrence is critical to determine whether additional surgery is required in patients with endoscopically-removed pT1 colorectal cancer (CRC). A reproducible assessment of this risk of recurrence based on histopathological parameters is crucial for relevant therapeutic decisions. The inter-observer reproducibility of these parameters was the subject of our study. Two pathologists independently analysed 163 endoscopically-removed pT1 CRC recorded in a local digestive cancer registry database (Finistère, France). Using haematoxylin-eosin-saffron (HES) and immunohistochemistry slides, they evaluated several parameters related to the risk of tumour recurrence according to the international pT1 CRC-dedicated guidelines. Based on Kappa and intra-class correlation coefficients, good to very good inter-observer agreement was obtained by analysing vertical and lateral margins, submucosal invasion, tumour differentiation and lymphovascular invasion. The reproducibility of tumour budding quantification was only fair on the basis of HES slides but reached a very good agreement using cytokeratin immunohistochemistry. Dual colour cytokeratin and podoplanin immunohistochemistry also improved inter-observer agreement for the detection of lymphovascular invasion. All patients with loco-regional nodal metastases (7 of 101 who underwent complementary surgery) or distant metastases (3 patients) were diagnosed as having a high risk of recurrence and requiring an additional surgery by the two observers. Our study showed that good to very good inter-observer agreement is achievable in evaluating the pathological parameters of recurrence risk in endoscopically-removed pT1 CRC. In addition to HES slides, the detection of lymphovascular invasion and tumour budding can benefit with more reproducible immunohistochemical analyses., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objectives: The aims of the study were (a) to describe the characteristics of all incident cases of pancreatic adenocarcinoma diagnosed in the population of the Finistère area between 2002 and 2011, (b) to report on their therapeutic management, and (c) to analyze survival and prognostic factors., Methods: All residents of the administrative region of Finistère who were diagnosed with pancreatic adenocarcinoma between January 2002 and December 2011 were registered in the digestive cancer registry. Survival data were analyzed using the Kaplan-Meier method and were compared using log-rank tests. Multivariate analysis was performed using a binary logistic regression model to identify prognostic factors., Results: A total of 1002 patients with a pancreatic adenocarcinoma were registered, of whom 60% had metastases at diagnosis. Only 10% of patients underwent a potentially curative negative margin resection (R0); their median survival was 22.0 months. The median survival of the overall population was 4.1 months. The stages of the disease and the patient's age were independent prognostic factors in multivariate analysis., Conclusions: Our study confirms the dramatic prognosis of this cancer. Because the tumor stage is the main prognostic factor in pancreatic adenocarcinoma, efforts should focus on the earlier diagnosis of pancreatic cancer.

Background: Colorectal cancer (CRC) mainly develops from colorectal adenomas (CRAs). MicroRNAs (miRs) are short non-coding transcripts that regulate gene expression by binding to target mRNAs, preventing their expression. It was suggested that miRs were involved in cancer as tumour suppressors or oncogenes, thereby being also potential cancer biomarkers. We conducted an expression analysis of miRNAs and several of their target mRNAs, by using microarrays and quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) (RT-qPCR), in CRA and CRC, as compared to normal mucosa (NOR), in order to identify candidate miRNAs involved in CRC progression., Results: Microarray, together with confirmatory RT-qPCR analyses, showed 17 significantly deregulated miRNAs in colorectal lesions. While, as expected, some miRNAs have been previously reported to be associated with CRC, including miR-21 and miR-145, others were new (miR-125a-5p and miR-320 family). Some miRNAs were specific for the CRC versus NOR comparison (miR-320b), or for the CRA versus NOR comparison (miR-15b or miR-16), but several of them (miR-21, miR-24, miR-145, mir-150, miR-378) were deregulated in both CRAs and CRCs, as compared to NOR. The impact of these changes in miR expression on target genes is suggested by the associated deregulation of these genes in CRA and CRC., Conclusions: We confirmed that several miRNAs were abnormally expressed in colorectal lesions, identified new deregulated miRs, and showed that several miRNAs could mark the transition from NOR to CRA, thereby marking progression from the early steps of cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.

Adenocarcinoma developed in Barrett's oesophagus is a tumour with an increasing incidence and still a poor prognosis. The only marker that can be used for surveillance remains dysplasia (intraepithelial neoplasia), especially when it is high-grade, that precedes intramucosal carcinoma. New forms of dysplasia have been described in complement to the classical intestinal type (foveolar dysplasia, basal crypt dysplasia). High-grade dysplasia and intramucosal carcinoma are diagnosed on biopsies taken during endoscopy. Standard endoscopy is now challenged by various techniques that represent recent major technical improvements (chromoendoscopy, virtual chromoendoscopy, optical frequency domain imaging, confocal laser endomicroscopy). In numerous cases, high-grade dysplasia and intramucosal carcinoma can be treated by endoscopic procedures, allowing a precise histopathological diagnosis on the resected specimen (endoscopic mucosal resection, submucosal endoscopic dissection) or destroying the neoplastic tissue. Radiofrequency ablation is currently considered as the best available technique for treatment of flat high grade dysplasia and for eradication of residual Barrett's mucosa after focal endoscopic mucosal resection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.

The TP53 gene is the most frequently mutated gene in human cancers. Barrett's esophagus provides an excellent model by which to understand the genetic events that lead from dysplasia to cancer. We screened for mutations in the TP53 gene by a combination of denaturing gradient gel electrophoresis and DNA sequencing in ten cases of adenocarcinoma arising in Barrett's mucosa. We have identified missense mutations in five of the ten samples, three transitions (R282W, G245S, R248W) and two transversions (E286Q and C176F). In one case we have analyzed biopsy specimens taken from the same site, one year before the patient developed an intra mucosal carcinoma. The mutation that was identified in this high grade dysplastic area was identical to that detected in the cancer. This would suggest TP53 mutations occur as an early genetic event in the development of Barrett's adenocarcinoma.

Objectives: The aim of this study was to analyze the evolution of treatment regimens and survival rates of stomach adenocarcinoma recorded in the Finistère cancer registry from 1984 to 1989., Methods: In a population of 838,627 inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated by the actuarial method, and compared using the logrank test and the Cox model., Results: Surgical resection was the main treatment for 661 patients (57%). The frequency of curative resection increased from 25% between 1984 and 1986 to 35% after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only symptomatic treatment. The survival rates of all patients were 43% at 1 year and 20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with cancer managed surgically, the factors associated with a better prognosis were young age, long duration of symptoms before diagnosis, ulcerated macroscopic aspect, limited tumour extension and curative surgical resection. In other patients, 2 factors were associated a with better prognosis: the absence of metastases and an endoscopic palliative treatment., Conclusions: Surgical resection is the main treatment of gastric adenocarcinoma. Although the frequency of surgery increased, the prognosis of gastric adenocarcinoma did not improve within this 6-year period.

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.

Dysplasia is the only marker for malignant potential in Barrett's esophagus. The histologic interpretation of dysplasia is sometimes difficult, particularly when attempting to distinguish dysplastic changes from those of a regenerating and inflammatory mucosa. In order to find an objective marker to identify patients with high risk of malignant transformation, the authors evaluated 497 biopsies from 66 patients with Barrett's esophagus with flow cytometry. The aim of the study was to correlate DNA content and proliferative abnormalities with histology. All biopsies classified histologically as negative for dysplasia had a diploid DNA content. The percentage of biopsies with an aneuploid DNA content increased with the histologic grade of dysplasia: 2 percent of indefinite dysplasia, 11 percent of low grade dysplasia, 44 percent of high grade dysplasia and 78 percent of biopsy specimens with cancer biopsies were aneuploid. Mean S and G2M fractions of diploid biopsy specimens increased with the severity of histologic changes. The S and G2M fraction threshold values that could differentiate patients that were negative for dysplasia from those with high grade dysplasia or cancer were 9 percent and 6 percent, respectively. Aneuploidy or G2M fraction greater than 6 percent was the best discriminating criteria between those two distinct groups of patients. All 6 patients with high grade dysplasia or cancer had aneuploid cell populations or increased G2M fraction, whereas none of the 35 patients whose biopsies were histologically negative for dysplasia had evidence of genomic instability or increased G2M fraction. Flow cytometric abnormalities were found in 10 out of 25 patients whose biopsies were classified as indefinite for dysplasia or low grade dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)