Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Factors associated with non-presentation in a multidisciplinary team meeting for colon cancer: A matched retrospective cohort study in a French area.

BACKGROUND: Survival of patients with colon cancer has increased in recent years due to advances in treatment and the implementation of multidisciplinary team meetings (MDTm). However, the organization of MDTm can be improved. The objectives of this work were to characterize patients with colon cancer who were not presented in MDTm and to analyse the reasons for their non-presentation. METHODS: The study was based on a retrospective cohort including patients with colon cancer diagnosed between 2014 and 2016. Risk factors for non-presentation in MDTm were investigated after 1:1 matching on age, gender and tumour location, using multivariate analysis. RESULTS: amongst 1616 patients diagnosed with colon cancer, 20.5% were not presented in MDTm. The most common reasons for non-presentation were 'advanced age or poor general condition' (22.6%) and 'superficial tumour' (20.5%), while 20.8% of non-presentation remained unexplained. Non-presentation in MDTm was associated with ECOG PS of 2 (OR 0.51, 95%CI 0.32-0.81, p = 0.005), best supportive care (OR 0.05, 95%CI 0.00-0.38, p = 0.016) and early death (OR 0.09, 95%CI 0.04-0.19, p<0.001). By contrast, patients with symptomatic tumours were more likely to be presented in MDTm than patients participating in mass screening (OR 2.16, 95%CI 1.09-4.32, p = 0.028). Presentation was significantly associated with diagnosis by a digestive surgeon (OR 2.16, 95%CI 1.22-3.92, p = 0.01) and a high UICC stage. CONCLUSIONS: This study identified factors associated with non-presentation in a multidisciplinary team meeting for colon cancer such as an advanced age or a superficial tumour, paving the way for targeted improvements.

Care Management and Survival of Patients Diagnosed with Synchronous Metastatic Colorectal Cancer: A High-Resolution Population-Based Study in Two French Areas.

Population-based studies provide the opportunity to assess the real-world applicability of current clinical practices. The present research evaluated the survival outcomes of different therapeutic strategies for colorectal cancer (CRC) with synchronous metastasis (SM). The differential impact of treatment sequence, viz. whether chemotherapy (CT) or primary tumor resection (PTR) was performed first, was also evaluated. METHODS: All CRC cases with SM diagnosed between 2006 and 2016 (N = 3062) were selected from two specialized digestive cancer registries from northwest France. Cox regression analysis was used to assess survival. Multivariable logistic regression was used to examine factors related to the combination of PTR and CT. RESULTS: The longest survival was observed in patients treated by PTR combined with CT (Group 4; N = 1159). Overall survival was 51.80% at one year (95% Confidence Interval (CI) 50.00-53.60%) and 9.40% at five years (95% CI, 8.30-10.60%). Survival did not differ with respect to the order of treatment in multivariable analysis (hazard ratio, 1.05; 95% CI, 0.88-1.24; p = 0.55). CONCLUSION: Regardless of the sequence of treatment, a PTR + CT offered the best survival in patients with CRC and SM, even though few were eligible for combination therapy (38%).

Improvement of participation rate in colorectal cancer (CRC) screening by training general practitioners in motivational interviewing (AmDepCCR).

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death in France (17,712 annual deaths). However, this cancer is preventable in the majority of cases by the early detection of adenomas. In France, the organized screening for CRC relies on general practitioners (GPs). The tests delivered by the GPs are carried out in 89% of cases. However, GPs do not systematically offer the test, because of time management and communication. METHODS: AmDepCCR is a cluster randomized trial. Patients are prospectively included by their GPs. The study is designed in 2 phases for the GPs: first, GPs who have never participated in motivational interviewing (MI) training will be recruited then randomly split in 2 groups. Secondly, a 6-day motivational interviewing training will be carried out for the intervention group. Then, patients will be included in both groups during a period of 1 year. The primary outcome will be the number of CRC screenings achieved in each group and its difference. The secondary outcome will be the reluctance to screening and the patient's self-estimated life expectancy at 0, 6, 12, and 24 months using the Health Belief Model (HBM). DISCUSSION: This study will help to know if GPs motivational interviewing is useful to improve organized CRC screening. In addition, it may help to improve communication between patients and GPs. GPs will be able to improve their practice in other fields of application through motivational interviewing (other screenings, addictions…). TRIAL REGISTRATION: 2019-A01776-51 NCT04492215 .

Influence of non-clinical factors on restorative rectal cancer surgery: An analysis of four specialized population-based digestive cancer registries in France.

BACKGROUND: This study aims to measure the association between deprivation, health care accessibility and health care system with the likelihood of receiving non-restorative rectal cancer surgery (NRRCS). METHODS: All adult patients who had rectal resection for invasive adenocarcinoma diagnosed between 2007 and 2016 in four French specialised cancer registries were included. A multilevel logistic regression with random effect was used to assess the link between patient and health care structure characteristics on the probability of NRRCS. RESULTS: 2997 patients underwent rectal cancer resection in 68 health care structures: 708 (23.63%) had NRRCS. The likelihood of receiving NRCCS was associated with patients' characteristics (97%): age, sub peritoneal rectal tumors, neoadjuvant therapy, residual tumour and stage III . There was no impact of European Deprivation Index or remoteness on NRRCS. Inter-health care structure variability was modest (3%), of which 50% was explained by the high group volume of colorectal procedures and the type of health care structure which were associated with less NRRCS (p<0.01). CONCLUSION: There is an influence of operating volume and type of structure on the probability of NRRCS, but it has truly little importance in explaining differences in performances. The probability of NRRCS is mainly affected by clinical determinant.

Socioeconomic Environment and Survival in Patients with Digestive Cancers: A French Population-Based Study.

Social inequalities are an important prognostic factor in cancer survival, but little is known regarding digestive cancers specifically. We aimed to provide in-depth analysis of the contextual social disparities in net survival of patients with digestive cancer in France, using population-based data and relevant modeling. Digestive cancers (n = 54,507) diagnosed between 2006-2009, collected through the French network of cancer registries, were included (end of follow-up 30 June 2013). Social environment was assessed by the European Deprivation Index. Multidimensional penalized splines were used to model excess mortality hazard. We found that net survival was significantly worse for individuals living in a more deprived environment as compared to those living in a less deprived one for esophageal, liver, pancreatic, colon and rectal cancers, and for stomach and bile duct cancers among females. Excess mortality hazard was up to 57% higher among females living in the most deprived areas (vs. least deprived) at 1 year of follow-up for bile duct cancer, and up to 21% higher among males living in the most deprived areas (vs. least deprived) regarding colon cancer. To conclude, we provide a better understanding of how the (contextual) social gradient in survival is constructed, offering new perspectives for tackling social inequalities in digestive cancer survival.

Ostomy prevalence and survival in elderly patients with stage III and IV rectal cancer.

AIM: Oncological strategies in the elderly population are often debated. The objective of this study was to investigate the survival rates and prevalence of ostomy in elderly patients operated on for stage III and IV rectal cancers. METHODS: This retrospective multicentric population-based study included 151 patients aged ≥75 years with stage III and IV rectal adenocarcinoma who underwent surgery between 2007 and 2014. Multivariable logistic regression was used to assess the impact of different prognostic factors. RESULTS: The median age of the patients was 81 years (range: 75-97 years) with 40 patients >85 years of age. Age was significantly correlated with overall survival (OS) in both stage III and IV cancers (P < 0.001). For patients ≥80 years the presence of comorbid conditions was associated with a lower chance of survival (P = 0.02). A digestive stoma was created in 67 (76.1%) patients with stage III cancer and 26 (29.54%) had a stoma reversal. A palliative derivative stoma was performed in half of patients with stage IV cancer. Adjuvant chemotherapy was independently associated with improved 5-year OS (P < 0.001). CONCLUSIONS: Age, comorbidities and adjuvant chemotherapy were independent predictors for OS. Resection of rectal tumors in fit elderly patients should be promoted; however, patients should be aware of the high risk of stoma. Geriatr Gerontol Int 2021; 21: 670-675.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

MSI-High RAS-BRAF wild-type colorectal adenocarcinomas with MLH1 loss have a high frequency of targetable oncogenic gene fusions whose diagnoses are feasible using methods easy-to-implement in pathology laboratories.

Targetable kinase fusions are extremely rare (<1%) in colorectal cancers (CRCs), making their diagnosis challenging and often underinvestigated. They have been shown particularly frequently among MSI-High, BRAF/KRAS/NRAS wild-type CRCs with MLH1 loss (MLH1loss MSI-High wild-type). We searched for NTRK1, NTRK2, NTRK3, ALK, ROS1, BRAF, RET, and NRG1 kinase fusions in CRCs using methods easy-to-implement in pathology laboratories: immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and fully automated real-time PCR targeted analyses. RNA-sequencing analyses were used for confirmation. Among 84 selected MLH1 deficient (IHC) CRCs cases, MLH1loss MSI-High wild-type CRCs consisted first in 19 cases after Idylla™ analyses and finally in 18 cases (21%) after RNA-sequencing (detection of one additional KRASG12D mutation). FISH (and when relevant, IHC) analyses concluded in 5 NTRK1, 3 NTRK3, 1 ALK, 2 BRAF, and 2 RET FISH positive tumors. ALK and NTRK1 rearranged tumors were IHC positive, but pan-TRK IHC was negative in the 3 NTRK3 FISH positive tumors. RNA-sequencing analyses confirmed 12 of 13 fusions with only one false positive RET FISH result. Finally, 12/18 (67%) of MLH1loss MSI-High wild-type CRCs contained targetable kinase fusions. Our study demonstrates the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on nonsequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs, as well as the high prevalence of these kinase fusions in MLH1loss MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.

Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST).

Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes. Thus, an adequate testing strategy permitting to diagnose the rare NTRK-rearranged GISTs is required. In this work, we studied about the performances of pan-TRK immunohistochemistry (IHC) and NTRK1/2/3 fluorescent in situ hybridization in a series of 39 GISTs samples. Among 22 patients with GISTs lacking KIT or PDGFRA mutations, BRAFV600E IHC permitted to diagnose 2/22 (9%) BRAFV600E-mutated GISTs and, among the 20 KIT, PDGFRA, and BRAF wild type tumors, 1/20 (5%), NTRK3-rearranged tumor was diagnosed using NTRK3 fluorescent in situ hybridization. Pan-TRK IHC using EPR17341 and A7H6R clones was negative in this NTRK3-rearranged sample. Pan-TRK IHC was frequently positive in NTRK not rearranged tumors without (24 samples analyzed) or with (15 samples analyzed) KIT or PDGFRA mutations with major discrepancies between the 2 IHC clones (intraclass correlation coefficient of 0.3042). Given the new therapeutic opportunity offered by anti-TRK targeted therapies to treat patients with advanced cancers including GISTs, it is worth to extend molecular analysis to NTRK fusions testing in KIT, PDGFRA, and BRAF wild type GISTs. Pan-TRK IHC appears not relevant in this field but performing a simple NTRK3 fluorescent in situ hybridization test consists in a valuable approach to identify the rare NTRK3-rearranged GISTs treatable using anti-TRK therapies.

Prognostic factors for stage III colon cancer in patients 80 years of age and older.

PURPOSE: Oncological strategies in the elderly population are debated. The objective of this study was to assess the factors predictive of poor prognosis in elderly patients with stage III colon cancer. METHODS: A retrospective review of demographic, pathologic, treatment, and outcome data from 308 patients with stage III colon adenocarcinoma who had undergone surgery between 2007 and 2014 was conducted. A proportional hazards model was used to assess the association of prognostic factors with disease-free survival (DFS) and overall survival (OS). RESULTS: The 5-year survival rate was 34.4% (95% CI 27.1-39.8%) and Charlson comorbidity index was a significant predictor of death (p < 0.01). The presence of perineural invasion (p = 0.03) and incomplete resection (p < 0.001) were significantly correlated with OS. The postoperative (30 days) mortality rate was 11.7%. Adjuvant chemotherapy was significantly associated with better OS (p < 0.001) independently of the regimens. Disease-free survival was significantly correlated with adjuvant chemotherapy (HR 0.63, 95% CI: 0.42-0.97, p = 0.034), Charlson comorbidity index (CCI 5; HR 1.61, 95% CI: 1.05-2.48, p = 0.029), and venous and/or perineural invasion (HR 1.54, 95% CI: 1.03-2.29, p = 0.035). CONCLUSION: Age, comorbidities, tumor histology, and adjuvant chemotherapy were independent predictors of prognosis in patients with stage III colon cancer. These data can be used to identify elderly patients with poor prognosis and to design future tailored randomized clinical trials. TRIAL REGISTRATION: ClinicalTrial.gov No. NCT04526314. Date of registration 25 August 2020.

Comparative evaluation of two colorectal cancer screening campaigns using different faecal occult blood tests in a French area.

OBJECTIVE: The aim of this study was to compare quality performance of the first colorectal cancer (CRC) screening campaigns (C) with the OC Sensor® Faecal Immunological Test (FIT) (C7 from 2016 to 2017) and the Hemoccult® guaiac-based test (C1 from 2004 to 2006). METHODS: The participation rate of the eligible population, screening fecal occult blood test (FOBT) performance indices, CRC and adenoma detection rate and time interval between test positivity and colonoscopy were studied. RESULTS: In C7, 35.9 % of the eligible population completed the screening process versus 47.6 % in C1 (p < 0.0001). The positivity rate was of 4.3 % for OC Sensor® FIT and 2.3 % for Hemoccult® test (p < 0.0001). A total of 3,252 colonoscopies were performed in C7 versus 2,005 in C1; 246 CRCs and 1,160 advanced adenomas (AA) were detected in C7 compared to 140 CRCs and 491 AA in C1 (p < 0.0001). The FOBT cancer detection rate increased significantly from 1.4 ‰ to 2.9 ‰ between the two campaigns, as did the FOBT AA detection rate, from 5.7 ‰ to 13.7 ‰. During C7, the mean time for colonoscopy after a positive FIT result was 84.3 days [95 % CI: 77.9-90.7]. There was no significant difference between the stages at diagnosis according to the time for colonoscopy within the first 6 months. CONCLUSIONS: CRC and AA detection rates increased significantly between the two campaigns. Longer follow-up will be required to show a potential decrease in the incidence of invasive CRCs.

Evaluation of KRAS, NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists?

AIM: We aimed to study the prognostic value of KRAS, NRAS, BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC)). METHODS: We led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS, NRAS, BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry). RESULTS: KRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)-proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00). CONCLUSION: Although being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC.

Trends in incidence of small bowel cancer according to histology: a population-based study.

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.

Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer.

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.

High reproducibility is attainable in assessing histoprognostic parameters of pT1 colorectal cancer using routine histopathology slides and immunohistochemistry analyses.

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.

Pancreatic Adenocarcinoma in the Finistère Area, France, Between 2002 and 2011 (1002 Cases): Population Characteristics, Treatment and Survival.

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.