Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Survival variability across hospitals after resection for pancreatic adenocarcinoma: A multilevel survival analysis on a high-resolution population-based study.

INTRODUCTION: Resection is the cornerstone of curative management for pancreatic ductal adenocarcinoma (PDAC). Hospital surgical volume influence post-operative mortality. Few is known about impact on survival. METHODS: Population included 763 patients resected for PDAC within the 4 French digestive tumor registries between 2000 and 2014. Spline method was used to determine annual surgical volume thresholds influencing survival. A multilevel survival regression model was used to study center effect. RESULTS: Population was divided into three groups: low-volume (LVC) (<41 hepatobiliary/pancreatic procedures/year), medium-volume (MVC) (41-233) and high-volume centers (HVC) (>233). Patients in LVC were older (p = 0.02), had a lower rate of disease-free margins (76.7% vs. 77.2% and 69.5%, p = 0.028) and a higher post-operative mortality than in MVC and HVC (12.5% and 7.5% vs. 2.2%; p = 0.004). Median survival was higher in HVC than in other centers (25 vs. 15.2 months, p < 0.0001). Survival variance attributable to center effect accounted for 3.7% of total variance. In multilevel survival analysis, surgical volume explained the inter-hospital survival heterogeneity (non-significant variance after adding the volume to the model p = 0.3). Patients resected in HVC had a better survival than in LVC (HR 0.64 [0.50-0.82], p < 0.0001). There was no difference between MVC and HVC. CONCLUSION: Regarding center effect, individual characteristics had little impact on survival variability across hospitals. Hospital volume was a major contributor to the center effect. Given the difficulty of centralizing pancreatic surgery, it would be wise to determine which factors would indicate management in a HVC.

Mid-Infrared Spectroscopy as a New Tool for Ruling Out Spontaneous Bacterial Peritonitis: A Proof-of-Concept Study.

BACKGROUND AND AIMS: A highly sensitive and specific point-of-care method for diagnosing spontaneous bacterial peritonitis (SBP) is currently lacking. The objective of the present study is to evaluate the diagnostic value of a rapid, easy-to-use, mid-infrared fiber evanescent wave spectroscopy (MIR-FEWS) method for ruling out SBP. PATIENTS AND METHODS: Cirrhotic patients (n = 256) at five centers in France were included for suspected SBP or for the scheduled evacuation of ascites fluid. The mid-infrared spectrum of 7 µL of an ascites fluid sample was recorded using a MIR-FEWS system. To define a model for the diagnosis of SBP, the patients were divided into a calibration group (n = 170) and a validation group (n = 86). RESULTS: Most of the patients were male (71%). The mean age was 60.25 years. Alcohol-related liver disease was the most common cause of cirrhosis. SBP was observed in 18% of the patients. For the diagnosis of SBP in the calibration and validation groups, respectively, the model gave areas under the receiver operating characteristic curves of 0.87 and 0.89, sensitivities of 90% and 87%, specificities of 78% and 80%, positive predictive values of 48% and 50%, negative predictive values of 97% and 96%, positive likelihood ratio of 4.09 and 4.35, negative likelihood ratio of 0.13 and 0.16, Youden index of 0.68 and 0.67, and correct classification rates of 80% and 81%. CONCLUSION: The results of this proof-of-concept study show that MIR-FEWS is a highly sensitive diagnostic method for ruling out SBP. The method warrants further investigation.

Sensitivity of fecal immunochemical test and risk factors for interval colorectal cancer in a French population.

BACKGROUND: Colorectal cancer (CRC) screening using fecal immunochemical testing (FIT) aims to detect pre-symptomatic colorectal lesions and reduce CRC mortality. AIMS: The objectives of this study were to determine the FIT sensitivity for diagnosis of CRC, the impact of diagnostic circumstances on treatment and survival, and risk factors for interval cancer (IC). METHODS: This population-based study evaluated the 2016-2017 CRC screening campaign in Finistère, France. CRCs were classified according to diagnostic circumstances: screen-detected CRC (SD-CRC), CRC with delayed diagnosis, IC after negative FIT (FIT-IC), post-colonoscopy CRC, CRC in non-responders and CRC in the excluded population. RESULTS: This study included 909 CRCs: 248 SD-CRCs (6% of positive FIT) and 60 FIT-ICs (0.07% of negative FIT). The FIT sensitivity for CRC was 80.5% (CI95%: 76.1-84.9) at the threshold of 30 µg hemoglobin/g feces used in France. In multivariate analysis, proximal (OR:6.73) and rectal locations (OR:7.52) were associated with being diagnosed with FIT-IC rather than SD-CRC. The FIT positivity threshold maximizing the sum of sensitivity and specificity was found to be 17 µg/g, with 14 additional CRCs diagnosed compared to the current threshold. CONCLUSIONS: Our study confirms the good sensitivity of FIT. A decrease of the FIT detection threshold could optimize sensitivity.

Real World Data for Pancreatic Adenocarcinoma from a Population-Based Study in France.

Pancreatic cancer is associated with high mortality rates, and most cases are diagnosed at advanced stages. This study aimed to evaluate the prognostic factors for survival in pancreatic adenocarcinoma. Data from the Finistere registry of digestive database were used in this analysis. This retrospective population-based study included 2117 patients with pancreatic adenocarcinoma diagnosed between 2005 and 2019. Cox regression was used to assess the impact of different prognostic factors. The overall median age was 74 (IQR 65.0−81.0). The majority of pancreatic adenocarcinoma 1120 (52.90%) occurred in the head of the pancreas. The type of surgical resection correlated with age (pancreaticoduodenectomy performed in 13.39% of patients aged under 65 years and only 1.49% of patients aged ≥ 80 years). For the entire cohort, 1-year mortality rate after diagnosis was 77.81%. Chemotherapy was associated with better survival for both operated (HR 0.17 95% CI 0.22; 0.64 p < 0.001) and unoperated patients (HR 0.41 95% CI 0.27; 0.61 p < 0.001). Palliative radiotherapy was associated with improved survival (HR 0.69 95% CI 0.56; 0.85 p < 0.001). Among operated patients, the presence of lung metastases (median 34.06; CI 20.06; 34.66) was associated with better survival compared with liver metastases (median 21.10; CI 18.10; 28.96), peritoneal carcinomatosis (median 11.00; CI 8.53; 14.63), or distant metastases (median 15.16; CI 12.66; 18.13) (p = 0.0001). Age, curative surgery, positive lymph nodes, chemotherapy, and palliative radiotherapy were corelated with overall survival. Surgical resection is the only potentially curative treatment, but less than a quarter of patients were eligible.

Predictors of Survival in Elderly Patients with Metastatic Colon Cancer: A Population-Based Cohort Study.

Oncological strategies in the elderly population are debated. The objective of this study was to determine the predictive factors of survival in patients aged 80 years and older with metastatic colon cancer. Data from four digestive tumour registry databases were used in this analysis. This population-based retrospective study included 1115 patients aged 80 years and older with stage IV colon adenocarcinoma diagnosed between 2007 and 2016. Cox regression was used to assess the impact of different prognostic factors. Age was significantly correlated with the surgical treatment (p < 0.001) but not with overall survival. Patients with a low comorbidity burden had better survival than patients with higher comorbidities scores (9.4 (0−123) versus 7.9 (0−115) months) (p = 0.03). Surgery was more common for proximal colon cancer (p < 0.001), but the location of the primary lesion was not correlated with improved survival (p = 0.07). Patients with lung metastases had a better prognosis than those with liver metastases (HR 0.56 95% CI 0.40, 0.77 p < 0.001); multiple organ involvement had the worst survival (HR 1.32 95% CI 1.15, 1.51 p < 0.001). Chemotherapy was associated with improved survival for both operated (HR 0.45 95% CI 0.35, 0.58 p < 0.001) and non-operated patients (HR 0.41 95% CI 0.34, 0.50 p < 0.001). The majority of patients receiving adjuvant treatment had a low comorbidity burden. In our study, the location of metastases but not the primary tumor location had an impact on overall survival. Low comorbidity burden, curative surgery, and chemotherapy had a significant advantage for elderly patients with metastatic colon cancer.

Incidence and Survival in Synchronous and Metachronous Liver Metastases From Colorectal Cancer.

Importance: Although treatment and prognosis of synchronous liver metastases from colorectal cancer are relatively well known, a comparative description of the incidence, epidemiological features, and outcomes of synchronous and metachronous liver metastases is lacking. The difference in prognosis between patients with synchronous and metachronous liver metastases is controversial. Objective: To investigate temporal patterns in the incidence and outcomes of synchronous vs metachronous liver metastases from colorectal cancer. Design, Setting, and Participants: This population-based cohort study used information from a French regional digestive cancer registry accounting for 1 082 000 inhabitants. A total of 26 813 patients with a diagnosis of incident colorectal adenocarcinoma diagnosed between January 1, 1976, and December 31, 2018, were included. Data were analyzed from February 7 to May 20, 2022. Main Outcomes and Measures: Age-standardized incidence was calculated. Univariate and multivariate net survival analyses were performed. Results: Of 26 813 patients with colorectal cancer (15 032 men [56.1%]; median [IQR] age, 73 [64-81] years), 4546 (17.0%) presented with synchronous liver metastases. The incidence rate of synchronous liver metastases was 6.9 per 100 000 inhabitants in men and 3.4 per 100 000 inhabitants in women, with no significant variation since 2000. The 5-year cumulative incidence of metachronous liver metastases decreased from 18.6% (95% CI, 14.9%-22.2%) during the 1976 to 1980 period to 10.0% (95% CI, 8.8%-11.2%) during the 2006 to 2011 period. Cancer stage at diagnosis was the strongest risk factor for liver metastases; compared with patients diagnosed with stage II cancer, patients with stage III cancer had a 2-fold increase in risk (subdistribution hazard ratio, 2.42; 95% CI, 2.08-2.82) for up to 5 years. Net survival at 1 year was 41.8% for synchronous liver metastases and 49.9% for metachronous metastases, and net survival at 5 years was 6.2% for synchronous liver metastases and 13.2% for metachronous metastases. Between the first (1976-1980) and last (2011-2016) periods, the adjusted ratio of death after synchronous and metachronous metastases was divided by 2.5 for patients with synchronous status and 3.7 for patients with metachronous status. Conclusions and Relevance: In this study, the incidence of colorectal cancer with synchronous liver metastases changed little over time, whereas there was a 2-fold decrease in the probability of developing metachronous liver metastases. Survival improved substantially for patients with metachronous liver metastases, whereas improvement was more modest for those with synchronous metastases. The differences observed in the epidemiological features of synchronous and metachronous liver metastases from colorectal cancer may be useful for the design of future clinical trials.

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.

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 .

Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications.

A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

Efficacy of Treatments for Cholestatic Pruritus: A Systemic Review and Meta-analysis.

Cholestatic itch is a disabling symptom that may be secondary to liver or biliary diseases. Management of cholestatic pruritus is complex. A systematic review and meta-analysis on the efficacy of treatments for cholestatic pruritus were performed. PubMed and Cochrane Library were searched using the algorithm "(hepatitis OR cholestatic OR liver) AND (pruritus OR itch) AND (management OR treatment OR treatments)" for 1975-2019. Of the 2,264 articles identified, 93 were included in a systematic review and 15 in a meta-analysis (studies evaluating pruritus with a visual analogue scale). Some treatments act by reducing levels of pruritogens in the enterohepatic cycle, others modify the metabolism or secretion of these pruritogens, or act on pruritus pathways. A further possible treatment is albumin dialysis. However, due to many heterogeneities in the reviewed studies it is difficult to identify and recommend an optimum treatment. Only 15 studies were included in the meta-analysis, due to the small number of randomized studies using a visual analogue scale.

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.

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.