Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases.

BACKGROUND: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS: A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). CONCLUSIONS: There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.

Should we screen for colorectal cancer in people aged 75 and over? A systematic review - collaborative work of the French geriatric oncology society (SOFOG) and the French federation of digestive oncology (FFCD).

BACKGROUND: We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations. METHODS: PUBMED database was searched in October 2021 for articles published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines. RESULTS: Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80-85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case. CONCLUSION: The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75-80 age group. IRB: An institutional review board composed of members of the 2 learned societies (SOFOG and FFCD) defined the issues of interest, followed the evolution of the work and reviewed and validated the report.

Biliary tract cancers have distinct epidemiological patterns and clinical characteristics according to tumour site.

BACKGROUND: Little is known about the epidemiology of biliary tract cancers over the last decade. We investigated trends in incidence, treatment and prognosis of biliary tract cancers according to anatomic site. METHODS: 714 biliary tract cancers recorded between 2012 and 2019 in the French population-based cancer registry of Burgundy were included. Trends in world age-standardized incidence were depicted using Poisson regression. RESULTS: Intrahepatic cholangiocarcinoma accounted for 40% of biliary tract cancer. Half of the patients were older than 75 years at diagnosis. Incidence of biliary tract cancer did not vary over time, except a slight increase in intrahepatic cholangiocarcinoma in men and a decrease in the ampulla in both sexes. Among non-metastatic patients, the proportion who underwent R0 resection ranged from 15% for intrahepatic cholangiocarcinoma to 58% for ampulla cancer (p < 0.001). Age, performance status and hospital type were associated with resection. Among unresected patients, 45% received chemotherapy. Older age, jaundice, increasing performance status and comorbidities index negatively affected chemotherapy administration. Net survival was higher for ampulla than for other sites, regardless of patient and treatment characteristics. CONCLUSION: Biliary tract cancers present different patterns in incidence. The ampulla site should be considered separately in clinical trials due to its better outcomes.

Compliance with follow-up guidelines after high-risk colorectal polyp removal: a population-based study.

BACKGROUND AND AIMS: After high-risk colorectal adenoma removal, colorectal cancer risk remains higher than that in the general population. Depending on polyp characteristics, a 3-month or 3-year follow-up colonoscopy is recommended, and clear follow-up instructions must be given to the patient. Our primary aim was to evaluate compliance with French follow-up recommendations. Second, we evaluated the impact of how the information was given and if patients actually underwent their control colonoscopy according to the instructions given. METHODS: We collected data from the Burgundy polyp population-based registry and medical records from the endoscopy centers of the area. Between June 30, 2014 and July 1, 2015, 405 patients were included in this study. RESULTS: Written follow-up instructions were provided to 345 patients (85.2%), and 184 of them (53.3%) complied with guidelines. For 29.9% the interval to follow-up colonoscopy was longer than recommended, and for 6.4% the interval was shorter. Among the 303 patients who had clear follow-up instructions, 42.2% had their control colonoscopy and 83.6% respected the stipulated interval. Follow-up instructions were found in the colonoscopy report in at least 49% of cases. CONCLUSIONS: Compliance with follow-up guidelines was poor: Inappropriate intervals were often longer than recommended. Patients with written follow-up instructions and those who underwent follow-up colonoscopy mostly followed these instructions. Ensuring compliance with guidelines and giving written instructions to patients should be primary goals to achieve effective follow-up. Gastroenterologist training should be improved in this way.

Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients.

Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23-90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz-Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin-based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54-months median follow-up, the 5-year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA-resected tumours, the prognostic factors for OS were grade and T stage.

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

BACKGROUND: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting. MATERIALS AND METHODS: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR). RESULTS: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007). CONCLUSION: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF. IMPLICATIONS FOR PRACTICE: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.

Clinical and economic impact of pharmacist interventions in an ambulatory hematology-oncology department.

OBJECTIVES: To evaluate clinical and financial impact of pharmacist interventions in an ambulatory adult hematology-oncology department. METHODS: All cancer patients receiving a first injectable immuno- and/or chemotherapy regimen were included in this prospective study over a one-year period. The clinical impact of pharmacist interventions made by two clinical pharmacists was rated using the Clinical Economic and Organizational tool. Financial impact was calculated through cost savings and cost avoidance. Main results: Five hundred and fifty-eight patients were included. A total of 1970 pharmacist interventions were performed corresponding to a mean number of 3.5 pharmacist interventions/patient. The clinical impact of pharmacist interventions was classified as negative, null, minor, moderate, major and lethal in 0, 84 (4%), 1353 (68%), 385 (20%), 148 (8%) and 0 cases, respectively. The overall cost savings were €175,563. One hundred and nine (6%) of all pharmacist interventions concerned immuno- or chemotherapy regimen for cost savings of €148,032 (84% of the total amount of cost savings). The cost avoidance was €390,480. Cost avoidance results were robust to sensitivity analyses with cost of preventable adverse drug event as main driver of the model. When the cost of employing a pharmacist was subtracted from the average yearly cost savings plus cost avoidance per pharmacist, this yielded a net benefit of €223,021. The cost-benefit ratio of the clinical pharmacist was €3.7 for every €1 invested. Principal conclusions: To have two full-time clinical pharmacists in a 55-bed ambulatory adult hematology-oncology department is both clinically and financially beneficial.

Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population.

OBJECTIVE: Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs. DESIGN: We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology. RESULTS: Age-standardised incidence of MPs in patients aged 50-74 years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024). CONCLUSION: Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.

Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC. METHODS: The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life. RESULTS: After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. CONCLUSION: Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC. LAY SUMMARY: Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.

Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases.

PURPOSE: To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3 rd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. CONCLUSION: This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC.

Time trends in colorectal cancer early postoperative mortality. A French 25-year population-based study.

BACKGROUND: Postoperative mortality after resection of colorectal cancer is an important issue. The aim of this study was to assess early postoperative mortality in a well-defined French population. METHODS: Data on 30- and 90-day postoperative mortality after resection for colorectal cancer were extracted from the digestive cancer registry of Burgundy. Time trends of postoperative mortality between 1989 and 2013 were described for the large population. Case-control studies (death within 30 or 90 days = cases, alive at 90 days = controls) focused on the association between postoperative mortality and surgical approach, obesity and other comorbidities over the last [2010-2013] period, using conditional logistic regressions. RESULTS: Among the 11,448 concerned patients, 30- and 90-day postoperative mortalities were 4.9 and 7.2%. Thirty-day operative mortality decreased from 7.2% (1989-1993) to 4.4% (2010-2013; p < 0.001) for colon cancer and from 4.2 to 3.3% for rectal cancer (NS). Diagnosis before 1997, male gender, advanced age, emergency surgery and palliative resection were associated with a significantly higher 30- and 90-day mortality rate. The univariate risk of mortality was two to three times higher for conventional open laparotomy and conversion than for laparoscopy-assisted surgery. The surgical approach was no longer significant in multivariate analysis. Emergency surgery and comorbidities were associated with higher 30- and 90-day postoperative mortality, whereas obesity was not specific. CONCLUSION: Postoperative mortality after colorectal resection decreased over time. Surgical approach had no influence on early mortality. Improvement in the management of the elderly and patients with comorbidities is a challenge to reduce postoperative mortality in the future.

Early Gastric Cancer: Trends in Incidence, Management, and Survival in a Well-Defined French Population.

BACKGROUND: Little is known about the epidemiology of early gastric cancer (EGC) in Western countries. The aim of this study was to analyze trends in the incidence, management, and survival of EGC in a well-defined population over a 30 year period. METHODS: Data were obtained from the population-based cancer Registry of Burgundy (France). Incidence rates were calculated by sex, age, and 10 year period of diagnosis. Net survival rates were calculated and a multivariate relative survival analysis performed. RESULTS: EGC represented 6.7 % of gastric cancer diagnosed between 1982 and 2011. Age-standardized incidence rates were higher in men (0.79/100,000) than in women (0.40/100,000). Between the periods 1982-1991 and 2002-2011, it decreased from 0.97 to 0.53 per 100,000 in men and from 0.44 to 0.30 per 100,000 in women. Overall, 19 % of the tumors were limited to the mucosa, 69 % to the submucosa, and 15 % invaded lymph nodes. Node invasion and male sex were the only significant prognostic factors. Five-year net survival was 50 % in node-positive patients and 85 % in node-negative patients (p < 0.001). In multivariate analysis, the relative risk of death in men compared to women was 2.3 and was 10.4 in patients with positive nodes compared to patients with negative nodes. CONCLUSIONS: EGCs are rare in France. The prognosis is favorable, except for node-positive cancers, which may benefit from the recently developed adjuvant chemotherapy for gastric cancer.

Frequency of and risk factors for the surgical resection of nonmalignant colorectal polyps: a population-based study.

BACKGROUND AND STUDY AIMS: The management of patients with colon polyps who are referred to surgery remains uncharacterized in a population-based setting. The aims of this study were to determine the frequency, risk factors, and outcomes of patients referred for surgical resection of colorectal polyps. PATIENTS AND METHODS: All patients who underwent a colonoscopy for positive fecal occult blood test in the setting of a population-based colorectal cancer screening program in France between 2003 and 2012 were analyzed. The primary outcome was the proportion of patients undergoing colorectal surgery for polyps without invasive carcinoma. Logistic regression analysis was applied to identify risk factors for surgical resection. RESULTS: Among 4251 patients with at least one colorectal polyp, 175 (4.1 %) underwent colorectal surgery. Risk factors for surgery included size, proximal polyp location, advanced histology (villous or high grade dysplasia), the endoscopy center, and colonoscopy performed during the first half of the study period. Subgroup analysis of 3475 colonoscopies performed by 22 endoscopists who performed at least 50 colonoscopies during the study period, identified the endoscopist as an additional risk factor. The adjusted proportions of referrals to surgery ranged from 0 to 46.6 % per endoscopist for polyps ≥ 20  mm (median 20.2 %). Overall, surgical complications occurred in 24.0 %, and one patient died following surgery (0.5 %). None of the 175 patients who underwent surgery were referred to a tertiary endoscopic center prior to surgery. CONCLUSIONS: In this population-based study, 4.1 % of patients with nonmalignant polyps were referred for surgical resection. The endoscopist was one important factor that was associated with surgical referral. To further decrease the proportion of inappropriate surgery in patients, endoscopists should refer their patients with large or difficult polyps to expert endoscopists prior to surgery.

Incidence and patterns of late recurrences in colon cancer patients.

Long-term recurrences of colon cancer raised questions about the possible benefit of prolonging the recommended active 5-year surveillance. The aim of this study was to determine, for the first time, the incidence and patterns of late 10-year recurrence following curative resection of colon cancer. Data were obtained from two French digestive cancer registries. A total of 3,622 patients under 85 years resected for cure for colon cancer diagnosed between 1985 and 2000 were included. Information regarding recurrences was actively collected. Cumulative failure rates at 10 years were estimated using Kaplan-Meier estimates corrected by cause-specific hazards, and multivariable analysis was performed using a model for the subdistribution of a competing risk proposed by Fine and Gray. The overall cumulative recurrence rate between 5 and 10 years after initial surgery was 2.9% for local recurrence and 4.3% for distant metastasis. Among men with no recurrence 5 years after diagnosis of colon cancer, 1 in 12 developed a recurrence between 5 and 10 years, and the corresponding cumulative rate was 7.8%. The frequency was 1 in 19 for women, corresponding to a cumulative rate of 5.2%. In the multivariate analysis, non-emergency diagnostic feature, female sex and age under 75 were associated with a lower risk of recurrence. Stage at diagnosis was not a predictor of late recurrence. Late recurrence after colon cancer resection with curative intent can occur. A regular clinical follow-up is necessary to detect early signs of possible recurrence.

[Screening and prevention of colorectal cancer]. / Dépistage et prévention du cancer colorectal.

Population-based studies have shown that guaiac faecal occult blood testing followed by colonoscopy in case of positivity can reduce colorectal cancer mortality. However attention has been given for alternative tests in particular to immunochemical faecal occult blood tests. It is now clear from available data that immunochemical tests outperform guaiac tests. They should be preferred for CRC screening. The one sample strategy has been adopted in most screening programmes. Given the superior performance characteristics of immunochemical, it is reasonable to assume that an organized programme using this type of test would lead to a greater reduction in colorectal cancer mortality and possibly of colorectal cancer incidence. Epidemiological studies allow us to define subjects at very high risk (genetic origin) and high risk for colorectal cancer. Colonoscopy screening is recommended in first degree relatives of patients with colorectal cancer or large adenoma diagnosed before 60 years or with two affected first-degree relatives, in subjects with an extended inflammatory bowel disease, or with a personal history of large bowel cancer or large adenoma.

Trends in incidence of infrequent and frequent synchronous metastases from colorectal cancer.

BACKGROUND: Population-based data on the incidence of frequent colorectal metastases are fairly scarce, while that on rare metastatic sites are lacking. AIMS: The aim of this study was to provide epidemiological indicators of metastatic sites frequency in patients with colorectal cancer. METHODS: Incidence was modelled using Poisson and Joinpoint regressions in a population-based cancer registry study including metastatic colorectal cancers diagnosed between 1991 and 2020 (N = 5,199). Tumor molecular markers were collected for the [2016-2020] period. RESULTS: Liver, peritoneum, lung and bone were the most frequent metastatic sites. Among frequent sites, incidence of liver and lung sites decreased in men respectively since 1999 and 2010, whereas in women incidence of liver and peritoneum sites increased steadily throughout the whole period. Each of the other sites concerned less than 3% of metastatic colorectal cancer cases and presented standardized incidence rates between 0.19 and 1.39 per 1,000,000. Among rare sites, incidence of adrenal glands, supraclavicular lymph node, mediastinum and ascites had doubled in [2016-2020] as compared to the 25 previous years. BRAFV600E variant was more frequent in presence of carcinomatosis, and absence of liver and lung metastasis while KRAS variant was more frequent in presence of lung metastasis. CONCLUSION: This study provides unprecedented incidence indicators for rare synchronous metastases of colorectal cancer.

Visceral fat and clinical outcome in patients receiving first-line chemotherapy with bevacizumab for metastatic colorectal cancer.

BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.

Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

Screening and management of portal hypertension in advanced hepatocellular carcinoma: A French practice survey.

BACKGROUND: Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are two major complications of cirrhosis that are closely linked and impact patients prognosis, particularly acute variceal bleeding (AVB). Therefore, PHT screening and AVB prophylaxis are major issues to improve the outcome of the patients, but practices may vary among physicians. METHODS: We submitted hepatologists, gastroenterologists and digestive oncologists to a questionnaire of 70 items about PHT screening and management to evaluate their practice. RESULTS: 95 out of 847 physicians responded to the questionnaire (hepatologists 63.2%, Oncologists/gastroenterologists 36.8%). In patients with advanced HCC, PHT was assessed by endoscopy in 80.0% of cases. HCC progression motivated a new for 12.6% of respondents while no intent to control was declared for 49.5% of them. AVB primary prophylaxis for large size esophageal varices (EV) was impacted by the presence of red marks at endoscopy. In the absence of a red mark, prophylaxis with non-selective betablockers (NSSB) was proposed in 70.5% of cases for patients undergoing TKI and 63.2% undergoing Atezolizumab/Bevacizumab, whereas the combination of endoscopic band ligation (EBL) and NSBB was preferred in 41.1% of patients undergoing TKI versus 53.7% undergoing Atezolizumab/Bevacizumab in case of a red mark. The initiation of a systemic treatment was lower in patients with an history of AVB <6 months, which was even more significant for Atezolizumab/Bevacizumab combination (51.6%) compared to tyrosine kinase inhibitors (72.6%) (p<0.001). Atezolizumab/Bevacizumab was initiated in 43% of participants in case of AVB <6 months versus 95% if >6 months (p<0.001). In case of AVB on Atezolizumab/Bevacizumab, 43.2% continued the treatment after regression of EV, 24.2% continued Atezolizumab alone and 14.7% permanently stopped the treatment. CONCLUSION: Strategies for screening and management of PHT in advanced HCC remain very heterogeneous among physicians, suggesting the need to improve PHT knowledge and dedicated studies for advanced HCC.