Reappraisal of the characteristics, management, and prognosis of intramucosal colorectal cancers and their comparison with T1 carcinomas

International audienceBackground and aims - The recent description of "invasive" forms of intramucosal carcinoma (IMC) has rekindled interest in studying the characteristics, management, and prognosis of IMCs and comparing them with T1 colorectal cancers (CRCs). Methods - This population-based study included 282 cases of IMC and 207 cases of T1 CRC diagnosed by colonoscopy after a positive fecal blood test through a screening program. Results - IMC presented mainly in the form of pedunculated polyps (68.4%) located in the distal colon (69.9%) ≥20 mm in size (60.6%). IMCs were resected endoscopically in 227 (80.5%) patients and surgically resected in 55 (19.5%) patients. Surgical patients had more right-sided, more sessile, and larger lesions. There was no sign of lymphovascular invasion. Compared with T1 CRCs, IMCs demonstrated lower rates of sessile polyps (31.6% vs 49.8%, P < .0001), primary and ultimate surgical treatment (19.5% vs 39.1% and 19.9% vs 78.7%, P < .0001, respectively), lymph node metastasis in surgical patients (0% vs 9.5%, P = .041), cancer recurrence and cancer-related mortality (0% vs 5.6% and 0% vs 2.5%, respectively), and bleeding after endoscopic resection (1.8% vs 8.7%, P = .001). By multivariate analysis of the pooled cohort (IMC + T1 CRC, n = 489), the factors significantly associated with first-line surgery were shown to be polyp characteristics and the gastroenterologist who performed the colonoscopy. Conclusions - IMCs account for a quarter of all screening-detected CRCs. They have an excellent prognosis regardless of whether endoscopic or surgical treatment is performed. IMCs differ significantly from T1 carcinomas in terms of management and prognosis

Coeliac-Like Disease Is a Rare Immune-Related Complication Induced by Nivolumab in NSCLC

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Submucosal dissection of a large colonic angiodysplasia in case of failure of conventional treatment

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Surgical rather than endoscopic resection of early-stage colorectal cancers promotes excessive imaging surveillance

International audienceBACKGROUND AND AIMS: Imaging surveillance after curative resection of colorectal cancer (CRC) is debated, particularly in cases of early-stage CRC. The aim of this study was to retrospectively analyze whether and how patients with screened stage 0 and stage 1 CRC were monitored by imaging. METHODS: A cohort of patients with stage 0 (intramucosal) or stage 1 (T1N0) CRC detected from 2003 to 2015 through the French national screening programme was included. All imaging findings were recorded. Statistical analyses were performed for the entire cohort (n = 450) and separately for the two groups (stage 0 n = 268, stage 1 n = 182). Factors associated with imaging surveillance, including the patient’s referring gastroenterologist, were determined by logistic regression. RESULTS: A total of 450 patients were followed up for 6.6 ± 3.9 years. Imaging surveillance was performed for 159 (35.3%), more often for those with stage 1 (66.5%) than stage 0 (14.2%) tumours (p &lt; 0.0001). Within the stage 1 group, 17 of the 47 patients (36.2%) treated by local (endoscopic or surgical transanal) resection alone were followed up by imaging monitoring. Factors significantly associated with surveillance in the entire cohort were the gastroenterologist assigned to the patient (p &lt; 0.0001) and surgical vs endoscopic resection (OR = 39.0, p &lt; 0.0001). The histological risk of lymph node metastasis was not significantly associated with imaging monitoring for stage 1 patients. Of the 5 patients who developed distant metastasis during follow-up, one was diagnosed through imaging surveillance. CONCLUSION: This study demonstrates excessive imaging surveillance for early-stage cancers. The use of surgical over endoscopic tumour resection could promote unnecessary surveillance

Management of T1 colorectal cancers detected at screening colonoscopy A study from the French national screening programme

International audienceAim : The main aim of this study was to examine the management strategies that were used and to determine the outcomes (survival and recurrence rate) of screen-detected T1-CRC.Methods : Medical records from 207 patients with T1-CRC diagnosed through the French national screening programme in one district from 2003 to 2015 were analysed. The 5-year overall, CRC-specific and CRC-free survival were calculated for the whole cohort and for the3 groups treated by endoscopic resection (ER) alone, ER followed by subsequent surgery (ERSS), and primary surgery (PS).Results : Of the 207 patients, 81 (39%) underwent PS, and 126 (61%) underwent primary ER, of whom 82 (64%) underwent subsequent surgery. The 5-year overall and cancer-specific survival rates were 95.5% (95% CI, 90.8; 97.9) and 98.8% (95% CI, 95.4; 99.7%), respectively.Long-term cancer-specific mortality and recurrence crude rates were 2.4% and 5.6%, respectively. The 5-year CRC-free survival rate was 96.1% (95% CI, 91.8; 98.1%) and did not differ among the 3 groups (ER alone, ERSS and PS).Conclusion : This study demonstrates the good prognosis of screen-detected T1-CRC, regardless of the treatment strategy used. But, there is a room to improve the screening programme quality with regard to the management of screen-detected CRC

Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlate With Rate of Infection

International audienceBackground & aims: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features.Methods: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received a infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC).Results: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938±1427 mg d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P=.046), IBD flare (OR, 2.71; P=.006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P=.02). The ΣAUC was higher in patients with an occurrence of infection (P=.04) and correlated with the number of infections (P=.04). Trough concentration of infliximab alone was not associated with infection.Conclusions: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level

Adjuvant chemotherapy benefit according to T and N stage in small bowel adenocarcinoma: a large retrospective multicenter study

International audienceBACKGROUND: Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. RESULTS: A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P &lt; .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or &lt;8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction &lt; .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction &lt; .05). CONCLUSION: In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations

A 3D-printed pedal fixator for connecting different pedal-operated tools reduces the number of mistakes during endoscopic submucosal dissection

Abstract Introduction: The particularity of endoscopic submucosal dissection (ESD) compared to endoscopic mucosal resection is the need of three feet pedals to activate electrosurgical unit, flushing and knife injection. The lack of connection between the various pedals of different shapes and brands leads to numerous pedals displacements and potential mistakes. The aim of this study was to evaluate an innovative pedal fixator (IPEFIX) to reduce pedal mistakes during ESD. Methods: This was a prospective, multicenter randomized study. Consecutive ESD procedures were randomly assigned to two groups: control group with the three pedals free and the IPEFIX group where the three pedals were linked by IPEFIX. The main outcome evaluated was the number of foot mistakes (wrong pedal, foot push beside the pedal). Results: 107 ESD were performed by 8 experts in 5 centers. The median number of mistakes per hour of ESD procedure was 0/h in the IPEFIX group and 1.9/h in the control group (p<0.001). The mean number of look down to control the position of the pedals was 2.2/h the IPEFIX group and 7.7/h in the control group (p<0.001). Mean replacements of the pedals was 0./h in the IPEFIX group and 1.7/h in the control group (p<0.001). Similar results were obtained in trainees in simulated ESD on animal models. Conclusion: IPEFIX is a simple device to connect different pedals during endoscopic procedure. It helps to reduce the numbers of foot mistakes during ESD and improve the comfort of the operator

Classification of PRSS1 variants responsible for chronic pancreatitis: An expert perspective from the Franco-Chinese GREPAN Study Group

Background PRSS1 was the first reported chronic pancreatitis (CP) gene. The existence of both gain-of-function (GoF) and gain-of-proteotoxicity (GoP) pathological PRSS1 variants, together with the fact that PRSS1 variants have been identified in CP subtypes spanning the range from monogenic to multifactorial, has made the classification of PRSS1 variants very challenging. Methods All currently reported PRSS1 variants (derived primarily from two databases) were manually reviewed with respect to their clinical genetics, functional analysis and population allele frequency. They were classified by variant type and pathological mechanism within the framework of our recently proposed ACMG/AMP guidelines-based seven-category system. Results The total number of distinct germline PRSS1 variants included for analysis was 100, comprising 3 copy number variants (CNVs), 12 5′ and 3′ variants, 19 intronic variants, 5 nonsense variants, 1 frameshift deletion variant, 6 synonymous variants, 1 in-frame duplication, 3 gene conversions and 50 missense variants. Based upon a combination of clinical genetic and functional analysis, population data and in silico analysis, we classified 26 variants (all 3 CNVs, the in-frame duplication, all 3 gene conversions and 19 missense) as “pathogenic”, 3 variants (missense) as “likely pathogenic”, 5 variants (four missense and one promoter) as “predisposing”, 13 variants (all missense) as “unknown significance”, 2 variants (missense) as “likely benign”, and all remaining 51 variants as “benign”. Conclusions We describe an expert classification of the 100 PRSS1 variants reported to date. The results have immediate implications for reclassifying many ClinVar-registered PRSS1 variants as well as providing optimal guidelines/standards for reporting PRSS1 variants