Impact of Annual Case Volume on Colorectal Endoscopic Submucosal Dissection Outcomes in a Large Prospective Cohort Study.

INTRODUCTION: The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed that ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection; reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort. METHODS: Between September 2019 and September 2022, colorectal ESD was consecutively performed at 13 participating centers classified as low volume (LV), middle volume (MV), and high volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching analyses were performed. RESULTS: Three thousand seven hundred seventy ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc , R0, and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers also achieved a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after propensity score matching, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers. DISCUSSION: Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts.

Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer.

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.

An international study on the use of peroral endoscopic myotomy in the management of Zenker's diverticulum.

BACKGROUND AND AIMS: The novel use of peroral endoscopic myotomy (POEM) in the treatment of Zenker's diverticulum (ZD) was recently described in case reports. The aim of this study is to report a multicenter experience with the POEM technique in the management of ZD. METHODS: This is a multicenter international retrospective study involving 10 centers. The Zenker's POEM technique was performed using principles of submucosal endoscopy. RESULTS: Seventy-five patients (73.3 ± 1.2 years, 33 women) were included with a mean Charleson comorbidity index of 4 ± .2. The mean size of ZD was 31.3 ± 1.6 mm (range, 10-89). The overall technical success rate was 97.3% (73/75). There were 2 technical failures because of the inability to locate the septum and failed tunnel creation. Adverse events occurred in 6.7% (5/75): 1 bleed (mild) conservatively managed and 4 perforations (1 severe, 3 moderate). The mean procedure time was 52.4 ± 2.9 minutes, and mean length of hospital stay was 1.8 ± .2 days. Clinical success was achieved in 92% (69/75) with a decrease in mean dysphagia score from 1.96 to .25 (P < .0001). The median length of follow-up was 291.5 days (interquartile range, 103.5-436). At the 12-month follow-up, 1 patient reported symptom recurrence. CONCLUSIONS: Endoscopic management of ZD using the POEM technique is novel and feasible with promising efficacy and safety results. Long-term follow-up is needed to ensure durability of response. In addition, comparative studies with other treatment modalities are warranted.

Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers.

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC.

Tumour growth increased following antiangiogenic interruption: the challenge of tumour evaluation.

Vascular endothelial growth factor inhibitors, led by bevacizumab, are considered the cornerstone of the therapy in metastatic colorectal carcinoma. We present the case of a patient with metastatic colorectal cancer who experienced rapid tumour growth with liver broad invasion after the withdrawal of an antivascular endothelial growth factor therapy, aflibercept. The rebound effect caused by the residual tumour inducing a regrowth after an initial controlled disease has already been stressed in mice and metastatic colorectal cancer patients following bevacizumab interruption. The use of liver volume evaluation was consistent with the Response Evaluation Criteria in Solid Tumours 1.1 criteria evaluation and might be a useful tool in patients with more than a half liver invasion. We describe for the first time the case of a major liver disease progression, confirmed by Response Evaluation Criteria in Solid Tumours 1.1 criteria and liver volume evaluation, after an antiangiogenic interruption in second line.

Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues.

BACKGROUND: Few data are available on second-line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this multicenter study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens. METHODS: Patients who received CT2 for ABTC at 17 French institutions after the failure of the gemcitabine-platinum combination were retrospectively studied. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Cox models were used for multivariate analyses. RESULTS: Among 603 patients who received first-line chemotherapy (CT1) for ABTC, 196 received CT2: 5-fluorouracil (5-FU) and irinotecan (n = 64), 5-FU and oxaliplatin (n = 21), 5-FU and cisplatin (n = 38), 5-FU or capecitabine (n = 40), sunitinib (n = 10), or other various regimens (n = 23). Among the 186 assessable patients, there were 22 partial responses and 70 stabilizations. After a median follow-up of 26.4 months, the median PFS and OS were 3.2 and 6.7 months, respectively. There was no significant difference in PFS or OS between CT2 regimens. Fluoropyrimidine-based doublet chemotherapy was not superior to fluoropyrimidine alone in terms of OS and PFS. In a multivariate analysis, a performance status of 0 to 1, disease control with CT1, and a carbohydrate antigen 19-9 (CA 19-9) level ≤ 400 IU/mL were significantly associated with longer PFS and OS. Grade 3 to 4 toxicity occurred in 32% of the patients. CONCLUSIONS: CT2 might provide disease control for selected patients with ABTC after the failure of gemcitabine-platinum, but the prognosis remains poor. No particular regimen seems superior to others, and this calls for new treatments. A good performance status, disease control with CT1, and a low level of CA 19-9 were associated with longer survival.

Resection of Late Pulmonary Metastases from Pancreatic Adenocarcinoma: Is Surgery an Option?

Patients with recurrences from pancreas adenocarcinoma have a poor survival rate despite new chemotherapy treatment options. Recurrences are mainly hepatic metastases or peritoneal dissemination and surgical treatment is not recommended. Late and single metachronous pulmonary recurrences are uncommon and may mimic primary lung carcinoma. We report two patients with late and unique pulmonary metastasis from pancreatic cancer. These two patients underwent surgical resection; three and five years later, they did not experience recurrences. Cases called for a surgical approach in late and unique pulmonary metastases from pancreatic cancer, and paved the way for a prolonged chemotherapy free period.

Endoscopic Ultrasound-Guided Enteroenterostomy for Afferent Limb Syndrome.

Afferent limb syndrome (ALS) is a rare complication of duodenopancreatectomy, resulting from the mechanical obstruction of the afferent limb usually after local malignancy recurrence. Management of ALS (ie, surgery and palliative therapy) is often unsatisfactory. We present 5 cases of endoscopic ultrasound-guided internal drainage of the afferent limb using lumen-apposing metal stents. All procedures were successful, with no related complications; 2 patients had a complete regression of their symptoms, one experienced cholangitis recurrence, and 2 patients died after some weeks because of their malignancies. Endoscopic ultrasound-guided enteroenterostomy offers a convenient and safe palliative solution for patients presenting ALS.

Endoscopic ultrasound-guided luminal remodeling as a novel technique to restore gastroduodenal continuity.

Pyloric exclusion is a method of treatment for duodenal injury. Surgery is usually needed to restore digestive continuity in due time, yet a new surgical procedure can be challenging due to fibrotic adhesion development. We present here a retrospective case series of three patients with pyloric exclusion who underwent endoscopic ultrasound-guided duodenal repermeabilization using metallic stents. All procedures were successful with no complication and allowed regular feeding. This case series shows that endoscopic ultrasound-guided recanalization is a feasible and safe procedure.

Do we need endoscopic ultrasonography for the workup of patients with esophageal motility disorder?

INTRODUCTION: Endoscopic ultrasonography (EUS) is advised in the workup of achalasia patients to rule out secondary achalasia or pseudoachalasia, and search for a typical esophageal wall thickening. The purpose of this study was to assess the clinical contribution of EUS findings in achalasia and other esophageal motility disorders (EMD). METHODS: We conducted a single center retrospective study at a tertiary referral centre. We included all patients with an EUS for the workup of a suspected EMD from January 2012 to December 2017. RESULTS: Sixty-nine patients were included, 52% were men, with a median (±SD) age of 61 ± 14 years. Median (±SD) Eckardt Score was 7 ± 2. EUS was normal in 26 (38%) patients, and showed an esophageal wall thickening in 43 (62%) patients. Three cases of secondary achalasia were diagnosed at mucosal biopsies: 2 esophageal carcinomas and one eosinophilic esophagitis. Esophageal wall thickening was not significantly associated with the type of EMD or achalasia subtype and there was no statistical correlation between the presence of a wall thickening at EUS and therapeutic outcomes. CONCLUSION: In our work, the presence of an esophageal wall thickening was not predictive of the type of EMD nor achalasia subtype or treatment outcome. The contribution of endoscopic ultrasonography in achalasia and other EMD seems limited.

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations.

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.

Mirizzi's syndrome in Roux-en-Y bypass patient successfully treated with cholangioscopically-guided laser lithotripsy via percutaneous gastrostomy.

Obesity and bariatric surgery are major risk factors in gallstone disease. In patients with a past history of Roux-en-Y gastric bypass, Mirizzi's syndrome is a challenging endoscopic situation because of the modified anatomy. Here we report the first case of a patient with a Roux-en-Y gastric bypass treated by intracorporeal lithotripsy with a digital single-operator cholangioscope following an endoscopic retrograde cholangiopancreatography (ERCP) using a percutaneous gastrostomy access.

Invasive pit pattern, macronodule and depression are predictive factors of submucosal invasion in colorectal laterally spreading tumours from a Western population.

BACKGROUND: Laterally spreading tumours are separated in subclasses: granular, homogenous or nodular mixed; and non-granular, flat or pseudodepressed. For every subtype, a proper risk of submucosal invasive cancer has been described in Asian series. OBJECTIVE: The aim of the study was to determine the rate of cancer and submucosal invasive cancer in a Western series of endoscopic-resected laterally spreading tumours and their endoscopic predictive factors. METHODS: A total of 374 laterally spreading tumours ≥20 mm were resected by endoscopy in our single centre between 2012-2016. We analysed endoscopic and pathological data from our prospective database, determining the rates of cancer and submucosal invasive cancer according to the subtype of laterally spreading tumour. RESULTS: The rates of submucosal invasive cancer for granular homogenous, granular nodular mixed, non-granular flat, non-granular pseudodepressed laterally spreading tumours were 4.9%, 15.9%, 3.0% and 19.4%, respectively. Endoscopic mucosal resection was used in 58.0% and endoscopic submucosal dissection in 42.0%. Endoscopic submucosal dissection was associated with a higher rate of en-bloc resection (87.3% vs 26.3%; p < 0.0001), and a lower risk of recurrence (7.6% vs 15.2%; p = 0.026). Adverse event rates were not statistically different (9.5% vs 6.4%, p = 0.26). Predictive endoscopic factors of submucosal invasive cancer were: invasive pit pattern (hazard ratio = 33 (8.81-143.3)), non-granular pseudodepressed laterally spreading tumours (hazard ratio = 11.9 (0.89-146.2)), and granular nodular mixed laterally spreading tumours (hazard ratio = 3.42 (0.99-13.0)). CONCLUSIONS: The risk of submucosal invasive cancer varies according to the laterally spreading tumour subtype. Three factors were associated with submucosal invasion and should justify an endoscopic submucosal dissection: non-granular pseudodepressed laterally spreading tumours, granular nodular mixed laterally spreading tumours subtypes and invasive pit pattern.

May we challenge the ENETS guidelines in pancreatic neuroendocrine neoplasms? A quiz for French experts.

INTRODUCTION: Recent guidelines have been published by a consensus of international experts (2016 ENETS (European NeuroEndocrine Tumor Society) guidelines). Nevertheless, in case of pancreatic neuroendocrine neoplasms (panNEN) the ENETS guidelines fail to propose a unique strategy in some situations, due to the lack of high-level of evidence and the absence of formal agreement between the experts drawing up the guidelines. MATERIAL AND METHODS: A survey of 25 questions on panNEN was sent to 104 French experts challenging the guidelines. Questions focused on clinical situations in localized G-1/2 panNEN, localized G-3 panNEN, metastatic G-1/2 panNEN, and metastatic G-3 panNEN for which multiple options were proposed by the ENETS guidelines. RESULTS: Fifty-seven experts (55%) have answered the survey. 18/25 questions obtained at least 50% similar responses, allowing a "consensus" or a "position statement". Among the results, surgery of small panNEN is preferred to surveillance in young patients; the temozolomide-capecitabine combination is favored instead of streptozotocin-based chemotherapy for G-1/2 metastatic panNEN. CONCLUSION: French experts are mostly in line with the European guidelines, but some differences do exist. Whilst waiting for prospective studies, this survey helps physicians to propose standardized procedures and identifies situations where a step forward has been enabled by French experts. This questionnaire paves the way for a simplified therapeutic algorithm of panNEN.

[Mid gut neuroendocrine tumors: News on medical treatment]. / Tumeurs neuroendocrines de l'intestin grêle : actualités sur le traitement médical.

CONTEXT: Mid gut neuroendocrine tumors (NET) are rare tumors whose incidence is increasing. Curative surgery remains the gold standard for the treatment of NETs of the small intestine. Surgery should be considered as soon as possible even if a metastatic stage is diagnosed. The management of unresectable well-differentiated metastatic NETs of the small intestine recently changed with the publication of trials demonstrating the benefit of targeted therapies and metabolic radiotherapy, leading to a change of practices and update of French and international recommendations. OBJECTIVE: The objective of this review is to present the recent data consisting of three phase III studies, which modify the management of well-differentiated metastatic midgut NETs and make an inventory of the available treatment options. DOCUMENTARY SOURCES: The documentary sources used were gathered through the PubMed website using keyword searching (neurendocrine tumor, mid gut, treatment). We also referred to recommendations of the European Society of neuroendocrine tumors (ENETS) trials presented at ESMO Congress 2015 (European Society for Medical Oncology). STUDY SELECTION: We excluded studies of exclusive extra-digestive NETs, poorly differentiated NETs, surgical treatments and phase I studies. RESULTS: We discussed three randomized phase III trials: CLARINET, RADIANT and NETTER studies. These studies demonstrated the efficacy of respectively somatostatin analogues, mTOR inhibitors and metabolic radiotherapy. CONCLUSION: This review highlights the validation by randomized studies of an mTOR inhibitor and metabolic radiotherapy in metastatic non-pancreatic digestive NETs unresectable well-differentiated grade of G1/2 in progression under somatostatin analogues.

Immune Checkpoint Inhibitor-Induced Colitis: Diagnosis and Management.

Immune checkpoint inhibitors are monoclonal antibodies indicated for an increasing number of malignant diseases. These agents can cause specific side effects, which need to be anticipated while clear patterns of management need to be established. Immune checkpoint inhibitor-mediated gastrointestinal side effects, including diarrhea and colitis, occur in up to 30% of patients. Severe colitis can lead to severe dehydration or intestinal perforation. Endoscopic lesions and histopathological features of immune checkpoint inhibitor-induced colitis are similar to an inflammatory bowel disease (IBD) flare. Patients with immune checkpoint inhibitor-induced diarrhea and colitis are treated with corticosteroids. Infliximab can be used in cases of corticosteroid failure. Rectosigmoïdoscopy or colonoscopy should be performed when severe immune checkpoint inhibitor-induced colitis is suspected, but endoscopic investigations should not delay treatment. Specific patient education as well as co-operation between oncologists and gastroenterologists is essential.