Impact of surgery after endoscopically resected high-risk T1 colorectal cancer: results of an emulated target trial.

BACKGROUND AND AIMS: We aimed to compare the long-term outcomes of patients with high-risk T1 colorectal cancer (CRC) resected endoscopically who received either additional surgery or surveillance. METHODS: We used data from routine care to emulate a target trial aimed at comparing 2 strategies after endoscopic resection of high-risk T1 CRC: surgery with lymph node dissection (treatment group) versus surveillance alone (control group). All patients from 14 tertiary centers who underwent an endoscopic resection for high-risk T1 CRC between March 2012 and August 2019 were included. The primary outcome was a composite outcome of cancer recurrence or death at 48 months. RESULTS: Of 197 patients included in the analysis, 107 were categorized in the treatment group and 90 were categorized in the control group. From baseline to 48 months, 4 of 107 patients (3.7%) died in the treatment group and 6 of 90 patients (6.7%) died in the control group. Four of 107 patients (3.7%) in the treatment group experienced a cancer recurrence and 4 of 90 patients (4.4%) in the control group experienced a cancer recurrence. After balancing the baseline covariates by inverse probability of treatment weighting, we found no significant difference in the rate of death and cancer recurrence between patients in the 2 groups (weighted hazard ratio, .95; 95% confidence interval, .52-1.75). CONCLUSIONS: Our study suggests that patients with high-risk T1 CRC initially treated with endoscopic resection may not benefit from additional surgery.

Closure of gastrointestinal perforations using an endoloop system and a single-channel endoscope: description of a simple, reproducible, and standardized method.

BACKGROUND: Several endoscopic treatments for iatrogenic perforations are currently available, with some limitations in terms of size, location, complexity, or cost. Our aims were to introduce a novel technique for closure, using an endoloop and clips, to assess its rate of technical success and post-resection complications. METHODS: For closure of large perforations (diameter ≥ 10 mm), two similar techniques were implemented, using a single-channel endoscope. An endoloop was deployed through the operating channel or towed by an endoclip alongside the endoscope. Several clips were utilized to fix it on the muscular layer of defect's margins. The defect was closed, by fastening the loop either directly or after being reattached to the mobile hook. RESULTS: This analysis included eleven patients (72% women, median age 68 years). Eight colorectal, one appendiceal, and two gastric lesions were resected, with a median perforation size of 15 mm. As confirmed by computed tomography, closure of wall defects was achieved successfully in all cases, using a median of 6 clips. Pneumoperitoneum was evacuated in 4 cases. The median hospitalization duration was 4 days, prophylactic antibiotics being prescribed for a median of 7 days. One patient had a small abdominal collection, without requiring drainage, while another presented post-resection bleeding from the mucosal defect. CONCLUSION: The novel techniques, utilizing a single-channel endoscope, clips, and an endoloop, ensuring an edge-to-edge suture of muscular layer, proved to be safe, reproducible, and easy to implement. They exhibit an excellent technical success rate and a minimal incidence of non-severe complications.

Preoperative Endoscopic Ultrasound-Guided Hepaticogastrostomy for Definite Biliary Drainage in Hilar Cholangiocarcinoma Laparoscopic Resection: A Hybrid Minimal-Invasive Technique.

BACKGROUND AND STUDY AIMS: Laparoscopic approach of perihilar cholangiocarcinoma (PHC) is still challenging. We report the original use of a endoscopic hepaticogastrostomy (EHG) for definite biliary drainage in order to avoid biliary reconstruction. PATIENTS AND METHODS: A 70-year-old man presenting with jaundice was referred for resection of a Bismuth type IIIa PHC. Repeated endoscopic retrograde cholangiopancreatography failed to drain the future liver remnant, enabling only right anterior liver section drainage. EHG was performed three weeks before surgery. A hepatogastric anastomosis was created, placing a half-coated self-expanding endoprosthesis between biliary duct of segment 2 and the lesser gastric curvature. RESULTS: A laparoscopic right hepatectomy extended to segment 1, common bile duct, and hepatic pedicle lymphadenectomy was performed. The left hepatic duct was sectioned and ligated downstream to the biliary confluence of segment 2-3 and 4 allowing exclusive biliary flow through the EHG. The patient was disease free at 12 months, postoperative outcomes were uneventful except three readmissions for acute cholangitis due to prosthesis obstruction. CONCLUSIONS: EHG may be used as definite biliary drainage technique in laparoscopic PHC resection, at the expense of prosthesis obstruction and cholangitis.

CT and MRI of Gastrointestinal Stromal Tumors: New Trends and Perspectives.

Gastrointestinal stromal tumors (GISTs) are defined as mesenchymal tumors of the gastrointestinal tract that express positivity for CD117, which is a c-KIT proto-oncogene antigen. Expression of the c-KIT protein, a tyrosine kinase growth factor receptor, allows the distinction between GISTs and other mesenchymal tumors such as leiomyoma, leiomyosarcoma, schwannoma and neurofibroma. GISTs can develop anywhere in the gastrointestinal tract, as well as in the mesentery and omentum. Over the years, the management of GISTs has improved due to a better knowledge of their behaviors and risk or recurrence, the identification of specific mutations and the use of targeted therapies. This has resulted in a better prognosis for patients with GISTs. In parallel, imaging of GISTs has been revolutionized by tremendous progress in the field of detection, characterization, survival prediction and monitoring during therapy. Recently, a particular attention has been given to radiomics for the characterization of GISTs using analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence with the aim of better characterizing GISTs and providing a more precise assessment of tumor burden. This article sums up recent advances in computed tomography and magnetic resonance imaging of GISTs in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning.

Comparison Between Radial and Femoral Artery Access for Transarterial Chemoembolisation in Patients With Hepatocellular Carcinoma.

PURPOSE: The purpose of this study was to compare the technical success rate, the selectivity of transarterial chemoembolisation (TACE), the complication rate, the radiation dose given to the patients and the hospitalization stay between TACE performed using femoral artery approach (FAA) and TACE performed using radial artery approach (RAA) in patients with hepatocellular carcinoma (HCC). METHODS: Between June 2020 and April 2022, 49 patients with HCC who underwent 116 TACEs (75 using FAA and 41 using RAA) were included. Differences in technical success rate, selectivity of micro-catheterization, radiation dose given to the patients, fluoroscopy time, hospitalization stay duration, and complication rate were compared between FAA and RAA using Fisher exact or Student t tests. RESULTS: No differences in technical success rates were found between RAA (93%; 39/41 TACEs) and FAA (100%; 75/75 TACEs) (P = .12). There were no differences between the two groups in terms of selectivity of catheterization, radiation dose, fluoroscopy time and hospitalization stay duration. Five patients had Grade 2 complications (hematoma) after FAA vs. one patient with one Grade 1 complication (radial artery occlusion) after RAA (5/75 [7%] vs. 1/41 [2%], respectively; P = .42). No major arterial access site complications occurred with FAA or RAA. CONCLUSIONS: This study confirms that RAA is a safe approach that does not compromise the technical efficacy and the selectivity of TACE compared to FAA in patients with HCC.

Bevacizumab plus FOLFIRI after failure of platinum-etoposide first-line chemotherapy in patients with advanced neuroendocrine carcinoma (PRODIGE 41-BEVANEC): a randomised, multicentre, non-comparative, open-label, phase 2 trial.

BACKGROUND: There is no standard second-line treatment after platinum-etoposide chemotherapy for gastroenteropancreatic neuroendocrine carcinoma. We aimed to evaluate the efficacy of FOLFIRI plus bevacizumab, and FOLFIRI alone, in this setting. METHODS: We did a randomised, non-comparative, open-label, phase 2 trial (PRODIGE 41-BEVANEC) at 26 hospitals in France. We included patients aged 18 years or older with locally advanced or metastatic gastroenteropancreatic neuroendocrine carcinoma or neuroendocrine carcinoma of unknown primary origin, documented progressive disease during or after first-line platinum-etoposide chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned (1:1; block size of three), without stratification, to receive FOLFIRI (irinotecan 180 mg/m2, calcium folinate 400 mg/m2 or levofolinate 200 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h) plus bevacizumab 5 mg/kg or FOLFIRI alone, intravenously, every 2 weeks until disease progression or unacceptable toxicity. Neither patients nor investigators were masked to group assignment. The primary outcome was overall survival at 6 months after randomisation, evaluated in the modified intention-to-treat population (all enrolled and randomly assigned patients who received at least one cycle of FOLFIRI). This study is now complete and is registered with ClinicalTrials.gov, NCT02820857. FINDINGS: Between Sept 5, 2017, and Feb 8, 2022, 150 patients were assessed for eligibility and 133 were enrolled and randomly assigned: 65 to the FOLFIRI plus bevacizumab group and 68 to the FOLFIRI group. 126 patients (59 in the FOLFIRI plus bevacizumab group and 67 in the FOLFIRI group) received at least one cycle of FOLFIRI and were included in the modified intention-to-treat population, 83 (66%) of whom were male and 43 (34%) were female, and the median age of the patients was 67 years (IQR 58-73). The primary tumour location was colorectal in 38 (30%) of 126 patients, pancreatic in 34 (27%), gastro-oesophageal in 22 (17%), and unknown in 23 (18%). After a median follow-up of 25·7 months (95% CI 22·0-38·2), 6-month overall survival was 53% (80% CI 43-61) in the FOLFIRI plus bevacizumab group and 60% (51-68) in the FOLFIRI group. Grade 3-4 adverse events that occurred in at least 5% of patients were neutropenia (eight [14%] patients), diarrhoea (six [10%]), and asthenia (five [8%]) in the FOLFIRI plus bevacizumab group, and neutropenia (seven [10%]) in the FOLFIRI group. One treatment-related death (ischaemic stroke) occurred in the FOLFIRI plus bevacizumab group. INTERPRETATION: The addition of bevacizumab did not seem to increase the benefit of FOLFIRI with regard to overall survival. FOLFIRI could be considered as a standard second-line treatment in patients with gastroenteropancreatic neuroendocrine carcinoma. FUNDING: French Ministry of Health and Roche SAS.

Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study.

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.

"Transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM): a new endoscopic treatment for suspicious deep submucosal invasion T1 rectal carcinoma.

BACKGROUND: Endoscopic techniques allow resections of deep submucosal invasion rectal carcinoma, but mostly are facing issues such as costs, follow-up care or size limit. Our aim was to design a new endoscopic technique, which retains the advantages over surgical resections while eliminating the disadvantages mentioned above. PATIENTS AND METHODS: We propose a technique for the resection of the superficial rectal tumours, with highly suspicious deep submucosal invasion. It combines steps of endoscopic submucosal dissection, muscular resection and edge-to-edge suture of the muscular layers, finally performing the equivalent of a "transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM). RESULTS: A 60-year-old patient was referred to our unit, following the discovery of a 15 mm distal rectum adenocarcinoma. The computed tomography and the endoscopic ultrasound examination revealed a T1 tumour, without secondary lesions. Considering that the initial endoscopic evaluation highlighted a depressed central part of the lesion, with several avascular zones, an F-TEM was performed, without severe complication. The histopathological examination revealed negative resection margins, without risk factors for lymph node metastasis, no adjuvant therapy being proposed. CONCLUSION: F-TEM allows endoscopic resection of highly suspicious deep submucosal invasion T1 rectal carcinoma and it proves to be a feasible alternative to surgical resection or other endoscopic treatments as endoscopic submucosal dissection or intermuscular dissection.

Imaging of Pancreatic Ductal Adenocarcinoma: An Update on Recent Advances.

Pancreatic ductal carcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Computed tomography (CT) remains the primary imaging modality for diagnosis of PDAC. However, CT has limitations for early pancreatic tumor detection and tumor characterization so that it is currently challenged by magnetic resonance imaging. More recently, a particular attention has been given to radiomics for the characterization of pancreatic lesions using extraction and analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence (AI) with the aim of better characterizing pancreatic lesions and providing a more precise assessment of tumor burden. This review article sums up recent advances in imaging of PDAC in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning. In addition, current applications of radiomics and AI in the field of PDAC are discussed.

Interobserver Variability and Accuracy of Preoperative CT and MRI in Pancreatic Ductal Adenocarcinoma Size Estimation: A Retrospective Cohort Study.

Purpose: To assess interobserver variability and accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) in pancreatic ductal adenocarcinoma (PDAC) size estimation using surgical specimens as standard of reference. Methods: Patients with PDAC who underwent preoperative CT and MRI examinations before surgery were included. PDAC largest axial dimension was measured by 2 readers on 8 MRI sequence and 2 CT imaging phases (pancreatic parenchymal and portal venous). Measurements were compared to actual tumour size at pathologic examination. Interobserver variability was assessed using intraclass correlation coefficients (ICC) and Bland-Altman plots. Differences in tumour size (Δdiameter) between imaging and actual tumour size were searched using Wilcoxon rank sum test. Results: Twenty-nine patients (16 men; median age, 70 years) with surgically resected PDAC were included. Interobserver reproducibility was good to excellent for all MRI sequences and the 2 CT imaging phases with ICCs between .862 (95%CI: .692-.942) for fat-saturated in-phase T1-weighted sequence and .955 (95%CI: .898-.980) for portal venous phase CT images. Best accuracy in PDAC size measurement was obtained with pancreatic parenchymal phase CT images with median Δdiameters of -2 mm for both readers, mean relative differences of -9% and -6% and no significant differences with dimensions at histopathological analysis (P = .051). All MRI sequences led to significant underestimation of PDAC size (median Δdiameters, -6 to -1 mm; mean relative differences, -21% to -11%). Conclusions: Most accurate measurement of PDAC size is obtained with CT images obtained during the pancreatic parenchymal phase. MRI results in significant underestimation of PDAC size.

Cinematic Rendering of Gastrointestinal Stromal Tumors: A Review of Current Possibilities and Future Developments.

Gastrointestinal stromal tumors (GISTs) are defined as CD117-positive primary, spindled or epithelioid, mesenchymal tumors of the gastrointestinal tract, omentum, or mesentery. While computed tomography (CT) is the recommended imaging modality for GISTs, overlap in imaging features between GISTs and other gastrointestinal tumors often make radiological diagnosis and subsequent selection of the optimal therapeutic approach challenging. Cinematic rendering is a novel CT post-processing technique that generates highly photorealistic anatomic images based on a unique lighting model. The global lighting model produces high degrees of surface detail and shadowing effects that generate depth in the final three-dimensional display. Early studies have shown that cinematic rendering produces high-quality images with enhanced detail by comparison with other three-dimensional visualization techniques. Cinematic rendering shows promise in improving the visualization of enhancement patterns and internal architecture of abdominal lesions, local tumor extension, and global disease burden, which may be helpful for lesion characterization and pretreatment planning. This article discusses and illustrates the application of cinematic rendering in the evaluation of GISTs and the unique benefit of using cinematic rendering in the workup of GIST with a specific emphasis on tumor characterization and preoperative planning.

A New Manganese Superoxide Dismutase Mimetic Improves Oxaliplatin-Induced Neuropathy and Global Tolerance in Mice.

Reactive oxygen species (ROS) are produced by every aerobic cell during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Superoxide Dismutases (SOD) are antioxidant proteins that convert superoxide anions (O2•-) to hydrogen peroxide (H2O2) and dioxygen. Using the differential in the level of oxidative stress between normal and cancer cells, SOD mimetics can show an antitumoral effect and prevent oxaliplatin-induced peripheral neuropathy. New Pt(IV) conjugate prodrugs (OxPt-x-Mn1C1A (x = 1, 1-OH, 2)), combining oxaliplatin and a Mn SOD mimic (MnSODm Mn1C1A) with a covalent link, were designed. Their stability in buffer and in the presence of sodium ascorbate was studied. In vitro, their antitumoral activity was assessed by the viability and ROS production of tumor cell lines (CT16, HCT 116, KC) and fibroblasts (primary culture and NIH 3T3). In vivo, a murine model of colorectal cancer was created with subcutaneous injection of CT26 cells in Balb/c mice. Tumor size and volume were measured weekly in four groups: vehicle, oxaliplatin, and oxaliplatin associated with MnSODm Mn1C1A and the bis-conjugate OxPt-2-Mn1C1A. Oxaliplatin-induced peripheral neuropathy (OIPN) was assessed using a Von Frey test reflecting chronic hypoalgesia. Tolerance to treatment was assessed with a clinical score including four items: weight loss, weariness, alopecia, and diarrhea. In vitro, Mn1C1A associated with oxaliplatin and Pt(IV) conjugates treatment induced significantly higher production of H2O2 in all cell lines and showed a significant improvement of the antitumoral efficacy compared to oxaliplatin alone. In vivo, the association of Mn1C1A to oxaliplatin did not decrease its antitumoral activity, while OxPt-2-Mn1C1A had lower antitumoral activity than oxaliplatin alone. Mn1C1A associated with oxaliplatin significantly decreased OIPN and also improved global clinical tolerance of oxaliplatin. A neuroprotective effect was observed, associated with a significantly improved tolerance to oxaliplatin without impairing its antitumoral activity.

Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers.

Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.

Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort.

BACKGROUND: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group. METHODS: This is a retrospective multicentre study. We included all consecutive patients with non-pre-treated LAPA or BRPA treated with FOLFIRINOX. RESULTS: We included 330 patients (57.9% male, 65.4% <65 years, 96.4% PS <2). Disease was classified as BRPA in 31.1% or LAPA in 68.9%. Objective response rate with FOLFIRINOX was 29.5% and stable disease 51%. Subsequent CRT was performed in 46.4% of patients and 23.9% had curative intent surgery. Resection rates were 42.1% for BRPA and 15.5% for LAPA. Main G3/4 toxicities were fatigue (15%), neutropenia (12%) and neuropathy (G2/3 35%). After a median follow-up of 26.7 months, median OS (mOS) and PFS were 21.4 and 12.4 months, respectively. For patients treated by FOLFIRINOX alone, or FOLFIRINOX followed by CRT, or FOLFIRINOX + /- CRT + surgery, mOS was 16.8 months, 21.8 months and not reached, respectively (p < 0.0001). CONCLUSIONS: FOLFIRINOX for LAPA and BRPA seems to be effective with a manageable toxicity profile. These promising results in "real-life" patients now have to be confirmed in a Phase 3 randomised trial.

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: The efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting. PATIENTS AND METHODS: We retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years. RESULTS: The study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8-10.2) and PFS (median, 5.5 months; 95% CI, 4.8-6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis. CONCLUSION: GnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.

Magnetic Resonance Imaging May Be Able to Identify the Origin of Neuroendocrine Tumor Liver Metastases.

OBJECTIVES: The aim of the study was to discriminate hepatic metastases from pancreatic neuroendocrine tumors (pNET) and hepatic metastases from midgut neuroendocrine tumors (mNET) with magnetic resonance imaging (MRI). METHODS: MRI examinations of 24 patients with hepatic metastases from pNET were quantitatively and qualitatively assessed by 2 blinded readers and compared to those obtained in 23 patients with hepatic metastases from mNET. Inter-reader agreement was calculated with kappa and intraclass correlation coefficient (ICC). Sensitivity, specificity, and accuracy of each variable for the diagnosis of hepatic metastasis from pNET were calculated. Associations between variables and primary tumor (i.e., pNET vs. mNET) were assessed by univariate and multivariate analyses. A nomogram was developed and validated using an external cohort of 20 patients with pNET and 20 patients with mNET. RESULTS: Interobserver agreement was strong to perfect (k = 0.893-1) for qualitative criteria and excellent for quantitative variables (ICC: 0.9817-0.9996). At univariate analysis, homogeneity on T1-weighted images was the most discriminating variable for the diagnosis of pNET (OR: 6.417; p = 0.013) with greatest sensitivity (88%; 21/24; 95% CI: 68-97%). At multivariate analysis, tumor homogeneity on T1-weighted images (p = 0.007; OR: 17.607; 95% CI: 2.179-142.295) and target sign on diffusion-weighted images (p = 0.007; OR: 19.869; 95% CI: 2.305-171.276) were independently associated with pNET. Nomogram yielded a corrected AUC of 0.894 (95% CI: 0.796-0.992) for the diagnosis of pNET in the training cohort and 0.805 (95% CI: 0.662-0.948) in the validation cohort. CONCLUSIONS: MRI provides qualitative features that can help discriminate between hepatic metastases from pNET and those from mNET.

Surgical management of insulinoma over three decades.

BACKGROUND: This paper reports our experience of the perioperative management of patients with sporadic, non-malignant, pancreatic insulinoma. METHODS: A retrospective monocentric cohort study was performed from January 1989 to July 2019, including all the patients who had been operated on for pancreatic insulinoma. The preoperative work-up, surgical management, and postoperative outcome were analyzed. RESULTS: Eighty patients underwent surgery for sporadic pancreatic insulinoma, 50 of which were female (62%), with a median age of 50 (36-70) years. Preoperatively, the tumors were localized in 76 patients (95%). Computed tomography (CT) and magnetic resonance imaging allowed exact preoperative tumor localization in 76% of the patients (64-85 and 58-88 patients, respectively), increasing to 96% when endoscopic ultrasonography was performed. Forty-one parenchyma-sparing pancreatectomies (PSP) (including enucleation, caudal pancreatectomy, and uncinate process resection) and 39 pancreatic resections were performed. The mortality rate was 6% (n = 5), with a morbidity rate of 72%, including 24 severe complications (30%) and 35 pancreatic fistulas (44%). No differences were found between formal pancreatectomy and PSP in terms of postoperative outcome procedures. The surgery was curative in all the patients. CONCLUSION: CT used in combination with endoscopic ultrasonography allows accurate localization of insulinomas in almost all patients. When possible, a parenchyma-sparing pancreatectomy should be proposed as the first-line surgical strategy.

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.

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study.

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.

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.