Objective: To investigate the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer. Background: Neoadjuvant immunotherapy has induced remarkable rates of pathologic complete response (pCR) in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined. Methods: This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I–III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery 3 to 5 weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pCR in more than 20% of patients). Results: Between February 2023 and September 2023, 42 patients were enrolled at 5 Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), 3 of which were above Clavien-Dindo grade 2. Two were grade 3b, and 1 was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pCR, whereas 61% had a major pathologic response. Conclusions: Neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients.

PURPOSE: Neoadjuvant immune checkpoint inhibition has shown promise in localized deficient mismatch repair (dMMR) colorectal cancer, yet the optimal treatment duration, regimen, and methods for response evaluation remain undefined. This trial aimed to investigate the efficacy and safety of neoadjuvant pembrolizumab for patients with localized dMMR colon cancer. METHODS: Participants received a single cycle of pembrolizumab (4 mg/kg, max 400 mg, every-6-weeks dosing regimen), followed by a preoperative endoscopy with biopsies and surgery 3-5 weeks later. The primary end point was pathologic complete response (pCR); secondary and exploratory end points included major pathologic response (MPR), safety, survival, and endoscopic response assessment. RESULTS: From February 2023 to March 2024, 85 patients (median age 74 years) were enrolled. All received pembrolizumab; one patient declined surgery. Among 84 patients, pCR was achieved in 44% (37 of 84; 95% CI, 33 to 55), and MPR in 57% (48 of 84; 95% CI, 46 to 68). Two (2%) patients died of complications within 30 days of surgery. At a median follow-up of 18.4 months (IQR, 16.3-21.1), one patient had a recurrence, resulting in overall and disease-free survival rates of 98% and 96%. Grade 3 adverse events occurred in 11% of patients (9 of 85; 95% CI, 3 to 16), with three treatment-related events. In 81 patients, the sensitivity, specificity, and accuracy of the biopsies for predicting pCR were 68%, 75%, and 72%, respectively. In 76 patients, the sensitivity, specificity, and accuracy of the endoscopic images for predicting pCR were 77%, 93%, and 86%, respectively. CONCLUSION: A single cycle of neoadjuvant pembrolizumab led to pCR in nearly half of patients undergoing surgery for localized dMMR colon cancer. The utility of endoscopic evaluation may inform future strategies for patient selection in nonoperative management pathways.

Endoscopic full-thickness resection (EFTR) has been shown to be a feasible and safe technique in several studies since the introduction of the full-thickness resection device (FTRD^®). This study aimed to describe our clinical experience and long-term follow up in in patients who underwent EFTR of benign and malignant colon lesions using FTRD. All patients with difficult adenomas or early adenocarcinomas referred for an EFTR to two centres in Denmark were included in this prospective consecutive study. The primary outcome was technical success with R0 resection and relapse-free follow up. The secondary outcome was procedure-related adverse events. Twenty-six patients were enrolled in the study. Technical success was achieved in 81% patients and R0 resection rate was 86%. Full-thickness resection was achieved in 86% patients. In 13 patients with malignant lesions, we obtained follow-up in 10 cases (two patients underwent surgery and one was non-compliant). Findings of the three-month follow up showed no residual tumour in all 10 cases. At the 12-month follow up, one patient had a late relapse. There were no residual or recurrent adenomas in the benign subgroup. Overall, adverse events were observed in 11.5% (3/26) patients with a perforation rate of 7.7%. EFTR with FTRD proves to be an additional technique for the treatment of difficult non-lifting colorectal lesions. For malignant lesions, EFTR is technically safe and feasible and can potentially treat small early low-risk tumours; however, some cases may require subsequent surgery according to the histological staging observed in the resected specimen.

Laparoscopically assisted transgastric endoscopic retrograde cholangiopancreatography (ERCP) is a common interventional procedure in patients with biliary disease and altered anatomy due to Roux-en-Y gastric bypass [1] [2] [3]. After access to the stomach, the operation field needs to be widely redraped to proceed with nonsterile ERCP. However, converting from the sterile to a nonsterile setting has become unnecessary with the introduction of single-use disposable duodenoscopes [4] [5]. The entire procedure can now be performed in a sterile manner. A 66-year-old woman with mild hypertension and diabetes presented with a history of repeated right upper quadrant abdominal pain. She had undergone cholecystectomy 30 years earlier for gallstone with biliary colic. In addition, she had a laparoscopic Roux-en-Y gastric bypass performed 13 years earlier, with successful weight loss and no postoperative complications. Magnetic resonance cholangiopancreatography revealed an 8-mm calculus in the common bile duct (CBD) ([Fig. 1]). An elective laparoscopic transgastric ERCP using the single-use/disposable duodenoscope (Exalt Model D; Boston Scientific Corporation, Marlborough, Massachusetts, USA) was planned. The operation was performed with the patient under general anesthesia. Laparoscopically, a 15-mm trocar was placed under the left costal arch and into the bypassed stomach and fixed with sutures ([Fig. 2]). Seamlessly, the procedure continued in the sterile setting with unpacking of the sterile duodenoscope ([Fig. 3]). The duodenoscope was introduced through the port ([Fig. 4]) and advanced to the duodenum. The CBD was cannulated, and the cholangiogram confirmed the presence in it of a bile stone. A sphincterotomy was performed, and the stone was extracted with a balloon catheter ([Video 1]). After the ERCP, the 15-mm port was removed and the gastrotomy sutured. Operative time was less than 1 h. The postoperative course was uneventful, and the patient was discharged after 24 h. Video 1 Transgastric endoscopic retrograde cholangiopancreatography performed using the single-use EXALT duodenoscope. The endoscope is introduced through the port, followed by cannulation, sphincterotomy, and stone removal with a balloon catheter. Our case demonstrates a successful transgastric ERCP procedure using the new single-use/disposable duodenoscope, thus introducing the possibility of performing this type of procedure in a completely sterile manner, reducing the risk of contamination and infection. This opens up new prospects in the use of single-use endoscopes, where the sterility of the scopes becomes a substantial asset. Endoscopy_UCTN_Code_TTT_1AU_2AC Publication Date: 18 June 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Purpose: Combined endoscopic laparoscopic surgery (CELS) is a minimally invasive alternative treatment for complex colonic polyps that can reduce surgical overtreatment. We report implementing a standardized treatment strategy with patients selected for CELS procedures via multidisciplinary team (MDT) conferences. Methods: This observational cohort study included 97 consecutive patients treated with CELS between 2016 and 2022. All cases were discussed by either a benign or malignant MDT. Two CELS techniques were employed: endoscopically assisted wedge resection (EA-WR) and laparoscopically assisted endoscopic mucosal resection (LA-EMR). Patients with suspected malignancies underwent step-up segmental resection (SR) if necessary. Primary outcomes were morbidity and mortality; secondary outcomes included adherence to MDT decisions, procedure durations, length of stay (LOS), histopathology, recurrence, and follow-up. Results: The approach decided by the MDT was unchanged in 81% of cases (79/97). Median age was 70 years and 43% were female. Lesions had a mean size of 31 mm and were predominantly located in the right colon. Technical success for lesion removal during the index procedure was 98% (95/97), with 93% completed by CELS alone. Median operative durations were shorter for EA-WR (52 min) and LA-EMR (73 min) than for SR (163 min, p < 0.001). Median LOS was 1 day for CELS and 5 days for SR ( p < 0.001). Eleven patients (11.3%) experienced complications; four required re-interventions. Adenocarcinomas were found in 15 patients (15/97, 12.6%), with treatment individualized based on intraoperative and histological findings. The recurrence rate for benign lesions was 4%; these recurrences were exclusively in the LA-EMR group. Conclusion: An MDT-guided strategy incorporating CELS, with optional intraoperative step-up, is an individualized and organ-preserving approach to managing complex colonic lesions that minimizes unnecessary surgical resections. This strategy has the potential to improve clinical decision-making and should be validated in multicenter settings.