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Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors ( n  = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 95% confidence interval 23–68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1) + CD8 + T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835 . A neoadjuvant treatment regimen of anti-PD-L1 monotherapy followed by anti-PD-L1 plus chemotherapy was well tolerated and led to a major pathologic response rate of 70% in patients with resectable gastric or gastroesophageal junction adenocarcinoma.

Background Looking to further reduce the operative trauma of laparoscopic cholecystectomy, we developed, in patients with no history of cholecystitis and a normal BMI, a scarless operation through the umbilicus. The operative technique, along with the results of the first 10 patients operated in this way, are fully described. Methods 10 female patients underwent transumbilical scarless laparoscopic cholecystectomy. Through the umbilicus, two trocars of 5 mm were introduced parallel to another with a bridge of fascia between them (one for the 5-mm laparoscope and the other for the grasper). With the help of one 1-mm Kirschner wire, introduced at the subcostal line and bent with a special designed device, the gallbladder was pulled up and the triangle of Callot was dissected free, clipped, cut, and the gallbladder was subsequently resected. Finally the gallbladder was taken out through the umbilicus and the umbilicus reconstructed. Results 10 female patients, mean age 36 years (range: 31–49), mean body mass index (BMI) 23 (range: 20–26), after one attack (six patients) or a second attack (four patients) and cholelithiasis confirmed by ultrasonography with no suspicion of inflammation were included in this preliminary study. Mean operative time was 70 minutes (range: 65–85) with no conversions; hospital stay was less than 24 hours with no complications. Conclusion Looking to reduce operative trauma and improve the cosmetic result following laparoscopic cholecystectomy, a transumbilical operative technique has been developed. Results of the operative procedure in a selected group of patients are encouraging with no signs of inflammation and normal BMI. The umbilicus can be developed as a natural port for performing various operative procedures with the help of the traction produced by thin Kirschner wires.

Background The short-term results of the Sigma trial show that laparoscopic sigmoid resection (LSR) used electively for diverticular disease offers advantages over open sigmoid resection (OSR). This study aimed to compare the overall mortality and morbidity rates after evaluation of the clinical outcomes at the 6-month follow-up evaluation. Methods In a prospective, multicenter, double-blind, parallel-arm, randomized control trial, eligible patients were randomized to either LSR or OSR. The short-term results and methodologic details have been published previously. Follow-up evaluation was performed at the outpatient clinic 6 weeks and 6 months after surgery. Results In this trial, 104 patients were randomized for either LSR or OSR, and the conversion rate was 19.2%. The LSR approach was associated with short-term benefits such as a 15.4% reduction in the major complications rate, less pain, and a shorter hospital stay at the cost of a longer operating time. At the 6-month follow-up evaluation, no significant differences in morbidity or mortality rates were found. Two patients died of cardiac causes (overall mortality, 3%). Late complications (7 LSR vs. 12 OSR; p  = 0.205) consisted of three incisional hernias, five small bowel obstructions, four enterocutaneous fistulas, one intraabdominal abscess, one retained gauze, two anastomotic strictures, and three recurrent episodes of diverticulitis. Nine of these patients underwent additional surgical interventions. Consideration of the major morbidity over the total follow-up period (0–6 months) shows that the LSR patients experienced significantly fewer complications than the OSR patients (9 LSR vs. 23 OSR; p  = 0.003). The Short Form-36 (SF-36) questionnaire showed significantly better quality of life for LSR at the 6-week follow-up assessment. However, at the 6-month follow-up assessment, these differences were decreased. Conclusions The late clinical outcomes did not differ between LSR and OSR during the 30-day to 6-month follow-up period. Consideration of total postoperative morbidity shows a 27% reduction in major morbidity for patients undergoing laparoscopic surgery for diverticular disease.

Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid. Patients were retrospectively grouped into: a positive group (with PD) and a negative group (without PD). Detectable mutations were found in the primary tumor of 68% ( n  = 19). Sensitivity of PD detection by tumor-guided cfDNA analysis was 91%, compared to 64% by conventional cytology. Within the positive group ( n  = 11), tumor-guided cfDNA was detected in all patients with ascites samples (4/4, 100%) and in 86% (6/7) of the lavage samples, opposed to 4/4 (100%) patients with ascites and 43% (3/7) with lavage by conventional cytology. Within the negative group ( n  = 8), conventional cytology was negative for all samples. In two patients, tumor-guided cfDNA was detected in peritoneal lavage fluid. Interestingly, these 2 patients developed PD within 6 months, suggesting a prognostic value of tumor-guided cfDNA detection. This study showed that tumor-guided cfDNA detection in peritoneal fluids of GC patients is feasible and superior to conventional cytology in detecting PD.

BackgroundIn search of improvement of patient assessment in the postoperative phase, C-reactive protein (CRP) is increasingly being studied as an early marker for postoperative complications following major abdominal surgery. Several studies reported an attenuated immune response in minimally invasive surgery, which might affect interpretation of postoperative CRP levels. The aim of the present study was to compare the value of CRP as a predictor for major postoperative complications in patients undergoing open versus laparoscopic colorectal surgery.MethodsA subgroup analysis from a randomized clinical trial (LAFA-trial) was performed, including all patients with non-metastasized colorectal cancer. In the LAFA trial, patients were randomized to open or laparoscopic segmental colectomy. In a subgroup of 79 patients of the LAFA trial, postoperative assessment of CRP levels was conducted routinely preoperatively and 1, 2, 24 and 72 h after surgery.ResultsThirty-seven patients were randomized to the open group and 42 patients to the laparoscopic group. Major complications occurred in 19% of laparoscopic procedures and 13.5% of open procedures (p = 0.776). CRP levels rise following surgical procedures. In uncomplicated cases, the rise in CRP levels was significantly lower at 24 and 72 h following laparoscopic resection in comparison to open resection. No differences in CRP levels were observed when comparing open and laparoscopic resection in patients with major complications.ConclusionIn patients with an uncomplicated postoperative course, CRP levels were lower following minimally invasive resection, possibly due to decreased operative trauma. No differences in CRP were observed stratified for surgical technique in patients with major complications. These results suggest that CRP may be applied as a marker for major postoperative complications in both open and minimally invasive colorectal surgery. Future research should aim to assess the role of standardized postoperative CRP measurements.

BackgroundCervical anastomotic strictures after esophagectomy cause significant disease burden. We aimed to study the technical feasibility and safety of intensive endoscopic therapy.MethodsIn this pilot study, we included 15 patients with an untreated benign cervical anastomotic stricture after esophagectomy. Intensive endoscopic therapy comprised three endoscopic modalities: in- and excision using a needle-knife, intralesional steroid injections and bougie dilation. In two endoscopic procedures, the stricture was dilated up to a luminal diameter of 18 mm. Patients were followed up to 6 months.ResultsA luminal diameter of 18 mm was achieved in 13 of 15 patients (87%) after two endoscopic procedures. No major adverse events related to the investigational treatment occurred. Median dysphagia scores significantly improved from 2 (IQR, interquartile range, 2–3) at baseline to 0 (IQR 0–1) after 14 days (p < 0.001). Eleven (73%) patients developed recurrent symptoms of dysphagia requiring a median of 1 (IQR 0–3) additional endoscopic dilation procedure.ConclusionsAchieving a luminal diameter of 18 mm in two procedures with intensive endoscopic therapy was technically feasible and effective in reducing dysphagia rapidly in patients with a cervical anastomotic stricture after esophagectomy. No major adverse events related to the investigational treatment were observed.

Background There is a paucity of data on the cost‐utility of endoscopic ultrasonography‐guided gastroenterostomy (EUS‐GE) compared with surgical gastrojejunostomy (SGJ) as palliative treatment of malignant gastric outlet obstruction. Methods In the ENDURO trial, 98 patients with malignant gastric outlet obstruction from 12 Dutch hospitals were randomized between EUS‐GE (N = 48) and SGJ (N = 50). Cost utility was evaluated from a healthcare perspective with a time horizon of 1 month. A bottom‐up approach was used to calculate the costs of each intervention, including the per‐minute price of the endoscopy and operating room (OR), considering personnel, construction, inventory and overhead costs. Other in‐hospital costs were calculated using insurance claim data. Effectiveness was displayed as quality‐adjusted life years (QALY). Bootstrapping was performed to estimate uncertainty. Results The calculated per‐minute price for the endoscopy room was €8.64 (US9.34). The per‐minute price for an OR was €11.78 (US 12.74). The mean intervention costs were estimated at €4405.40 (US4762.68) for EUS‐GE and €3393.71 (US 3668.93) for SGJ. Mean total in‐hospital costs were lower following EUS‐GE (€5172 [US5591]) than after SGJ (€10,458 [US 11,306]), mainly due to a shorter length of hospital stay following EUS‐GE. Bootstrapping showed that 99.9% of iterations resulted in lower costs for EUS‐GE. Mean difference in 1‐month QALY contribution was 0.004 in favor of EUS‐GE. Most iterations fall within the bottom right quadrant (95.6%) of the cost‐effectiveness plane, indicating lower costs and improved QALY contribution for EUS‐GE. Discussion In this study, EUS‐GE was more cost effective than SGJ. The additional intervention costs were clearly outweighed by a decrease in in‐hospital costs after the procedure. Key Summary Summarize the established knowledge on this subject ◦ Malignant gastric outlet obstruction can be treated by surgical gastrojejunostomy (SGJ) and endoscopic ultrasonography‐guided gastroenterostomy (EUS‐GE) in patients with a good performance status. ◦ Recent trials have shown superiority of EUS‐GE to SGJ in terms of oral intake tolerability and length of hospital stay. ◦ Data is scarce on whether EUS‐GE is more cost‐effective than SGJ. What are the significant and/or new findings of this study? ◦ Mean intervention costs were lower after SGJ (€3393.71 vs. €4405.40), but mean total in‐hospital costs were lower after EUS‐GE (€5172 vs. €10,458). ◦ Incremental difference in mean total costs was €4305 after one month and in QALY contribution was 0.004, favoring EUS‐GE. ◦ Bootstrapping showed that 99.9% of iterations resulted in lower costs for EUS‐GE. ◦ EUS‐GE was more cost effective than SGJ as palliative treatment for malignant gastric outlet obstruction, primarily caused by a decrease in in‐hospital costs after EUS‐GE.

Background Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic leak is a key component of surgical planning, including the opportunity to create a defunctioning stoma. Objective The purpose of this study was to identify and quantify the risk factors for anastomotic leak to minimize risk by either not restoring bowel continuity or protecting the anastomosis with a temporary diverting stoma. Methods Potentially relevant studies were identified from the following databases: PubMed, Embase and Cochrane Library. This meta-analysis included studies on transabdominal resection for rectal cancer that reported data about anastomotic leak. The risk for anastomotic leak after rectal cancer surgery was investigated. Preoperative, intraoperative, and postoperative factors were extracted and used to compare anastomotic leak rates. All variables demonstrating a p value < 0.1 in the univariate analysis were entered into a multivariate logistic regression model to determine the risk factors for anastomotic leak. Results Twenty-six centers provided individual data on 9735 patients. Selected preoperative covariates (time before surgery, age, gender, smoking, previous abdominal surgery, BMI, diabetes, ASA, hemoglobin level, TNM classification stage, anastomotic distance) were used as independent factors in a logistic regression model with anastomotic leak as dependent variable. With a threshold value of the receiver operating characteristics (ROC) curve corresponding to 0.0791 in the training set, the area under the ROC curve (AUC) was 0.585 ( p  < 0.0001). Sensitivity and specificity of the model’s probability > 0.0791 to identify anastomotic leak were 79.1% and 32.9%, respectively. Accuracy of the threshold value was confirmed in the validation set with 77.8% sensitivity and 35.2% specificity. Conclusions We trust that, with further refinement using prospective data, this nomogram based on preoperative risk factors may assist surgeons in decision making. The score is now available online ( http://www.real-score.org ).