In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived tumor organoids (PDTO) show enormous potential for preclinical testing; however, cultured tumor cells lose important characteristics, including the consensus molecular subtypes (CMS). To better reflect the cellular heterogeneity, we established the colorectal cancer organoid–stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that xenotransplantation or coculture with CAFs improves the transcriptomic fidelity and instructs subtype-specific stromal gene expression. Furthermore, functional profiling in coculture exposed CMS4-specific therapeutic resistance to gefitinib and SN-38 and prognostic expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as a common target. Our results demonstrate that colorectal cancer phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for a faithful representation of molecular subtypes and therapy responses ex vivo. Significance: Systematic characterization of the organoid–stroma biobank provides a resource for context dependency in colorectal cancer. We demonstrate a colorectal cancer subtype memory of PDTOs that is independent of specific driver mutations. Our data underscore the importance of functional profiling in cocultures for improved preclinical testing and identification of stromal resistance mechanisms. This article is featured in Selected Articles from This Issue, p. 2109

Background: Robotics represents the most technologically advanced approach in minimally invasive surgery (MIS). Its application in general surgery has increased progressively, with some early experience reported in emergency settings. The present position paper, supported by the World Society of Emergency Surgery (WSES), aims to provide a systematic review of the literature to develop consensus statements about the potential use of robotics in emergency general surgery. Methods: This position paper was conducted according to the WSES methodology. A steering committee was constituted to draft the position paper according to the literature review. An international expert panel then critically revised the manuscript. Each statement was voted through a web survey to reach a consensus. Results: Ten studies (3 case reports, 3 case series, and 4 retrospective comparative cohort studies) have been published regarding the applications of robotics for emergency general surgery procedures. Due to the paucity and overall low quality of evidence, 6 statements are proposed as expert opinions. In general, the experts claim for a strict patient selection while approaching emergent general surgery procedures with robotics, eventually considering it for hemodynamically stable patients only. An emergency setting should not be seen as an absolute contraindication for robotic surgery if an adequate training of the operating surgical team is available. In such conditions, robotic surgery can be considered safe, feasible, and associated with surgical outcomes related to an MIS approach. However, there are some concerns regarding the adoption of robotic surgery for emergency surgeries associated with the following: (i) the availability and accessibility of the robotic platform for emergency units and during night shifts, (ii) expected longer operative times, and (iii) increased costs. Further research is necessary to investigate the role of robotic surgery in emergency settings and to explore the possibility of performing telementoring and telesurgery, which are particularly valuable in emergency situations. Conclusions: Many hospitals are currently equipped with a robotic surgical platform which needs to be implemented efficiently. The role of robotic surgery for emergency procedures remains under investigation. However, its use is expanding with a careful assessment of costs and timeliness of operations. The proposed statements should be seen as a preliminary guide for the surgical community stressing the need for reevaluation and update processes as evidence expands in the relevant literature.

The purpose of this review was to identify the relationship between the gut microbiome and the development of postoperative complications like anastomotic leakage or a wound infection. Recent reviews focusing on underlying molecular biology suggested that postoperative complications might be influenced by the patients’ gut flora. Therefore, a review focusing on the available clinical data is needed. In January 2017 a systematic search was carried out in Medline and WebOfScience to identify all clinical studies, which investigated postoperative complications after gastrointestinal surgery in relation to the microbiome of the gut. Of 337 results 10 studies were included into this analysis after checking for eligibility. In total, the studies comprised 677 patients. All studies reported a postoperative change of the gut flora. In five studies the amount of bacteria decreased to different degrees after surgery, but only one study found a significant reduction. Surgical procedures tended to result in an increase of potentially pathogenic bacteria and a decrease of Lactobacilli and Bifidobacteria. The rate of infectious complications was lower in patients treated with probiotics/symbiotics compared to control groups without a clear relation to the systemic inflammatory response. The treatment with synbiotics/probiotics in addition resulted in faster recovery of bowel movement and a lower rate of postoperative diarrhea and abdominal cramping. There might be a relationship between the gut flora and the development of postoperative complications. Due to methodological shortcomings of the included studies and uncontrolled bias/confounding factors there remains a high level of uncertainty.

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch^© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens. One hundred nine patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis and multivariable analysis. A dose reduction due to side effects was necessary in 46 (42%) patients. Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Comparison of patients with dose reduction versus patients with full dosage showed no significant difference on overall survival (p = 0.430). Subgroup analysis revealed dose reduction in patients with N2 stage disease was associated with improved survival. Patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups. Contrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis. We believe this can in part be explained by better adaption to interindividual pharmacokinetics and longer time of treatment.

To compare proximal gastrectomy with double-tract reconstruction and total gastrectomy in patients with gastroesophageal junction (AEG II-III) and gastric cancer. We conducted systematic searches in Medline, Web of Science, and Cochrane Library until December 20, 2021 (PROSPERO registration number: CRD42021291500). Risk of bias was assessed using the revised Cochrane risk of bias tool and the ROBINS-I tool, as applicable. Evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. One randomized controlled trial (RCT) and 13 non-RCTs with 1,317 patients (715 patients with total gastrectomy and 602 patients with proximal gastrectomy with double-tract reconstruction) were included. Patients treated by total gastrectomy had a significantly higher proportion of advanced cancer stages International Union Against Cancer IB-III (odds ratio: 0.68, 95% confidence interval: 0.51-0.91, P = .01). This heterogeneity biases the observed improved overall survival of patients after proximal gastrectomy with double-tract reconstruction (odds ratio: 0.67, 95% confidence interval: 0.44-1.01, P = .05). Both procedures were comparably efficient regarding perioperative parameters. Postoperative/preoperative bodyweight ratio (mean difference: 3.56, 95% confidence interval: 1.32-5.79, P = .002), postoperative/preoperative serum-hemoglobin ratio (mean difference 3.73, 95% confidence interval: 1.59-5.88, P < .001), and postoperative serum vitamin B₁₂ levels (mean difference 42.46, 95% confidence interval: 6.37-78.55, P = .02) were superior after proximal gastrectomy with double-tract reconstruction, while postoperative/preoperative serum-albumin ratio (mean difference 1.24, 95% confidence interval: -4.76 to 7.24, P = .69) and postoperative/preoperative serum total protein ratio (mean difference 1.12, 95% confidence interval: -2.77 to 5.00, P = .57) were not different. Health-related quality of life data were reported in only 2 studies, which found no significant advantages for proximal gastrectomy with double-tract reconstruction. Proximal gastrectomy with double-tract reconstruction offers advantages in postoperative nutritional parameters compared to total gastrectomy (GRADE: moderate quality of evidence). Oncological effectiveness of proximal gastrectomy with double-tract reconstruction cannot be assessed (GRADE: very low quality of evidence). Further thoroughly planned randomized controlled trials in Western patient cohorts are necessary to improve treatment for gastric cancer patients.