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Background/Objectives: Peritoneal metastases represent a common manifestation of advanced gastrointestinal malignancies and are associated with poor survival. Their early detection is essential for adequate tumor staging, prognosis, and treatment selection, especially to avoid unnecessary surgery. Intraoperative peritoneal lavage has been established as a diagnostic tool to detect occult peritoneal disease. However, reported techniques, analytical methods, and detection rates vary considerably. The objective of this review was to summarize current approaches to intraoperative peritoneal lavage, evaluate different detection methods, and assess their clinical relevance. Methods: A literature search was performed using the PubMed database for studies published between 2015 and 2025. The search terms “intraoperative peritoneal lavage” or “peritoneal fluid cytology” were used. Studies were included if they evaluated peritoneal lavage as a diagnostic method for detecting malignant cells, including all primary tumors and disease stages. Articles focusing on lavage as a therapeutic intervention or lacking methodological details were excluded. Results: Physiological saline solution was used for lavage in all included studies, with volumes ranging from 10 to 1000 mL. Sampling was predominantly performed immediately after abdominal access in various abdominal sites. Detection methods varied widely, with conventional cytology being most frequently used, while molecular techniques were used in a smaller number of studies. Positive detection rates showed broad variations and were higher in advanced tumor stages. Conventional cytology showed limited detection rates compared to molecular approaches. Conclusions: Intraoperative peritoneal lavage remains a valuable but methodologically heterogeneous diagnostic tool with limited detection rates when relying on conventional cytology alone. Molecular techniques seem to improve the detection rate of occult peritoneal disease but require further standardization and validation before routine clinical implementation. The technique of peritoneal lavage should be standardized by implementing an international consensus including lavage sites, volume of applied fluid, and detection method.

Background Microsatellite instability (MSI) occurs in several cancer types and is commonly used for prognosis and as a predictive biomarker for immune checkpoint therapy. Methods We analyzed n = 263 formalin‐fixed paraffin‐embedded (FFPE) tumor specimens (127 colorectal cancer (CRC), 55 endometrial cancer (EC), 33 stomach adenocarcinoma (STAD), and 48 solid tumor specimens of other tumor types) with a capillary electrophoresis based multiplex monomorphic marker MSI‐PCR panel and an amplicon‐based NGS assay for microsatellite instability (MSI+). In total, n = 103 (39.2%) cases with a known defect of the DNA mismatch repair system (dMMR), determined by a loss in protein expression of MSH2/MSH6 (n = 48, 46.6%) or MLH1/PMS2 (n = 55, 53.4%), were selected. Cases with an isolated loss of MSH6 or PMS2 were excluded. Results The overall sensitivity and specificity of the NGS assay in comparison with the MSI‐PCR were 92.2% and 98.8%. With CRC cases a nearly optimal concordance was reached (sensitivity 98.1% and specificity 100.0%). Whereas EC cases only show a sensitivity of 88.6% and a specificity of 95.2%, caused by several cases with instability in less than five monomorphic markers, which could be difficult to analyze by NGS (subtle MSI+ phenotype). Conclusions MSI analysis of FFPE DNA by NGS is feasible and the results show a high concordance in comparison with the monomorphic marker MSI‐PCR. However, cases with a subtle MSI+ phenotype, most frequently manifest in EC, have a risk of a false‐negative result by NGS and should be preferentially analyzed by capillary electrophoresis. Microsatellite instability (MSI) analysis of formalin‐fixed paraffin‐embedded (FFPE) DNA by NGS is feasible and the results show a high concordance in comparison with the monomorphic marker MSI‐PCR (overall sensitivity and specificity of the NGS assay in comparison with the MMR‐IHC/MSI‐PCR were 92.2% and 98.8%). However, cases with a subtle MSI+ phenotype, most frequently manifest in endometrial cancer (EC), have a risk of a false‐negative result by NGS and should be preferentially analyzed by capillary electrophoresis.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1/E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth.

PurposeSeveral targeted agents demonstrated efficacy in early clinical trials for gastrointestinal (GI) cancers, but in many cases, phase-III trials and/or approval by the European Medicines Agency (EMA) are lacking. The primary focus of this study was to assess the regulatory processes associated with use and reimbursement of off-label treatment in precision oncology and to evaluate the benefit of targeted therapy in a real-world population in Germany.MethodsOur cohort comprises 137 patients with GI cancers and is biased towards cancer entities with a high frequency of known targetable alterations, such as cholangiocarcinoma. Genetic testing was used to identify molecular targets, and therapy response was evaluated based on CT scans.ResultsA molecular target for precision oncology was identified in 53 patients and 43 requests for cost coverage were submitted to health insurance companies. 60% of the requests received approval after initial application and another 7% after appeal. Half of the rejected requests were denied despite ESCAT IA level evidence. The median time between initiation of molecular testing and start of therapy was 75 days. 35 patients received matched targeted therapies (n = 28) or, in the case of MSI, immunotherapy (IO) (n = 7). We observed a trend in favor of molecular therapy when compared to the immediate prior treatment.ConclusionRelevant treatment options were identified by molecular testing in a significant subset of patients. When targeted therapies that lack EMA approval are considered, treatment initiation may be delayed by the duration of the molecular analysis and the regulatory processes.

Purpose The purpose of this study was to identify prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) treated with resection and to investigate the effect of adjuvant chemotherapy (CT). Methods Patients with ICC diagnosed between 2000 and 2015 treated at Hannover Medical School were included. Clinicopathologic characteristics were analyzed in univariate and multivariate analysis. In a matched pair survival analysis, patients with or without adjuvant CT were matched by these prognostic factors. Results Two hundred and ten patients were included. Median survival was 28.7 months, 1-, 3-, and 5-year survival rates were 72.8%, 29.6%, and 14.1%, respectively. In multivariate analysis, lymph node involvement ( p  = 0.006, HR 1.84), larger tumor size ( p  = 0.013, HR 1.79), vascular invasion ( p  = 0.038, HR 1.70), and prolongation of prothrombin time ( p  < 0.001, HR 4.20) were significantly related to poor survival. Thirty-nine patients received adjuvant CT of which 60% had lymph node involvement. Each 25 patients with and without adjuvant CT were matched to the identified prognostic factors. The median survival of patients with adjuvant CT was 33.5 months, compared to 18 months in the control group ( p  = 0.002). The 1-, 3-, and 5-year survival rates were 96, 36, and 12%, compared to 60, 4, and 0% in non-treated patients. Conclusions We identified several prognostic factors for patients with ICC treated with resection. Our data support the use of adjuvant CT in patients with ICC. The results of prospective randomized controlled studies will clarify the role of adjuvant CT in the future.

In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in ‘ultramutated’ sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple café-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer.