Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III "PREVENT"- (FLOT9) trial of the AIO /CAOGI /ACO.

BACKGROUND: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. METHODS: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021. DISCUSSION: If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .

[Updated S3-Guideline for Prophylaxis, Diagnosis and Treatment of Gallstones. German Society for Digestive and Metabolic Diseases (DGVS) and German Society for Surgery of the Alimentary Tract (DGAV) - AWMF Registry 021/008]. / Aktualisierte S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) zur Prävention, Diagnostik und Behandlung von Gallensteinen.

This guideline provides evidence-based key recommendations for the prevention, diagnosis and therapy of gallstones and upgrades the 2007 version. The guideline was developed by an interdisciplinary team of gastroenterologists and surgeons, and patient support groups under the auspice of the German Society for Gastroenterology and Metabolic Diseases and the German Society for General Surgery and Surgery of the Alimentary Tract. The guideline used structural S3 consensus-based methodology and includes statements on clinical practice, medical education, prevention, quality assurance, outcome analysis, and integration of outpatient and inpatient care for patients with gallstone diseases.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma.

BACKGROUND: Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options. METHODS: We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE). RESULTS: A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application). CONCLUSION: After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.

First Clinical Data of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as Salvage Therapy for Peritoneal Metastatic Biliary Tract Cancer.

BACKGROUND: Patients suffering from peritoneal metastasis of biliary tract cancer were treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). PATIENTS AND METHODS: This was a study carried out at a single institution, tertiary referral center certified for therapy of peritoneal disease. Retrospective data analysis was performed of prospective data for PIPAC with intra-peritoneal low-dose doxorubicin (1.5 mg/m2) and cisplatin (7.5 mg/m2) delivered at intervals of 6 weeks. The outcome criteria were microscopic pathological response, survival, and adverse events [Common Terminology Criteria of Adverse Events (v4.0)]. RESULTS: A total of 13 patients (male/female=8/5) with a mean age of 58 (range=37-75) years underwent 17 PIPAC procedures without intraoperative complications. The mean number of PIPAC applications was 1.3 (range=0-3). Due to non-accessibility of the abdominal cavity in two patients (15.4%) and rapid clinical deterioration in six patients (46%), five patients underwent two or more PIPAC applications and were, therefore, eligible for histological analysis to assess carcinoma regression. Overall tumor regression of any degree was determined in 4/5 patients. An overall median survival of 85 days (95% confidence interval(CI)=59.2-110.4 days) after the first PIPAC application was observed. No complications greater than Common Terminology Criteria of Adverse Events (v4.0) level 2 occurred. CONCLUSION: PIPAC can induce objective regression of systemic chemotherapy-resistant peritoneal metastasis of biliary tract cancer. However, due to a rapid clinical deterioration of the patients, almost two-thirds of the patients cannot undergo repetitive PIPAC courses.