Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

Laparoscopic Electromyography and Electrostimulation of the Gastrointestinal Tract Before Placement of Theranostic Devices.

NEED: Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. TECHNICAL SOLUTION: A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. PROOF OF CONCEPT: Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. NEXT STEPS: Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. CONCLUSION: We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

Minimally-invasive temporary gastric stimulation: A pilot study to predict the outcome of electronic gastric stimulation with the Enterra™ system.

INTRODUCTION: Gastroparesis (GP) is defined as delayed gastric emptying (GE) without any obstruction of the pylorus. It can be divided into idiopathic, diabetic, post surgical and rare causes. Electronic gastric stimulation (EGS) - Enterra Medtronic™ - is a part of GP therapy. Although its positive impact has been reported in open label trials, randomized controlled trials failed in demonstrating a positive outcome. The aim of this pilot study was to establish a reliable prediction for permanent gastric stimulation. PATIENTS AND PROCEDURE: 6 female patients underwent laparoscopic implantation of 2 temporary electrodes. The Enterra™ system was connected and taped to the skin. Baseline and postoperative gastroparesis cardinal symptom index (GCSI), a validated index for GP therapy, was assessed. Response to EGS was defined as a 50% decrease of baseline GCSI. RESULTS: 4 of 6 patients responded to temporary EGS. 3 of 4 responders underwent permanent implantation. 1 non-responder received a permanent Enterra™ at another institution. After a median follow up time of 9months the responder group GCSI remained low, whereas the non-responder GCSI had increased. Moreover, the health care system was saved € 30,678.03 by this test stimulation concept. CONCLUSION: Laparoscopic implantation of a temporary EGS system predicts the outcome of permanent gastric stimulation and is cost-saving.

Robot-guided neuromapping during nerve-sparing taTME for low rectal cancer.

PURPOSE: Intraoperative pelvic neuromapping with electrophysiological evaluation of autonomic nerve preservation during robotic total mesorectal excision (TME) for rectal cancer is conventionally performed by the bedside assistant with a hand-guided probe. Our goal was to return autonomy over the neuromonitoring process to the colorectal surgeon operating the robotic console. METHODS: A recently described prototype microfork electrostimulation probe was evaluated intraoperatively during abdominal robotic-assisted transanal TME (taTME) surgery for low rectal cancer in three consecutive male patients. RESULTS: An intraoperative video demonstrates the good control and maneuverability of the prototype probe with electrophysiological confirmation of bilateral pelvic autonomic nerve preservation. CONCLUSIONS: This study presents the first in situ application of a new microfork probe for fully robot-guided neuromapping in three patients undergoing TME surgery for low rectal cancer.

Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.

BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting. METHODS: Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or > or =5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4-6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998. FINDINGS: 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI -8 to 30; odds ratio [OR] 1.62, 0.74-3.59; p=0.23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35-8.66; p=0.0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p<0.0001). INTERPRETATION: Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. FUNDING: Merck-Serono, Sanofi-Aventis, and Pfizer.