Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro.

We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. The experiments were designed to reflect the conditions of intraperitoneal chemotherapy. CASY® (Cell Analysis System) technology was used to compare the impact of incubation temperature/duration and drug concentration on the viability of the cancer cell lines versus normal human dermal fibroblasts. Two incubation scenarios were explored: (i) hyperthermic intraperitoneal chemotherapy (HIPEC) with 1 h of incubation at 42 °C, and (ii) pressurized intraperitoneal aerosol chemotherapy (PIPAC) with several successive incubations at 37 °C. Under HIPEC conditions, oxaliplatin induced a potent temperature-dependent growth inhibition of colon cancer cells not seen with the duplex drug. Under PIPAC conditions, the duplex drug achieved the same growth inhibition at a fraction of the dose level required with oxaliplatin. Gastric and ovarian cancer cells were more sensitive to cisplatin plus doxorubicin than to the duplex drug under PIPAC conditions. The duplex drug suggests itself, notably in cases of platinum resistance, as an alternative or addition to intraperitoneal chemotherapies when platinum-based PIPAC technology is used. Using it with HIPEC technology is not recommended. Higher doses of the duplex drug will enhance growth inhibition, albeit at the cost of a severely reduced difference in chemosensitivity between tumor and normal cells. Our findings provide orientation for PIPAC-based personalized intraperitoneal chemotherapy.

A comparative study of laparoscopic and open Nissen fundoplication for GERD in Georgia.

AIM: The study compares and analyzes the effectiveness and outcomes of open A. Chernousov modified Nissen fundoplication (CMNF) and laparoscopic total fundoplication in Georgia for gastroesophageal reflux disease (GERD) concerning perioperative course, postoperative complications, symptomatic relief, recurrent disease and the need for reinterventional surgery. MATERIALS AND METHODS: A prospective randomized trial was performed. Twohundred fortythree patients with GERD were randomized, 123 patients underwent open CMNF procedure and 120 patients of laparoscopic total fundoplication. Pre- and postoperative tests included endoscopy, X-Ray, patient questionnaire (GERD - HQRL scale) and clinical assessment. Patients were followed for 10 years. RESULTS: This prospective randomized trial showed good and excellent long-term results after open and laparoscopic total fundoplication for GERD (92,7% vs 88,5% respectively) (p=0,03). After open CMNF procedure there were 3 cases of postoperative ventral hernia, 9 cases of mild dysphagia. There was no recurrence. After laparoscopic approach there were 7 cases of solid and transient dysphagia, 3 cases of hard stenosis of cardiacs caused by wrap. There were 2 cases of recurrence, 3 cases of reflux and 1 case of epigastral trocar hernia. CONCLUSION: In Georgia as well as throughout the world laparoscopic total fundoplication at the present time is the preferred method of choice for the treatment of GERD. It has best cosmetic effect, less pain and wound problems, shorter hospital stay, early return to work. Open CMNF is safe and effective procedure too. It prevents slippage syndrome and is characterized by better control of reflux and less frequency of recurrence and guarantees slightly better long-term functional results. KEY WORDS: Antireflux surgery, GERD, Modified Nissen fundoplication, Prospective randomized trial.