A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement

Abstract

Peritoneal carcinomatosis (PC) is manifested in up to 40% of gastric cancer (GC) patients, after which their 5-year survival drops to less than 5%. The currently most acceptable treatment option for advanced GC (AGC) is systemic chemo and radio therapies with however generally very unsatisfying results and this led to a resurgence of interest in regional therapies like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Small trials have indicated an association with prolonged survival when applying this technique to AGC manifesting with PC. High procedure-related morbidity and mortality associated with the CRS-HIPEC approach have however brought by a polemic on the merits of the latter: with the advent of regulatory approval of more effective as well as novel, more personalized treatment options in AGC, along with advances in tailoring investigational agents specifically for peritoneal delivery, there clearly is a need to outline the appropriate role of CRS-HIPEC in this disease.In a clear objective to improve the therapeutic efficiency of HIPEC, there have been immense developments in the technical aspects of this technology including the use of nanotechnology in more precise drug delivery systems (DDS) or choice of more efficient drugs such as gene-target technology, laparoscopy and so on. Henceforth, in this review, we will be highlighting the past and current status of the CRS + HIPEC procedure, shedding light on the pros and cons in order to boost up the efficiency of this multimodality approach.

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy, Part II: Implementation

“…The chemoperfusate should circulate evenly throughout the abdominopelvic cavity to allow the heat and chemotherapy agent to contact all peritoneal surfaces and to prevent pooling, which could lead to a focal hyperthermic injury, postoperative ileus, bowel perforation, or fistula formation . The patient must remain paralyzed during the perfusion of the chemotherapy agent because coughing can cause the fluid to spill (Alan Gwertzman, MD; anesthesiologist; oral communication; June 16, 2017).…”

“…Cytoreductive surgery with HIPEC is a viable treatment option for patients with abdominopelvic cancer with peritoneal carcinomatosis . Morbidity and mortality have improved for patients who have undergone this procedure since it was first performed in 1955 …”

Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy, Part I: Introduction and Indications

“…He developed a staging system as a prognostic tool to indicate the extent of PC disease on the tissue surface . Although physicians can determine staging before the procedure with computed tomography (CT) or magnetic resonance imaging, Sugarbaker believed it was best to determine staging during an abdominopelvic cavity exploration, at which time the surgeon may decide whether to continue the procedure either as an attempt to cure PC or as a palliative measure …”

“…Heat also increases the pharmacokinetics (eg, absorption, distribution) of chemotherapeutic agents, causing greater medication uptake and penetration into cancer cells after CRS by increasing cell membrane permeability and improving membrane transport . Additionally, thermodynamics inhibits cancer cells from excreting medications, which increases cumulative medication concentrations in those cells …”

“…The HIPEC delivery system allows for a high concentration of chemotherapy medication to be delivered regionally into the peritoneal cavity while avoiding high systemic blood levels, resulting in direct contact and an increased reaction rate between the medication and cancer cells . According to different studies, the peritoneal‐plasma barrier allows medication levels to be 20 to 50 times, or 20 to 1,000 times, greater than that of the plasma and with less systemic toxicity because of a slow rate of clearance from the peritoneal cavity . The peritoneal plasma barrier maintains a constant high gradient between the peritoneal cavity and the plasma compartment, which decreases medication clearance from the peritoneum.…”