Volume 1, Issue 2 -

Background : The current treatment of choice for peritoneal carcinomatosis from gastric cancer is systemic chemotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a new aggressive form of loco-regional treatment that is currently being used in pseudomyxoma peritoneii, peritoneal mesothelioma and peritoneal carcinomatosis from colorectal cancer. It is still under investigation for its use in gastric cancer. Methods : The literature between 1970 and 2016 was surveyed systematically through a review of published studies on the treatment outcomes of CRS and HIPEC for peritoneal carcinomatosis from gastric cancer. Results : Seventeen studies were included in this review. The median survival for all patients ranged from 6.6 to 15.8 months. The 5-years overall survival ranged from 6 to 31%. For patients with complete cytoreduction, the median survival was 11.2 to 43.4 months and the 5-years overall survival was 13 % to 23%. Important prognostic factors were found to be a low peritoneal carcarcinomatosis index (PCI) score and the completeness of cytoreduction. Conclusion : The current evidence suggests that CRS and HIPEC has a role to play in the treatment of peritoneal carcinomatosis from gastric cancer. Long term survival has been shown for a select group of patients. However, further studies are needed to validate these results.

Mesothelial cells (MCs) form the superficial anatomic layer of serosal membranes, including pleura, pericardium, peritoneum, and the tunica of the reproductive organs. MCs produce a protective, non-adhesive barrier against physical and biochemical damages. MCs express a wide range of phenotypic markers, including vimentin and cytokeratins. MCs play key roles in fluid transport and inflammation, as reflected by the modulation of biochemical markers such as transporters, adhesion molecules, cytokines, growth factors, reactive oxygen species and their scavengers. MCs synthesize extracellular matrix related molecules, and the surface of MC microvilli secretes a highly hydrophilic protective barrier, “glycocalyx”, consisting mainly of glycosaminoglycans. MCs maintain a balance between procoagulant and fibrinolytic activation by producing a whole range of regulators, can synthetize fibrin and therefore form adhesions. Synthesis and recognition of hyaluronan and sialic acids might be a new insight to explain immunoactive and immunoregulatory properties of MCs. Epithelial to mesenchymal transition of MCs may involve serosal repair and remodeling. MCs might also play a role in the development and remodeling of visceral adipose tissue. Taken together, MCs play important roles in health and disease in serosal cavities of the body. The mesothelium is not just a membrane and should be considered as an organ.

Malignant mesothelioma (MM) is a malignancy arising from the mesothelial cells lining the thoracic and abdominal serosal cavities. The pleural space is the most commonly affected site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. The different types of mesotheliomas are generally considered as distinct diseases with specific risk factors, therapeutic strategies and prognoses. Epidemiological and clinical differences between pleural and peritoneal MM raise questions about the involvement of different molecular mechanisms. Since the BAP1 gene is involved in the BAP1 cancer syndrome and seems to be a prognostic factor in MM, this review presents an overview of BAP1 alterations in mesothelioma comparing pleural and peritoneal localizations.

Background : Multimodal therapeutic strategies have improved the outcome of peritoneal metastases (PM). However, objective assessment of therapy response remains difficult in PM, since radiological studies have a poor accuracy for low-volumetric disease. There is an obvious need for a histological gold standard allowing assessment of tumor response to treatment in PM. Content : We propose to perform peritoneal punch biopsies with a diameter of 3 to 5 mm in all four abdominal quadrants. We propose a four-tier Peritoneal Regression Grading Score (PRGS), defined as Grade 1: complete response (absence of tumor cells), Grade 2: major response (major regression features, few residual tumor cells), Grade 3: minor response (some regressive features but predominance of residual tumor cells), Grade 4: no response (tumor cells without any regressive features). Acellular mucin and infarct-like necrosis should be regarded as regression features. We recommend reporting the mean and the worst value of the regression grades obtained. When complete tumor response is suspected intraoperatively, a peritoneal cytology should be sampled. Summary : A generic, unique score for the assessment of histological tumor response to chemotherapy in PM makes sense because of the clinical impact of histological response to therapy and because the organ of metastasis (peritoneum) is the same. By adopting PRGS, different centers will be able to use a uniform terminology and grading that will allow meaningful comparison of their results. Outlook : PRGS has now to be validated in several gastrointestinal and gynecological cancer types and may be useful both in clinical and research settings.

Background : Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a drug delivery technique with superior pharmacological properties for treating peritoneal metastasis (PM). Adding electrostatic loading ( e PIPAC) as an adjunct to aerosol and artificial hydrostatic pressure improved tissue uptake in a preclinical model. Methods : We report the first e PIPAC use in 3 patients with PM of hepatobiliary-pancreatic (HBP) origin. All 3 patients received concomitant palliative systemic chemotherapy that was discontinued in two patients. PIPAC with cisplatin 7.5 mg/m 2 and doxorubicin 1.5 mg/m 2 was applied intraperitoneally at a pressure of 12 mmHg and a temperature of 37% °C for 30 min. Additionally, a voltage 7,500–9,500 V and a current≤10 µA were applied over a stainless steel brush electrode emitting a stream of electrons. Results : e PIPAC was technically feasible. No intraoperative complication was noted. The procedures were well tolerated with no adverse event CTCAE > 2. Patient 1 with PM of unknown origin (CUP with HBP phenotype) showed an objective histological and radiological response and survived 11 months. Patient 2 with ductal pancreatic cancer underwent secondary resection after ePIPAC with no residual PM; however, tumor recurred 5 months later. Patient 3 with adenocarcinoma of the gallbladder showed a radiological regression of liver infiltration and is alive after 22 months without histological evidence of PM. Conclusion : ePIPAC is technically feasible, is well tolerated and can induce tumor regression of PM in HBP cancers with and without concomitant systemic chemotherapy. These preliminary results justify prospective clinical studies with ePIPAC.