Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study.

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. PATIENTS AND METHODS: We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. RESULTS: Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. CONCLUSIONS: The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies.

Indication of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer (Gastripec, Gastrichip).

Background: Gastric cancer (GC) is associated with a poor prognosis mostly due to peritoneal metastasis, which will develop in time during the patient's disease history. To prevent and treat peritoneal metastasis, different kinds of treatment regimens have been described. Summary: In this review, we addressed two main topics - prophylaxis and treatment of peritoneal metastasis in GC. Prevention should be directed towards diminishing cancer cell spillage and reducing adherence of cancer cells to the abdominal cavity. Postoperative washing of the abdomen with or without chemotherapy and additional heat are herein discussed. Key Messages: Treatment of existing peritoneal metastasis is effective in patients with limited disease and tumour spread. Cytoreductive surgery including resection of peritoneal metastasis followed directly with hyperthermic intraperitoneal chemotherapy can increase overall survival and progression-free survival in selected patients. Drugs, duration and time schedules of intraperitoneal chemotherapy are reviewed and presented. Intraperitoneal chemotherapy seems to improve the prognosis of patients with GC and peritoneal metastasis after complete resection of both primary and metastatic tumours.

HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques.

(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms "intraperitoneal chemotherapy AND gastric cancer". Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50-200 mg/m2 cisplatinum and 30-40 mg/m2 mytomycin C at 42-43 °C for 60-90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties.

[Peritoneal carcinomatosis of gastric cancer : Treatment options for peritoneal carcinomatosis of gastric cancer]. / Peritonealkarzinose des Magenkarzinoms : Therapeutische Möglichkeiten bei Peritonealkarzinose des Magenkarzinoms.

BACKGROUND: Gastric cancer is one of the most aggressive malignant diseases of the gastrointestinal tract with a high rate of metastasis. Peritoneal metastasis occurs in up to 60% of all patients and synchronously in up to 30% in locally advanced gastric cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been an established treatment option in selected patients for several years, as the HIPEC serves as an alternative administration route. OBJECTIVE: This article presents a schematic display of the various treatment options depending on the extent of peritoneal carcinomatosis in a gastric cancer. METHODS: A literature search and analysis of the current literature on the treatment of gastric cancer with peritoneal metastases were carried out. A differentiation was made between limited and extensive peritoneal carcinomatosis together with the appropriate treatment strategy. RESULTS: Principally, individual systemic chemotherapy is the backbone of treatment of gastric cancer with peritoneal metastases. In selected patients and in cases of limited peritoneal carcinomatosis, CRS and HIPEC can be conducted and survival is improved; however, CRS is still contraindicated in cases of extensive peritoneal carcinomatosis and in exceptional cases pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be carried out. CONCLUSION: In selected patients CRS and HIPEC can lead to an improvement with respect to overall and disease-free survival. In cases of extensive peritoneal carcinomatosis, individualized chemotherapy remains the major treatment option.

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer]. / Zytoreduktive Chirurgie und hypertherme intraperitoneale Chemotherapie beim Magenkarzinom.

BACKGROUND: Gastric cancer with peritoneal metastases is associated with an extremely poor prognosis. Developed multimodal treatment concepts, which include a combination of perioperative systemic treatment and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), show promising results with respect to improvement of the long-term survival. METHODS: This article contains a review of the literature of published studies on the topic of gastric cancer and peritoneal metastasis. RESULTS: The prognosis of patients with gastric cancer peritoneal carcinomatosis shows an extremely limited median survival of 7 months under palliative second-line systemic treatment. The median survival time increased to 12 months with cytoreductive surgery and in combination with HIPEC showed a positive effect on survival in individual studies. EXPERT OPINION: Treatment recommendations for patients with peritoneal metastases of gastric cancer should be carried out by experts in surgical reference centers.

Systemic Chemotherapy Including Ramucirumab in Combination With Pressurized Intra-Peritoneal Aerosol Chemotherapy Is a Safe Treatment Option for Peritoneal Metastasis of Gastric Cancer.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopic technique for local chemotherapy. It has been used for treatment of peritoneal metastasis of gastric cancer (PM GC) in combination with systemic therapy. VEGFR2 antagonist ramucirumab is a second-line therapy for GC, and has been suspected to cause wound healing disorders. METHODS: This is a retrospective single center cohort study of patients with PM GC, who received PIPAC treatment in combination with systemic chemotherapy with and without ramucirumab. Data on patients' characteristics and their perioperative courses were collected and complication rates were compared with regard to preoperative use of ramucirumab and time between last dose of systemic therapy and PIPAC treatment. RESULTS: Fifty patients underwent 90 PIPAC treatments for PM GC in 3 years. Overall postoperative morbidity was 11% with 6% severe complications. The mean interval between systemic therapy and PIPAC was 20 days. Neither the length of interval nor the use of ramucirumab had an effect on complication rates. CONCLUSION: Our study suggests that addition of ramucirumab to pre-PIPAC systemic therapy, irrespective of the length of the treatment-free interval before PIPAC, does not increase the risk of postoperative complications and is therefore a safe option for treatment of PM GC.