Gastric cancer: modern approaches and prospects of treatment for peritoneal carcinomatosis (literature review)

Gastric cancer (gc) is one of the most common cancers worldwide. The majority of newly diagnosed gastric cancer cases present with distant metastases. Peritoneal carcinomatosis (pc) is the most unfavorable type of progression of primary gc, which occurs in 14–43 % of patients. The purpose of the study was to highlight modern approaches to the treatment of gc with pc. Material and methods. We analyzed 136 publications available from pubmed, medline, cochrane library, and elibrary databases. The final analysis included 46 studies that met the specified parameters. Results. The modern approaches to the treatment of gc with peritoneal carcinomatosis were reviewed, namely: cytoreductive surgery (crs), combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (crs/hipec); neoadjuvant intraperitoneal/systemic chemotherapy (nips) and pressurized intraperitoneal aerosol chemotherapy (pipac). The results of large randomized trials and meta-analyses were analyzed. Benefits and limitations of these trials were assessed. Conclusion. The peritoneal cancer index (pci) and the level of cytoreduction are two key prognostic factors for increasing the median overall survival. By reducing tumor volume through cytoreductive surgery, it is possible to allow tumor cells to re-enter the proliferative phase of the cell cycle and make them more sensitive to antitumor agents. The hematoperitoneal barrier is the main reason that prevents the effective delivery of drugs from the systemic bloodstream to the abdominal cavity, which is why the effect of systemic chemotherapy on peritoneal metastases is extremely limited. Intraperitoneal chemotherapy offers a more effective and intensive regional therapy, creating a so-called «depot» of a chemotherapy drug, thereby prolonging the effect of the administered drugs. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (crs + hipec) using the combination of surgical resection, cytotoxic chemotherapy, hyperthermic ablation of the tumor and hydrodynamic flushing, is a promising approach in the treatment of gc with peritoneal carcinomatosis.

Early Postoperative Extubation is Associated with Shorter Hospitalization and Improved Short-Term Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant operative time, hospital resources, and morbidity. We examine factors associated with hospital length of stay (LOS) and early overall survival (OS) after CRS/HIPEC. Materials and Methods Patients who underwent CRS/HIPEC were evaluated for factors associated with LOS. Institutional learning curve influence was addressed by comparing early vs late cohorts. Variables with P < .200 after univariate analysis were considered for inclusion in multivariate linear regression modeling. Independent factors associated with OS were evaluated using the Kaplan-Meier method. Results Seventy patients underwent CRS/HIPEC (mean age 52.3 years, 64.3% female, and 68.6% Caucasian). Presence of any surgical complication was found in 26 (37.1%), 28 (40%) remained intubated postoperatively, and the mean Peritoneal Carcinomatosis Index (PCI) score was 14.4 ([Formula: see text]10.4). Mean intensive care unit and hospital LOS were 2.9 days ([Formula: see text]2.3) and 9.6 days ([Formula: see text]3.6), respectively. After adjusting for covariates, only shorter time to postoperative ambulation (regression coefficient .92, P = .001) and early extubation (regression coefficient −1.90, P = .018) were associated with decreased hospital LOS on multivariate analysis. Immediate postoperative extubation conferred an independent early survival benefit on Kaplan-Meier analysis (mean OS 714.8 vs 473.4 days, P = .010). There was no difference in hospital LOS or OS between early and late cohorts. Conclusion Early postoperative extubation and shorter time to ambulation are associated with decreased hospital LOS. Moreover, CRS/HIPEC patients extubated immediately postoperatively have an early survival benefit. Every effort should be made to achieve early postoperative extubation and mobilization in CRS/HIPEC patients.

Hyperthermic Intraperitoneal Chemotherapy in the Treatment Armamentarium of Epithelial Ovarian Cancer: Time to End the Dichotomy

<b><i>Background:</i></b> Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies. <b><i>Summary:</i></b> There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials. <b><i>Key Messages:</i></b> HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.

Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review

Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term “morbidity” should be defined more clearly by the authors.

Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) vs CRS alone for treatment of endometrial cancer with peritoneal metastases: a multi-institutional study from PSOGI and BIG RENAPE groups

Objective To investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone. Methods We conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) were included. Two groups of 30 women were matched and compared: “CRS + HIPEC” which used HIPEC after CRS, and “CRS only” which did not use HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS). Results In “CRS plus HIPEC” group, 96.7% of women were treated for recurrence, while in “CRS only” 83.3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p = 0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p = 0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p = 0.511). Conclusion The use of HIPEC combined to CRS did not have any significance as regard the DFS and OS over CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.