Pressurized intraperitoneal aerosol chemotherapy in nonresectable carcinomatosis from colorectal cancer

Peritoneal carcinomatosis colorectal cancer unfortunately represents a frequently encountered condition during the natural history of this malignancy which has been considered for a long period of time as a terminal event. However, once new surgical and oncological therapies have been reported significant changes have been reported in the management of these cases. Therefore, cytoreductive surgery to no residual disease as a stand-alone procedure or in association with intraperitoneal hyperthermic chemotherapy has been proposed and significant benefits in terms of survival have been reported; unfortunately not all patients with peritoneal carcinomatosis are candidates for this combined approach, especially if extended, nonresectable lesions are present. In such cases pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proposed with promising results. The aim of the current paper is to review the most important studies conducted on this issue.

Intrapleural hyperthermic chemotherapy induces pro-immunogenic e-selectin expression in the vasculature of malignant pleural mesothelioma

Objective Malignant pleural mesothelioma (MPM) is a deadly disease with dismal prognosis. Prior studies combining surgery with intrapleural hyperthermic chemotherapy (IPHC) have shown improved survivals in selected patients with MPM. However, the mechanisms by which IPHC acts on MPM and its microenvironment remains unknown. Here we focus on tumor endothelial adhesion molecule expression patterns. Methods First, we determined the impact of IPHC on MPM tumor and vascular compartments in vitro using a novel bioincubater for hyperthermic cell culture. The cytotoxicity of normo (37 °C) / hyperthermic (42 °C for 60 minutes) cisplatin/carboplatin therapies were evaluated on four MPM (MSTO211H, H-Meso, AE17 and AB12) and one endothelial (EC-RF24) cell lines at a minimum of 24 hours using a presto-blue assay. Second, we treated endothelial cells with IPHC (60 min, 42 °C at optimized cytotoxic concentrations) and determined its impact on pro-immunogenic adhesion molecule (E-selectin, VE-cadherin, VCAM and Connexin-43) expression at 24 hours by Western blot. Results Tumor and endothelial cell viability decreased with increasing doses of both chemotherapeutics but was not affected by hyperthermia (IC50 with or without hyperthermia of each cell line at 24 hours reported in Figure 1A). Interestingly, endothelial cell line IC50 was much higher than that of MPM tumor cells for both chemotherapeutics (Figure 1A). Pro-immunogenic adhesion molecule E-Selectin was increased at 24 hours by IPHC with both chemotherapeutics while VE-Cadherin, VCAM and Connexin-43 were not affected (Figure 1B). Conclusion Hyperthermia adds no cytotoxicity to intrapleural chemotherapy. However, IPHC favors pro-immunogenic endothelial E-selectin expression. The latter could help induce patient immunity against their MPM and improve survival. Confirmation of these findings in vivo is mandatory.

Prospects for the use of the method of intravesical hyperthermic chemotherapy in the treatment of patients with non-muscle invasive bladder cancer

The aim: to compare disease-free survival time (DFS) in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant hyperthermic intravesical chemotherapy and standard BCG therapy. Materials and methods: patients were divided into 2 groups. Group 1 (control) included patients who received adjuvant therapy after TURB with BCG vaccine (BCG therapy group; n=50), group 2 (study group) included patients (HIVEC® therapy group; n=46 ), who received adjuvant intravesical chemotherapy using a Combat BRS HIVEC® device for local hyperthermia. Results: median follow-up was 23 months (range 4 - 36). Tumor recurrence was reported in 19 patients receiving intravesical BCG therapy and in 8 patients receiving intravesical hyperthermic chemotherapy. The incidence of DFS in patients receiving chemohyperthermy was statistically higher than in patients receiving BCG therapy (log-rank test result: p=0.029). Conclusions: The method of hyperthermic intravesical chemotherapy significantly increased the 2-year disease-free survival rate - 82.6 % versus 62 % BCG therapy group (p=0.025). Its use in the future will allow increasing the frequency of organ-preserving treatment of patients with primary and recurrent muscular-non-invasive bladder tumors

Postoperative bleeding in a patient with appendiceal mucinous adenocarcinoma and liver dysfunction patient: A case-report

Background: Appendiceal malignant tumors are rare in the clinic, and the incidence rate of gastrointestinal tumors is only approximately 0.5%. Our aim is to describe our experience with this rare disease and to increase knowledge on the diagnosis and treatment of appendiceal malignant tumors. Case presentation: We report the case of a 69-year-old woman who was admitted to the hospital due to dyspepsia. The patient was a carrier of hepatitis B virus, and liver dysfunction was diagnosed preoperatively. Abdominal enhanced computed tomography and colonoscopy showed that the appendix was significantly enlarged and dilated, and effusion and appendicitis were observed. Mucinous adenocarcinoma and appendiceal abscesses were not excluded because of the lack of specificity, which makes it difficult to diagnose the disease before a surgery. Laparoscopic appendectomy was performed, and a rapid frozen pathological examination showed a mucinous tumor of the appendix. Intraperitoneal hyperthermic chemotherapy with cisplatin was administered. The patient had abdominal hemorrhage on the fifth day after the surgery. After active treatment, she was discharged from the hospital 19 days after the surgery.Conclusions: The diagnosis of appendiceal malignant tumors mainly depends on preoperative imaging and microscopic results,and highly suspected patients, rapid pathological examination is needed during the operation., and so on. Notably, for elderly patients with hepatitis B infection and liver dysfunction, there is a probability of postoperative bleeding.

Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.