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Background. The survival rate of patients with ovarian malignancies depends on the prevalence of the tumor process, the volume of surgical treatment, and the size of the residual tumor. At the first stage, an «aggressive» surgical tactic of removing all macroscopically determined tumor foci with subsequent antitumor drug therapy is recommended. However, the results of treatment remain unsatisfactory, which dictates the need to search for new methods of treatment.Objective: to evaluate the effectiveness of implantable port systems for intraperitoneal chemotherapy administration in the treatment of patients with advanced stages of ovarian cancer.Materials and methods. 37 cases of stage IIIC ovarian cancer were studied for the period 2018–2019. At the first stage of treatment, a cytoreductive operation was performed. At the second stage, the patients were randomly randomized into three groups: group 1 (n = 9) – installation of a port system + hyperthermic intraperitoneal chemoperfusion followed by intraperitoneal chemotherapy; group 2 (n = 11) – hyperthermic intraperitoneal chemoperfusion followed by systemic intravenous chemotherapy; group 3 (n = 17) – control group, intravenous administration of antitumor drugs. The observation period is 27 months. In the study groups, the indicators of age distribution, the degree of malignancy of the neoplasm, the volume of the residual tumor, and the relapse-free survival were analyzed.Results. Trends towards differences in progression-free survival were found in all study groups. In group 1, there was no relapse in all patients. In group 2, relapses amounted to 18.2 %, in group 3–23.5 %. G3 ovarian cancer (6 (66.7 %) and 6 (54.5 %) cases, respectively) prevailed in groups 1 and 2; G1 ovarian cancer (9 (52.9 %) cases) prevailed in group 3. Discussion. Features of the chemical composition and method of administration of the drug increase the effectiveness of local exposure to tumor cells. The introduction of cytostatic agents into the abdominal cavity leads to minimal systemic toxicity, which exceeds the results of standard intravenous therapy.Conclusion. An advantage in the relapse-free survival of patients after hyperthermic intraperitoneal chemoperfusion in combination with an implantable port system was found in comparison with standard methods of treatment.

Aim: Alterations in circadian rhythms caused by tumor growth are thought to be clinically relevant as they affect the prognosis and treatment response. We aimed to evaluate the chronotherapeutic approach in rats with ovarian cancer receiving cisplatin intravenously (IV) or with hyperthermic intraperitoneal chemoperfusion (HIPEC) and to assess daily variations in tumor and intestinal epithelium proliferation. Methods: In the pilot study, we used 12 intact rats and 12 rats with transplantable ovarian cancer, which were euthanized at ZT0 (08:00, lights on), ZT6, ZT12 and ZT18. In the main study, we used 45 rats with transplantable ovarian cancer. Animals were randomized into five groups: control, HIPEC with cisplatin at ZT0 (08:00), HIPEC with cisplatin at ZT12 (20:00), IV cisplatin at ZT0 and IV cisplatin at ZT12. We assessed the proliferation rate of tumor and small intestinal epithelium, apoptosis in small intestinal epithelium, and levels of γ-H2AX (DNA damage/repair marker) in kidneys and liver. Survival was calculated in each group. Results: Ascitic ovarian cancer disrupted daily variations in intestinal epithelium proliferation and DNA damage/repair in rats. Ovarian carcinoma exhibited no daily variation in mitotic activity. In animals receiving IV cisplatin, massive cell damage in the renal medulla and cystic changes within renal tubules were observed, unlike in rats receiving HIPEC. Tumor mitotic activity was lower in morning-treated groups. The median survival of rats in the control group was 8.5 days (95% CI 6.0– 22.0), in HIPEC at ZT0 40.5 days (95% CI 28.0– 47.0, p< 0.001) and in HIPEC at ZT12 32.0 days (95% CI 28.0– 37.0, p< 0.001). Conclusion: In a rat model, ovarian tumor growth disrupted daily variations in intestinal epithelium proliferation and caused genotoxic stress in tumor-free tissues. HIPEC with cisplatin at ZT0 had a better efficacy/toxicity profile than HIPEC with cisplatin at ZT12 and IV administration at both time points. [ABSTRACT FROM AUTHOR]

Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC (n = 12, 20 mg/kg) or intravenously (i.v., n = 9, 4 mg/kg). The subgroups of three animals were used for the initial, intermediate, and late phases of the pharmacokinetic assessment. The animals were sacrificed on days 1 and 5. Blood, liver, kidney, and ovaries were evaluated for platinum content. Histological and immunohistochemical evaluation was undertaken in the liver and kidney. A trend for higher blood plasma platinum levels was observed for HIPEC compared to i.v. Significantly lower (p < 0.001) relative platinum binding to the proteins was observed in HIPEC animals compared to the i.v. administration. A five-fold higher concentration of cisplatin in HIPEC resulted in a ca. 2.5-fold increase in total blood platinum and ca. two-fold increase in blood ultrafitrable platinum (“free” Pt). Immunohistochemistry revealed higher kidney and liver damage after i.v. administration of cisplatin compared to HIPEC, although a five-fold higher dose of cisplatin was applied in HIPEC. Together with relatively lower absorption to the systemic circulation in HIPEC, higher protein binding is probably the primary reason for lower observed toxicity in HIPEC animals.

Heat shock proteins (HSPs) are important factors in the response of cancer cells to thermo‑ and chemotherapy. Transient hyperthermic intraperitoneal chemoperfusion (HIPEC) therapy results in the upregulation of HSP expression, which may compromise the efficacy of additional anticancer treatments. The aim of the present study was to monitor the kinetics of HSP expression in tumor cells and patients with gastric cancer following HIPEC. Thus, in vitro and in vivo experiments were conducted to investigate the expression of two HSP family members, HSP70 and HSP90. Cells from two gastric tumor strains were subjected to HIPEC‑mimicking treatment, and HSPs expression was analyzed at specific time points up to 48 h. Serum HSP concentrations were analyzed in patients with gastric cancer who had previously received cytoreductive surgery plus HIPEC treatment. The in vitro experiments indicated a significant elevation of HSP90 expression in gastric adenocarcinoma cells following hyperthermic treatment. However, HSP70 expression increased from 4 h up to 20 h post‑exposure and decreased to normal levels 36 h post‑exposure. Analysis of HSPs in serum samples collected from 22 patients with gastric cancer confirmed that serum HSP90 and HSP70 levels increased following HIPEC therapy, peaking at 18 h and returning to normal 24 h post‑exposure. It is therefore advisable to apply the second round of HIPEC or chemotherapy at least 24 h following the first treatment to minimize any potential thermoresistance and chemoresistance of tumor cells. [ABSTRACT FROM AUTHOR]

The tolerability and efficiency of peritonectomy in combination with hyperthermic intraperitoneal chemoperfusion were studied in patients with pseudomyxoma peritonei. Data from 10 patients were analyzed. The pattern of complications classified as surgical and chemotherapy- associated ones is presented. The long-term results of treatment are demonstrated.

Justification and objectives Patients affected by gynecological or gastrointestinal tract neoplasms that evolve to peritoneal carcinomatosis experience a significant drop in their quality of life, high morbidity and short survival times with currently available chemotherapeutic schemes. The surgical treatment based on cytoreduction and the employment of hyperthermic intraperitoneal chemotherapy in the intra-operative period is a true challenge to anesthesiologist. Case report A 67 years old patient diagnosed with mucinous adenocarcinoma of the Appendix associated with mucinous carcinomatosis, was submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), under general anesthesia and epidural block. Volume replacement was performed with crystalloids, colloids and blood products to support an important ascites volume drained during the procedure. The target was the strict control of hydro-electrolytic and acid-basic equilibrium. The patient was referred to the ICU and evolved to a hospital discharge on the third postoperative day. Conclusion The neoplastic compromise of the peritoneum has long been considered to be a pre-terminal state. The advent of CRS/HIPEC represent an alternative promising with numerous challenges to the anesthesiologist regarding the metabolic and hemodynamic adjustment, which once again demand training and ongoing study from the perioperative team. [ABSTRACT FROM AUTHOR]

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC. Patients and methods: Forty-nine GC patients with serosal invasion ( n = 19), limited peritoneal metastases ( n = 20), or disseminated peritoneal metastases and tense ascites ( n = 10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified. Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months ( p = 0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively ( p = 0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients. Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of treatment and the factors influencing the postoperative recurrence and survival time for pseudomyxoma peritonei (PMP). A total of 39 patients with PMP who received treatment were analyzed in The General Hospital of PLA (Beijing, China) between 2002 and 2011. The patients received cytoreductive surgery (CRS) and 25 cases of PMP recurred. Seven patients received postoperative hyperthermic intraperitoneal chemoperfusion (HIPEC). The median follow-up was 40 months. There were eight mortalities in this period. The 5- and 10-year survival rates were 89.0 and 35.0%, respectively. The medians of overall survival (OS) and recurrence time were 37 and 4 months, respectively. Multivariate analyses revealed that pathological subtype was able to influence the recurrence (P=0.042) and OS (P=0.033) times, as an independent prognostic factor. HIPEC was significantly associated with postoperative recurrence time (P=0.017). Patients with disseminated peritoneal adenomucinosis had a more favorable prognosis. CRS combined with HIPEC was able to extend the postoperative recurrence time for patients with PMP. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an innovative treatment of the peritoneal carcinomatosis with potential iatrogenicity. This observational study was designed to improve our understanding of HIPEC''s impact on the renal and respiratory functions, on temperature, blood cells counts, body fluids/electrolytes and acid-base balance. Methods: We retrospectively analyzed the perioperative care of 20 patients that underwent HIPEC with oxaliplatin (n =19) and mitomycin C (n =1). The abdominal cavity was filled with the peritoneal dialysis fluid with dextrose 5%: volume of 2L/m2. Follow-up for the study was stopped on postoperative day 7. Results: The main changes were appearing just after the HIPEC procedure: increased diuresis, lactic acidosis, hyponatremia and hyperglycaemia (despite aggressive intravenous insulin therapy). In our series, there was no renal failure or impact on blood cells counts until the 7th day, neither some changes on the arterial blood gases. Conclusion: Hyperglycemia might explain increased diuresis of lactic acidosis and the rapid installation of hyponatremia. Taken together, these results suggest that glycemic control must be improved in order to avoid the other metabolic disturbances. [Copyright &y& Elsevier]

Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC (n = 12, 20 mg/kg) or intravenously (i.v., n = 9, 4 mg/kg). The subgroups of three animals were used for the initial, intermediate, and late phases of the pharmacokinetic assessment. The animals were sacrificed on days 1 and 5. Blood, liver, kidney, and ovaries were evaluated for platinum content. Histological and immunohistochemical evaluation was undertaken in the liver and kidney. A trend for higher blood plasma platinum levels was observed for HIPEC compared to i.v. Significantly lower (p < 0.001) relative platinum binding to the proteins was observed in HIPEC animals compared to the i.v. administration. A five-fold higher concentration of cisplatin in HIPEC resulted in a ca. 2.5-fold increase in total blood platinum and ca. two-fold increase in blood ultrafitrable platinum ("free" Pt). Immunohistochemistry revealed higher kidney and liver damage after i.v. administration of cisplatin compared to HIPEC, although a five-fold higher dose of cisplatin was applied in HIPEC. Together with relatively lower absorption to the systemic circulation in HIPEC, higher protein binding is probably the primary reason for lower observed toxicity in HIPEC animals. [ABSTRACT FROM AUTHOR]

Citral is a widely used penetration enhancer that has been used to assist the delivery of drugs through the skin. In this study we aimed to investigate the effectiveness of combination treatments of citral with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer and to unravel the underlying mechanism by which citral increased the efficacy of HIPEC. In vitro experiments indicated that citral increased cytoplasmic absorption of pirarubicin and potentiated the effects of pirarubicin on colorectal cancer cells to induce apoptosis. Intracellular reactive oxygen species (ROS) activity was elevated after single or combo treatments with pirarubicin, leading to compromised NF-κB signaling. Therefore, the results suggested that the effects of citral were mediated by increasing cell permeability and ROS productions. Furthermore, the colorectal xenograft model was used to evaluate the efficacy of the combo treatment at the histological and molecular levels, which showed that the cotreatment with citral for colorectal cancer increased the efficacy of HIPEC with pirarubicin with respect to both ascite control and tumor load. The results indicated that citral was an effective additive for HIPEC with pirarubicin for colorectal cancer, which warrant further effort to explore the translational application of this new treatment regimen.

Survival of rats with advanced ovarian cancer after intraperitoneal (i.p.) administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet and effects of these treatment modalities on leukocyte count were evaluated in two independent series of experiments. Hyperthermic intraperitoneal chemoperfusion with dioxadet (15 mg/kg) provided median survival of rats of 49 days (95% CI 28-70), i.p. administration of dioxadet (1.5 mg/kg) of 28 days (95% CI 16-36; P = 0.020). Single i.p. injection of dioxadet caused a significant decrease in total number of leukocytes (17-52%), granulocytes (18-75%), lymphocytes (18-62%) and monocytes (12-46%) in the peripheral blood of tumour-bearing rats compared to untreated animals. After HIPEC with dioxadet, the total number of leukocytes, granulocytes, lymphocytes and monocytes in peripheral blood of rats remained significantly higher than the corresponding values in the group with dioxadet.

The aim of this study was to evaluate the effects of treatment and the factors influencing the postoperative recurrence and survival time for pseudomyxoma peritonei (PMP). A total of 39 patients with PMP who received treatment were analyzed in The General Hospital of PLA (Beijing, China) between 2002 and 2011. The patients received cytoreductive surgery (CRS) and 25 cases of PMP recurred. Seven patients received postoperative hyperthermic intraperitoneal chemoperfusion (HIPEC). The median follow-up was 40 months. There were eight mortalities in this period. The 5- and 10-year survival rates were 89.0 and 35.0%, respectively. The medians of overall survival (OS) and recurrence time were 37 and 4 months, respectively. Multivariate analyses revealed that pathological subtype was able to influence the recurrence (P=0.042) and OS (P=0.033) times, as an independent prognostic factor. HIPEC was significantly associated with postoperative recurrence time (P=0.017). Patients with disseminated peritoneal adenomucinosis had a more favorable prognosis. CRS combined with HIPEC was able to extend the postoperative recurrence time for patients with PMP.

Aim: To evaluate the safety and effectiveness of our new cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) program., Methods: Retrospective review of patients with gastrointestinal malignancies who were suitable candidates for CRS and HIPEC between 12/1/2009 and 10/1/2010. All clinicopathologic data were reviewed with a special focus on the surgical outcome and the postoperative morbidity and mortality., Results: Fourteen patients were identified. Median age was 64 years; seven were female. The primary tumors were: colonic (29%), appendiceal (36%), peritoneal mesothelioma (14%), gastric (7%), adenocarcinoma of unknown primary (7%), and gastrointestinal stromal tumor (7%). Eleven patients (79%) received CRS/HIPEC, three for palliation. Three patients that did not undergo CRS/HIPEC had an average peritoneal cancer index (PCI) of 25. The eight patients that underwent curative CRS/HIPEC had an average PCI of 10 and a completeness of cytoreduction score of 0 (87.5%) or 1 (12.5%). Postoperative morbidity was 36%; the worst adverse event was Grade 3 ileus. Mortality rate was 0%., Conclusion: CRS with HIPEC is safe and feasible at tertiary institutions with fledgling programs. PCI is an accurate predictor of surgical outcomes.