Identifying the incidence of respiratory complications following diaphragmatic cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy.

INTRODUCTION: In patients with peritoneal carcinomatosis (PC), the incidence of respiratory complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is not well established. We aimed to describe the center-specific incidence and patient characteristics associated with respiratory complications following CRS and HIPEC in patients receiving treatment for PC. MATERIALS AND METHODS: We used the University Hospital of Arrixaca study database to identify patients who underwent CRS and HIPEC for PC. Patients who experienced a post-operative respiratory complication were categorized according to the National Cancer Institute-Common Terminology Criteria for Adverse Events. Multivariable regression methods were used to identify independent risk factors for developing a respiratory complication following CRS and HIPEC. RESULTS: Between 2008 and 2017, we identified 247 patients who underwent CRS and HIPEC for PC. A total of eight patients (3.2%) were categorized as having a post-operative respiratory complication. A diaphragmatic peritonectomy and a PC index of > 14 were identified as independent risk factors for developing a respiratory complication. Radiographic evidence of a pleural effusion was identified in 72 patients who had CRS of the diaphragmatic peritoneum; however, only 6 (8.3%) of these patients required pleural drainage. CONCLUSIONS: Only 3.2% of patients developed a symptomatic respiratory complication following CRS and HIPEC. A pleural effusion was identified in almost all patients requiring a diaphragmatic peritonectomy as part of their CRS; however, less than one in ten of these patients required pleural drainage. Prophylactic insertion of a pleural drainage tube is, therefore, not indicated following CRS and HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies.

BACKGROUND: The aim of this study was to analyze the results short term perioperative of patients with peritoneal surface malignancies undergoing cytoreduction with peritonectomy and HIPEC under a controlled fast track protocol and evaluate the factors related to the failure of implementation of the protocol. PATIENTS AND METHOD: We prospectively analyzed a consecutive series of patients (N = 156) with peritoneal surface malignancies treated by cytoreductive surgery with peritonectomy procedures and HIPEC from September 2008 until December 2014, in whom a fast track protocol was implemented. We limited the protocol to patients who had optimal cytoreduction, HIPEC administration, and not more than one digestive anastomosis. All patients signed informed consent for surgery and the perioperative multimodal recovery program. RESULTS: A total of 156 consecutive patients, with a median age of 57 years were included in the study. Median PCI was 8 (IQR: 0-32). Morbidity rate (Clavien-Dindo) was 25.6%, with a major morbidity rate (Clavien-Dindo III-IV) of 11.5%. One hundred and three patients (66%) completed the protocol. Multivariate analysis identified the following independent factors, which were related to failure of the protocol: age over 57 years (OR = 3.159, 95% CI: 1.286-7.758, p < 0.05), the realization of a digestive anastomosis (OR = 3.834, 95% CI: 1.562-9.414, p < 0.005) and occurrence of postoperative complications (OR = 18.704, 95% CI: 6.888-50.790, p < 0.001) CONCLUSIONS: Our data support the idea that in selected patients undergoing cytoreductive surgery and HIPEC, with a low PCI and especially no necessity to perform a digestive anastomosis, the implementation of a fast track program is feasible.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review.

The objective of this review was to evaluate morbidity, mortality and survival outcomes of elderly patients with peritoneal carcinomatosis. A systematic literature search and standardized data collection of primary research publications until June 2016 on morbidity, mortality and survival outcomes in adults aged 65 and older with peritoneal carcinomatosis treated with cytoreduction and HIPEC was performed, using PubMed, EMBASE, Scopus, ClinicalTrials.gov and Cochrane. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Nine studies were included. Severe morbidity of all elderly patients ranges from 17% to 56% in centers with high experience. In-hospital and 30-day mortality ranges from 0% to 8%. In only two studies were the differences in morbidity and mortality statistically significant related to the control group. However, older adults undergoing cytoreductive surgery and HIPEC consistently had lower survival rates across all study settings and procedure types than younger individuals. In studies that stratified for elderly patients, PCI, completeness of cytoreduction, tumor histology and albumin levels were predictive factors of survival. None of these studies examined quality of life, which precludes including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using a meta analysis.

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

OBJETIVE: To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS: We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS: A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION: HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

HIPEC in ovarian cancer: treatment of a new era or is it the end of the pipeline?

Ovarian cancer is the leading cause of death from gynecological cancer in western countries. The absence of an effective screening program as well as specific symptoms, makes the diagnosis difficult and often made in advanced stages of the disease, in the presence of peritoneal dissemination. The complete cytoreduction of the disease and tumor sensitivity to systemic chemotherapy based on platinums, are the two main prognostic factors. However in patients with complete cytoreduction the recurrence rate is high. The microscopic component of the disease at the end of the cytoreduction is responsible for these recurrences and the use of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in the same time of surgery has been proposed as a reasonable therapeutic option for treatment. However, the absence of sufficient levels of scientific evidence to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination does not allow a general recommendation outside of clinical trials. The main objective of this study is to identify the strengths and weaknesses of HIPEC treatment in ovarian cancer with peritoneal dissemination, and to know which points can be improved in the future.

The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction.

BACKGROUND: We analyzed the role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) on the microscopic component of the disease in patients with a first recurrence of platinum-sensitive ovarian cancer after complete cytoreduction (CCR). PATIENTS AND METHODS: We analyzed the data of 54 patients who were operated on between January 2001 and July 2012 with the diagnosis of platinum-sensitive recurrent ovarian cancer. In all patients, it was possible to achieve a CCR. Patients were divided into two groups: group I (cytoreduction alone) consisted of 22 surgical patients and group II (cytoreduction and HIPEC) consisted of 32 patients. RESULTS: There were no significant differences in any of the preoperative variables studied. After a multivariate analysis of factors identified in the univariate analysis, only the presence of tumors with undifferentiated histology (hazard ratio 2.57; 95% CI 1.21-5.46; p < 0.05) was an independent factor associated with a reduced disease-free survival. The 1- and 3-year disease-free survival was 77 and 23% in patients from group I and 77 and 45% in patients from group II, respectively, with a tendency, but no significant differences (p = 0.078). There was no significant difference in postoperative morbidity between the two groups. CONCLUSIONS: The administration of HIPEC in patients in whom it is possible to achieve a CCR of the disease has not increased postoperative morbidity and mortality rates in our center. HIPEC with paclitaxel is effective in the treatment of microscopic disease in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction, although with no statistically significant difference.

Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer.

BACKGROUND: We analyze the efficacy of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) for microscopic residual disease in patients with stage IIIC/IV ovarian cancer after a complete cytoreduction of their disease. PATIENTS AND METHODS: We analyzed the data of 87 consecutive patients diagnosed with stage IIIC/IV ovarian cancer operated between December 1998 and July 2011. In every patient it was possible to achieve a complete cytoreduction of their disease. (Since January 2008, our center has incorporated the use of HIPEC in patients with peritoneal surface malignancies, including patients with peritoneal dissemination of primary ovarian cancer.) RESULTS: Of 87 patients, 52 were treated with HIPEC (paclitaxel 60 mg/m(2), 60 min, 42 °C). After a univariate analysis, factors associated with lower disease-free interval were: performing a gastrointestinal anastomosis, operative time greater than 270 min, poorly differentiated histology, and not being treated with HIPEC. After multivariate analysis, independent prognostic factors included not being treated with HIPEC [hazard ratio (HR) 8.77, 95 % CI 2.76-14.42, p < 0.01] and the presence of poorly differentiated tumors (HR 1.98, 95 % CI 1.45-8.56, p < 0.05). Disease-free survival at 1 and 3 years was 66 and 18 %, respectively, in patients without HIPEC and 81 and 63 %, respectively, in patients treated with HIPEC (p < 0.01). HIPEC administration did not alter the results obtained for disease-free survival in patients with undifferentiated tumors. CONCLUSIONS: The treatment of the microscopic disease following complete cytoreduction with HIPEC in patients with advanced ovarian cancer is effective and can prolong disease-free survival. This survival benefit was not seen in undifferentiated tumors.

Therapeutic treatment with poly(ADP-ribose) polymerase inhibitors attenuates the severity of acute pancreatitis and associated liver and lung injury.

BACKGROUND AND PURPOSE: The mortality associated with acute pancreatitis (AP) is largely attributable to abnormalities that occur in distant organs and supportive care remains the only treatment for patients with these complications. Recently, prophylactic pharmacological blockade of poly(ADP-ribose) polymerase (PARP) enzymes has been shown to attenuate the severity of the disease. However, the clinical relevance of PARP inhibitors administered after the onset of AP remains uncertain. The aim of the present study was to investigate the therapeutic effects of PARP inhibitors in established AP. EXPERIMENTAL APPROACH: Mice were fed a choline/methionine-deficient/ethionine-supplemented (CMDE) diet to induce AP. PARP inhibitors were given at 36 h after the onset of CMDE diet. Severity of pancreatitis was assessed by measurements of serum amylase, lipase, IL-1beta and IL-6, and histological grading. Serum hepatic enzymes, myeloperoxidase (MPO) activity and morphological changes were measured as indicators of hepatic insult. Lung injury was evaluated by MPO activity and morphological changes. Survival rates of mice were monitored for 7 days. KEY RESULTS: CMDE diet administration resulted in a significant increase in serum amylase, lipase, IL-1beta, IL-6, alanine aminotransferase and aspartate aminotranferase levels, indicating AP and associated liver injury. Analysis of the histopathological changes in pancreas, liver and lung revealed extensive tissue damage. Treatment of mice with PARP-inhibitors after the onset of AP was associated with a reduction in the severity of AP and, accordingly, with a reduced mortality rate. CONCLUSIONS AND IMPLICATIONS: Our results support the therapeutic application of PARP inhibitors in the treatment of established AP.