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PurposeThe aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease.MethodsIn a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC.ResultsThe 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44–58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7–19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors.ConclusionsThis selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

SUMMARY:Nuclear factor (NF)-B plays a central role in acute pancreatitis. We studied cerulein (CER)-induced pancreatitis in NF-B knockout (KO) mice. NF-B KO mice and normal control littermate wild-type (WT) mice were given four hyperstimulating doses of cerulein every hour to elicit secreatagogue-induced pancreatitis. Malonildialdehyde activity, glutathione levels, myeloperoxidase activity, TNF-␣, and NF-B binding activity and its inhibitory protein IB␣ were studied in the pancreas. Furthermore, we measured plasma lipase and amylase and the histological damage. KO mice had reduced malonildialdehyde levels (WT ϩ CER ϭ 4.083 Ϯ 0.95 mol/g; KO ϩ CER ϭ 1.513 Ϯ 0.63 mol/g), decreased myeloperoxidase activity (WT ϩ CER ϭ 19.3 Ϯ 2.39 mU/g; KO ϩ CER ϭ 10.21 Ϯ 2.05 mU/g), increased glutathione levels (WT ϩ CER 6.22 Ϯ 2.46 mol/g; KO ϩ CER ϭ 15. 516 Ϯ 2.92 mol/g), and reduced serum levels of amylase (WT ϩ CER ϭ 2519 Ϯ 656.9 U/L; KO ϩ CER ϭ 916 Ϯ 280.4 U/L) and lipase (WT ϩ CER ϭ 1420 Ϯ 170 U/L; KO ϩ CER ϭ 861 Ϯ 172. 3 U/L). KO mice showed reduced pancreatic NF-B activation, decreased TNF-␣ tissue content, and reduced histologic alterations. Our data suggest that KO mice have an attenuated cerulein-induced pancreatitis and help to define the possible interaction between NF-B activation and oxidative stress in this deleterious event. (Lab Invest 2003, 83:1723-1732.

Objective To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC).Design A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM.Population Patients with recurrent EOC.Methods Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C.Main outcome measures Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates.Results The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease £2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction.Conclusions Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.