Fournier's Gangrene: Literature Review and Clinical Cases.

BACKGROUND: Fornier gangrene is an extremely rare disease of the genitals. This disease is a result of the urogenital tract, anorectal area, and genital skin infections, appearing usually in immunocompromised patients with diabetes, obesity, and malignant neoplasms. The basic treatment of Fournier gangrene includes an emergency surgical intervention combined with antibiotic therapy and detoxification. METHODS: A review of recent papers comprising studies and reviews published in 2005-2016 was performed. The clinical cases were studied at the Department of Purulent Surgery Central Clinical Hospital No. 1, where 7 patients were diagnosed and treated. RESULTS: The etiology, pathogenesis, clinical and laboratory presentation, diagnosis, treatment, and prognosis of Fournier gangrene are described in this article. The authors have described several clinical cases of patients with Fournier gangrene and with necrotic cellulitis and fasciomyositis of anterior abdominal wall, which is a manifestation of Fournier gangrene. Making allowance for the unfavorable epidemiological situation of syphilis in Russia, the increase in the incidence of complicated, atypical chancre, and therefore, the need for differentiation of Fournier gangrene with such manifestations of syphilis as necrotizing, esthiomenous chancre, indurative edema, the appropriate clinical examples are well explained in this article.

Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma.

OBJECTIVES: Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. METHODS: Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed. RESULTS: The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were younger age <60 years (P < .01), complete or near complete (R0-1) versus incomplete (R2-3) resection (P < .02), low versus high histologic grade (P < .01), and the use of cisplatin versus mitomycin-C during HIPEC (P < .01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89-2.41; P = .13). CONCLUSION: Operative CRS with HIPEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM.

Analysis of factors associated with outcome in patients undergoing isolated hepatic perfusion for unresectable liver metastases from colorectal center.

AIM: To define the indications for hyperthermic isolated hepatic perfusion (IHP) in patients with unresectable liver metastases (LM) from colorectal cancer (CRC) with particular focus on IHP's utility as a second-line option for patients whose tumors have progressed following combination systemic chemotherapy treatment. METHODS: From June 1994 through July 2005, 120 patients with unresectable CRC LM underwent IHP with melphalan (n = 69), tumor necrosis factor (TNF) (n = 10) or both (n = 41). Hepatic arterial infusion (HAI) with floxuridine started 6-8 weeks post IHP in 46 (38%). Patients were followed for toxicity, radiographic response, and overall survival (OS). Wilcoxon rank-sum and Fisher's exact tests were used to compare parameters by response category; survival and hepatic progression-free survival were calculated by the Kaplan-Meier method. RESULTS: Of 79 males and 41 females, 96 (80%) received prior chemotherapy. There were five (4%) operative/treatment mortalities. There were 69 responses in 114 evaluable patients (61%). Total melphalan dose and combination melphalan/TNF were each associated with response; age, preoperative carcinoembryonic antigen (CEA), prior chemotherapy for established LM, tumor burden, and post-IHP HAI therapy were not. Median overall survival was 17.4 months and 2-year survival was 34%. Factors found to be independently related to survival were preoperative CEA <30 ng/mL and use of post-IHP HAI (P < 0.015). CONCLUSIONS: IHP results in marked tumor regression and prolonged survival in patients with CRC LM. Continued development of IHP in this clinical setting is warranted.

Percutaneous hepatic perfusion in patients with metastatic liver cancer: anesthetic, hemodynamic, and metabolic considerations.

BACKGROUND: Percutaneous hepatic perfusion (PHP), a regional cancer therapy, entails insertion of percutaneous catheters to isolate hepatic vasculature and enable simultaneous hepatic venous hemofiltration of high-dose chemotherapy. PHP has been shown to be safe and to benefit some patients with liver metastases. METHODS: We examined hemodynamic and metabolic changes as well as anesthetic implications during PHP in patients with metastatic liver cancer enrolled in clinical trials of escalating doses of melphalan between 2001 and 2006. RESULTS: Fifty-one patients underwent 136 PHPs with general anesthesia. Diagnoses included neuroendocrine tumors, melanoma, and metastatic carcinomas. Based upon available data derived from all procedures, incorporating multiple procedures per patient, after occlusion of the inferior vena cava and during hepatic perfusion, there were decreases in mean arterial (-15.4 +/- 1 and -7.4 +/- 1 mmHg, respectively) and central venous pressure (-5.4 +/- 0.3 and -5.6 +/- 0.3 mmHg) and increases in heart rate (11 +/- 1 and 13.4 +/- 0.9 bpm) (all p < 0.0001) which resolved with completion of the procedure. During vascular isolation, patients received norepinephrine (13% of procedures), phenylephrine (70%), or both agents (11%). During hepatic perfusion with melphalan, compared to baseline, there were decreases in pH (-0.09 +/- 0.01) and bicarbonate (-3.3 +/- 0.6 mmol/L) (both p < 0.0001) and, upon completion of procedure, increases (2.6 +/- 0.4 mmol/L) in bicarbonate, compared to values during hepatic perfusion (p < 0.0001). CONCLUSIONS: PHP therapy can be associated with transient but significant hemodynamic and metabolic perturbations. In order to assure patient comfort and facilitate timely diagnosis and treatment of associated hemodynamic and metabolic changes, we favor administration of general anesthesia, rather than sedation, for patients undergoing PHP.

Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion.

Peritoneal carcinomatosis is a frequent mode of metastasis in patients with gastric, duodenal, or pancreatic cancer. Survival in this setting is short and therapeutic options are limited. This analysis examines the outcomes of 18 patients treated with operative cytoreduction and continuous hyperthermic peritoneal perfusion. Eighteen patients (6 males and 12 females) with gastric (n = 9), pancreatic (n = 7), or duodenal (n = 2) cancer were treated on protocol. Patients underwent optimal cytoreduction (complete gross resection, 11; minimal residual disease, 7) and a 90-minute perfusion with cisplatin. Clinical parameters and tumor and treatment characteristics were analyzed. Survival curves were estimated using the Kaplan-Meier method. Procedures included gastrectomy (n = 8), pancreaticoduodenectomy (n = 3), and hemicolectomy (n = 2). After cytoreduction, patients had no evidence of residual disease (n = 11), fewer than 100 implants less than 5 mm (n = 1), more than 100 implants between 5-10 mm (n = 3), or multiple implants with greater than 1 cm (n = 3). Five patients received a postoperative intraperitoneal dwell with 5-fluorouracil and paclitaxel. There was one perioperative mortality, and complications occurred in 10 patients. The median progression-free survival was 8 months (mean, 10 months; range, 1-47 months) with a median overall survival of 8 months (mean, 18 months; range, 1-74 months). In this cohort, peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease. Investigation of novel therapeutic approaches should be considered.

Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies.

PURPOSE: We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. PATIENTS AND METHODS: The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. RESULTS: A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. CONCLUSION: Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique.

Isolated hepatic perfusion for the treatment of patients with colorectal cancer liver metastases after irinotecan-based therapy.

BACKGROUND: Irinotecan given with 5-fluorouracil and leucovorin is currently used as first-line therapy for patients with metastatic colorectal cancer (CRC). However, the response duration is <1 year, and second-line systemic chemotherapy has limited efficacy. We analyzed the efficacy of isolated hepatic perfusion (IHP) for patients with progressive CRC liver metastases after irinotecan. METHODS: Between March 1993 and February 2003, 124 patients with CRC liver metastases underwent IHP on institutional review board-approved protocols. The overall treatment mortality was 4% (5 of 124). Twenty-five patients (10 women and 15 men; mean age, 53 years) were identified who had progressive liver metastases by carcinoembryonic antigen, imaging studies, or both after irinotecan. A 1-hour hyperthermic IHP (mean hepatic temperature, 40.0 degrees C) with melphalan 1.5 mg/kg (mean total dose, 100 mg) was administered via laparotomy. Perfusion with an oxygenated extracorporeal circuit was established with inflow via a cannula in the gastroduodenal artery and common hepatic artery inflow occlusion. Outflow was via a cannula in an isolated segment of the inferior vena cava. During IHP, portal and inferior vena caval flow were shunted to the axillary vein. Patients were assessed for radiographical response, recurrence pattern, and survival. RESULTS: The mean number of prior irinotecan cycles in 25 patients was 6 (range, 2-14), and it was given primarily as second-line therapy. The median number of liver metastases before IHP was 10 (range, 1-50), and the median percentage of hepatic replacement by tumor was 25%. The mean operative time was 9 hours (range, 6-12 hours), and the median hospital stay was 11 days (range, 8-76 days). There was 1 complete response and there were 14 partial responses in 25 patients (60%), with a median duration of 12 months (range, 5-35 months). Disease progressed systemically in 13 of 25 patients at a median of 5 months (range, 3-16 months). The median overall survival was 12 months (range, 1-47 months), and the 2-year survival was 28%. CONCLUSIONS: For patients with progressive CRC liver metastases after irinotecan, IHP has good efficacy in terms of response rate and duration. Continued evaluation of IHP with melphalan as second-line therapy in this clinical setting is justified.

Treatment of patients with unresectable primary hepatic malignancies using hyperthermic isolated hepatic perfusion.

Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Isolated hepatic perfusion (IHP) is a regional treatment technique that isolates the organ to allow delivery of high-dose chemotherapy, biological agents, and hyperthermia directly to unresectable cancers confined to the liver. This study presents our experience using IHP with melphalan with or without tumor necrosis factor (TNF) to treat patients with hepatocellular carcinoma or adenocarcinoma of hepatobiliary origin. Nine patients with unresectable primary hepatic malignancies underwent a 60-minute IHP with 1.5 mg/kg melphalan with or without 1.0 mg TNF. Four patients failed one or more previous treatment regimens, and the mean hepatic replacement by tumor was 41% (range 10% to 75%). Patients were monitored for response, toxicity, time to recurrence, and survival. Six (67%) of nine patients experienced greater than 50% regression of tumor by objective radiographic imaging and an additional patient had a 45% reduction in tumor burden. Mean time to progression was 7.7 months for those who responded to treatment. Patients who had a response to therapy had an average overall survival of 16.3 months. IHP can be performed safely and has significant antitumor activity in patients with unresectable primary hepatic malignancies. Hepatic progression continues to be the dominant factor influencing survival in this group of patients.

Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver.

PURPOSE: Liver metastases are the sole or life-limiting component of disease in the majority of patients with ocular melanoma who recur. Because median survival after diagnosis of liver metastases is short and no satisfactory treatment options exist, we have conducted clinical trials evaluating isolated hepatic perfusion (IHP) for patients afflicted with this condition. EXPERIMENTAL DESIGN: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP using 1.5 mg/kg of melphalan (mean total dose 105 mg). Via laparotomy, perfusion inflow was established with a cannula in the gastroduodenal artery and outflow via a cannula positioned in an isolated segment of the retrohepatic inferior vena cava. Portal and infra-renal inferior vena cava blood flow was shunted externally to the axillary vein using a veno-veno bypass circuit. Patients were assessed for toxicity, radiographic response, and survival. RESULTS: There was no treatment related mortality and transient grade 3/4 hepatic toxicity was observed in 19 patients (65%). Mean length of operation and hospital stay was 8.3 h and 10 days, respectively. There were 3 (10%) complete responses (duration: 12, 14+, 15 months) and 15 partial responses (52%; mean duration: 10 months). The initial site of disease progression included liver in 17 of 25 patients (68%) who recurred. At a median follow-up of 30.7 months the median actuarial progression-free and overall survivals were 8 and 12.1 months, respectively. CONCLUSIONS: IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly in liver, continued clinical evaluation of hepatic directed therapy in this patient population is justified.