Hyperthermic Peritoneal Perfusion Research Articles

Closed continuous hyperthermic peritoneal perfusion model in mice with peritoneal dissemination of colon 26

An original model of closed continuous hyperthermic peritoneal perfusion (CHPP) in mice is presented and was found to support the efficacy of intraperitoneal hyperthermia. Closed CHPP was performed after intraperitoneal inoculation of transplantable colon 26 cells into a mouse. Colon 26 cells (5 × 104) were injected into 18 mice. The mice were then allocated to six groups of three each and subjected to peritoneal perfusion over time. Peritoneal washings from each mouse were sampled and counted by the cytosmear method. On day 10 after inoculation, colonies of the disseminated tumour were seen on the mesentery by staining with 0.1% methylene blue for 5 min. The number of tumour nodules on the mesentery was counted. The number of washed-out tumour cells decreased the most at 24 h after inoculation, and 76% of the inoculated cells did not wash out during the peritoneal perfusion procedure. CHPP was performed after 24 h when colon 26 cells were injected into the peritoneal cavity because this status may represent micrometastasis. The total number of nodules on the mesentery in the CHPP group was significantly smaller than that in the control (p<0.02). In conclusion, because this treatment model is similar to the clinical CHPP, the biostaining model might be useful for the evaluation of peritoneal dissemination and it was unique and valuable in demonstrating an effective treatment for the prevention of peritoneal dissemination.

Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)—report of six cases

Background. Malignant mixed mesodermal tumours (MMMT) of the female genital tract are rare and heterogeneous malignancies that impart grim prognosis. These tumours are characterized by an admixture of malignant epithelial and stromal elements comprising carcinomatous and sarcomatous neoplastic cells. Thus far, almost 350 cases of MMMT have been recorded in the international medical literature. Due to its rarity, there is no agreement on the best treatment strategy in women with metastasized MMMT.Methods. Six women (mean age 59 years) with metastasized MMMT defined to the peritoneal cavity have been treated by cytoreductive surgery plus hyperthermic peritoneal perfusion plus postoperative adjuvant chemotherapy. All patients have been pre-treated by surgery for primary tumour and one by systemic chemotherapy. As cytostatics for hyperthermic peritoneal perfusion, we have used Mitomycin in a dosage of 18 mg/m2 plus Melphalan in a dosage of 25 mg/m2. As adjuvant treatment CDDP 40 mg/m2/dl, Mitomycin 7 mg/md2/dl and Ifosfamid 100 mg/kg 24 h/dl was applicated via intraaortic catheter three times with a treatment free interval of 3 weeks.Results. A complete cytoreduction without remnant tumour formations in the peritoneal cavity could be carried out in all six patients. The postoperative course was uneventful in all cases except for one where a spontaneous small bowel perforation and prolonged gall secretion had to be treated by re-operation. One patient died 4 months later by pneumonia without evidence of disease. Four patients are without evidence of disease after 2, 4, 14 and 19 months, whereas one patient developed liver metastases after 9 months still treated by systemic chemotherapy.Conclusion. Complete cytoreduction plus hyperthermic peritoneal perfusion plus adjuvant chemotherapy seems to be an effective treatment for recurrent or metastasized MMMT. Further studies have to define the value of this new treatment strategy for this rare tumour entity.

Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy.

Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

Abdominal Malignant Mesothelioma Following Autologous Bone Marrow Transplantation: A Case Report

Secondary malignancies are a well-known late complication occurring in patients who undergo bone marrow transplant (BMT) during childhood. A boy with acute lymphoblastic leukemia experienced a BM relapse at the age of 14 years and underwent an autologous BMT conditioned with TBI and melphalan. Sixteen years later a malignant mesothelioma of the peritoneum was diagnosed. A surgical approach according to the Sugarbaker technique and hyperthermic peritoneal perfusion with CDDP and Adriamycin were performed. The patient is alive and well after a follow-up of 20 months. To the authors' knowledge this is the first case of mesothelioma as a secondary malignancy after BMT.

Abdominal Malignant Mesothelioma Following Autologous Bone Marrow Transplantation: A Case Report

Secondary malignancies are a well-known late complication occurring in patients who undergo bone marrow transplant (BMT) during childhood. A boy with acute lymphoblastic leukemia experienced a BM relapse at the age of 14 years and underwent an autologous BMT conditioned with TBI and melphalan. Sixteen years later a malignant mesothelioma of the peritoneum was diagnosed. A surgical approach according to the Sugarbaker technique and hyperthermic peritoneal perfusion with CDDP and Adriamycin were performed. The patient is alive and well after a follow-up of 20 months. To the authors' knowledge this is the first case of mesothelioma as a secondary malignancy after BMT.

Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer

Background. Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. Methods. From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42°C to 43°C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. Results. When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. Conclusions. P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP. (Surgery 2002;131:521-8.)

Laparoscopic continuous hyperthermic peritoneal perfusion

Chang, Eugene MDa; Alexander, Richard H. mda; Libutti, Steven K mda; Hurst, Ronald MDa; Zhai, Suoping PhDa; Figg, William D MDa; Bartlett, David L MDa,* Author Information

The use of docetaxel in continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) for peritoneal recurrence of gynecological malignancies resistant to systemic chemotherapy. A feasibility and pharmacokinetic study

The use of docetaxel in continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) for peritoneal recurrence of gynecological malignancies resistant to systemic chemotherapy. A feasibility and pharmacokinetic study

Acid-Base Balance according to Intravenous Fluid during Continuous Hyperthermic Peritoneal Perfusion

Background : Continuous hyperthermic peritoneal perfusion (CHPP) has been introduced ta improve the survival of cancer patients. However CHPP induced acute change of body temperature and intra-abdominal pressure could produce various abnormal physiologic responses, especially acid-base and electrolyte imbalance. The purpose of this study was to eveluate the effeets of intravenaus fluids, plasma solution and Hartmann's solution on acid-base status and electrolyte concentrations during CHPP and to determine strategies for safer fluid management. Methods : Thirty five patients with ovarian cancer were divided into two groups; Group 1 (16 patients) was supplied with plasma solution and Group 2 (19 patients) was supplied with a Hartman solution as the intravenous fluid. Closed peritoneal irrigation was done with perfusate at a temperature of 47℃ for 90 min under general anesthesia. Body temperature, hemodynamic parameters (mean arterial pressure MAP, heart rate HR), blood gas tensions (PaO2, PaCO2), acid-base parameters (pH, base deficit BD) and electrolytes (sodium, potassium, calcium) were measured at 10 min before CHPP, 30, 60, 90 min after the initiation of CHPP, and 30 mm after the end of CHPP. Results : There were no significant changes in body temperature, MAP, HR, PaO2, PaCO2 during CHPP in both groups. pH measured at postCHPP in group 2 was significantly 1ower than that measured in group 1. Base deficits measured at 30, 60, 90 min after the initiation of CHPP and 30 min after the end of CHPP in group 2 were significantly lower than those measured in group 1. Potassium and calcium ion concentations did not show statistical significance during CHPP in both groups. 7 patients in group 1 whose calcium ion level dropped by more than 209o of the initial value needed a calcium injection but only 1 patient in group 2 needed a calcium injection. Conclusion : It appears that hemodynamic stability was maintained well during CHPP between the two group. A plasma solution may be more idea1 in reducing acidic tendencies and base deficits than a Hartmann's solution but a plasma solution supplied group requires frequent evaluation and a supply of calcium for adequate serum calcium levels. (Korean J Anesthesiol R01; 40: 144-149)

Malignant peritoneal mesothelioma treated by continuous hyperthermic peritoneal perfusion chemotherapy

Malignant mesothelioma of the peritoneum is a rare tumour for which the therapeutic approach has not yet been standardized. The efficacy of the current regimes is limited. Effective locoregional therapy is crucial, since this tumour is most often confined to the peritoneal cavity at the time of the initial diagnosis and remains there for much of its clinical course. If and when haematogenous metastases occur, they rarely contribute to the death of the patient, which is often caused by the overgrowth of the primary tumour and its local complications. A case of diffuse malignant peritoneal mesothelioma treated by cytoreductive surgery and continuous hyperthermic peritoneal perfusion with cisplatin is reported. The patient received systemic combination chemotherapy postoperatively. She is in good condition and free of disease 28 months after her treatment. Continuous hyperthermic peritoneal perfusion chemotherapy has recently been used in patients with secondary peritoneal carcinomatosis from digestive and gynecological malignancies with promising results. It is also possible that the same treatment alone or in combination with systemic chemotherapy may be effective in the treatment of primary peritoneal malignancies, as in the case of diffuse peritoneal mesothelioma.

Efficacy of Continuous Hyperthermic Peritoneal Perfusion for the Prophylaxis and Treatment of Peritoneal Metastasis of Advanced Gastric Cancer: Evaluation by Multivariate Regression Analysis

Thirty-two patients with advanced gastric cancer underwent continuous hyperthermic peritoneal perfusion (CHPP) combined with surgery: to prevent peritoneal recurrence in 15 patients without peritoneal metastasis (prophylactic CHPP) and to treat 17 patients with peritoneal metastases (therapeutic CHPP). The postoperative outcome was compared with that of control patients treated with surgery alone. Peritoneal recurrence was less frequent (26%) and the 5-year survival rate was significantly higher (39%) in the patients with prophylactic CHPP than in 40 control patients (42 and 17%, respectively). The patients with therapeutic CHPP showed significantly better median survival than did 20 control patients (11 vs. 6 months). Cox multivariate regression analysis revealed that CHPP was an independent prognostic factor in the prophylactic study (hazard ratio = 0.3965), and that the independent prognostic factor in the therapeutic study was not CHPP but complete resection of the peritoneal metastasis. Thus, CHPP has no marked benefit for established peritoneal metastasis. CHPP for the prevention of peritoneal recurrence may have a beneficial effect on long-term survival, but a prospective randomized trial is needed to clarify its prognostic value.

The Effects of Continuous Hyperthermic Peritoneal Perfusion (CHPP) on Cardiopulmonary Parameters in the Basis of Systemic Oxygen Balance

Background : Intra-operative application of continuous hyperthermic peritoneal perfusion (CHPP) in advanced cancer has been introduced as an effective and safe method to lessen the complication and enhance the effectiveness of its treatment. But CHPP induced acute change of body temperature and intra-abdominal pressure would produce various abnormal physiologic response. Now, we investigated to evaluate and understand the trend of changes of cardiac and oxygen parameters during CHPP. Methods : Closed peritoneal irrigation was done with perfusate at temperature 47oC for 90 min under general anesthesia. Cardiac and oxygen parameters were measured at 10 min before CHPP, 30, 60, 90 min after the initiation of CHPP, 30 min after the end of CHPP with Swan-Ganz catheter application. Results : Hemodynamic parameters; Systemic vascular resistance index and mean arterial pressure were decreased trend during CHPP. Pulmonary capillary wedge pressure and cardiac index were increased during CHPP. Oxygen parameters; AaDO2 and shunt fraction were increased during CHPP and O2 index were decreased during CHPP. Oxygen balance; O2 consumption and delivery increased during CHPP. Conclusions : We confirmed that systemic oxygen consumption and delivery were increased during CHPP but AaDO2 and shunt fraction were increased which could decrease systemic oxygen delivery. We should need more careful monitoring and proper treatment for maintaining stable hemodynamics and systemic oxygen balance during and after CHPP. (Korean J Anesthesiol 1999; 36: 449∼454)

A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis

In the article by Bartlett et al. (Bartlett DL, Buell JF, Libutti SK, Reed E. Lee KB, Figg WE, Venzon DJ. Alexander HR. A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis. Cancer 1998;83(6):1251-61), Table 4 was missing critical information. The table is printed below. The authors regret the error.

A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis

A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis

A Phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis

Tumor necrosis factor (TNF), hyperthermia, and cisplatin have synergistic cytotoxicity against cancer cells in vitro. This combination may be well suited to the regional treatment of peritoneal tumor spread in patients. Continuous hyperthermic peritoneal perfusion (CHPP) is a technique that allows uniform delivery of cytotoxic agents and heat to the peritoneal surface. A Phase I trial of CHPP with TNF and cisplatin was conducted to define the maximum tolerated dose (MTD) for TNF and cisplatin under moderate hyperthermia in the treatment of peritoneal carcinomatosis. Twenty-seven patients with peritoneal carcinomatosis underwent exploratory laparotomy and tumor debulking followed by a 90-minute CHPP with cisplatin (100-350 mg/m2) and TNF (0-0.3 mg/L). Perfusion parameters included a perfusate volume of 3-9 L, a peritoneal temperature of 42-43 degrees C, and a flow rate of 1.5 L/minute. Sodium thiosulfate was administered systemically during and after the perfusion as a cisplatin binding agent. There was no operative or treatment-related mortality in this study. CHPP resulted in a 14-fold higher area under the concentration versus time curve (AUC) for cisplatin in the perfusate compared with plasma, and a 4854-fold higher AUC for TNF. The MTD was defined as 250 mg/m2 cisplatin plus 0.1 mg/L TNF. The dose-limiting toxicity was renal insufficiency. No other systemic toxicity was identified, and no significant regional toxicity was identified. The median time to toleration of a regular diet was 8 days (range, 5-20 days). The favorable regional pharmacologic profile of the combination of cisplatin and TNF suggests that these agents administered via CHPP warrant further evaluation as prophylaxis against or treatment for peritoneal carcinomatosis.

CONTINUOUS HYPERTHERMIC PERITONEAL PERFUSION THERAPY COMBINED WITH PARAAORTIC LYMPH NODE DISSECTION FOR SEROSAL EXPOSED GASTRIC CANCER

The aim of this study is to evaluate the usefulness of intraoperative continuous hyperthermic peritoneal perfusion therapy (CHPP) combined with paraaortic lymph node dissection for the patients with serosal exposed gastric cancer. The survival and recurrent rates between CHPP combined (CHPP(+)) group (n=29) and CHPP not combined (CHPP(-)) group (n=35) were discussed. In 7 peritoneal disseminated cases the apoptosis index before and after CHPP were examined at several lesions of peritoneal dissemination. The 3-year survival rates were 42.6% in CHPP(+) group and 46.4% in CHPP(-) group and the rates in n4(-) cases were 72.5% and 48.1% respectively. The rates of peritoneal recurrence were 31.0% in CHPP(+) group and 34.3% in CHPP(-) group. Especially in the n4(-) cases, the rates were 16.7% in CHPP(+) and 30.8% in CHPP(-). And no peritoneal recurrence was observed in n4(-) cases with the mean intraperitoneal temperature was more than 42°C. The apoptosis index was 3.5±2.3% before CHPP or 51.5±7.5% after CHPP. In conclusion, CHPP is effective as a local therapy and paraaortic node dissection combined with CHPP is useful for the patients with no paraaortic lymph node metastasis and those whose mean intraperitoneal temperature had been maintained at more than 42°C.

進行胃癌症例に対する腹腔内持続温熱灌流-現状と将来

進行胃癌症例に対する腹腔内持続温熱灌流-現状と将来

Anaesthesia for intra-peritoneal perfusion of hyperthermic chemotherapy. Haemodynamic changes, oxygen consumption and delivery.

We investigated the intra-operative application of intraperitoneal perfusion of hyperthermic chemotherapy and its effects on cardiovascular status and oxygen consumption and delivery in 11 patients following laparotomy for surgical resection of recurrent tumours or peritoneal metastases. Closed peritoneal irrigation was carried out with perfusate at a temperature of 45-47 degrees C. External cooling was applied during the procedure to prevent systemic hyperthermia. Data were collected 5 min before the commencement of the hyperthermic peritoneal perfusion, at 5, 30, 60 and 90 min during perfusion and 5 min after perfusion was discontinued. During the hyperthermic perfusion period, the core body temperature increased significantly but remained within clinically acceptable values. Heart rate, central venous pressure and pulmonary artery pressure increased significantly during perfusion; these returned to control values immediately after discontinuation of perfusion, except for the heart rate, which remained high. Mean arterial pressure, cardiac output, oxygen delivery and oxygen consumption did not change significantly although a metabolic acidosis developed during the study period. These findings suggest that the intraperitoneal perfusion of hyperthermic chemotherapy may be safe in humans, provided that appropriate monitoring, cooling and technical support are applied.

Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination

The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Treatment of peritoneal carcinomatosis by continuous hyperthermic peritoneal perfusion with cisplatin.

There is considerable clinical and experimental evidence to suggest that the intraperitoneal administration of cisplatin via continuous hyperthermic peritoneal perfusion (CHPP) has potential clinical efficacy. The treatment is ideally suited for patients with small-volume peritoneal implants but technically appears to provide the best method of uniformly distributing hyperthermia and chemotherapy to the entire peritoneal cavity. In addition, preclinical data suggest that clinically attainable temperatures and a relatively brief exposure are sufficient for significant cell killing. Further work exploring the possibility of combining biologic agents with chemotherapy in this setting or the use of systemic agents used in combination with CHPP is needed. The technique is also attractive because of the relative technical ease with which it can be administered. If initial phase I and phase II studies demonstrate a therapeutic effect using this approach, then clearly large-scale multiinstitutional phase III studies will be required to established its therapeutic potential.