Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis.

Intraperitoneal chemo-hyperthermia with mitomycin C was used to treat 28 patients with far advanced digestive adenocarcinoma and histologically confirmed peritoneal carcinomatosis. Surgical resection of the primary tumor was possible in 17 cases. After closure of the abdominal wall, intraperitoneal chemo-hyperthermia was performed for 90 to 120 minutes under general anesthesia and 32 degrees C hypothermia, through 3 intraperitoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 6 liters of peritoneal dialysate heated to an inflow temperature of 46-49 degrees C. No mortality occurred, and there were 2 post-operative complications, with transitory biological side effects. In 9 out of 10 patients with preoperative malignant ascites, the ascites cleared after treatment. One-year survival rate was 54.2%. These encouraging preliminary results show that intraperitoneal chemohyperthermia with mitomycin C is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive cancers.

Intra-Peritoneal Chemo-Hyperthermia (CHIP): a new therapy in the treatment of the peritoneal seedings. Preliminary report.

After an experimental study in dogs, authors report a new therapeutic device for peritoneal seedings (Intra-Peritoneal Chemo-Hyperthermia) and their preliminary results in five patients. They observed no mortality and no morbidity with this protocol using Mitomycin as antimitotic and hyperthermia as sensibilisation agent. This new technique means important technological and time investment but preliminary results appear to be encouraging and authors intend to standardize the present apparatus in order to go on using this device and obtain more experience.

Experience of three years with intra-operative radiation therapy using the Lyon intra-operative device.

Since November 1985, we have performed 54 Intra-Operative Radiation Therapy (IORT) interventions, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality, morbidity, and average of survival rates were compared with a non-randomized control group: mortality and morbidity rates were similar in the two groups, with or without IORT. The follow-up period was too short for any valid conclusions about IORT in gastric cancer to be reached. However, in the case of unresectable pancreatic cancer, a significant difference was observed in survival rates when patients were treated by surgery alone or surgery and IORT (4.7 months), and when they were treated by surgery, IORT and external postoperative radiotherapy (8.9 months) (p less than 0.05). The study also examined the relief of abdominal and back pain in patients with unresectable pancreatic cancer: in our experience, survival was longer and more comfortable for patients treated with surgery and IORT. In conclusion, it appears that today IORT is without doubt a good palliative treatment for unresectable pancreatic cancer, but more experience is needed before a conclusion can be reached regarding resectable pancreatic cancer and gastric cancer.

[A new technic of intraoperative radiotherapy: the Lyon intraoperative device]. / Une nouvelle technique de radiothérapie intra-opératoire: le "Lyon intra operative device".

Since November 1985, we performed Intra Operative Radiation Therapy in 53 cases, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality and morbidity were not increased by the use of Intra Operative Radiation Therapy. Our follow up is too short to get any valid conclusions about IORT in gastric cancer. However, for unresectable pancreatic cancer, we observed an improvement of the survey when patients were treated by "Surgery, IORT and External post operative radiotherapy". We also studied the relief of abdominal and back pain of unresectable pancreatic cancer: in our experience, the survey was longer and more confortable for patients treated with surgery and IORT. In conclusion it appears that today IORT is surely a good palliative treatment for unresectable pancreatic cancer, and longer experience is needed to conclude for resectable pancreatic cancer and for gastric cancer.

[Effect of fibrin glue on lymphostasis during lymph node excisions. Prospective randomized study in 40 patients]. / Efficacité d'une colle de fibrine sur la lymphostase au cours des curages ganglionnaires. Etude prospective randomisée sur 40 patients.

To evaluate the efficacy of fibrin glue for lymphostasis during axillary and inguinal lymph node removal, we conducted a prospective randomized study including 40 patients. Post-operative mortality and morbidity rates were not different throughout the 2 groups. However they were significant decreasement in drainage duration, in drainage quantity and in hospital duration in the group "with" fibrin when compared with the group "without".

[Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia with mitomycin C. Initial experience]. / Traitement des carcinoses péritonéales par chimio-hyperthermie intra-péritonéale avec mitomycine C. Première expérience.

Intra-peritoneal chemo-hyperthermia with mitomycin C was used to treat 9 patients with very advanced gastrointestinal cancers with peritoneal seedings. Resection of the primary tumor was possible in 3 cases. After temporary of closure of the abdominal wall, 90 to 120 minutes of intra-peritoneal chemo-hyperthermia was performed under general anaesthesia with 32 degrees C of systemic hypothermia, via 3 intra-peritoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 61 of peritoneal dialysate warmed at the inflow temperature of 46 to 49 degrees C. We observed no mortality or morbidity. There were only minor and temporary laboratory side effects and for 6 patients, no malignant cells could be found in the ascitic fluid after intra-peritoneal chemo-hyperthermia. In six patients, we conserved an improvement in the Karnofsky index 3 to 7 months after intra-peritoneal chemo-hyperthermia. These results show that intraperitoneal chemo-hyperthermia with mitomycin C is a safe and reliable treatment for peritoneal seedings in severely advanced gastrointestinal cancers and encourage us to proceed with this new therapeutic modality.

[Cancers of the stomach and peritoneal carcinoses: will hyperthermia be a new therapeutic approach?]. / Cancers de l'estomac avec carcinoses péritonéales: l'hyperthermie sera-t-elle une nouvelle voie thérapeutique?

Overall survival rate of gastric adenocarcinoma is poor whatever the therapeutic is. Main reasons for this poor prognosis are regional failure and local recurrences. Using hyperthermia could be of interest in peritoneal carcinomatosis during gastric carcinoma: in vitro cytotoxic effect of hyperthermia is well known. Using hyperthermia in combination with intra peritoneal chemotherapy could improve local control. Preliminary results of pilot studies treating peritoneal carcinomatosis with intra peritoneal chemohyperthermia are reported.

[Intraperitoneal hyperthermic chemotherapy in the treatment of peritoneal carcinosis of digestive origin. A case report and physiopathology]. / Chimio-hyperthermie intra-péritonéale (CHIP) dans le traitement des carcinoses péritonéales d'origine digestive. Rapport d'une observation et données physiopathologiques.

The authors describe their first experience of IP hyperthermochemiotherapy using mitomycin C under hypothermic coverage at 32 degrees C, in a female patient with peritoneal carcinosis secondary to stomach cancer. Postoperative complications were not observed. Tested mitomycin blood levels evidenced good absorption via the peritoneal route. 4 months later, the patient is doing well and the authors are propounding the method be started in a series of patients, in order to assess its long-term efficacy.

[Intraperitoneal chemo-hyperthermia with mitomycin C. Development and in vivo study of tolerability in dogs]. / Chimio-hyperthermie intra-péritonéale (CHIP) avec mitomycine C (MMC). Mise au point et étude in vivo de la tolérance chez le chien.

Peritoneal carcinosis is relatively frequent in the clinical course of digestive cancers (48% in cases with invasion of the serous membrane). Despite various therapeutic strategies, prognosis is almost always unfavourable, survival after 6 months is extremely rare. Because of the known in vitro anti-tumour effect of hyperthermia and its chemosensitizing effect during Mitomycine C therapy, we decided to develop a technique based on these two anticancer effects: intraperitoneal hyperthermia and intraperitoneal chemotherapy. Termed CHIP, or chemo-hyperthermia intraperitoneal, this new method could be used for the treatment of peritoneal carcinosis. We report here results of the necessary animal experimentation before such a method could be proposed for human anticancer therapy.

Treatment of malignant peritoneal effusion in digestive and ovarian cancer.

Intra Peritoneal Chemo Hyperthermia (IPCH) with Mitomycin C (MMC) or Cisplatinum (CP) was used to treat 32 patients with far advanced digestive or ovarian cancers and peritoneal carcinomatosis. Surgical resection of the primary tumor has been possible in 18 cases. After closure of the abdominal wall, a 90 minutes IPCH as performed under general anaesthesia and 32 degrees C general hypothermia, through 3 intraperitoneal drainages realizing a closed circuit, using 10 mg/l of MMC or 15 to 25 mg/l of CP in 6 l of peritoneal dialysate heated at the inflow temperature of 46 to 49 degrees C. The mortality rate was 3% and the morbidity rate was 3%. In 11 out of 12 patients with preoperative malignant ascites, no more ascites could be found after IPCH. For peritoneal carcinomatosis from digestive origin, median survival was 11.2 months and 1 year survival rate was 46.9%. These encouraging preliminary results show that IPCH is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive or ovarian cancers.

Tolerance of intraperitoneal chemohyperthermia with mitomycin C: in vivo study in dogs.

Tolerance of intraperitoneal chemohyperthermia (IPCH) with mitomycin C (2 mg/kg) by irrigation of the peritoneal cavity via a closed circuit system was evaluated in Beagle dogs for possible use in the management of human peritoneal carcinomatosis. Of dogs, 24 underwent three digestive anastomoses each. They were randomized into three groups: control (n = 6), intraperitoneal hyperthermia (n = 8) and IPCH (n = 10). Peritoneal temperatures were maintained between 41-43 degrees C for 60 min. Tolerance was evaluated through clinical follow-up, biological samples (serum electrolytes, blood counts and serum enzymes), histological examinations and post-mortem macro- and microscopic controls of anastomosis. Mortality and morbidity rates were not different in the three groups. No anastomotic leakage occurred. Evidence of biological toxicity was minimal. Histological examinations showed no definitive tissue damage. IPCH appears to be a safe and reliable device in dogs. Plans to combine IPCH with MMC in surgical resection of patients with peritoneal carcinomatosis are underway.

Intraoperative chemohyperthermia in the management of digestive cancers. A general review of literature.

Intraoperative chemohyperthermia is a new method in the treatment of peritoneal seedings from digestive cancers, which combines surgery, intraperitoneal chemotherapy (mitomycin C and/or cisplatyl) and peritoneal hyperthermia. After a brief reminder on the general principles concerning high temperature action, a review of literature is made: 5 teams have performed this technique. We differentiate the indications, design features and results of each team. The results show a mean survival after 2 years of 35% (in peritoneal carcinomatosis) up to 78% (in gastric serosal invasion, peritoneal seeding free). The best result of the method is the drying up of cancerous ascites, allowing a more comfortable survival.

A new device for the treatment of pleural malignancies: intrapleural chemohyperthermia preliminary report.

The prognosis of malignant pleural tumors remains extremely unfavorable. The aim of this study is to evaluate the combination of intrathoracic intrapleural chemotherapy and intrapleural hyperthermia (ITCH) in these diseases. Under anesthesia, 5 men were studied. After pleurectomy for mesothelioma (3/5) or adenocarcinoma (2/5), ITCH is carried out for over 60 min, either with mitomycin C (4/5) or cisplatin (1/5). No pre- or postoperative death occurred. The maximal pleural temperature is 42.6 degrees C. The blood level of mitomycin C never reached the systemic toxic level. All the patients were discharged from the surgical ward, 3 are still alive 15 months later. Therefore, ITCH appears to be a safe and reliable therapy.

Quimio-hipertermia intraperitoneal con mitimicina C en cáncer avanzado con carcinomatosis peritoneal: primera experiencia / Intraperitoneal chemo-hypertermia with mytomicina C

La quimiohipertermia intraperitoneal (ITCH) con Mitomicina C (MMC) fue usada en el tratamiento de 7 pacientes con cancer gastrointestinal avanzado y carcinomatosis peritoneal. La reseccion primaria del tumor fue posible en 2 casos. La IPCH se realizo despues del cierre de la pared abdominal durante 90 y 120 minutos bajo anestesia general con previa hipotermia a 32º Celsius, a traves de un circuito cerrado formado con 3 drenajes de silicona intraperitoneal; se uso concentracion de 10 mg/L de MMC en 6000 mL de liquido precalentado a 46-49º Celsius. No observamos ni mortalidad ni morbilidad. Otros autores han informado efectos biologicos secundarios ligeros y temporales; no hubo celulas malignas en el liquido ascitico despues de la IPCH. Igualmente observamos en 6 pacientes un incremento en el indice de Karnofsky, 3 y 7 meses despues de la IPCH. Estos resultados nos permiten confirmar que la IPCH con MMC es un metodo sin riesgo, que puede ser usado en el tratamiento del cancer gastrointestinal avanzado con carcinomatosis peritoneal.