Kanji Katayama

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

BACKGROUNDnThe 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%.nnnMETHODSnA 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnOur triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes ⩽ 3000/mm3 and/or platelets ⩽ 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second‐look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two‐year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P < 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti‐cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.RésuméLa perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsquune carcinose dorigine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors dun second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. Lascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de lintestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.ResumenLa perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de “second look”, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.

Prophylaxis with intraoperative chemohyperthermia against peritoneal recurrence of serosal invasion-positive gastric cancer

Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a prophylactic treatment for peritoneal recurrence after curative resection of 79 advanced gastric cancers. The control group consisted of 81 patients with advanced gastric cancer who underwent curative surgery during the same period. CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline solutions warmed at 43.5°C by a special CHPP device. In patients with pathologically confirmed serosal invasion-positive tumors, the survival rate of the CHPP group was significantly higher than that of the control group. A survival advantage for stage IV patients was also obtained by CHPP. However, there was no survival advantage between the CHPP group and the control group with serosal invasion-negative tumors. Adverse effects were observed in four patients who underwent CHPP: One developed severe bone marrow suppression, and transient hyperazotemia was ebserved in the other three. There was no difference in the incidence of mortality and morbidity between the two groups. These results indicate that CHPP is a safe, readily available prophylactic therapy for peritoneal recurrence after gastric cancer surgery.RésuméLa perfusion continue hyperthermique (CHPP) avec une solution contenant 30 mg de mytomycine C (MMC) et 300 mg de cisplatine (CDDP) a été utilisée comme traitement prophylactique pour prévenir la récidive péritonéale chez 79 patients avec un cancer gastrique avancé réséqué. Un groupe composé de 81 patients avec un cancer gastrique avancé qui ont eu une chirurgie à visée curatrice pendant la même période de temps a servi de contrôle. La CHPP, perfusion de MMC et de CDDP mélangés au sérum physiologique réchauffé à 43.5°C par un appareil spécial, était administrée pendant 60 minutes. Lorsque lenvahissement séreux a été confirmé par lexamen anatomopathologique, la survie des patients ayant eu la CHHP était significativement plus longue que lorsque les patients navaient pas eu de CHHP. La survie des patients classés stade IV était également améliorée. Il ny avait aucune amélioration, par contre, de la survie lorsque la couche séreuse nétait pas envahie. Des effets secondaires ont été observés chez quatre patients qui ont une CHHP: un a développé une aplasie médullaire sévère, alors que les trois autres nont eu quune hyperazotémie transitoire. Il ny avait, en définitive, aucune différence de mortalité ou de morbidité entre les deux groupes. Ces résultats indiquent que la CHPP est sûre et facilement disponible comme thérapie prophylactique contre la récidive péritonéale après résection de cancer gastrique.ResumenLa perfusión hipertérmica peritoneal continua (CHPP) con una solución que contiene 30 mg de mitomicina C y 300 mg de cisplatino ha sido introducida como tratamiento profiláctico para prevenir recurrencia peritoneal luego de la resección curativa en 79 pacientes con cáncer gástrico avanzado. El grupo control consistió en 81 pacientes con cáncer gástrico avanzado que fueron sometidos a cirugía curativa en el mismo período de tiempo. La CHPP fue realizada durante 60 minutos con solución salina con MMC y CDDP calentada a 43.5°C por medio de un sistema de CHPP. En los pacientes con invasión serosa confirmada histológicamente, la tasa de sobrevida del grupo CHPP fue significativamente mayor que la del grupo control. También se detectó una ventaja de sobrevida en los pacientes en estado IV tratados con CHPP. Sin embargo, no se encontró ventaja en cuanto a sobrevida entre el grupo CHPP y el grupo control en los pacientes con tumores negativos para invasión serosa. Efectos adversos fueron registrados en 4 pacientes con CHPP:1 desarrolló severa depresión de la médula ósea, e hiperazotemia transitoria fue observada en los otros 3 pacientes. Sin embargo, no se halló diferencia en cuanto a mortalidad y morbilidad entre los dos grupos. Estos resultados indican que la CHPP es una modalidad terapéutica segura y fácilmente disponible para prevenir la recurrencia peritoneal luego de cirugía por cáncer.