Toshiharu Sawa

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.

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.

Prognostic factors in primary gastrointestinal leiomyosarcoma: A retrospective study

Thirty-six patients who were admitted for surgical resection of leiomyosarcomas of the gastrointestinal tract to the Department of Surgery II, Kanazawa University Hospital, Kanazawa, Japan and its affiliates are included in the study. Follow-up data on survival is available for 32 patients. The clinico-pharmacologic variables, such as tumor site, tumor size, cellularity, mitotic index, and DNA ploidy pattern were analyzed and the results proved to correlate with the prognosis. Thirteen (41%) of the patients presented with distant metastases and/or recurrences, with hematogenous metastasis being the predominant type of recurrence. Local recurrences and/or distant metastases were significantly correlated with survival (p<0.001), as was tumor site (p<0.03), tumor size (p< 0.04), surgical treatment (p=0.05), and DNA ploidy pattern (p=0.06). Neither the mitotic index nor the cellularity proved to be significantly correlated with survival. Furthermore, some of the patients with local recurrences or distant metastases survived long after resection of recurrent tumors. In view of the results, aggressive surgical resection may be an efficient treatment of recurrences.RésuméTrente six patients admis pour lexérèse chirurgicale dun léiomyosarcome gastro-intestinal dans lunité de chirurgie II du Département de Chirurgie à Karrazawa University Hospital, Karrazawa, Japan, ont été sélectionés pour cette étude. Des renseignements concernant la survie était disponibles chez 32 patients. Les données clinico-pharmacologiques comprenant le site et la taille de la tumeur, la cellularité, lindex mitotique et le caractère diploÏde de lADN ont été analysés. Les résultats correlaient positivement avec le pronostic. Treize patients (41%) avaient des métastases à distance et/ou des récidives. Les métastases dorigine hématogène étaient très fréquentes. La récidive locale et la survenue de métastases à distance étaient correlées de faÇon significative avec la survie (p<0.001), la localisation de la tumeur (p<0.03), la taille de la tumeur (p< 0.04) et le traitement chirurgical (p=0.05), mais pas avec le type de diploÏdie de lADN (p=0.06). Ni la cellularité ni lindex mitotique ne correlaient avec la survie de faÇon significative. De plus plusieurs patients ayant une récidive locale associée à des métastases à distance ont eu des survies prolongées après résection des récidives. Au vue de ces résultats, un traitement chirurgical agressif des récidives semble efficace.ResumenSe seleccionaron 36 pacientes entre aquellos hospitalizados para resectión quirÚrgica de leiomiosarcomas del tracto gastrointestinal en el Departamento de Cirugía II, Hospital de la Universidad de Kanazawa, Japón, y los departamentos de círugía afiliados, para el presente estudio; la informatión relativa a sobre vida pudo ser obtenida en 32 de ellos. Las variables clinico-farmacológicas, taies como tamaño del tumor, ubicación, celularidad, indice mitótico y patrón ploidial de DNA fueron analizadas; los resultados aparecieron correlacionandose con el pronóstico. Trece (41%) de los pacientes se presentaron con metastasis distantes y/o recurrencias, las metastasis hematogénicas siendo el tipo predominante de recurrencia. Las recurrencias locales y/o las metástasis distantes aparecieron significativamente correlacionados con la sobrevida (p< 0.001), así como con la ubicación del tumor (p<0.03), el tamaño del tumor (p<0.04), el tratamiento quirÚrgico (p= 0.05) y el patrón ploidial de DNA (p=0.06). Ni el índice mitótico ni la celularidad demostraron correlación con la sobrevida.Además, algunos pacientes con recurrencia local o con metastasis distantes sobrevivieron por largo periodo después de resección de tumores recurrentes.En vista de estos resultados, la resección quirurgica agresiva puede representar una modalidad eficaz de tratamiento de la recurrencia.

Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases

The influence of operative treatment and chemotherapy on the prognosis in 93 gastric cancer patients with liver metastasis was studied. Chemotherapy included the systemic administration of mitomycin C (MMC) (39 patients), an intra-hepatoarterial infusion of MMC (MMC IAC group) (19 patients) and an intra-hepatoarterial infusion of MMC and cisplatin (CDDP) (MMC + CDDP IAC group) (24 patients). Either MMC or MMC and CDDP were given in 1–4 courses every 3–4 weeks from the first one to two post operative weeks. The response rate was 4 per cent (1/23), 29 per cent (5/17) and 73 per cent (17/23) for MMC systemic administration, MMC IAC and MMC + CDDP IAC, respectively, with a significantly high rate of effectiveness for the MMC + CDDP IAC. In addition, regarding the median survival period, the MMC + CDDP IAC group showed 11.8 months, as compared with 2.9 months for other chemotherapeutic treatments, indicating a good prognosis regardless of any possible resection of the primary lesion. A Cox proportional hazard model revealed the treatment by MMC + CDDP IAC alone to be a significant independent factor. These results indicated that MMC + CDDP intra-arterial chemotherapy is an effective approach to gastric cancer with liver metastasis.

Effects of Neoadjuvant Chemotherapy on High-Grade Advanced Gastric Cancers

Twenty-nine cases with high-grade advanced gastric cancer were preoperatively treated with PMUE therapy by a combined use of CDDP 75mg/m2, MMC1Omg/body, Etopocide 150mg/body and UFT 400mg/day. The mean number of courses administered was 2.9 (1–9 courses). The patients received a mean of 1.6 courses (1–4 courses) preoperatively and 1.3 courses postoperatively. The response rate was 62% (18/29), and all the responders were judged as partial response. The resectability rate was 79% and the potentially curable cases were found in 11 cases. The one year survival rate and median survival from initial therapy were 66% and 19.5 months. However, patients with nonresectable tumor showed no survival advantage by the neoadjuvant chemotherapy. These results indicate that the neoadjuvant chemotherapy induces the down staging for the patients with high-grade advanced gastric cancer. In these patients, neoadjuvant chemotherapy and then surgery should be considered.

TOW CASES OF TUBE FEEDING CERVICAL ESOPHAGOSTOMY

Tow cases were constructed a tube feeding cervical esophagostomy by an esophageal dilation technique, and elemental diet was controlled well for a long term. Esophageal dilation technique is as follows; at first balloon tube was inserted into the esophagus via the nasal cavity, and esophagus was dilated by the balloon filling with the contrast medium, then esophagostomy was performed by the double lumen needle which was inserted into the cervical esophagus under the fluoroscopy. This techniques is easy, and less painful for patient, and valuable for a long-term enteral hyperalimentation.