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The concept of immunochemosurgery in gastric cancer

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Abstract

To evaluate the effectiveness of adjuvant immunochemotherapy in advanced adenocarcinoma of the stomach, patients who had undergone radical subtotal gastrectomy for stage III gastric carcinoma were randomized to receive immunochemotherapy or not. For immunotherapy,Streptococcus pyogenes preparation (picibanil) was given intramuscularly every week, and for chemotherapy, either MFC (mitomycin C, 5-fluorouracil, and cytosine arabinoside) regimen or FME (5-fluorouracil and methyl-CCNU) regimen was given. Immunotherapy was started at the fourth or fifth postoperative day and chemotherapy was started at the eighth to tenth postoperative day.

To evaluate the immune status of patients, various immune parameters such as 1-chloro-2, 4-dinitrobenzene (DNCB) test, T-lymphocyte count, PHA- and concanavalin-A-stimulated lymphoblastogenesis, and antibody-dependent cellular cytotoxicity (ADCC) activity were checked before surgery and 3–4 months postoperatively.

One hundred and thirty-eight patients were chosen for study during a 5-year period. Seventy-four patients received postoperative immunochemotherapy and 64 patients received no further anticancer therapy following their operation. All patients had been followed for at least 5 years since they underwent surgery. Survival rate and immune status were compared between the 2 groups. Patient characteristics and preoperative values for the immune status of the 2 groups were similar to each other.

The 5-year survival rate of the postoperative immunochemotherapy group was 44.6%, whereas that of the surgery alone group was 23.4%. The difference is statistically significant (p<0.05). All the postoperative values of immune parameters showed more favorable data in the postoperative immunochemotherapy group.

Postoperative immunochemotherapy is no longer adjuvant, but is an essential systemic therapy to prolong patient survival and cure disease. This author proposes to use the termimmunochemosurgery instead of “surgery and adjuvant immunochemotherapy” for gastric cancer.

Résumé

Dans le souci d'évaluer l'efficacité de l'immunochimiothérapie complémentaire pour traiter le cancer avancé de l'estomac traité par gastrectomie radicale subtotale, les patients ont été sélectionnés au hasard pour être soumis ou non à l'immunochimiothérapie. L'immunothérapie fut effectuée à l'aide de préparations de streptocoques pyogènes (picibanil) administrées chaque semaine et la chimiothérapie par MFC (mitomycine C, 5-FU, et cytosine arabinoside) ou par FME (5-FU et methyl-CCNU). L'immunothérapie fut entreprise 4 ou 5 jours après l'intervention et la chimiothérapie 8 à 10 jour après l'acte opératoire.

Pour apprécier la condition immunologique du malade, différents paramètres immunologiques furent contrôlés avant l'opération et 3–4 mois après l'intervention: 1-chloro-2, 4-dinitrobenzène (DNCB) test, compte des lymphocytes T, PHA et concanavaline A, lymphoblastogénèse stimulée et ADCC.

Cent trente huit malades furent choisis au cours d'une période de 5 ans. Soixante quatorze malades furent traités et soixante quatre ne furent pas soumis à l'immunochimiothérapie. Tous ont été suivis depuis plus de 5 ans. Le taux de survie et la condition immunologique furent comparés entre les 2 groupes. Les valeurs de la condition immunologique et les caractéristiques cliniques des malades étaient identiques.

Le taux de survie à 5 ans après immunochimiothérapie fut de 44.6% et seulement de 23.4% après chirurgie isolée. La différenceest donc statistiquement significative (p<0.05). Toutes les valeurs post-opératoires des paramètres immunologiques furent plus favorables chez les malades du groupe traité par immunochimiothérapie.

Pour l'auteur l'immunochimiothérapie post-opératoire n'est pas seulement un traitement complémentaire mais une méthode essentielle de traitement général permettant de prolonger la vie des malades et d'envisager la guérison. Il propose d'employer le terme d'immuno-chimio-chirurgie au lieu de celui de chirurgie associée à l'immunochimiothérapie complémentaire.

Resumen

Con el fín de valorar la efectividad de la inmunoquimioterapia adyuvante en el adenocarcinoma avanzado de estómago, se procedió a aleatorizar pacientes que habían sido sometidos a gastrectomía subtotal por carcinoma estado III, para recibir o nó inmunoquimioterapia. Para inmunoquimioterapia se administró una preparación de Streptococcus pyogens (picibanil) por vía intramuscular cada semana, y para quimioterapia se administró un regimen de MFC (mitomicina-C, 5-fluoruracilo, y citosina arabinosida) o de FME (5-fluoruracilo y metil-CCNU). La inmunoterapia fue iniciada en el cuarto o quinto día postoperatorio y la quimioterapia en el octavo al décimo día postoperatorio.

Para la valoración del estado inmunológico de los pacientes se determinaron diversos parámetras, tales como la prueba de 1-cloro-2,4-dinitrobenceno (DNCB), el recuento de linfocitos-T, la linfoblastogenesis estimulada por PHA- y concanavalina-A, y la actividad citotóxica celular dependiente de anticuerpos (ADCC), antes de la operación y 3 a 4 meses después de la operación.

Ciento treinta y ocho pacientes fueron escogidos para el estudio en el curso de un periodo de 5 años. Setenta y cuatro pacientes recibieron inmunoquimioterapia postoperatoria y 64 pacientes no recibieron terapia anticancerosa después de la operación. Todos han sido seguidos por no menos de 5 años después de la cirugía. Se compararon las tasas de supervivencia y el estado inmunológico en los 2 grupos. Las características de los pacientes y los valores preoperatorios del estado inmunológico fueron similares en los 2 grupos.

La tasa de supervivencia a 5 años en el grupo de inmunoquimioterapia postoperatoria fue de 44.6%, en tanto que la de la del grupo de cirugía solamente fue de 23.4%. Esta diferencia es estadísticamente significativa (p<0.05). Todos los valores de los parámetros inmunológicos mostraron datos más favorables en el grupo de inmunoquimioterapia postoperatoria.

La inmunoquimioterapia postoperatoria ya no es de carácter adyuvante sino una forma esencial de terapia sistémica para lograr una prolongación de la supervivencia y para curar la enfermedad. El autor propone utilizar el término “inmunoterapia adyuvante” en el manejo del cáncer gástrico.

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  1. Department of Surgery and Cancer Research Institute, College of Medicine and Seoul National University Hospital, Seoul National University, Seoul, Korea

    Jin -Pok Kim M.D., F.A.C.S.

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  1. Jin -Pok Kim M.D., F.A.C.S.
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Kim, J.P. The concept of immunochemosurgery in gastric cancer. World J. Surg. 11, 465–472 (1987). https://doi.org/10.1007/BF01655811

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