picibanil and Esophageal-Neoplasms

A 52-year-old woman with thoracic esophageal carcinoma was admitted to our hospital. Standard radical esophagectomy was carried out via a right posterolateral thoracotomy and laparotomy. A drainage tube was removed from the right side of the chest on the 9th postoperative day. Three days later a chest roentgenogram showed massive left pleural effusion, and a tube was inserted into the left pleural cavity. The volume of the effusion was 900 ml/day and chylothorax was diagnosed. Conservative therapy was applied for 30 days, but chyle leakage persisted. Intra-pleural infusion of OK-432, a Su-strain of Streptococcus pyogenes, and doxycycline hydrochloride was carried out to seal the leakage point. The effusion stopped immediately after the procedure. There were no major side effects. This procedure should be considered the treatment of choice for patients with persistent chylothorax not responding to initial conservative management.

Topics: Chronic Disease; Chylothorax; Esophageal Neoplasms; Esophagectomy; Female; Humans; Middle Aged; Picibanil; Pleurodesis

Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients' sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible.

Topics: Adjuvants, Immunologic; Aged; Antibodies, Neoplasm; Antibody Formation; Antibody Specificity; Antigens, Neoplasm; Cancer Vaccines; Esophageal Neoplasms; Female; Glucans; Humans; Immunoglobulin G; Male; Membrane Proteins; Middle Aged; Picibanil; Receptor, ErbB-2; Recombinant Proteins; Vaccines, Combined

Nutritional deficiencies are believed to be instrumental in producing reduced immune responses in a variety of animal species. Malnutrition may result in an increase or a decrease in immune functions, depending upon its degree, and also the timing and severity of the nutritional protein deprivation. Our experimental data suggest that there is a significant impairment of cytotoxic activity against K-562 and of the ability of spleen cells to produce interferon in protein-deprived mice in comparison with control mice. Paradoxically accelerated tumor growth after administration of OK-432 or Lentinan was also noted in protein-deficient tumor-bearing mice. In addition, a clinical randomized study of advanced or recurrent gastric cancer patients treated with MMC and FT(MF) with or without lentinan was performed. We recognized excellent end-point results only in the lentinan-treated patients with normal protein levels, while no effect of this agent was seen in patients with low serum protein levels (below 5.9/dl). Aggressive postoperative chemotherapy for cases with distant lymph node metastasis was performed under active nutritional support without any depression of metabolic and immunological states, resulting in a good 5-year survival rate (36.9%).

Topics: Adjuvants, Immunologic; Animals; Esophageal Neoplasms; Humans; Lentinan; Mice; Mice, Inbred C3H; Neoplasms; Nutrition Disorders; Picibanil; Stomach Neoplasms

Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies.Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to <50 mL/day, we performed pleurodesis with Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing.In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct.

Topics: Adult; Antineoplastic Agents; Chylothorax; Drug Therapy, Combination; Esophageal Neoplasms; Esophagectomy; Etilefrine; Humans; Male; Middle Aged; Octreotide; Picibanil; Pleural Effusion; Pleurodesis

It is sometimes difficult to decide a treatment strategy for postoperative recurrence of esophageal cancer. Such recurrent esophageal cancer cases often present with extremely poor prognosis. We report a case of an 85-year-old man with a massive recurrent tumor of mediastinum 3 years after esophagectomy for squamous cell carcinoma (T3N2M0, Stage III) of the intrathoracic esophagus. The operative procedures were transhiatal esophagectomy and gastric reconstruction via posterior mediastinal route. Endoscopic local injection of OK-432 and balloon dilation was given to this patient after mediastinal recurrence. This patient lived for two years and three months after recurrence without severe side effects. Local injection of OK-432 is effective as a palliative therapy for recurrent case.

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagectomy; Humans; Male; Neoplasm Staging; Picibanil; Time Factors; Tomography, X-Ray Computed

The greater omentum contains abundant lymphoid tissues composed of a lot of macrophages and lymphocytes, and plays an important role in a host defense system in the peritoneal cavity. Also, it is well known to be an initial site of peritoneal disseminated metastases. We experienced a rare case of a 60-year-old man with postoperative recurrence of esophageal cancer that presented itself in the greater omentum of the gastric tube reconstructed through a mediastinal route, as well as through mediastinal lymph-nodes. We performed CT-guided radiofrequency ablation (RFA) for recurrent omental tumor that was refractory to chemoradiation therapy and growing rapidly adjacent to the trachea. In combination with local control using RFA, we attempted a systemic immunotherapy using OK-432, by subcutaneous injection around RFA to accelerate host antitumor immune responses induced by antigen stimulation by RFA, based on the immunological property of the omentum. RFA induced a significant therapeutic effect on the omental tumor with massive necrotic change. However, no apparent size reduction was seen in the metastatic mediastinal lymph nodes, although an increase of peripheral blood lymphocytes was observed before and after RFA, and systemic host immune responses were stimulated by OK-432.

Topics: Antineoplastic Agents; Catheter Ablation; Esophageal Neoplasms; Esophagoplasty; Humans; Immunotherapy; Male; Mediastinal Neoplasms; Middle Aged; Omentum; Peritoneal Neoplasms; Picibanil

Cancer patients have often been reported to have impaired immune function, and the effect of treatment modalities, such as surgery, irradiation, and chemotherapy, in depressing patients' immunity has also been reported. In this investigation, the effect of treatment on the cellular immunity of esophageal cancer patients was evaluated.. Immunological parameters, such as natural killer (NK) activity and lymphocyte subsets in peripheral blood, were measured in 32 esophageal cancer patients on 5 occasions (on the day of admission, 2 days before surgery, and 1 week, 1 month, and 2 months after surgery).. NK activity was greatly impaired shortly after the operation, and the percentages of lymphocytes as a whole, and CD8+, CD16+, and CD57+ lymphocytes were significantly decreased, on the other hand, a postoperative increase in the CD4+/CD8+ ratio was observed. No significant depression of immune function by postoperative irradiation was observed.. The results of this study suggest that cellular immunity, especially cytotoxicity, shortly after esophagectomy may be greatly impaired by the surgical stress of esophagectomy and an added effect of chemotherapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Chemotherapy, Adjuvant; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunity, Cellular; Killer Cells, Natural; Lymphocyte Count; Lymphocyte Subsets; Male; Middle Aged; Neoplasm Staging; Picibanil; Radiotherapy, Adjuvant

We here report a case presenting with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after having been treated for pleurodesis with OK-432, which is a lyophilized preparation of an attenuated strain of Streptococcus pyogenes. The patient, who had undergone a subtotal esophagectomy 4 years previously, was referred to our department after the diagnosis of a metastatic lung tumor. A right lower lobectomy of the lung was performed, and prolonged air leakage from a pulmonary fistula thereafter developed because of the dissection of severe pleural adhesion. OK-432 (5 klinische einheiten) was administered to the pleural cavity 3 times. On the 13th postoperative day, the patient began to complain of general fatigue and nausea. SIADH was diagnosed based on laboratory findings such as hyponatremia, serum hypo-osmolality and a high excretion of sodium in the urine. A restriction of the fluid intake with a sodium supplement resulted in the return to a normal serum level within 2 weeks. We therefore concluded that the intrapleural instillation of OK-432 had apparently caused SIADH in this case, because no other causes could be found.

Topics: Antineoplastic Agents; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Inappropriate ADH Syndrome; Lung Diseases; Lung Neoplasms; Middle Aged; Picibanil; Pleural Diseases; Pleurodesis; Pneumonectomy; Respiratory Tract Fistula; Tissue Adhesions; Treatment Outcome

This paper delineates which lymph nodes should be dissected due to the high frequency of metastasis associated with different types of primarily lesions of the thoracic esophagus. In cancer involving the upper third of the esophagus (Iu), lymph flow was found to be primary from the superior mediastinal area to the cervical area; in that involving the middle third (Im), it was broadly distributed from the superior, middle, and inferior mediastinal region to the cervical and abdominal regions; and in that involving the lower third (Ei), it tended to extend from the inferior mediastinal region to the abdominal region, with single primary metastatic nodes also being noted in this area. The significance of the "top" nodes, namely, the nodes located along the right recurrent laryngeal nerve in the upper portion of the thorax, was also investigated, and it was confirmed that the prognosis for patients with metastases to both the top nodes and other nodes was unfavorable. An immunohistochemical study on mediastinal lymph flow using the anti-Su-Ps antibody demonstrated interactions between top nodes and cervical and/or thoracic nodes.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Lymph; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Picibanil; Postoperative Complications

Combination therapy consisting of radiation and local administration of OK-432 was administered to 73 patients with esophageal cancer without distant metastases. Seventy patients were examined. The average age was 71 years. There were 60 males and 10 females. The mean tumor length was 7.0 cm.. One mg of OK-432 was administered endoscopically to and around the cancerous lesion at the beginning of radiotherapy and a second dose of 0.5 mg of OK-432 was given in the same manner 2 weeks later. X-ray irradiation was given at a daily dose of 1.6-1.8 Gy, five fractions a week. The average total dose was 61.1 Gy.. Complete responses were obtained in 49 of the 70 patients (70.0%), and partial responses (PR) in the remaining 21. The 5-year cause-specific survival rate of the 70 patients was 33.1%. The 5-year survival rate of the 49 patients with CR was 44.9%, and there were no patients with PR who survived more than 2 years. The 5-year survival rate of the 13 patients with T1 (UICC, 1987) was 79.6%, of the 24 patients with T2/3 41.1%, and of the 33 patients with T4 11.6%. The 5-year survival rates of the 18 patients with tumors less than 5 cm in length and the 40 patients with tumors 5 to 10 cm were 59.9 and 37.9%, respectively. In the patients with tumors more than 10 cm in length, the 4-year survival rate was 14.6%. Sixty-nine of the 70 patients were discharged in good condition and were able to take food orally.. This combination therapy may contribute not only to the survival rate, but also to patients' quality of life.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Injections, Intralesional; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Pilot Projects; Radiotherapy Dosage; Remission Induction; Survival Rate

Two cases with osteolytic bone metastases from cervical cancer and esophageal cancer treated by local therapy were reported. The first case is a 53-year-old female with bone metastases of left ischium developed 1 year after hysterectomy. She was treated by intratumor injection of sizofiran (SPG) 20 mg/w and radiation therapy. After 4 weeks, ischias pain decreased and bone lesion showed remarkable calcification (PR) 8th months later. The second case is a 58-year-old male with bone metastases of the left tibia and fibula developed 1 year after surgery. He was treated by intratumor injection of SPG 20 mg/w x 4 and OK-432 1.0 KE/w x 8 after radiation therapy. After 4 weeks, pain and swelling of left leg decreased and bone lesions showed remarkable calcification (PR) three months later. We suggest that intratumor injection of SPG and OK-432 with radiation therapy was effective for osteolytic bone metastases.

Topics: Adult; Bone Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Injections, Intralesional; Male; Middle Aged; Picibanil; Radiotherapy Dosage; Sizofiran; Uterine Cervical Neoplasms

We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Peplomycin; Picibanil; Postoperative Period

Local administration of OK-432, a biological response modifier, was combined with radiation in 30 patients with esophageal cancer as a pilot study. Complete response was obtained in 22 of 30 patients (73.3%); and partial response was obtained in the remaining eight cases (26.7%). Complete response was obtained in all eight patients with a tumor less than 5 cm in length. In the group with tumors 5-10 cm in length, complete response was obtained in 11 of 14 cases (78.6%); and partial response was obtained in 3 of 14 cases. In the group with a tumor length of more than 10 cm, complete response was obtained in 3 of 8 cases (37.5%); and partial response was obtained in 5 of 8 cases. One-year, 2-year, and 3-year survival rates of the 30 patients, including four patients who died of other diseases, were 67.9%, 40.8% and 29.0%, respectively. This new combination therapy may contribute not only to local control, but also to survival.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Picibanil; Pilot Projects; Radiation-Sensitizing Agents; Survival Rate

We studied the effects of OK-432 administered preoperatively on the cellular immunity and prognosis of patients with esophageal cancer. The preoperative injection of OK-432 was effective to preserve the NK activity in the peripheral blood. Especially the local priming and eliciting with OK-432 seemed to contribute to the activation of NK cells in the regional lymph nodes and to the improved prognosis of the patients.

Topics: Esophageal Neoplasms; Humans; Immunity, Cellular; Injections, Intradermal; Injections, Intralesional; Killer Cells, Natural; Picibanil; Preoperative Care; Prognosis

A patient with metastatic liver tumor from esophageal cancer having an anomaly of the hepatic artery was treated by regional immunochemotherapy using two infuserports, which were implanted transfemoral to the right and the left hepatic artery, respectively. The schedule of this therapy was as follows: CDDP (30 mg/m2) on day 1 and 8, 5-FU (1,000 mg/m2) on day 1, 2, 8, 9, 15 and 22, and OK-432 (1 KE/body) on day 3-6, 10-13 and 16-20 were administered via the hepatic artery; and OK-432 (5 KE/body) was also injected intramuscularly three times a week. After the first course of this therapy was performed via the left hepatic artery, metastatic foci in the left lobe regressed, while those in the right lobe progressed markedly. Thereafter, the second course was performed via the right hepatic artery, and then the third course was via both right and left hepatic artery. Following these trials, metastatic foci of the right and the left lobes showed remarkable regression. These results suggest that the effect of immunochemotherapy is closely related with the local concentration of anti-cancer agents.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps; Infusions, Intra-Arterial; Injections, Intramuscular; Liver Neoplasms; Male; Middle Aged; Picibanil; Tegafur; Uracil

The endogenous induction of tumor necrosis factor serum (TNS) for cancer immunotherapy was undertaken in the immediate postoperative period using Lentinan as the primer and OK-432 as the inducer. The changes in several immunological markers of the blood were assayed and compared with a control group to clarify the effects of this treatment. Plasma TNF-alpha levels were elevated two to three hours after eliciting treatment. The neutrophil count was elevated on the 7th postoperative day (POD) and the natural killer (NK) cell activity was transiently suppressed on the 1st POD, but NK cells possessing a high activity (Leu7-CD16+) were preserved until the 7th POD. Helper/inducer (CD4+) and killer cells (CD8+ CD11-) tended to increase, and suppressor (CD8 bright+ CD11+) cells tended to decrease in the induction group. There was no difference in the levels of prostaglandin E2 (PGE2) between the groups, but a marked elevation of interferon-gamma was evident on the 1st POD in the induction group. This treatment may be useful as postoperative adjuvant immunotherapy for cancer due to its ability to induce cytokines and activate host immune mechanisms.

Topics: Aged; Antigens, CD; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD4-Positive T-Lymphocytes; Esophageal Neoplasms; Female; Humans; Immunotherapy; Interferons; Lentinan; Leukocyte Count; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Postoperative Period; Remission Induction; Stomach Neoplasms; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Forty-three patients with advanced cancer were evaluated for the changes of absolute counts of peripheral blood lymphocytes and lymphocyte subsets during chemotherapy or chemoimmunotherapy. In 27 patients who did not respond to the therapy, whole lymphocytes, T cells, helper/inducer T cells and NK cells decreased significantly in number. In contrast, they showed little decrease in 16 cases responded to the therapy. In situ immunohistochemical analysis of the tumor infiltrating lymphocytes was performed on the carcinoma tissues obtained from 25 gastric cancer patients. T cell infiltration, in which helper/inducer T cells were predominant over suppressor/cytotoxic T cells, and NK cell infiltration were found in most of the tissues comprised various carcinoma types of histology. Furthermore, an analysis of a gastric cancer patient treated with systemic administration of 3 BRMs and intratumoral injection of OK-432 indicated that infiltration of cytotoxic T cells and NK cells augmented by cytokines such as IFN-gamma produced from activated helper/inducer T cells and NK cells. Therefore, it is suggested that movements of helper/inducer T cells and NK cells relate to the response to chemotherapy and participate in prognosis of advanced cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Colonic Neoplasms; Esophageal Neoplasms; Female; Humans; Immunologic Factors; Injections, Intralesional; Interferon-gamma; Killer Cells, Natural; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neoplasms; Picibanil; Remission Induction; Stomach Neoplasms; T-Lymphocytes, Helper-Inducer

We devised new combination therapy of radiation and local administration of OK-432 and performed for 26 patients with esophageal cancer between March, 1987 and December, 1988 as a pilot study. The average age was 73 years. Among 26 patients, male were 20 and female were six. Patients were irradiated at the schedule of under 2 Gy/day and the dose of TDF (time, dose and fractionation factor) 100 totally. OK-432, 10KE was endoscopically administered around cancer lesion at the beginning of the radiotherapy, and two weeks later, 5KE was given in the same manner. Complete response was obtained 20 out of 26 cases (77%) and partial response was obtained in the remaining six cases (23%). All six patients with tumor length less than five cm showed complete response. All 16 patients who could not eat food orally before treatment, became to take food enough orally after the treatment and could discharge in good condition. One year and two years survival rate of 26 patients by Kaplan Meier method were 67.4% and 47.2%, respectively. Six patients with tumor length less than five cm, are all alive without a sign of recurrence. This combination therapy will improve not only the response rate and the survival rate, but also the quality of life of patients with esophageal cancer.

Topics: Aged; Biological Products; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Male; Picibanil; Survival Rate

In the present study, we measured in vitro production of IFN-gamma induced by OK432 in peripheral mononuclear cells (PMC) and investigated the relationship between the skin reaction to Su-Ps, an extract of Streptococcus Pyogenes, and purified protein derivative (PPD) and the productibility of IFN-gamma in patients with gastric and esophageal cancers. PMC isolated with the Ficoll-conray centrifugation technique were adjusted to 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum and incubated over 7 days at 37 degrees C in the presence of OK432 at 0.17 KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. The results are summarized as follows. 1. The production of IFN-gamma in PMC from patients with negative skin reaction to Su-Ps and PPD was significantly decreased as compared with the value obtained from patients who were positive in these skin tests (p less than 0.001). 2. In vitro production of IFN-gamma induced by OK432 was significantly correlated with the degree of skin tests to Su-Ps and PPD as well (r = 0.48, r = 0.41, p less than 0.01, respectively). Thus, it is concluded that the assay of IFN-gamma produced in PMC cultures is useful to evaluate the immunological status of patients with cancer.

Topics: Bacterial Proteins; Biological Products; Esophageal Neoplasms; Female; Humans; Interferon-gamma; Leukocytes, Mononuclear; Male; Mitogens; Picibanil; Skin Tests; Stomach Neoplasms; Tuberculin Test; Tumor Cells, Cultured

OK-432 has been injected endoscopically into 4 patients with an unresectable esophageal or gastric cancer. Three months after the initial injection, a remarkable improvement in the symptoms and a reduction of the tumor size was recognized in all 4 patients. This study indicates that an OK-432 injection provides considerable benefits to patients with an advanced esophageal or gastric cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Biological Products; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Esophagoscopy; Gastroscopy; Humans; Injections; Male; Middle Aged; Picibanil; Remission Induction; Stomach Neoplasms

Factors influencing the depression of natural killer (NK) activity and its prevention were studied in 57 esophageal cancer patients. NK activity off peripheral blood mononuclear cells was measured by a 51Cr-release assay against K-562 target cells. NK activity in esophageal cancer patients was significantly lower than that in healthy individuals and tended to be lower compared with those in stomach and colon cancer patients. The depression of NK activity was significantly correlated with the reduction of serum albumin level, creatinine height index of nutritional assessment. The activity was also suppressed in proportion to the size of cancer and its staging. Both preoperative radiation and surgery markedly depressed NK activity. Postoperative depression recovered to the Preoperative level 4 weeks after operation. These results indicated that malnutrition, cancer bearing and therapeutic stress were associated with the depression of NK activity. As the preventive measures against such depression of NK activity, avoidance of preoperative radiation and better selection for two-stage operation enhanced recovery of the depressed NK activity. Furthermore, the preoperative administration of OK-432, as n immuno-activator, could be effective to minimize a decrease of NK activity related to radiation and surgery, and to accelerate its recovery to the level before treatment.

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cytotoxicity, Immunologic; Esophageal Neoplasms; Female; Humans; Killer Cells, Natural; Male; Middle Aged; Neoplasm Staging; Nutrition Disorders; Picibanil; Risk Factors

Multidisciplinary treatment for advanced esophageal carcinoma, which is not resectable in many cases, has become an important subject to study. We have reported the effectiveness of thermotherapy in treatment of esophageal carcinoma by basic experiments using three cell strains of human esophageal carcinoma designated as SGF-3,4,5. Based on the results of the basic experiments, we have performed thermotherapy combined with radiotherapy, chemotherapy and immunotherapy on cases of advanced esophageal carcinoma since October 1985. As for the basic experiment, proliferation of SGF-3 was inhibited at more than 40 degrees C, SGF-4 at more than 41 degrees C and SGF-5 at more than 42 degrees C. We did not observe the recovery of the growth of SGF-3 after heating at 41 degrees C for 72 hours and 42 degrees C for more than 24 hours. And the growth of SGF-4 after heating at 42 degrees C for more than 48 hours did not recover either. No recovery of the growth of SGF-5 after heating at 42 degrees C for 72 hours was noted. Based on the data, combined therapy was performed in 12 patients with advanced esophageal carcinoma. The evaluation of the local response to the combined thermotherapy revealed CR in five cases, PR in five and NC in two.

Topics: Aged; Aged, 80 and over; Cell Division; Cell Line; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Hot Temperature; Humans; Hyperthermia, Induced; In Vitro Techniques; Male; Middle Aged; Picibanil

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.

Topics: Adult; Aged; Cytotoxicity, Immunologic; Esophageal Neoplasms; Humans; Interferon Type I; Interleukin-2; Killer Cells, Natural; Middle Aged; Picibanil; Spleen; Stomach Neoplasms; T-Lymphocytes, Regulatory

Topics: Aged; Aged, 80 and over; Biological Products; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Male; Picibanil; Pilot Projects; Radiotherapy Dosage; Remission Induction

Using the Su-PS skin test, an attempt was made to evaluate whether or not this reaction could become a useful immune parameter in patients with gastrointestinal cancer. The conclusions were as follows: Late-stage patients with gastric cancer showed a weak response in the Su-PS skin test when examined preoperatively. The skin reaction to Su-PS was shown to become stronger than in the PPD and PHA test when patients received OK-432 treatment. Patients with advanced cancer having longer survival (more than 7 months) showed stronger response in the Su-PS skin test that patients having short survival (less than 6 months). It was suggested that the Su-PS skin test was useful for evaluating the immune response to OK-432 treatment.

Topics: Biological Products; Colonic Neoplasms; Esophageal Neoplasms; Humans; Intradermal Tests; Pancreatic Neoplasms; Phytohemagglutinins; Picibanil; Polysaccharides, Bacterial; Skin Tests; Stomach Neoplasms; Tuberculin Test

Topics: Adult; Age Factors; Aged; Cytotoxicity Tests, Immunologic; Esophageal Neoplasms; Female; Humans; Killer Cells, Natural; Leukocyte Count; Male; Middle Aged; Picibanil; Sex Factors; Stomach Neoplasms

The effect of treatment with bacterial preparations on blood flow in normal and malignant tissues was investigated, clinically and experimentally. The time course of the local effect of the preparations was recorded by Laser Doppler Velocimetry (LDV) via a probe on the surface of normal and malignant tissues directly over the injection site. Experimentally, no definite enhancement of blood flow with OK-432, a streptococcal preparation, was observed in nude mice. Clinically, intradermal administration of OK-432 or tuberculin (PPD) resulted in an approximate 11-or 4-fold increase in blood flow, respectively. The injection of OK-432 into malignant tissues, such as dermal cancer and breast cancer with direct extension to the skin, resulted in an approximate 3.5-fold increase. The results suggested that bacterial preparations can act as an adjuvant to enhance drug delivery to tumor tissue in cancer chemotherapy, and that the enhancement of blood supply is induced by immune response.

Topics: Adult; Aged; Animals; Biological Products; Blood Volume; Breast Neoplasms; Esophageal Neoplasms; Female; Humans; Lidocaine; Lung Neoplasms; Male; Mice; Mice, Nude; Microcirculation; Middle Aged; Picibanil; Regional Blood Flow; Skin; Skin Neoplasms

During the period from October 1972 to January 1983, 462 patients with squamous cell carcinoma of the esophagus were admitted to Toranomon Hospital. Those patients with carcinoma of the hypopharynx, cervical esophagus, or cardia extending to the esophagus were excluded from the study. Resection and reconstruction were carried out in 295 patients with a resectability rate of 63.9 percent and an operative mortality rate of 1.7 percent. The 5 year survival rate for 101 patients who had resection with minimum 5 year follow-up was 34.7 percent. Although the ultimate outcome is largely influenced by the tumor type representing malignancy, it is worthwhile to make all efforts to resect the tumor with a negative surgical margin and to resect concomitant lesions if there are any. Surgeons should not be discouraged by the length or size of a tumor. The extent of positive lymph node is closely related to long-term results. However, systemic lymph node dissection should be carried out because 5 year survival can then be expected, even when positive nodes are dissected from various areas.

Topics: Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Esophagoplasty; Humans; Lymph Node Excision; Lymphatic Metastasis; Picibanil

We have been interested in direct activity of OK-432 on cancer lesion and applied a combined therapy of perifocal administration of OK-432 with radiation for 2 cases as a new trial. Following results were obtained. Histological efficacy as Ef3 at resected specimen was observed in one case and complete regression of cancer lesion was confirmed by X-ray, fiber scope and biopsy after combined therapy of perifocal administration of 10 KE of OK-432 with radiation of 2400 rad in total.

Topics: Aged; Biological Products; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Male; Picibanil

Based on the experimental results that operative stress of thoracotomy or laparothoracotomy has enhanced tumor growth remarkably in rats compared with laparotomy, a new combined treatment with by-pass operation, irradiation and immunochemotherapy was investigated in 39 advanced thoracic esophageal cancer patients. At by-pass operation, abdominal esophagus was divided and its proximal stump was closed immediately. Cervical esophagus was then divided and its distal stump was pulled out to the right supraclavicular region to make outer fistula. Thus, anticancer drug was poured into the esophagus through outer fistula very easily just before irradiation and then irradiation was performed under the condition that the lesion was immersed in the drugs. As anticancer agent, Mitomycin-C, 5-Fluorouracil or Bleomycin was given alternately. Lately, the combination of 5-Fluorouracil and Vitamin A was preferably used. The changes of immunological parameters and the survival after the onset of treatment was reported.

Topics: Adult; Aged; Bleomycin; Drug Therapy, Combination; Esophageal Neoplasms; Esophagoplasty; Fluorouracil; Humans; Immunotherapy; Middle Aged; Mitomycins; Picibanil; Prognosis; Skin Tests

Topics: Biological Products; Breast Neoplasms; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Mouth Neoplasms; Neoplasms; Pharyngeal Neoplasms; Picibanil; Radiotherapy Dosage