Treatment emergent affective switch: a controlled study.

OBJECTIVE: To study the clinical features of treatment emergent affective switch (TEAS) in comparison with spontaneous mania. METHODS: Twelve patients with TEAS within a 12-week period (average) of starting standard antidepressant medication were compared with 12 patients with spontaneous mania. RESULTS: Patients with TEAS were older, had longer duration of illness, more previous episodes, higher prevalence of subclinical hypothyroidism, and reported more previous episodes of mania associated with antidepressant use. TEAS was less severe, with a lower incidence of psychotic symptoms, lower Young Mania Rating Scale index score and rarely required hospitalization. The interval from intervention to response and remission was similar in both groups. CONCLUSION: TEAS was less severe, but had similar duration when compared with spontaneous mania. These results cannot directly answer the question of whether there is a causal relationship between antidepressant use and TEAS. While it is also possible that patients with longer duration of illness and higher cycle frequencies are more likely to experience episodes, it is difficult to attribute lesser severity of TEAS episodes to these clinical factors. Our observations are consistent with the suggestion that patients with longer duration of illness and previous history of TEAS may be at a greater risk of switching to mania during the use of antidepressants.

A case of biliary cystadenoma with obstructive jaundice.

Biliary cystadenoma is a rare cause of obstructive jaundice. We report a case of a 78-year-old Japanese man with biliary cystadenoma presenting repetitive abdominal pain and jaundice. Ultrasound sonography revealed a hyperechoic mass in the left lateral lobe of the liver. Histological examination revealed a biliary cystadenoma. Intracystic hemorrhage was assumed to be the cause of obstruction of the bile ducts.

[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].

A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.

Effect of glucocorticoid replacement on tumor growth after adrenalectomy in mice.

We studied the effects of glucocorticoid replacement on tumor growth after adrenalectomy of Meth A sarcoma in mice. Tumor growth was inhibited in the adrenalectomized mice when a minimum dose of corticosterone, 0.3 mg/day, was given for replacement, and higher doses led to an even greater inhibition. Corticosterone had no effect on tumor growth in the irradiated mice. Sinecomitant immunity in the case of growth of the retransplanted excised tumor was compromised in the adrenalectomized mice. In vivo neutralization and immunosuppressive activities were absent in the spleen cells of the adrenalectomized mice. It would thus appear that adrenalectomy suppresses tumor growth by mechanisms other than glucocorticoid ablation. For optimum tumor control, glucocorticoid replacement after adrenalectomy should be in excess of the minimum daily requirements.

Appraisal of distal splenorenal shunt in the treatment of esophageal varices: an analysis of prophylactic, emergency, and elective shunts.

From June, 1969 to February, 1987, distal splenorenal shunt was carried out on 78 patients with esophagogastric varices. The operations were urgent in 9, elective in 40, and prophylactic in 29 patients. There were 52 males and 26 females. Age ranged from 16 to 76 years with an average of 53 years. Thirty-seven patients were alcoholics. Hepatitis B surface antigen was positive in only 15.5%. The causes of portal hypertension were cirrhosis of the liver in 67, chronic hepatitis in 5, idiopathic portal hypertension in 4, primary biliary cirrhosis in 1, and fatty liver in 1 patient. Fifty-two patients were in Child's class A, 18 in class B, and 8 in class C. Emergency shunts were performed only when conservative therapy had failed to stop variceal bleeding. Prophylactic operations were done in patients having Child's class A or class B liver disease and risky varices, in varices larger than 5 mm in diameter and/or varices with red color signs such as cherry red spots. Forty-two patients underwent the original Warren shunt, but the remaining 36 had modified distal splenorenal shunt with expanded polytetrafluoroethylene interposition. The operative mortality rates were 11.1% in the emergency group, 2.5% in the elective group, and 3.4% in the prophylactic group. The overall operative and hospital death rates were 3.8% and 7.7%, respectively. The patency rate was 94.1% and the incidence of rebleeding from esophageal varices was 3.8%. Hepatic encephalopathy, although mild to moderate in degree, was observed in 14.7% of 75 patients excluding 3 operative deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC + FT + PSK group showed a significant increase in 5 year survival from the other groups (p less than 0.05). Moreover the survival rate was significantly higher in the MMC + FT + PSK group than in the MMC + FT group (p less than 0.01). According to the analysis on stratification, the MMC + FT + PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p less than 0.01 or p less than 0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

[Clinical studies on effect of cefbuperazone on surgical infections].

We conducted clinical studies on the efficacy and safety of cefbuperazone (CBPZ) on surgical infections with the following results. 1) In evaluable 32 patients, CBPZ was evaluated to be clinically effective in 23 (71.9%) and the efficacy rate was better in those who were administered 4 g/day of CBPZ (87.5%, 14/16) than in those who were given 2 g/day (57.1%, 8/14). 2) Antibacterial activity of CBPZ was evaluated in 41 isolated bacterial strains. Pathogen eradication rate by bacterial species was 75.6% (31/41). CBPZ exerted excellent antibacterial effects on Escherichia coli (100%, 8/8) and anaerobic bacteria such as Bacteroides (88.9%, 8/9). Resistant bacteria to CBPZ were Enterococcus faecalis and Pseudomonas aeruginosa. 3) No serious side effects were noted in any of the 34 patients who entered in this study. Abnormal laboratory test results were noted in 2 patients (5.9%) and they were transient elevation of transaminases and alkaline phosphatase. From the results shown above, CBPZ appears to be a highly useful antibiotic for the treatment of surgical infection.

Emergency distal splenorenal shunt for medically uncontrollable variceal haemorrhage.

Emergency distal splenorenal shunt was prospectively carried out on 14 patients presenting with active bleeding from esophagogastric varices which was not controllable by medical treatment. Patients were composed of nine males and five females. Age ranged from 34 to 76 years with an average of 56.2. Underlying liver disease were cirrhosis of the liver in seven, cirrhosis and hepatocellular carcinoma (HCC) in five, primary biliary cirrhosis in one, and chronic hepatitis in one instance. Preoperatively, the Child's classification was A in one, B in five, and C in eight patient. Two patients underwent the original Warren shunt but the remaining 12 were treated by modified distal splenorenal shunts using Gore-Tex interposition. Three patients with Child's class C disease died within one month (operative mortality 21.4%). An oldest woman transiently had hepatic encephalopathy but recurrent variceal bleeding was not observed in any of the patients. Distal splenorenal shunt is a safe and reliable means in the treatment of medically intractable variceal hemorrhage.

Prophylactic distal splenorenal shunt for child's class A and B patients at high risk of bleeding.

During recent 17 years, prophylactic distal splenorenal shunt was carried out on 29 patients. Patients were composed of 18 males and 11 females. Age ranged from 34 to 66 years with an average of 52.4. All patients had risky esophagogastric varices; varices larger than 5 mm in diameter and or varices with red color signs such as cherry red spots endoscopically. Underlying liver disease were cirrhosis of the liver in 27, chronic hepatitis in one, and idiopathic portal hypertension in one. Twenty-three patients were in Child's class A and six were in class B. Thirteen patients underwent the original Warren shunt but the remaining 16 had modified distal splenorenal shunts with expanded polytetrafluoroethylene interposition. Portal-azygos disconnection was routinely performed. One patients (3.4%) died of hepatic failure on the 6th postoperative day. Four patients (14.3%) developed hepatic encephalopathy of mild to moderate degree but no patients have suffered from variceal bleeding until now. The 5-, 10-, and 15-year survival rates were all 85.5 per cent. It is concluded that distal splenorenal shunt is a safe and reliable method to prevent variceal bleeding in a selected group of patients.

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC + HCFU group than in the MMC only group (Z-test: p less than 0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC + HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p less than 0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.

[A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II)].

A multi-institutional cooperative study of postoperative immunochemotherapy for gastric cancer was studied using PSK and/or OK-432 combined with Tegafur (FT) and/or MMC. A total of 3,630 gastrectomized patients from 412 institutions were entered into the study using 6 randomly assigned protocols. Unbiased background cases were analyzed by 4-year or 5-year survival rates (SVR) for each protocol. The efficacy of combined PSK with FT was noticed in all cases of curative operation macroscopically and in n(-) X ps(+) cases (4-y SVR). The combination of MMC, FT and PSK produced better survival than MMC with FT or PSK administration in all cases of macroscopic curative operation (5-y SVR) and in non-curative operation (4-y SVR). The combination of MMC, FT, PSK and OK-432 was effective for poorly differentiated cancer (4-y SVR). Immunochemotherapy with MMC, FT, PSK and OK-432 was more effective in patients with preoperative positive PPD skin test than in those with negative PPD skin test. These results suggested that adjuvant immunochemotherapy using PSK and/or OK-432 combined with MMC and FT is effective for the improved survival of gastrectomized patients with gastric cancer.

The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability.

The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability.

Langerhans cells and prognosis in patients with gastric carcinoma.

Infiltration of Langerhans cells (LC) and macrophages into tumor tissues was investigated using immunohistochemical methods, anti-S-100 protein and anti-lysozyme antibodies in 174 cases of gastric carcinoma. Varying population densities of S-100-positive LC were noted in tumor tissues; lysozyme-positive macrophages, however, were found in almost equal quantities. LC were mainly interspersed among the tumor cells, whereas macrophages were present in the stroma and around the necrotic foci. Although the survival time of patients with Stage I, II or IV gastric carcinoma did not relate to the density of LC, survival time in Stage III patients correlated well with the density of LC. In patients with a marked infiltration of LC, survival time was longer than in cases of only a slight infiltration (P less than 0.001). Therefore, LC in immunological defense mechanisms of the host against the tumor may be clinically effective in a certain phase of tumor development.

[In vitro chemosensitivity of various human tumors evaluated by the succinate dehydrogenase inhibition (SDI) test (2)].

In vitro chemosensitivity was evaluated by succinate dehydrogenase inhibition (SDI) test in 94 human tumors including 59 gastric cancers, 27 colo-rectal cancers and 8 malignant lymphomas. Tumor fragments were exposed to 12 kinds of antitumor drugs at ten times peak plasma concentration. Evaluable rates were 86/94 (91%) for all cases, 56/59 (95%) for gastric cancers, 22/27 (81%) for colo-rectal cancers and 8/8 (100%) for malignant lymphomas. The mean of SD activity was decreased to 48% of that of control cells with aclacinomycin, 49% with carboquone, 53% with actinomycin D, 54% with mitomycin C and 54% with daunomycin for gastric cancers, 59% with adriamycin for colo-rectal cancers and 33% with cyclophosphamide (40487 S), and 33% with actinomycin D, 37% with vinblastine and 39% with adriamycin for malignant lymphomas. When the SD activity was reduced to below 50% by antitumor drugs, the chemosensitivity was defined as positive. The antitumor drugs which had a higher chemosensitive-positive rate were aclacinomycin, carboquone and mitomycin C for gastric cancers, adriamycin for colo-rectal cancers and 40487 S, daunomycin and vinblastine for malignant lymphomas. Our results suggest that the origin of a tumor is a critical factor in its chemosensitivity.

[In vitro chemosensitivity testing evaluated by intracellular ATP level: ATP assay].

In vitro chemosensitivity was evaluated by bioluminescence ATP assay in 12 human tumors including 7 gastric cancers and 5 colo-rectal cancers. Tumor fragments minced with scissors were exposed to 6 kinds of antitumor drugs: carboquone, adriamycin, aclacinomycin A, mitomycin C, cisplatin and 5-FU at peak plasma concentration or ten times peak plasma concentration. After 3 days at 37 degrees C, each tumor fragment suspension was washed with phosphate-buffered saline, boiled for 3 min and assayed for its intracellular ATP level using the luciferin-luciferase method. The ATP level of the drug-untreated group was 6.01 +/- 4.55 X 10(-10) moles/mg tissue protein in gastric cancers and 9.77 +/- 8.46 X 10(-10) moles/mg tissue protein in colo-rectal cancers. The percentages of cases in which the ATP level was reduced to less than 50% by the antitumor drugs were 70% for carboquone, 11% for adriamycin, 30% for aclacinomycin A, 45% for mitomycin C, 13% for cisplatin and 18% for 5-FU at peak plasma concentration, and 90% for carboquone, 78% for adriamycin, 80% for aclacinomycin A, 82% for mitomycin C, 63% for cisplatin and 82% for 5-FU at ten times peak plasma concentration. The test for chemosensitivity prediction is thus available at peak plasma concentration of antitumor drugs in ATP assay.

Clinicopathological features of mucosal carcinoma of the stomach with lymph node metastasis in eleven patients.

Of 568 patients with mucosal carcinoma of the stomach, only 11 (1.9 per cent) had a lymph node metastasis. The clinicopathological findings in these 11 patients are reviewed. Diameters of the lesions were over 2.0 cm. Seven were located in the body of the stomach and four in the antrum. Nine showed depressed lesions comprised of poorly differentiated adenocarcinoma and two were classed as elevated lesions consisting of well and moderately differentiated adenocarcinomas. There were six with accompanying peptic ulcers, all of which revealed depressed lesions with poorly differentiated adenocarcinoma. Metastases to proximal perigastric lymph nodes were found in eight while there were three with involvement of distant lymph nodes. All patients were surgically treated and all are doing well except for one who died of hepatic failure one month after operation. We recommend that the standard operation with lymph node dissection is essential, even in cases of mucosal carcinoma.

Partial hepatectomy alters sensitivity of rat hepatocytes to 5-fluorouracil.

The sensitivity to 5-fluorouracil (5-FU) and the metabolism of 5-FU in the regenerating rat liver were investigated in vitro. Determination of cell viability using the succinate dehydrogenase inhibition test showed that the hepatocytes of the partially hepatectomized liver were more sensitive to 5-FU, compared to findings in the case of normal liver. The activities of 5-FU phosphorylation of the 3 pathways were higher in the regenerating than in the intact liver and the peak increase was seen 36 h after partial hepatectomy. The activity of 5-FU degradation decreased to about 30% at 36 h and then gradually increased reaching the normal range at 72 h after partial hepatectomy. These results suggest that the metabolic changes of 5-FU may be one of the causes for increased 5-FU susceptibility in the regenerating liver.

[Surgery and adjuvant therapy of gastric cancer].

A remarkable improvement of prognosis has been obtained in surgery for patients with gastric cancer in Japan. This is attributed to the standardization of prophylactic lymphadenectomy and the prescription of adjuvant anticancer chemotherapy. Postoperative long-term cancer chemotherapy (PLCC), available from 1970, using MMC, Tegafur and PSK in addition to curative surgery has prolonged the survival time of patients with serosal and/or secondary lymphatic metastasis. To confirm the efficacy of adjuvant chemotherapy on a wide basis, the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer was organized in 1975. The first and the second study revealed that postoperative bolus injection of MMC and long-term administration of Tegafur improved the survival rate of patients with stage III and lymphatic with serosal metastasis. The third pilot study showed that immunotherapy using PSK and/or OK-432 with anticancer drugs might be effective for gastric cancer. To promote extensive investigations of a large number of patients, the Japanese Foundation for Multidisciplinary Treatment of Cancer was founded in 1980, and the first study suggested that immunochemotherapy using MMC, Tegafur, PSK and OK-432 is effective for gastric cancer. Efficacy of MMC and Tegafur treatment was obtained in some types, such as female cases, those with undifferentiated adenocarcinoma of Borrmann types II and IV and those given curative resection. It is therefore necessary to seek a proper regimen for each type of patient for the concept of Type-oriented Therapy (TOT).