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BACKGROUNDFor patients with non-small cell lung cancer the TNM staging system and other conventional prognostic factors fail to predict accurately the outcome of treatment and survival. This study attempts to determine the prognostic value for survival of the proportions of CD4+ lymphocytes in the pleural cavity (PLY) of patients with resectable non-small cell lung cancer.METHODSLymphocytes in the pleural cavity separated from 51 patients with non-small cell lung cancer were examined by flow cytometry to measure the proportions of CD4+ PLY. Univariate and multivariate analyses were performed to assess the association between the proportion of CD4+ PLY and survival.RESULTSThe 5 year survival rate of patients with percentage CD4+ PLY of ⩽30% was 84% whereas that of patients with %CD4+ PLY >30% was 26.9%. The difference in survival between the %CD4+ PLY ⩽30% and %CD4+ PLY >30% groups was significant (p30% was also significant (p =0.015). Multivariate analysis showed that the proportion of CD4+ PLY (hazard ratio=6.9, 95% CI 0.045 to 0.47) and nodal status (hazard ratio=22.7, 95% CI 0.006 to 1.806) are significant and independent prognostic factors for the survival of patients with lung cancer.CONCLUSIONSThe proportion of CD4+ PLY may help to select patients who are likely to have a poorer prognosis after surgery and therefore may be suitable for consideration of adjuvant treatments. These results need confirmation in a larger prospective study.

Thymic epithelial tumors are mainly consisted of thymoma, thymic carcinoma, and thymic carcinoid. And thymic carcinoma is very rare neoplasm. The classification of thymic carcinoma has remained a subject of controversy for many years. The outline of thymic carcinoma has been clarified by "Atlas of Tumor Pathology: Tumors of the Mediastium (AFIP)" and "Histrogical Typing of Tumours of the Thymus (WHO)" published recently. Squamous cell carcinoma is by far the most common in Japan. Thymic carcinoma is a predilection for male. The peak of age was 40-60 years. Thymic carcinoma already had contiguous invasion around neighbor organs, dissemination, and lymph node metastases or distant metastases at diagnosis. Two third of patients with thymic carcinoma performed surgery, and most of them performed adjuvant radiotherapy or chemotherapy. 5-year survival of thymic carcinoma was 33-50%. Histologic tumor type, type of tumor margin, growth pattern, nuclear atypia, necrosis and mitotic activity were correlated with survival. In this paper thymic carcinoma is reviewed mainly based on recently literatures and results obtained from a questionnaire on thymic epithelial tumors in Japan.

The extent of lymphatic metastasis is the most important factor in the prognosis for non-small cell lung cancer (NSCLC). Therefore, suppression of lymphatic metastasis provides an improvement in survival time in lung cancer patients. We established a new patient-like model for lung cancer metastasis by orthotopic implantation in severe combined immunodeficiency (SCID) mice and demonstrated the lymphogenous spread histologically using human NSCLC cell lines. The cardinal features of this model are a simple procedure and a similarity to the metastatic form of human lung cancer. The purpose of this study is to assess the inhibitory action of uracil-tegafur (UFT) and cis-diamminedichloroplatinum(II) (CDDP) on lymphatic metastasis and life span prolongation in our lymphogenous metastatic model system using SCID mice.The inhibition ratios of mediastinal lymph node metastasis were 86.2, 94, and 92.1% for 12 mg/kg body UFT, 17 mg/kg body UFT, and 10 mg/kg body CDDP, respectively. The administration of anticancer drugs prolonged the life span by 4.6 days (17 mg/kg body UFT) and 8 days (10 mg/kg body CDDP) in MST.We demonstrated that UFT alone and CDDP alone suppressed mediastinal metastasis and prolonged the life span in our lymphogenous metastatic model. Regardless of the administration route and characteristics of anticancer drugs, cytostatic or cytotoxic, our model is capable of evaluating the inhibitory effect of drugs on lymphatic metastasis. This model should make an important contribution to our understanding of the mechanism and selection of drugs for antilymphatic metastasis in lung cancer.

The purpose of this study was to evaluate the possibility of differential diagnosis of tumors, such as breast cancer, by measuring the mammary electrical bioimpedance via the skin surface noninvasively and by examining the relationship between the tissue structure of the breast and electrical bioimpedance. The mammary electrical bioimpedance was measured in 24 patients with breast cancer. Taking into account the measurement results and the distribution of the mammary glands and fatty tissue, a breast model with tumors was proposed. Based on this model, the distributions of the electric potential and electric field in the tissue were theoretically analyzed by the three-dimensional finite element method. In clinical cases, the Re values of the diseased breast were significantly larger than those of the contralateral healthy breast. In theoretical analysis based on the breast model, the Re value of mammary electrical bioimpedance varied due to the structure of the breast, that is, the ratio of fatty tissue to mammary gland and the presence of mammary tumors. The results of the measurement agreed with the theoretical analyses. These results suggest that differential diagnosis of breast tumors is possible by measuring the mammary electrical bioimpedance using noninvasive electrodes on the skin.

Rare subtypes of lung cancer, that is, carcinoid, adenoid cystic carcinoma, muco-epidermoid carcinoma and adenosquamous carcinoma, were described. These tumors except adenosquamous carcinoma, are generally low malignant and slow growing and arise from upper airway. Complete surgical resection is the best treatment. Sometime tracheobronchoplastic surgery is recommended. Adenosquamous carcinoma is more malignant than adenocarcinoma or squamous carcinoma.

An animal model of metastasis with features similar to those of lung cancer metastasis in humans is required for an understanding of the cellular and molecular mechanisms of human lung cancer metastasis. Ma-44 cell lines derived from human squamous cell lung cancer were percutaneously injected (2-3 x 10(4)) into the left lung of SCID mice. After orthotopic implantation, Ma-44 cell lines formed tumors in the left lung at a high rate (17/25, 68%), and many of those metastasized to mediastinal lymph nodes (13/17, 76%) by the 14th day, but not to other organs. After the ectopic implantation, the Ma-44 cell line inoculated subcutaneously (2-3 x 10(5)) formed a tumor at the inoculation site by the 28th day (all mice), but did not metastasize to any organs. The Ma-44 cell line inoculated intravenously (2-3 x 10(5)) formed metastases in the lungs (37/50, 74%), and these pulmonary metastases metastasized to the mediastinal lymph nodes at low rate (3/37, 8%) by the 14th day. The orthotopic sites of implantation are critical for the metastatic ability of transplanted tumors in SCID mice. Since non-small cell lung cancer (NSCLC) grows at the primary site in humans, lymphogenous metastasis occurs frequently, and blood-born metastasis occurs at moderate rate, our orthotopic SCID mice model was similar to the metastatic behavior of NSCLC in humans. Thus, this model may be useful for elucidating the mechanism of lymphogenous metastasis in human lung cancer, and testing the anti-metastatic efficacy of therapeutic agents in vivo.

Acinic cell carcinoma of the salivary glands is a rare cancer representing a low grade malignancy. The recurrence of a tumor is sometimes encountered, usually within 5 years of initial operation. We describe an unusual recurrence after a long interval following primary surgery. In 1987, a 60-year-old woman underwent excision of a mass in the superficial lobe of the right parotid gland under the preoperative diagnosis of a benign tumor. A histologic diagnosis of acinic cell carcinoma was made by examining sections from the resected mass. The patient noted several small nodules in the right parotid region in 1995, but she did not visit our clinic until 1998 when tenderness developed. A locally recurrent tumor and cervical lymph nodes containing metastases were resected and postoperative radiotherapy was given 11 years after the first operation. At least 10 years of follow-up may be necessary for patients with acinic cell carcinoma because of slow-tumor growth.

The latest revision of the International System for Staging Lung Cancer was published in June 1997. We discuss the following 4 major items in the new TNM staging system. 1) The fact that stage I was divided into stage IA (T1N0M0) and IB (T2N0M0) is reasonable, as the survival prospects for the subsets differ significantly. 2) The fact that stage II was divided into stage IIA (T1N1M0) and IIB (T2N1M0) is not appropriate, However, there is no significant survival difference between the T1N1M0 subset and the T2N1M0 subset, because there are fewer T1N1M0 cases. 3) The fact that the T3N0M0 subset was shifted into stage IIB is reasonable. Patients who undergo resection of tumors invading the parietal pleura, neighboring lobe, and main bronchus within 2 cm of the carina in the T3N0M0 group have a good prognosis, but those who undergo resection of tumors invading the rib, intercostal muscle, and diaphragm in the T3N0M0 group have a poor prognosis. 4) The decision to designate satellite lesions within the lobe of the primary tumor as T4 is controversial, because it is very difficult to determine whether satellite lesions are metastases from other lesions or if they are primary synchronous neoplasms.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

We examined the effect of recombinant IFN-alpha and IFN-gamma on induction of LAK cells from peripheral blood mononuclear cells (PBMNCs) in 7 pre-operative breast cancer patients and 4 healthy volunteers. Significant LAK activity was developed from PBMNCs of pre-operative breast cancer patients and healthy volunteers after incubation for 4 days with IL-2 (presence of IL-2 vs. absence of IL-2). Incubation of PBMNCs of pre-operative breast cancer patients with 1000 U/ml of IFN-alpha for 4 days suppressed the LAK activity significantly (P0.05). By contrast, incubation of PBMNCs of pre-operative patients with 1000 U/ml of IFN-gamma for 4 days increased the LAK activity significantly (P0.05). Significant cytotoxicity against MCF-7 cells (estrogen receptor positive human breast cancer cell line) was developed from PBMNCs of pre-operative breast cancer patients at 20:1 and 40:1 E/T ratios after incubation for 4 days with IL-2 (absence of IL-2 vs. 20:1 or 40:1, P0.05, P0.05), whereas PBMNCs of healthy volunteers did not. Stimulation of LAK cells with IFN-gamma produced a significant augmentation of cytotoxic activity against MCF-7 (P0.05), while IFN-alpha suppressed the cytotoxicity significantly (P0.05). These findings suggested that combined stimulation by IFN-gamma and IL-2 might be a reasonable treatment for breast cancer patients.

We examined the effect of OK-432 on induction of cytotoxic T lymphocytes (CTL) directed against autologous tumor cells (ATC) and lymphokine-activated killer (LAK) cells from mononuclear cells separated from regional lymph node cells (RLMNCs) of 49 lung cancer patients. We also examined the phenotypic changes of RLMNCs during incubation with or without OK-432. Significant CTL activity and LAK activity against ATC developed from RLMNCs after stimulation with OK-432 or IL-2. Sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432 also developed significant CTL activity and LAK activity from RLMNCs. The CTL activity produced by OK-432 alone was as high as the CTL activity developed by IL-2 alone, OK-432 plus IL-2, or IL-2 plus OK-432. There was no significant difference in the CTL activities achieved by these four treatments. The proportion of CD25+ cells in RLMNCs after incubation with OK-432 was twice that before incubation. Although OK-432 increased IL-2 receptor expression on RLMNCs, it showed no synergistic effect with IL-2 in developing CTL and LAK activity. After incubation with OK-432, the proportion of HLA-DR + cells was also increased significantly. Moreover, the proportions of HLA-ABC+ and HLA-DR+ (class I and class II major histocompatibility complex antigens) cells in ATC were significantly larger than in Daudi cells. OK-432 alone could develop CTL activity against ATC from the RLMNCs of lung cancer patients that was as high as that developed by IL-2 alone or by sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432. The CTL developed from the RLMNCs of lung cancer patients may recognize class I and/or II antigens on the surface of ATC. These results indicated that treatment with OK-432 might be therapeutically useful for lung cancer patients as a CTL inducer rather than a LAK inducer.

Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility has been discussed that chemoendocrine therapy combined with endocrine agents is more effective.In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breast cancer, we ran a pilot study during the period from July 1994 to July 1996.Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2) i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10%), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response rate was 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity and hematological toxicity, but these were clinically well tolerated. No serious cardiac, liver or renal symptom was seen.Based on these results, we consider the addition of high-dose toremifene to the CAF therapy to be useful in the treatment of advanced and recurrent breast cancer.

Surgery is the first-line therapy for thymoma. Postoperative radiotherapy should be given for all invasive thymomas, followed by chemotherapy in some cases. Even if the resection is not complete, surgery is effective therapy because most thymomas are local and slow growing. Multidrug chemotherapy including cisplatin is effective against thymoma. Thymic cancer is histologically varied. Surgery is only one effective therapy for thymic cancer. Although no definitive chemotherapy regimen for thymic cancer has yet been established, we feel that the cisplatin, doxorubicin, cyclophosphamide, vincristine 4-drug combination regimen is effective in thymic cancer patients. Seminoma out of mediastinal germ cell tumor (GCT) is expected to have a good prognosis after surgery and radio-/chemotherapy. Although the prognosis for those with nonseminomatous GCT has recently improved due to chemotherapy and surgery, it is still poor.

Azatyrosine is known to convert ras, raf or c-erbB-2-transformed NIH3T3 cells to a normal phenotype. We attempted to identify the signal-transduction process triggered by oncogenic c-ErbB-2 that was inhibited by azatyrosine. Azatyrosine did not suppress activation of Ras induced by introduction of c-ErbB-2. However, it inhibited increases in phosphorylation of c-Raf-1 induced by oncogenic c-ErbB-2. Furthermore, azatyrosine inhibited activation of the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element in response to stimulation by oncogenic c-ErbB-2. These results suggest that this agent acts downstream of Ras in signal transduction from oncogenic c-ErbB-2 to nuclear factors. Moreover, we found that azatyrosine was incorporated into proteins instead of tyrosine. The simultaneous presence of a high concentration of tyrosine inhibited the conversion to a normal phenotype of transformed cells by azatyrosine. These results strongly suggest that incorporation of azatyrosine into proteins might convert the transformed cells in to cells with a normal phenotype.

Recently, it was suggested that splice variants of the surface glycoprotein CD44 (CD44v) were associated with tumor metastasis in some cancers. We examined the expression of variant forms of CD44 in 31 non-small cell lung carcinomas (NSCLCs) and in 8 normal lung tissue samples by reverse transcription-PCR (RT-PCR). CD44v3, CD44v5, CD44v6, and CD44v7 were not expressed or were weakly expressed in normal lung tissue (0 of 8). In contrast, CD44v3, CD44v5, CD44v6, or CD44v7 was expressed in 28 of 31 (90.3%) NSCLCs. Additionally, we examined the expression of CD44v6, which has been shown to be related to metastasis, in 5 normal lungs and 30 NSCLCs by RT-PCR and immunohistochemical analysis to clarify which cells express CD44v6 in NSCLC specimens. Thirty-six of 61 (59%) NSCLCs variably expressed CD44v6 by RT-PCR, and cancer cells were selectively immunostained by anti-CD44v6 antibodies in 23 of 30 (76.7%) NSCLCs. The results of immunohistochemical analysis almost correlated with those of RT-PCR. NSCLCs with lymph node metastasis expressed significantly more v6 exon than did those without lymph node metastasis [23 of 29 (79.3%) versus 13 of 32 (40.6%); P0.01]. There was a significant association between the intensity of v6 expression by RT-PCR and the frequency of cases showing lymph node metastasis (Cochran-Armitage's test, P0.002). In conclusion, this study demonstrated that in NSCLC, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC.

Total calcium is routinely measured after thyroidectomy in a clinical setting, while the measurement or calculation of the free calcium level is not generally performed. We reviewed total and free calcium levels in patients who underwent lobectomy (n = 15), subtotal thyroidectomy (n = 15) and total thyroidectomy (n = 15). Postoperative total calcium levels decreased significantly in comparison to preoperative levels in all thyroidectomies (p0.01), and this fall was significantly related to the extent of surgery (p0.01). In contrast, there was no significant difference between preoperative and postoperative free calcium levels in patients undergoing lobectomy, although we found a decrease in free calcium levels after both subtotal and total thyroidectomy. Total protein levels decreased regardless of the type of operation. Serum total calcium levels were thought to be altered by serum protein levels through the change of protein-bound calcium levels. When examined for free calcium levels, some patients were administered unnecessary calcium supplementation because hypocalcemia had been judged from the total calcium level. Since the wrong diagnosis may be given with regard to hypoparathyroidism by measurement of total calcium levels alone, we propose that free calcium levels should be routinely measured or calculated after thyroidectomy.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.

At age 35, the patient was diagnosed with left breast carcinoma (T4bN0M0, Stage IIIb) during her first pregnancy, and underwent mastectomy of the left breast and bilateral oophorectomy. Although CPA was administered as adjuvant chemotherapy after the operation, left pelvic pain developed about a year after the operation, and bone metastasis was detected from the imaging diagnosis. Then, the therapy was switched to UFT (600 mg/day) and tamoxifen (20 mg/day), which markedly relieved the pain along with bone scintiscan (NC) and simple X-P (NC). Five years have passed since the operation, and the progress is excellent. There is neither increase of pain nor adverse reactions to drugs. Furthermore, the patient received breast reconstruction operation at her strong insistence in the third year after operation, and has achieved a high quality of life (QOL).

We report a case of a 60 year-old man with an umbilical polyp composed of the aberrant pancreas and small intestinal mucosa. This is an extremely rare lesion which originates in remnants of omphalomesenteric duct and is usually diagnosed in the infant period. Microscopic examination disclosed the aberrant pancreas with exocrine glands and ducts, but no islets of Langerhans. The above findings suggested that the pancreas might have been HEINRICH II in type.

We described two patients of thyroid cancer with tracheal invasion. A 54-aged female visited our hospital with complaint of the neck pain. Echography showed a tumor in the right lobe of the thyroid. In operation the thyroid tumor invaded the trachea and right recurrent nerve. A 24-aged male visited our hospital with complaint of a mass of the left side neck. Echography showed a tumor in the left lobe of the thyroid. In operation the thyroid tumor invaded the trachea, lymph node and left recurrent nerve. In these two cases we could find thyroid tumors invaded into the trachea by echography. We re-evaluated the utility of echography.

The intraarterial arm injection of freshly isolated autologous lymphocytes to a patient with upper extremity secondary lymphedema brought about a rapid and remarkable reduction in arm swelling. The protein components in the edema fluid were analyzed by two-dimensional electrophoresis before and after lymphocyte injection. We observed the appearance of a novel protein spot, with an isoelectric point of 6.5, in an electropherogram as early as 30 minutes after the lymphocyte injection. Immunoblotting using antibody against human total serum proteins suggested that the novel protein was not derived from the serum. Because incubation in vitro of the lymphedema fluid with the isolated lymphocytes produced a new protein spot, corresponding to the novel protein observed in vivo, we suspect that the novel protein originated from limited hydrolysis of a unique protein present in the arm edema fluid. Significance of the novel protein and the role of limited proteolysis after lymphocyte injection in the management of lymphedema are examined.

Among 8 patients with spontaneous esophageal rupture, mean age was 46.5 years, and there was only one female. Vomiting after drinking was the main cause of onset. In 4 patients who underwent drainage of the thoracic cavity or initial treatment by surgery within 24 hrs after onset, closure after layer-layer suture of the site of rupture was made in two patients in whom definitive diagnosis was obtained at the first medical examination and early discharge was possible. A definitive diagnosis was obtained after drainage of the thoracic cavity in the other two patients, and esophagectomy without thoracotomy was performed on the 55th day after onset in one and the other patient received only conservative treatment without surgery, both patients were discharged. Of 4 patients who underwent treatment after 24 hrs, two patients who recovered included one who received only conservative treatment and another who underwent closure by suture of the site of rupture and covering with a pedicled omental flap 12 days after onset. The other two patients died of MOF after operation. We propose the following guidelines for treatment of this condition; In patients in whom surgical treatment is possible within 24 hrs after onset, closure by layer-layer suture of the site of rupture may be indicated. In cases in which more than 24 hrs has elapsed after rupture spontaneous closure sometimes can be expected in patients with a rupture would less than 2 cm. In patients accompanied with progressing mediastinitis or pyothorax with drainage procedure surgical treatment is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Since taxol (NSC 125975) and tiazofurin (NSC 286193) attack at two different sites in microtubular synthetic processes, we tested the rationale that the two drugs might be synergistic in human ovarian (OVCAR-5), pancreatic (PANC-1) and lung carcinoma (H-125) cells and in rat hepatoma 3924A cells. In human OVCAR-5, PANC-1, H-125 and rat 3924A cells, for taxol the anti-proliferative IC50 was 0.05, 0.06, 0.03 and 0.04 microM, respectively; for tiazofurin IC50 = 8.3, 2.3, 1.8 and 6.9 microM. Thus, the concentrations for taxol required for IC50 for inhibiting cell proliferation were 166-, 38-, 60- and 173-fold lower than those for tiazofurin. Taxol and tiazofurin proved synergistic in all four cell lines tested. The synergism of taxol with tiazofurin should have implications in the clinical treatment of human solid tumors with particular relevance to ovarian, pancreatic, lung and hepatocellular carcinomas.

We studied the incidence of thyroid nodules in healthy adults, who had no history of thyroid disease, in Tokushima, Japan, where goiter is not considered endemic. Examination was performed by palpation and using a 10-MHz real-time sonographic scanner. Palpable thyroid nodules were present in two (0.9%) of 227 men and in four (1.8%) of 224 women. On the other hand, nodules were detected by ultrasonography in 42 men (18.5%) and 47 women (21.0%). There was no significant difference in the incidence detected by ultrasonography between men and women in any of the age groups, except in men above 60 years old. It is concluded that thyroid nodules are not an uncommon disorder even in men. Since, clinically, the incidence of nodularity appears to be higher in women than in men, there may be difference between men and women in the development of nodules until they become clinically detectable.

A 54-year-old female with incomplete type of Behçet's disease was operated on because of impending rupture of the thoracic aneurysm. There was a saccular pseudoaneurysm below the left subclavian artery, and a punched out lesion of the aorta was recognized. The defect of the aortic wall was closed with a PTFE patch. Before and after the operation, we have given prednisolone. The postoperative course was uneventful. Two years later, there was no recurrence of pseudoaneurysm near the PTFE patch. In many reports, aneurysms of Behçet's disease are saccular pseudoaneurysms, and have high incidence of complications about anastomosis postoperatively. We need a further follow-up about this patient.

Left postpneumonectomy syndrome was managed by injection of sulfur hexafluoride (SF6) into the pleural space. This measure permitted irradiation of a contralateral, second primary lung cancer without resulting pulmonary fibrosis. Such use of SF6 may be an option for prophylaxis against postpneumonectomy syndrome.

To investigate the characteristics of interval breast cancer in mass screening, comparisons were made of the following three groups: interval group (21 interval breast cancer cases), mass screening group (87 breast cancer cases detected by mass screening) and outpatient group (266 breast cancer cases diagnosed at outpatient clinics). There were no differences among the three groups in terms of the case distribution by age or obesity, but significant differences in the case distribution according to nodal involvement and tumor size. Histological grading of the malignancy of the primary tumors disclosed that the incidence of breast cancer showing frequent mitoses was high in the interval group compared to the mass screening and outpatient groups. The 7-year cumulative disease-free survival rate was 75.3% in the interval group, 90.0% in the mass screening group and 83.1% in the outpatient group. The mean tumor size of the interval cases at the time of mass screening, back-calculated on the basis of the estimated tumor doubling time, was 1.5 cm in diameter, smaller than that of the mass screening group. It is surmised that interval breast cancer is characterized by marked proliferation of the tumor cells and has a poorer prognosis than the other group cases. These findings might be due to the marked proliferation of interval breast cancer rather than because of cases having been overlooked at the time of the last screening.

A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation.A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease.Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer.The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

To investigate the characteristics and the prognosis of interval breast cancer, 21 interval cases were reviewed and compared with a total of 87 patients with breast cancer detected by mass screening and 266 found in outpatient clinics on the basis of the clinicopathological features. The postoperative cumulative 7-year disease-free rates were 61.1%, 81.4% and 69.0% in the interval cases, mass screening cases and outpatient clinic cases, respectively. The percentage of cases showing frequent mitoses in cancer cells was statistically higher for interval cancer than for the other breast cancers. The average tumor size of the interval cases calculated from the speculated tumor doubling times, was 1.51 cm. It is surmised that interval breast cancer is characterized by a marked proliferation of tumor cells and has a poorer prognosis than the other breast cancers. This might be due to the marked proliferation of interval breast cancer rather than under-counting because there were no malignant findings at the time of the last screening.

Retrospective group study on post-thymectomy myasthenia gravis (post-Tm MG) was carried out. Five hundred and twenty-seven resected thymoma cases (133 cases with MG and 394 cases without MG) were collected from 9 hospitals. Post-Tmx MG occurred in 18 out of 394 cases -4.6% of thymoma without MG-, and these 18 patients with post-Tmx MG were investigated retrospectively. As to surgical procedures, the mode of operation, either thymectomy or thymo-thymectomy was not thought to be an important factor in the pathogenesis of post-Tmx MG. These 18 patients could be divided into 7 with early onset and 11 with late onset. In the early onset group, post-Tmx MG occurred within 6 months after the operation, and these 7 patients may have had subclinical MG at the time of the initial operation. In the late onset group, post-Tmx MG was noted in 5 patients when recurrence of the tumor was confirmed, the latest being 11 years after operation. The pathogenesis of post-Tmx MG could not be clarified in the other 6 patients (33.3%). For further evaluation of these 6 cases, a prospective studies with large scale are needed.

The treatment of thymoma, thymic cancer and thymic germ cell tumor was reviewed in the literature. The major treatment of thymoma is surgery with or without radiation. The chemotherapy for the thymoma is now investigated in the world. CDDP, ADM, VCR, CPA or BLM are usually used, but the most effective combination of these drugs is not known. Thymic cancer is a rarer and more malignant disease than thymoma. Though the postoperative treatment is investigated as well as thymoma, only a few successful cases by chemotherapy have been reported. Chemotherapy (PVB, VAB-6, PEB) for testicular germ cell tumor is also effective for thymic germ cell tumor including seminoma. Though the combination therapy of radiation and surgery has been popular, chemotherapy will be used more frequently for seminoma in future.

We had 3 cases of intramural cyst of the esophagus with ciliated epithelium. In Case 1, 13-year-old man, the cyst was lined with ciliated columnar epithelium and had a smooth muscle layer. In Case 2, 37-year-old female, the cyst was lined with ciliated stratified epithelium and had some layers of smooth muscle. In Case 3, 42-year-old male, the cyst was lined with ciliated columnar epithelium and had a smooth muscle layer. In all cases, cartilaginous tissue was not found. They had no complaints and the abnormal shadow was found by chance Chest X-ray film. When the cyst did not have typical diagnostic criteria, clear division into esophageal cyst or bronchogenic cyst is difficult. The bronchus and the esophagus are of the foregut origin, so we suppose the middle type cyst, between esophageal and bronchial, may exist. In Case 2, the cyst was diagnosed as esophageal, because it had some muscle layers. But in Case 1 and Case 3, as the cyst did not have typical diagnostic criteria, we diagnosed them as the inclusion cyst of the esophagus, not as esophageal, not as bronchogenic.

A 64-year-old male admitted with feeling of a foreign body at the esophagus in swallowing. Esophageal radiologic findings showed a serrated type shadow defect 6 cm in diameter at the middle thoracic esophagus. Endoscopic findings revealed a elevated type tumor at a site 32 cm from the incisor dentition. The biopsy specimens showed squamous cell carcinoma. The operation was performed with right thoracotomy, subesophagotomy, and reconstruction of gastric tube via substernum. Macroscopically, a elevated type tumor of 5.5 x 4.0 x 2.0 cm covered by normal esophageal mucosa at the periphery was recognized. Histologically, most of the tumor was adenoid cystic carcinoma differentiating to squamous cell carcinoma in the epithelium. Immunohistological stain of actin, S-100 protein indicated that the tumor may have originated from an esophageal gland. Histologic stage was mp, ly(-), v(-), n(-), stage I. Surgical curability was CIII. Postoperative irradiation for prevention of recurrence has been conducted. The patient survives without tumor at present 4 months later.

We report an immunohistochemical study of the distribution and number of interdigitating reticulum cells (IDC) and S-100 beta-positive small lymphocytes (S-100 beta + lymphocytes) in 53 thymomas and 11 thymic carcinomas. All 53 thymomas showed the presence of IDC in the tumor parenchyma. In most cases of predominantly lymphocytic and mixed-type thymoma, IDC clustered in areas, that corresponded to locations that had medullary differentiation and contained accumulated mature lymphocytes. By contrast, in most of the predominantly epithelial-type thymomas, IDC were scattered rather than forming clusters. The distribution and number of IDC were correlation with the histological type of thymoma but not with invasiveness. In thymic carcinomas, IDC were scattered in tumor nests. In 47 of the 53 thymomas (89%), infiltrating S-100 beta + lymphocytes were readily recognized. The remaining six cases without S-100 beta + lymphocytes were noninvasive thymoma. We conclude that the degree of S-100 beta + lymphocyte infiltration is correlated with the stage of thymoma and may be a marker of thymoma malignancy.

Thymoma is a low malignant, slow growing tumor and rarely metastasizes hematogenously or lymphogenously. Therefore, the local treatment by surgery or irradiation has been the main therapy for this tumor. In this paper, we reviewed the chemotherapy for thymoma in literature. Cis-platinum, doxorubicin, vincristine, cyclophosphamide and corticosteroid are mainly used by various dosages and various combinations. Papers concerning the chemotherapy for thymoma were reports of a single or a few cases. The chemotherapy is now effective for some kinds of malignant tumor. The chemotherapy for thymoma should be systematically studied.

Serum level of sex hormone-binding globulin (SHBG) was measured by immunoradiometric assay in fifty two breast cancer patients and twenty nine healthy female volunteers. The results are as follows: 1) Although the serum SHBG concentration showed no significant difference between the breast cancer group and the healthy control group, the serum SHBG concentration in postmenopause was significantly higher in the breast cancer group (63.8 +/- 31.2nmol/ml/ml; mean +/- S.D.) than in the healthy control group (40.1 +/- 15.4nmol/ml). 2) Subsequently in the postmenopausal breast cancer group, the serum SHBG concentration was significantly higher in the estrogen receptor (ER)-negative cancer group (97.8 +/- 12.7nmol/ml) than in the ER-positive cancer group (55.8 +/- 32.1nol/ml). 3) No significant relationships were showed between the serum SHBG concentration and obesity or serum estradiol concentration in postmenopausal patients. 4) The serum SHBG concentration showed significant decrease 3 months after radical operation for breast cancer in postmenopausal patients. These results suggest the possibility of the SHBG synthesis in breast cancer tissue.

Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand, in the same patients, the serum luteinizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia. The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5β-pregnane-3α,17α,20α-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian & Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.

The most important problem during FBS examination in infants is respiratory care. A new ventilation method using the channel of the FBS is proposed for respiratory care during FBS examination in infants. An FBS with a channel of more than 1.2 mm in diameter was directly inserted into the trachea under general anaesthesia without an orotracheal tube. The first step of this ventilation is the flushing of pure O2 into the lung as inspiration through the channel of the FBS. The second step is the aspiration of expiratory gas through the channel by a vacuum pump. Ventilation during the FBS examination is maintained by the repetition of these two steps by the operation of a stop-cock. Experiments in dogs, and clinical use showed that this method of respiratory care is effective and safe with certain limitations. Clinically, inspection with the FBS could be performed continuously for five minutes in most cases.

The effect of adriamycin (ADM) infused intraarterially as a preoperative procedure was analyzed retrospectively in 15 patients with primary advanced breast cancer. A high clinical response rate (CR+ PR) of 73% (11/15) was obtained by the treatment, and also remarkable degenerative changes of tumor cells were histologically noted in 10 out of 15 surgical specimens (67%). A correlation between the dose of ADM infused and the rate of tumor regression was observed. A significantly higher concentration of ADM was detected in metastatic lymph nodes and tumors obtained 3-4 weeks after intra-arterial infusion of ADM than that in normal mammary gland. As for side effects, alopecia, leukocytopenia, anorexia, nausea and vomiting occurred at high frequencies. The side effects due to this treatment were considered to be tolerable. Prognostically, a good survival rate was not observed using preoperative treatment with intra-arterial ADM infusion.

The concentration of cefotiam (CTM) in the serum and the bloodless lung with time is discussed. Five patients who were undergone pneumonectomy or lobectomy, were given 1 g of CTM intravenously during the operation. Blood samples and lung samples were collected 15, 30, 60, 90, 120, and 300 minutes after the administration. The CTM levels in the blood and the lung samples were measured by the agar well bioassay. The CTM levels in the lung samples were modified as the CTM levels in the bloodless lung by calculating the contained blood volume, as lung samples were proven to have a mean value of 34.2% of blood in weight. The serum CTM level was 73.3 micrograms/ml at 15 minutes after injection and then decreased gradually. The CTM level in bloodless lung was elevated during the first 60 minutes, became equal to that of the blood during next 30 minutes and then exceeded the serum levels thereafter. These results indicate that the distribution of CTM to the bloodless lung was excellent and a satisfactory preventative effect against postsurgical infection could be expected.

We recently encountered a tracheal schwannoma presenting as a polypoid mass. Computed tomography (CT) was very effective in evaluation of the size, shape and site of this rare tumour. Furthermore, CT images in the prone position made it easy to exclude tumour extension into the mediastinum.