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Nano-sized materials are widely used in consumer products, medical devices and engineered pharmaceuticals. Advances in nanotechnology have resulted in materials smaller than the nanoscale, but the biologic safety of the sub-nanosized materials has not been fully assessed. In this study, we evaluated the toxic effects of sub-nanosized platinum particles (snPt) in the mouse liver. After intravenous administration of snPt (15 mg/kg body weight) into mice, histological analysis revealed acute hepatic injury, and biochemical analysis showed increased levels of serum markers of liver injury and inflammatory cytokines. In contrast, administration of nano-sized platinum particles did not produce these abnormalities. Furthermore, snPt induced cytotoxicity when directly applied to primary hepatocytes. These data suggest that snPt have the potential to induce hepatotoxicity. These findings provide useful information on the further development of sub-nanosized materials.

The results of clinical studies on 16 reconstruction procedure after total layer chest wall resection in 14 cases of malignant tumor of the chest wall were reported. The 14 cases consisted of two cases with recurrent primary chest wall tumor, two cases of primary breast cancer, seven cases of recurrent breast cancer, and others. The reconstruction procedure after total layer chest wall resection was conducted using only various myocutaneous flaps (eight cases using latissimus dorsi of the resected side, three cases using the abdominitis of the resected side, three cases using latissimus dorsi of the non-resected side, and two cases using a pectoralis major myocutaneous flap of the non-resected side). reconstruction only using a myocutaneous flap proved to be satisfactory for preventing early stage postoperative respiratory distress and maintaining the stability of the chest wall and respiratory function during prolonged observation. Namely, use of myocutaneous flap is the best approach of reconstruction the chest wall after total layer chest wall resection. We confirmed that reconstruction with latissimus dorsi myocutaneous free flap of the non-resected side with microvascular anastomosis of thoracodorsal vessels was useful for posterior chest wall tumors invading the latissimus dorsi muscle. Also, our results demonstrated the insertion of an omental flap under the myocutaneous flap was useful for cases with secondary chest wall infection or vascular damage caused by preoperative high dose irradiation.

A total of 26 lung cancer cases accompanied by pleural dissemination were resected between June 1977 and June 1988. Of these 16 cases were male and 10 cases were female. Their age was 34-78, and the average age was 56.7 years. The histologic type was adenocarcinoma in 23 cases, 1 was large cell carcinoma, 1 was combined adenosquamous cell carcinoma, and 1 was combined adeno-small cell carcinoma. Of these 23 adenocarcinoma cases, 15 were well differentiated, 7 were moderately differentiated, and 1 was poorly differentiated. There was no correlation between tumor size and pleural dissemination. Pleural effusion was observed in 8, 5 had bloody effusion and the other 3 had yellow effusion. Exact preoperative diagnosis and evaluation of extent was very difficult in pleural dissemination cases except for the pleural effusion cases. Concerning the operation method in these cases pleuropneumonectomy was performed in 10, pleurolobectomy in 6, and lobectomy in 10. Prognosis of cases of resected pleural dissemination was very poor. The median survival time was 16 months, The 1-year survival rate was 56.3%, the 2-year survival rate was 23.2%, the 3-year survival rate was 15.4%, and the 4-year survival rate was 7.7%. There was no 5-year survivor in lung cancer cases of this group. Malignant pleural effusion cases had a poorer prognosis, with 6 of 8 cases dying within 1 year from operation. No remarkable therapeutic effects were achieved by adjuvant chemotherapy. In the single case of preoperative hyperthermia, histological therapeutic effect (Ef 2) was recognized. These results suggest that there is no indication of operation in malignant pleural effusion cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixteen malignant tumors of soft tissue (15 cases) were treated with low voltage direct current (DC therapy) with or without systemic chemotherapy. Two platinum or stainless steel electrodes were placed in the tumor and around 10 volts of direct current was passed for 1 hour. In cases in which chemotherapy was performed, single or combined anticancer agents consisted of ADM and BLM were administered simultaneously with DC therapy by systemic route. Ten cases (11 tumors) out of 15 cases received no other local treatment. Histological examination was performed in 6 of 11 lesions, and in all lesions pathological therapeutic effects were recognized. Decrease in tumor size was observed in 9 lesions. In 2 cases the tumors disappeared completely after DC therapy only. In one case receiving DC therapy with chemotherapy, the tumor decreased dramatically and became resectable. Main complications were slight pain during treatment and slight fever after treatment, but special treatment for these complications was not necessary. Our results suggested that DC therapy with or without systemic chemotherapy was useful for local control of malignant tumors. And also if DC therapy had been performed simultaneously with chemotherapy the therapeutic effects seemed to be more emphasized than single use of these therapies.

Lung cancer is characterized by a varied histologic background and as a result has a wide range of histologic types compared to cancer of other organs. There is remarkable difference in malignancy according to histologic type, therefore a definitive diagnosis before treatment is essential to determine therapeutic strategy. Recently definitive diagnostic rates of 99% have been obtained by various diagnostic procedures. The value of surveys especially those including sputum cytology is discussed. Also laser therapy with Nd-YAG laser and/or administration of hematoporphyrin derivative plus photoradiation by an argon dye laser and tumor localization with fluorescence photoradiation by a krypton ion laser are discussed.

The nuclear DNA content in morphologically identified tumor cells was analyzed in 4-micron histologic sections from 58 patients with lung carcinoma who survived for at least five years. Thirty-three of the carcinomas were invasive squamous bronchial carcinomas and 25 were pulmonary adenocarcinomas. In all squamous carcinomas, the majority of tumor cells were found to exhibit DNA values exceeding the normal tetraploid and/or diploid region. In contrast, some of the pulmonary adenocarcinomas were found to be composed of a majority of tumor cells with DNA values in the normal diploid region. The results indicate that invasive squamous bronchial carcinomas, in general, are tumors with aneuploid DNA patterns indicative of a high malignant potential and that malignancy grading based on DNA measurements does not add any significant prognostic information to that obtained by morphologic diagnosis.

We performed several basic studies concerning lung cancer and their results were applied clinically. One was the establishment of cultured lung cancer cell strains and they were employed for sensitivity tests of anticancer agents and to study histogenesis of oat cell carcinoma and monoclonal antibody. Another study was the experimental induction of lung cancer in dogs. We succeeded in inducing canine central type lung cancer. Using epithelial cells from the various stages recognized in the carcinogenetic process. We measured DNA distribution and nuclear protein amounts, and we indicated the relationship between the carcinogenetic process and DNA pattern. Among 2,633 lung cancer cases 1,072 were resected. The 5-year survival of the latest 384 resected cases was 80.3% in stage I. The reasons for this relatively high survival rate is probably because of increased numbers of early stage central type lung cancer due to increasing sputum cytology surveys. Adjuvant therapy was performed using nocardia rubra cell wall skeleton and/or chemotherapy with CDDP. However, significantly better results were not obtained. The surgical results were discussed in 425 cases aged 70 years and over. The therapeutic results and indications of photodynamic therapy in early stage central type lung cancer were presented.

The usual surgical treatment for fungus ball type pulmonary aspergillosis is lobectomy, but in cases of aspergillosis located in a post-lobectomy space a second lobectomy is difficult because of the accompanying inflammatory process. A 53-year-old male underwent left upper lobectomy for pulmonary tuberculosis eight years ago. Six year postoperatively, he developed fungus ball type aspergillosis in the post-lobectomy space with bronchopleural fistula and recurrent hemoptysis. We performed an omental pedicle flap plombage via the post-sternal route to resect the pleural cavity fungus ball. The post operative course was uneventful and clinically the bronchopleural fistula was closed.

We reported a dumbbell type tumor of the posterior mediastinum. The patient was an asymptomatic 40-year-old male. An abnormal shadow in the right lower lung field was pointed out in a mass survey. We recognized a dumbbell type tumor in the posterior mediastinum by chest CT and MRI. The tumor invaded the intervertebral canal through the spinal foramen. It was most clearly seen by MRI myelography. Operation was performed with the patient in a prone position and with an L-shaped skin incision of the back and 11th intracostal thoracotomy and Th11 laminectomy. The dumbbell type tumor was completely removed by this operation. The pathological diagnosis was Schwannoma. The post operative course was good. The one-stage operation is useful for dumbbell type tumors of the posterior mediastinum.

The clinical efficacy of photodynamic therapy (PDT) was evaluated in cases of early-stage lung cancer. Haematoporphyrin derivative was used as a photosensitizer and an argon dye laser and excimer dye laser were used as the light sources. A total of 199 lesions in 165 patients with lung cancer were treated by PDT. Forty-five lesions in 40 patients, which had been detected only by sputum cytology, were endoscopically suggestive of early-stage lung cancer. All patients showed normal chest X-ray findings. Thirty lesions in 26 patients were treated by PDT only, with or without other conservative treatment because of poor pulmonary function or for other reasons. All lesions initially showed complete remission. Recurrences were seen in three cases. Nine patients died of unrelated causes and one patient died after a recurrence. The other 16 patients are alive and apparently free of the disease. Fifteen lesions were treated surgically after PDT because the effectiveness of PDT was uncertain. Among these, five lesions showed complete remission histologically. Three of the PDT-only patients have now survived for more than five years. The longest surviving patient has gone eight years without apparent recurrence.

Photodynamic therapy (PDT) using hematoporphyrin derivative (HpD) was performed in 100 cases with lung cancer. The efficacy and limitation of this therapy were evaluated in this paper. Of these 19 cases were early stage lung cancer (Ia) and there were 16 stage I, 11 stage II, 38 stage III and 16 stage IV. The indications of PDT to obtain complete cure should be limited to cases of early stage lung cancer satisfying the following conditions. The focus should be visible endoscopically. Submucosal tumor invasion should be limited to within the bronchial cartilage. The dose of HpD should be more than 2.5 mg/kg body weight but less than 5mg. The light dose should be more than 180 Joules/cm2 in cases of superficial tumor. In advanced lung cancer cases, PDT was effective to treat the local lesion for the improvement of performance status. Combination PDT with surgery made it possible to increase the indications of surgery or reduce the extent of resection area in some cases.

Direct current therapy (DC therapy), consisting of the application of electric current directly to the lesion, with chemotherapy using BLM was performed in 4 advanced inoperable lung cancer patients in whom chemotherapy and radiotherapy were not effective or could not be performed. Fluoroscopically two electrodes were inserted percutaneously into the tumor under local anesthesia. The distance between the two electrodes was about 3-4 cm. About 10 volts of direct current for 1 hour (totally over 40 coulombs) was passed between them using a DC treatment processor model 85 (Inter Nova Co., Ltd.), and simultaneously 15-30 mg of BLM was administered intravenously according to the general condition of the patient. The histologic type was adenocarcinoma in 3 cases and there was 1 large cell carcinoma. This treatment was performed once in 3 cases and twice in another. A reduction of tumor size was recognized in 3 cases (2 adenocarcinomas and 1 large cell carcinoma). In another adenocarcinoma case it was not measurable in size because of infiltrative shadow but histologically tumor destruction was recognized within a short period after DC therapy. The complications were mainly slight fever and light pain during the procedure. There was one small amount of hemoptysis and one pneumothorax but it was not necessary to perform special treatment for these complications. DC therapy with chemotherapy is based on our basic experimental experience that some anticancer agents accumulate around the electrodes in lung tissue when direct current is passed. In addition, current itself has cytocidal effects in some cases. Our clinical experience suggested the usefulness of this therapy to treat lung cancer lesions locally.(ABSTRACT TRUNCATED AT 250 WORDS)

A murine monoclonal antibody designated 1G12 has been produced by immunizing mice with A549 human lung adenocarcinoma. Using radiolabeled monoclonal antibody 1G12, a sensitive radioimmunoassay to detect 1G12 antigen has been developed. The antigen was detected on the surface of peripheral blood mononuclear cells (PBMC). A study was performed to examine the frequency of distribution of this antigen on the surface of PBMC from healthy donors and patients with cancer. An antigen level of above 30 units per 1 x 10(6) PBMC was considered positive. None of 41 healthy donors (0%) and 16 of 96 patients (16.7%) with benign diseases of the lung, ovary, and uterus were positive. In contrast, 27 of 41 patients (65.8%) with lung cancer, 14 of 18 patients (77.8%) with ovarian cancer, and 16 of 27 patients (59.2%) with uterine cervical cancer had elevated levels of 1G12 antigen. When patients were grouped by stages of cancer, PBMC from patients in relatively early stages (stages I and II) also gave positive results, i.e., 9 of 17 patients (59.2%) with lung cancer, 6 of 10 patients (60%) with ovarian cancer, and 11 of 22 patients (50%) with uterine cervical cancer of these stages were positive. These results suggest that the detection of 1G12 antigen on PBMC of patients may be useful for early diagnosis of cancers.

Clinical studies have been conducted on BRL 28500 (a formulation containing 15 parts ticarcillin (TIPC) plus 1 part clavulanic acid (CVA]. BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with intraperitoneal infections or biliary tract infections. Drug concentrations in the ascites were determined. A total of 76 cases was treated with BRL 28500. These cases included 49 intraperitoneal infections (suppurative peritonitis 29, postoperative peritonitis 20) and 18 biliary tract infections (cholecystitis 5, cholangitis 13). Nine cases were excluded from evaluation according to the committee's assessment. The clinical improvement as assessed by surgeons in charge increased with the duration of continued treatment and efficacies were assessed as 57.1% on day 5, 63.1% on day 7 and 77.8% on day 10 in intraperitoneal infections. Corresponding results in biliary tract infections were 38.9%, 40.0% and 42.9%, respectively. From these results, it is clear that the degree of improvement is related to the duration of treatment. The clinical usefulness as assessed by surgeons in charge of the study was 63.8% in intraperitoneal infections (suppurative peritonitis 75.0%, postoperative peritonitis 47.4%) and 58.8% in biliary tract infections (cholecystitis 100%, cholangitis 41.7%). The overall rate of usefulness was 62.5%. The clinical efficacy rates as assessed by the committee were 81.6% in intraperitoneal infections (suppurative peritonitis 93.1%, postoperative peritonitis 65.0%) and 66.7% in biliary tract infections (cholecystitis 100%, cholangitis 53.8%). In cases where causative organisms were isolated, the efficacies were 92.9% in suppurative peritonitis, 58.8% in postoperative peritonitis, 50.0% in cholangitis and overall, 69.2%. In cases from which TIPC-resistant organisms were isolated, the overall efficacy rate was 65.4% (suppurative peritonitis 88.9%, postoperative peritonitis 58.3% and cholangitis 40.0%). Regarding bacteriological effect as assessed by the committee, the eradication rate was 76.9% in intraperitoneal infections and 40.0% in biliary tract infections (71.0% overall). In cases from whom ticarcillin-resistant organisms were isolated the corresponding rates were 68.4% and 33.3% respectively, (63.6% overall). In 4 patients with peritonitis drug levels in the ascites were determined following administration of BRL 28500 by drip infusion. Good levels of both TIPC and CVA were detected 1 to 3.5 hours after administration.(ABSTRACT TRUNCATED AT 400 WORDS)