Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma.

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.

Acute hemodynamic effects of a new inotropic agent (OPC-8212) in patients with congestive heart failure.

The acute effects of OPC-8212, a newly synthesized orally effective inotropic agent, were assessed clinically. Eleven patients with moderate congestive heart failure received a single mean dose of 6.5 mg/kg body weight of the drug. Eight hours after administration, the cardiac and stroke work indexes increased by 11% (p less than 0.01) and 20% (p less than 0.005), respectively, with concomitant decreases in the diastolic pulmonary artery (25%, p less than 0.005) and right atrial pressures (33%, p less than 0.01). There were no significant changes in blood pressure or heart rate. The contractile state of the left ventricle was also assessed by the shift of the Starling curve. To construct the function curve, lower body negative pressure was used to regulate the venous return to the heart. An inotropic effect of the agent was confirmed by the shift of this function curve upward and to the left, even when an augmentation of the cardiac output was masked by the marked reduction in preload. The hemodynamic and clinical effects of OPC-8212 were encouraging and the drug appears to be promising for the treatment of congestive heart failure.

Appearance of a different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL.

A case of pyothorax-associated lymphoma (PAL) is reported. A 76-year-old Japanese man developed a lymphoma in the pleural cavity after 46 years duration of pyothorax due to pulmonary tuberculosis. The histologic diagnosis of biopsy specimen was diffuse large cell lymphoma of B cell type. The lymphoma cells contained the monoclonal Epstein-Barr virus (EBV) determined by the analysis of terminal repeat of EBV genome and expressed EBV nuclear antigen 2 and latent membrane protein 1 (LMP1). He received antineoplastic chemotherapy and was induced to complete remission (CR). After 19 months of CR, the lymphoma developed again in the thoracic wall. Histopathology and immunohistochemical phenotypes of recurrent tumor were almost the same as those of the primary tumor with the exception of a little more frequent expression of LMP1. The EBV genome in lymphoma cells was monoclonal, however, the clone was different from that of the primary tumor. After antineoplastic chemotherapy, minor EBV-positive clones in primary lymphoma might survive and develop into recurrent tumor. These results suggest that the PAL starts as poly- or oligoclonal proliferation of B lineage cells. This poly- or oligoclonality of PAL at the initial stage may suggest underlying immunosuppressive conditions in the development of PAL.

[Pulmonary suture granuloma with Aspergillus after partial resection for lung cancer; report of a case].

We reported an extremely rare case of suture granuloma using monofilament nylon. A 76-year-old female had suffered from cough for 1 month. She had undergone partial resection for pulmonary squamous cell carcinoma 2 years previously. Chest X-ray and computed tomography (CT) detected a mass shadow adjacent to the previous surgical repair, and local recurrence of carcinoma was suspected. Thoracotomy was performed. Incisional biopsy revealed no recurrence sign, therefore partial resection was performed. Histopathological study and bacterial culture resulted suture granuloma with Aspergillus. The granuloma was caused not by foreign body reaction but by transbronchial infection. This case emphasizes that suture granuloma as pseudotumor may be indistinguishable from recurrent cancer.

[Left-sided adult Bochdalek hernia with right lung cancer; report of a case].

Bochdalek hernia is a common congenital anomaly in neonatal patients with risky respiratory distress and high mortarity, but can be seen in adults. A case of left-sided adult Bochdalek hernia with right lung cancer is reported. A 71-year-old female had been performed radition therapy for lung cancer in the right lower lobe. She was admitted to our hospital due to advanced lung cancer and pneumonia. On the 7th day after admission, she felt dyspnea and abdominal distention due to herniation of the stomach through the posterolateral defect of the diaphragma into the left hemithorax. Her condition did not allow us a radical surgery of Bochdalek hernia, so that we performed a palliative surgery, that is reduction of the stomach and gastrostomy. After surgery, her respiratory distress was lightened and she came to be able to ingest. She was less uncomfortable until she died due to progression of the lung cancer.

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones.

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.

Synthesis of antimicrobial agents. 3. Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones.

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.

Surgical treatment of chronic empyema. A new one-stage operation.

The operative results in a series of 92 patients with chronic empyema were reviewed. Of these, 46 had empyema with an underlying fistula, and 46 had empyema without fistulization. Twenty-one underwent decortication, 65 were treated by our technique, and six were treated by a modification of the Eloesser technique. These techniques were employed with priority given in the order just cited. Our technique involves decortication of the visceral peel and obliteration of the dead space by collapsing of the parietal wall without rib resection. Cure was obtained with decortication alone in 20 of 21 patients. Sixty of 65 patients treated by our technique were cured without deformation of the thoracic cage. In all patients treated by the modified Eloesser technique, obliteration of the empyema cavity was achieved secondarily by thoracoplasty combined with a pedicled muscle flap. Postoperative pulmonary function studies demonstrated a significant improvement in vital capacity and forced expiratory volume in 1 second in patients treated by decortication or by our technique. With the modified Eloesser technique, in contract, pulmonary function tended to decline.

Surgical results for small cell lung cancer based on the new TNM staging system. Thoracic Surgery Study Group of Osaka University, Osaka, Japan.

BACKGROUND: Operation with combined chemotherapy has been recently recommended for very early stage of small cell lung cancer without lymph node metastasis. METHODS: A retrospective study was undertaken in 91 patients who had undergone pulmonary resection for small cell lung cancer according to the new international staging system. RESULTS: The 5-year overall probability of survival was 37.1%. The 5-year survival rate was 100% for p-stage 0, 56.1% for p-stage IA, 30.0% for p-stage IB, 57.1% for p-stage IIA, and 42.9% for p-stage IIB. In the p-stage IA-IIB patients who underwent a complete resection, the 5-year survival rate of the patients treated by operation with chemotherapy was better than that of patients treated by operation alone. In addition, the 5-year survival rate of the patients who had four or more courses of chemotherapy was 80.0%. CONCLUSIONS: These results suggest that operation should be considered for p-stage IA-IIB patients and more than four courses of combined chemotherapy might be desirable in these resectable cases.

Effects of direct percutaneous transluminal coronary angioplasty treatment of acute myocardial infarction on plasma levels of haemostatic and fibrinolytic factors.

Although thrombolytic therapy is used widely for treatment of acute myocardial infarction (AMI), thrombolysis itself increases thrombin activity and may cause reocclusion of infarct-related vessels. Direct percutaneous transluminal coronary angioplasty (PTCA) is an effective treatment for AMI; however, it is not clear what effects PTCA has on coagulation and fibrinolysis. We investigated coagulation and fibrinolytic factor concentrations before and after direct PTCA. Plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, plasmin-(alpha 2-antiplasmin complex (PAP), tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI)-1 antigen were followed in twelve patients treated with direct PTCA for AMI. Before PTCA, only TAT concentrations were significantly elevated compared to normal controls. D-dimer, TAT, PAP and PAI-1 concentrations were similar before and after PTCA. Eleven patients had no recurrent ischaemia and no restenosis on follow-up coronary angiography. These data confirm that direct PTCA is less likely than thrombolysis to affect coagulation and fibrinolysis.

Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.

We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.

Sustained inotropic effects of a new cardiotonic agent. OPC-8212 in patients with chronic heart failure.

OPC-8212, a newly synthesized noncatecholamine, nonglycosidic, orally effective inotropic agent, has been shown to exert a potent cardiotonic action in acute administration to patients with heart failure. However, its long-term effect has not yet been established. Eight patients with dilated cardiomyopathy (New York Heart Association functional class II-III) were given a single dose of 60 mg of OPC-8212 daily for 4 to 8 weeks. OPC-8212 produced symptomatic improvement in four patients. Though there were no detectable changes in arterial pressure and left ventricular end-diastolic dimension, heart rate and end-systolic dimension significantly decreased after administration of OPC-8212. Baseline fractional shortening rose significantly and depression of shortening in response to acute pressor stress (afterload mismatch) was corrected after OPC-8212. The end-systolic pressure-dimension relation was shifted to the left with a steeper slope. These findings indicate that the inotropic state was substantially enhanced by the drug. No adverse effects were observed in any patient. Thus, the drug appears to hold promise for the chronic treatment of patients with moderate congestive heart failure who are essentially asymptomatic at rest, but develop severe impairment of cardiac function in a stressed state.

Synchronous primary adenocarcinoma of the lung and leiomyosarcoma of the small intestine.

The occurrence of synchronous epithelial cancer of the lung and leiomyosarcoma of the small intestine is rare. We report here the case of a 62-year-old man with adenocarcinoma of the lung in clinical stage IIIB (T4N0M0). After two courses of chemotherapy (cisplatin, 80 mg/m2 and mitomycin C, 8 mg/m2) the patient developed symptoms of a small bowel obstruction. Palliative surgical resection was performed and a leiomyosarcoma of the small intestine was found and defined by an immunohistological study. The resection ameliorated the patient's symptoms. The patient died of disseminated adenocarcinoma 26 months following chemotherapy.

Solitary squamous papilloma of the bronchus associated with human papilloma virus type 11.

A 79-year-old female presented with persistent dry cough, and a chest radiograph showed a mass shadow in the right upper lung. Bronchoscopic examination revealed that the right main bronchus was severely obstructed by a polypoid tumor, which was diagnosed pathologically as squamous papilloma. After the failure of the attempted endobronchial snare to remove the tumor, right upper lobectomy was performed. The polymerase chain reaction (PCR) examination showed the presence of human papilloma virus type 11 DNA in the resected tumor, suggesting that this virus was the cause of this solitary squamous papilloma of the lung.

Safe pleural contraction employing a new tip for electrosurgical units. An ex vivo experiment.

BACKGROUND: Certain pulmonary lesions are treated by lung tissue contraction induced by heat administered by laser or electrosurgical unit (ES). ESs are comparatively less expensive, less complicated and more ubiquitous than a lasers but with their conventional tip carries the a risk of damaging the pleura. We developed a large ball tip (M-tip) for ES and evaluated its effect on the pleura in comparison with that of Nd:YAG laser in ex vivo lung. METHOD: We employed lobes obtained through surgical resection. Using the Nd:YAG laser, the lung was irradiated for 2 seconds at levels of 5, 10 and 20 watts (10, 20 and 40 Joules). Using the M-tip ES, the pleura received treatment at levels of 10, 20 and 40 watts for 2 seconds (20, 40 and 80 Joules) in spray coagulation mode. Upon completion of these procedures, 144 tissue specimens obtained from 24 lobes were examined under light microscopy. RESULTS: Upon the application of Nd:YAG at 20 Joules, 22 (92%) of 24 visceral pleura demonstrated amorphous degeneration. With the application of ES at 40 Joules watts, 24 (100%) samples examined demonstrated amorphous degeneration (P = 0.47). Of the samples where pleural destruction was evident (Nd:YAG; 40 Joules, ES; 80 Joules), an accompanying air leak pattern (pleural destruction associated with slight parenchymal contraction) was observed in 5 (21%) of the samples treated with Nd:YAG and in 10 (42%) of those treated with the M-tip ES (p = 0.12). CONCLUSION: The M-tip ES induced proper contraction of the pleura with relatively little destructive damage to the pleura at 40 Joules. Accordingly, it may be possible to induce pleural contraction using this new device with the same degree of safely that the Nd:YAG laser provides.

Which type of diffuse emphysema is adequately contracted by the Nd:YAG laser. An ex-vivo experiment.

Diffusely emphysematous lungs are not always effectively contracted by laser therapy; however, which type of diffuse emphysema that responds to laser therapy remains unclear. We macroscopically and histopathologically examined human lung tissue, which was resected from patients with carcinoma, after irradiation with an Nd:YAG laser. Forty-six lung lobes were irradiated with a non-contact mode Nd:YAG laser at a power setting 15 watts. Macroscopically, twenty samples of normal lungs revealed moderate contraction, fourteen samples of predominantly centrilobular diffuse emphysema showed significant contraction, and eight samples of predominantly panlobular diffuse emphysema with a slight elastic network showed slight contraction. Histopathologically, the normal lungs showed amorphous change of the collagen and severely contracted elastic fibers (amorphous degeneration) at the pleura and some parenchymal coagulation; the predominantly centrilobular diffuse emphysema showed contraction of elastic fibers and collagen (coagulative degeneration) in the pleura and adequate contraction of the elastic fibers in the parenchyma and the predominantly panlobular diffuse emphysema showed only slight coagulation of the visceral pleura and very little coagulation of the parenchyma. On ex-vivo lung, panlobular emphysema was inadequately contracted by laser therapy, due to elastic recoil. Centrilobular emphysema responded to laser treatment, due to the severe contraction of the elastic fibers.

Intrapulmonary mature teratoma.

Intrapulmonary teratoma is reported in a 22-year-old male. A chest X-ray in a physical examination showed a round shadow in the left hilum of a 22-year-old man who, on admission, reported slight malaise and a decrease in body weight. Computed tomographic scan and magnetic resonance imaging of the chest showed a heterogeneously dense cystic lesion. The preoperative diagnosis was anterior mediastinal teratoma, and the tumor was located in the anterior segment of the left upper lobe after thoracotomy. Segmentectomy of the left upper division showed a 4.0 x 3.5 cm tumor diagnosed as an intrapulmonary mature teratoma--the 27th such case reported in the English-language literature. This is, to the best of our knowledge, the first intrapulmonary teratoma involving magnetic resonance imaging.

Are superficial bullae with broad bases suitable for ablation?

Superficial bullae with broad bases are not suitable for resection, because the residual lung is too deformed to re-expand adequately when we resect them. Therefore, we believe superficial bullae with broad bases are suitable for ablation. It is not clear, however, whether ablated superficial bullae with broad bases remain contracted after treatment or not. We examined the morphologic changes of ablated superficial bullae with broad bases on chest computed tomographs. Ten patients with superficial bullae with broad bases that could be identified on computed tomograph underwent ablation using an electrocoagulator. These bullae were examined by chest computed tomograph preoperatively and again one, three and 12 months after surgery. There were no intra-operative complications. Postoperatively, the only complication was prolonged air leak (more than 7 days) in 1 (10%) patient. Pneumothorax after the operation presented in 1 (10%) patient. Morphologically, a disappearance of air space associated with bulla-wall thickness was observed in 9 (90%) of the 10 heat-ablated lesions and air space decreased in 1 (10%) lesion. Heat ablation proved to be effective in patients with SBBs. Lesions remained contracted for at least one year after the operation.

Unsuspected lung cancer accompanied by catamenial pneumothorax.

A 45-year-old nonsmoking woman with repeated coughing and dyspnea on effort was admitted to our hospital diagnosed with right-sided pneumothorax on chest X-ray. Chest computed tomography showed neither bullae nor nodules. Chest drainage failed to completely reexpand the lung, necessitating video-assisted thoracic surgery. Thoracoscopy showed pleural thickening in the apical segment without bullae or air leakage, dark-brown pigmentation of the diaphragm, and an unsuspected small nodule about 5 mm in diameter on the diaphragmatic surface of the right lower lobe. Pneumothorax was treated by mechanical abrasion of parietal pleura and upper lobe wedge resection. The lower lobe and nodule were wedge-resected using staplers. The nodule was bronchioloalveolar carcinoma of Noguchi's type B. To improve curability and check for diaphragmatic lesions, right posterolateral thoracotomy was conducted on post-video-assisted thoracic surgery day 28. Aggressive intraoperative lymph node exploration yielded no remarkable histological findings. Nonanatomical lower lobe wedge resection was done and the diaphragm with pinhole-like perforations was partially resected. The resected lung showed no cancerous tissue. Endometrial tissue was histologically confirmed in the resected diaphragm. The patient has remained asymptomatic in 14-month follow-up. This is, to our knowledge, the first lung cancer accompanied by catamenial pneumothorax.

[The role of surgery for chronic empyema of the advanced ages].

Chronic empyema, a sequelae of pulmonary tuberculosis, is now a only tuberculosis-related disease which was remained to be treated surgically. The candidates who have basically poor respiratory function are now attained advanced age. Over a 15 years period (1980-95), 22 patients 70 years of age or older underwent surgical intervention for chronic empyema at our hospital. There were 17 men and 5 women, ranging from 70 to 80 years of age (median age 75.0). They were 15.3% of all 145 surgically treated patients during same period. The empyema continued latent from 25 to 58 years (average 39.8 years). On admission they complained of productive cough (9), fever (9), hemosputam (5) and mass on the chest wall. Their Hugh-Johnes classification for dyspnea was I.: 4, II.: 6, III.: 11, IV.: 1 respectively. Their %VC ranged from 31.5 to 79.0 (average 54.8). In fifteen patients, tubercle bacilli (5), aspergillus (3) and other bacteria (9) were discovered in the empyema space. Surgical procedures consisted of 1 pneumonectomy (4.5%), 12 decortication or curettage of empyema wall (54.5%), 4 extraperiosteal air plombage (18%) and 5 other procedures (muscle or omental plombage, thoracoplasty, fenestration and others) (22.7%). There were no operative death and no lethal postoperative complication. In contrast, lethal postoperative complications such as GVIID, MOF and gastrointestinal bleeding occurred in the younger group. There were 2 cases of late respiratory failure in 70 years or older and 6 cases in younger group. Seventy-four years man who, preoperative %VC 33.0, underwent pneumonectomy died of asphyxia 6 month postoperatively. Another 74 years man who, preoperative %VC 76.1, developed respiratory failure after relapse of pulmonary tuberculosis. Four patients of younger group who developed late respiratory failure had all received thoracoplasty as a second operation. Other 2 patients, preoperative %VC 33.0 and 27.4 respectively, had undergone pneumonectomy. The risk of lethal postoperative complication or late respiratory failure were dependent mainly on preoperative respiratory function or surgical procedure selected rather than the age of patients.