[21-year-old man with squamous cell carcinoma of the lung].

Lung cancer among people in their twenties is rare and accounts for only 0.1-0.4% of all cases. We describe a case of squamous cell carcinoma of the lung in a 21-year-old man. The otherwise healthy patient presented with a 1 month history of cough. Chest radiography showed a well-defined round mass 5 cm in size in the right lower lobe. Computed tomography also showed a 3 cm hilar lymph node. Bronchoscopy revealed a white polypoid mass obstructing the right basal bronchus. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma of the lung. Clinical diagnosis was T2N1M0, stage IIB lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed. Lymph node metastases were proven histologically in the pretracheal, subcarinal, hilar, and intrapulmonary regions. Pathological diagnosis was T2N2M0, stage IIIA lung cancer. Endobronchial and mediastinal lymph node metastases were found 2 months after surgery. He received 3 rounds of chemotherapy with cisplatin and docetaxel and irradiation to the right hilum and mediastinum at a total dose of 60 Gy in 30 fractions. He is alive 6 months after surgery.

[Endobronchial neurinoma treated with left lower lobectomy].

Benign endobronchial tumors are rare, and among these endobronchial neurinoma is extremely rare. We describe a case of endobronchial neurinoma successfully treated with left lower lobectomy. A 58-year-old man presented with an 8-month history of cough. During this period he was repeatedly treated with antibiotics for pneumonia of the left lower lobe. Chest X-ray showed atelectasis of the left lower lobe. Computed tomography (CT) of the chest showed a mass in the left main and lower lobe bronchi. Bronchoscopy revealed the mass almost completely obstructing the left main bronchus. Although transbronchial biopsy was inconclusive and yielded necrotic tissue with Aspergillus hyphae, lung cancer was highly suspected based on clinical and radiographic findings. He underwent left lower lobectomy and was discharged 14 days after surgery in good condition. Pathological diagnosis was an endobronchial neurinoma 4 cm in size arising from the left basal bronchus. On immunohistochemical staining, the tumor was positive for S-100 protein and negative for a-smooth muscle actin. He took itraconazole at a daily dose of 200 mg orally for 6 months. He remains well 52 months after surgery without any evidence of recurrence.

[Diffuse malignant pleural mesothelioma].

Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.

[Evaluation of open window thoracostomy for chronic tuberculous empyema with broncho-pleural fistula; a retrospective analysis of 33 cases].

We report here our 13-year experience treating chronic tuberculous empyema by open window thoracostomy. The subjects were 33 patients (28 males and 5 females) with a median age of 70 (range: 56-83) years who underwent surgery between January 1990 and December 2002. Patients with a history of pulmonary resection or thoracoplasty were excluded. All patients complained of cough and purulent sputum related to the presence of bronchopleural fistula. Previous illnesses included pulmonary tuberculosis (n = 20) and tuberculous pleurisy (n = 14) treated by artificial pneumothorax (n = 1) or chemotherapy (n = 22). Median duration from the initial episode of tuberculosis to surgery was 44 (range: 1-60) years. Mycobacterium tuberculosis (n = 9), Aspergillus fumigatus (n = 6), methicillin-resistant Staphylococcus aureus (MRSA) [n = 5], and Pseudomonas aeruginosa (n = 5) were representative microorganisms isolated from empyema. Preoperative mean %VC was 48 (range: 31-74)%. Mean follow-up was 34 (range: 1-131) months. Seven patients died of empyema-related disease within 6 months postoperatively. Nine patients underwent curative surgery to close the thoracostomy, including extrapleural pneumonectomy (n = 5), muscular transposition with thoracoplasty (n = 3), and lobectomy with muscular transposition and thoracoplasty (n = 1). In 17 patients, the thoracostomy was left open throughout the observation period because of severe impairment of pulmonary function. In elderly patients with severely impairment of pulmonary function, open window thoracostomy does not control empyema well and has a high rate of mortality.

[Extrapleural completion pneumonectomy combined with chest wall resection for complex aspergilloma].

Completion pneumonectomy for complex aspergilloma remains challenging for thoracic surgeons. This pneumonectomy procedure often requires extrapleural dissection. Although extrapleural dissection is effective in preventing intraoperative contamination of the operative field, it is associated with massive bleeding. In addition, when the pleura has been severely thickened, it is difficult to conduct extrapleural dissection. We herein report 2 patients who underwent an extrapleural completion pneumonectomy combined with chest wall resection. In this technique, we avoided extrapleural dissection where dense pleural adhesions existed. Instead, we performed an en-bloc chest wall resection. This technique can decrease the amount of bleeding and prevent contamination of the operative field. It can also reduce the size of post-pneumonectomy space, and decrease the chance of post-pneumonectomy empyema and bronchial stump fistula. We advocate that extrapleural completion pneumonectomy combined with chest wall resection be considered in case that extrapleural dissection is extremely difficult.

[Metastatic lung tumor: report of two cases].

We herein report 2 cases of metastatic lung tumor. The first case was a 59-year-old female, who had undergone a left radical mastectomy for the treatment of breast cancer 18 years before. She was found to have a pulmonary nodule in the left lower lobe on the routine chest radiograph. She underwent a video-assisted thoracic surgery (VATS) partial resection of the left lower lobe. Tumor was diagnosed as a lung metastasis of the breast cancer microscopically. The second case was a 77-year-old man, who had undergone a right nephrectomy for the treatment of renal cell carcinoma. He was found to have 2 nodules in the right lung (1 in the middle lobe and the other in the lower lobe) on the follow-up computed tomography (CT) scan of the chest. He underwent VATS partial resections of the right middle and lower lobes. While the tumor in the lower lobe was diagnosed as a lung metastasis of the renal cell carcinoma, the tumor in the middle lobe turned out a primary lung cancer.

Morbidity and mortality after 94 extrapleural pneumonectomies for empyema.

BACKGROUND: Extrapleural pneumonectomy is still indicated in some patients with empyema. We examined morbidity and mortality after this high-risk operation. METHODS: Between 1979 and 1998, 94 (92 chronic, 2 postsurgical) patients with empyema underwent extrapleural pneumonectomy. There were 79 men and 15 women (mean age, 59 years). Eighty-eight patients had a history of tuberculosis, and 53 had undergone a therapeutic pneumothorax. The right side was operated on in 50 patients and left in 44. RESULTS: Operative mortality was 8.5%. Fifteen major complications (1 esophageal perforation, 9 empyemas, and 5 bronchopleural fistulas) occurred in 13 patients. Eight patients required reexploration for hemorrhage. Reexploration was a risk factor for empyema. Bronchopleural fistulas occurred only on the right side. Eighty-nine percent of the 86 operative survivors were free of empyemas at 5 years. Overall 5-year survival was 83%, and survival was better in patients without than in those with empyema. CONCLUSIONS: Extrapleural pneumonectomy for empyema has acceptable morbidity and mortality. Postoperative empyema affects prognosis. Covering a bronchial stump with muscle is recommended, especially when the operation is performed on the right side.

[A case of idiopathic subglottic stenosis successfully treated with endoscopic laser treatment].

A 24-year-old woman presented with an abnormal sound in her neck. She had no history of previous surgery, endotracheal intubation or neck trauma. She had been aware of this abnormal sound since she was 12 years old, but paid no attention to it. She had been recommended to visit a hospital for a neck examination. Stridor was heared in the neck ["coming from the throat"?]. Peak flow was markedly suppressed in pulmonary function tests, and the flow volume loop indicated upper airway stenosis. Bronchoscopy revealed subglottic tracheal stenosis, and magnetic resonance imaging showed that the cricoid cartilage was normal. Nd-YAG laser treatment was performed in Mitsui Memorial Hospital and her symptoms were improved. Biopsy of the stenotic area of the trachea showed dense fibrous tissue proliferation in the submucosa. Neither granuloma nor vasculitis was found in the biopsy specimen. No systemic disease capable of inducing tracheal stenosis was found on systemic examination. From these clinical and pathological findings, we diagnosed idiopathic subglottic stenosis.

[Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage].

From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.

Purification, cDNA cloning, and characterization of a new serpin with megakaryocyte maturation activity.

A new member of the serine protease inhibitor (serpin) superfamily with megakaryocyte maturation activity was purified, and its cDNA was cloned and characterized. The predicted amino acid sequence consisting of 380 residues was unique and was 38% identical to the serpin plasminogen activator inhibitor type 2 (PAI-2). The recombinant factor expressed in Chinese hamster ovary cells showed species-specific activity on the induction of megakaryocyte maturation in vitro. When injected into mice, the factor indeed elicited an increase in the number of platelets in plasma. The sequence alignment indicated that the factor possessed a lysine residue at the P1 position, suggesting that it might function as an inhibitor of Lys-specific proteases. Although we could not show any inhibitory activities toward several known Lys-specific proteases, we detected the activity toward protease activity present in the culture supernatant of COLO 201 cells. These results suggested that the protein might influence the maturation of megakaryocytes via action as a serpin.

A novel proteinase, glucagon-degrading enzyme, secreted by a human pancreatic cancer cell line, HPC-YO.

Sixty-four kinds of cell lines were examined as to their ability to degrade glucagon using conditioned-media obtained from their protein-free cultures. Two human tumor cell lines were shown to produce this activity, and the cell line, HPC-YO, established from a human pancreatic carcinoma was shown to produce the highest level of activity. The glucagon-degrading enzyme (GDE) was purified from HPC-YO conditioned-medium by a combination of ion-exchange, gel filtration, and hydroxylapatite column chromatographies. The purified GDE also degraded vasoactive intestinal polypeptide (VIP) and secretin, however, it did not cleave EGF, gastrin, insulin, somatostatin, substance P, neurotensin, or growth hormone. The molecular weight of GDE is 83,000, as determined on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of GDE was blocked, and the five partial amino acid sequences obtained on lysyl-endopeptidase digestion were determined to be N-L-T-E-E-Y-D-V-S-D-G-E-I-E-L-L-Y-E-K, V-E-T-Y-Y-D-L-L-F-E-K, L-Y-W-F-L-D-E-A-K, S-N-S-T-S-Y-V-K, and Y-Y-A-S-T-S-Y-D-D-T-Y-K. The same or homologous amino acid sequences have not been found in known proteins, demonstrating that GDE is a novel peptidase that degrades the secretin family: glucagon, VIP, and secretin.

Role of lipid modification on a starch-debranching enzyme, Klebsiella pullulanase: comparison of properties of lipid-modified and unmodified pullulanases.

Klebsiella pullulanase is a lipoprotein synthesized as a precursor with a signal peptide, which is processed by lipoprotein signal peptidase. To clarify the role of lipid modification of pullulanase, we purified lipid-modified wild-type and the unmodified (mutant) pullulanases and compared their properties. The Km and Vmax values of both pullulanases for pullulan were the same. The optimal pH and temperature, the stabilities over pH and temperature ranges, the specificity of substrates, and the patterns of inhibition of the lipid-modified and unmodified pullulanases were also the same. However, we found that the wild-type pullulanase formed trimers whereas the unmodified enzyme did not, and that the migrations of the two enzymes on sodium dodecyl sulphate/electrophoresis were different when the samples were applied on the gel without heating. The results presented in this paper and in previous work show that the correct processing and translocation of pullulanase in K. aerogenes require modification of lipid. However, the enzymatic properties and physical stabilities of pullulanase were not affected by the lipid modification.

Role of lipid modification on a starch-debranching enzyme, Klebsieila pullulanase: comparison of properties of lipid-modified and unmodified pullulanases.

Klebsiella pullulanase is a lipoprotein synthesized as a precursor with a signal peptide, which is processed by lipoprotein signal peptidase. To clarify the role of lipid modification of pullulanase, we purified lipid-modified wild-type and the unmodified (mutant) pullulanases and compared their properties. The Km and Vmax values of both pullulanases for pullulan were the same. The optimal pH and temperature, the stabilities over pH and temperature ranges, the specificity of substrates, and the patterns of inhibition of the lipid-modified and unmodified pullulanases were also the same. However, we found that the wild-type pullulanase formed trimers whereas the unmodified enzyme did not, and that the migrations of the two enzymes on sodium dodecyl sulphate/electrophoresis were different when the samples were applied on the gel without heating. The results presented in this paper and in previous work show that the correct processing and translocation of pullulanase in K. aerogenes require modification of lipid. However, the enzymatic properties and physical stabilities of pullulanase were not affected by the lipid modification.

Entire nucleotide sequence of the pullulanase gene of Klebsiella aerogenes W70.

We determined the entire nucleotide sequence of the Klebsiella aerogenes W70 pullulanase gene (pulA) contained on a 4.2-kilobase-pair fragment of plasmid pPB174. The amino acid composition deduced from an open reading frame of 3,288 base pairs agreed closely with that determined for the intracellular pullalanase. The precursor enzyme consisted of 1,096 amino acid residues and contained a hydrophobic N-terminal signal peptide and the consensus sequence for the bacterial prelipoprotein signal peptide cleavage site.