Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer.

We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.

[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.

[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.

[Posterior mediastinal paraganglioma with a 60-year history; report of a case].

We report a case of a 68-year-old man with a posterior mediastinal tumor. He remembered having difficulty in food passage through his esophagus in childhood. The preoperative thoracic computed tomography (CT) revealed a 5 x 3 cm mass with strong enhancement in the posterior mediastinum. A right thoracotomy was performed to resect this indeterminate mass. Complete resection was achieved. The pathologic diagnosis was paraganglioma. Postoperatively, he experienced more comfortable food passage through his esophagus than ever before. There has been no sign of recurrence 3 years after the operation. The tumor was clinically diagnosed as benign paraganglioma because of its long silent course.

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.

[Needle tract implantation of thymoma after transthoracic needle biopsy].

A 53-year-old man was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under ultrasonic examination. The histopathological diagnosis was thymoma and thymo-thymectomy was performed. The tumor recurred in the right anterior chest wall 10 years later. It is suggested that the thymoma tissue had been implanted in the needle tract. To our knowledge, this is the 2nd reported case of thymoma which has been implanted in the needle tract.

[Cavernostomy and simultaneous removal of fungus ball of pulmonary aspergilloma].

Between 1991 and 2000, 21 patients (16 male and 5 female) underwent 28 cavernostomies for the treatment of pulmonary aspergilloma. The median age was 59.4 years (range 37-85 years). The mean %VC was 59.6 (range 30.4-91.2), and the mean FEV 1.0 was 1.51 ml (range 0.64-2.67 ml). The mean body mass index was 17.6 (range 12.7-23.2). The most common complaint was hemoptysis. The underlying lung disease was tuberculosis in 17 cases, atypical mycobacteriosis in 2, and unclassified in 2. All cases had been diagnosed as complex aspergilloma. The mean surgical duration was 136 minutes (range 85-203 min.) and the mean blood loss during surgery was 242 ml(range 5-810 ml). No death or major complications occurred in the postoperative course. During follow-up, 4 patients died of massive hemoptysis, cancer, respiratory failure or an unknown cause. Relapses of aspergilloma occurred in 9 patients (42.9%). Recavernostomy was performed safely on 5 patients. In conclusion, although the relapse rate of aspergilloma was high after cavernostomy, safe reoperations were performed. Cavernostomy is thus an effective treatment in high-risk patients.

Expression and prognostic significance in lung cancer of human tumor-associated antigen RCAS1.

A new monoclonal antibody (MAb), 22-1-1, acts against a novel tumor-associated antigen (Ag) strongly expressed in human uterine cervical adenocarcinomas. A cDNA encoding the Ag recognized by the 22-1-1 MAb has been isolated and called RCAS1 (receptor-binding cancer antigen expressed on SiSo cells). RCAS1 can induce growth arrest and apoptosis in RCAS1 receptor-positive cells including T cells and natural killer cells in vitro. These results suggest that RCAS1 is involved in tumor escape from the immune system. Immunohistochemical analysis revealed the relationship between RCAS1 expression and clinicopathological variables (age, sex, smoking, histology, differentiation grade, pathological T factor, N factor and stage) and the prognostic significance of RCAS1 in 66 lung-cancer patients who underwent curative operations: 33 adenocarcinomas, 24 squamous-cell carcinomas, 3 large-cell carcinomas, 4 adenosquamous carcinomas and 2 small-cell carcinomas. Median follow-up period of 64 non-small-cell carcinomas (NSCLCs) was 67.4 months. RCAS1 was expressed in 74.2% of lung cancers. RCAS1 in NSCLC cases with advanced T factor or pathological stage or in poorly differentiated adenocarcinomas was highly expressed. Furthermore, RCAS1 expression inducing apoptosis of tumor-infiltrating lymphocytes was a significant prognostic factor in NSCLC (p<0.03).

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.

Sequences of cytotoxic T-lymphocyte epitopes in the Epstein-Barr virus (EBV) nuclear antigen-3B gene in a Japanese population with or without EBV-positive lymphoid malignancies.

Latent infection antigens of EBV, including EBV nuclear antigens (EBNAs) and latent membrane proteins, are expressed in latently infected and immortalized B cells but work as target antigens for host cytotoxic T-lymphocyte (CTL) responses in an HLA class I-restricted manner. Among these latent antigens, the immunodominant CTL epitopes in EBNA3B (EBNA3B 399-408 and EBNA3B 416-424) are well characterized. Mutations and strain differences in these sequences, compared to the prototype A sequence, reduce CTL responses to latently infected B cells. These EBNA3B CTL epitopes in the normal Japanese population and in 2 lymphoid neoplasias, pyothorax-associated lymphoma (PAL) and nasal natural killer-cell lymphoma, were directly sequenced by PCR. Most EBV in peripheral blood leukocytes (PBLs) from healthy Japanese donors exhibited the prototype A sequence, with mutations in approximately 20% (3/16). The sequence of EBNA3B CTL epitopes in lymphoma tissue was obtained in 6 PAL cases, and 5 exhibited mutations or strain differences compared to the prototype A sequence. Furthermore, the EBNA3B sequence in PAL tissue was different from that in PBLs of the same patient or 1 of the sequences found in PBLs. However, the EBNA3B gene in nasal lymphoma tissues exhibited predominantly the prototype A sequence. Because PAL cells expressed EBNA3B mRNA, detected by RT-PCR, but nasal lymphoma cells did not, mutations and strain differences of the sequences of EBNA3B CTL epitopes were specific findings in EBNA3B-positive lymphomas.

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.

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.

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.

[Autopsy case of adenoid cystic carcinoma of the trachea: endobronchial treatment improves quality of life].

A 67-year-old man presented with dyspnea on exertion. Bronchoscopic examination revealed a tumor arising from the middle portion of the trachea and extending to the right main bronchus. The pathological diagnosis was adenoid cystic carcinoma. Radiotherapy and subsequent endobronchial electrocautery were performed, and elicited a partial response. In the clinical course. Dumon and Ultraflex stents were placed in the trachea asynchronically. Brachytherapy and esophageal stent placement were also performed for tumor control in the trachea and esophagus. Autopsy revealed that the tumor had invaded the trachea and esophagus, and bacterial mediastinitis was also demonstrated. Because the tumor was successfully controlled during the following 4 years and 9 months, we concluded that endobronchial therapy such as stent placement or electrocautery is useful for maintaining good quality of life.

Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.

High-resolution CT findings of diffuse bronchioloalveolar carcinoma in 38 patients.

OBJECTIVE: The purpose of this study was to analyze the high-resolution CT features of diffuse bronchioloalveolar carcinoma and determine the useful findings in differential diagnosis. MATERIALS AND METHODS: High-resolution CT scans of 38 patients with pathologically proven diffuse bronchioloalveolar carcinoma were reviewed. Sequential CT scans were obtained in 15 patients. The high-resolution CT findings were compared with those of eosinophilic pneumonia (n = 22), multiple pulmonary metastases (n = 12), and tuberculosis (bronchogenic: n = 22; miliary: n = 12). RESULTS: High-resolution CT findings of diffuse bronchioloalveolar carcinoma included ground-glass opacity (n = 29), consolidation (n = 29), nodules (n = 28), centrilobular nodules (n = 26), peripheral distribution (n = 19), and air bronchogram (n = 18). According to the major features, high-resolution CT findings of diffuse bronchioloalveolar carcinoma could be classified into three patterns: predominantly ground-glass (n = 4), consolidative (n = 22), and multinodular (n = 12). Most patients with diffuse bronchioloalveolar carcinoma had a mixture of these findings. The frequency of findings of diffuse bronchioloalveolar carcinoma on high-resolution CT was not different from that of tuberculosis, but the predominant distribution of the nodules and areas of ground-glass attenuation differed between the two. Difference in distribution between bronchioloalveolar carcinoma and bronchogenic tuberculosis included ground-glass opacity remote from the consolidation and a lower lung predominance. CONCLUSION: Although these high-resolution CT findings are not specific, the combination of consolidation and nodules and the coexistence of centrilobular nodules and remote areas of ground-glass attenuation are characteristic of diffuse bronchioloalveolar carcinoma.

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.

HLA-A alleles of patients with pyothorax-associated lymphoma: anti-Epstein-Barr virus (EBV) host immune responses during the development of EBV latent antigen-positive lymphomas.

Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV) latent antigen-positive lymphoma resembling EBV-transformed lymphoblastoid cell lines (LCLs) and develops in non-immunocompromised patients. Thus, deficient anti-viral-antigen immune responses might be involved in the development of PAL. As MHC class I-restricted cytotoxic T lymphocytes (CTLs) are the major constituent of anti-viral immune responses, the HLA allele type and its expression may affect the development of PAL. Flow-cytometric analyses of PAL cell lines and LCLs using the W6/32 monoclonal antibody revealed that expression of HLA class I varied among cell lines. Although one PAL cell line, OPL-2, exhibited low expression, an LCL and another PAL cell line, OPL-1, strongly expressed HLA class I. Among the EBV latent infection genes, EBV nuclear antigens 2, 3, 4 and 6 and latent membrane proteins can induce efficient CTL responses in combination with HLA-A2 or -A11. HLA-A alleles of PAL patients were determined using low-resolution PCR-based typing with HLA-A locus sequence-specific primer combinations. The antigen frequencies of HLA-A2 and -A11 in PAL patients were not significantly different from those in the normal Japanese population. Although HLA class I antigen should be expressed during the course of lymphomagenesis, no HLA-A alleles influenced the development of overt PALs.

[Stump curettage cytologic examination of excised tumor is more sensitive than histologic examination].

Some malignant lung tumors relapse on the cutting line in spite of a negative histologic stump. Histologic examination is limited to only few sites of excised sample. Conversely, stump curettage cytologic examination is useful to examine the whole area. We conducted a simultaneous histological and cytological study to assess the value of stump curettage cytologic examination. Forty-two staple-excised peripheral small lesions (< 3 cm in diameter) from 35 patients, aged 50 to 82 years, were assessed. Ten were subject to VATS and 32 to thoracotomy. Preoperative diagnoses were: 15 undiagnosed lesions (lung cancer: 8, benign lesion: 7), 18 lung cancers and 9 metastatic cancer. The whole area of the excised stump was curetted before observing the cross section to prevent malignant cell contamination. After that, the sample was cut vertically to staple line and pathologically examined. Thirty-eight percent (11/29) of histologically negative stumps were cytologically positive. Twenty-seven malignant lesions underwent only excision and 6 stumps were finally cytologically positive. Two of 6 cytological positive lesions relapsed at the staple site were excised at the second operation. Stump curettage cytological examination was more sensitive than histological examination to detect malignant cell contamination.