Analysis of pulmonary nodules caused by nontuberculous mycobacteriosis in 101 resected cases: multi-center retrospective study.

BACKGROUND: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports. METHODS: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka. RESULTS: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence. CONCLUSIONS: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.

Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer.

To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P=0.0023). Smoking status (never smoker vs. smoker, P=0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P=0.0011), but not EGFR amplification (P=0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P=0.0125), but not correlated with prognosis (P=0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.

EGFR polymorphism of the kinase domain in Japanese lung cancer.

BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy. MATERIALS AND METHODS: We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. RESULTS: EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers. CONCLUSIONS: EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.

EGFR exon 20 insertion mutation in Japanese lung cancer.

Mutations of the epidermal growth factor receptor (EGFR) gene have been reported in non-small cell lung cancer (NSCLC), especially in female, never smoker patients with adenocarcinoma. Some common somatic mutations in EGFR, including deletion mutations in exon 19 and leucine to arginine substitution at amino acid position 858 (L858R) in exon 21, have been examined for their ability to predict sensitivity to gefitinib or erlotinib. On the other hand, previous report has shown that the insertion mutation at exon 20 is related to gefitinib resistance. We investigated the exon 20 EGFR mutation statuses in 322 surgically treated non-small cell lung cancer cases. Two hundred and five adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by direct sequences. EGFR insertion mutations at exon 20 were found from 7 of 322 (2.17%) lung cancer patients. We also detected the 18 deletion type mutations in exon 19, and 25 L858R type mutations in exon 21. There was a tendency towards higher exon 20 insertion ratio in never smoker (never smoker 4.4% versus smoker 1.3%, p=0.0996) and female (female 4.5% versus male 1.3%, p=0.0917). Two exon 20 insertion cases were treated with gefitinib and failed to response. EGFR insertion mutation in exon 20 could not be ignored from Japanese lung cancers.

Late sequelae of lobectomy for primary lung cancer: fibrobullous changes in ipsilateral residual lobes.

BACKGROUND: Late complications after lobectomy for primary lung cancer are rare. Progressive fibrobullous changes in the ipsilateral residual lobes were observed in some of the long-surviving patients after lobectomy for lung cancer. We report clinical details of this late complication. METHODS: Between 1975 and 1997, we selected 39 patients (35 males and 4 females) from a total of 1321 patients who underwent lobectomy for primary lung cancer. RESULTS: The incidence rate of this complication was 3%; this increased to 5.6% in patients who had survived for 5 years or more. A chest roentgenogram revealed fibrobullous changes on an average of 2.5 years (range 3 months-6 years) after lobectomy; these changes progressed throughout the ipsilateral lobes over several years. Ten patients (26%) required continuous oxygen therapy. The fibrobullous lungs of 21 (54%) patients were infected with nontuberculous mycobacterium, aspergillus, methicillin-resistant Staphylococcus aureus, and unidentified bacteria in 5, 4, 1, and 11 patients, respectively. Twenty-four patients died of the following causes: cancer (8, 33%), respiratory failure and chronic infections related to this complication (10, 42%), and other diseases (6, 25%). Three patients underwent successful surgical intervention for treating chronic infection of the destroyed lungs (omentopexy 1, completion pneumonectomy 2). CONCLUSIONS: Fibrobullous lung should be recognized as an important late complication that develops in lung cancer patients after lobectomy.

L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer.

Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496) and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinico-pathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers.

Right partial anomalous pulmonary venous connection found during lobectomy for coexisting lung cancer and tuberculosis: report of a case.

Herein, we report a rare case of a 59-year-old man in whom a partial anomalous pulmonary venous connection was found during an operation for coexisting lung cancer and tuberculosis. It was observed that the anomalous vein drained only from the right upper lobe into the right superior vena cava. The middle and lower pulmonary veins connected normally, and there was no atrial septal defect or any other anomalous condition. An upper lobectomy for coexisting lung cancer and tuberculosis with ligation of the partial anomalous pulmonary venous connection was successfully performed.

Total pleural covering technique for intractable pneumothorax in patient with Ehlers-Danlos syndrome.

We report a patient with vascular-type Ehlers-Danlos syndrome (vEDS) who developed pneumothorax and was treated with a total pleural covering technique (TPC). A 24-year-old man developed repeat pneumothorax with intermittent hemo-sputum. Based on unusual radiological manifestations of lung lesions and physical findings, EDS was suspected as an underlying cause of the pneumothorax. Surgical treatment was performed using a mediastinal fat pad and TPC, and no relapse was seen up to 2 years after surgery. TPC is a less invasive surgical approach for selected patients with vEDS. Accurate underlying diagnosis of vEDS and systemic evaluation of vascular complications are necessary before planning surgery.

Simple technique for reconstruction of superior vena cava and brachiocephalic vein after removal for thoracic malignancies.

A ringed polytetrafluoroethylene graft was applied to reduce clamping time for a patent major vein. In case 1, after suturing the ringed graft to the right appendage, the other end was inserted in the distal direction of the left brachiocephalic vein and secured by ligation. In case 2, to repair an extensive superior vena cava defect, the graft was wrapped with the remnant venous wall and fixed with a continuous suture. Only 5 minutes were required to reconstruct the left brachiocephalic vein and 20 minutes for the superior vena cava. Long-term graft patency was obtained without thrombosis.

Thymic carcinoma with adenoid cystic carcinomalike features with distant metastases.

Adenoid cystic carcinoma (ACC), which is a subtype of the nonpapillary adenocarcinoma of the thymus, is extremely rare. We report a patient with thymic carcinoma with ACC-like features presented with multiple bone and pulmonary metastases that underwent surgery. The present case firstly demonstrated that thymic carcinoma with ACC-like features could have metastatic potential.

Pulmonary carcinosarcoma with an osteosarcomatous component.

Pulmonary carcinosarcoma is a rare disease entity defined as a neoplasm, which has biphasic features consisting of both epithelial and sarcomatous components. It has been reported that the most frequent epithelial component is squamous cell carcinoma, while the most frequent sarcomatous component is rhabdomyosarcoma. Pulmonary carcinosarcomas with osteosarcoma components are even rarer. We report a case of a potentially curative resection for carcinosarcoma with an osteosarcoma component. Thoracic surgeons should be aware of this rare tumor when lung tumors with ossification are encountered.

Surgical results and staging of non-small cell lung cancer with interlobar pleural invasion.

The aim of this study was to compare the survival rates of non-small cell lung cancer (NSCLC) with interlobar pleural invasion (IPI) with that of patients with other T2 and T3 diseases according to the seventh TNM staging system. One thousand and one patients with pathologic T2 and T3 NSCLC (according to the seventh staging criteria) treated between 1980 and 2004 were retrospectively evaluated. Among these, 682 patients were pathologically staged as T2 without IPI (T2 group), 25 as T2 with IPI (IPI group) and 294 as T3 (T3 group). The 5-year survival rate for the T2, IPI and T3 groups were 52.0, 31.1 and 36.3%, respectively. In patients without nodal involvement, the 5-year survival rates of the T2N0, IPIN0 and T3N0 groups were 60.9, 40.0 and 45.9%, respectively. The survival rate was significantly different between the T3N0 and T2N0 groups (P < 0.001) and between the IPIN0 and T2N0 (P = 0.020) groups. There was no significant difference in the survival rate between the IPIN0 and T3N0 groups (P = 0.644). In patients without nodal involvement, the survival of NSCLC with IPI is similar to that of the T3 disease.

Polymorphisms in intron 1 of the EGFR gene in non-small cell lung cancer patients.

The epidermal growth factor receptor (EGFR) gene is highly polymorphic and its expression and activity may be affected by various polymorphisms. There have been several studies examining associations between EGFR polymorphisms and clinical outcome of lung cancer therapy; however, the underlying mechanism is largely unknown. The present study investigated EGFR polymorphism status and its correlation with clinicopathological features in Japanese non-small cell lung cancer (NSCLC) patients. We investigated 5 polymorphisms in the EGFR gene (-216G/T, -191C/A, 8227G/A, D994D and R497K) in 274 surgically-treated NSCLC patients. TaqMan single nucleotide polymorphism (SNP) genotyping assays and a PCR-based assay were used to analyze these polymorphisms. In our cohort of patients we did not find any evidence of the -191C/A polymorphism. Our results showed that the patients with the 8227GA or AA type in intron 1 had a significantly better prognosis with the anti-EGFR therapy than the patients with the GG type (p=0.0448) in terms of recurrence of lung cancer. No significant association was observed between 3 other SNPs (-216G/T, D994D and R497K) and clinicopathological features. The EGFR 8227G/A polymorphism in intron 1 may be associated with clinical outcome in NSCLC patients treated with EGFR tyrosine kinase inhibitors.

Carinoplasty with telescope anastomosis for tuberculous bronchial stenosis.

A 25-year-old women developed severe stenosis of the right main bronchus after medical treatment for pulmonary tuberculosis in the right upper lobe. She underwent a right upper sleeve lobectomy with partial excision of the right main bronchus and right side of the carina. Reconstruction was performed using telescopic anastomosis between the carina and intermediate bronchus. Her symptoms improved immediately.

Cisplatin-based chemotherapy followed by surgery for malignant nonseminomatous germ cell tumor of mediastinum: one institution's experience.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of cisplatin-based chemotherapy followed by surgery for patients with a malignant nonseminomatous germ cell tumor (NSGCT) of the mediastinum. METHODS: Ten patients with malignant NSGCTs received cisplatin-based induction chemotherapy and then underwent surgery. The clinicopathological characteristics of these 10 patients were examined retrospectively. RESULTS: A partial response to induction chemotherapy was noted in eight patients and no response in two. The induction chemotherapy was tolerated well by all the patients. Each patient underwent complete surgical resection of the residual tumor following chemotherapy. A yolk sac tumor was detected in one patient and malignant teratoma along with a yolk sac tumor in one patient postoperatively. The overall survival of the 10 patients was 67% at 60 months of follow-up. The survival rate at 60 months was poorer for the patients whose resected specimens exhibited the presence of viable cells than for those whose specimens were free of viable cells. CONCLUSION: Postchemotherapy surgical resection of the residual tumor plays an integral role in the management of patients with NSGCT. The presence of viable tumor cells in the resected specimens is associated with poor survival.

Successful video-thoracoscopic drainage for descending necrotizing mediastinitis.

Descending necrotizing mediastinitis (DNM) is a rare but severe disease with a high mortality rate. We report a case of a 77-year-old woman with DNM who was treated using video-thoracoscopic drainage and a Blake drain. She was admitted to our hospital with a 3-day history of a sore throat. Computed tomography (CT) revealed a peritonsillar abscess descending into the anterior and posterior mediastinum below the carina. She was diagnosed with DNM, and emergency surgery was performed. The mediastinal abscess was drained via video-thoracoscopy, and a 24F Blake drain was inserted into the mediastinum. Following mediastinal drainage, cervical drainage was performed for treatment of the retropharyngeal abscess. The outcome of videothoracoscopic mediastinal drainage was satisfactory, and no further invasive treatment was required. We believe that video-thoracoscopic mediastinal drainage is an effective, minimally invasive treatment for DNM with subcarinal spread. Blake drains are useful for mediastinal drainage.

EGFR R497K polymorphism is a favorable prognostic factor for advanced lung cancer.

INTRODUCTION: It has been reported that the R497K polymorphism of the epidermal growth factor receptor (EGFR) gene has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib. MATERIALS AND METHODS: We investigated the EGFR mutations and/or R497K polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of exon 13 was analyzed by PCR-RFLP method. RESULTS: EGFR mutations at kinase domain were found from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous Lys497 allele was present. No correlation existed between R497K EGFR genotype and clinico-pathological features, such as gender, smoking status, and pathological subtypes. CONCLUSIONS: EGFR mutation status was not correlated with R497KEGFR genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not correlated with disease outcome. In node-positive patients, however, R497K EGFR was significantly associated with better overall survival. This association was attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib treated NSCLC patients, the prognosis was not different between the EGFR wild type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated with favorable prognosis of advanced lung cancers and correlated with chemosensitivity.

A novel EGFR mutation D1012H and polymorphism at exon 25 in Japanese lung cancer.

INTRODUCTION: Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC). However, EGFR mutations status at C-terminal domain has not been reported in detail. MATERIALS AND METHODS: We investigated the EGFR mutation and polymorphism statuses at C-terminal domain in 398 surgically treated NSCLC cases. Two hundred and sixty-eight adenocarcinoma cases were included. The presence or absence of EGFR mutation and polymorphism was analyzed by direct sequences. RESULTS: A novel EGFR somatic mutation at exon 25 (G3034, D1012H) was found from 1 of 398 lung cancer patients. During sequencing of EGFR C-terminal domain in NSCLC, 194 EGFR polymorphism (C2982T) cases were identified at exon 25. The polymorphism statuses were not correlated with gender, smoking status (never smoker vs. smoker), pathological subtypes and EGFR mutations. The EGFR polymorphism ratio was significantly higher in younger NSCLC (< or =60, 56.8%) than in older NSCLC (>60, 45.6%, P = 0.0467). The EGFR polymorphism ratio was significantly higher in lymph node positive NSCLC (57.4%) than in lymph node negative NSCLC (44%, P = 0.0168). In 46 total gefitinib treated NSCLC patients, exon 25 polymorphism was not correlated with prognosis. CONCLUSION: EGFR mutation at C-terminal in lung cancers seemed to be extremely rare, however, this D1012H mutation might be a role in EGFR function. EGFR polymorphism at exon 25 might be correlated with progression of NSCLC.