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Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence.This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008.Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR.At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

Owing to the advent of effective drugs for tuberculosis in the mid-twentieth century, few cases require surgery for active tuberculosis in the present day in areas where effective drugs are available. However, surgical techniques developed to combat tuberculosis in the predrug era are still useful to manage the challenging chest pathology of our time surgically, such as destroyed lung or postresectional empyema. Thoracoplasty and open window thoracostomy are representative procedures and discussed in detail in this review.

Clofazimine (CFZ) is used to treat pulmonary non-tuberculous mycobacterial (NTM) infection; however, its pharmacokinetics remain unexplored in patients with pulmonary NTM, and the relationship between CFZ serum concentration and adverse effects has not been investigated. The objectives of this study were to characterize the pharmacokinetics of CFZ in pulmonary NTM disease treatment and to investigate the relationship between the steady-state CFZ serum concentration and adverse effects. A prospective observational study was conducted on 45 patients with pulmonary NTM treated with CFZ (UMIN000041053). A maximum of five serum samples per patient were taken at the CFZ trough, and serum concentration was measured using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetics of CFZ were analyzed using a nonlinear mixed effect model. The relationships among steady-state CFZ serum concentration and adverse effects, pigmentation, and heart rate-corrected QT (QTc) interval were investigated. Twenty-six patients had M. avium or M. intracellulare infection and nineteen had M. abscessus infection. The primary CFZ dosage was 50 mg/day. The estimated apparent CFZ clearance, apparent volume of distribution, and half-life were 2.4 L/h, 2,960 L, and 36 days, respectively. The combined use of rifampicin and CFZ significantly reduced CFZ exposure by 22%. Although there was no relationship between CFZ serum concentration and pigmentation intensity, the QTc interval was significantly correlated with CFZ serum concentration. The estimation of accurate pharmacokinetics for CFZ required approximately 5 months of monitoring. The relationship between the serum concentration and specific adverse effects of CFZ confirmed that CFZ serum concentration was not associated with pigmentation but did affect the QTc interval.

The incidence of nontuberculous mycobacterial lung disease (NTMLD) is increasing worldwide, the number of lung surgeries is increasing accordingly. The disease is progressive and is characterized by exertional intolerance, respiratory dysfunctions, and impaired health-related quality of life (HRQOL). Treatment comprises multidrug antibiotic treatment combined with lung resection. The incremental shuttle walk distance (ISWD) is a standard tool for assessing the patients' tolerance to lung resection. The exertional tolerance, physical functions and HRQOL among pre-surgical patients with NTMLD are clinically important, but not fully studied yet from the viewpoint of physiotherapy. The purpose of this study was to explore the clinical significance of ISWD for assessing the exercise capacity of pre-surgical patients with NTMLD. For peripheral muscle evaluation, the strength of the quadriceps femoris muscle was measured. HRQOL was evaluated using scores of the St. George's Respiratory Questionnaire (SGRQ). Thirty-three patients (mean age 54.9 ± 13 years) were enrolled. The mean ISWD was 505 ± 134 m, shorter than the reference values (ISWD %predicted: 96 ± 27%). Regression analysis showed significant associations between ISWD and percent-predicted vital capacity (r = 0.38, p = 0.03) and percent quadriceps force/body weight (r = 0.54, p = 0.001). HRQOL assessed by SGRQ scores was correlated with ISWD (r < -0.4, p < 0.05). Multiple regression analysis showed that ISWD was significantly associated with leg muscle strength and with HRQOL. In conclusion, ISWD is useful to evaluate the exercise capacity among pre-surgical patients with NTMLD, The Tohoku journal of experimental medicine, 250(1), pp.43-48; 2020

Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes.Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage.Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07).An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Two types of re-operations for inflammatory lung diseases are presented:thoracoplasty and cavernostomy. Thoracoplasty is used to obliterate a residual pleural space after upper lung resection with prolonged air leak. Usually, the 2nd to the 6th ribs are resected, according to the extent of the space. Posteriorly the ribs should be removed to the costotransverse joint to achieve sufficient space obliteration. The tip of the scapula is resected in case of the resection of the 6th rib, otherwise the scapula would impinge on the 7th rib. The resection of the 1st rib should be avoided because of a subsequent severe scoliosis. Cavernostomy is a procedure to open the infected cavity of the residual lung. Aspergillus and non-tuberculous mycobacteria are the most frequent pathogens. The site of skin incision depends on the location of the cavity:midaxially incision for an anterior cavity and paravertebral incision for a posterior cavity. Cutting "septum" in the cavity makes it a single space, contributing to sufficient drainage by gauze. The closure of the cavity will be considered after several months or years when the cavity is sterilized and the patient's nutritional status becomes well. These 2 procedures are effective in treating refractory lung inflammation after lung resection, although they are quite traditional.

Purpose: To investigate the exercise capacity and health-related quality of life (HRQOL) of surgical patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) preoperatively versus 6 months postoperatively. Methods: This prospective observational study included patients with NTM-PD and was conducted at a single center. The intervention was surgical resection plus perioperative and post-discharge physical therapy. The physical function was assessed preoperatively and 6 months postoperatively using the 6-minute walk test (6MWT). HRQOL was assessed preoperatively and 6 months postoperatively using the Short-Form 36 (SF-36) health survey questionnaire and St. George’s Respiratory Questionnaire. The postoperative HRQOL was compared between patients with and without preoperative clinical symptoms. Results: In total, 35 patients were analyzed. The preoperatively symptomatic group had significantly lower preoperative HRQOL than the preoperatively asymptomatic group (p, Annals of Thoracic and Cardiovascular Surgery, 28(2), pp. 103-110; 2022

Background Mycobacterium abscessus complex pulmonary disease is notoriously difficult to treat by medication alone. We report our experience with resectional surgery combined with preoperative and postoperative multidrug chemotherapy for the treatment of patients with M. abscessus complex pulmonary disease. Methods This is a retrospective review of 33 patients undergoing lung resection for M. abscessus complex pulmonary disease at a single center in Japan between January 2008 and December 2019. Results The median age of patients was 54.0 (interquartile range [IQR], 49.0-66.0) years; 27 (81.8%) were female. Nodular-bronchiectatic was the most common disease type (n = 24, 72.7%). Disease was limited in 18 (54.5%) patients and extensive in 15 (45.5%). The median duration of preoperative multidrug chemotherapy employing oral and parenteral antibiotics was 10.0 (IQR, 3.0-18.0) months. A total of 34 anatomical lung resections were performed as follows: 22 lobectomies, 5 segmentectomies, 4 combined resections, 2 bilobectomies, and 1 pneumonectomy. No operative mortalities and 4 (13.3%) morbidities occurred. The median duration of multidrug chemotherapy after the surgery was 18.0 (IQR, 12.0-31.0) months. Postoperative sputum-negative status was achieved in 31 (93.9%) patients; all 23 patients obtaining preoperative negative conversion remained negative, and 8 (80.0%) of 10 patients with preoperative positive sputum became negative postoperatively. Recurrence was observed in 2 (6.5%) patients. The recurrence-free probabilities were 96.3%, 96.3%, and 80.2% at 1 year, 3 years, and 5 years, respectively. Conclusions Combined with preoperative and postoperative multidrug chemotherapy, resectional surgery can be performed safely and achieve favorable outcomes for patients with M. abscessus complex pulmonary disease.

The clinical importance of Mycobacterium abscessus subsp. abscessus (M. abscessus) lung disease has been increasing, but few studies have assessed the clinical characteristics associated with the treatment outcome. We retrospectively analyzed 75 consecutive patients with M. abscessus lung disease diagnosed at a tertiary hospital from January 2004 to April 2018. Among 52 patients with sufficient clinical data, 19 patients (42.2%) achieved treatment success. Compared with 26 (57.8%) patients in the treatment failure group, body mass index (BMI) (19.8 vs 17.5 kg/m2, P = 0.022), previous nontuberculous mycobacterial (NTM) lung disease (26.3% vs 61.5%, P = 0.034), the presence of cavitary lesions (31.6% vs 69.2%, P = 0.017), and the bronchiectasis score (3.0 vs 5.0, P = 0.003) were significantly different in the treatment success group. Multivariate analysis showed that age (adjusted hazard ratio (aHR), 0.94; 95% confidence interval (CI), 0.90 to 0.99; P = 0.010), the presence of cavitary lesions (aHR, 0.34; 95% CI, 0.12 to 0.94; P = 0.039), and previous NTM lung disease (aHR, 0.28; 95% CI, 0.09 to 0.86; P = 0.026) were negatively associated with treatment success. This is the first study to show that previous NTM lung disease might be a clinically important factor related to unfavorable treatment outcomes in M. abscessus lung disease patients. To increase our understanding the characteristics of M. abscessus lung disease, this factor should be independently analyzed in future research.

Objectives Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. Methods This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. Results The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Conclusions Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era.

Linezolid (LZD) is classified as a WHO group 5 drug used in the treatment of tuberculosis (TB). Although its efficacy and long-term safety have not yet been established, it is being increasingly used in the treatment of multidrug resistant tuberculosis (MDR-TB) and extensive multidrug-resistant tuberculosis (XDR-TB). The current study is a single-center retrospective clinical analysis of hospitalized M/XDR-TB patients in Fukujuji Hospital involving 26 patients (18 men and 8 women) consecutively treated with combinations of anti-TB drugs including LZD from 2009 to 2015. The sputum culture results were negative after using LZD for an average period of 28.0 ± 12.0 (average ± SD) days. LZD was reduced or withdrawn in 11 cases due to adverse effects. Nineteen cases including 3 XDR-TB patients were operated on, and their TB was treated following surgery. The average time from the initiation of LZD therapy to surgery was 87.6 ± 38.7 (average ± SD) days. Favorable clinical outcome was maintained in 23 surviving patients, while 3 patients died during treatment because of end stage cancer and aspiration pneumonia. Our study showed that LZD might be clinically effective in the treatment of M/XDR-TB patients in Japan.

Background Successful surgical treatment of patients with Mycobacterium avium complex pulmonary disease is thought to require complete removal of parenchymal destructive lesions. This study aimed to evaluate the short-term and long-term outcomes and the predictors of microbiological recurrence after surgery for M avium complex pulmonary disease. Methods We conducted a retrospective review of 184 patients undergoing unilateral lung resection for M avium complex pulmonary disease at a single center in Japan between January 2008 and December 2017. Results Median age of the 184 patients was 55.5 years; 133 were female (72.3%). All but 2 patients had anatomical lung resection. A total of 116 patients had limited disease and underwent complete resection (63.0%); the remaining 68 patients had extensive disease and underwent debulking surgery (37.0%). No operative mortalities occurred. In 18 of 184 patients, 21 morbidities occurred (9.8%), including 3 bronchopleural fistulas (1.6%). Postoperative sputum-negative status was achieved in 183 patients (99.5%). Microbiological recurrences occurred in 15 patients (8.2%). By multivariate analysis, extensive disease was an independent risk factor for recurrence (hazard ratio, 5.432; 95% confidence interval, 1.372-21.50; P = .016). Recurrence-free rates were significantly higher in patients with limited disease compared with those with extensive disease (99.0%, 97.4%, and 95.0% versus 93.0%, 89.2%, and 75.1% at 1, 3, and 5 years, respectively; P Conclusions Complete resection of parenchymal destructive lesions can achieve excellent microbiological control for patients with limited M avium complex pulmonary disease. The efficacy of debulking surgery in patients with extensive disease needs further investigation.

Nontuberculous mycobacteriosis (NTM) has been increasing recently. The treatment of choice of NTM is chemotherapy. Surgical treatment is sometimes indicated for patients with refractory NTM. When NTM lesion is enlarging despite of chemotherapy, there are 2 possibilities:intractable NTM and co-existing lung cancer. A 67-year-old male had been treated for fibro-cavitary NTM in the right upper lobe with chemotherapy. The cavitary lesion, however, was growing in spite of 6 months treatment. We suspected of a co-existing lung cancer because SCC level and standardized uptake value (SUV) in positron emission tomography (PET)-computed tomography (CT) were high. Bronchoscopy was performed but revealed no malignancy. He underwent a right upper lobectomy and the intraoperative pathology indicated NTM with no malignancy. After the operation, SCC levels decreased. This is a rare case with preoperative high SCC level which seemed to be related to NTM lesion.

A symposium entitled "Legacies of surgery for tuberculosis and succession to the next generation" was held at the 89th annual meeting of The Japanese Society for Tuberculosis in Gifu. The purpose of the symposium was to look back at the history of surgery for tuberculosis and development of surgical techniques. The contribution of those techniques to the next generation was also discussed. Many unique and universal techniques such as segmentectomy, thoracoplasty, muscle flap plombage, greater omental plom- bage, open window thoracotomy, cavernostomy, and decortication have matured during a long history. Based on the development of antituberculous drugs, surgery seems to have a less important role. However, surgical techniques are still required for multi-drug resistant tuberculosis and non- tuberculous mycobacteriosis. Core techniques are apjlied in the surgery for many thoracic diseases, such as lung cancer, mycosis, pyothorax, and mesothelioma. This manuscript summarizes the presentations.

The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB).This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB.The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital.Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC.Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

The incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, while that of tuberculosis (TB) is decreasing in many industrialized countries, including Japan. However, the long-term evaluation of clinico-epidemiological features of NTM-PD in relation to TB are limited. We aimed to clarify the long-term changes in the epidemiology and clinical features of NTM-PD in relation to those of TB at a nationally-designated TB center in Japan.We reviewed all mycobacterial examination records at Fukujuji Hospital between 2006 and 2016. Cases of NTM-PD were defined according to the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. The current characteristics of Mycobacterium avium complex pulmonary disease (MAC-PD) were compared with those in the 1980s and circa 2000.We identified a total of 3,546 pulmonary TB cases and 2,155 NTM-PD cases. While the annual number of incident pulmonary TB cases remained stable over the study period (P = 0.59), that of NTM-PD cases increased significantly from 165 to 278 (P 0.01). The mean age of pulmonary TB cases increased from 59.7 ± 16.3 to 66.2 ± 21.7 years, whereas that of NTM-PD cases remained unchanged. Regarding the age distribution, the greatest increases were observed in patients over 75 years for TB and in patients 50-74 years for NTM. The most common causative organism for NTM was Mycobacterium avium complex (87.3%), M. abscessus complex (5.5%) and M. kansasii (3.9%). Among patients with MAC-PD, the proportion of the nodular bronchiectatic (NB) form increased significantly from 60.0% to 84.4% between circa 2000 and 2016 (P 0.01). Significant increases in the NB form were observed in both males (33.3%-70.7%, P 0.01) and females (71.3%-89.2%, P 0.01).The annual number of incident NTM-PD cases increased markedly. In contrast to patients with TB, the mean age of new NTM-PD patients did not increase in the last 10 years. Among MAC-PD patients, the proportions accounted for by the NB form increased significantly in both sexes.

BACKGROUND Although Mycobacterium gordonae isolation from respiratory samples is usually regarded as contamination, M. gordonae can cause definite pulmonary disease. The establishment of a standard diagnostic criteria of pulmonary disease that is caused by this low virulence mycobacterium is obviously necessary. METHODS We performed clinical research on over 200 cases in which M. gordonae was isolated over an 8-year period, focusing on the M. gordonae subtype. Sequence analysis of rpoB was performed to identify the genotypes. RESULTS A total of 287 respiratory samples (209 cases) were positive for M. gordonae. Twenty-seven cases (12.9%) had a positive culture more than twice and 11 of these cases (5.3%) had more than three positive cultures. Ultimately, three cases (1.4%) were newly diagnosed as M. gordonae pulmonary disease using our own diagnostic criteria. In all of the identified M. gordonae cases, the cultures tested positive with a Mycobacteria Growth Indicator Tube test at 24 days; however, in patients with definitive pulmonary disease, the cultures were positive at 9 days. A subtype analysis revealed that all of the definitive disease cases had subtype C. CONCLUSION The time taken to detect a positive culture and subtype of the isolates could be used as the diagnostic criteria for definite M. gordonae pulmonary disease.

OBJECTIVE Body weight loss in patients with Mycobacterium avium complex (MAC) pulmonary disease can be fatal. The administration of nutritional supplements should be an important component in the treatment of this disease. Objective data regarding the association between the nutritional status and disease severity have not been reported. This cross-sectional study aimed to compare the nutritional status and radiological severity scores in MAC pulmonary disease patients. METHODS We retrospectively reviewed the records of 40 patients who were admitted to our institution for the treatment of MAC pulmonary disease between July 2008 and July 2010. Nutritional indices, including the ideal body weight ratio, triceps skinfold, mid-upper arm muscle circumference, and percentage of predicted resting energy expenditure, were compared with the radiological severity scores. Quantitative values of the extent of nodules, infiltration shadows, cavities, and bronchiectasis on the computed tomography scans were used to evaluate the radiological severity scores. RESULTS The patients suffered from a significantly decreased percentage of ideal body weight, body fat and muscle mass. The average radiological score was 17.6±8.4 points. The percentage of ideal body weight (p

Background According to the 2007 American Thoracic Society/Infectious Diseases Society of America statement on nontuberculous mycobacterial diseases, more evidence for the benefits of adjuvant nontuberculous mycobacterial lung disease surgical intervention is needed before its wide application can be recommended. Methods A retrospective review was conducted of 60 consecutive patients who met American Thoracic Society/Infectious Diseases Society of America diagnostic criteria and underwent pulmonary resection for localized nontuberculous mycobacterial lung disease between January 2007 and December 2011. All patients were receiving chemotherapy before resection. Results Included were 41 women (68%) and 19 men (32%), with a median age of 50 years (range, 20 to 72 years). Of these, 55 patients (92%) had Mycobacterium avium complex disease. Bronchiectatic disease was noted in 29 patients, cavitary disease in 25, both in 4, and nodular disease in 2. The indications for resection were a poor response to drug therapy in 52 patients, hemoptysis in 6, and a secondary infection in 2. Sixty-five pulmonary resections were performed: 1 pneumonectomy, 3 bilobectomies, 39 lobectomies, 17 segmentectomies, 3 lobectomies plus segmentectomies, and 2 wedge resections. There were no operative deaths, and all patients attained sputum-negative status postoperatively. Eleven postoperative complications occurred in 8 patients (12%); relapse was observed in only 2 (3%). Conclusions Pulmonary resection combined with chemotherapy is safe, with favorable treatment outcomes, for patients with localized nontuberculous mycobacterial lung disease. Our results support the liberal use of operations for nontuberculous mycobacterial lung disease whenever indicated.

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases.

Aim: Small dense (sd)-low-density lipoprotein (LDL) is a potent atherogenic lipoprotein. The overall atherogenicity of this lipoprotein can be precisely assessed by quantifying sd-LDL rather than by measuring the LDL size. We studied the effects of representative lipid-lowering agents (statin and fibrate) on sd-LDL-cholesterol (C) in patients with type 2 diabetes. Methods: Sd-LDL-C was measured by the precipitation method established by Hirano and Ito. Large buoyant (lb)-LDL-C was calculated by subtracting sd-LDL-C from LDL-C. Type 2 diabetes patients (n=72) were administered lipid-lowering agents for three months: patients with hypercholesterolemia received 1 mg of pitavastatin and those with hypertriglyceridemia received 100 mg of micronized fenofibrate. Results: Pitavastatin reduced LDL-C by 25% and reduced TG by 8%. The statin decreased sd-LDL-C by 26%, and lb-LDL-C by 22%. Fenofibrate reduced TG by 38% and increased HDL-C by 14%. The fibrate decreased sd-LDL-C by 23% without changing LDL-C. The pitavastatin-induced reduction of sd-LDL-C was significantly correlated with the reduction of LDL-C and apo B, whereas the fenofibrate-induced reduction of sd-LDL-C was correlated with the reduction of TG. Conclusion: Both statin and fibrate reduce the potency of atherogenic sd-LDL particles, but via different mechanisms: the former decreases total-LDL including sd-LDL, while the latter decreases sd-LDL specifically.

Objective Multidrug-resistant tuberculosis remains a significant health problem. The best available treatment for multidrug-resistant tuberculosis is the combination of pulmonary resection and antituberculous chemotherapy. We herein report the results of pulmonary resection combined with chemotherapy for multidrug-resistant tuberculosis at our institution during the years 2000 through 2002. Methods Between 1983 and 2002, 87 patients underwent 95 pulmonary resections for multidrug-resistant tuberculosis. Of these, the 30 (34%) patients operated on from January 1, 2000, to December 31, 2002, are reviewed in the present study. All patients were maintained on multidrug regimens preoperatively and postoperatively. Indications for surgical intervention included persistently positive sputum and a high risk of relapse. Thirty-three pulmonary resections were performed, consisting of pneumonectomy (n = 12), lobectomy (n = 17), and segmentectomy (n = 4). The bronchial stump was reinforced with a latissimus dorsi muscle flap in 29 resections. Results There was no operative mortality. Bronchopleural fistulas occurred in 2 patients. Five patients had a space problem. All patients attained sputum-negative status after the operation. Relapse occurred in 3 patients: 2 had a relapse at the bronchial stump, and the remaining patient had a relapse in the postlobectomy space. One late death occurred. Of the 29 survivors, 27 (93%) were free from disease, with a median follow-up of 24 months (range, 8-47 months). Conclusions An increasing number of patients with multidrug-resistant tuberculosis are requiring resectional surgery in the 21st century. Pulmonary resection combined with chemotherapy achieves high cure rates with acceptable morbidity and remains the treatment of choice for multidrug-resistant tuberculosis.

Background Pneumonectomy is considered in the treatment of nontuberculous mycobacterial infections when an entire lung is affected. However, this procedure carries high morbidity. We report on our experience in using pneumonectomy for treating patients with nontuberculous mycobacterial infections. Methods Between 1983 and 2002, 53 patients infected with nontuberculous mycobacteria underwent 55 pulmonary resections. Of these patients, 11 (3 men, 8 women) underwent pneumonectomy (5 right, 6 left). Median age was 57 years (range, 43 to 69 years). Mycobacterium avium complex disease occurred in 10 patients and Mycobacterium abscessus disease in 1. Indications for pneumonectomy included multiple cavities in one lung and destruction of an entire lung. The bronchial stump was covered with a latissimus dorsi muscle flap in 7 patients and with an intercostal pedicle flap in 2. Results Operating time ranged from 142 to 477 minutes (median, 360 minutes). The median intraoperative blood loss was 555 mL (range, 130 to 1,245 mL). There was no operative mortality. Bronchopleural fistula occurred in 3 patients. All fistulas were observed after right pneumonectomy, and were treated by reclosure of the bronchus. Empyema occurred in 1 patient, who was treated with irrigation. All patients achieved sputum-negative status after surgery. Two late deaths occurred. One patient died of respiratory failure 11 months after surgery. A second patient, the only patient who had recurrent disease, died of respiratory failure 4 years postoperatively. Conclusions Despite bronchial stump protection, right pneumonectomy carries a risk for bronchopleural fistula. Nonetheless, pneumonectomy can result in high cure rates in patients with nontuberculous mycobacterial infections.

Objective: Since the introduction of clarithromycin, it has been assumed that pulmonary Mycobacterium avium complex (MAC) disease can be treated with medication alone. This study examines whether surgery can still play an important role in the management of MAC lung disease in the current era. Methods: Between April 1993 and January 2001, 21 patients (11 men and 10 women) underwent a pulmonary resection for MAC infection. The median age of the patients was 56 years (range: 27–67 years). None of the patients were immunocompromised. Regimens employing clarithromycin were initiated preoperatively in all patients. The indications for surgery were failure of drug therapy in 19 patients and discontinuation of chemotherapy because of drug toxicity in two patients. The pulmonary resections (19 right lung, 2 left lung) performed included lobectomy in 16 patients, pneumonectomy in three, bilobectomy in one, and lobectomy plus segmentectomy in one. Results: All of the patients survived the surgery. Six major postoperative complications occurred in six patients (28.6%) and these included two bronchopleural fistulas after right pneumonectomy, two space problems, one prolonged air leak, and one case of interstitial pneumonia. All postoperative complications were manageable, and four of these were treated surgically. All patients had sputum-negative status after their operation. Relapse occurred in two patients (9.5%) at six months and two years postoperative, respectively. The first patient, who originally had a right upper lobectomy, underwent a left upper lobectomy during the follow-up period, attaining sputum conversion. The second patient underwent a right pneumonectomy and then died of respiratory failure four years postoperatively. This one late death was the only fatality. Conclusions: Although it is associated with relatively high morbidity, surgery provides a high sputum conversion rate for patients whose MAC disease responds poorly to drug therapy. Even in the present clarithromycin era, pulmonary resection remains the treatment of choice when MAC lung disease has not been successfully eradicated by drug treatment alone. q 2002 Elsevier Science B.V. All rights reserved.

OBJECTIVE To present the long-term outcome of multidrug-resistant tuberculosis (MDR TB) patients. METHODS An observational study of 291 MDR TB cases that were diagnosed from 1990 to 2011 at the Fukujuji Hospital in Japan. RESULTS The frequency of relapse after cure was 3/168 (1.8%) during a mean follow-up of 4.4 years. Among 16 failure cases, eight patients were negative in later years. One case among the nine lost-to-follow-up patients with culture conversion returned 1.5 years later with positive culture. CONCLUSIONS Chronic-positive patients remain positive for years and require observation. Lost to follow-up cases may relapse.

While the prevalence of pulmonary tuberculosis has been decreasing, the prevalence of nontuberculous mycobacterial lung disease has been increasing. Unlike tuberculosis, nontuberculous mycobacterial disease is not communicable. However, their indolent nature may result in extensive parenchymal destruction, causing respiratory failure and vulnerability to airway infection. Nontuberculous mycobacterial lung disease, therefore, has been becoming a significant health problem. According to the 2007 American Thoracic Society/Infectious Diseases Society of America statement on nontuberculous mycobacterial diseases, the primary treatment is a multidrug treatment regimen. However, its efficacy is less than satisfactory for Mycobacterium avium complex lung disease, which is the most common type of nontuberculous mycobacterial lung diseases, and for Mycobacterium abscessus lung disease, which is notoriously resistant to chemotherapeutic drugs. The statement, therefore, has proposed a multidisciplinary treatment approach for these types of nontuberculous mycobacterial lung diseases: a combination of multidrug treatment regimen and adjuvant resectional surgery. This review covers the rationale, indication, procedure, and outcome of surgical treatment of nontuberculous mycobacterial lung disease. The rationale of surgery is to prevent disease progressing by removing the areas of lung most affected, harboring the largest amounts of mycobacteria. The indications for surgery include a poor response to drug therapy, the development of macrolide-resistant disease, or the presence of a significant disease-related complication such as hemoptysis. The surgical procedures of choice are various types of pulmonary resections, including wedge resection, segmentectomy, lobectomy, or pneumonectomy. The reported series have achieved favorable treatment outcomes in surgically treated patients with acceptable morbidity and mortality rates.

A 69-year-old man with squamous cell carcinoma( SCC) of the left lower lobe of the lung underwent lobectomy. One year later, radiography performed during check-up revealed pneumonia. After 1 week, he was admitted to the hospital because of dyspnea. Three tumors in his trachea and bronchus had narrowed the respiratory tract, and these were diagnosed as recurrence of SCC. The patient was treated with radiation and bronchofiberscopic ethanol injection (BEI) therapy, following which the tumors reduced remarkably in size; he recovered from respiratory insufficiency and was able to go home. He stayed home for 2 months; however, tumor enlargement was detected subsequently and the patient was at risk of suffocation. This time, the patient received combination therapy that included radiation, TS-1, and BEI. Subsequently, his respiratory airway reopened. BEI offers a quick and safe treatment option and has a rapid effect; therefore, we consider it useful for the treatment of malignant tracheobronchial stenosis.

Sclerosing hemangioma is unusual pulmonary tumor. During a routine care evaluation, an abnormal shadow was detected in the chest X-ray films of a 38-year-old woman. Chest computed tomography scanning showed a nodule, 3.9 cm in diameter, in the left S6 pulmonary segment. Bronchoscopy performed before the operation could not establish the diagnosis. Since low-grade malignant tumor wassuggested by frozen section analysis at surgery, segmentectomy of left S6 and sampling of interlober lymph node were performed. The tumor was diagnosed as a plmonary sclerosing hemangioma. Metastatic leasion in the interlober lymph node was pathologically confirmed.

A 39-year-old female was referred to our hospital due to repeated right pneumothorax. Each episode was related to the onset of menstruation, suggesting catamenial pneumothorax. Thoracoscopy showed multiple blue berry spots on the diaphragm. Partial resection of the diaphragm including these lesions were performed. But she had a recurrent right pneumothorax. Treatment with a gonadotropin-releasing hormone analogue was started, resulting in failure to introduce menopose and the pneumothorax repeatedly appeared again. Reoperation was intentionally done at the time of menstruation enable to find the lesion. Patient is free from pneumothorax more than 6 years after surgery.

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.

We describe a case of a large bronchial fistula and empyema after right upper lobectomy that was treated successfully with open window thoracostomy followed by a latissimus dorsi myocutaneous flap and limited thoracoplasty. A latissimus dorsi myocutaneous flap can provide immediate airtight closure of a large bronchial fistula, allowing lavage and curettage of the empyema cavity to reduce the chance of postoperative infection. An important aspect of this technique is that the deepithelialized skin side rather than muscle is sutured to an opening of the bronchus. As compared with other techniques, a latissimus dorsi myocutaneous flap is superior in that it requires a single incision and does not require an intraop-erative change of position. In addition, the technique causes little dysfunction of the chest and shoulder and preserves the vascular supply to ensure the viability of the flap even if it was divided in a previous operation.

We have performed pulmonary resection combined with chemotherapy for multidrug-resistant tuberculosis (MDR-TB). Postoperative complications of pulmonary resection for MDR-TB include space problem, prolonged air leak, bronchopleural fistula with or without empyema, chylothorax, and relapse. Indication, surgical technique, postoperative management, and follow-up of reoperation (thoracoplasty and muscle plombage, clousure of bronchopleural fistula, resuture of bronchial stump, open window thoracostomy, and 2nd pulmonary resection) for these complications are described.

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis., Background Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1–6.0]), ofloxacin (aOR: 2.5 [1.6–3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3–2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7–4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7–4.3]), ofloxacin (aOR: 2.3 [1.3–3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4–2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4–6.0]). Conclusions In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary., Editors' Summary Background In 2010, 8.8 million people developed tuberculosis—a contagious bacterial infection—and 1.4 million people died from the disease. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze and usually infects the lungs (pulmonary tuberculosis). The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Tuberculosis can be cured by taking several powerful antibiotics regularly for at least 6 months. The standard treatment for tuberculosis comprises an initial intensive phase lasting 2 months during which four antibiotics are taken daily followed by a 4-month continuation phase during which two antibiotics are taken. However, global efforts to control tuberculosis are now being thwarted by the emergence of M. tuberculosis strains that are resistant to several antibiotics, including isoniazid and rifampicin, the two most powerful, first-line (standard) anti-tuberculosis drugs. Why Was This Study Done? Although multi-drug resistant tuberculosis (MDR-TB) can be cured using second-line anti-tuberculosis drugs, these are more expensive and more toxic than first-line drugs and optimal treatment regimens for MDR-TB have not been determined. Notably, there have been no randomized controlled trials of treatments for MDR-TB. Such trials, which compare outcomes (cure, treatment failure, relapse, and death) among patients who have been randomly assigned to receive different treatments, are the best way to compare different anti-tuberculosis drug regimens. It is possible, however, to get useful information about the association of various treatments for MDR-TB with outcomes from observational studies using a statistical approach called “individual patient data meta-analysis.” In observational studies, because patients are not randomly assigned to different treatments, differences in outcomes between treatment groups may not be caused by the different drugs they receive but may be due to other differences between the groups. An individual patient data meta-analysis uses statistical methods to combine original patient data from several different studies. Here, the researchers use this approach to investigate the association of specific drugs, numbers of drugs and treatment duration with the clinical outcomes of patients with pulmonary MDR-TB. What Did the Researchers Do and Find? The researchers used three recent systematic reviews (studies that use predefined criteria to identify all the research on a given topic) to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. They obtained individual patient data from the authors of these studies and estimated adjusted odds (chances) of treatment success from the treatment and outcome data of 9,153 patients with MDR-TB provided by 32 centers. The use of later generation quinolones, ofloxacin, and ethionamide/prothionamide as part of multi-drug regimens were all associated with treatment success compared to failure, relapse or death, as were the use of four or more likely effective drugs (based on drug susceptibility testing of mycobacteria isolated from study participants) during the initial intensive treatment phase and the use of three or more likely effective drugs during the continuation phase. The researchers also report that among patients who did not die or stop treatment, the chances of treatment success increased with the duration of the initial treatment phase up to 7.1–8.5 months and with the total duration of treatment up to 18.6–21.5 months. What Do These Findings Mean? These findings suggest that the use of specific drugs, the use of a greater number of effective drugs, and longer treatments may be associated with treatment success and the survival of patients with MDR-TR. However, these findings need to be interpreted with caution because of limitations in this study that may have affected the accuracy of its findings. For example, the researchers did not include all the studies they found through the systematic reviews in their meta-analysis (some authors did not respond to requests for individual patient data, for example), which may have introduced bias. Moreover, because the patients included in the meta-analysis were treated at 32 centers, there were many differences in their management, some of which may have affected the accuracy of the findings. Because of these and other limitations, the researchers note that, although their findings highlight several important questions about the treatment of MDR-TB, randomized controlled trials are urgently needed to determine the optimal treatment for MDR-TB. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001300. The World Health Organization provides information on all aspects of tuberculosis, including MDR-TB; its guidelines for the programmatic management of drug-resistant tuberculosis are available The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the treatment of tuberculosis and on MDR-TB The US National Institute of Allergy and Infectious Diseases also has information on all aspects of tuberculosis, including a drug-resistant tuberculosis visual tour MedlinePlus has links to further information about tuberculosis (in English and Spanish) TB & ME, a collaborative blogging project run by patients being treated for multidrug-resistant tuberculosis and Medecins sans Frontieres, provides information about MDR-TB and patient stories about treatment for MDR-TB The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, also provides personal stories about treatment for tuberculosis

The prevalence of pulmonary disease caused by nontuberculous mycobacteria (NTM) has been increasing in Japan. Adjuvant resectional surgery is often recommended to lessen disease progression when the response to drug therapy is poor. In all likelihood, as affected cases of NTM disease increase, so will the number of operations. The goal of this study was to determine the current status of NTM surgery in Japan by analyzing data from the annual survey of the Japanese Association for Thoracic Surgery (JATS).Data were obtained from annual surveys conducted between 2008 and 2012. The annual number of operations for pulmonary NTM disease was tabulated nationwide and in each region (Hokkaido, Tohoku, Kanto, Tokyo, Chubu, Kinki, Chugoku/Shikoku, and Kyushu). For comparison, the numbers for pulmonary tuberculosis and tuberculoma operations were also obtained.The annual number of operations for pulmonary NTM disease nationwide increased each year between 2008 and 2012: 292 (2008), 323 (2009), 452 (2010), 440 (2011), and 514 (2012); an overall increase of 76%. Conversely, the annual numbers of operations for pulmonary tuberculosis were stable: 145 (2008), 181 (2009), 117 (2010), 113 (2011), and 107 (2012), as were the annual numbers of operations for tuberculoma: 386 (2008), 341 (2009), 320 (2010), 390 (2011), and 351 (2012).Data from the JATS annual survey demonstrate a steady increase in the number of NTM surgeries in Japan. General thoracic surgeons will continue to increasingly encounter NTM patients who are candidates for surgery until a magic bullet against NTM disease is available.

Mycobacterium avium complex (MAC) is the most common nontuberculous mycobacterial pathogen in Japan. There are 2 major types of clinical manifestations of MAC disease, including fibrocavitary disease and nodular bronchiectatic disease. Primary treatment of MAC disease is medical treatment. Standard multidrug regimens employ clarithromycin, rifampicin, and ethambutol. Aminoglycoside (streptomycin or kanamycin) is added if necessary. Patients whose disease is predominantly localized to 1 lung and who can tolerate resectional surgery may be considered for surgery under the following circumstances; poor response to drug therapy, the development of macrolide-resistant MAC disease, or the presence of hemoptysis. Surgery for MAC lung disease can achieve favorable treatment outcome. However, surgery is associated with significant morbidity, especially when pneumonectomy is performed. When surgical intervention is considered necessary for MAC patients, pulmonary resection should be performed before MAC lung disease has progressed too extensively to avoid pneumonectomy.

Purpose: We examined the influence of inflammatory cytokine levels on postoperative early recurrence in patients who underwent curative lung cancer surgery. Methods: In 107 patients who underwent curative pulmonary resections for non-small cell lung cancer (NSCLC) from November 2007 to June 2008, we measured serum interleukin-6 (IL-6) levels preoperatively, and on postoperative day (POD) 0, 1, and 2. Between July 2009 and August 2009, 1 year after the date of enrollment of the last patient, we investigated survival status of each patient and identified a group with recurrence.Results: Among 107 patients, 29 patients developed recurrence with a mean follow-up of 18.1 months (range 14 to 21). P-stage was significantly more advanced in the recurrence group than in the non-recurrence group (p = 0.005). Serum IL-6 levels on POD 1 were significantly higher in the recurrence group than in the non-recurrence group (p = 0.007). In Cox's proportional hazards regression, P-stage and serum IL-6 levels on POD 1 were significant independent predicting factors for postoperative early recurrence (p = 0.006, p = 0.003).Conclusions: The higher the serum IL-6 levels on POD 1, the higher the risk of early postoperative recurrence, even when curative pulmonary resection can be accomplished in lung cancer patients.

Mycobacterium avium complex (MAC) lung disease is the most common nontuberculous mycobacterial lung disease in Japan and is difficult to treat. Multidrug regimen employing clarithromycin, rifampicin, and ethambutol is not a panacea. Pulmonary resection may be beneficial to patients whose disease is predominantly localized to one lung and who can tolerate resectional surgery under the following circumstances: poor response to drug therapy, the development of macrolide-resistant MAC disease, or the presence of hemoptysis. Resectional surgery for MAC lung disease can achieve favorable treatment outcome. However, this type of surgery is associated with a relatively high morbidity and should be performed by experienced hands.

Background The purpose of this study was to demonstrate our surgical experience for focal bronchiectasis in the setting of modern diagnostic modalities and state-of-the-art medical treatment in a developed country. Methods Thirty-one patients undergoing 33 lung resections for the treatment of focal bronchiectasis from 1991 to 2009 were reviewed. The mean age was 54 years. Twenty-nine patients (94%) were female; 21 patients (68%) had nontuberculous mycobacterial infection; and 22 patients (71%) received preoperative multiple-drug regimens containing clarithromycin. Five patients (16%) were in an immunocompromised status. All were diagnosed by chest computed tomography scan, and either the right middle lobe or left lingula were involved in 29 (94%). The curve for relapse-free interval was estimated by Kaplan-Meier methods. The factors that affected this curve were examined using Cox's regression analysis. Results Operative morbidity and mortality were 18% and 0%, respectively. All patients became asymptomatic postoperatively. During the median follow-up of 48 months (11 to 216), 8 patients (26%) experienced recurrence, and the mean relapse-free interval was 34 months (3 to 216). By univariate analysis, an immunocompromised status ( p = 0.017), Pseudomonas aeruginosa infection ( p = 0.040), the preoperative extent of bronchiectatic lesion ( p = 0.013), and the extent of residual bronchiectasis after surgery ( p = 0.003) were significantly associated with the shorter relapse-free interval. By multivariate analysis, an immunocompromised status ( p = 0.039), Pseudomonas aeruginosa infection ( p = 0.033), and the extent of residual bronchiectasis ( p = 0.009) were independent and significant factors. Conclusions Complete resection of bronchiectasis while the disease is localized and is free from Pseudomonas aeruginosa infection is the key for a success. Also, immunocompromised status was suggested to be a risk factor.

Wound infection and empyema complicating pulmonary resection is considered surgical site infection (SSI). Wound infection after pulmonary resection rarely occurs when preventative measures against SSI are taken. Empyema complicating pulmonary resection is organ/space SSI, and one of the most devastating complications after pulmonary resection. Postresectional empyema is often associated with bronchopleural fistula, which makes the management of empyema difficult and needs expertise. The initial treatment of postresectional empyema should include prompt surgical drainage by closed tube thoracostomy and institution of appropriate antibiotics. Definitive treatment of empyema includes complete obliteration of empyema space and secure closure of bronchopleural fistula if applicable. "Prevention is better than cure" does apply to SSI.

To assess whether there is any difference in postoperative morbidity and mortality after pneumonectomy between patients with multidrug-resistant tuberculosis (MDR-TB) and patients with non-tuberculous mycobacterial (NTM) infections. Between January 2000 and December 2007, 61 patients with MDR-TB and 60 patients with NTM infections underwent 66 and 64 pulmonary resections, respectively. Of these, 33 patients were analyzed who underwent a pneumonectomy, including 22 patients with MDR-TB (seven right, 15 left) and 11 patients with NTM infections (seven right, four left). All bronchial stumps were covered with the latissimus dorsi. Patients with NTM infections were predominantly more female, older, thinner, and presented with a higher frequency of culture-positive sputum at operation than patients with MDR-TB. Operative mortality was zero. Morbidities were bronchial stump dehiscence (n=1) and mycobacterial empyema (n=1) for patients with MDR-TB, and acute respiratory failure (n=1), bronchial stump dehiscence (n=5) and mycobacterial empyema (n=2) for patients with NTM infections. Prevalence of bronchial stump dehiscence was significantly higher in patients with NTM infections (P=0.010). Five of six dehiscences occurred after right pneumonectomy. The optimal management of the bronchial stump in the setting of pneumonectomy for NTM infections needs further investigation.

Although the results of medical treatment for multidrug-resistant tuberculosis (MDR-TB) has improved, adjuvant surgical treatment remains achieving better outcomes for MDR-TB patients. We have performed pulmonary resection for MDR-TB patients aggressively. Indications for surgery include (1) persistent positive sputum despite state-of-the-art chemotherapy and (2) a high risk of relapse. For 56 patients undergoing 61 pulmonary resections for MDR-TB between January 2000 and June 2007 at our institution, the overall cure rate was 98%. An aggressive treatment approach to MDR-TB continues to be justified until a panacea for this refractory disease is available.

Empyema remains challenging for thoracic surgeons. This review covers diverse aspects of acute empyema and chronic empyema and its surgical treatment. The triphasic nature of thoracic empyema (stages I, II, and III) is also addressed. The principles of empyema treatment are early diagnosis and early treatment. For acute empyema (empyema in stages I and II), early surgical intervention, such as video-assisted thoracoscopic debridement, is recommended when conventional chest tube drainage has failed. Radical treatments of chronic empyema (empyema in stage III) include (1) removal of the empyema space (decortication with or without lung resection) and (2) obliteration of the pleural space with muscle flaps or omentum flaps, or by thoracoplasty. Decortication is the procedure of choice for patients with reexpandable underlying lung. When bronchopleural fistula exists in the underlying lung, the fistula should be securely closed. For those patients whose underlying lung cannot be expected to reexpand, the procedure of choice is either concomitant removal of the affected lung with the empyema space or obliteration of the pleural space. For patients who are not eligible for the above-mentioned radical treatment, open-window thoracostomy can be considered. This procedure is not only performed as a definitive treatment of empyema but also as a preparatory treatment for radical procedures. Radical procedures are performed when patients recuperate. Choosing the most suitable operation based on the stages of empyema, the conditions of the underlying lung, and the conditions of a patient holds the key to success.

Although tuberculosis is mainly managed medically today, thoracic surgery continues to play a key role in its diagnosis and treatment in selected subgroups of patients. In certain scenarios such as multi-drug-resistant tuberculosis, advanced tuberculous empyema and symptomatic bronchial stenosis, modern thoracic surgery may represent the only effective means of management in selected patients. Advances in thoracic surgery in recent years, in particular the use of Video-Assisted Thoracic Surgery, not only reduce postoperative morbidity for individual patients, but may potentially allow a wider range of tuberculosis patients to benefit from surgery. Respiratory physicians and thoracic surgeons should continue to work together to ensure that tuberculosis patients who may benefit from surgery are identified for prompt and effective intervention.

Objective Human salusin-α and -β are two-related peptides processed from the same precursor, preprosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Thus we investigated the effects of salusin-α and -β on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE−/−) mice. Methods Saline (vehicle), salusin-α or -β (0.6nmol/kg/h) was continuously infused through osmotic mini-pumps into 13-week-old ApoE−/− mice for 8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester accumulation (foam cell formation), and its related gene expression in exudate peritoneal macrophages were determined. Results After 4-week infusion of salusin-β, atherosclerotic lesions were 2.6 times greater than vehicle controls, which paralleled 1.9-fold increase in foam cell formation and up-regulation of scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol acyltransferase-1 (ACAT1). In contrast, salusin-α decreased serum total cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1 down-regulation. After 8-week infusion of salusin-α, atherosclerotic lesions were significantly suppressed by 54% compared with vehicle controls. Conclusions Our study provided the first evidence that salusin-β accelerates the development of atherosclerotic lesions associated with up-regulation of scavenger receptors and ACAT1 in ApoE−/− mice. Whilst, salusin-α exerts anti-atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1 expression.

Although pulmonary resection can be performed with low operative morbidity and mortality in patients with lung cancer, surgery for infectious lung disease still carries high postoperative complication rates. Major complications include massive intraoperative blood loss, bronchopleural fistula, empyema, and post-resectional space. One of the keys to reduce the complication rates is that patients should be kept on chemotherapy for at least 3 months prior to operation. Other keys are the following. First, painstaking extrapleural dissection is recommended to dissect dense adhesion in order to reduce blood loss and to prevent the operative field being contaminated. Second, the bronchial stump should be covered with muscle flap to prevent bronchopleural fistula. Third, when the post-resectional space is anticipated, myoplasty or thoracoplasty should be performed to reduce the size of space. Finally, patients should continue to be on chemotherapy after the surgery for the prevention of relapse.