[Surgical Experience with Three Cases of Open-window Thoracostomy for Chronic Empyema Under Local Anesthesia].

We may encounter patients with chronic empyema for whom open-window thoracostomy is unavoidable. However, patients with chronic empyema are sometimes at high-risk for surgery under general anesthesia. We, herein, present our surgical experience with three chronic empyema cases who underwent open-window thoracostomy under local anesthesia. Indications for open-window thoracostomy under local anesthesia were raised PaCO2 in Case 1, old age and poor performance status in Case 2, and a history of esophageal reconstruction and vocal cordoplasty in Case 3. All patients were well during the surgery. Case 1 developed type 2 respiratory failure postoperatively and had to be put on a ventilator, but finally recuperated. The sedatives used could have exacerbated raised PaCO2 in this patient, and careful selection of anesthetic agents is mandatory. Considering pain and stress that patients suffer during open-window thoracostomy under local anesthesia, case selection is necessary. Nevertheless, we believe that open-window thoracostomy under local anesthesia is an effective option for high-risk patients.

Pharmacokinetics and Adverse Effects of Clofazimine in the Treatment of Pulmonary Non-Tuberculous Mycobacterial Infection.

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.

Time to Incurable Recurrence for Patients Treated With Pulmonary Metastasectomy for Colorectal Cancer.

BACKGROUND: 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. METHODS: This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008. RESULTS: 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. CONCLUSION: 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.

Low-dosage ethambutol, less than 12.5 mg/kg/day, does not worsen the clinical outcomes of pulmonary Mycobacterium avium and Mycobacterium intracellulare disease: a retrospective cohort study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Clinical risk factors related to treatment failure in Mycobacterium abscessus lung 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.

[Re-operation for Inflammatory Lung Diseases].

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.

Incremental Shuttle Walk Distance as an Indicator for Functional Exercise Capacity of Pre-Surgical Patients with Nontuberculous Mycobacterial Lung Disease.

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.

[Nontuberculous Mycobacteriosis Resistant for Chemotherapy which was Suspected to Coexist with Lung Cancer].

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.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

[LEGACIES OF SURGERY FOR TUBERCULOSIS AND SUCCESSION TO THE NEXT GENERATION].

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.

[Reoperation for multidrug-resistant pulmonary tuberculosis].

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.

[Successful surgical treatment for catamenial pneumothorax at the time of menstruation].

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.

[Pulmonary sclerosing hemangioma with lymph node metastasis].

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.

[Remarkable improvement in dyspnea following bronchofiberscopic ethanol injection therapy -a case report].

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.

Epidemiological characteristics of nontuberculous mycobacteriosis and bronchiectasis: comparative study using national mortality statistics from 1970 to 2015 in Japan.

Background: This study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases. Methods: We analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system. Results: The total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis. Conclusions: The trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.

Surgical Management of Mycobacterial Infections and Related Complex Pleural Space Problems: From History to Modern Day.

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.

Outcomes of Surgical Treatment for Mycobacterium abscessus Complex Pulmonary Disease.

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.

A Novel Approach to Extensive Clarithromycin-Resistant Mycobacterium avium Complex Pulmonary Disease.

A 48-year-old woman with extensive clarithromycin-resistant Mycobacterium avium complex pulmonary disease (MAC-PD) was successfully treated by left lower lobectomy and lingulectomy following combination treatment of intravenous/inhaled amikacin plus bronchial occlusion by Endobronchial Watanabe Spigots (EWSs). A left pneumonectomy was initially indicated for removing all the lesions, but the procedure would have been barely tolerated by the patient. However, her preoperative combination treatment sufficiently reduced the lesions requiring resection to allow surgical preservation of the left upper division. This novel approach might be promising for patients with Mycobacterium avium complex lung disease whose pulmonary reserve will not allow an extensive parenchymal resection.