Temporary Stenting for Anastomotic Stenosis after Tracheal Resection of Adenoid Cystic Carcinoma: A Case Report.

A 51-year-old man who noticed discomfort in the pharynx was found to have a tracheal tumor on physical examination. He was diagnosed as having adenoid cystic carcinoma by a transbronchial biopsy and underwent tracheal segmental resection via a collar incision. He was additionally treated with radiation therapy owing to a positive surgical margin, and he subsequently developed anastomotic tracheal stenosis. Silicon stent placement to open the airway was performed for the tracheal stenosis. One year after stent placement, the trachea was dilated, so the stent was removed, and he is still under follow-up without recurrence free 1.5 years after stent replacement.

Involvement of 27-hydroxycholesterol on the progression of non-small cell lung cancer via the estrogen receptor.

The oxysterol 27-hydroxycholesterol (27HC) promotes the proliferation of breast cancer cells as a selective estrogen receptor modulator (SERM), but it is mostly produced by alveolar macrophages in vivo. The present study evaluated hypothesis that 27HC may also promote the proliferation of lung cancer cells. In the tumor and nontumor regions of lung tissue from 23 patients with non-small cell lung cancer (NSCLC) who underwent lung cancer surgery, we compared the 27HC content and its synthetic and catabolic enzyme expressions (CYP27A1 and CYP7B1), the expressions of the estrogen receptor (ER) gene and its target gene cMYC by using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS), real-time RT-PCR, and immunohistochemical staining. In addition, we evaluated the effects of 27HC and ß-estradiol (E2) treatments on the proliferation of a cultured lung cancer cell line (H23 cells) expressing ERß. In squamous cell carcinoma and in adenocarcinoma, the 27HC content was significantly higher in the tumor region than in the nontumor region, and in cancer grade III than in the other cancer grades. CYP27A1-positive macrophages were histologically detected in the nontumor regions of both cancer types, whereas the gene and protein expressions of ERß, as well as the CYP7B1 and cMYC genes, were significantly increased in the tumor tissues. In cultured H23 cells, proliferation was significantly increased by 27HC and E2 treatments for 48 h. Similar to breast cancer, the present results supported idea that the 27HC produced from alveolar macrophages promotes the proliferation of lung cancer cells highly expressing ER through the SERM action. Therefore, 27HC should be an important target for cancer therapy of NSCLC.

Metachronous Primary Lung Cancer Occurring during the Spontaneous Regression of Locally Advanced Lung Cancer: A Rare Case Report.

A 71-year-old man was diagnosed as having right primary lung squamous cell carcinoma, clinical stage IIIA, but he refused treatment. However, the right upper lobe nodule and lymph node (LN) #4R showed gradual shrinking without treatment. Four years after the diagnosis, a new nodule was detected in the left lung field. We considered that this new nodule might be metachronous primary lung cancer, and hence resected it for diagnosis and treatment. The tumor in the left lung was diagnosed as basaloid squamous cell carcinoma, and that in LN #4R was diagnosed as squamous cell carcinoma with keratinization. Therefore, the patient was diagnosed as having metachronous primary lung cancer that developed during the spontaneous regression of locally advanced lung cancer.

Sex-, age-, and organ-dependent improvement of bile acid hydrophobicity by ursodeoxycholic acid treatment: A study using a mouse model with human-like bile acid composition.

Cyp2a12-/-Cyp2c70-/- double knockout (DKO) mice have a human-like hydrophobic bile acid (BA) composition and show reduced fertility and liver injury. Ursodeoxycholic acid (UDCA) is a hydrophilic and cytoprotective BA used to treat various liver injuries in humans. This study investigated the effects of orally administered UDCA on fertility and liver injury in DKO mice. UDCA treatment prevented abnormal delivery (miscarriage and preterm birth) in pregnant DKO mice, presumably by increasing the hydrophilicity of serum BAs. UDCA also prevented liver damage in six-week-old DKO mice, however liver injury emerged in UDCA-treated 20-week-old female, but not male, DKO mice. In 20-week-old male UDCA-treated DKO mice, conjugated plus unconjugated UDCA proportions in serum, liver, and bile were 71, 64, and 71% of the total BAs, respectively. In contrast, conjugated plus unconjugated UDCA proportions in serum, liver, and bile of females were 56, 34, and 58% of the total BAs, respectively. The UDCA proportion was considerably low in female liver only and was compensated by highly hydrophobic lithocholic acid (LCA). Therefore, UDCA treatment markedly reduced the BA hydrophobicity index in the male liver but not in females. This appears to be why UDCA treatment causes liver injury in 20-week-old female mice. To explore the cause of LCA accumulation in the female liver, we evaluated the hepatic activity of CYP3A11 and SULT2A1, which metabolize LCAs to more hydrophilic BAs. However, there was no evidence to suggest that either enzyme activity was lower in females than in males. As female mice have a larger BA pool than males, excessive loading of LCAs on the hepatic bile salt export pump (BSEP) may be the reason for the hepatic accumulation of LCAs in female DKO mice with prolonged UDCA treatment. Our results suggest that the improvement of BA hydrophobicity in DKO mice by UDCA administration is sex-, age-, and organ-dependent.

A Rare Case of Chest Wall Castleman's Disease with Calcification.

Castleman's disease with calcification of the chest wall is very rare, and there have been few reports of such cases to date. A 57-year-old woman was referred to our hospital for a tumor with calcification on her left lateral chest wall, which was detected on chest computed tomography. Findings of her chest magnetic resonance imaging suggested schwannoma or a solitary fibrous tumor, and therefore, we performed surgery for diagnostic and therapeutic purposes. Pathologically, the tumor with calcification was diagnosed as Castleman's disease of the hyaline-vascular type. After the surgery, the patient has had no obvious symptoms and continues to undergo regular follow-up examinations.

Investigation of EGFR mutations in non-small cell lung cancer usually undetectable by PCR methods.

Epidermal growth factor receptor (EGFR) mutations are the most significant genomic drivers of non-small cell lung cancer (NSCLC) and determine the efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. PCR methods are used clinically for the detection of EGFR mutations. The Scorpion Amplification Refractory Mutation System (Scorpion-ARMS) and the cobas® EGFR Mutation Test v2 (cobas v2) are widely used PCR methods. However, those PCR methods only selectively detect the common EGFR mutations. The aim of the present study was to reveal the true frequency of EGFR mutations in NSCLC by investigating EGFR mutations usually undetectable by PCR methods by using direct sequencing. A total of 70 Japanese patients who underwent lung resection for NSCLC between September 2016 and March 2019 were included in the present study. Subsequently, PCR methods and direct sequencing were performed. In total, 29 mutations were detected by cobas v2. In total, 41 patients were identified as EGFR wild-type by cobas v2, among whom direct sequencing detected mutations in 3 patients. Subsequent Scorpion-ARMS was performed in the 3 patients in whom direct sequencing detected mutations. In total, one exon 21 L858R + G863D compound mutation was identified as a L858R single mutation, and two other mutations were undetectable. Moreover, 1 patient who was 'wild-type' on cobas v2 but 'EGFR mutation' on direct sequencing developed recurrence after surgery and responded to EGFR-TKI treatment. In present study, the percentage of undetectable EGFR mutations by cobas v2 was 9.4% in 32 mutations. It was inferred that the cause of the discrepancy in the mutation type (L858R + G863D in exon 21, and L858R in exon 21) between cobas v2 and Scorpion ARMS was due to the different limit of detection between these two PCR methods. In conclusion, the findings of the present study suggested that a selective mutation detection method may decrease the opportunity of patients with NSCLC to receive EGFR-TKI therapy. Thus, the development of a screening test to determine the EGFR status as wild-type or mutant is required for EGFR-TKI therapy.

Atypical carcinoid with multiple central airway metastases: A case report.

A 51-year-old man was found to have multiple polypoid tracheal and bilateral main bronchial tumors during postoperative follow-up of atypical carcinoid. He underwent transtracheal biopsy, and was diagnosed as having central airway metastases of the atypical carcinoid. He underwent chemotherapy, but the effects were unfavorable. Owing to the risk of airway obstruction, he was referred to our hospital for interventional bronchoscopy. Carcinoid tumors usually present as peripheral lung lesions or solitary endobronchial abnormalities, but rarely appear as multiple central airway lesions. We present a very rare case of multiple central airway metastases of atypical carcinoid, controlled by bronchoscopic treatment.

Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human-Like Bile Acid Composition.

Western-style high-fat/high-sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD-induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild-type (WT) and human-like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography-tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD-induced change of gut microbiota inhibited BA deconjugation and 7α-dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human-like hydrophobic BA composition.

Hepatocellular adenoma, approximately half and predominantly inflammatory subtype, in 38 Japanese patients with several differences in age, gender, and clinical background factors from Western populations.

AIM: Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. METHODS: To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. RESULTS: Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. CONCLUSIONS: In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

Leiomyosarcoma of the transverse colon with lymph node metastasis and malignant transformation: a case report.

BACKGROUND: The concept of GIST was established in 1998, clearly differentiating between gastrointestinal leiomyosarcoma and GISTs among gastrointestinal mesenchymal tumors. Lymph node metastasis is extremely rare in true gastrointestinal leiomyosarcoma, and there are no reports of malignant transformation from leiomyoma. CASE PRESENTATION: The patient was an old woman who had undergone endoscopic mucosal resection for an Is polyp on the left side of the transverse colon at the age of 73. She was diagnosed with leiomyoma with positive surgical margins. Subsequently, she presented to our institution with a sensation of pressure in the upper abdominal region as a chief complaint at the age of 76 years. Abdominal computed tomography and colorectal endoscopy showed a tumor lesion with invagination of the intestines in the transverse colon, the same site as that of the previously resected leiomyoma. A biopsy suggested a smooth muscle tumor, and we performed partial left transverse colectomy and lymph node dissection under a diagnosis of recurrence and enlargement of the previously incompletely resected leiomyoma. Histopathological examination revealed spindle-shaped tumor cells, and the mitotic activity was 30-40/10 high-power field. Tumor cells were immunohistologically positive for α-smooth muscle actin and h-caldesmon; partially positive for desmin; negative for c-kit, CD34, DOG-1, and the S-100 protein; and showed a Ki-67 labeling index of 70-80%. She was diagnosed with leiomyosarcoma malignantly transformed from leiomyoma. Metastasis was found in 1 of the 14 resected lymph nodes. The patient did not undergo adjuvant chemotherapy, but has survived with no recurrence at 2 years after the surgery. CONCLUSIONS: We have reported a case of leiomyosarcoma of the transverse colon with lymph node metastasis that was malignantly transformed from a leiomyoma.

Comparison of the amino acid profile between the nontumor and tumor regions in patients with lung cancer.

Energy metabolism in cancer cells is reprogrammed to meet the energy demands for cell proliferation under strict environments. In addition to the specifically activated metabolism of cancer, including the Warburg effect and glutaminolysis, most amino acids (AAs) are utilized for gluconeogenesis. Significant increases in AAs and energy metabolites in the tumor region occur in gastric and colon cancers. However, a different AA-related energy metabolism may exist in lung cancer because of the abundant blood supply to lung tissue. This study compared the profiles of AAs and their related metabolites in energy metabolism, analyzed by an HPLC-MS/MS system, between tissues from nontumor and tumor regions collected from 14 patients with non-small cell lung cancer (NSCLC). In the energic metabolism precursor categories, the glucogenic AAs, which included the pyruvate precursors (Ser, Gly, Thr, Ala, and Trp), the α-ketoglutarate precursors (Glu, Gln, and Pro) and the succinyl-CoA precursors (Val, Ile, and Met) were significantly increased in the tumor region compared to in the nontumor region. However, no significant differences existed between the two regions in the ketogenic AAs (Leu, Lys, and Tyr). These differences were not observed between the subgroups with and without diabetes mellitus in the two regions. The metabolites on the left-hand side of the TCA cycle were significantly higher in the tumor region, but no differences in metabolites in the right-hand side. The mRNA expressions of major AA transporters and cancer proliferation factors were also significantly increased in the tumor region, compared to these in their counterparts. In lung cancer, glucogenic AAs that are actively transported from circulating fluids would be predominantly utilized for gluconeogenesis, with and without diabetes mellitus. The characteristics of the AA-related metabolism would be associated with tissue-specific cell proliferation in patients with NSCLC.

Impaired bile acid metabolism with defectives of mitochondrial-tRNA taurine modification and bile acid taurine conjugation in the taurine depleted cats.

Taurine that conjugates with bile acid (BA) and mitochondrial-tRNA (mt-tRNA) is a conditional essential amino acid in humans, similarly to cats. To better understand the influence of acquired depletion of taurine on BA metabolism, the profiling of BAs and its intermediates, BA metabolism-enzyme expression, and taurine modified mt-tRNAs were evaluated in the taurine deficient diet-supplemented cats. In the taurine depleted cats, taurine-conjugated bile acids in bile and taurine-modified mt-tRNA in liver were significantly decreased, whereas unconjugated BA in serum was markedly increased. Impaired bile acid metabolism in the liver was induced accompanied with the decreases of mitochondrial cholesterol 27-hydroxylase expression and mitochondrial activity. Consequently, total bile acid concentration in bile was significantly decreased by the low activity of mitochondrial bile acid synthesis. These results implied that the insufficient dietary taurine intake causes impaired bile acid metabolism, and in turn, a risk for the various diseases similar to the mitochondrial diseases would be enhanced.

Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition.

The bile acid (BA) composition in mice is substantially different from that in humans. Chenodeoxycholic acid (CDCA) is an end product in the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, in humans, the gut microbiota converts the primary BAs, cholic acid and CDCA, into deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. In contrast, the mouse Cyp2a12 reverts this action and converts these secondary BAs to primary BAs. Here, we generated Cyp2a12 KO, Cyp2c70 KO, and Cyp2a12/Cyp2c70 double KO (DKO) mice using the CRISPR-Cas9 system to study the regulation of BA metabolism under hydrophobic BA composition. Cyp2a12 KO mice showed the accumulation of DCAs, whereas Cyp2c70 KO mice lacked MCAs and exhibited markedly increased hepatobiliary proportions of CDCA. In DKO mice, not only DCAs or CDCAs but also DCAs, CDCAs, and LCAs were all elevated. In Cyp2c70 KO and DKO mice, chronic liver inflammation was observed depending on the hepatic unconjugated CDCA concentrations. The BA pool was markedly reduced in Cyp2c70 KO and DKO mice, but the FXR was not activated. It was suggested that the cytokine/c-Jun N-terminal kinase signaling pathway and the pregnane X receptor-mediated pathway are the predominant mechanisms, preferred over the FXR/small heterodimer partner and FXR/fibroblast growth factor 15 pathways, for controlling BA synthesis under hydrophobic BA composition. From our results, we hypothesize that these KO mice can be novel and useful models for investigating the roles of hydrophobic BAs in various human diseases.

Miliary Lung Metastases from Genital Large Cell Neuroendocrine Carcinomas.

We herein report two cases of miliary lung metastases from genital carcinoma in uterine cervix and endometrium. Notably, these patients were unable to receive any anti-tumor chemotherapy due to rapid progression causing respiratory failure, and they ultimately died of disease progression within only a month after the first visit to our hospitals. A postmortem examination confirmed the diagnosis of genital large-cell neuroendocrine carcinoma (LCNEC). Chest physicians should be aware of genital LCNEC with a dismal prognostic entity as an important differential diagnosis of miliary lung metastases.

Giant retroperitoneal schwannoma in a 52-year-old man.

Schwannoma in the retroperitoneal space is rare, and it is extremely rare in patients with no history of neurofibromatosis. We present a case of giant retroperitoneal schwannoma in a 52-year-old man who did not have neurofibromatosis. Because malignant transformation would be extremely rare in this circumstance, close imaging follow-up could avert the necessity for complete resection. The possibility of schwannoma should be considered when evaluating retroperitoneal tumors with the characteristic findings, even if there is no connection between the tumor and the intervertebral foramina.

[A Case of Synchronous Liver Metastasis of Ascending Colon Cancer with Pathological Complete Response to S-1/Oxaliplatin (SOX) and Bevacizumab].

A 77-year-old man was diagnosed with ascending colon cancer with synchronous liver metastasis. Per our policy we first only performed a right hemicolectomy (pSSN2H2M0, stage IV). We then planned S-1 and oxaliplatin (SOX) plus bevacizumab (Bmab) chemotherapy as a neoadjuvant for the resection of liver metastasis. After 4 courses, enhanced CT and EOB-MRI findings showed the liver tumor had significantly decreased in size with no side effects, and we performed a partial liver resection for the S7 lesion. Postoperatively, histopathological analysis revealed only a fibrotic lesion and no cancerous cells in the resected specimen, indicating that chemotherapy had downgraded the tumor to Grade 3. Adjuvant chemotherapy was not continued owing to the patient's refusal, but no recurrence was noted 18 months after the second operation. SOX plus Bmab chemotherapy is, therefore, effective in terms of its anti-tumor effects, tolerance, and accessibility. We believe SOX plus Bmab chemotherapy can be considered as an effective option for cases with synchronous liver metastasis of colon cancer as neoadjuvant chemotherapy for interval liver resection.

Hepatic histopathological changes and dysfunction in primates following exposure to organic arsenic diphenylarsinic acid.

Organic arsenic diphenylarsinic acid (DPAA[V]) accumulates at high concentrations in the liver of primates after its subchronic administration. However, no studies on the hepatic effects of organic arsenic compounds, including DPAA(V), on primates have been reported to date. To clarify the toxicokinetics of DPAA(V) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of DPAA(V) for 28 days. Four histopathological changes in the specimens were observed and pathologically evaluated. Atypical ductular proliferation was found in the DPAA(V)-exposed liver throughout the period. Inflammatory cell infiltration in Glisson's capsules and lipid droplets were seen at earlier periods after administration. Conversely, inflammatory cell infiltration in liver lobules was seen later after administration. In this experiment, we did not confirm the hepatic dysfunction of DPAA(V)-exposed monkeys by blood chemistry tests. To compensate for this, we further investigated the blood from a patient who exhibited several neurological symptoms after DPAA(V) exposure. Her blood chemistry test values for aspartate transaminase, alanine transaminase, and lactate dehydrogenase were elevated, suggesting that her liver may have been damaged by DPAA(V) exposure. Together, these findings suggest that the accumulation of DPAA(V) may induce differential histopathological changes in primate hepatocytes, resulting in decreased liver function. This is the first report to investigate the liver of primates pathologically after exposure to organic arsenic DPAA(V). Our findings will help expand our knowledge regarding the effect of DPAA(V) on the liver of primates.

Breast metastasis of pulmonary pleomorphic carcinoma: a case report.

BACKGROUND: Lung cancer rarely metastasizes to the breast, and breast metastasis of pulmonary pleomorphic carcinoma has not been previously reported. CASE PRESENTATION: The patient was a 66-year-old woman who became aware of a mass in the right breast and visited a physician. She was referred to our department for close examination, upon which she was diagnosed with double cancer (right breast cancer and left lung cancer). Needle biopsy findings for the mammary tumor were similar to those for the lung biopsy specimen, but spindle cell or metaplastic carcinoma were possibilities. The initial diagnosis was primary breast cancer. Left upper lobectomy and lymph node dissection were performed for left lung cancer. Both the lung and mammary tumors grew rapidly during the wait for surgery. The white blood cell count was within the normal range at the first examination, but was markedly increased and remained at a high level after surgery for lung cancer. Preoperative chemotherapy was initially planned for the mammary tumor, but surgical treatment was selected in consideration of the clinical course, and right mastectomy and full thickness skin graft were performed. However, the disease rapidly aggravated and the patient died 5 months after the first examination. CONCLUSION: The final diagnosis was pulmonary pleomorphic carcinoma with metastasis to the breast on postoperative histopathological examination. We describe this case as the first reported example of breast metastasis of pulmonary pleomorphic carcinoma.

Synthesis and biological activity of a novel fungicide, pyraziflumid.

Pyraziflumid was discovered as a novel SDHI fungicide chemically characterized by the 3-(trifluoromethyl)pyrazine-2-carboxamide group. This chemical series showed particularly high fungicidal activities against a broad spectrum of plant diseases in the case of N-(biphenyl-2-yl) as well as N-(1,1,3-trimethylindan-4-yl)carboxamides. Various N-(biphenyl-2-yl)pyrazine-2-carboxamides were synthesized, and their structure-activity relationships were studied. The optimization of the fungicidal performance of the series finally led to the identification of pyraziflumid, which could control a wide range of plant diseases. In this report, details of the structure-activity relationships from the lead compound to pyraziflumid are described.

Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease.

BACKGROUND AND AIMS: It remains unclear whether transbronchial lung biopsy (TBLB) is useful for diagnosing Mycobacterium avium complex (MAC) lung disease. METHODS: Thirty-eight consecutive patients with MAC lung disease, who were evaluated with TBLB tissue culture between June 2006 and May 2010, were included. Bronchial washing (BW) and histopathological evaluation were performed in all patients. The positivity rates of BW and TBLB tissue culture, and typical histopathological findings for MAC disease were investigated. Furthermore, all patients were divided into two groups according to the presence of intrabronchial purulent or mucopurulent secretion and the clinical, bacteriological and pathological characteristics were compared between the two groups. RESULTS: The positive culture rates of BW and TBLB specimens for MAC were 100% (38 patients) and 28.9% (11 patients). BW materials were much more sensitive for culture positivity than TBLB specimens (P < 0.0001). Typical pathological findings for MAC disease were present in the TBLB specimens of only 11 patients (28.9%). Intrabronchial secretion was identified in 15 patients (39.5%, secretion-positive group) and absent in 23 patients (60.5%, secretion-negative group). Typical histopathological findings for MAC disease were more common in the secretion-positive group than in the secretion-negative group (53.3% vs 13.0%, P = 0.01), although the radiological classification and smear positivity of BW were not different between the two groups. CONCLUSION: TBLB for pathological and bacterial investigations would provide only a limited value for MAC diagnosis. Moreover, the presence of intrabronchial secretion may be an important manifestation of ongoing airway damage, which would require early treatment.