Successful thoracoscopic operative approach for refractory pneumothorax in interstitial lung disease under local anaesthesia.

Refractory pneumothorax associated with interstitial lung disease (ILD) remains a challenging condition due to the patient's tolerability and lung compliance that restrict the feasibility of aggressive interventions. Additionally, many cases recur after improvement with treatment, and reports of successful management for this complicated condition are limited. Herein, we report the case of a 60-year-old man with ILD, utilizing home oxygen therapy, who experienced a successful recovery from a surgical intervention under local anaesthesia for pneumothorax. This case highlights the potential for operative intervention under local anaesthesia as a viable option for patients who do not respond to internal approaches.

Methotrexate-associated lymphoproliferative disorder: A rare pancreatic tumor diagnosed via endoscopic ultrasound-guided fine-needle biopsy.

A 73-year-old woman with a history of rheumatoid arthritis treated with methotrexate (MTX) for the last 10 years was referred to our hospital for a pancreatic tumor examination. Contrast-enhanced abdominal computed tomography revealed a 20-mm-diameter hypovascular tumor in the pancreatic tail. A hypoechoic mass with heterogeneous internal echo was found on an endoscopic ultrasound (EUS). An EUS-guided fine-needle biopsy (EUS-FNB) was performed with a 22-gauge Franseen-tip needle. Histologic examination of EUS-FNB specimens from the pancreatic tumor revealed the proliferation of atypical spindle cells. Immunohistochemical staining for CD20 and Ki-67 was positive in the atypical cells. Immunohistochemical staining for CD3 was partially positive in the atypical cells. Epstein-Barr virus-encoded RNA in situ hybridization showed positive staining. MTX-related lymphoproliferative disorder (MTX-LPD) with Epstein-Barr virus infection was diagnosed. MTX treatment was immediately discontinued, and treatment was initiated by a hematologist. However, her condition rapidly deteriorated, and she died of multiple organ failure 4 weeks after diagnosis. MTX-LPD can complicate gastrointestinal lesions. However, most lesions are localized in the stomach and rarely complicate pancreatic lesions. MTX-LPD is classified as an "iatrogenic" LPD. Therefore, immediate action, such as MTX discontinuation, is necessary. In conclusion, endoscopists should be aware that MTX-LPD lesions can occur in the pancreas and gastrointestinal tract. Moreover, EUS-FNB can be useful in the diagnosis of this rare pancreatic tumor.

Pulmonary tuberculosis presenting with cluster sign and galaxy sign.

In a routine medical check-up, a healthy man in his 20s was found to have an upper left lung abnormality. Subsequent chest CT revealed the cluster sign (CS) and galaxy sign (GS). Although tests such as sputum analysis and interferon-gamma assays reduced the likelihood of tuberculosis, these abnormalities remained unchanged. A lung biopsy indicated non-caseating granuloma unrelated to tuberculosis. Initially suspected of sarcoidosis, the patient later developed fever and malaise. Follow-up CT showed CS progressing to a cavitatory shadow and GS intensification. The detection of Mycobacterium tuberculosis (M. tuberculosis) in a subsequent sputum analysis prompted treatment with antitubercular drugs, leading to symptom relief.CS and GS are usually associated with sarcoidosis but can also occur in tuberculosis, connected to slower pathogen growth and lower isolation rates. Furthermore, pulmonary tuberculosis may ultimately be present even when biopsies show non-caseating granulomas that are not typical of M. tuberculosis and sputum culture results are negative for M. tuberculosis Tuberculosis should not be ruled out lightly, and patients should be carefully followed-up.

A multicenter, open-label, phase II trial of pemetrexed plus bevacizumab in elderly patients with previously untreated advanced or recurrent nonsquamous non-small cell lung cancer.

BACKGROUND: Although the incidence of lung cancer in elderly individuals has been increasing in recent years, the number of clinical trials designed specifically for elderly patients with advanced non-small cell lung cancer (NSCLC) is still limited. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of pemetrexed (PEM) plus bevacizumab (Bev) combination chemotherapy in elderly patients with nonsquamous NSCLC. METHODS: A total of 29 elderly patients (≥75 years old) with nonsquamous NSCLC were enrolled in this multicenter, open-label, phase II study, and 27 patients were finally analyzed. PEM at 500 mg/m2 on day 1 plus Bev at 15 mg/kg on day 1 were administered triweekly. The primary endpoint was the investigator-assessed objective response rate. RESULTS: The median age at initiating chemotherapy was 80 years old. Almost all patients (92.6%) had adenocarcinoma histology. The median number of cycles administered was 6, and the objective response rate was 40.7%. The median progression-free survival, overall survival and 1-year survival were 8.8 months, 27.2 months and 79%, respectively. The treatment was well-tolerated, and no treatment-related death was observed. CONCLUSION: Combination chemotherapy with PEM plus Bev in elderly patients with previously untreated advanced non-squamous NSCLC exhibited favorable antitumor activity and tolerability, suggesting that a combination of PEM plus Bev might be a promising treatment option for this population.

Short-term inhalation of sargramostim with concomitant high-dose steroids does not hasten recovery in moderate COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) inhalation may alleviate pulmonary inflammation caused by viral pneumonia. To investigate this, we evaluated its efficacy on COVID-19 pneumonia. METHODS: This double-blind, randomised, placebo-controlled study (ClinicalTrials.gov: NCT04642950) evaluated patients in the first half of 2021 at seven Japanese hospitals. Hospitalised patients with COVID-19 pneumonia with moderate hypoxaemia inhaled sargramostim or placebo for 5 days. The primary endpoint was days to achieve a ≥ 2-category improvement from baseline on a modified 7-category ordinal scale. Secondary endpoints included degree of oxygenation, defined by amount of oxygen supply, and serum CCL17 level. RESULTS: Seventy-five patients were randomly assigned in a 2:1 ratio to receive sargramostim or placebo, of which 47 and 23 were analysed, respectively. No difference was observed between groups regarding the primary endpoint (8.0 and 7.0 days for sargramostim and placebo, respectively) or in the secondary endpoints, except for CCL17. A post hoc sub-analysis indicated that endpoint assessments were influenced by concomitant corticosteroid therapy. When the cumulative corticosteroid dose was ≤500 mg during Days 1-5, recovery and oxygenation were faster in the sargramostim group than for placebo. Bolus dose corticosteroids were associated with temporarily impaired oxygenation and delayed clinical recovery. The increase in serum CCL17, a candidate prognostic factor, reflected improvement with sargramostim inhalation. The number of adverse events was similar between groups. Two serious adverse events were observed in the sargramostim group without causal relation. CONCLUSIONS: Inhaled sargramostim was likely to be effective for COVID-19 pneumonia unless the concomitant corticosteroid dose was high.

Investigating Viral Involvement in Immunocompromised Patients Using Comprehensive Infectious Disease Testing Including FilmArray Respiratory Panel 2.1 on Bronchoscopy: A Retrospective Study.

Introduction Reports are rare on the usefulness of the FilmArray Respiratory Panel 2.1 (FARP) using lower respiratory tract specimens. This retrospective study assessed its use, as part of a comprehensive infectious disease panel, to detect the viral causes of pneumonia using bronchoalveolar lavage samples from immunosuppressed patients. Methods This study included immunocompromised patients who underwent bronchoalveolar lavage or bronchial washing by bronchoscopy between April 1, 2021, and April 30, 2022. The collected samples were submitted for comprehensive testing, including FARP test; reverse transcription polymerase chain reaction (RT-PCR) for cytomegalovirus, varicella-zoster virus DNA, and herpes simplex virus; PCR for Pneumocystis jirovecii DNA; antigen testing for Aspergillus and Cryptococcus neoformans; and loop-mediated isothermal amplification method for Legionella. Results Out of 23 patients, 16 (70%) showed bilateral infiltrative shadows on computed tomography and three (13%) were intubated. The most common causes of immunosuppression were anticancer drug use (n=12, 52%) and hematologic tumors (n=11, 48%). Only two (9%) patients tested positive for severe acute respiratory syndrome coronavirus 2 and adenovirus by FARP. Four patients (17%) tested positive for cytomegalovirus by RT-PCR, but no inclusion bodies were identified cytologically. Nine (39%) patients tested positive for Pneumocystis jirovecii by PCR, but cytology confirmed the organism in only one case. Conclusions Comprehensive infectious disease testing, performed using bronchoalveolar lavage samples collected from lung lesions in immunosuppressed patients, showed low positive detection by FARP. The viruses currently detectable by FARP may be less involved in viral pneumonia diagnosed in immunocompromised patients.

Colonic gallstone ileus treated by a transanal ileus tube followed by spontaneous gallstone dislodgement: A case report.

A 71-year-old obese woman was referred to our hospital with lower left abdominal pain. Computed tomography showed a 46 mm elliptic calcification lodged in the sigmoid-descending colon junction (SDJ), which had been detected 5 years prior but was not within the gall bladder at presentation. Therefore, we diagnosed colonic gallstone ileus with obstructive colitis caused by a gallstone. Colonoscopy revealed a smooth gallstone impacted at the sigmoid-descending colon junction, which was not fixed and could be pushed proximally with the endoscope. Dislodgement of the stone was unsuccessful with both a large polypectomy snare and a retrieval basket. Considering the high risk of surgery, we chose a non-surgical treatment strategy for obstructive colitis. Accordingly, a transanal ileus tube was placed to drain the proximal portion of the gallstone. The drainage of the colon by the ileus tube was satisfactory; the proximal colon was decompressed, ameliorating the obstructive colitis. Five days after tube placement, a colonoscopy revealed spontaneous passage of the gallstone into the rectum where it was finally removed. Cholecystocolonic fistula formation was confirmed by magnetic resonance imaging. We decided to surgically close the cholecystocolonic fistula to prevent future retrograde biliary infections. The surgery used a surgical stapler and was successful, with an uneventful postoperative course. Since radical surgical treatment of colonic gallstones and cholecystoenteric fistulas has a risk of postoperative morbidity and mortality, this case illustrates the importance of thoroughly considering nonsurgical interventions and surgeries for the safe treatment of colonic gallstone ileus.

A case of a thoracic mass negative on thoracentesis diagnosed by cryobiopsy from the visceral pleura.

Thoracoscopy under local anaesthesia is recommended for malignant tumours with negative pleural effusion cytology. Cryobiopsy from the visceral pleura by thoracoscopy under local anaesthesia can provide more diagnostic options for patients with thoracentesis-negative malignant effusions. Here we present the first case in which this technique was used. The patient had a pleural metastasis that could not be diagnosed even with rapid cytology of the parietal pleura biopsy. Indications, technical pitfalls, and safety tips are discussed.

Elevated plasma levels of Krebs von den Lungen-6 and geographic appearance on high-resolution computed tomography are associated with diffuse alveolar damage in autopsy cases of acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Although diffuse alveolar damage (DAD) is a histopathological hallmark of acute respiratory distress syndrome (ARDS), its detection without lung biopsy is challenging. In patients with ARDS, the specificity of the Berlin definition to diagnose DAD as a reference standard is not adequately high, making it difficult to adequately diagnose DAD. The purpose of this study was to investigate the relationship between DAD and clinical findings, including KL-6 and geographic appearance, in ARDS patients and to identify more specific diagnostic criteria for DAD. METHODS: Among all adult autopsy cases at a tertiary hospital in Japan between January 2006 and March 2021, patients with ARDS who met the Berlin definition criteria were included. The patients' conditions were classified according to histopathological patterns as DAD or non-DAD, and clinical characteristics, laboratory data, and high-resolution computed tomography (HRCT) findings were compared between the two groups. RESULTS: During the study period, 27 met the Berlin definition (median age: 79 years, 19 men), of whom 18 (67%) had DAD and 9 (33%) did not. In the non-DAD group, histopathologic findings revealed organizing pneumonia in seven patients and pulmonary hemorrhage in two patients. On HRCT at onset, patients with DAD had more geographic appearance than those without DAD (89% vs. 44%). In patients with geographic appearance and elevated KL-6 (> 500 U/mL), the sensitivity and specificity for DAD diagnosis were 56% and 100%, respectively. All three patients with no geographic appearance and normal KL-6 did not have DAD. CONCLUSIONS: Geographic appearance on HRCT combined with KL-6 levels may predict the presence of DAD in patients with ARDS.

Findings of virtual bronchoscopic navigation can predict the diagnostic rate of primary lung cancer by bronchoscopy in patients with peripheral lung lesions.

BACKGROUND: Despite being minimally invasive, bronchoscopy does not always result in pathological specimens being obtained. Therefore, we investigated whether virtual bronchoscopic navigation (VBN) findings were associated with the rate of diagnosis of primary lung cancer by bronchoscopy in patients with peripheral lung lesions. METHODS: This study included patients with suspected malignant peripheral lung lesions who underwent bronchoscopy at St. Luke's International Hospital between October 2013 and March 2020. Patients diagnosed with primary lung cancer were grouped according to whether their pathology could be diagnosed by bronchoscopy, and their clinical factors were compared. In addition, the distance between the edge of the lesion and the nearest branch ("distance by VBN") was calculated. The distance by VBN and various clinical factors were compared with the diagnostic rates of primary lung cancer. RESULTS: The study included 523 patients with 578 lesions. After excluding 55 patients who underwent multiple bronchoscopies, 381 patients were diagnosed with primary lung cancer. The diagnostic rate by bronchoscopy was 71.1% (271/381). Multivariate analysis revealed that the lesion diameter (odds ratio [OR] 1.107), distance by VBN (OR 0.94) and lesion structure (solid lesion or ground-glass nodule; OR 2.988) influenced the risk of a lung cancer diagnosis. The area under the receiver operating characteristic curve for diagnosis based on lesion diameter and distance by VBN was 0.810. CONCLUSION: The distance by VBN and lesion diameter were predictive of the diagnostic rates of primary lung cancer by bronchoscopy in patients with peripheral lung lesions.

Combined treatment with endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate for refractory pneumothorax in COVID-19.

Coronavirus disease 2019 (COVID-19) causes pneumothorax or mediastinal emphysema in approximately 1% of patients. According to the British Thoracic Society guidelines, the next treatment option for patients with persistent pneumothorax despite chest drainage is pleurodesis or surgery. In fact, there are reports of autologous blood pleurodesis or surgery for the treatment of pneumothorax caused by COVID-19. However, elderly patients or patients in poor general condition may not be able to tolerate surgical invasion. In this report, we present two patients who did not respond to chest drainage or pleurodesis and who were not suitable for surgery because of their poor general condition. These patients were successfully treated with an endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate. This method may be an option for the treatment of refractory pneumothorax in COVID-19.

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study.

BACKGROUND: Bronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM. METHODS: This retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort. RESULTS: In total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score. CONCLUSIONS: Bronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.

A Case of Nonsmall-Cell Lung Cancer with Anaphylaxis after 41 Courses of Pembrolizumab along with Adrenal Insufficiency as an Immune-Related Adverse Event.

In this report, we present a case of nonsmall-cell lung cancer with anaphylaxis after 41 courses of pembrolizumab along with adrenal insufficiency as an immune-related adverse event (irAE). A 73-year-old man with no allergic disease started pembrolizumab for postoperative recurrence of lung cancer. After four courses, tumor shrinkage was observed and maintained thereafter. After the 39th course, his serum sodium level and random serum cortisol level decreased. Adrenal insufficiency was considered; however, the patient was asymptomatic. Furthermore, his serum sodium level improved spontaneously; therefore, he was followed up. At the end of the 40th course, rhinorrhea and pharyngeal discomfort were noted; however, they were mild and resolved spontaneously. Immediately after administration of the 41st course, he developed pembrolizumab-induced anaphylaxis with percutaneous oxygen saturation decreased. The symptoms quickly improved after intramuscular adrenaline were administered and did not recur. Three months after discharge, the patient was urgently examined for vomiting and anorexia. His serum sodium levels decreased to 119 mEq/L, and an adrenocorticotropic hormone stimulation test was performed. It showed a low response, and the patient was diagnosed with secondary adrenal insufficiency as an irAE of pembrolizumab and treated with hydrocortisone, which quickly improved his serum sodium levels and symptoms. When adrenal insufficiency develops due to irAEs, patients may be susceptible to allergic reactions.

Reproducibility of peripheral branches in virtual bronchoscopic navigation using VINCENT and LungPoint software for peripheral lung lesions.

BACKGROUND: Recently, virtual bronchoscopic navigation (VBN) has become frequently used for the pathological specimen collection of peripheral lung lesions using various VBN software packages. Herein, we examined the reproducibility of peripheral branches in VBN software using LungPoint and VINCENT versions 4.0 and 5.5. METHODS: This study included patients suspected of malignant peripheral lung lesions who underwent bronchoscopy at our hospital from February 2016 to April 2017. Computed tomography was taken at a thickness of 1.25 mm in all cases, and VB images were created based on the computed tomography data using LungPoint, or VINCENT version 4.0 or 5.5. One observer read the program-generated VB images and compared how many branches could be visualized with the lobe bronchus as the primary branch. RESULTS: A total of 129 patients (n = 131 lesions) underwent bronchoscopy, with 82 cases of primary lung cancer. Pathological bronchoscopic diagnosis was done in 63 cases, resulting to a diagnostic rate of 76.8%. VB images generated by LungPoint, and VINCENT versions 4.0 and 5.5 reproduced an average of 4.3, 3.47, and 5.12 branches, respectively, with significant differences (p < 0.05) between them. CONCLUSIONS: VINCENT version 5.5 exhibits better reproducibility of peripheral branches than LungPoint for VBN.

A surgically treated case of severe upper gastrointestinal hemorrhage with gastritis cystica polyposa.

BACKGROUND: Gastritis cystica polyposa (GCP) is a recently recognized entity histologically characterized by hyperplasia and cystic dilatation of the gastric glands spreading through the submucosal layer. Its symptoms include those affecting the upper gastrointestinal tract, such as upper abdominal pain, nausea, and anorexia, although some patients might be asymptomatic. GCP rarely causes severe hemorrhage. Recently, we encountered a GCP case that exhibited severe hemorrhage. CASE PRESENTATION: A 53 year-old man visited the emergency department complaining of hematemesis. He underwent distal gastrectomy and Billroth II reconstruction for duodenal ulcers 32 years ago. Upper gastrointestinal endoscopy detected bleeding from the reddened mucosa at the anastomosis; thus, tentative endoscopic hemostasis was conducted. Despite medical treatment with transfusion, melena with significant hemodynamic impairment persisted. He was treated again with endoscopic hemostasis and interventional radiology (IVR) but remained unresponsive to these procedures. He eventually underwent partial resection of the anastomosis site with Roux-en-Y reconstruction and finally achieved excellent postoperative recovery. Histopathological examination of the resected specimen suggested a GCP bleeding. CONCLUSIONS: GCP can indeed cause severe hemorrhage. Hemorrhage caused by GCP may not respond to endoscopic hemostasis or IVR; therefore, surgical treatment should be decided without delay.

Thymic epithelial tumor treatment in Japan: analysis of hospital cancer registry and insurance claims data, 2012-2014.

INTRODUCTION: Thymic epithelial tumors are a rare type of neoplasm. Accordingly, it is difficult to perform phase III trials in patients with thymic epithelial tumors, and thus, no standard treatment has been established for these tumors. In this study, we aimed to investigate the current status of thymic epithelial tumor treatment in Japan. METHODS: This retrospective observational study enrolled patients with thymic epithelial tumor whose data were recorded in a nationwide Hospital-based Cancer Registry that was linked with health insurance claims data for the registered patients between 2012 and 2014. The patients' treatment details were obtained from a health insurance claims database. RESULTS: A total of 813 patients with thymoma and 547 with thymic carcinoma were included in the analysis. Overall, 549 (67.5%) thymoma patients underwent surgical resection alone. Among patients with thymic carcinoma, 230 (42.0%) underwent initial surgery, and 124 (53.9%) received subsequent radiotherapy and chemotherapy. Chemotherapy regimens varied across the hospitals; overall, 21 and 22 regimens were used to treat thymoma and thymic carcinoma, respectively. Platinum-based combination regimens were predominantly selected for both diseases. CONCLUSIONS: This study revealed the real-world patterns of thymic epithelial tumor treatment in Japan. Although the nature of this study did not enable the determination of optimal treatment strategies, the simultaneous analysis of nationwide registry, insurance, efficacy and prognostic data may contribute to the establishment of a standard treatment strategy for rarely occurring cancers such as thymic epithelial tumor.

Primary Synovial Sarcoma of the Mediastinum with Long-term Follow-up.

Chest radiography showed a right posterior mass on the mediastinum of an 84-year-old woman. The mass had been growing gradually for four years. Surgical excision was performed, and a pathological examination found the mass to be consistent with primary synovial sarcoma (SS) of the mediastinum. To our knowledge, this is a rare case in which follow-up imaging was able to be performed over a period of four years. This disease is aggressive, and its early diagnosis is key to achieving a cure. It is important to consider primary SS in the differential diagnosis of a primary intra-thoracic tumor, even if the tumor grows slowly.

Small Cell Lung Cancer in a 20-year-old Non-Smoking Man with Systemic Sclerosis.

Small cell lung cancer (SCLC) is a neuroendocrine tumor, and the median age of onset is about 70 years old. A 20-year-old non-smoking man with known systemic sclerosis presented with discomfort in his left chest. Chest X-ray showed a mass shadow in the left upper zone. A transbronchial lung biopsy revealed small cell carcinoma, and imaging studies reached the diagnosis of extensive disease small cell lung cancer. He had concurrent interstitial lung disease with a non-specific interstitial pneumonia pattern and anti-Scl-70 antibodies. He died eight months after the diagnosis during fifth-line chemotherapy. We herein report the youngest case to date of SCLC with systemic sclerosis.

Tunable separations based on a molecular size effect for biomolecules by poly(ethylene glycol) gel-based capillary electrophoresis.

We report novel capillary gel electrophoresis (CGE) with poly(ethylene glycol) (PEG)-based hydrogels for the effective separations of biomolecules containing sugars and DNAs based on a molecular size effect. The gel capillaries were prepared in a fused silica capillary modified with 3-(trimethoxysilyl)propylmethacrylate using a variety of the PEG-based hydrogels. After the fundamental evaluations in CGE regarding the separation based on the molecular size effect depending on the crosslinking density, the optimized capillary provided the efficient separation of glucose ladder (G1 to G20). In addition, another capillary showed the successful separation of DNA ladder in the range of 10-1100 base pair, which is superior to an authentic acrylamide-based gel capillary. For both glucose and DNA ladders, the separation ranges against the molecular size were simply controllable by alteration of the concentration and/or units of ethylene oxide in the PEG-based crosslinker. Finally, we demonstrated the separations of real samples, which included sugars carved out from monoclonal antibodies, mAbs, and then the efficient separations based on the molecular size effect were achieved.