Endobronchial Ultrasonography With Guide Sheath for the Diagnosis of Peripheral Pulmonary Lesions in Japan: A Literature Review.

We evaluated the usefulness of endobronchial ultrasonography with guide sheath (EBUS-GS) for the diagnosis of peripheral pulmonary lesions (PPLs) in Japan. We searched the PubMed/Medline database using the keywords "EBUS guide sheath" for Japanese studies on EBUS-GS published between January 2004 and August 2023. We included 32 original articles that evaluated the diagnostic yield of EBUS-GS for PPLs. Case reports and conference abstracts were excluded due to limited information available for quality assessment. The diagnostic yield of EBUS-GS was 73.6% for 2996 malignant lesions, 65.4% for 752 ground-glass nodules, 59.4% for 414 benign lesions, 61.3% for 1114 lesions of size ≤2 cm, and 75.6% for 1246 lesions of size >2 cm; it was 69.4% for lesions located in the upper lobe (n=793), 71.9% for the middle lobe/lingula (n=121), and 62.5% for the lower lobe (n=334). None of the patients experienced severe complications. In this review, EBUS-GS is effective for the diagnosis of malignant and benign PPLs. A multimodality approach is needed to further enhance its diagnostic performance.

Pneumocystis jirovecii pneumonia mortality risk associated with preceding long-term steroid use for the underlying disease: A multicenter, retrospective cohort study.

OBJECTIVE: Long-term steroid use increases the risk of developing Pneumocystis pneumonia (PcP), but there are limited reports on the relation of long-term steroid and PcP mortality. METHODS: Retrospective multicenter study to identify risk factors for PcP mortality, including average steroid dose before the first visit for PcP in non-human immunodeficiency virus (HIV)-PcP patients. We generated receiver operating characteristic (ROC) curves for 90-day all-cause mortality and the mean daily steroid dose per unit body weight in the preceding 10 to 90 days in 10-day increments. Patients were dichotomized by 90-day mortality and propensity score-based stabilized inverse probability of treatment weighting (IPTW) adjusted covariates of age, sex, and underlying disease. Multivariate analysis with logistic regression assessed whether long-term corticosteroid use affected outcome. RESULTS: Of 133 patients with non-HIV-PcP, 37 died within 90 days of initial diagnosis. The area under the ROC curve for 1-40 days was highest, and the optimal cutoff point of median adjunctive corticosteroid dosage was 0.34 mg/kg/day. Past steroid dose, underlying interstitial lung disease and emphysema, lower serum albumin and lower lymphocyte count, higher lactate dehydrogenase, use of therapeutic pentamidine and therapeutic high-dose steroids were all significantly associated with mortality. Underlying autoimmune disease, past immunosuppressant use, and a longer time from onset to start of treatment, were associated lower mortality. Logistic regression analysis after adjusting for age, sex, and underlying disease with IPTW revealed that steroid dose 1-40 days before the first visit for PcP (per 0.1 mg/kg/day increment, odds ratio 1.36 [95% confidence interval = 1.16-1.66], P<0.001), low lymphocyte counts, and high lactate dehydrogenase revel were independent mortality risk factor, while respiratory failure, early steroid, and sulfamethoxazole/trimethoprim for PcP treatment did not. CONCLUSION: A steroid dose before PcP onset was strongly associated with 90-day mortality in non-HIV-PcP patients, emphasizing the importance of appropriate prophylaxis especially in this population.

Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.

PURPOSE: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. METHODS: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. RESULTS: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6-82.7 mm). In the full analysis set, the adjusted mean change in VAS was - 22.07 and - 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was - 2.99 mm (95% confidence interval [CI] - 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. CONCLUSION: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. CLINICAL TRIAL REGISTRATION: JapicCTI-184143/jRCT2080224082 (October 5, 2018).

Value of adding ultrathin bronchoscopy to thin bronchoscopy for peripheral pulmonary lesions: A multicentre prospective study.

BACKGROUND AND OBJECTIVE: The diagnostic yield of thin bronchoscopy with radial probe endobronchial ultrasound (rEBUS) of peripheral pulmonary lesions into which the rEBUS probe cannot be inserted is unsatisfactory. In such cases, adding ultrathin bronchoscopy may be an option. We evaluated the efficacy of sequential ultrathin bronchoscopy for peripheral pulmonary lesions into which the rEBUS probe could not be inserted during thin bronchoscopy. METHODS: In this multicentre prospective study, patients with peripheral pulmonary lesions ≤30 mm in diameter underwent rEBUS-guided transbronchial biopsy using a 4.0 mm diameter thin bronchoscope. In patients with lesions into which a rEBUS probe could not be inserted using that bronchoscope, bronchoscopy using a 3.0 mm diameter ultrathin bronchoscope was performed. RESULTS: A total of 342 patients were enrolled and 340 were analysed. Among them, 87 patients with lesions of a median longest diameter of 17.5 mm underwent thin bronchoscopy followed by ultrathin bronchoscopy. Of the 87 patients, the rEBUS probe was successfully inserted into the lesions via the ultrathin bronchoscope in 50 patients (57.5%). Of the 87 patients, the diagnostic yields of thin bronchoscopy and ultrathin bronchoscopy were 12.6% (11 of 87) and 41.4% (36 of 87), respectively (p < 0.001). CONCLUSION: Ultrathin bronchoscopy affords a higher diagnostic yield for lesions into which a rEBUS probe cannot be inserted via a thin bronchoscope.

Broken Tip of a Disposable Saliva Ejector as a Bronchial Foreign Body in a Patient With Severe Physical and Intellectual Disabilities.

Oral care for patients with severe physical and intellectual disabilities is important to prevent the development of systemic diseases and maintain or improve their health. Foreign bodies accidentally aspirated into the respiratory tract can cause critical problems. To our knowledge, this is the first case report of aspiration of a broken tip of a disposable saliva ejector in a patient with severe physical and intellectual disabilities. The patient's strong bite broke off the ejector's tip during oral care. The foreign body was removed by flexible bronchoscopy without any complications. Such cases are sometimes asymptomatic or mildly symptomatic; thus, learning how to appropriately respond is essential for caregivers and family doctors. In addition, this device is widely used in clinical practice, and such risks should be widely known. Moreover, manufacturers should develop more robust equipment for oral care.

Pneumocystis jirovecii Pneumonia in Three Patients With Breast Cancer Receiving Neoadjuvant Dose-Dense Chemotherapy.

We report three cases of Pneumocystis jirovecii pneumonia (PJP) during dose-dense neoadjuvant chemotherapy for breast cancer. All patients presented with symptoms (e.g., fever), and computed tomography showed diffuse ground-glass shadows. Bronchoalveolar lavage was performed, and the diagnosis was confirmed by polymerase chain reaction for Pneumocystis jirovecii. All patients had completed three or four courses of dose-dense epirubicin-cyclophosphamide chemotherapy and received prednisolone for preventing chemo-induced nausea and vomiting. Moreover, lymphocytopenia was observed in all patients. Since the onset of PJP in preoperative neoadjuvant chemotherapy can be life-threatening and leads to delayed surgery, careful consideration of prophylaxis for PJP is required.

Thoracic Empyema Caused by Campylobacter rectus.

Campylobacter rectus is a campylobacterium considered to be a primary periodontal pathogen. Thus, C. rectus has rarely been isolated from extraoral specimens, especially in the thoracic region. We herein report a case of thoracic empyema in which Campylobacter infection was suspected after Gram staining of the pleural effusion, and C. rectus was isolated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fusobacterium nucleatum was also detected. Molecular identification was performed using polymerase chain reaction amplification and a sequencing analysis of the 16S rRNA gene. Estimation of the causative bacteria using Gram staining led to the proper culture and identification of the causative bacteria.

Guide sheath versus non-guide sheath method for endobronchial ultrasound-guided biopsy of peripheral pulmonary lesions: a multicentre randomised trial.

BACKGROUND: Guide sheaths (GSs) have been widely used during radial probe endobronchial ultrasound-guided transbronchial biopsy (rEBUS-TBB) of peripheral pulmonary lesions. However, it remains unknown whether a GS enhances the diagnostic yield. We compared the diagnostic yields of small peripheral pulmonary lesions between rEBUS-TBB with and without a GS. METHODS: In eight institutions, patients with peripheral pulmonary lesions ≤30 mm in diameter were enrolled and randomised to undergo rEBUS-TBB with a GS (GS group) or without a GS (non-GS group) using a 4.0-mm thin bronchoscope, virtual bronchoscopic navigation and fluoroscopy. The primary end-point was the diagnostic yield of the histology specimens. RESULTS: A total of 605 patients were enrolled; ultimately, data on 596 (300 in the GS group and 296 in the non-GS group) with peripheral pulmonary lesions having a longest median diameter of 19.6 mm were analysed. The diagnostic yield of histological specimens from the GS group was significantly higher than that from the non-GS group (55.3% versus 46.6%; p=0.033). Interactions were evident between the diagnostic yields, procedures, lobar locations (upper lobe versus other regions; p=0.003) and lesion texture (solid versus part-solid nodules; p=0.072). CONCLUSIONS: The diagnostic yield for small peripheral pulmonary lesions afforded by rEBUS-TBB using a GS was higher than that without a GS.

Pneumocystis Pneumonia in a Patient with Ovarian Cancer Receiving Olaparib Therapy.

We herein report a case of pneumocystis pneumonia (PCP) in a 77-year-old woman with ovarian cancer who was receiving olaparib therapy. After the patient's second relapse of ovarian cancer, she was administered olaparib as maintenance therapy following successful completion of docetaxel and carboplatin therapy. On receiving olaparib, she showed symptoms of a fever and malaise. Based on laboratory and imaging findings, she was diagnosed with PCP. After treatment with corticosteroids and trimethoprim/sulfamethoxazole followed by atovaquone, the patient's general condition improved. The lymphocytopenia observed after olaparib administration may have been associated with the development of PCP.

Japanese Spotted Fever Complicated With Life-Threatening Ventricular Tachycardia and Acute Cardiac Damage.

A 67-year-old man with high-grade fever and systemic erythema visited our hospital. Based on his symptoms and history of outdoor activities, we considered the possibility of rickettsial diseases, especially Japanese spotted fever (JSF). He was treated with antibiotics. After hospitalization, the patient complained of palpitations, and electrocardiography revealed ventricular tachycardia (VT). He was successfully treated with electrical defibrillation. Moreover, echocardiography showed decreased wall motion at the apex. However, coronary angiography showed no coronary artery-related stenosis. JSF was confirmed via polymerase chain reaction using a biopsy sample of the erythema. Subsequently, the patient was discharged without complications. To our knowledge, this is the first reported case of JSF complicated with VT and acute cardiac damage.

Snowball-like appearance on radial endobronchial ultrasonography in a patient with invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA), which is a relatively rare lung adenocarcinoma, is considered a high-grade subtype and is associated with a poor prognosis. IMA is difficult to diagnose by computed tomography because it requires differentiation from inflammatory diseases, such as atelectasis, infectious pneumonia, and organizing pneumonia. Thus far, no reports of radial endobronchial ultrasonography (EBUS) findings in IMA have been published. This article presents a case of IMA with a characteristic shadow, snowball-like appearance on radial EBUS in a 67-year-old Japanese man.

A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7-14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.

Direct Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from Domestic Cat to Veterinary Personnel.

Two veterinary personnel in Japan were infected with severe fever with thrombocytopenia syndrome virus (SFTSV) while handling a sick cat. Whole-genome sequences of SFTSV isolated from the personnel and the cat were 100% identical. These results identified a nosocomial outbreak of SFTSV infection in an animal hospital without a tick as a vector.

Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101).

LESSONS LEARNED: This phase II trial evaluated the efficacy of erlotinib for patients with non-small cell lung cancer with leptomeningeal metastasis. The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance-conferring T790M mutation. The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%-54.3%). The median time to progression was 2.2 months. The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis. BACKGROUND: Leptomeningeal metastases (LM) occur in approximately 5% of patients with non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. However, no prospective study has identified an active chemotherapeutic drug in this setting. METHODS: Patients were considered eligible to receive erlotinib if they had NSCLC with cytologically confirmed LM. The objective cytological clearance rate, time to LM progression (TTP), overall survival (OS), quality of life outcomes, and pharmacokinetics were analyzed. This study was closed because of slow accrual at 21 of the intended 32 patients (66%). RESULTS: Between December 2011 and May 2015, 21 patients (17 with activating epidermal growth factor receptor [EGFR] mutations) were enrolled. The 17 cerebrospinal fluid specimens available were all negative for the T790M mutation, which confers erlotinib resistance. The clearance rate was 30.0% (95% confidence interval [CI]: 11.9%-54.3%), the median TTP was 2.2 months, and the median OS was 3.4 months. Significantly longer TTP and OS times were observed in patients with mutant EGFR (p = .0113 and p < .0054, respectively). The mean cerebrospinal fluid penetration rate was 3.31% ± 0.77%. There was a good correlation between plasma and cerebrospinal fluid (CSF) concentrations, although there was no clear correlation between pharmacokinetic parameters and clinical outcome. CONCLUSION: Erlotinib was active for LM and may be a treatment option for patients with EGFR-mutated NSCLC and LM.

Endobronchial metastasis of ovarian cancer rescued by tumor ablation and a self-expanding hybrid stent: A case report and review of the literature.

Tracheal stenosis caused by malignancy is a life-threatening complication. Herein, we performed tumor ablation and airway stenting using a hybrid stent on a patient with upper tracheal stenosis caused by endobronchial metastasis of ovarian cancer. To date, only 9 cases of endobronchial metastasis of ovarian cancer have been reported. This is the first reported case of endobronchial metastasis in the upper part of the trachea, which had a favorable outcome after tumor ablation as a sequential treatment and use of a hybrid stent. In addition, 10 cases of endobronchial metastasis of ovarian cancer, including ours and other case reports, were reviewed.

Clinical Evaluation of Endoscopic Bronchial Occlusion with an Endobronchial Watanabe Spigot for the Management of Intractable Pneumothorax, Pyothorax with Bronchial Fistula, and Postoperative Air Leakage.

Objective The present study aimed to evaluate the clinical effectiveness of endoscopic bronchial occlusion (EBO) with endobronchial Watanabe spigots (EWSs) for the management of prolonged pulmonary air leaks, such as intractable pneumothorax, pyothorax with bronchial fistula, and postoperative air leakage. Methods This was a retrospective study. Between April 2005 and March 2018, we recruited 21 patients with intractable pneumothorax (10 cases), pyothorax with bronchial fistula (7 cases), and postsurgical pulmonary fistula (4 cases) in whom appropriate drainage for 2 weeks had been unsuccessful and who were unsuitable for surgery. An EWS was inserted using a flexible bronchoscope via an endotracheal or a tracheostomy tube. Results The mean number of sessions with EWS procedures was 1.94, and the mean number of inserted EWS per patient was 6.5. In addition to EWS procedures, pleural washing and pleural adhesion therapy were performed in all cases with pyothorax, whereas pleural adhesion therapy was performed in three patients with pneumothorax. The successful treatment rate was 85.7%. Reduction of air leakage was observed in 19/21 patients. The mean duration of reduction of air leaks was 4.1 days (median, 1; range, 0-24 days) following EWS procedures. The mean duration from tube insertion to chest tube removal was 43.4 days (median, 29; range, 16-105 days). Complications included spigot migration and infection (aspergillosis); no complications caused significant mortality. Conclusion Performing EBO using an EWS appears to be a reasonable option for the management of intractable pneumothorax, pyothorax with pulmonary fistula, and postoperative air leakage.

Bronchial mucoepidermoid carcinoma, recurrent asthmatic symptoms, and pneumonia presenting in pregnancy.

We report the case of a 37-year-old pregnant Japanese woman (34th week of gestation) with a left main bronchus mucoepidermoid carcinoma. She had left lower lung pneumonia episodes for eight weeks that had been associated with bronchial asthma. Bronchoscopy revealed a membranous endobronchial tumour obstructing most of the left main bronchus. We delivered the baby without any problems by caesarean section, followed by tumour cauterization using a rigid bronchoscope under general anaesthesia. After that, we performed a sleeve resection of the main left bronchus. At one-year follow-up, the patient was disease-free and her baby was growing well.

Clinical features and treatment outcomes of opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia-lymphoma (ATL) at a single institution from 2006 to 2016.

As opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia/lymphoma (ATL) pose a serious problem, it is necessary to clarify their clinical characteristics and outcomes in these patients. We retrospectively analyzed the clinical features and outcomes of opportunistic infections in 127 HTLV-1 carriers and 153 ATL patients between 2006 and 2016. The cumulative incidence rates of opportunistic infections among HTLV-1 carriers and ATL patients were 1.5% (2/127) and 6.5% (10/153), respectively. The etiology of opportunistic infections was as follows: fungal infections (3 cases), pneumocystis pneumonia, and cytomegalovirus (CMV) infections. Even after aggressive treatment, the prognosis of opportunistic infections was poor (50% of overall survival at 28 days). Regarding prognostic factors affecting the OS of opportunistic infections, higher SOFA scores (especially the respiratory subscore) and higher LDH values were identified by univariate analysis. Moreover, 3 out of 6 patients achieved spontaneous remission of ATL as the short-term outcome after the development of opportunistic infection. However, 5 out of 6 surviving patients exhibited ATL progression or relapse after a median of 194 days (133-226) after contracting an opportunistic infection as the long-term outcome of ATL. In conclusion, opportunistic infections should be carefully followed among HTLV-1 carriers and ATL patients because of their aggressive clinical course and poor outcomes. Furthermore, early diagnosis and subsequent prompt treatment are necessary in clinical practice.

Severe tracheal stenosis after first administration of pembrolizumab rescued by Dumon Y-stent in a lung cancer patient.

A 70-year-old woman diagnosed with advanced, non-resectable programmed cell death ligand 1-positive-non-small-cell lung carcinoma was treated with pembrolizumab as first-line therapy. Soon after therapy initiation, she presented with severe dyspnea, and chest computed tomography revealed a soft tissue mass in the lower trachea of the right main bronchus. During bronchoscopy, she became severely hypoxic, and we performed endoscopic tumor ablation and Dumon Y-stent placement. We considered this severe deterioration caused by pseudoprogression, and suggest that it is necessary to perform bronchoscopy and to prepare for the bronchial intervention when treating patients with immune checkpoint inhibitors.

Pulmonary Actinomyces graevenitzii Infection Diagnosed by Bronchoscopy using Endobronchial Ultrasonography with a Guide Sheath.

A 75-year-old man visited our hospital complaining of a low-grade fever, dry cough, and chest abnormal shadow. Chest computed tomography revealed a nodule with a cavity in the right upper lobe. Endobronchial ultrasonography (EBUS) of the lesion suggested that the lesion was benign. Actinomyces graevenitzii was cultured from the specimen obtained by bronchoscopy using endobronchial ultrasonography with a guide sheath technique and was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. The patient was treated with intravenous ampicillin; subsequently, his condition improved. We believe that careful observation of EBUS findings may be useful for the differential diagnosis.