Atezolizumab-related sclerosing cholangitis with multiple liver abscesses in a patient with lung squamous cell carcinoma: A case report.

A 76-year-old man underwent an operation for lung squamous cell carcinoma in the right lower lobe, followed by initial adjuvant therapy with atezolizumab, an antibody against anti-programmed death-ligand 1 (PD-L1). On day 4 after atezolizumab treatment, the patient developed general malaise and fatigue. He was diagnosed with atezolizumab-induced sclerosing cholangitis. Steroid treatment was started, and patient's condition, including symptoms, laboratory data and imaging findings, improved. Antibiotic treatments were ended on day 40, and the steroid dose was gradually reduced. Multiple liver abscesses were observed on day 106, and another treatment with antibiotics became necessary. The patient eventually recovered from liver abscesses. Sclerosing cholangitis induced by immune checkpoint inhibitor is rare, and the long-term clinical data about this adverse effect is limited. Hence, we think it is important to raise an alarm over sclerosing cholangitis coupled with liver abscesses after immunosuppressive therapy.

A retrospective study of the efficacy of combined EGFR­TKI plus VEGF inhibitor/cytotoxic therapy vs. EGFR­TKI monotherapy for PD­L1­positive EGFR­mutant non­small cell lung cancer: North Japan Lung Cancer Study Group 2202.

The present multicenter study was performed to compare the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy with that of combined EGFR-TKI plus vascular endothelial growth factor receptor (VEGF) inhibitor/cytotoxic therapy in patients with programmed death-ligand 1 (PD-L1)-positive EGFR-mutant non-small cell lung cancer (NSCLC). Data from patients with PD-L1-positive EGFR-mutant NSCLC were collected from 12 institutes. Survival in patients treated with first- and second-generation EGFR-TKIs, osimertinib (third-generation EGFR-TKI), and combined EGFR-TKI plus VEGF inhibitor/cytotoxic therapy was analyzed by multiple regression analysis with adjustments for sex, performance status, EGFR mutation status, PD-L1 expression level, and the presence or absence of brain metastasis using a Cox proportional hazards model. Data from a total of 263 patients were analyzed, including 111 (42.2%) patients who had received monotherapy with a first- or second-generation EGFR-TKI, 132 (50.2%) patients who had received osimertinib monotherapy, and 20 (7.6%) patients who had received combined EGFR-TKI plus VEGF inhibitor/cytotoxic therapy (hereafter referred to as combined therapy). Multiple regression analysis using the Cox proportional hazards model showed that the hazard ratio (95% confidence interval) for progression-free survival was 0.73 (0.54-1.00) in the patients who had received osimertinib monotherapy and 0.47 (0.25-0.90) in patients who had received combined therapy. The hazard ratio for overall survival was 0.98 (0.65-1.48) in the patients who had received osimertinib monotherapy and 0.52 (0.21-1.31) in patients who had received combined therapy. In conclusion, combined therapy was associated with a significant reduction in the risk of progression compared with first- and second-generation EGFR-TKI monotherapy, and therefore, may be promising for the treatment of patients of NSCLC.

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data.

Introduction: Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017. Methods: This multicenter observational study was conducted by the Japanese Lung Cancer Society using PMACS data with the newly created central registration system regarding patients with NSCLC who received pembrolizumab monotherapy between February 1, 2017 and June 30, 2017; a new database was created by adding the clinical information regarding prognosis for 3 years after therapy to the existing data collected by PMACS. Results: A total of 300 patients from 43 facilities were enrolled in this study. The median overall survival and progression-free survival after pembrolizumab initiation were 558 and 188 days, respectively. Moreover, the 1- and 3-year survival rates were 58.9% and 33.7%, respectively. Results of multivariate analysis revealed performance status (p < 0.0001), histology (p = 0.0118), previous chemotherapy (p = 0.0007), programmed death-ligand 1 expression status (p = 0.0195), and previous steroid use (p = 0.0460) as significant factors that affected overall survival. The toxicity profile was similar to that previously reported. Conclusions: In this first attempt to use PMACS data, we successfully collected clinical information and found the real-world efficacy and safety of pembrolizumab.

Real-world outcomes of chemotherapy for lung cancer patients undergoing hemodialysis: A multicenter retrospective cohort study (NEJ-042).

INTRODUCTION: Malignant tumors are the major cause of death in hemodialysis patients. Management of these patients remains challenging as there is no evidence that chemotherapy is beneficial, and a lack of information about actual clinical practice. METHODS: This multicenter retrospective study included hemodialysis patients who were diagnosed with lung cancer from January 2002 to June 2018. We reviewed their clinical information including patient characteristics associated with lung cancer and end-stage renal disease, regimen, efficacy and safety of chemotherapy, and outcomes. RESULTS: A total of 162 patients from 22 institutions in Japan were registered. Of 158 eligible patients, 91 received chemotherapy (80 as palliative chemotherapy and 11 as chemoradiotherapy) and 67 received best supportive care only regardless of cancer stage. In small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients who received cytotoxic chemotherapy, the objective response rates (ORR) and median overall survival (OS) were 68.1 %, 12.3 months and 37.0 %, 8.5 months, respectively. The ORR and median OS in patients with EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) were 44.4 % and 38.6 months. The treatment-related adverse events (Grade 3 or higher) induced by cytotoxic chemotherapy were myelosuppression and febrile neutropenia; treatment-related death (TRD) was observed in one patient. TRD occurred in 3 of 18 patients who received EGFR-TKI. CONCLUSION: Chemotherapy should be considered for hemodialysis patients with EGFR-mutant NSCLC and SCLC. However, the survival benefits of chemotherapy for NSCLC patients with EGFR-wild type are unclear; physicians should carefully consider whether to offer chemotherapy to this patient subset.

Comparison of sputum specimens and nasopharyngeal swab specimens for diagnosis of acute human metapneumovirus-related lower respiratory tract infections in adults.

BACKGROUND: To detect human metapneumovirus, tests besides reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens are less accessible. Immunochromatography assays are rapid and simple without the need of any special equipment but sometimes are insufficiently sensitive. This study describes the usefulness of immunochromatography assays to detect human metapneumovirus in adult patients with human metapneumovirus-related acute lower respiratory tract infection using sputum specimens. METHODS: This prospective single-center study enrolled adults and adolescents aged ≥16 years with signs and symptoms of an acute respiratory illness who were diagnosed with acute lower respiratory tract infection. The presence of human metapneumovirus infection was confirmed by seroconversion. Immunochromatography assays and real-time RT-PCR were performed to compare the efficacy of nasopharyngeal swab specimens and sputum specimens. Comparative results were obtained via McNemar's test. RESULTS: Overall, 337 patients were recruited in this study; 63 (18.7%) patients were seroconverted. Sputum specimens showed significantly higher positivity rates than nasopharyngeal swab specimens with both immunochromatography assays (p = 0.0008) and real-time RT-PCR (p = 0.014). Among 29 patients with pneumonia who had concordant positive real-time RT-PCR results for both nasopharyngeal swab specimens and sputum specimens, 21 (72.4%) had a higher viral load in the sputum specimens. CONCLUSIONS: Sputum specimens are more useful in detecting human metapneumovirus than nasopharyngeal swab specimens in adult patients with acute lower respiratory tract infection.

Legionella pneumonia immediately after recovery from COVID-19.

We experienced a patient with Legionella pneumonia developing immediately after discharge from COVID-19 recovery. Antibiotic treatment was successful. The source of Legiolella infection was proven to be bathtub water in this case. It is very important to accurately detect pathogens, particularly in the time of pandemics such as COVID-19.

Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).

BACKGROUND: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. METHODS: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. RESULTS: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. CONCLUSION: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

Phase I/II study of biweekly nab-paclitaxel in patients with platinum-pretreated non-small cell lung cancer: NJLCG1402.

BACKGROUND: NJLCG1402 was a phase I/II trial investigating biweekly nanoparticle albumin-bound paclitaxel (nab-PTX) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: The study included patients aged ≥20 years with previously treated NSCLC. Nab-PTX (100-150 mg/m2 ) was administered biweekly in a 28-day cycle. The phase I portion was performed to determine the recommended phase II dose of nab-PTX. In the phase II portion, the primary endpoint was the objective response rate. Secondary endpoints were disease control rate, progression-free survival, overall survival, and safety. RESULTS: A total of 15 patients received biweekly nab-PTX (100-150 mg/m2 ) and 12 patients in phase II were treated with 150 mg/m2 . In the phase I portion, 150 mg/m2 was determined as the recommended dose. Among those treated with 150 mg/m2 , the objective response rate was 22%, and the median progression-free and overall survival was 3.6 and 11.2 months, respectively. Adverse events grade ≥3 were observed in 39% of patients. CONCLUSIONS: Biweekly nab-PTX monotherapy was well tolerated and exhibited favorable antitumor activity in patients with previously treated NSCLC.

A useful and safe method for retrieving a round metallic object from an airway.

The endoscopic net forceps with the support of a laryngeal mask airway are a dependable choice for retrieving a round metallic object from an airway.

Phase II Study of Low-Dose Afatinib Maintenance Treatment Among Patients with EGFR-Mutated Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1601 (NJLCG1601).

LESSONS LEARNED: Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety. BACKGROUND: Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated. METHODS: Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity. RESULTS: Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%). CONCLUSION: Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.

[[TUBERCULOSIS DIAGNOSIS FOLLOWING A VISIT TO THE EMERGENCY ROOM].]

We aimed to evaluate the clinical char- acteristics of patients admitted to the emergency room (ER) and diagnosed with tuberculosis. [Method] We conducted a retrospective study of patients aged ; 16 years admitted to the hospital between April 1980 and March 2015 and diagnosed with tuberculosis. We com- pared patient clinical characteristics and type of tuberculosis between ER and non-ER patients. We also compared the incidence of delayed diagnosis of tuberculosis between ER patients with and without respiratory symptoms. We compared the tuberculosis encounter rate and the time to diagnosis of tuberculosis in ER and non-ER patients. [Results] A total of 255 patients, including 54 ER and 201 non-ER patients were enrolled in this study. The average age J was higher in ER patients than in non-ER patients (71.7? 16.3 vs. 63.3 ?20.3 years, p=0.006). The reasons for visiting the ER included acute conditions such as fracture of the lumbar spine, acute myocardial infarction, hemorrhagic gastric ulcer, brain infarction, and carbon monoxide intoxication, requiring immediate treatment. The time to diagnosis of tuberculosis in ER patients without respiratory symptoms (n=21) was approximately three times longer than that in patients with respiratory symptoms (n=33) as urgent treatment is priori- tized. The tuberculosis encounter rate was 1/1,800 for pa- tients transported by ambulance and 1/22,000 for emergency outpatients. The time to diagnosis of tuberculosis for patients transported by ambulance was approximately 4-6 days lon- ger than that for emergency outpatients or non-ER patients. [Conclusion] Physicians should seek to rule out the possi- bility of tuberculosis in all patients admitted to the ER, even where more urgent clinical conditions are prioritized.

[Occurrence and clinical characteristics of tuberculosis among home medical care patients].

OBJECTIVE: To clarify the occurrence and clinical characteristics of tuberculosis among home medical care patients, we conducted a retrospective study of patients who received home medical care from our hospital. SUBJECTS AND METHODS: We investigated 502 patients (mean age, 79.5 years) who received home medical care from our hospital between January 2003 and December 2012. The newly notified tuberculosis cases aged > or = 70 years in the general population in Miyagi were defined as the control group. Among the patients receiving home medical care, we evaluated the clinical characteristics of the patients with tuberculosis. RESULTS: Four of the 502 patients (0.8%) developed tuberculosis. Using the person-years method, the case rate of tuberculosis was calculated as 298.3 per 100,000 among home medical care patients. Compared with the control group, home medical care patients had a greater incidence of tuberculosis (298.3 vs. 36.06; rate ratio, 8.27; 95% confidence interval, 3.06-22.3; p < 0.001). When home medical care patients visited the hospital or were transported there by ambulance, they were initially often diagnosed with aspiration pneumonia. Moreover, the time interval to the onset of disease from the introduction of home medical care varied among cases (3-192 months). CONCLUSION: Patients receiving home medical care are at high risk of contracting tuberculosis. Therefore, for the medical staff involved in treating home medical care patients, the onset of tuberculosis should be carefully considered in daily medical practice.

[A case of septic pulmonary embolism due to Peptostreptococcus micros with multiple infection of the head and neck].

A 46-year-old man with no underlying diseases visited our hospital with otorrhea, ocular motility disorder of the left eye, dizziness and loss of appetite which had lasted for two months. Chest radiography and computed tomography (CT) showed bilateral multiple pulmonary nodules and cavities. Furthermore, CT of the head and neck revealed bilateral mastoiditis, a left orbital abscess and a deep neck abscess. Peptostreptococcus micros was cultured from blood and otorrhea specimens. In addition, P. micros DNA was detected with the polymerase chain reaction (PCR) method in the specimens from the site of culture-negative lesions (i.e. sputum, bronchoalveolar lavage, neck abscess). Thus, we diagnosed the lung lesions as septic pulmonary embolisms (SPEs). The clinical findings of the head and neck had improved following antibiotics treatment for five weeks, and follow-up chest radiography and CT showed that all lesions almost disappeared. Since some SPE patients demonstrate a slow progression, SPE should be included in the differential diagnosis of multiple pulmonary nodules such as Wegener's glanulomatosis or neoplasm.