Acute Hepatitis E Infection during Chemotherapy for Lung Cancer: A Case Report.

Acute hepatitis E, one of the causes of acute liver injury, has been increasingly diagnosed in developed countries in recent years. Misdiagnosis of acute hepatitis E virus (HEV) infection as drug-induced liver injury (DILI) may lead to discontinuation of effective chemotherapy. Thus, viral hepatitis, including hepatitis E, must be ruled out in the diagnosis of DILI. A 78-year-old woman with lung adenocarcinoma and multiple bone metastases received maintenance therapy with pemetrexed + pembrolizumab for a year. Increased aspartate aminotransferase and alanine aminotransferase levels, indicating acute liver injury, were observed. Initially, DILI was suspected, and she was given medications to lower the levels of hepatic enzymes. She was later admitted to the hospital with the chief complaint of general malaise and anorexia. Serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated (381 and 854 U/L, respectively). Acute HEV infection was diagnosed based on the detection of serum HEV immunoglobulin A antibodies. The patient received liver support therapy, and the serum hepatic enzymes recovered to normal levels. Chemotherapy was resumed without any subsequent relapse of hepatic enzyme elevation. When DILI is suspected during chemotherapy, exclusion of viral hepatitis is mandatory, which can be achieved by measuring markers of hepatitis viruses, including HEV, and examining the patient's detailed medical history.

Safety of bronchoscopy in patients with malignant hematologic disorders.

BACKGROUND: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. METHODS: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. RESULTS: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09-0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18-25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14-0.73, p = 0.01). CONCLUSIONS: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.

Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.

BACKGROUND: Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. CASE PRESENTATION: A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. CONCLUSIONS: Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Gefitinib successfully administered in a lung cancer patient with leptomeningeal carcinomatosis after erlotinib-induced pneumatosis intestinalis.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. CASE PRESENTATION: A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. CONCLUSION: PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult. CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass. CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2-positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM.

[Evaluation of mycobacterial infections using 18F-fluorodeoxyglucose-positron emission tomography: results of nine cases].

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) is a useful technique for distinguishing malignant and benign lesions, although the occurrence of false-positive results in cases involving benign lesions is possible. We evaluated nine patients with mycobacterial infections who underwent FDG-PET/CT from April 2008 to July 2010. FDG-PET/CT was performed 1-2h (during the early and late phases) after administration of FDG at a dose of 185 MBq/individual after fasting for at least 5h. Out of the nine patients, four were diagnosed with pulmonary nonmycobacterium tuberculosis, two with pulmonary tuberculosis, two with tuberculous lymphadenopathy, and one with pleural tuberculoma. All patients had a maximum standardized uptake value (SUV(max)) of > 2.5, and the SUV(max) increased from the early to the late phase. One lesion that occurred due to tuberculous pleurisy after treatment demonstrated high FDG uptake, similar to the other cases. It is difficult to distinguish mycobacterial infections from malignant diseases using FGD-PET alone; hence, the use of high-resolution CT and bacteriological tests is required for diagnosis and distinction.

Early diagnosis of tuberculous peritonitis in peritoneal dialysis patients using the T-SPOT test.

A 49-year-old man was admitted with peritonitis nine months after starting continuous ambulatory peritoneal dialysis (CAPD) for kidney failure. Ceftazidime and cefazolin were started. Peritoneal dialysate culture was negative for bacteria, but antibiotic treatment was continued because peritonitis improved. Twenty days later, the patient was discharged with no signs of peritonitis. However, 40-day culture of the original peritoneal dialysate detected Mycobacterium tuberculosis, and peritonitis recurred, leading to readmission. A T-SPOT test was performed and was positive in 4 days. Anti-tuberculosis therapy was started, which cured the peritonitis. The T-SPOT test may enable early diagnosis of tuberculosis.

Spindle cell carcinoma with cystic brain metastasis: Successful treatment with stereotactic radiotherapy and anti­programmed cell death­1 antibodies: A case report.

Cystic brain metastasis is a rare condition that mainly originates from lung or breast adenocarcinomas. By contrast, pulmonary spindle cell carcinoma, a rare type of non-small cell carcinoma, has not been reported with this condition. Cystic brain metastases are characterized by larger tumor sizes with increased peritumoral edema compared with solid metastases. Therefore, specific treatment strategies are required for intracranial disease control. Immunotherapy has recently been demonstrated to be crucial for treating pulmonary sarcomatoid carcinomas based on high programmed cell death-ligand 1 (PD-L1) expression observed in these cancers. The present report describes the case of an 82-year-old man diagnosed with pulmonary spindle cell carcinoma, a rare subtype of sarcomatoid carcinoma. At 7 months after the diagnosis, the patient complained of a walking disturbance for which de novo brain metastasis with peritumoral edema was the causative agent. The brain tumor had a large cystic component, and thus, an Ommaya reservoir catheter was implanted for cyst aspiration but collapsed early without sufficient volume reduction. The patient was transferred to receive twice-split gamma knife treatment, which shrank the solid compartment and reduced the cyst volume, thereby relieving neurological defects. The patient was subsequently treated with immunotherapy targeting programmed cell death-1 based on the high PD-L1 expression in the lung tumor specimen. The thoracic tumors regressed following immunotherapy and progression-free survival was maintained for 16 months. To the best of our knowledge, the present report provides the first description of focal and systemic therapies for pulmonary spindle cell carcinoma with cystic brain metastasis. The report also discusses the treatment strategies for cystic brain metastases and reviews cases of pulmonary spindle cell carcinoma treated with immune checkpoint inhibitors.

Risk factors and interventions for developing recurrent pneumonia in older adults.

Background: Pneumonia is common among older adults and often recurrent. Several studies have been conducted on the risk factors for pneumonia; however, little is known about the risk factors for recurrent pneumonia. This study aimed to identify the risk factors for developing recurrent pneumonia among older adults and to investigate methods of prevention. Methods: We analysed the data of 256 patients aged 75 years or older who were admitted for pneumonia between June 2014 and May 2017. Moreover, we reviewed the medical records for the subsequent 3 years and defined the readmission caused by pneumonia as recurrent pneumonia. Risk factors for recurrent pneumonia were analysed using multivariable logistic regression analysis. Differences in the recurrence rate based on the types and use of hypnotics were also evaluated. Results: Of the 256 patients, 90 (35.2%) experienced recurrent pneumonia. A low body mass index (OR: 0.91; 95% CI: 0.83‒0.99), history of pneumonia (OR: 2.71; 95% CI: 1.23‒6.13), lung disease as a comorbidity (OR: 4.73; 95% CI: 2.13‒11.60), taking hypnotics (OR: 2.16; 95% CI: 1.18‒4.01) and taking histamine-1 receptor antagonist (H1RA) (OR: 2.38; 95% CI: 1.07‒5.39) were risk factors. Patients taking benzodiazepine as hypnotics were more likely to experience recurrent pneumonia than patients not taking hypnotics (OR: 2.29; 95% CI: 1.25-4.18). Conclusion: We identified several risk factors for recurrent pneumonia. Among them, restricting the use of H1RA and hypnotics, in particular benzodiazepines, may be useful in preventing the recurrence of pneumonia in adults aged 75 years or older.

Factors Associated With the Improvement of Left Ventricular Systolic Function by Continuous Positive Airway Pressure Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a potential risk factor in cardiovascular diseases, including arrhythmia, coronary artery disease, and heart failure (HF). Continuous positive airway pressure (CPAP) therapy is an effective therapy for OSA and the underlying HF, partly through a 5-9% increase in the left ventricular ejection fraction (LVEF). However, the data on the factors associated with the efficacy of CPAP on LVEF in patients with HF complicated by OSA are scarce. This study aimed to investigate whether LVEF improves in patients with OSA and HF after 1 month of CPAP therapy, and to clarify which factors are associated with the degree of LVEF improvement. Method: This was a prospective, single-arm, open-label study. We enrolled moderate-to-severe patients with OSA and HF who were being followed up at the cardiovascular center of Toranomon Hospital (Tokyo, Japan). The parameters of sleep study and LVEF were assessed at the baseline and after 1 month of CPAP. The multivariate regression analyses, with changes in LVEF as a dependent variable, were performed to determine the factors that were associated with the degree of LVEF improvement. Results: We analyzed 55 consecutive patients with OSA and HF (mean age: 60.7 ± 12.2 years, mean LVEF value: 37.2 ± 9.8%). One month of CPAP treatment decreased the apnea-hypopnea index (AHI) from 45.3 ± 16.1 to 5.4 ± 4.1 per hour, and the LVEF improved from 37.2 ± 9.8 to 43.2 ± 11.7%. The multivariate regression analyses demonstrated that age and body mass index (BMI) were significant determinants of LVEF improvement. Conclusion: The LVEF improved significantly after 1 month of CPAP therapy in Japanese patients with OSA and HF. Multivariate regression analyses indicated that an improvement in LVEF was likely to be observed in young patients with obesity.

Effects of olmesartan on blood pressure and insulin resistance in hypertensive patients with sleep-disordered breathing.

The increased risk of cardiovascular morbidity and mortality among patients with sleep-disordered breathing (SDB) has been linked to arterial hypertension and insulin resistance. However, an effective antihypertensive agent for patients with SDB has not been identified. We investigated the effect of the angiotensin II subtype 1 receptor blocker olmesartan in hypertensive patients with SDB. This prospective, one-arm pilot study included 25 male patients with untreated SDB (mean age, 52.7 ± 11.4 years). We measured blood pressure, oxygen desaturation index (ODI), cardiac function using echocardiography, and insulin resistance using the homeostasis model assessment (HOMA) before and after 12 weeks of olmesartan therapy (mean dose, 17.6 ± 4.4 mg/day). Olmesartan significantly decreased systolic blood pressure (151.4 ± 8.0 vs. 134.0 ± 7.4 mmHg; P < 0.001), diastolic blood pressure (93.4 ± 7.1 vs. 83.9 ± 6.3 mmHg; P < 0.001), and HOMA index (3.7 ± 2.9 vs. 2.8 ± 1.9; P = 0.012). Furthermore, left ventricular ejection fraction significantly increased at 12 weeks (68.1 ± 5.1 vs. 71.6 ± 5.4%; P = 0.009). However, body mass index (BMI) and degree of SDB did not change (BMI, 26.6 ± 4.0 vs. 26.6 ± 4.2 kg/m2, P = 0.129; 3% ODI, 29.5 ± 23.1 vs. 28.2 ± 21.0 events/h, P = 0.394). Olmesartan significantly reduced blood pressure and insulin resistance in hypertensive patients with SDB without changing BMI or SDB severity.

Endotracheal granulation after tracheostomy in acute respiratory distress syndrome from COVID-19.

Granulation tissue formation is one of the late complications of tracheostomy. It can cause stomal stenosis secondary to chondritis because of disproportionate excision of the anterior cartilage. Clinicians should carefully determine the incision point, which is typically located half way between the cricoid cartilage and the sternal notch.

Outcomes of Video-Assisted Thoracic Surgical Lung Biopsy for Interstitial Lung Diseases.

PURPOSE: Surgical lung biopsy (SLB) is an important diagnostic tool for interstitial lung disease (ILD), yet the risk factors for SLB are still debatable and long-term outcomes remain unknown. METHODS: We retrospectively reviewed the records of 85 consecutive patients with ILD who underwent SLB by video-assisted thoracic surgery (VATS) from 2008 to 2019. Risk factors for complications and differences of outcomes between idiopathic pulmonary fibrosis (IPF) and other ILDs were examined. RESULTS: All patients who underwent VATS had no mortality or acute exacerbation of ILD within 90 days of SLB. The rate of complication was 9.4%, and there were no statistically significant risk factors for complications. While the IPF group was not significantly different from the non-IPF group with regard to surgical parameters or complications, patients with IPF had significantly higher rates of mortality (50% vs. 9% in 5 years; p <0.001) and readmission due to acute exacerbation (75% vs. 8% in 5 years; p <0.001). CONCLUSION: VATS lung biopsy for ILD can be a safe approach regardless of underlying phenotypes. An accurate diagnosis of IPF via SLB may be beneficial for correct patient management.

[A case of allergic bronchopulmonary mycosis caused by Schizophyllum commune presenting with hyperattenuated mucoid impaction].

A 64-year-old woman was admitted to our hospital because of cough, bloody sputum and chest pain in January 2007. Chest computed tomography (CT) on admission revealed hyperattenuated mucoid impaction and consolidation in the right S3b. She was given a diagnosis of allergic bronchopulmonary mycosis caused by Schizophyllum commune. Treatment with 200 mg/day itraconazole and 15 mg/day oral prednisolone was begun, and her symptoms and consolidation resolved. In December 2007, consolidation in the left lower lobe appeared after itraconazole was stopped and replaced with oral prednisolone with inhaled fluticasone propionate. She again received 200 mg/day itraconazole and 15 mg/day oral prednisolone, resulting in a reduction in her consolidation. In May 2008, itraconazole was stopped and oral prednisolone was changed to inhaled salmeterol fluticasone propionate. In November 2008, her symptoms appeared again, and chest CT demonstrated hyperattenuated mucoid impaction and consolidation in the right S8. A transbronchial biopsy revealed granulomatosis, Charcot-Leyden crystals, and mucus infiltrated by eosinophils and fungi. Schizophyllum commune was isolated from her bronchial lavage fluid. A recurrence of allergic bronchopulmonary mycosis was diagnosed. Retreatment with itraconazole and oral prednisolone resulted in improvement of her symptoms and chest radiographic findings. To the best of our knowledge this is the first reported case of allergic bronchopulmonary mycosis caused by Schizophyllum commune presenting with hyperattenuated mucoid impaction.

[A case of pulmonary tumor thrombotic microangiopathy caused by carcinoma (salivary duct carcinoma) ex pleomorphic adenoma].

A 53-year-old man with carcinoma (salivary duct carcinoma) ex pleomorphic adenoma was admitted to our hospital because of dyspnea. He received chemotherapy in July 2007, and was subsequently followed up without chemotherapy. A chest CT scan revealed multiple faint ground glass attenuation bilaterally. Contrast-enhanced CT did not reveal any emboli in the large pulmonary arteries. An echocardiogram showed severe pulmonary hypertension. Tc-99m-MAA lung perfusion images showed multiple small defects in both lungs. The serum level of vascular endothelial growth factor (VEGF) was normal. He died of heart failure 23 days after admission. An autopsy was performed, and microscopic examination revealed tumor cell embolism, intimal fibrocellular proliferation of the small arteries, fibrin thrombi and recanalization. A diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM) was made. Immunohistochemical staining of the tumor cells for VEGF was weakly positive. To the best of our knowledge this is the first reported case of PTTM caused by a salivary gland tumor.

Hepatoid adenocarcinoma of the lung mimicking metastatic hepatocellular carcinoma.

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma: a report of two cases.

Pathological transformation to squamous cell carcinoma after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment has been reported, but details of the transformation remain unclear. We report two cases with transformation to squamous cell carcinoma. The first case was a 61-year-old man who was an ex-smoker with stage IV lung adenocarcinoma harbouring EGFR exon 19 insertion. He experienced squamous cell transformation after 28 months of erlotinib therapy. Next-generation sequencing (NGS) analysis showed EGFR T790M and genomic alterations in PTEN, PDGFR, and HRAS. The second case was a 72-year-old man who was an ex-smoker with stage IV lung adenocarcinoma harbouring EGFR exon 21 L858R. He experienced squamous cell transformation after nine months of erlotinib therapy. NGS analysis showed EGFR T790M and genomic alterations in PTEN, SMARCB1, TP53, and KIT. Both patients had PTEN genomic alterations and the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway might play an important role in squamous cell transformation.

IgG4-related disease in the differential diagnosis of lung nodules.

IgG4-related disease is an evolving entity of immune-mediated origin. We report a case of IgG4-related disease mimicking lung cancer with pleural dissemination. A 76-year-old male non-smoker was admitted to our hospital because of chest X-ray abnormality. Chest computed tomography scan showed a lung nodule measuring 26 × 14 mm with tiny nodules on the adjacent pleural surface. Wedge resection by video-assisted thoracoscopic surgery (VATS) was performed to aid diagnosis. Pathological findings of the nodule consisted of lymphoid follicular hyperplasia with lymphoplasmacytic infiltrate, fibrosis, and obstructive vasculitis. Focal and scattered thickening of the pleura with lymphoplasmacytic infiltrate was also observed. The IgG4/IgG ratio in the most prominent area exceeded 80%. Thus, we made a diagnosis of IgG4-related lung and pleural disease. To our knowledge, there has been no report of IgG4-related lung disease mimicking lung cancer with pleural dissemination.

Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis with a unique imaging presentation of organizing pneumonia: A case report.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of blood vessel inflammation diseases of autoimmune origin. Myeloperoxidase (MPO) ANCA is closely related to ANCA associated AAV. The MPO-ANCA positive AAV patients have lung involvement at high rates; however, there are only a few reported cases with organizing pneumonia (OP). A 78-year-old man was presented to our hospital due to a fever of 38 °C despite a whole month of antibiotics treatment. Chest computed tomography image revealed restricted consolidations visible in the middle lobe of the right lung and the upper lobe of the left lung, which suggested an OP pattern. MPO-ANCA and urine occult blood tests were positive. Histopathological examination of the transbronchial biopsy revealed OP and mucus plug. Histological findings on renal biopsy showed necrotizing glomerulonephritis related to AAV. The patient was diagnosed with MPO-ANCA positive AAV and was treated with systemic corticosteroid therapy, from which he recovered rapidly. Thus, when diagnosing OP, the possibility of AAV should be considered by ordering patients' serum ANCA and occult hematuria tests.