A prolonged multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales due to horizontal transmission of the IncN plasmid.

A multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales (IMP-6-CPE) occurred at an acute care hospital in Japan. This study was conducted to understand the mechanisms of IMP-6-CPE transmission by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing and whole-genome sequencing (WGS), and identify risk factors for IMP-6-CPE acquisition in patients who underwent abdominal surgery. Between July 2013 and March 2014, 22 hospitalized patients infected or colonized with IMP-6-CPE (Escherichia coli [n = 8], Klebsiella oxytoca [n = 5], Enterobacter cloacae [n = 5], Klebsiella pneumoniae [n = 3] and Klebsiella aerogenes [n = 1]) were identified. There were diverse PFGE profiles and sequence types (STs) in most of the species except for K. oxytoca. All isolates of K. oxytoca belonged to ST29 with similar PFGE profiles, suggesting their clonal transmission. Plasmid analysis by WGS revealed that all 22 isolates but one shared a ca. 50-kb IncN plasmid backbone with blaIMP-6 suggesting interspecies gene transmission, and typing of plasmids explained epidemiological links among cases. A case-control study showed pancreatoduodenectomy, changing drains in fluoroscopy room, continuous peritoneal lavage and enteric fistula were associated with IMP-6-CPE acquisition among the patients. Plasmid analysis of isolates in an outbreak of IMP-6-CPE suggested interspecies gene transmission and helped to clarify hidden epidemiological links between cases.

Orotate phosphoribosyltransferase is overexpressed in malignant pleural mesothelioma: Dramatically responds one case in high OPRT expression.

OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases RESULTS: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.

Bronchoscopy for Pulmonary Peripheral Lesions With Virtual Fluoroscopic Preprocedural Planning Combined With EBUS-GS: A Pilot Study.

BACKGROUND: Virtual fluoroscopic preprocedural planning (VFPP) is a figure in which the trace lines between the trachea and the target lesions are constructed along the connecting bronchus on Ray Summation image similar to fluoroscopy. The lines can be displayed at any angle with 3D imaging. This system was applied to bronchoscopy as a reference for forceps guidance under the fluoroscopy, as a new type of navigation. The objective of this study was to demonstrate the feasibility of VFPP. METHODS: Patients with pulmonary peripheral lesions (PPLs) with long axis ≤30 mm were recruited. Bronchoscopy with endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed by using simultaneous display of VFPP. RESULTS: For 27 patients with 27 lesions, endobronchial ultrasonography with a guide sheath with simultaneous display of VFPP was performed. The median lesion size was 20.2 mm (range, 10 to 30 mm). The median examination time was 24.5 minutes (range, 12 to 50 min). Diagnosis was made for 17 lesions of the total 27. Lung cancer was diagnosed in 12 lesions, nontuberculous mycobacterial disease in 1 lesion, lymphoid hyperplasia in 1 lesion, and inflammation in 3 lesions. In 10 lesions, no diagnosis was made. The diagnostic rate of the procedure was 63.0%. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for malignant disease were 66.7%, 100%, 45.5%, 100%, and 73.9%, respectively. CONCLUSION: VFPP was easy to prepare and useful for selecting target bronchi. This study confirms feasibility of the VFPP as an adjunct to minimally invasive transbronchial biopsy of pulmonary peripheral lesions.

[An Elderly Patient with Non-Small Cell Lung Cancer Who Responded to Salvage S-1 Monotherapy after Gefitinib Therapy].

S-1 is one of the effective chemotherapy regimens for treating non-small cell lung cancer. We report of an elderly patient with non-small cell lung cancer who responded to S-1 monotherapy following gefitinib therapy. An 83-year-old woman was diagnosed with advanced adenocarcinoma of the lungs (cT3N3M1a, Stage IV). Considering her age, monotherapy with vinorelbine was administered as first-line chemotherapy. Despite the completion of four courses, she was diagnosed with progressive disease. Thereafter, after considering her status as a non-smoking woman, gefitinib was introduced as second-line chemotherapy, which resulted in significant tumor size reduction.Tumor regrowth was identified 16 months later, and gefitinib was switched to erlotinib, but the tumor kept increasing in size.S -1 monotherapy was introduced as fourth-line chemotherapy, and the tumor began to decrease in size again. A partial response was obtained after 10 months, without serious adverse effects. Gefitinib following S-1 monotherapy resulted in long-term tumor size control for a total of 27 months in an elderly patient with advanced non-small cell lung cancer.S -1 monotherapy might be one of the options for salvage therapy after gefitinib treatment becomes ineffective.

Pseudomesotheliomatous carcinoma due to pleural metastasis from renal pelvic cancer.

A 78-year-old man was referred to our department with a one-week history of dyspnea and coughing. A chest X-ray showed massive left pleural effusion. Computed tomography revealed diffuse irregular thickening of the left pleura similar to malignant mesothelioma and multiple nodules in both lungs. The patient died of respiratory failure nine days after hospitalization. An autopsy revealed metastasis to the pleura and lungs from urothelial carcinoma of the left kidney.

Successful removal of a distally located foreign body using a guide sheath.

This report presents the case of successful removal of a distally located foreign body using a guide sheath (GS). A 78-year-old man was brought for x-ray examination after a dental treatment at a local clinic. A dental instrument, a diamond bur, was missing after the treatment. The chest x-ray revealed a needle-like instrument located in the peripheral right middle lobe. The distally located foreign body was removed with a flexible bronchoscope using a curette and a biopsy forceps placed through a GS. This is the first report of use of a GS to remove a foreign body.

Multiple tuberculous nodules with metachronous changes: a case report.

BACKGROUND: Spontaneous regression of lesions occurs in non-infectious benign diseases, such as sarcoidosis, as well as in infectious diseases, such as tuberculosis. Lung cancer and malignant lymphoma, on the other hand, rarely follow a similar course. We report a rare case of lung tuberculosis that presented with multiple nodules with metachronous changes in size. CASE PRESENTATION: We describe the case of a 50-year-old immunocompetent Japanese man with pulmonary tuberculosis in the form of multifocal nodules. He came to our hospital because of a chest X-ray abnormality. During the course of observation, some nodules reduced while others enlarged in size. Two years after the first visit, fever and pleural effusion appeared. The sputum examination turned out to be positive for tuberculosis. A course of anti-tubercular agents resolved the pleural effusion and multifocal nodules. CONCLUSION: Differences in the manner of granuloma formation suggest that the local immune response can be different even in the same lung field.

[A case of Wegener granulomatosis after treatment for non-tuberculous mycobacteriosis].

A 67-year-old woman with a history of non-tuberculous mycobacteriosis due to Mycobacterium avium in 2002 and 2006 was admitted because of low-grade fever and cavitary lesions in both lungs on chest computed tomography (CT). Bronchial brushing cytology by bronchoscopy did not yield mycobacterium. Her serum antineutrophil cytoplasmic antibodies (MPO-ANCA) level was elevated and PR3 ANCA was negative. A surgical lung biopsy revealed basophilic necrosis with cavitary lesions and necrotizing vasculitis compatible with Wegener granulomatosis (WG). In the resected specimen, several hyalinizing nodules with caseous necrosis, probably associated with previous mycobacterium infection, were also seen. Because her disease was limited to the lungs, we successfully treated her with corticosteroids and methotrexate. WG is considered to be a type of ANCA-associated vasculitis, and microbial infections have been associated with initiation and relapse of WG. This case clearly demonstrated that lesions of WG occurred after mycobacterial infection in the lung. We believe that this case was ANCA production in association with bacterial infection.