Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma.

Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites. METHODS AND RESULTS: The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H-scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1-dominant (SCLC-A), NEUROD1-dominant (SCLC-N), ASCL1/NEUROD1 double-negative with POU2F3 expression (SCLC-P), and negative for all three markers (SCLC-I). In whole slides, 40 SCLC-A (52%), 20 SCLC-N (26%), 15 SCLC-P (20%), and two SCLC-I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens. CONCLUSION: The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.

Preoperative prognostic nutritional index as a predictor of outcomes in elderly patients after surgery for lung cancer.

BACKGROUND AND OBJECTIVE: The prognostic nutritional index (PNI) is based on the serum albumin level and lymphocyte count, and is a useful predictor of survival in various cancers. However, the utility of PNI in lung cancer has not been examined. The aim of this study is to assess PNI as a prognostic factor in elderly patients after surgery for primary lung cancer. METHODS: A retrospective review was performed in 131 elderly patients (≥75 years old) with lung cancer who underwent curative operations at our hospital from July 2008 to December 2014. Survival was calculated by the Kaplan-Meier method. The effects of PNI and clinicopathological factors on survival were evaluated in univariate and multivariate Cox regression analyses. RESULTS: The 5-year cancer-specific survival (CSS) rates of patients with PNI ≥ 45 and <45 were 76.2% and 47.8%, respectively (P = 0.0166), and the 5-year overall survival (OS) rates were 61.9% and 39.8%, respectively (P = 0.0275). Among patients who died within 5 years, mortality due to other diseases was 31%. Univariate analysis identified gender (P = 0.003), serum carcinoembryonic antigen (CEA) (P = 0.009), PNI (P = 0.027), c-stage (P = 0.005), histological type (P = 0.001) and p-stage (P < 0.001) as prognostic factors. In multivariate analysis, CEA (HR 2.487, P = 0.0169), PNI (HR 2.737, P = 0.0289) and p-stage (HR 3.294, P = 0.007) were independent prognostic factors in elderly patients after curative surgery for lung cancer. CONCLUSIONS: CEA, PNI and p-stage are independent prognostic factors in elderly patients after surgery for primary lung cancer. Therefore, determination of preoperative PNI may be useful for treatment planning in elderly patients with lung cancer.

[A Case of Myocardial and Cutaneous Metastases of Squamous Cell Lung Cancer Post Left Pneumonectomy and Radical Surgery for Cutaneous Metastasis during Nivolumab Therapy].

BACKGROUND: Concomitant myocardial and cutaneous metastases of squamous cell lung cancer after left pneumonectomy are very rare. Although nivolumab is used as a standard second-line chemotherapy for non-small cell lung cancer(NSCLC), its efficacy for concomitant myocardial and cutaneous metastases remains unclear. CASE: A 66-year-old man with no chief complaints was diagnosed with myocardial metastasis by CT scan. The patient underwent radical left pneumonectomy for squamous cell lung cancer 12 months previously and had rejected adjuvant chemotherapy with pT2aN1M0- II B(7th edition). A skin lesion in the left side of the neck was diagnosed as cutaneous metastasis by cytological examination. First-line treatment with cisplatin plus gemcitabine was administered; it was then replaced with nivolumab as a second-line chemotherapy after the progression of the disease due to myocardial metastasis. Fortunately, after 5 courses of nivolumab, there was a reduction in the cutaneous metastasis, which allowed complete resection, and reduction in the volume of myocardial metastasis. The patient is alive 30 months after left pneumonectomy and 18 months after the diagnosis of relapse. Nivolumab treatment is on-going. CONCLUSION: Complete resection of a cutaneous metastasis of squamous cell lung cancer and a reduction in the volume of myocardial metastasis were achieved following nivolumab treatment. Thus, nivolumab is a useful chemotherapy for concomitant cutaneous and myocardial metastases of squamous cell lung cancer.

[Successful Treatment of Acute Empyema Due to Rupture of Pyogenic Liver Abscess].

Cases of rescue after rupture of pyogenic liver abscess into the thorax are rare. Here, we report 2 cases of rescue in patients with acute empyema due to rupture of a suppurative abscess into the thorax. Case 1:A 61-year-old male had high fever of 39 °C and right abdominal pain. Thoracic computed tomography(CT) showed encapsulated pleural effusion in the right thorax and ring-like enhancement in the right liver. The diagnosis was acute empyema caused by rupture of liver abscess. The pathogenic bacteria were Streptococcus group. The drain was removed after 6 days and the patient was discharged 32 days after surgery without reefing the diaphragm. Case 2:A 74-year-old male had a high fever of 39 °C and right chest pain. CT showed encapsulated pleural effusion in the right thorax, but not in the lung, and a low density area in the posterior segment of the liver. The diagnosis was acute empyema caused by rupture of liver abscess. The pathogenic bacteria were Streptococcus group and Bacteroides. The drain was removed after 8 days and the patient was discharged 32 days after surgery without reefing the diaphragm. CONCLUSION: Pathogenic bacteria in a pyogenic liver abscess are usually Gram-negative rods, but recently have also been reported to be Streptococcus anginosus group( SAG). Coinfection with SAG and anaerobic bacteria occurs in elderly patients, compromised hosts, and patients with a severe malignant disease. Therefore, early drainage using surgical treatment regardless of reefing the diaphragm should be considered to control severe infection due to liver abscess rupture.

[Pulmonary Lipomatous Hamartoma Suspected to be an Endobronchial Lipoma].

We report a rare case of pulmonary lipomatous hamartoma. A 61-year-old male was referred to our hospital due to abnormal mass densities on a chest radiograph. Thoracic computed tomography (CT) revealed a tumor with a maximum diameter of 42 mm. Bronchoscopic examination indicated the presence of a tumor at the orifice of the lateral segmental bronchus which was obstructed by the tumor. Endobronchial lipoma, was suspected by transbronchial biopsy, and we carried out a left upper lobectomy to prevent obstructive pneumonia. The pathological diagnosis was lipomatous hamartoma.

[Mediastinal Nonseminomatous Germ Cell Tumor with Sarcoid-like Reaction in the Regional Lymph Nodes].

A 26-year-old man was admitted because of an abnormal shadow on a chest roentgenogram. Computed tomography(CT) revealed a very large tumor in the anterior mediastinum and bilateral mediastinal lymphadenopathy. Examination of a CT-guided biopsy specimen revealed a yolk-sac tumor. The patient received 4 courses of bleomycin, etoposide, and cisplatin chemotherapy. After chemotherapy, the tumor was markedly reduced in size, but the lymphadenopathy remained. The patient underwent thoracoscopic biopsy of the mediastinal lymph nodes. Sarcoid nodules were found in all the biopsied nodes, and the lymphadenopathy was thought to be a sarcoid-like reaction associated with the germ cell tumor. Resection of the residual tumor was performed according to the treatment algorithm of the International Germ Cell Cancer Collaborative Group. There were no viable tumor cells in the resected tissue. The patient is free of recurrence and without any sign of generalized sarcoidosis 3 years after the surgery.

Pulmonary artery reconstruction for non-small cell lung cancer: Surgical management and long-term outcomes.

OBJECTIVE: Pulmonary artery (PA) reconstruction is performed to avoid pneumonectomy for non-small cell lung cancer (NSCLC). Our objective was to assess the safety and efficacy of performing PA reconstruction without systemic heparinization during resections of NSCLC. METHODS: Among 3537 patients with resected NSCLC between 2008 and 2019, 130 (3.7%) patients underwent PA reconstruction to avoid pneumonectomy without intraoperative systemic heparinization. We investigated surgical outcome. The median follow-up time was 37 months. RESULTS: As to PA reconstruction, tangential suture, patch closure (autologous pericardium), end-to-end anastomosis, and conduit were performed in 56, 26, 32, and 16 patients (autologous pericardium, 13; resected pulmonary vein, 3), respectively. Combined bronchial sleeve resection was performed in 68 (52%) patients. The mean operative time was 261 minutes. The procedure-related complications were 2 PA thromboses with pericardial conduit requiring completion pneumonectomy and 2 massive hemoptysis of a bronchopulmonary fistula leading to death (operative mortality, 1.5%). PA bending and mechanical stenosis were due to the lengthening by the conduit. Seventy-five patients had other complications, the most frequent being arrhythmia. One patient was at stage 0 after induction chemoradiotherapy; 26, stage I (9 IA and 17 IB); 43, stage II (19 IA and 24 IB), 55 stage III (49 IIIA and 6 IIIB); and 5, stage IV. Five-year overall survival, cancer-specific survival, and recurrence-free survival rates were 49.2%, 61.8%, and 37.1%, respectively. CONCLUSIONS: PA reconstruction without intraoperative systemic heparinization during resections of NSCLC was performed with a very low risk of thrombosis as well as perioperative bleeding.

Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza.

BACKGROUND AND OBJECTIVE: The antiviral neuraminidase inhibitor oseltamivir (OSV) is used to treat influenza. The macrolide clarithromycin (CAM) is used to treat bacterial infections and has anti-inflammatory and immunomodulatory activities. This retrospective study investigated the immunomodulatory effects of CAM in children presenting with influenza A. METHODS: The study recruited 40 children with acute influenza, and grouped them according to the treatment received: 5-day treatment with OSV (n = 14), CAM (n = 8), OSV + CAM (n = 12) and untreated (n = 6). The before and after treatment comparisons were made of the level of secretory IgA (sIgA) against influenza A virus (H3N2) and (H1N1), total sIgA, viral RNA copy numbers in nasopharyngeal aspirates and disease symptoms. RESULTS: Infection induced anti-viral mucosal sIgA in the nasopharyngeal aspirates of most patients of all treatment groups. Particularly prominent increases in the levels were found in the CAM and OSV + CAM groups. Low induction of anti-viral sIgA was observed in the OSV group, but the addition of CAM to OSV augmented sIgA production and restored local mucosal sIgA levels. The frequency of residual cough in the OSV + CAM group was significantly lower than in the other groups including the group treated with OSV. CONCLUSIONS: CAM boosted the nasopharyngeal mucosal immune response in children presenting with influenza A, even in those treated with OSV who had low production of mucosal anti-viral sIgA, and alleviated the symptoms of influenza.

Salvage surgery for lung cancer with tracheo-oesophageal fistula during concurrent chemoradiotherapy.

A 48-year-old man presenting with cough, dysphagia and chest pain was diagnosed with advanced inoperable squamous cell carcinoma located in the right S2 with mediastinal lymph node metastases invading the oesophagus (c-T4N2M0 stage IIIB). Concurrent chemoradiotherapy (66 Gy) was planned, but he developed a tracheo-oesophageal fistula during the chemoradiotherapy course (26 Gy). A right sleeve pneumonectomy with oesophagectomy, cervical oesophagostomy and enterostomy were performed. Although bilateral recurrent nerve palsy occurred, he recovered via enhanced rehabilitation and was discharged 28 days after the salvage surgery. Three months after the initial surgery, staged reconstruction surgery of the stomach was performed. Intensive rehabilitation resulted in restored swallowing ability. He is alive with recurrent disease 12 months after surgery. This is the first report of salvage surgery for advanced lung cancer with tracheo-oesophageal fistula during concurrent chemoradiotherapy.

Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans.

Longitudinal study of 29 patients with Meniere's disease with follow-up of 10 years or more (In commemoration of Professor Emeritus Isamu Watanabe).

CONCLUSIONS: A final incidence of bilateral involvement was 20.7%. Episodic spells of vertigo were completely controlled in 23 of 29 patients, while 11 of 29 patients demonstrated over 70 dB hearing loss. OBJECTIVE: To analyze the clinical course of 29 patients with Meniere's disease during follow-up of 10 years or more. METHODS: The subjects were 29 patients with a mean follow-up of 18.3 years. The hearing level was measured by the pure tone average (PTA) of four frequencies at the initial and the final examination, and it was classified into four categories according to the American Academy of Otolaryngology-Head and Neck Society (AAO-HNS) criteria. The control of vertigo was evaluated by the modified AAO-HNS criteria. RESULTS: At enrolment two patients had bilateral involvement. In the period of follow-up, bilateral involvement emerged in four more patients. The hearing levels at the final examinations were as follows: 3 patients, <25 dB; 6 patients, 26-40 dB; 9 patients, 41-70 dB; and 11 patients, >70 dB. The control of vertigo according to the modified AAO-HNS guideline was class A in 23 patients, class B in 2 patients, and class C in 1 patient; the remaining 3 patients could not be evaluated.

Influence of premature rupture of membrane on the cerebral blood flow in low-birth-weight infant after the delivery.

Cerebral white matter injury, usually called periventricular leukomalacia (PVL), is the most common form of injury to preterm infants that is associated with adverse motor and cognitive outcomes. Intrauterine infection may be an important etiological factor in PVL, and premature rupture of the membranes (PROM) can be identified antepartum. In order to investigate the pathophysiology of cerebral white matter injury induced by PROM, the cerebral blood flow (CBF) of the internal carotid artery and the vertebral artery was measured by neck ultrasonography. The CBF was determined in 84 low-birth-weight infants with gestational ages ranging from 24 to 35 weeks, including 71 infants without PROM and 13 infants with PROM. The mean blood flow velocity and diameter of each vessel were measured on postnatal days 0-70. The intravascular flow volume was determined by calculating the mean blood flow velocity and the cross-sectional area. The mean blood pressures were recorded, and the ejection fraction was determined. The total cerebral blood flow (CBF) was significantly lower in infants with PROM than in infants without PROM from day 10 to day 70. The ejection fraction was significantly higher in infants with PROM than in infants without PROM on days 0, 5, 10, 21, and 42. There was no difference in the mean blood pressure between infants with PROM and infants without PROM. The results of the present study suggest that PROM may decrease cerebral blood flow after the birth.