Efficacy and Safety of Nivolumab in Patients with Advanced Non-small-cell Lung Cancer and Poor Performance Status.

Background: Nivolumab efficacy in patients with non-small-cell lung cancer (NSCLC) and performance status (PS) of 2-4 is unclear. We aimed to compare survival, treatment efficacy, and safety in patients with NSCLC with poor PS who received nivolumab plus best supportive care (BSC) with those in patients who received BSC alone in a palliative care unit (PCU). Patients and methods: This retrospective study included 99 consecutive patients with NSCLC who received nivolumab plus BSC or BSC alone between December 2015 and March 2018. Results: In total, 43 patients with PS of 0-1 (good PS group) and 20 patients with PS of 2-4 (poor PS group) received nivolumab plus BSC; the remaining 36 patients received BSC alone in the PCU (PC group). Median overall survival was 32 days [95% confidence interval (CI), 21-43] in the poor PS group and 31 days (95% CI, 25-37) in the PC group (hazard ratio, 0.653; 95% CI, 0.368-1.158; P = 0.137). Moreover, median overall survival in patients with PS of 3 or 4 among the poor PS group was not significantly longer than that in the PC group (HR, 1.235; 95% CI, 0.646-2.360; P = 0.516). The frequency of severe pneumonitis in the poor PS group was significantly higher than that in the good PS group (25% vs. 2%, P = 0.010). Conclusion: Survival benefit of nivolumab in patients with NSCLC with poor PS, especially 3 or 4, was not confirmed. Further studies with larger numbers of patients are required to confirm our results.

The case of double primary lung adenocarcinomas with an EGFR mutation and ALK translocation successfully treated with alectinib at the post-surgical recurrence.

A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence. J. Med. Invest. 64: 305-307, August, 2017.

[Thoracoscopic Temporary Segmental Bronchus Incision Technique for Fissureless Lobectomy].

Several thoracoscopic fissureless lobectomy techniques have been reported;however, the indications for the same remain controversial. One of the reasons for conversion to open lobectomy is the swelling or inflammation of lymph nodes between the lobar bronchus and the adjacent pulmonary artery. In this report, we advocate temporary segmental bronchus incision technique(T-BIT)and describe its application for lung cancer patients with fused fissures. T-BIT involves initial segmental bronchus incision before lobar bronchus stapling to safely dissect the lymph nodes between the lobar bronchus and the pulmonary artery. Eight patients who underwent thoracoscopic fissureless lobectomy with T-BIT between August 2014 and August 2016 were included in the study. Five patients underwent left upper lobectomy, one underwent left lower lobectomy, and 2 underwent right middle lobectomy. With T-BIT, complete peribronchial lymph node dissection was easily performed in all patients. There were no intraoperative complications, such as pulmonary artery bleeding or pulmonary injury. The postoperative chest tube drainage time was 2.5±0.5 days. Taken together, T-BIT appears useful for lymph node dissection in thoracoscopic fissureless lobectomy.

[Extended Right Pneumonectomy with Partial Resection of the Left Atrium without Cardiopulmonary Bypass].

A 62-year-woman suffered a palpitation for 1 years and was admitted to our hospital with complaints of hemosputum. Chest computed tomography(CT) revealed right hilum tumor diffusely invaded to left atrium. The patient was resected without cardiopulmonary bypass, the interatrial groove (Waterston's or Sondergaard's groove) was carefully dissected and right pneumonectomy with systematic lymph nodes dissection and partial left atrium resection were performed. The posteoperative left atrial volume decreased to half of preoperative volume (from 73 ml to 36 ml) judging from 3D-CT scan. Her postoperative course was uneventful and palpitation, disappeared postoperatively. The histlogical examinarion revealed pleomorphic carcinoma with mediastinal single lymph nodes matastasis (#7), the pathological stage was pT4N2M0. She did not receive adjuvant chemotherapy, but has had no sign of recurrence for 3 years after surgery.

Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus.

AIMS: This open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥ 24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS(®) system. RESULTS: There were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (-3.8 mg/dL vs. -1.4 mg/dL, p=0.014; -2.3% vs. -0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=-1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. CONCLUSION: Switching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM.

Impact of minimum contrast media volumes during elective percutaneous coronary intervention for prevention of contrast-induced nephropathy in patients with stable coronary artery disease.

Contrast-induced nephropathy (CIN) is an important complication following percutaneous coronary intervention (PCI). The clinical importance of a minimum contrast media volume (CMV) for PCI to prevent CIN has not been well evaluated. The purpose of this study was to evaluate the impact of minimum CMV to prevent CIN after PCI. In this study, 2052 consecutive patients who underwent elective PCI in our institute were analyzed. We divided patients into two groups according to CMV: a minimum CMV PCI group [CMV ≤50 ml (n = 94)] and a non-minimum CMV PCI group [CMV >50 ml (n = 1958)]. CIN occurred in 160 (7.8 %) patients. The incidence of CIN was significantly lower in the minimum CMV PCI group than in the non-minimum CMV PCI group (2.1 vs. 8.1 %; P = 0.03). According to multivariate analysis, elderly patients and diabetes mellitus patients were at high risk of developing CIN in this study population. When analyzing only high-risk patients, the incidence of CIN was also significantly lower in the minimum CMV group than in the non-minimum CMV group (2.6 vs. 10.3 %; P = 0.03). Minimum CMV PCI could reduce the incidence of CIN, particularly in high-risk patients; as such, defining the minimum CMV clinical cut-off values may be useful for the prevention of CIN.

Non-high-density cholesterol level as a predictor of maximum carotid intima-media thickness in Japanese subjects with type 2 diabetes: a comparison with low-density lipoprotein level.

AIM: To determine whether non-high-density lipoprotein cholesterol (non-HDL-C) level, in comparison with low-density lipoprotein cholesterol (LDL-C) level, is useful for predicting the values of various surrogate atherosclerosis markers in Japanese subjects with type 2 diabetes (T2DM). METHODS: Data were retrieved from medical records of 265 subjects with T2DM who underwent laboratory tests to evaluate for atherosclerosis by using the following parameters: brachial-ankle pulse wave velocity, mean and maximum carotid intima-media thickness (mean CIMT and max-CIMT), and ankle-brachial index, with simultaneous fasting blood sampling for routine lipid parameters. RESULTS: In a multiple stepwise regression analysis, non-HDL-C level, but not LDL-C level, positively correlated with max-CIMT (ß coefficient = 0.14, F = 6.84). Stepwise logistic regression analysis revealed that a 0.26 mmol/L (10 mg/dL) increase in non-HDL-C level, but not LDL-C level, was significantly associated with high risk of max-CIMT (≥1.1 mm; odds ratio, 1.096; 95 % confidence interval, 1.003-1.202; p = 0.046). However, in a receiver operating characteristic curve (ROC) analysis, the addition of non-HDL-C level to the three significant independent variables obtained from the stepwise analyses did not significantly increased the area under the ROC curve (from 0.7789 to 0.7864, p = 0.4343). CONCLUSIONS: Non-HDL-C levels may be non-inferior to LDL-C level for the prediction of high-risk max-CIMT in Japanese subjects with T2DM.

Chronic hyperglycemia may attenuate the serum-uric-acid-lowering effect of low-dose febuxostat in Japanese patients with type 2 diabetes mellitus.

AIMS: This study investigated the independent predictors of the serum uric acid (sUA)-lowering effect of low-dose febuxostat, a novel xanthine oxidase inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Data of 130 T2DM patients who had been taking febuxostat 10 mg once daily for elevated sUA (≥7 mg/dl) for at least 12 weeks were retrieved from medical records. Spearman's rank correlation coefficients were calculated to determine the correlations between sets of two independent continuous variables. Multiple stepwise linear regression analysis was used to determine independent predictors of the percent change of sUA levels after 12 weeks of febuxostat treatment (%ΔsUA). RESULTS: Among all patients, %ΔsUA was significantly correlated with age (ρ = 0.192, P = 0.030) and mean glycated hemoglobin (HbA1c) level (ρ = -0.186, P = 0.036). Multiple stepwise linear regression analysis of all patients revealed that major independent factors contributing to %ΔsUA were mean HbA1c (ß = -3.14, P = 0.022) and mean glycated albumin (ß = -0.743, P = 0.013) levels. CONCLUSIONS: High HbA1c and glycated albumin levels significantly attenuated the sUA-lowering effect of low-dose febuxostat in Japanese patients with T2DM. Further detailed analysis using a larger population is warranted to confirm these findings.

Intraoperative rupture of an interlobar bronchial artery aneurysm: a case report.

Here we report the rare case of an intraoperative bronchial artery aneurysm (BAA) rupture. An asymptomatic 52-year-old woman was found to have bilateral, multiple dilated bronchial arteries feeding the BAA that was further connected to the pulmonary artery on computed tomography and angiography. Transcatheter arterial embolization was thought not to be succeed. During a thoracoscopic procedure, the BAA ruptured suddenly and was treated with a thoracotomy under percutaneous cardiopulmonary support (PCPS). For anatomical complex BAA like the present case, the use of an open procedure and the preparation of PCPS are strongly recommended.

Chitosan tubes can restore the function of resected phrenic nerves.

OBJECTIVES: We previously reported that the phrenic nerve could be morphologically repaired by implantation of a chitosan nanofibre tube (C-tube). In the current study, we investigated whether implantation of C-tubes could improve the function of an injured phrenic nerve using a beagle dog model. METHODS: Seven beagle dogs underwent right thoracotomy under general anaesthesia. An approximately 5 mm length of the right phrenic nerve was resected. Five dogs had a C-tube implantation (C-tube group) and other two dogs did not have the C-tube implantation (control group). Diaphragm movements were longitudinally measured by X-ray fluoroscopy before surgery, immediately after the surgery, and 3, 6 and 12 months after the surgery. The diaphragm movement was determined by diaphragm levels at inspiration and expiration phases, and the excursion difference between them was calculated. At 12 months after the surgery, rethoracotomy was performed to examine electrical phrenic nerve conduction. The C-tube and phrenic nerve were then excised for histological assessment of nerve regeneration. RESULTS: Three of the five animals of the C-tube group showed improvement of diaphragm movement with time. In these three animals, slow phrenic nerve conduction was observed. Histological assessment showed that the injured nerve was connected by newly regenerating nerve fibres surrounded by granulation tissue within the C-tube. On the other hand, the animals in the control group and two animals of the C-tube group showed neither improved diaphragm movement, nor electrical conduction to the diaphragm. No nerve fibre regeneration was found by histology. CONCLUSIONS: Our results suggest that, in addition to morphological improvement, C-tube implantation can functionally improve the injured phrenic nerve by promoting phrenic nerve regeneration.

Successful percutaneous transluminal septal myocardial ablation through a right superior septal artery for a patient with hypertrophic obstructive cardiomyopathy.

Percutaneous transluminal septal myocardial ablation (PTSMA) has been widely accepted as a therapeutic option for patients with hypertrophic obstructive cardiomyopathy (HOCM). To achieve success in PTSMA, we need to explore the target septal arteries, including any anomalous branches that feed the hypertrophic septal myocardium causing left ventricular outflow tract obstruction. An HOCM case in which PTSMA was performed through a dominant right superior septal (RSS) artery is presented. In cases without an effective septal branch artery arising from the left anterior descending artery, an RSS artery should be sought as an alternative route for PTSMA.

Pericardial fat volume is an independent risk factor for the severity of coronary artery disease in patients with preserved ejection fraction.

OBJECTIVES: The aim of this study was to assess the relationship between the pericardial fat volume (PFV) and the characteristics of coronary plaques in patients with ischemic heart disease (IHD). BACKGROUND: It has been suggested that pericardial adipose tissue promotes plaque development in coronary artery disease (CAD). METHODS: We analyzed the cardiac computed tomography scans in consecutive patients suspected of CAD. PFV was quantified using validated software and indexed to body surface area, and the severity of coronary stenosis was evaluated in the patients who underwent coronary angiography. A total of 105 subjects (mean age, 68±10 years) with IHD were categorized into tertiles of body surface area-indexed PFV values (PFVi, cm3/m2): low-tertile, PFVi < 81.2 cm3/m2; mid-tertile, 81.2 cm3/m2 ≤ PFVi ≤ 114 cm3/m2; high-tertile, PFVi > 114 cm3/m2. Their body mass index (BMI), waist circumference, Gensini score (GS), and coronary plaque component were evaluated. RESULTS: The GS was significantly different between the high-tertile and the low-tertile groups, indicating a stepwise decrease in GS from high-tertile to mid-tertile and to low-tertile. PFVi had a significant positive correlation with BMI (p=0.0001) and GS (p<0.0001). However, no significant association was found between GS and BMI. On the multivariate analysis, high PFVi remained an independent predictor for the coronary artery disease severity (p<0.001), while BMI and waist circumference were not independent predictors. CONCLUSIONS: Obese patients were found to have more PFVi, and the characteristics of their coronary lesions were more severe. Pericardial adipose tissue as unique ectopic fat might be more highly associated with IHD progression.

[Solitary pulmonary metastasis of low-grade uterine endometrial stromal sarcoma resected 31 years before].

A 74-year-old female underwent hysterectomy and bilateral ovariectomy for uterine endometrial stromal sarcoma( ESS), low grade, at another hospital 31 years previously. When the patient was admitted for pneumonia, a lung tumor was pointed out on her chest X-ray and computed tomography( CT) scan. Chest X-ray showed an oval figure shadow of about 3.5 cm in diameter in the right lower lung field.Chest CT scan revealed an irregular form tumor of 3.5 cm in diameter in the right S8 of the lung. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan identified an abnormal accumulation of FDG at the tumor site. A pulmonary metastasis of the ESS was suspected by transbronchial lung biopsy, and the patient underwent the thoracoscopic partial resection of the right lower lobe of the lung.Histologically, the tumor was diagnosed as metastasis of the ESS, low grade.

Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

BACKGROUND: The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. METHODS: In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. RESULTS: Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. CONCLUSIONS: Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

Long-term serial angiographic outcomes after sirolimus-eluting stent implantation.

OBJECTIVE: We evaluated, using quantitative coronary angiography, the natural history of change that occurred in target lesions after successful sirolimus-eluting stent (SES) implantation. BACKGROUND: Percutaneous coronary intervention with drug-eluting stents (DES) has significantly reduced the rate of repeated target lesion revascularization. However, early studies have raised concerns regarding the "late catch-up" phenomenon of DES. METHODS: Between June 2004 and March 2007, consecutive 217 patients with 306 lesions without restenosis at early angiographic follow-up underwent late angiographic follow-up (early follow-up: 11.2 ± 2.1 months and late follow-up: 29.4 ± 5.2 months). Predictors of late catch-up were identified with univariate and multivariate regression analyses. RESULTS: Although reference vessel diameter did not significantly change during follow-up [3.15 mm (interquartile range (IQR): 2.81-3.49 mm), 3.12 mm (IQR: 2.79-3.47 mm), and 3.08 mm (IQR: 2.76-3.46 mm) at postprocedure, and early and late angiographic follow-up, respectively; P = 0.2653], late loss (LL) significantly increased during follow-up [0.05 mm (IQR: 0.00-0.13 mm) and 0.08 mm (IQR: 0.01-0.19 mm) at early and late follow-up, respectively; P < 0.0001]. Univariate analysis showed previous intervention, adjunctive use of cutting balloon, lesion length, and progression of MLD, LL, %DS at early follow-up as predictors of late catch-up. Multivariate regression analysis identified %DS at early follow-up as a predictor of late catch-up (OR 1.076, CI 1.039-1.114, P < 0.0001). CONCLUSION: Significant and continuous progression of neointima after SES implantation was observed in the present study. Larger LL may be a sign of late catch-up phenomenon.

New re-entry device for revascularization of chronic coronary total occlusions: preliminary single Japanese center experience.

BACKGROUND: Although retrograde approach for coronary chronic total occlusion (CTO) has been introduced, the procedure is still time and resource consuming. A simplified antegrade approach mightbe another resort. The aim of this study was to evaluate a new device designed to facilitate guidewire re-entry into the true lumen of a CTO from the adjacent subintimal space. METHODS: Patients with CTO were entered into a prospective registry regardless of lesion characteristics. A new metal-tip catheter was used initially in primary use cases. If it created subintimal tracking, a new re-entry tool (a flat balloon with 2 exit ports offset by 180 degrees) was used as a platform to attempt guidewire penetration into the distal true lumen. In rescue use cases after unsuccessful conventional wiring, the re-entry procedure was subsequently attempted. RESULTS: In 11 CTO lesions attempted, device success was achieved in 8 cases (72.7%). Re-entry procedure success rate was higher in primary use cases (80%) compared to rescue use cases (33.3%). Retrograde approach was conducted immediately after unsuccessful antegrade procedure using this device in the other 3 cases and successful recanalization was achieved in all cases. All lesions were stented, resulting in TIMI 3 flow without major complications. CONCLUSION: A new coronary re-entry device may provide another strategic option in the antegrade approach to recanalize CTOs.

Myasthenia gravis complicated with lung cancer and middle mediastinal thymoma.

Myasthenia gravis complicated by lung cancer is rare, and the association between myasthenia gravis and lung cancer is unclear. Thymoma located in the middle mediastinum is very rare. We describe a case of myasthenia gravis complicated with lung cancer and middle mediastinal thymoma in a 69-year-old woman.

[Total port-access robot-assisted lobectomy for lung cancer].

We reported 2 cases of total port-access right lower lobectomy with hilar and mediastinal lymph nodal dissection using the da Vinci surgical system through subcostal trans-diaphragmatic approach. In case 1, the operating time was 6 hours 00 minutes, and the total blood loss was little. In case 2, the operating time was 6 hours 30 minutes, and the total blood loss was little. The da Vinci surgical system provides a high-resolution stereoscopic image and allows remote, tremor-free, and scaled control of endoscopic surgical instruments with 7 degrees of freedom. Minimally invasive robot-assisted lobectomy is an effective procedure and may add benefits for both surgeon and patients.

The glycated albumin to glycated haemoglobin ratio increases along with the fibrosis stage in non-alcoholic steatohepatitis.

BACKGROUND: We previously reported that the indicator of glycaemic control, glycated albumin (GA) levels, are low in relation to glycaemia in patients with high alanine aminotransferase (ALT) levels in non-alcoholic fatty liver disease because of chronic inflammation, and that the GA/glycated haemoglobin ratio (G/H ratio) is inversely correlated with hepatic function in patients with chronic liver disease. The severity of liver fibrosis is known to be a good indicator for surveillance, and for determining the prognosis and optimal treatment of non-alcoholic steatohepatitis (NASH). In this study, we aimed to investigate the clinical usefulness of measuring the G/H ratio for predicting the severity of liver fibrosis in patients with NASH. METHODS: The study subjects were 36 patients with histologically diagnosed NASH (19 men, 17 women; mean age 54.8±12.2 years, body mass index 28.3±5.0 kg/m2). The relationships of the G/H ratio to hepatic function tests and fibrosis stage in the liver were investigated. RESULTS: The G/H ratio in patients with NASH was inversely correlated with ALT (P<0.001) and platelet count (P<0.0001). Furthermore, the G/H ratio was positively correlated with the fibrosis stage in liver (P=0.003). CONCLUSIONS: These results suggest that the G/H ratio increases along with the fibrosis stage in patients with NASH.

[Rapid multidisciplinary therapy for an advanced lung cancer patient with severe tracheal stenosis resulting in long-term survival].

A 61-year-old female was admitted to our hospital due to dyspnea and facial edema. A chest CT scan showed stenosis of the trachea and superior vena cava due to a tumor around the trachea. She underwent partial resection of the tracheal tumor via a rigid bronchoscope introduced into the trachea, and placement of a Dumon Y-stent. Undifferentiated non-small cell lung cancer was diagnosed. After airway management, she underwent cisplatin-based chemoradiotherapy and total 56 Gy stereotactic radiotherapy for the tumor. The tumor size was reduced by 40% immediately after chemoradiotherapy. Six months after the tracheal stent insertion, bone metastases were pointed out, and we changed the chemotherapy regimen to gefitinib. She has been in good condition without tumor growth for more than six years after tracheal stent insertion.