Down-regulating Effect of a Standardized Extract of Cultured Lentinula edodes mycelia on Cortactin in Prostate Cancer Cells Is Dependent on Malignant Potential.

BACKGROUND/AIM: The incidence and mortality rates of prostate cancer have been increasing worldwide. Although prostate cancer cells grow slowly in the local original site, once the cancer cells spread to distant organs they grow rapidly and show very aggressive features. Cortactin is a protein that regulates the actin cytoskeleton and plays crucial roles in cancer metastasis. Up-regulated cortactin is correlated with the metastatic capacity of prostate cancer cells. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been previously reported to have cortactin-down-regulating effects on human pancreatic cancer cells. In the present study, the effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated. MATERIALS AND METHODS: LNCaP.FGC, DU145, and PC-3 are human prostate cancer cell lines. LNCaP.FGC is well differentiated, androgen-dependent, and poorly metastatic. DU145 is less differentiated, androgen-independent, and moderate metastatic. PC-3 is less differentiated, androgen-independent, and highly metastatic. The effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated by western blot. RESULTS: In vitro AHCC® treatment decreased cortactin levels in LNCaP.FGC and DU145 cells but did not change those in PC-3 cells. CONCLUSION: AHCC® treatment down-regulated cortactin expression in poor and moderate metastatic LNCaP.FGC and DU145 cells but showed no effect on cortactin expression in the highly metastatic PC-3 cells. Further studies are required to elucidate the mechanism of the resistance to AHCC® treatment in highly metastatic PC-3 cells.

Combination of DYRK2 and TERT Expression Is a Powerful Predictive Marker for Early-stage Breast Cancer Recurrence.

BACKGROUND/AIM: DYRK2 is a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase induces degradation of telomerase reverse transcriptase (TERT). The expression of both proteins in breast cancer were investigated as predictors of recurrence. PATIENTS AND METHODS: Two hundred and twenty-one patients with early breast cancer treated at our institute between 2000 and 2009, were included. We used immunohistochemical analyses to measure the expression of DYRK2 and TERT and correlated it with clinicopathological factors and survival. RESULTS: DYRK2 and TERT were positive in 58 (26%) and 86 (39%) of 221 patients, respectively. There was no correlation between DYRK2 and TERT expression and clinicopathological factors. Better disease-free survival was observed in the DYRK2-positive group (p=0.032), and poorer disease-free survival was noted in the TERT-positive group (p=0.023). The DYRK2-positive TERT-negative group exhibited significantly better disease-free survival than the other groups (p=0.006). CONCLUSION: The combination of DYRK2 and TERT may be a powerful tool to stratify breast cancer patients.

Long-term survival of thoracoscopic surgery compared with open surgery for clinical N0 adenocarcinoma.

BACKGROUND: Early stage non-small cell lung cancer (NSCLC) is good candidate for video-assisted thoracoscopic surgery (VATS). Long-term outcome compared between VATS and open surgery remains unclear. The aim of this study was to assess the long-term outcome of VATS in early stage adenocarcinoma. METHODS: A retrospective study was performed in 546 patients which were operated between January 2006 and December 2010 in our institute and of those, 240 (220 lobectomies, and 20 segmentectomies) were clinical N0 adenocarcinoma. One hundred and thirty-five patients underwent VATS and 105 patients for open surgery. Long-term oncological outcomes were compared in both groups. RESULTS: There were significant differences in age, gender, Blinkman index, clinical T factor and tumor size between two groups. VATS group showed statistically longer operation time (P=0.01), less blood loss (P=0.005), shorter length of stay (P=0.001), and less dissected number of lymph nodes (P<0.001) compared with open surgery. Disease-free survival in VATS was significantly better than open surgery (5- and 10-year survival; VATS, 91.4%, 79.0%; open, 85.1%, 73.6%; respectively, P=0.04). Overall survival in VATS was not different from open (P=0.58). Propensity matched disease-free and overall survival was not significantly different between two groups. Multivariate Cox regression analysis showed that age [P=0.04, 95% confidence interval (CI): (1.02-6.81)] in overall and T factor [P=0.01, 95% CI: (1.41-17.3)] in disease-free survival was prognostic significant after propensity matching. CONCLUSIONS: Our study demonstrated that long-term outcome in VATS for early stage adenocarcinoma was equivalent to open surgery. VATS may be a treatment of choice for promising long-term prognosis.

CDX2 Expression and Prognostic Factors of Resectable Pulmonary Large Cell Neuroendocrine Carcinoma.

BACKGROUND AND AIM: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm, and its clinical features and management are still limited. We evaluated the clinicopathological factors, including CDX2 immunohistochemical expression, to predict survival in patients with LCNEC. PATIENTS AND METHODS: In all, 50 patients with LCNEC who underwent surgery at 4 institutes between 2001 and 2017 were included. Clinicopathological characteristics were evaluated for prognostic factors and statistically analyzed by Kaplan-Meier curve with a log-rank test or Cox regression models. We used immunohistochemical (IHC) analysis to determine the expressions of CDX2 and compared them with clinicopathological factors and survival. RESULTS: Sixteen of the 50 cases (32%) were CDX2 positive. No correlation was found between the CDX2 expression by IHC and clinicopathological factors. Multivariate analysis identified adjuvant chemotherapy (hazard ratio [HR] =2.86, 95% confidence interval [CI] = 1.04-8.16, P = .04) and vascular invasion (HR = 4.35, 95% CI = 1.21-15.63, P = .03) as being associated with a significantly worse rate of recurrence-free survival. CONCLUSION: CDX2 was expressed in 1/3 of LCNEC but not associated with prognostic factor. Adjuvant chemotherapy and vascular invasion were associated with a negative prognostic factor of LCNEC.

Additional Embolization for Intra-aneurysmal Blood Flow Resumption after Stent-assisted Embolization of Cerebral Aneurysms.

Objective: Stent-assisted aneurysmal embolization (SAAE) is an effective treatment for aneurysms with a low risk of recurrence. In rare cases, retreatment is necessary due to recanalization of blood flow into the aneurysm. However, only a few studies have reported on retreatment. We examined the efficacy and complications of stent-assisted aneurysm embolization for large or wide-neck aneurysms at our hospital. Methods: Between July 2010 and June 2018, 293 patients underwent stent-assisted aneurysm embolization at our hospital. Among them, 12 (2 women, 10 men, mean age: 62 years) needed retreatment. We evaluated the initial treatment of these 12 patients, and the methods and results of their retreatment. Results: Six of the 12 retreated patients were treated using the simple technique. It was possible to treat nine patients (75%) without placing new stents, but three needed additional stents. We were able to guide the microcatheter into the aneurysm using the trans-cell technique even with two overlapping stents. We achieved complete embolism in seven patients (58%), and remnants were observed in the neck in five (42%) patients. No complications were associated with our surgery. We were able to perform follow-up for 10 patients and there was no recurrence. Conclusion: Embolization should be considered in recurrent cases after the initial stent-assisted coil embolization. We achieved good results and reduced the recurrence rate by selecting the appropriate treatment in each case.

Transposition of pulmonary veins for mobilization of residual right middle and lower lobes after carinal right upper lobectomy: a unique pulmonary hilar mobilization technique for safe tension-free airway anastomosis.

Unique right hilar mobilization was performed by pulmonary venous transposition of the right middle and lower lobe veins to the opening of the right upper pulmonary vein to achieve tension-free airway anastomosis after carinal right upper lobectomy for a patient with adenoid cystic carcinoma. The right middle and lower lobes were reconstructed safely thereafter by side-to-end anastomosis between the side of the lower trachea and intermediate bronchus with acceptable suturing tension.

Effects of MaquiBright® on improving eye dryness and fatigue in humans: A randomized, double-blind, placebo-controlled trial.

This study aims to investigate the effects of MaquiBright®, also known as BrightSight®, a standardized maqui berry extract, on improving eye dryness and fatigue in Japanese subjects (aged 30-60 years) experiencing eye dryness, eye fatigue, and ≥4 h of visual display terminal (VDT) work daily. Seventy-four participants were equally but randomly assigned to either a MaquiBright® (MB) or a placebo (P) group, wherein each participant consumed one capsule daily for 4 weeks of the appropriate treatment (MaquiBright® 60 or 0 mg). Eye dryness and fatigue were measured using the Schirmer's test, tear break-up time (BUT) test, pupillary response, and flicker test before intake and 4 weeks after intake. Furthermore, subjective symptoms were assessed using the Visual Analogue Scale (VAS) method and the Dry Eye-related Quality of Life Score (DEQS) questionnaire. The MB group demonstrated a significantly higher lacrimal fluid production in both eyes (increased 6.4 ±â€¯8.1 mm, P = 0.005) in Schirmer's test compared to the P group before VDT load (playing a video game) at 4 weeks after intake. In the VAS method after VDT load, the reduction of subjective symptoms in eye fatigue (P = 0.047) and stiff shoulders (P = 0.035) were significantly higher in the MB group than in the P group as well as bothersome ocular symptoms (P = 0.037) by the DEQS. No adverse events were reported. Thus, the consumption of 60 mg of MaquiBright® per day for 4 weeks reduced eye dryness and seemed to alleviate eye fatigue.

Impact of Acacia bark extract tablets on the skin of healthy humans: a randomized, double-blind, placebo-controlled study.

This study investigated the effects of proanthocyanidins derived from Acacia (Acacia mearnsii) bark extract in healthy Japanese adult subjects experiencing uncomfortable skin symptoms. All subjects were randomly allocated into two groups (n = 33 each) using a computerized random-number generator. The subjects received either Acacia bark extract tablets or placebo for 8 weeks. Evaluations included water content in the stratum corneum, transepidermal water loss (TEWL), Skindex-16, dermatology life quality index (DLQI), visual analog scale for desire to scratch, and blood tests. At 4 weeks, the symptom/feeling score of DLQI, subjective symptoms related to uncomfortable skin, and the desire to scratch were significantly reduced in the intervention group than in the placebo group. At 8 weeks, the intervention group exhibited significantly lower TEWL on facial skin than that in the placebo group. In conclusion, the intake of Acacia bark extract tablets reduced TEWL and improved dry and uncomfortable skin.

Symptomatic Brainstem Cavernoma of Elderly Patients: Timing and Strategy of Surgical Treatment. Two Case Reports and Review of the Literature.

BACKGROUND: Brainstem cavernomas (BSCs) are rare and difficult to treat. The treatment strategy for symptomatic lesions in elderly patients remains unclear. In this review, we discuss the optimal treatment strategy and consider effective surgical strategies in elderly patients. CASE DESCRIPTION: The clinical data of 8 elderly patients (age >70 years) with symptomatic BSCs drawn from the literature and 2 of our cases are summarized in this review. The mean patient age was 73.3 ± 3.13 years, and the most common location was the pons. Multiple rebleeding before surgery was seen in at least 4 cases, with clinical presentation and surgical approach varying depending on the location. Surgical removal was performed in 9 cases, and 1 case was treated with radiosurgery. The mean duration of clinical follow-up was 26.1 ± 18.2 months. Neurologic improvement was found in 5 cases, and postoperative decline was seen in 1 of the surgery cases. CONCLUSIONS: Radical resection of the cavernoma with severe symptoms might be recommended in elderly patients, especially in those with multiple rebleeding events. From the viewpoint of surgery, we consider the subacute phase the optimal time to remove cavernomas in elderly hemorrhagic patients. However, multiple rebleeding events might exacerbate the neurologic deficit. Therefore, the subacute phase from the first or second rebleeding might be the best time for the surgical resection. At surgical intervention, preservation of the surrounding brain should be prioritized over complete removal of the cavernoma and hematoma.

How to manage tumor located between upper division and lingular segment "S3+S4 segmentectomy and S3b+S4 segmentectomy".

Segmentectomy is one of the treatment of choice for small-sized non-small cell lung cancer (NSCLC). Although simple segmentectomy is feasible even if under thoracoscopy, complicated segmentectomy which contains more than two segmental plane divisions is difficult especially thoracoscopic surgery. We here present the case of totally thoracoscopic segmentectomy between upper division and lingular segment. In the first case, the 64-year-old female patient admitted for further examination and treatment of left lung ground glass nodule. Tumor located between upper division (S3) and lingular (S4) segment was operated by bi-segmentectomy and intraoperative frozen section pathology showed minimally invasive adenocarcinoma. Systematic nodal dissection was followed after retrieval of specimens. A3b A3a+c, and A4 was individually divided and followed by division of B3 and B4. Finally, intersegmental veins V1+2a and V1+2d was identified between segments and V3a+b was divided. In the second case, the 76-year-old female patient with left lung nodule between upper division (S3b) and lingular (S4) segment was operated by bi-segmentectomy. Since sealing test revealed air leakage from resected segmental planes, fibrin glue was applied to stop air leakage and direct suturing by 4-0 prolene between S3a+S3c and S5 was performed. Target lesion between upper division and lingular segments may be resected safely if appropriate demarcation lines are identified regardless of without highly sophisticated imaging systems.

Prognostic Significance of BMI-1 But Not MEL-18 Expression in Pulmonary Squamous Cell Carcinoma.

AIM: We investigated the possibility of BMI-1 and MEL-18 to predict survival in patients with pulmonary squamous cell carcinoma. MATERIALS AND METHODS: One hundred and ninety-nine patients underwent surgery in our Institute between 1995 and 2005. We used immunohistochemical (IHC) analysis to determine the expressions of BMI-1 and MEL-18 and compared them with clinicopathological factors and survival. RESULTS: Forty-one of 199 cases (21%) were BMI-1-positive. No correlation was found between BMI-1 and MEL-18 expression by IHC and clinicopathological factors. Five-year overall survival in the BMI-1-positive group (66.8%), but not MEL-18, was significantly better than that in the negative group (45.5%, p=0.04). In multivariate analysis, positive BMI-1 was a better prognostic factor of overall survival (hazard ratio (HR)=0.561, 95% confidence interval (CI)=0.271-1.16, p=0.12). CONCLUSION: BMI-1 expression, but not MEL-18, is associated with a favorable prognosis and is a possible prognostic factor of pulmonary squamous cell carcinoma.

Robotic Surgery for Thoracic Disease.

Robotic surgeries have developed in the general thoracic field over the past decade, and publications on robotic surgery outcomes have accumulated. However, controversy remains about the application of robotic surgery, with a lack of well-established evidence. Robotic surgery has several advantages such as natural movement of the surgeon's hands when manipulating the robotic arms and instruments controlled by computer-assisted systems. Most studies have reported the feasibility and safety of robotic surgery based on acceptable morbidity and mortality compared to open or video-assisted thoracic surgery (VATS). Furthermore, there are accumulated data to indicate longer operation times and shorter hospital stay in robotic surgery. However, randomized controlled trials between robotic and open or VATS procedures are needed to clarify the advantage of robotic surgery. In this review, we focused the literature about robotic surgery used to treat lung cancer and mediastinal tumor.

Flow-mediated dilation in the inactive limb following acute hypoxic exercise.

The purpose of this study was to elucidate the effect of acute aerobic exercise performed under hypoxic conditions on flow-mediated dilation (FMD) in the inactive limb. Seven males participated in the study. The subjects performed two submaximal leg cycling on a semirecumbent ergometer at the same relative intensity (60% peak oxygen uptake) in normoxia [inspired oxygen fraction (FIO2) = 0·21] and hypoxia (FIO2 = 0·12-0·13) for 30 min. The brachial artery diameter and blood velocity during exercise were measured via ultrasound, and the antegrade and retrograde shear rates were calculated. Before and 5, 30 and 60 min after exercise, brachial artery FMD was measured in normoxia. FMD was estimated as the percentage increase in peak diameter from the baseline diameter at prior occlusion (%FMD) and as the controlling changes in baseline diameter (the corrected-%FMD). No difference in antegrade shear rate during exercise was detected between the normoxic and hypoxic conditions, whereas the retrograde shear rate was larger during hypoxic exercise. The %FMD decreased significantly at 5 min after exercise in both normoxia and hypoxia, and it returned to pre-exercise levels within 60 min of recovery. Significant decreases in FMD at 5 min after exercise had disappeared when the baseline diameter was controlled using an analysis of covariance (the corrected-%FMD). No significant differences were observed between the normoxic and hypoxic trials in the %FMD and corrected-%FMD following exercise. These results suggest that hypoxia has no impact on endothelial function in the inactive limb following acute aerobic exercise.

Auger ionization beats photo-oxidation of semiconductor quantum dots: extended stability of single-molecule photoluminescence.

Despite the bright and tuneable photoluminescence (PL) of semiconductor quantum dots (QDs), the PL instability induced by Auger recombination and oxidation poses a major challenge in single-molecule applications of QDs. The incomplete information about Auger recombination and oxidation is an obstacle in the resolution of this challenge. Here, we report for the first time that Auger-ionized QDs beat self-sensitized oxidation and the non-digitized PL intensity loss. Although high-intensity photoactivation insistently induces PL blinking, the transient escape of QDs into the ultrafast Auger recombination cycle prevents generation of singlet oxygen ((1) O2 ) and preserves the PL intensity. By the detection of the NIR phosphorescence of (1) O2 and evaluation of the photostability of single QDs in aerobic, anaerobic, and (1) O2 scavenger-enriched environments, we disclose relations of Auger ionization and (1) O2 -mediated oxidation to the PL stability of single QDs, which will be useful during the formulation of QD-based single-molecule imaging tools and single-photon devices.

Perioperative management in myasthenia gravis: republication of a systematic review and a proposal by the guideline committee of the Japanese Association for Chest Surgery 2014.

Thymectomy is regarded as a useful therapeutic option for myasthenia gravis (MG), though perioperative management in MG patients is largely empirical. While evidence-based medicine is limited in the perioperative management of MG patients, treatment guidelines are required as a benchmark. We selected issues faced by physicians in clinical practice in the perioperative management of extended thymectomy for MG, and examined them with a review of the literature. The present guidelines have reached the stage of consensus within the Japanese Association for Chest Surgery.

Video-assisted thoracic surgery for pneumothorax: republication of a systematic review and a proposal by the guideline committee of the Japanese association for chest surgery 2014.

OBJECTIVE: The purpose of this consensus conference was to determine whether video-assisted thoracic surgery (VATS) improves clinical outcomes compared with conventional thoracotomy in patients undergoing surgery for pneumothorax, and to outline evidence-based recommendations for the use of VATS. METHODS: Before the consensus conference, the best available evidence was reviewed, with systematic reviews, randomized trials, and nonrandomized trials all taken into consideration in descending order of validity and importance. At the consensus conference, evidence-based interpretative statements were created, and consensus processes were used to determine the ensuing recommendations. The Medical Information Network Distribution Service in Japan (Minds) system was used to label the levels of evidence for the references and the classes of recommendations. RESULTS AND RECOMMENDATIONS: The consensus panel agreed upon the following statements and recommendations for patients with pneumothorax undergoing surgery: 1. VATS is broadly indicated as surgery for pneumothorax. 2. VATS is judged to be less invasive, as it results in minimal postoperative pain, the periods of chest tube placement and hospitalization are short, and it shows a trend toward early realization of social integration. 3. There is no difference in terms of safety and complications between VATS and open thoracotomy. 4. As it is anticipated that VATS will result in a higher recurrence rate than open thoracotomy, it may be desirable to add a supplemental procedure during surgery. In summary, VATS can be recommended as pneumothorax surgery (Recommendation grade: Level B).

Clinicopathological analysis of pleomorphic carcinoma of the lung: diffuse ZEB1 expression predicts poor survival.

OBJECTIVES: Pleomorphic carcinoma (PC) of the lung is a rare epithelial tumor. The clinicopathological characteristics and prognostic factors of PC are controversial. The information on the ZEB1 gene, which crucially impacts survival of patients with other malignant tumors, is limited for PC. MATERIALS AND METHODS: Clinicopathological characteristics of 62 patients with PC were investigated in this study. Associations between immunohistochemical expression of ZEB1 and clinical factors, including patient prognosis, were examined. The patient population consisted of 51 (82.2%) men and 11 (17.8%) women, with a mean age of 65.5 years (range, 31-81 years). RESULTS: The overall survival rate of the 42 patients, for whom follow-up was available, was 68.3% at 5 years. Using TNM criteria, 7 (11.3%), 11 (17.7%), 3 (4.8%), 21 (33.8%), 15 (24.2%), 2 (3.2%), and 3 (4.8%) patients were classified under pathological stage IA, IB, IIA, IIB, IIIA, IIIB and IV carcinomas, respectively. Fifteen (24.1%) patients had tumors consisting entirely of spindle and giant cells (PC component). The other 47 (75.8%) cancers contained additional carcinoma components (i.e., adenocarcinoma (34/62, 54.8%), squamous cell carcinoma (7/62, 11.3%), adenosquamous carcinoma (4/62, 6.5%) and large cell carcinoma (2/62, 3.2%)). Four of 7 (57.1%) stage IA (<20mm) tumors consisted only of spindle and giant cells. ZEB1 expression was observed only in the PC component. Diffuse expression of ZEB1, was defined as positive nuclear staining in ≥75% of cancer cells, and was found in the PC component in 12 patients. Multivariate analysis revealed that lymph node metastasis, pleural invasion, and diffuse ZEB1 expression in the PC component predicted poorer disease-specific survival (p=0.007, 0.022, and 0.016, respectively). CONCLUSION: This is the first report to indicate that ZEB1 may be used as an immunohistochemical prognosticator of PC, which may be useful for histological assessment of PC in biopsy and surgical specimens.

Video-assisted thoracic surgery for lung cancer: republication of a systematic review and a proposal by the guidelines committee of the Japanese Association for Chest Surgery 2014.

BACKGROUND: Patients with early-stage non-small cell lung cancer (NSCLC) are candidates for surgical intervention with curative intent. For these early-stage lung cancer surgeries, video-assisted thoracic surgery (VATS) is considered. The purpose of this article is to propose a recommendation for this according to the evidence and provide information for patients with operable early-stage lung cancer from the Japanese Association for Chest Surgery. The clinical question here is whether VATS lobectomy is recommended for patients with clinical stage I NSCLC. METHODS: The Japanese Association for Chest Surgery guidelines committee reviewed and summarized the available literature and assessed the quality of the evidence. The available literature on VATS was examined using references from MEDLINE. The recommendations were provided according to the Medical Information Network Distribution Service in Japan (Minds). RESULTS: VATS lobectomy may be considered and applied to patients with clinical stage I NSCLC; however, well-established evidence is lacking. VATS showed better or at least equivalent outcomes regarding intra- or postoperative complications compared with thoracotomy, with less invasiveness. Additionally, long-term survival by VATS lobectomy was suggested to be at least equivalent, although there is a lack of evidence. CONCLUSIONS: VATS lobectomy by an experienced surgeon is associated with minimal invasiveness and an outcome equivalent to that of open lobectomy in stage I NSCLC. (Recommendation grade: Level C1).

Downregulation of DYRK2 can be a predictor of recurrence in early stage breast cancer.

This study investigated the potential of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase gene, to predict disease-free survival for patients with early stage breast cancer. Two hundred and seventy-four patients with breast cancer underwent surgery from January 2000 to December 2009. All patients were in stage I or II. Immunohistochemical (IHC) analysis was used to determine the expression of DYRK2, which was examined for its association with clinicopathological factors or prognosis. A total of 85 of 274 cases (31%) were DYRK2 positive. No correlation was found between DYRK2 expression by IHC and clinicopathological factors such as tumor size, histological grade, hormone receptor status, and HER2 status; however, lymph node involvement was closely associated with DYRK2 expression. Ten-year disease-free survival in the DYRK2-positive group without node metastasis (95.9%) was significantly better than that in the DYRK2-negative group (87.3%, p = 0.015). These data show that DYRK2 expression is associated with lymph node involvement and is a possible predictive factor of breast cancer recurrence.