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.

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.

Pulmonary resection after chemoradiotherapy for advanced non-small cell lung cancer: the impact of presurgical radiation therapy.

PURPOSE: Chemoradiation therapy (CRT) is recommended as standard care for stage III non-small cell lung cancer (NSCLC), but some patients experience local recurrence after the treatment. Surgical resection after CRT involves high surgical risk, but is expected to increase the curability. This study was performed to investigate the impact of presurgical CRT on the postoperative outcome, focusing especially on the effect of radiation therapy. METHODS: Twenty-six patients with stage III (N2 or T3-4) NSCLC underwent pulmonary resection after CRT. A radiation dose up to 40-70 Gy was given with concurrent chemotherapy. The morbidity, mortality and survival after surgical resection were examined. RESULTS: Lung resection was performed as lobectomy (73 %) or pneumonectomy (19 %). Postoperative complications occurred in 12 patients (morbidity 46.1 %). The overall 5-year survival of the entire cohort was 69.7 %. The factors associated with favorable long-term survival included a pathological complete response (CR) and mediastinal node negative condition after CRT, and microscopic complete resection. CONCLUSION: Surgical resection for stage III patients after CRT may provide a survival benefit with acceptable morbidity. The surgical morbidity may be increased by prior radiation therapy, thus, surgeons should be familiar with the available countermeasures to reduce the surgical risk.

Sentinel node navigation surgery by thoracoscopic fluorescence imaging system and molecular examination in non-small cell lung cancer.

PURPOSE: The application of sentinel node navigation surgery in non-small cell lung cancer (NSCLC) is not popular because of the difficulty of sentinel node identification and the low incidence of complications after systemic lymph node dissection. We report the intraoperative assessment of sentinel node metastasis by thoracoscopic ICG fluorescence imaging system and real-time reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Sixty-one patients who underwent surgery between January 2009 and December 2010 were investigated for sentinel node biopsy. ICG fluorescence imaging was applied by an infrared light CCD system, and sentinel nodes were identified and dissected. Intraoperative real-time quantitative RT-PCR to determine the expression of cytokeratin 19 (CK-19) was performed for evaluation of metastasis and finally histologic examination of hematoxylin and eosin-stained, paraffin-embedded sections. RESULTS: Sixteen (80%) of 20 patients with segmentectomy and 33 (80.5%) of 41 with lobectomy were identified for sentinel lymph nodes. The total identification rate was 80.3% (49 of 61). The false-negative rate was 2.1% (1 of 49). The overall accuracy rate was 78.7% (48 of 61 patients). Disease of four of these patients was upstaged to stage IIA by RT-PCR for CK-19 expression, which was positive for sentinel nodes and micrometastases. CONCLUSIONS: These results demonstrated that thoracoscopic ICG fluorescence imaging-guided surgery and real-time quantitative RT-PCR were useful for sentinel node biopsy and might be a powerful tool for more focused pathologic or molecular evaluation for staging.

Splice variant HE4-V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma.

The human epididymis 4 (HE4) gene product, also known as whey-acidic-protein four-disulfide core domain protein 2, was identified as the transcript expressed in the epididymis and respiratory tract. HE4 is also expressed in lung adenocarcinoma. We investigated mRNA expressions of full-length HE4 and splice variants in lung adenocarcinoma, and the clinical impact of these genes was evaluated. One hundred and fifty-two patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We employed immunohistochemical analysis to determine the expression of HE4 and molecular analysis to evaluate full-length HE4 or splice variant gene expression in pulmonary adenocarcinoma. All of the 152 cases were full-length HE4 mRNA-positive; 88 of the 152 (57.9%) were HE4-V1-positive, and 140 of the 152 (92.1%) were HE4-V3-positive. Regarding the relationship between the clinicopathological characteristics of patients and these gene expressions, the histological subtype, tumor size, and vascular invasion were significantly associated with HE4-V3 expression. HE4-V3 expression was also closely correlated with the prognosis. The 5-year disease-free survival in the HE4-V3 high expression group showed a significantly favorable prognosis compared with the low expression group (p = 0.02). The 5-year overall survival rate in the HE4-V3 high expression group was significantly higher than in the HE4-V3 low expression group (p = 0.028). These data showed that high-level HE4-V3 expression is associated with a favorable prognosis in lung adenocarcinoma. Further investigation of HE4 splice variants may offer a new insight into this possibility.

Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression.

The human epididymis 4 (HE4) protein is expressed in the epididymis and respiratory tract. We previously reported that HE4 is also expressed in pulmonary adenocarcinoma. The purpose of this study was to investigate serum levels of HE4 as a biological marker in pulmonary adenocarcinoma. As the trained set, 102 patients with pulmonary adenocarcinoma who underwent surgery in our institute from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and 16 cases of benign lung disease. In the validation, we used 104 patients with pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes of serum HE4 levels were investigated in 35 patients. The level of HE4 was determined by enzyme immunometric assay and compared with clinicopathological factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were significantly higher than in healthy controls and benign lung disease. Receiver operating characteristic curve showed that HE4 was a good discriminator of pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 % confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4 levels were significantly correlated with age, nodal status, and carcinoembryonic antigen. Furthermore, postoperative increase of HE4 serum levels showed a significant correlation with recurrence (p = 0.032). The 5-year overall survival rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4-negative group (p = 0.001). These data showed that HE4 expression in sera is associated with progression of pulmonary adenocarcinoma and a possible biomarker.

Successful treatment of esophageal repair with omentum for the spontaneous rupture of the esophagus (Boerhaave's syndrome).

Spontaneous rupture of the esophagus (Boerhaave's syndrome) is a critical disease. Most patients should undergo surgery for primary closure and drainage of the mediastinum and thorax. We treated a total of 7 cases of spontaneous rupture of the esophagus between December 2000 and August 2007. The time delay was 3 hours to 4 days (mean 16.7 hours) and the length of longitudinal tears ranged from 3 to 10cm (mean: 5.6cm). All cases underwent pedicled omental flap repair to reinforce the suture line. We introduced our technique by pedicled omental flap for successful treatment.

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.

Prognostic significance of HE4 expression in pulmonary adenocarcinoma.

We investigated the possibility of human epididymis 4(HE4) to predict survival for patients with pulmonary adenocarcinoma. One hundred and thirty-seven patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis to determine the expression of HE4 and compared with the clinicopathological factors and survival. Serum levels of HE4 in lung adenocarcinoma were investigated by enzyme immunometric assay. Fifty-seven of 137 cases (41.6%) were HE4 positive. It was found that there was no correlation between HE4 expression by immunohistochemistry and clinicopathological factors, however, adenocarcinoma subtype was significantly associated with HE4 expression. Sera in lung adenocarcinoma were significantly higher than in healthy control. Five-year disease-free survival in the HE4-positive group (44.6%) was significantly different from that in the negative group (82.3%, p = 0.001) by immunohistochemistry. The five-year overall survival rate was 60.1% in the HE4-positive group, as compared with 90.8% in the HE4-negative group (p = 0.001). In multivariate Cox regression analysis, positive HE4 protein expression was a worse prognosis factor of disease-free and overall survival (HR = 3.7, 95%CI = [1.7-8.4], p = 0.001; HR = 5.5, 95%CI = [1.8-17.2], p = 0.003, respectively), in addition to nodal status as a powerful value. When HE4 expression in adenocarcinoma cases except the BAC were analyzed, nodal status and HE4 expression were independent prognostic factors in disease-free and overall survivals. These data showed that HE4 expression is associated with a worse prognosis and is a possible prognostic factor of lung adenocarcinoma.

Clinical impact of segmentectomy compared with lobectomy under complete video-assisted thoracic surgery in the treatment of stage I non-small cell lung cancer.

BACKGROUND: Segmentectomy for small or early stage non-small cell lung cancer (NSCLC) has been controversial. Further, video-assisted thoracic surgery (VATS) for lung cancer was accepted during the past decade. We here compared the outcome between VATS segmentectomy and VATS lobectomy for stage I NSCLC. METHODS: In the retrospective study, 109 consecutive patients in stage I underwent surgery at Oita University Hospital (Oita, Japan) between September 2003 and October 2008. VATS segmentectomy was performed in 38 patients and VATS lobectomy with systemic lymphadenectomy was performed in 71 patients. After clinicopathologic factors were compared in both groups, local recurrence rates and survivals were compared. RESULTS: Five of 38 VATS segmentectomy and eight of 71 VATS lobectomy patients relapsed during the follow-up period (median 27.5 mo). In the relapsed patients after VATS segmentectomy, three (7.9%) were local recurrences and two (5.3%) were distant metastases. On the other hand, four (5.6%) were local recurrence and four (5.6%) were distant metastases in the VATS lobectomy group. There was no significant difference between the two groups. Furthermore, there was no difference in recurrence-free and overall survival between segmentectomy and lobectomy. CONCLUSIONS: Although the sample size is small, VATS segmentectomy is one of the appropriate procedures for stage I NSCLC.

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.

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.

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.

Esophagectomy in patients aged over 80 years with esophageal cancer.

BACKGROUND/AIMS: Esophagectomy for esophageal cancer is one of the most invasive surgical procedures. However, with the recent aging of the population, clinicians are increasingly encountering patients with advanced age (over 80 years) who require treatment for esophageal cancer. Patients in this age group tend to be regarded as at high risk in terms of surgical treatment. In the present study, the authors examined perioperative complications and clinical outcome in esophagectomy in patients aged over 80 years compared with those aged 70-79 and discuss the risk and appropriateness of esophagectomy in the older group. METHODOLOGY: Of patients with esophageal cancer at our institute, 25 were aged over 80 years, while 95 were aged 70-79 years. We statistically compared those who underwent esophagectomy; 8 in the older group and 62 in the younger group. The oldest patient was an 84-year-old man. Among the 8 older patients, 7 were male and 1 was female. All cases were histologically confirmed as squamous cell carcinoma and this series included 1 case in Stage 0, 3 in Stage I and 4 in Stage III. Total thoracic esophagectomy was performed in 5 patients, transhiatal blunt dissection in 2 and lower thoracic esophagectomy in 1. RESULTS: Rate of surgical treatment was significantly lower in the older group than in the younger group (32.0% vs. 65.3%, p < 0.001). No significant difference was observed in postoperative complications or mortality. Regarding clinical postoperative outcome in the older group, there were 5 deaths: 1 related to surgery, 2 to other causes (at 5 and 12 months), 2 to cancer (4 and 11 months). The remaining patients were alive at 31, 60, and 88 months. No significant difference was observed in overall or disease specific survival after surgery between the 2 groups. CONCLUSION: No statistically significant differences were apparent in morbidity, mortality or clinical outcome in the 2 groups. Since surgery seems to confer similar symptomatic improvements and survival in patients aged over 80 to those expected for patients aged 70-79, we believe that surgeons should not withhold esophagectomy in patients aged over 80 years because of advanced age alone.

Giant yolk sac tumor operated under percutaneous cardiopulmonary support (PCPS) and aspiration device.

We here report the case of an 18-year-old man with a giant yolk sac tumor that is resected under percutaneous cardiopulmonary support (PCPS). Because this patient had severe dyspea when he lay in a supine position, we resected the tumor. We used PCPS during the operation for the induction and maintenance of ventilation because his trachea and left main bronchus were collapsed by the tumor. Also, we used a vacuum aspiration device that is commonly used for facilitating difficult vaginal deliveries. We propose that several devices, such as a PCPS and vacuum aspiration device, are useful for the operation of a mediastinal tumor with dyspnea.

Left sleeve Basal segmentectomy for broncholithiasis.

Broncholithiasis is an uncommon pulmonary problem that may present with life-threatening complications. We report one case of broncholithiasis. A 49-year-old female presented with hemoptysis. Chest X-ray and computed tomography (CT) showed left interlobar lymph node calcification near the interlobar pulmonary artery, and calcification continued into the basal bronchus. Bronchoscopy demonstrated pedunculated granulation tissue in the left B8 bronchus obstructing the lumen. We did not recommend endobronchial removal because of the risk of bleeding, so we proposed surgical treatment. We performed left basal segmentectomy associated with bronchoplasty to preserve pulmonary function. It is important to gain proximal control of the pulmonary artery before dissection of its branches and to approach the pulmonary artery from the periphery to avoid massive intraoperative bleeding. The intrabroncholuminal stone was composed of 61% calcium carbonate and 39% calcium phosphate. The postoperative course was not eventful, and the bronchoscopical findings confirmed a good surgical outcome.

Survivin expression predicts early recurrence in early-stage breast cancer.

BACKGROUND: The apoptosis inhibitor survivin is one of the most specific proteins in breast cancer patients. The role of this protein in predicting prognosis is still controversial. PATIENTS AND METHODS: Survivin mRNA was measured using quantitative TaqMan reverse transcription-PCR in 76 samples, including 48 early-stage breast cancer tissues and adjacent normal tissues, from patients with operable tumors, and was tested for correlation with established clinicopathological factors, or disease-free survival (DFS). RESULTS: Comparing the survivin expression in 78 breast cancer patients with the clinicopathological factors (age, menopausal status, nodal category, tumor histology, tumor size, histological grade, ER and PgR status, and type of operation), T factor (T1-T4) was significantly associated with a high survivin mRNA ratio (p=0.0104). The proportion of tumors with a high survivin mRNA ratio was greater in node-positive than in node-negative tumors (p=0.0001), and in grade III tumors compared to grade I or grade II tumors (p =0.0001). Patients with low survivin expression showed significantly better disease-free survival than patients with high survivin expression in stage I and II breast cancer (p<0.0001, log-rank). Survivin expression alone is a powerful prognostic factor for disease-free survival of breast cancer patients without nodal involvement (HR: 0.024, 95% CI: 0.001-0.446, p=0.0123) using Cox multivariate regression analysis. CONCLUSION: Survivin is an indicator of the recurrence of early-stage breast cancer. Survivin might be used as a new marker to stratify early-stage breast cancer patients for more optimal treatment modalities, or it could be a promising target for therapy.

Down-regulation of the human PRL-3 gene is associated with the metastasis of primary non-small cell lung cancer.

BACKGROUND: Phosphatase of the regenerating liver (PRL)-3 protein tyrosine phosphatase gene is expressed in colon cancer metastasis. To investigate the role of this gene in metastatic lung cancer, we compared PRL-3 gene expression between primary cancers, metastatic lung cancer, and normal lung tissue. MATERIALS AND METHODS: Five metastatic tumor and normal samples from non-small cell lung cancer patients were obtained at the National Hospital Organization Kumamoto Medical Center (Kumamoto, Japan). For a quantitative evaluation of RNA expression by PCR, we used Taqman PCR methods. RESULTS: Although PRL-3 gene expression levels in the primary lesions were slightly decreased compared with those in the normal tissues, those in the metastatic lesions were extremely down-regulated in the synchronous metastatic case. In 2 of these 3 cases, the metastatic tumors showed down-regulated PRL-3 gene expression at 10 times less than that of the normal tissue, and the other tumor showed a slightly weaker expression. CONCLUSION: These data suggest that a down-regulation of the PRL-3 gene is important in lung cancer metastasis and provide a new hypothesis of lung cancer metastases.

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.