Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy

BackgroundProgrammed death ligand-1 (PD-L1) expression in cancer is often associated with cancer aggressiveness and responsiveness to treatment with PD-1 pathway inhibitors. We conducted a systematic study on the expression of membranous PD-L1 (mPD-L1) and nuclear PD-1-L1 (nPD-L1) in prostate needle biopsy specimens of prostate cancer patients who underwent primary radiotherapy and analyzed the association between PD-L1 expression and clinicopathological characteristics and prognosis of patients.MethodA total of 971 cancer-containing prostate needle biopsy cores from 172 patients were immunohistochemically stained with anti-PD-L1 antibody. The association of PD-L1 expression with Gleason score and tumor volume percentage was evaluated for each biopsy core. Total of 171 patients were divided according to mPD-L1 or nPD-L1 expression, and clinicopathological characteristics were compared between the positive and negative groups. The prognostic significance of mPD-L1, nPD-L1 and common prognostic factors were analyzed in terms of biochemical recurrence.ResultTotal of 15% and 46% of biopsy cores were stained positive for mPD-L1 and nPD-L1, respectively. There was a positive correlation between Gleason score and mPD-L1 and a negative correlation between Gleason score and nPD-L1. Between mPD-L1 and nPD-L1, there was no significant correlation. There was intraindividual heterogeneity in PD-L1 expression among different Gleason scores. For mPD-L1, only pretreatment PSA was significantly higher in the positive group than in the negative, but not Gleason score and T stage. For nPD-L1, Gleason score and T stage were significantly higher in the positive group than in the negative. Both mPD-L1 and nPD-L1 expression were not predictive of BCR-free survival in univariate and multivariate analyses.ConclusionsOur results suggest that PD-1 pathway inhibitor may be a potential therapeutic option in high risk prostate cancer patients as early as neoadjuvant setting. The novel discovery of PD-L1 expression in the nucleus of PC should be subjected to further research.     

老年复发性小肝癌患者行再切除术与经皮射频消融术的疗效分析

目的 探讨再次手术切除与经皮射频消融在老年复发性小肝癌患者中的临床疗效。方法 回顾性分析2008 年1 月至2014 年1 月淮安第一医院收治的56 例肝癌术后以小肝癌形式复发的老年患者。其中再次手术切除治疗34例（手术切除组）,经皮射频消融治疗22例（射频消融组）。比较两组的一般情况、术后生化指标、并发症发生情况以及生存状况,使用SPSS 20.0 统计学软件进行分析。结果 射频消融组患者治疗后TBIL、ALT、AST、ALB指标优于手术切除组（P＜0.05）;手术切除组患者并发症发生数（31例次）明显高于射频消融组（8 例次）（ P＜0.05）。射频消融组术后1、3、5 年无瘤生存率（86.4%、54.5%、45.5%）均明显好于手术切除组（61.8%、26.5%、14.7%）,差异均有统计学意义（P＜0.05）。结论 经皮射频消融对老年复发性小肝癌患者的远期治疗效果优于手术再切除,而且射频消融具有创伤小、肝功能影响小、术后并发症低等优点。     

Changing patterns in the clinical characteristics of Korean patients with breast cancer during the last 15 years

HYPOTHESIS: Breast cancer has become the most common cancer in Korean women in recent years, with continuously increased incidence rates attributed to westernized lifestyles. DESIGN: Retrospective case series evaluating the changing patterns of clinical characteristics in breast cancer during the last 15 years. SETTING: Hospitalized patients with breast cancer in a university medical center. PATIENTS: A total of 5001 breast cancer patients who underwent surgery between July 1989 and March 2004 at the Asan Medical Center. MAIN OUTCOME MEASURE: Clinicopathologic data were collected using the online Korea Breast Cancer Registration Program, including factors such as age, symptoms, stage, surgery, reconstruction, risk factors, and survival. RESULTS: The median age of patients slightly increased from 44 years in 1991 to 46 years in 2003. The most frequent age group was the fifth decade (41.7%) and premenopausal women younger than 50 years (64.9%). The proportion of asymptomatic patients detected by screening mammography increased from 3.8% in 1991 to 21.0% in 2003 (P<.001). The proportion of early breast cancer (stages 0 and I) increased from 34.2% in 1991 to 48.8% in 2003 (P=.013). Breast-conserving surgery has increased continuously from 5.1% in 1991 to 39.1% in 2003 (P<.001). Twelve percent of all patients who underwent mastectomies had immediate reconstruction, and the proportion showed an increasing trend, especially in skin-sparing mastectomy and transverse rectus abdominis myocutaneous flap reconstruction. Five-year observed survival rates were 84.1%. Five-year survival rates according to stages were as follows: (1) 98.5%, stage 0; (2) 95.3%, stage I; (3) 86.0%, stage II; (4) 65.0%, stage III; and (5) 29.3%, stage IV. The number of patients with specific risk factors, such as early menarche and late first delivery, significantly increased. Of 263 high-risk patients examined for the BRCA mutation, mutations were found in 20 patients (7.6%), with 13 cases with BRCA1 and 7 cases with BRCA2. CONCLUSIONS: The present study showed a continuous increase in the number of patients with breast cancer; the proportion of young patients, asymptomatic patients, early breast cancer, breast-conserving surgery, and immediate reconstruction after mastectomy; and the number of patients with risk factors. These results suggest that the clinical characteristics of Korean breast cancer patients reflect the patterns of Western countries.     

Lobectomy and Prophylactic Central Neck Dissection for Papillary Thyroid Microcarcinoma: Do Involved Lymph Nodes Mandate Completion Thyroidectomy?

Background

The present study was designed to investigate the necessity of completion thyroidectomy for patients who underwent thyroid lobectomy for low-risk papillary thyroid microcarcinoma (PTMC) that was later pathologically diagnosed as central lymph node (CLN) metastasis.

Methods

Between 1986 and 2001, we assessed 551 patients who underwent thyroidectomy with prophylactic ipsilateral central compartment neck dissection, and 409 patients were followed-up completely. Thyroid lobectomy were performed in 281 and 128 patients, respectively. The patients were divided into two groups according to CLN metastasis. Clinicopathological profiles and follow-up details were investigated by retrospective chart review.

Results

The CLN-positive and -negative groups were comprised of 43 (15.2 %) and 238 patients (84.8 %), respectively. The mean ages of the two groups were not significantly different (p > 0.05). The mean tumor size of the CLN-positive group (6.8 mm) was significantly larger than that of the CLN-negative group (5.6 mm; p < 0.05). Microscopic capsular invasion was significantly higher in the CLN-positive group (51.2 vs. 23.9 %; p < 0.05). Overall, 21 patients (7.4 %, 21/281) experienced recurrence. Among these, 2 (4.7 %, 2/43) and 19 (8.0 %, 19/238) were in the CLN-positive and -negative groups, respectively. There was no significant correlation between CLN metastasis and tumor recurrence.

Conclusions

Postoperative recurrence was lower in the CLN-positive group, and there was no significant correlation between CLN metastasis and tumor recurrence. Our results suggest that it is not necessary to perform completion thyroidectomy for PTMC patients who have undergone thyroid lobectomy and who have been pathologically diagnosed with CLN metastasis.     

Double umbilical cord blood transplantation for children and adolescents

Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.     

Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.     

Establishment of the Psychometric Properties of a Disaster Resilience Measuring Tool for Healthcare Rescuers in China:A Cross-Sectional Study

The aim of this study was to test the validity and reliability of a tool for measuring the disaster resilience of healthcare disaster rescuers.A cross-sectional...     

A Cadaveric Study of Thread Cubital Tunnel Release with Newly Developed Threads

ObjectiveThe percutaneous thread transection technique is a surgical dissecting method using a dissecting thread inserted through a needle under ultrasound guidance without skin incision. As the new dissecting threads were developed domestically, this cadaver study was conducted to compare the effectiveness and safety between the new threads (ultra V sswire and smartwire-01) and a pre-existing commercial dissecting thread (loop & shear) by demonstrating a modified looped thread cubital tunnel release. MethodsThe percutaneous cubital tunnel release procedure was performed on 29 fresh cadaveric upper extremities. The preexisting commercial thread was used in 5 upper extremities. The two newly developed threads were used in 24 upper extremities. Two practitioners performed the procedures separately. After the modified looped thread cubital release, anatomical and histological analyses were performed by a blinded anatomist. The presence of the dissected cubital tunnel and damaged adjacent soft tissue was assessed. ResultsOut of the 29 cadaveric upper extremities, 27 specimens showed complete dissection of the Osborne ligament and the proximal fascia of the flexor carpi ulnaris muscle. One specimen was incompletely dissected in each of the ultra V sswire and smartwire-01 groups. There were no injuries of adjacent structures including the ulnar nerve, ulnar artery, medial antebrachial cutaneous nerve, or flexor tendon with either the commercial thread or the newly developed threads. The anatomical analysis revealed clear and sharp incisional margins of the cubital tunnel in the Smartwire-01 and loop & shear groups. All three kinds of threads maintained proper linear elasticity for easy handling during the procedure. The smartwire-01 provided higher visibility in ultrasound than the other threads. ConclusionThe newly developed threads were effective and safe for use in the thread cubital tunnel release procedure.     

Decellularized Pig Kidney with a Micro-Nano Secondary Structure Contributes to Tumor Progression in 3D Tumor Model

In spite of many anti-cancer drugs utilized in clinical treatment, cancer is still one of the diseases with the highest morbidity and mortality worldwide, owing to the complexity and heterogeneity of the tumor microenvironment. Compared with conventional 2D tumor models, 3D scaffolds could provide structures and a microenvironment which stimulate native tumor tissues more accurately. The extracellular matrix (ECM) is the main component of the cell in the microenvironment that is mainly composed of three-dimensional nanofibers, which can form nanoscale fiber networks, while the decellularized extracellular matrix (dECM) has been widely applied to engineered scaffolds. In this study, pig kidney was used as the source material to prepare dECM scaffolds. A chemical crosslinking method was used to improve the mechanical properties and other physical characteristics of the decellularized pig kidney-derived scaffold. Furthermore, a human breast cancer cell line (MCF-7) was used to further investigate the biocompatibility of the scaffold to fabricate a tumor model. The results showed that the existence of nanostructures in the scaffold plays an important role in cell adhesion, proliferation, and differentiation. Therefore, the pig kidney-derived matrix scaffold prepared by decellularization could provide more cell attachment sites, which is conducive to cell adhesion and proliferation, physiological activities, and tumor model construction.