[Methylthioadenosine phosphorylase and p16 as surrogate diagnostic markers for CDKN2A homozygous deletion in brain tumors].

Objective: To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. Methods: A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined. Results: Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion (P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions: MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

[Pay attention to molecular pathological diagnosis of pediatric glioma].

Glioma is one of the most common central nervous system tumors in children.Increasing studies show that compared with adults, some gliomas in children have unique molecular genetic characteristics and completely different biological behaviors, although they are similar to adults in morphology and nomenclature. Therefore, pediatric glioma is by no means a "miniature version" of adults. In the 5th edition of WHO classification of central nervous system tumors published in the end of 2021, one of the most important revisions is the division of the classification into adult-type and pediatric-type diffuse gliomas, and the latter is further divided into pediatric-type diffuse low-grade gliomas and pediatric-type diffuse high-grade gliomas. In addition to histological morphology and clinical features, the basis of classification includes more molecular features. Therefore, in clinical practice, we need to pay more attention to the significance of molecular pathological diagnosis in the diagnosis and treatment of gliomas in children.

[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

[Advancement in endovascular therapy of aortoiliac occlusive disease].

Aortoiliac occlusive disease (AIOD) refers to the stenosis and occlusion of the distal abdominal aorta and(or) bifurcation of the aortoiliac artery,which is mainly caused by atherosclerosis,leading to pelvic and lower limb ischemia.Open surgery has always been the main treatment for complex AIOD.However,in recent years,with the development of endovascular surgery technologies and medical instruments,its treatment concept has been greatly changed.More and more clinical evidence has proved that the long-term efficacy of endovascular therapy is not inferior to that of traditional open surgery,so minimally invasive endovascular therapy has become the preferred treatment for AIOD.

[Effects of protein disulfide isomerase on hyperglycemia and hypoxia/reoxygenation injury in H9c2 cardiomyocytes].

Objective: To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease. Methods: We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected. Results: PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) µmol/L、(10.0±1.0) µmol/L、(11.7±1.0) µmol/L vs (4.2±1.8) µmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) µg/L、(1.64±0.27) µg/L、(1.20±0.14) µg/L vs (2.62±0.12) µg/L, all P<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(all P<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) µg/L vs (3.03±0.10) µg/L、(2.06±0.05) µg/L vs (2.31±0.06) µg/L、(1.83±0.07) µg/L vs (1.96±0.11) µg/L、(1.20±0.06) µg/L vs (1.39±0.09) µg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) µg/L vs (0.59±0.09) µg/L、(0.62±0.04) µg/L vs (0.53±0.05) µg/L、(0.55±0.14) µg/L vs (0.51±0.12) µg/L、(0.48±0.12) µg/L vs (0.35±0.08) µg/L] in response to different treatments in cultured H9c2 cardiomyocytes (all P<0.05). Conclusion: PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.

[Clinicopathological features and molecular characteristics of tall cell and hobnail variants of papillary thyroid carcinoma].

Objective: To investigate the clinicopathological and molecular genetic characteristics of tall cell variant and hobnail variant of papillary thyroid carcinoma (PTC). Methods: Twenty-one cases of tall cell variant (TCV-PTC) of PTC (TCV-PTC) and ten cases of hobnail variant of PTC (HV-PTC), as the highly aggressive group, were collected from Xuanwu Hospital from August 2009 to August 2015. Twenty-two cases of follicular variant and 21 classical PTC cases were included as control. Relevant clinical and pathologic data were obtained, and in some cases, paraffin samples were selected for gene mutation spectrum analysis using second generation sequencing. Results: There were 18 males and 56 females; 57 patients were younger than 55 years of age, and 17 patients were 55 years or older. The mean tumor size was 1.6 cm for the high-aggressive group (TCV-PTC and HV-PTC), 1.1 cm for the follicular subtype, and 1.6 cm for the classical type. There were 54 cases with thyroid capsule invasion, 24 cases with extra-thyroidal invasion, and 45 patients with lymph node metastases. Regional recurrence occurred in 7 cases, no recurrence in 54 cases, and 13 patients were lost to follow-up. The highly aggressive group was more likely to show extra-thyroidal invasion, lymph node metastases and recurrence than those with classical PTC (P<0.05). Within this cohort, BRAF V600E mutation was detected in 53 cases and TERT promoter mutation in 6 cases. Compared with the single mutation group and no mutation group, BRAF and TERT promoter co-mutation group was more commonly detected in older age, male, larger tumor size and more prone to extra-thyroid invasion (P<0.05). In addition, among BRAF and TERT co-mutation cases, the highly-aggressive group accounted for the highest proportion (5/6). Conclusions: TCV-PTC and HV-PTC, as highly-aggressive variants of PTC, show more aggressive biologic behavior (more lymph node metastasis, external thyroid invasion and recurrences) than the classical and follicular variants of PTC. Coexisting BRAF and TERT promoter mutations may be associated with invasive biologic behavior.

[Extraskeletal mesenchymal chondrosarcoma in central nerve system: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

[Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas].

Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case (P>0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations (P>0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.

[Chordoid glioma: a clinicopathological study].

Objective: To analyze the clinicopathological features of chordoid glioma. Methods: A total of 12 cases of chordoid gliomas from 2009 to 2020 in Xuanwu Hospital of Capital Medical University and General Hospital of Chinese People's Liberation Army were retrospectively analyzed. The clinical and imaging characteristics, pathologic and molecular characteristics were analyzed, and the relevant literature was reviewed. Results: All 12 patients (4 males and 8 females) aged from 25 to 67 years (mean 39 years) and mainly had a history of headache or/and vision loss. MRI showed that the lesions located in the third ventricle, and they showed abnormal enhancement. Pathologically, these 12 cases displayed the morphologic characteristics of chordoid gliomas, including papillary structures in two cases. Immunohistochemically, GFAP and vimentin were expressed in all 12 cases (12/12). TTF1 was also expressed in all cases (10/10). CD34 and CKpan were seen in 11 cases (11/12). EMA with dot-and/or-ring like positivity was seen in 9 cases (9/10). Tissues were available in nine chordoid gliomas for Sanger sequencing to detect PRKCA and IDH gene mutation, and eight cases (8/9) showed PRKCA gene D463H mutation. None of these cases showed IDH1 R132 and IDH2 R172 mutation. All 12 patients underwent surgery, and four were lost to follow up. The remaining eight patients were progression or recurrence free at last follow-up in January 2021. Conclusions: Chordoid gliomas have relatively distinguishing clinical and histopathological features. PRKCA gene mutation in chordoid gliomas can be considered as a biomarker for the diagnosis and differential diagnosis of chordoid gliomas, and may provide a direction for future targeted therapy.

[Clinicopathological features of diffuse leptomeningeal glioneuronal tumor].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). Methods: Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed. Results: The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients. Conclusions: DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

[Drug-coated balloons versus bare metal stent for treatment of femoropopliteal lesions:36 month follow-up results of single center].

Objective: To examine the therapeutic effects of drug-coated balloon (DCB) and bare metal stent (BMS) on primary femoropopliteal disease (FPAD) in the real world. Methods: This was a retrospective analysis of single-center follow-up results at 12,24,and 36 months of patients with FPAD lesions that were treated with DCB and BMS at Department of Aortic and Vascular Surgery, Fu Wai Hospital.One-to-one propensity score matching(PSM) was performed to balance the covariance between DCB group (137 cases) and BMS group (100 cases). Freedom from clinically driven target lesion reintervention rate(fCD-TLR) was determined by Kaplan-Meier curve.Log-rank test was used to compare the rates of fCD-TLR between DCB and BMS groups at 12,24,36 months post-operation. Results: After PSM, there were both 71 patients in each group,aged (68.0±9.6) years(range: 46 to 90 years) and (68.8±7.3) years(range: 48 to 87 years),lesion lengths were (119.6±14.2)mm(range:40 to 380 mm) and (110.8±13.1)mm(range:40 to 400 mm). The median follow-up period were 24.3 months (range:5.8 to 55.1 months).There was no death,amputation or reintervention within the 30 days after operation.The rates of fCD-TLR for DCB group at 12,24 and 36 months were 97.2%,85.9%,69.1%, and 95.8%,83.1%,59.2% for BMS group.There was no statistical difference between the two groups by Log-rank test (P=0.551). Conclusion: DCB and BMS can both maintain favorable clinical effects in FPAD patients at 12,24,36 months post-operation.

[Distribution and metabolism of toxicants in rats with phenol burn].

Objective: To study the distribution and metabolism of toxicants in rats after phenol burn. Methods: In February 2019, SPF-grade healthy SD male rats were transdermally exposed to 6 mg/kg phenol to create a 5% body surface burn model of rats. High performance liquid chromatography was used to determine phenol content in rat plasma and kidney tissues after 0.25, 0.75, 2, 4, 8, 16, and 32 h, respectively. The kinetic parameters of phenol were calculated by DAS 2.0 software, and the kidney targeting of phenol was evaluated. Results: The area under the blood concentration-time curve at 0-8 h (AUC(0-8)) of the rat after phenol burn was (28.741±6.485) µg/ml·h, and the area under the blood concentration-time curve from 0 to infinite time (AUC(0-∞)) was (30.354±6.424) µg/ml·h, half-life (t(1/2)) was (2.111±0.632) h, peak concentration (C(max)) was (16.287±4.870) µg/ml, mean residence time (MRT) was (1.854±0.148) h. The target efficiency (DTE) of rat kidney was 2.91. Conclusion: Phenol burn rats have fast percutaneous absorption, rapid elimination of phenol, and have high clearance rate, short MRT, and weak substance accumulation. Phenol has relatively obvious selectivity to the kidneys.

Most Orthopaedic Studies Using the National Inpatient Sample Fail to Adhere to Recommended Research Practices: A Systematic Review.

BACKGROUND: The National Inpatient Sample (NIS) database is accessible, inexpensive, and increasingly used in orthopaedic research, but it has complex design features that require nuanced methodological considerations for appropriate use and interpretation. A recent study showed poor adherence to recommended research practices for the NIS across a broad spectrum of medical and surgical fields, but the degree and patterns of nonadherence among orthopaedic publications remain unclear. QUESTIONS/PURPOSES: In this study, we sought: (1) to quantify nonadherence to recommended research practices provided by the Agency for Healthcare Research and Quality (AHRQ) for using the NIS data in orthopaedic studies from 2016-2017; and, (2) to identify the most common nonadherence practices. METHODS: We evaluated all 136 manuscripts published across the 74 orthopaedic journals listed on Scimago Journal & Country Rank that used the NIS from January 2016 through December 2017. Of those studies, 2% (3 of 136) were excluded because NIS was not used for analysis. The studies were evaluated for adherence to seven recommended research practices by the AHRQ: (1) identifying observations as hospitalization events rather than unique patients; (2) not performing state-level analyses; (3) limiting hospital-level analyses to data from year 1988-2011; (4) not performing physician-level analyses; (5) avoiding the use of nonspecific secondary diagnosis codes to infer in-hospital events; (6) using survey-specific analysis methods that account for clustering, stratification, and weighting; and (7) accounting for data changes in trend analyses spanning major transition periods in the data set (1997-1998 and 2011-2012). RESULTS: Overall, 93% (124 of 133) of the studies did not adhere to one or more practices. For each of the research practices assessed, 80% (106 of 133) of the studies did not account for the clustering and stratification in survey design; 56% (75 of 133) implied records were unique patients rather than hospitalization events; 41% (54 of 133) inappropriately used secondary diagnosis codes to infer in-hospital events. CONCLUSIONS: Nearly all manuscripts published in orthopaedic journals using the NIS database in 2016 and 2017 failed to adhere to recommended research practices. Future research quantifying variations in study results on the basis of adherence to recommended research practices would be of value. CLINICAL RELEVANCE: With the ubiquitous presence of large-database studies in orthopaedic journals, our work points to the importance of rigorous methodological appraisal when evaluating results, and encourages journals to require the use of the methodology checklists upon submission of such studies. More research is needed to determine whether deviations from recommended research practices actually lead to biased conclusions that affect patient care and policy-related decisions.

[High-grade gliomas with H3 G34R mutation: a clinicopathological study].

Objective: To analyze the clinicopathological features and probable mechanisms of high-grade gliomas with H3 G34R mutation. Methods: Five cases of high-grade gliomas with H3 G34R mutation were collected at Xuanwu Hospital, Capital Medical University, Beijing, China, from 2016 to 2019. The clinical and pathological data for each case was retrospectively reviewed. Results: The 5 patients (2 males and 3 females) aged from 15 to 45 years (mean 23 years), and had a history of headache or motor weakness. Four of them were younger than 20 years of age. Magnetic resonance imaging showed that the lesions of 3 cases were seen separately in frontal lobe, parietal lobe or temporal lobe, 1 case involved both frontal lobe and parietal lobe, and otherwise multiple lobes were involved in 1 case. Contrast enhancement could be observed in 2 cases. Pathological examination showed that glioblastoma was the most common entity, with or without primitive neuronal component. All 5 cases showed that H3 G34R was diffusely positive in tumor nuclei with ATRX loss. Moreover, p53 was overexpressed in 4 cases. None of them showed Olig2 expression. Two patients showed disease progression after surgery at 18 months and 24 months, respectively. The latter of the two deceased 3 months after tumor progression. Conclusions: The clinicopathological and molecular genetics features of high-grade gliomas with H3 G34R mutation have relatively similar clinicopathological and genetic features, and more commonly seen in young adults (vs. older adults). Thus, these tumors may be discussed further as a distinct tumor entity.

[Surgical treatment of total subclavian artery occlusion: a single center experience of 67 cases].

Objective: To examine the outcomes of surgical repair for patients with total subclavian artery occlusion. Methods: A retrospective analysis was performed on 67 patients with subclavian artery occlusion disease admitted at Ward 1 of Aortic and Vascular Surgery Center, Fuwai Hospital from January 2016 to July 2019. The age was, and There were 51 male patients and 16 females with an age of (61.7±8.2) years (range: 37 to 79 years). The t-test, Mann-Whitney U-test, χ(2) test, and Fisher's exact test were used to analyze the factors related to the technique success. The Kaplan-Meier curve was used to calculate the cumulative patency rate and plot the corresponding survival curves, and the Log-rank test was used for comparison. The length from the subclavian artery ostial to the occlusion area was used as a variable to plot the receiver operating characteristic curve, and the optimal cut-off value was determined by the Youden index. Results: Eighteen patients received open surgery. Forty-nine patients with subclavian artery occlusion accepted endovascular repair, of which 38 patients succeeded (31 cases on left side and 3 cases on right side). Fifteen patients failed with endovascular therapy, of which 10 cases received elective surgery and 5 cases received conservative therapy. The success rate of endovascular repair was 69.4%(34/49). Among them, the success rate of left subclavian artery occlusion was 81.6%(31/38), while the right side was 3/11. Patients with the length from the subclavian artery ostial to the occlusion area ≥6 mm were more likely to get success (23/34 vs. 4/15, χ(2)=5.506, P=0.019). In the endo-group, one patient had hemorrhage in the left chest. In the open-group, one patient had lymphatic leakage. Follow-up period ranged from 3 to 46 months with a median of 22 months. The patency of endovascular repair group and the open surgery group was 92.6% and 90.8% at 12-month, while 82.9% and 84.3% at 24-month, respectively. The cumulative patency rates of smoking patients and non-smoking patients after endovascular treatment were 70.2% vs. 100% (P=0.048) at 24-month. No independent prognosis factors were identified through the Cox proportional risk model which significantly affected postoperative patency rates for patients with subclavian artery occlusion. Conclusions: Part of patients with subclavian artery occlusion can be treated by endovascular therapy. The success rate of left subclavian artery occlusions is higher than right sides. The length from the subclavian artery ostial to the occlusion area affected the success rate of repair.

Poor Access to Breast Reconstruction: A Geographical Shortage of Plastic Surgeons Relative to Breast Surgeons in the United States.

BACKGROUND: Breast cancer surgery involves removal of cancer performed by a breast surgeon and reconstruction performed by a plastic surgeon. Historically, many women have not undergone breast reconstruction surgery (BRS), with current literature suggesting that geographic barriers may play a role. Our objective was to determine if there is a geographic shortage of plastic surgeons in the United States and to assess for trends in access to BRS for rural, suburban, and urban populations. METHODS: A database investigation of the 2018 membership for the American Society of Breast Surgeons and the American Society of Plastic Surgeons was performed. We searched for a breast surgeon's geographic presence by zip code and looked for the presence of a plastic surgeon within 10 and 20 miles. Zip codes were then categorized as urban, suburban, or rural. Within each population category, the average numbers of breast surgeons and plastic surgeons were quantified. RESULTS: Twenty-five percent of breast surgeon zip codes had no plastic surgeons located within 10 miles; 10% of breast surgeon zip codes had no plastic surgeon within 20 miles. There were on average 7.03 breast surgeons in each urbanized area. Suburban and rural areas had an average of 1.14 and 1.00 breast surgeons, respectively. There were on average 10.97 plastic surgeons per urbanized area. Suburban and rural areas had, on average, 0.23 and 0.06 plastic surgeons, respectively. CONCLUSIONS: A national comparison of the geographical distribution between breast surgeons and plastic surgeons indicates a shortage of plastic surgeons, especially in rural and suburban areas.

[Implication of BRAF V600E and CTNNB1 gene mutations in the pathological classification of craniopharyngioma].

Objective: To investigate the clinicopathological significance of BRAF V600E and CTNNB1 gene mutations in adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). Methods: The retrospective study included a total of 67 craniopharyngiomas diagnosed from October 2009 to August 2018 at Xuanwu Hospital, Capital Medical University. The immunohistochemical staining for ß-catenin and BRAF V600E expression, Sanger sequencing of exon 3 of CTNNB1, BRAF mutation analysis by scorpions amplification refractory mutation system (ARMS) fluorescence quantitative PCR were performed. Univariate survival analysis was used to correlate with tumor recurrence. Results: Of the 67 patients, 53 were ACPs and 14 were PCPs. Four patients underwent multiple operations and one of them presented with malignant transformation into squamous cell carcinoma. Histologically, ACPs were characterized by whorl-like cell clusters, peripheral palisaded layer, stellate reticulum, finger-shaped protrusions, ghost cells and wet keratinous substances. While PCPs usually consisted of mature squamous epithelium associated with fibrovascular stroma resulting in papillary appearance. The nuclear immunopositivity for ß-catenin was observed in 73.6% (39/53) of ACPs, and it was absent in PCPs (0/14). The nuclear translocation of ß-catenin usually presented at whorl-like structures or around ghost cells. Of all the cases, mutations analysis in exon 3 of ß-catenin gene CTNNB1 were successful in 46 cases and 42.1% (16/38) of ACP showed CTNNB1 gene mutation, while none of the PCPs harbored CTNNB1 gene mutation (0/8). The cytoplasmic immunopositivity for BRAF V600E mutant protein was found in all PCPs (14/14) and negative in all ACPs (0/53). ARMS-PCR results showed that BRAF V600E mutations were observed in 13/14 of PCPs but not seen in ACPs (0/53). Follow-up data were available in 35 patients with duration of 2 to 120 months. Ten patients experienced recurrences after the first surgery. Upon univariate survival analysis, only subtotal excision was found to be associated with increased recurrence (P=0.032), while pathological type, postoperative radiotherapy and CTNNB1 gene mutation were not (P>0.05). Conclusions: There is significant difference in the expression of BRAF V600E and CTNNB1 genes between ACP and PCP, and their immunohistochemical and molecular detection therefore can be used in the diagnosis and differential diagnoses of craniopharyngiomas.

miR-133b acts as a tumor suppressor and negatively regulates EMP2 in glioma.

In recent years, the incidence of neuroglioma (glioma) has trended towards a younger age-group. Gene therapy has been widely implemented and a growing number of microRNAs associated with glioma have been identified., Herein, we detected the expression of micro RNA - miR-133b - in glioma by qPCR and also its effect on cell viability, survival and apoptosis of in vitro U87 and A172 cells. The binding effect of miR-133b on epithelial membrane protein-2 (EMP2) was verified and we then investigated the effect of EMP2 on in vitro glioma cells and tested the expression of apoptosis related factors after administration of altered miR-133b and EMP2 expressions. We found that miR-133b was down-regulated in glioma compared to adjacent non-tumorous tissue and also that its over-expression inhibits cell viability and survival and enhances apoptosis in the U87 and A-172 cells. Moreover, miR-133b effectively binds to EMP2, down-regulates its expression and negates its normal function. EMP2 normally promotes cell apoptosis and reduces cell viability and survival while miR-133b over-expression regulates the expression of apoptotic-associated protein and activates the apoptotic pathway, thus counteracting EMP2 regulation of opposite expression effects. Further, miR-133b can be considered a tumor suppressor because of its low expression and effects on cell apoptosis via down-regulating EMP2 expression and activating the apoptotic cell pathway in glioma. EMP2 is a risk factor for glioma, and miR-133b should prove a potential target for glioma clinical prevention and treatment.