Quality of Radiotherapy Workforce Training within the USA.

The training, competency requirements and scope of practice of professionals within a radiation oncology department vary across countries. The purpose of this review is to shed light on the current status of radiotherapy training in the USA by discussing current benchmarks for medical residency, physics residency, radiation therapy and dosimetry training programmes. Although there are notable strengths, the US radiotherapy workforce training system also faces several challenges when it comes to standardising education to develop a competent workforce that meets societal needs. Continued efforts are needed at a systemic level to improve training in areas such as brachytherapy and proton therapy, promote research involvement and develop trainees who are equipped to form a competent radiation therapy workforce.

Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study.

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Long noncoding RNA Chaer mediated Polycomb Repressor Complex 2 (PRC2) activity to promote atherosclerosis through mTOR signaling.

OBJECTIVE: Recent studies highlighted long noncoding RNAs (lncRNAs) have been implicated in many biological processes and diseases. However, atherosclerosis is a major risk factor for cardiovascular disease, but the detailed mechanism of atherosclerosis progression remained unclear. In this study, we mainly focused on the role of lncRNA Chaer in atherosclerosis. PATIENTS AND METHODS: RT-PCR was used to detect the expression of lncRNA Chaer in atherosclerosis patients and animal model. Moreover, the expression of Chaer in vascular smooth muscle cell dysfunction model was also measured. Proliferation ability was tested by CCK-8 and cyclin D1 assay, through loss- and gain-of-function approaches. Western-blot was used to measure the expression of H3 lysine 27 methylation, when Chaer was in different levels. RIP and ChIP assay discovered an interaction between Chaer and PRC2 through mTOR signaling. RESULTS: Here we identified a heart-enriched long non-coding RNA, named Cardiac Hypertrophy Associated Epigenetic Regulator (Chaer). We found that the Chaer was highly expressed in serum samples from 28 patients with atherosclerosis, compared with 28 healthy volunteers. Chaer was dramatically upregulated in atherosclerotic plaques of ApoE-/- mice. We also found that the expression of Chaer was upregulated in vascular smooth muscle cell injury model. Through loss- and gain-of-function approaches, we showed that Chaer promotes cell proliferation and induces apoptosis in vitro. Mechanistically, Chaer interacts with Polycomb Repressor Complex 2 (PRC2) through inhibiting histone H3 lysine 27 methylation. Further, this interaction is induced upon mTOR signaling pathway. CONCLUSIONS: According to the results, we found that lncRNA Chaer was closely related to the progression of atherosclerosis, which could be a previously uncharacterized lncRNA-dependent epigenetic checkpoint.

Does having a rotator cuff repair prior to reverse total shoulder arthroplasty influence the outcome?

AIMS: The number of rotator cuff repairs that are undertaken is increasing. Reverse shoulder arthroplasty (RSA) is the procedure of choice for patients with rotator cuff arthropathy. We sought to determine whether patients who underwent rotator cuff repair and subsequent RSA had different outcomes compared with a matched control group who underwent RSA without a previous rotator cuff repair. PATIENTS AND METHODS: All patients with a history of rotator cuff repair who underwent RSA between 2000 and 2015 with a minimum follow-up of two years were eligible for inclusion as the study group. Outcomes, including the American Shoulder and Elbow Surgeons (ASES) scores, were compared with a matched control group of patients who underwent RSA without having previously undergone rotator cuff repair. RESULTS: The study group included 45 patients. Their mean age was 69 years (sd 8.6) and 27 patients (60%) were women. The mean ASES score improved from 43.1 to 76.6 two years postoperatively, and to 66.9 five years postoperatively. There was no significant difference between the outcomes at two years in the two groups (all p ≥ 0.05), although there was significantly more improvement in ASES scores in the control group (44.5 vs 33.4; p = 0.01). However, there was no significant difference between ASES scores at two and five years when baseline ASES scores were matched in the two groups (p = 0.42 at two years; p = 0.35 at five years). CONCLUSION: Significant improvements in ASES scores were seen following RSA in patients who had previously undergone rotator cuff repair. They had higher baseline ASES scores than those who had not previously undergone this surgery. However, there was no significant difference in outcomes between the two groups, two years postoperatively. Previous rotator cuff repair does not appear to affect the early outcome after RSA adversely.

Highly Variable Expression of ESR1 Splice Variants in Human Liver: Implication in the Liver Gene Expression Regulation and Inter-Person Variability in Drug Metabolism and Liver Related Diseases.

Estrogen receptor alpha (ESR1) plays an important role in many tissues including the liver. Numerous alternative splice variants of ESR1 exist that encode ESR1 proteins with varying functions. We aim to study ESR1 genomic organization and its mRNA expression profile in human liver by incorporating information from literature and genomic databases (Ensembl, NCBI and GTEx), and employing a quantitative method to measure all known ESR1 mRNA splice variants in 36 human livers. We re-constructed ESR1 genomic organization map that contains 29 exons. ESR1 mRNA splice variants with varying 5' untranslated region (5'UTR) and/or missing each of eight coding exons are readily detectable in liver and other tissues. Moreover, we found extensive inter-individual variability in splice variant pattern of ESR1 transcripts. Specifically, ESR1 transcripts lacking first coding exon are the main transcripts in liver, which encode ESR1 proteins missing N-terminal 173 amino acids (for example, ERα46), reported previously to have either constitutive activity or dominant negative effects depending on cellular context. Moreover, some livers predominantly express ESR1 transcripts missing exon 10 or 16, encoding C-terminal truncated ESR1 proteins with varying ESR1 activities. Inter-person variability in ESR1 expression profile may contribute to inter-person variability in drug metabolism and susceptibility to liver related diseases.

Oncologic outcomes and patient-reported quality of life in patients with oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation.

OBJECTIVE: It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND METHODS: An observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups. RESULTS: All patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33-83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008). CONCLUSION: Definitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.

Factors influencing late stage of breast cancer at presentation in a district Hospital - Segamat Hospital, Johor.

INTRODUCTION: In Malaysia, late stage presentation of breast cancer (stage III or IV) has been a healthcare problem that varies geographically throughout the country. This study aims to understand the factors influencing late stage of breast cancer at presentation among Malaysian women in Segamat Hospital, Johor, which is a district hospital. METHODS: A retrospective descriptive study was conducted on secondary data of all newly diagnosed breast cancer women from 1st August 2011 to 28th February 2014. Secondary data includes age, ethnicity, marital status, family history, education level, occupation, presenting symptom, duration of symptom, tumour size, tumour pathology, tumour grading, oestrogen, progesterone and HER-2 receptor status were collected and analysed using SPSS version 20.0.0. RESULT: In total, data from 52 women was analysed and two women were excluded for incompleteness as these women defaulted. Late stage at presentation was 59.6% of all new cases (17.3% stage III and 42.3% stage IV). The commonest age group of all women diagnosed with breast cancer was in the 5th decade. Majority of them were Malay, married and housewives with no family history of breast cancer. The statistically significant factors associated with late stage at presentation include Malay ethnicity (p=0.019), presenting symptoms other than breast lump (p=0.047), and duration of breast lump more than 3 months (p=0.009). DISCUSSION/CONCLUSION: The study demonstrated presentation at late stage of breast cancer is a major health concern among Malaysian women in district hospital. This may be attributed to different sociocultural beliefs, strong belief in complementary and alternative medicine, lack of awareness, and difficult accessibility to healthcare services.

Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply.

BACKGROUND: Flap viability after transfer depends on blood flow from the arterial blood supply below the fascia. This study evaluated survival of a pedicle flap with a perforator lateral branch and flow-through blood supply, compared with that of a flap with a flow-end blood supply and perforator terminal branch. METHODS: Forty Sprague-Dawley rats, 20 in each group, were assigned to transfer of a superficial epigastric artery pedicle island flap with a flow-through or flow-end configuration of blood supply. Laser Doppler imaging was used to evaluate flap perfusion 2 h, 3 days and 5 days after surgery. The rats were killed on day 5, and lead oxide-gelatine-enhanced flap angiography and histology with haematoxylin and eosin staining was performed. Dorsal midline tissue was excised for quantification of vascular endothelial growth factor by western blot assay. RESULTS: On day 5 after surgery, the flow-through group exhibited a significantly greater mean(s.d.) flap survival area (97·8(3·5) versus 80·8(10·2) per cent; P = 0·003), microvascular density (303(19) versus 207(41) per mm(2) ; P < 0·001) and perfusion (8·64(0·14) versus 5·95(0·14) perfusion units; P < 0·001) than the flow-end group. The flow-through group exhibited more angiosomes connected by dilated vascular anastomoses between the skin and subcutaneous fasciae. CONCLUSION: The flow-through blood supply improved pedicle perforator flap survival. Surgical relevance Perforator flap failure is mainly the result of impaired blood supply, as a flow-end blood configuration is nourished only by the perforator terminal branch of the artery. This work showed that the flow-through blood supply nourished by the perforator lateral branch improved flap survival, with dilatation of collateral vascular anastomoses and increased neoangiogenesis. The use of a flow-through configuration improves perforator flap survival and could therefore minimize morbidity resulting from flap necrosis.

Autophagic program is regulated by miR-325.

Autophagy is required for the maintenance of cardiomyocytes homeostasis. However, the abnormal autophagy could lead to the development of heart failure. Autophagy is enhanced during myocardial ischemia/reperfusion; it remains to elucidate the molecular regulation of autophagy. We report here that miR-325, ARC and E2F1 constitute an axis that regulates autophagy. Our results showed that miR-325 expression is upregulated upon anoxia/reoxygenation and ischemia/reperfusion. Cardiomyocyte-specific overexpression of the miR-325 potentiates autophagic responses and myocardial infarct sizes, whereas knockdown of miR-325 inhibited autophagy and cell death. We searched for the downstream mediator of miR-325 and identified that ARC is a target of miR-325. ARC transgenic mice could attenuate autophagy and myocardial infarction sizes upon pressure-overload-induced heart failure, whereas ARC null mice exhibited an increased autophagic accumulation in the heart. The suppression of ARC by miR-325 led to its inability to repress autophagic program. In exploring the molecular mechanism by which miR-325 expression is regulated, our results revealed that the transcription factor E2F1 contributed to promote miR-325 expression. E2F1 null mice demonstrated reduced autophagy and myocardial infarction sizes upon ischemia/reperfusion. Our present study reveals a novel autophagic regulating model that is composed of E2F1, miR-325 and ARC. Modulation of their levels may provide a new approach for tackling cardiac failure.

Carbon-13 urea breath test for Helicobacter pylori infection in patients with uninvestigated ulcer-like dyspepsia: an evidence-based analysis.

BACKGROUND: Dyspepsia is a condition defined by chronic pain or discomfort in the upper gastrointestinal tract that can be caused by Helicobacter pylori. The carbon-13 urea breath test (¹³C UBT) is a non-invasive test to detect H. pylori. OBJECTIVES: We aimed to determine the diagnostic accuracy and clinical utility of the ¹³C UBT in adult patients with ulcer-like dyspepsia who have no alarm features. DATA SOURCES: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2003 and 2012. REVIEW METHODS: We abstracted the sensitivity and specificity, which were calculated against a composite reference standard. Summary estimates were obtained using bivariate random effects regression analysis. RESULTS: From 19 diagnostic studies, the ¹³C UBT summary estimates were 98.1% (95% confidence interval [CI], 96.3-99.0) for sensitivity and 95.1% (95% CI, 90.3-97.6) for specificity. In 6 studies that compared the ¹³C UBT with serology, the 1¹³C UBT sensitivity was 95.0% (95% CI, 90.1-97.5) and specificity was 91.6 % (95% CI, 81.3-96.4). The sensitivity and specificity for serology were 92.9% (95% CI, 82.6-97.3) and 71.1% (95% CI, 63.8-77.5), respectively. In 1 RCT, symptom resolution, medication use, and physician visits were similar among the ¹³C UBT, serology, gastroscopy, or empirical treatment arms. However, patients tested with ¹³C UBT reported higher dyspepsia-specific quality of life scores. LIMITATIONS: Processing of the ¹³C UBT results can vary according to many factors. Further, the studies showed significant heterogeneity and used different composite reference standards. CONCLUSIONS: The ¹³C UBT is an accurate test with high sensitivity and specificity. Compared with serology, it has higher specificity. There is a paucity of data on the ¹³C UBT beyond test accuracy. PLAIN LANGUAGE SUMMARY: Breath test for detecting bacteria in patients with ulcer-like symptoms. Dyspepsia is a condition that causes long-term pain or discomfort in the upper abdomen. Symptoms can include heartburn, burping, bloating, nausea, or slow digestion. Dyspepsia can be caused by a bacterium that also causes ulcers and stomach cancer. Half of the world's people are believed to be infected with these bacteria. A test has been developed to detect the bacteria in a breath sample. Our review determined the accuracy of this breath test in adults with ulcer-like symptoms. From 19 studies, the breath test correctly identified 98% of patients with the bacteria and 95% of patients without the bacteria, as determined by a reference standard. Six studies compared the breath test to a blood test that is currently used. Both the breath and blood tests performed well in correctly identifying patients with the bacteria. However, the blood test was incorrectly positive in 20 more patients who did not have the bacteria according to the breath test. This means that more patients would have received unnecessary treatment. Thus, the breath test is an accurate test to detect the bacteria in adult patients who have ulcer-like symptoms. But the many differences among the studies in our review included several steps taken to perform the breath test and the reference standards used to compare a blood test with the breath test.

The histone deacetylase SIRT2 stabilizes Myc oncoproteins.

Myc oncoproteins are commonly upregulated in human cancers of different organ origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway-mediated proteolysis, and exert oncogenic effects by modulating gene and protein expression. Histone deacetylases are emerging as targets for cancer therapy. Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell proliferation. Affymetrix gene array studies revealed that the gene most significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4. Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc oncoproteins for ubiquitination and degradation, and small-molecule SIRT2 inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein expression, and suppressed neuroblastoma and pancreatic cancer cell proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2 inhibitors decreased Aurora A expression. Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies.

High prevalence of smoking among patients with suspected tuberculosis in South Africa.

There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). There are no data validating the accuracy of self-reported smoking in TB patients and limited data about the prevalence of smoking in TB patients from high-burden settings. We performed a cross-sectional analysis of 500 patients with suspected TB in Cape Town, South Africa. All underwent comprehensive diagnostic testing. The accuracy of their self-reported smoking status was determined against serum cotinine levels. Of the 424 patients included in the study, 56 and 60% of those with active and latent TB infection (LTBI), respectively, were current smokers. Using plasma cotinine as a reference standard, the sensitivity of self-reported smoking was 89%. No statistically significant association could be found between smoking and active TB or LTBI. In Cape Town, the prevalence of smoking among patients with suspected and confirmed TB was much higher than in the general South African population. Self-reporting is an accurate measure of smoking status. These results suggest the need to actively incorporate tobacco cessation programmes into TB services in South Africa.

Bexarotene induces dyslipidemia by increased very low-density lipoprotein production and cholesteryl ester transfer protein-mediated reduction of high-density lipoprotein.

A common dose-limiting side effect of treatment with the retinoid X receptor agonist bexarotene is dyslipidemia. We evaluated the effects of bexarotene on plasma lipid metabolism in patients with metastatic differentiated thyroid carcinoma and investigated the underlying mechanism(s) in apolipoprotein (APO) E*3-Leiden mice without (E3L) and with human cholesteryl ester transfer protein (CETP; E3L.CETP). To this end, 10 patients with metastatic differentiated thyroid carcinoma were treated with bexarotene (300 mg/d) for 6 wk. Bexarotene increased plasma triglyceride (TG; +150%), primarily associated with very low-density lipoprotein (VLDL), and raised plasma total cholesterol (+50%). However, whereas bexarotene increased VLDL-cholesterol (C) and low-density lipoprotein (LDL)-C (+63%), it decreased high-density lipoprotein (HDL)-C (-30%) and tended to decrease apoAI (-18%) concomitant with an increase in endogenous CETP activity (+44%). To evaluate the cause of the bexarotene-induced hypertriglyceridemia and the role of CETP in the bexarotene-induced shift in cholesterol distribution, E3L and E3L.CETP mice were treated with bexarotene through dietary supplementation [0.03% (wt/wt)]. Bexarotene increased VLDL-associated TG in both E3L (+47%) and E3L.CETP (+29%) mice by increasing VLDL-TG production (+68%). Bexarotene did not affect the total cholesterol levels or distribution in E3L mice but increased VLDL-C (+11%) and decreased HDL-C (-56%) as well as apoAI (-31%) in E3L.CETP mice, concomitant with increased endogenous CETP activity (+41%). This increased CETP activity by bexarotene-treatment is likely due to the increase in VLDL-TG, a CETP substrate that drives CETP activity. In conclusion, bexarotene causes combined dyslipidemia as reflected by increased TG, VLDL-C, and LDL-C and decreased HDL-C, which is the result of an increased VLDL-TG production that causes an increase of the endogenous CETP activity.

[P53 expression and clinical significance in oral squamous cell carcinoma].

P53 protein expression was investigated in oral squamous cell carcinomas and oral premalignant lesions by monoclonal antibody Do-1 and immunohistochemistry technique. 4 of 12 (33.3%) samples of severe epithelial dysplasia and 25 of 44 (56.8%) samples of squamous cell carcinoma expressed P53 protein while all the normal mucosa, mild and moderate epithelial dysplasia were negative. The P53 expression in carcinomas was associated with differentiation, lymph node metastasis and tumour stage. This result indicated that P53 genic mutation might be an early event in oral mucosa carcinogenesis and related to oral tumor progression. Detection of P53 protein probably has clinical significance in identifying the premalignant lesions of oral mucosa and predicting the prognosis of oral carcinomas.

[Effect of lidocaine on cardiovascular response to stomach tube intubation before surgery].

UNLABELLED: The purpose of this study was to observe the effect of lidocaine on cardiovascular responses to stomach-tube intubation. 80 patients (ASA I-II) were randomly divided into two groups: study group with 2% lidocaine 5 ml throat surface anesthesia (n = 40) and control group without lidocaine (n = 40). Hemodynamic variables including systolic blood pressure (SBp), heart rate (HR), and rate-pressure product (RPP) were measured before, immediately, 1 min, 3 min, ore stable than that in control group (P < 0.05 or P < 0.01). CONCLUSION: 2% lidocaine can effectively prevent cardiovascular responses to the intubation.

Tracheoesophageal fistula in a patient with recurrent Hodgkin's disease. A case for hope or despair.

Tracheoesophageal fistula (TEF) is a devastating complication of malignancies; however, those associated with Hodgkin's disease (HD) may carry a better prognosis. We present a patient with recurrent HD and TEF.

[The construction of 2 BS cell lines overexpressing PKC beta I isoform and the priliminary analysis of the relationship between expression of PKC beta I and cell proliferation].

Using gene transfection technique, we have constructed a series of human embryonic lung cell lines that overexpress stably a full length cDNA encoding the beta I isoform of PKC for the first time. BS-PKC 3 is a cell line containing about 3 fold greater PKC activity than parental cell lines or control cells that carry an integrated vector lacking the cDNA inset. In comparison with control cells and parental cells, these cells exhibit significantly enhanced growth rate. The expression of oncogene c-myc which is relating closely to cell proliferation is also increased obviously in BS-PKC 3 cell. We have firstly evidence that the overexpression PKC beta I affect the level of the expression of c-myc in the 2 BS cells. It seems that there may be one of the molecular mechanisms of the effect on the proliferation in the 2 BS cells by PKC beta I.

Oral cancer progression and c-erbB-2/neu proto-oncogene expression.

Monoclonal antibody PAb3 to c-erbB-2/neu protein was utilized in the immunoperoxidase staining of 86 human specimens from oral mucosa. These tissue specimens represented a spectrum from 7 normal to 9 simple hyperplasia, 15 mild dysplasia, 14 moderate dysplasia, 20 severe dysplasia and 21 squamous cell carcinoma. Our study indicated that as the cells acquire a more malignant phenotype, there was a progressive increase in neu expression. It also suggested that neu may be involved in the development of oral cancers and that its evaluation in the early stages may assist in the diagnosis and management of oral cancers.