Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.

BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast. METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy. RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20). CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.

Development and Validation of a Lifestyle Behavior Tool in Overweight and Obese Women through Qualitative and Quantitative Approaches.

There is a paucity of effective intervention tools for overweight/obese women to assess, guide and monitor their eating behavior. This study aimed to develop a lifestyle intervention tool, assess its acceptability and usefulness, and verify its construct validity in overweight/obese women. The 6P tool (Portion, Proportion, Pleasure, Phase, Physicality, Psychology) was developed and 15 women with a body mass index (BMI) ≥ 25 kg/m2 were interviewed to assess its perceived acceptability and usefulness. Subsequently, the revised 6P tool was tested in 46 women with a BMI ≥ 25 kg/m2. The Three-Factor Eating Questionnaire (TFEQ), International Physical Activity Questionnaire-Short (IPAQ), and weight were measured at baseline and one-month. Most participants were satisfied with the presentation of the 6P tool (86.8%), and agreed it was useful in guiding healthy eating (81.6%) and raising awareness of eating behavior (97.4%). There were significant improvements in cognitive restraint (p = 0.010) and disinhibition (p = 0.030) (TFEQ), portion size (P1), pleasure behaviors (P3), and total composite 6P score (p < 0.001). However, there was no significant reduction in weight or increase in physical activity. The 6P tool is acceptable and presents with good validity for assessing lifestyle behaviors.

3D Laparoscopic common bile duct exploration with primary repair by absorbable barbed suture is safe and feasible.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP), with interval laparoscopic cholecystectomy (LC), is the most common treatment approach for common bile duct (CBD) stones. However, recent studies show that single-stage laparoscopic CBD exploration (LCBDE) is safe and feasible. Three-dimensional (3D) laparoscopy enhances depth perception and facilitates intracorporeal suturing. The application of 3D technology for LCBDE is emerging, and we report our case series of 3D LCBDE. METHODS: We audited the 27 consecutive 3D LCBDE performed from July 2017 to January 2020. We have a liberal policy for magnetic resonance cholangiopancreatography (MRCP) in patients with deranged liver function tests (LFT). All CBD explorations were done through choledochotomy with a 5 mm flexible choledochoscope and primarily repaired with an absorbable barbed suture without a stent or T-tube. RESULTS: The mean age of patients was 68 (range 44-91) years, and 12 (44%) were male. The indications for surgery were choledocholithiasis 67% (n=18), cholangitis 22% (n=6), and gallstone pancreatitis 11% (n=3). About 67% (n=18) had pre-operative ERCP. About 37% (n=10) had pre-operative biliary stent. Pre-operative MRCP was done in 74% (n=20), and the mean diameter of CBD was 14.5 mm (range 7-30). The median operative time was 160 (range 80-265) min. The operative drain was inserted in 18 patients. One patient each (4%) had a bile leak and a retained stone. There was no open conversion, readmission, or mortality. CONCLUSION: 3D LCBDE with primary repair by an absorbable barbed suture is safe and feasible. RELEVANCE FOR PATIENTS: This paper emphasized that one stage LCBDE should be a treatment option which is comparable with two stage ERCP followed by LC to treat CBD stones. In addition, 3D technology and barbed sutures use in LCBDE are safe and useful.

Use of del Nido Cardioplegia for Adult Heart Surgery: How Long Is Not Too Long?

The most apparent practical advantage of del Nido cardioplegia (DNC) is that it allows the surgeon a longer arrest period before a subsequent dose is needed, as opposed to the conventional St. Thomas' cardioplegia solution where the recommended ischemic time is ∼15-20 minutes. In this study, we explored the incidence of arrhythmia after cross-clamp removal as a surrogate for a safe myocardial ischemic time with the use of DNC in adult heart surgery. A total of 113 patients who had undergone heart valve repair and/or replacement surgery at the National University Hospital, Singapore, were investigated. This single-center retrospective study was conducted on a population where DNC had been used for myocardial protection between January 2017 and April 2019. Cardioplegia ischemic time interval groups were not significant predictors of postoperative arrhythmia, defibrillation, and intraoperative intra-aortic balloon pump usage. Crude comparison of postoperative outcomes showed no significant differences in any other postoperative variables, including mortality and total hospital stay. From the results of the present study, it appears that there is no optimal ischemic time interval for the administration of DNC within a 120-minute time period. It is likely that DNC has a redosing interval of, and may provide adequate myocardial protection, for up to 120 minutes.

Assessment of accuracy of Australian health service death data: implications for the audits of surgical mortality.

BACKGROUND: The Victorian Audit of Surgical Mortality (VASM) investigates all surgically related deaths in Victoria, Australia, as a surgical educational activity aimed to make surgery safer. Whilst data collected within the audit are regularly reviewed for accuracy, there has never been a review of the data provided from health services. METHODS: Two-year death data provided by one Victorian health service were reviewed. Hospital notes for 4 months of each year were analysed to assess patients dying under surgical care. These data were compared to referrals to the VASM over the same period. RESULTS: Of the 3907 patient deaths recorded, 35.1% were reviewed. During their final admission, 178 (13%) patients underwent a procedure (93 medical and 85 surgical). Only 29.2% of these were recorded in the health service data set. Eighteen patients died under the care of a surgeon without a procedure, meaning that 103 deaths should have been reported to the VASM of which only 55.3% (57/103) were reported. CONCLUSION: There were major errors in the health service database resulting in under-reporting of deaths to the VASM which could have education and policy repercussions. For improvements to the safety and quality of health services, it is critical that all deaths are accurately recorded by health services and reported to the relevant bodies with internal verification processes.

Remote cerebellar hemorrhage as a complication of lumbar spine surgery.

Remote cerebellar hemorrhage (RCH) is a rare yet potentially fatal complication of supratentorial and spinal surgery, where there has been either intentional or accidental breach of the dura. We present a case of RCH following a L4-5 decompression laminectomy complicated by an intraoperative dural tear which was detected and repaired at the time of surgery. Despite prompt intra-operative repair of the dura, there was persistent cerebrospinal fluid leak as evidenced by a high subfascial epidural drain output which resulted in bilateral intraparenchymal cerebellar hemorrhage. The patient was managed conservatively and recovered without neurological deficits.

Sudden sex hormone withdrawal and the effects on body composition in late pubertal adolescents with gender dysphoria.

Background Sex hormones initiate profound physical and physiological changes during the pubertal process, but to what extent are they responsible for continuing the body composition changes of late adolescence and what happens to body composition on sudden sex hormone withdrawal? Methods Thirty-six healthy, phenotypically and chromosomally normal late and post-pubertal individuals aged 15-17 years with gender dysphoria (transgirls - birth-registered males identifying as female n = 11; and transboys - birth-registered females identifying as male n = 25) underwent Tanita body composition analysis at 0, 6 and 12 months during reproductive hormone suppression with Triptorelin as part of the standard therapeutic protocol. Results and conclusions In the transgirl cohort, paired t-test analysis demonstrated a significant decrease in height and lean mass standard deviation scores over the 12-month period, going against an expected trajectory over that time. In contrast, oestrogen suppression appeared not to affect the body composition of transboys; their measurements were not significantly different at baseline and after 12 months of treatment. The withdrawal of sex hormone secretion does not appear to have a significant impact on female post-pubertal body composition, in contrast to that seen at the menopause. This suggests that other factors may preserve normal body balance in adolescents in the absence of sex steroids.

Perspectives of young Chinese Singaporean women on seeking and processing information to decide about vaccinating against human papillomavirus.

Human papillomavirus (HPV) vaccination uptake in Singapore is low among young women. Low uptake has been found to be linked to low awareness. Thus, this study aimed to understand active and passive vaccine information-seeking behavior. Furthermore, guided by the Elaboration Likelihood Model (ELM), this study examined young women's (aged 21-26 years) processing of information they acquired in their decision to get vaccinated. ELM postulates that information processing could be through the central (i.e., logic-based) or peripheral (i.e., heuristic-based) route. Twenty-six in-depth interviews were conducted from January to March 2016. Data were analyzed using thematic analysis. Two meta-themes-information acquisition and vaccination decision-revealed the heuristic-based information processing was employed. These young women acquired information passively within their social network and actively in healthcare settings. However, they used heuristic cues, such as closeness and trust, to process the information. Similarly, vaccination decisions revealed that women relied on heuristic cues, such as sense of belonging and validation among peers and source credibility and likability in medical settings, in their decision to get vaccinated. The findings of this study highlight that intervention efforts should focus on strengthening social support among personal networks to increase the uptake of the vaccine.

Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML).

Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, developing agents that target histone methylation remains to be in the early stage. We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range of anticancer effects in various human cancers. Here, focusing on acute myeloid leukemia (AML) as a model, we reported a less toxic analog of DZNep, named D9, which is shown to be efficacious in AML cell lines and patient-derived samples in vitro, as well as AML tumorigenesis in vivo. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy.

Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis.

UNLABELLED: Several studies have yielded conflicting results on the role of antibiotic prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta-analysis was carried out to investigate the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality. METHODOLOGY: Randomized controlled trials and cohort studies investigating impact of prophylactic systemic antibiotic used in acute necrotizing pancreatitis were retrieved from online databases. An overall analysis was done with all studies (Group 1), followed by subgroup analyses with randomized controlled trials (Group 2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality in each group using random effects model. RESULTS: Eleven studies involving 864 patients were included. No significant differences in the incidence of infected pancreatic necrosis were observed with prophylactic antibiotic use in all groups. Prophylactic antibiotic use was not associated with significant differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p = 0.04). There was no statistical difference in the incidence of fungal infections and surgical interventions. CONCLUSION: Antibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death.

3-Deazaneplanocin A (DzNep) is a potential epigenetic drug for the treatment of various cancers. DzNep has been reported to deplete histone methylations, including oncogenic EZH2 complex, giving rise to epigenetic modifications that reactivate many silenced tumor suppressors in cancer cells. Despite its promise as an anticancer drug, little is known about the structure-activity relationships of DzNep in the context of epigenetic modifications and apoptosis induction. In this study, a number of analogues of DzNep were examined for DzNep-like ability to induce synergistic apoptosis in cancer cells in combination with trichostatin A, a known histone deacetylase (HDAC) inhibitor. The structure-activity relationship data thus obtained provide valuable information on the structural requirements for biological activity. The studies identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH.

PDK1 signaling toward PLK1-MYC activation confers oncogenic transformation, tumor-initiating cell activation, and resistance to mTOR-targeted therapy.

UNLABELLED: Although 3-phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to the phosphoinositide 3-kinase (PI3K)-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency. Intriguingly, PDK1-PLK1-MYC signaling induces an embryonic stem cell-like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self-renewal. Finally, we show that a PLK1 inhibitor synergizes with an mTOR inhibitor to induce synergistic antitumor effects in colorectal cancer by antagonizing compensatory MYC induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting MYC-associated tumorigenesis and therapeutic resistance. SIGNIFICANCE: This work identifies PDK1­PLK1-MYC signaling as a new oncogenic pathway driving oncogenic transformation and CSC self-renewal. Targeted inhibition of PDK1/PLK1 is robust in targeting MYC dependency in cancer cells. Thus, our findings provide important insights into cancer and CSC biology and have significant therapeutic implications.