Training Paradigms in Hepato-Pancreatico-Biliary Surgery: an Overview of the Different Fellowship Pathways

Hepato-pancreatico-biliary (HPB) surgery, and the training of HPB surgeons, has evolved significantly over the last several decades. The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO) ACGME fellowship, the American Society of Transplant Surgeons (ASTS) fellowship, and the Americas Hepatopancreaticobiliary Association (AHPBA) fellowship. These fellowships offer variable experiences in pancreas, liver, and biliary cases, and each pathway offers a unique perspective on HPB surgery. The CGSO ACGME, ASTS, and AHPBA fellowships represent decades of work by the three major surgical leadership stakeholders to improve and ensure quality training of future HPB surgeons. The best care is provided by the HPB surgeon who has been trained to understand the importance of all available treatment options within the context of a multidisciplinary setting. The three fellowship pathways are outlined in this paper with the nuances and variations characteristic of the different training programs highlighted

Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy.

OBJECTIVE: The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction. METHODS AND RESULTS: Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8+/-11.6 years. Coronary endothelial dysfunction (epicardial constriction>20% or increase in coronary blood flow<50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipid-lowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p=0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p<0.01). CONCLUSIONS: Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation

Persistent changes in lipoprotein lipids after a single infusion of ascending doses of MDCO-216 (apoA-IMilano/POPC) in healthy volunteers and stable coronary artery disease patients

Background and aims: Effects of single ascending doses of MDCO-216 on plasma lipid and lipoprotein levels were assessed in human healthy volunteers and in patients with stable coronary artery disease (CAD). Methods: MDCO-216 was infused at a single dose of 5, 10, 20, 30 or 40 mg/kg over 2 h and blood was collected at 2, 4, 8, 24, 48, 168 and 720 h after start of infusion (ASOI). Lipoprotein lipids were assessed by FLPC and by 1H NMR. Results: Plasma concentrations of free cholesterol (FC) displayed a rapid and dose-dependent rise, peaking at 8 h, but remaining above baseline until 48 h ASOI, whereas levels of esterified cholesterol (CE) increased at lower doses but not at higher doses, and even decreased below baseline at the highest dose. Plasma cholesterol esterification rate (CER) decreased with a first nadir between 4 and 8 h and a second nadir at 48 h ASOI. Taken over all subjects receiving MDCO-216, the increase in FC at 8 h correlated inversely with the drop in CER at 4 h but positively with the increase in basal and scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux capacities at 2 h ASOI. Upon FPLC analysis, FC was found to increase first in high density lipoproteins (HDL) and very low density lipoproteins (VLDL) and later (at 48 or 168 h ASOI) in low density lipoproteins (LDL). CE initially decreased in LDL and HDL but after 24 h started to increase in VLDL and LDL whereas HDL-CE was still below baseline at 48 h. Phospholipids (PL) showed the same pattern as FC. Triglycerides (TG) also rose rapidly, most prominently in VLDL, but also in LDL and HDL. Apolipoprotein E (Apo-E) in VLDL increased at 4-8 h but returned to baseline at 24 h ASOI. 1H NMR analysis showed a rapid and dose-dependent increase in HDL particle size, peaking at 2 h and returning to baseline at 24 h, and a small increase in HDL particle concentration. After infusion of the 40 mg/kg dose, LDL and VLDL-particles also increased in number and size. Conclusions: A single administration of MDCO-216 caused rapid changes in lipid levels and lipoprotein composition, some of which persisted for at least 7 days

Towards a novel biologically-inspired cloud elasticity framework

With the widespread use of the Internet, the popularity of web applications has significantly increased. Such applications are subject to unpredictable workload conditions that vary from time to time. For example, an e-commerce website may face higher workloads than normal during festivals or promotional schemes. Such applications are critical and performance related issues, or service disruption can result in financial losses. Cloud computing with its attractive feature of dynamic resource provisioning (elasticity) is a perfect match to host such applications. The rapid growth in the usage of cloud computing model, as well as the rise in complexity of the web applications poses new challenges regarding the effective monitoring and management of the underlying cloud computational resources. This thesis investigates the state-of-the-art elastic methods including the models and techniques for the dynamic management and provisioning of cloud resources from a service provider perspective. An elastic controller is responsible to determine the optimal number of cloud resources, required at a particular time to achieve the desired performance demands. Researchers and practitioners have proposed many elastic controllers using versatile techniques ranging from simple if-then-else based rules to sophisticated optimisation, control theory and machine learning based methods. However, despite an extensive range of existing elasticity research, the aim of implementing an efficient scaling technique that satisfies the actual demands is still a challenge to achieve. There exist many issues that have not received much attention from a holistic point of view. Some of these issues include: 1) the lack of adaptability and static scaling behaviour whilst considering completely fixed approaches; 2) the burden of additional computational overhead, the inability to cope with the sudden changes in the workload behaviour and the preference of adaptability over reliability at runtime whilst considering the fully dynamic approaches; and 3) the lack of considering uncertainty aspects while designing auto-scaling solutions. This thesis seeks solutions to address these issues altogether using an integrated approach. Moreover, this thesis aims at the provision of qualitative elasticity rules. This thesis proposes a novel biologically-inspired switched feedback control methodology to address the horizontal elasticity problem. The switched methodology utilises multiple controllers simultaneously, whereas the selection of a suitable controller is realised using an intelligent switching mechanism. Each controller itself depicts a different elasticity policy that can be designed using the principles of fixed gain feedback controller approach. The switching mechanism is implemented using a fuzzy system that determines a suitable controller/- policy at runtime based on the current behaviour of the system. Furthermore, to improve the possibility of bumpless transitions and to avoid the oscillatory behaviour, which is a problem commonly associated with switching based control methodologies, this thesis proposes an alternative soft switching approach. This soft switching approach incorporates a biologically-inspired Basal Ganglia based computational model of action selection. In addition, this thesis formulates the problem of designing the membership functions of the switching mechanism as a multi-objective optimisation problem. The key purpose behind this formulation is to obtain the near optimal (or to fine tune) parameter settings for the membership functions of the fuzzy control system in the absence of domain experts’ knowledge. This problem is addressed by using two different techniques including the commonly used Genetic Algorithm and an alternative less known economic approach called the Taguchi method. Lastly, we identify seven different kinds of real workload patterns, each of which reflects a different set of applications. Six real and one synthetic HTTP traces, one for each pattern, are further identified and utilised to evaluate the performance of the proposed methods against the state-of-the-art approaches

Concise Reporting of Benign Endometrial Biopsies is an Acceptable Alternative to Descriptive Reporting

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility

The Importance of the Pathologist’s Role in Assessment of the Quality of the Mesorectum

Total mesorectal excision (TME) is considered standard of care for rectal cancer treatment. Failure to remove the mesorectal fat envelope entirely may explain part of observed local and distant recurrences. Several studies suggest quality of the mesorectum after TME surgery as determined by pathological evaluation may influence prognosis. We aimed to determine the prognostic value of the plane of surgery as well as factors influencing the likelihood of a high-quality specimen by reviewing the literature. A pooled meta-analysis of relevant outcome data was performed where appropriate. A muscularis propria resection plane was found to increase the risk of local recurrence (RR 2.72 [95 % CI 1.36 to 5.44]) and overall recurrence (RR 2.00 [95 % CI 1.17 to 3.42]) compared to an (intra)mesorectal plane. Plane of surgery is an important factor in rectal cancer treatment and the documentation by pathologists is essential for the improvement of TME quality and patient outcome

Persistence of Fimbrial Tissue on the Ovarian Surface Following Salpingectomy

BACKGROUND: Salpingectomy is recommended as a risk-reducing strategy for epithelial tubo-ovarian cancer. The gold standard procedure is complete tubal excision. OBJECTIVE: To assess the presence of residual fimbrial/tubal tissue on ovarian surfaces following salpingectomy. DESIGN: Prospective analysis of patients undergoing salpingo-oophorectomy +/- hysterectomy for benign indications, early cervical cancer or low risk endometrial cancer at a UK National Health Service Trust. Salpingectomy +/- hysterectomy was performed initially, followed by oophorectomy within the same operation. Separately retrieved tubes and ovaries were serially sectioned and completely examined histologically. The main outcome measure was histologically identified fimbrial/ tubal tissue on ovarian surface. Chi-square/Fisher's exact tests evaluated categorical variables (SPSS-23). RESULTS: 25 consecutive cases (mean age= 54.8 years (SD=5.0), comprising 41 adnexae (9= unilateral, 16= bilateral) were analysed. 17 (68.0%), 5 (20.0%) and 3 (12.0%), procedures were performed by consultant gynaecologists, subspecialty/specialist trainees and consultant gynaecological oncologists respectively. 12/25 (48.0%) were laparoscopic and 13/25 (52.0%) involved laparotomy. 4/25 (16.0%, CI: 4.5%, 36.1%) patients or 4/41 (9.8%, CI: 2.7%, 23.1%) adnexae showed residual microscopic fimbrial tissue on the ovarian surface. Tubes/ ovaries were free of adhesions in 23 cases. Two cases had dense adnexal adhesions but neither had residual fimbrial tissue on the ovary. Residual fimbrial tissue was not significantly associated with surgical route or experience; (consultant= 3/20 (15%), trainee= 1/5 (20%), p=1.0). CONCLUSION: Residual fimbrial tissue remains on the ovary following salpingectomy in a significant proportion of cases and could impact the level of risk-reduction obtained

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes