K. Raj Prasad

Piezo1 integration of vascular architecture with physiological force

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

A systematic review and meta-analysis of portal vein ligation versus portal vein embolization for elective liver resection.

INTRODUCTION This meta-analysis aimed to review the percentage increase in future liver remnant (FLR) and perioperative outcomes after portal vein ligation (PVL) and portal vein embolization (PVE) before liver resection. METHODS An electronic search was performed of the MEDLINE, EMBASE, and PubMed databases using both subject headings (MeSH) and truncated word searches to identify all articles published that related to this topic. Pooled risk ratios were calculated for categorical outcomes and mean differences for secondary continuous outcomes using the fixed-effects and random-effects models for meta-analysis. RESULTS Seven studies involving 218 patients met the inclusion criteria. There was no difference in the increase in FLR between the 2 groups 39% (PVE) versus 27% (PVL; mean difference [MD] 6.04; 95% CI, -0.23, 12.32; Z = 1.89; P = .06). Similarly, there was no difference in the morbidity (risk ratio [RR], 1.08; 95% CI, 0.55, 2.09; Z = 0.21; P = .83) and mortality (RR, 0.87; 95% CI, 0.19, 3.92; Z = 0.18; P = .85) in the 2 groups after liver resection. While awaiting liver resection after PVL and PVE, no difference was noted in the number of patients developing disease progression (RR, 0.93; 95% CI, 0.52, 1.66; Z = 0.24; P = .81). In a subset analysis comparing FLR with PVE and PVL as part of the procedure called an associating liver partition with PVL for staged hepatectomy (ALPPS), there was a significant increase in FLR in favor of ALPPS (MD, -17.09; 95% CI, -32.78, -1.40; Z = 2.14; P = .03). CONCLUSION PVL and PVE result in comparable percentage increase in FLR with similar morbidity and mortality rates. The ALPPS procedure results in an improved percentage increase in FLR compared with PVE alone.

Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: A review and consensus statement

K. Raj Prasad, Richard S. Young, Patrizia Burra, Shu-Sen Zheng, Vincenzo Mazzaferro, Duk Bog Moon, and Richard B. Freeman Department of Hepatobiliary Surgery and Transplantation, St. James’s University Hospital, Leeds, United Kingdom; Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy; Division of Hepatobiliary and Pancreatic Surgery, Zhejiang University, Hangzhou, People’s Republic of China; Gastro-Intestinal Surgery and Liver Transplantation, National Cancer Institute, Milan, Italy; Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; and Division of Transplantation, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH

Predictors of blood transfusion requirement in elective liver resection

BACKGROUND Liver resection remains major surgery frequently requiring intra-operative blood transfusion. Patients are typically over cross-matched, and with blood donor numbers falling, cross-matching and transfusion policies need rationalizing. AIM To identify predictors of peri-operative blood transfusion. METHODS A retrospective review of elective hepatic resections over a 4-year period was performed. Twenty-six variables including clinicopathological variables and intra-operative data were collated, together with the number of units of blood cross-matched and transfused in the immediate peri-operative period (48 h). Multivariate regression analysis was performed to identify independent predictors of blood transfusion, and a Risk Score for transfusion constructed. RESULTS Five hundred and eighty-nine patients were included in the study, and were cross-matched with a median 10 units of blood. Seventeen per cent of patients received a blood transfusion; median transfusion when required was 2 units. Regression analysis identified seven factors predictive of transfusion: haemoglobin <12.5 g/dL, pre-operative biliary drainage, coronary artery disease, largest tumour >3.5 cm, cholangiocarcinoma, redo resection and extended resection (5+ segments). Patients were stratified into high or low risk of transfusion based on Risk Score with a sensitivity of 73% [receiver-operating characteristic (ROC) 0.77]. CONCLUSIONS Patients undergoing elective liver resection are over-cross-matched. Patients can be classified into high and low risk of transfusion using a Risk Score, and cross-matched accordingly.

How can we Enhance Undergraduate Medical Training in the Operating Room? A Survey of Student Attitudes and Opinions

BACKGROUND AND PURPOSE Teaching in the operating room (OR) may add substantial value to undergraduate medical education but at present, the value of this as a core-learning environment is unclear. We assessed student attitudes to see how the experience may be improved. METHODS All medical students from University of Leeds, UK were invited to complete an online-based questionnaire. The questionnaire gathered quantitative and qualitative responses relating to previous experiences, acquired benefits, and desired improvements. Students rated their overall satisfaction on a 10-point scale. RESULTS A total of 292 students (20.8%) responded to the survey, out of whom 91.4% had previous OR experience. The median overall satisfaction was 7/10; 43.1% described bad or unfavorable experiences. Common themes included feeling intimidated, unwelcome, or ignored by staff, unrealistic expectations of knowledge, and poor or inadequate learning experiences. Benefits of attending the OR were improvements in scrub technique (82.3%), knowledge of anatomy (72.3%), anesthetics (67.5%), and surgical procedures (86.1%). Desired improvements included more opportunity to participate in the procedure (74.4%), encouragement from supervisors (73.6%), improved teaching (71.4%), and better induction to the OR environment (56%). DISCUSSION AND CONCLUSIONS Overall satisfaction of OR teaching is reasonable and many benefits are derived from attending the OR. However, bad experiences are common and this is detrimental to the student learning experience. The experience may be of increased value to undergraduate medical education within a dedicated and structured surgical teaching program.

Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom

OBJECTIVES The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.

Epidural versus local anaesthetic infiltration via wound catheters in open liver resection: a meta‐analysis

This meta‐analysis was designed to systematically analyse all published studies comparing local anaesthetic infiltration with wound catheters and epidural catheters in open liver resection.

Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor

Objective—Vascular endothelial growth factor (VEGF) acts, in part, by triggering calcium ion (Ca2+) entry. Here, we sought understanding of a Synta66-resistant Ca2+ entry pathway activated by VEGF. Approach and Results—Measurement of intracellular Ca2+ in human umbilical vein endothelial cells detected a Synta66-resistant component of VEGF-activated Ca2+ entry that occurred within 2 minutes after VEGF exposure. Knockdown of the channel-forming protein Orai3 suppressed this Ca2+ entry. Similar effects occurred in 3 further types of human endothelial cell. Orai3 knockdown was inhibitory for VEGF-dependent endothelial tube formation in Matrigel in vitro and in vivo in the mouse. Unexpectedly, immunofluorescence and biotinylation experiments showed that Orai3 was not at the surface membrane unless VEGF was applied, after which it accumulated in the membrane within 2 minutes. The signaling pathway coupling VEGF to the effect on Orai3 involved activation of phospholipase C&ggr;1, Ca2+ release, cytosolic group IV phospholipase A2&agr;, arachidonic acid production, and, in part, microsomal glutathione S-transferase 2, an enzyme which catalyses the formation of leukotriene C4 from arachidonic acid. Shear stress reduced microsomal glutathione S-transferase 2 expression while inducing expression of leukotriene C4 synthase, suggesting reciprocal regulation of leukotriene C4–synthesizing enzymes and greater role of microsomal glutathione S-transferase 2 in low shear stress. Conclusions—VEGF signaling via arachidonic acid and arachidonic acid metabolism causes Orai3 to accumulate at the cell surface to mediate Ca2+ entry and downstream endothelial cell remodeling.

Endovascular management of arterial conduit pseudoaneurysm after liver transplantation: a report of two cases.

We describe two cases of pseudoaneurysms in liver-transplant iliac artery conduits, which were successfully treated with endovascular stent grafting.

A cost effective analysis of a laparoscopic versus an open left lateral sectionectomy in a liver transplant unit

INTRODUCTION This study aimed to assess the cost effectiveness of a laparoscopic left lateral sectionectomy (LLLS) compared with an open (OLLS) procedure and its role as a training operation as well as the learning curve associated with a laparoscopic approach. METHOD Between 2004 and 2013, a prospectively maintained database was reviewed. LLLS were compared with age- and sex-matched OLLS. In addition, the outcomes of LLLS with a consultant as the primary surgeon were compared with those performed by trainees. RESULTS Forty-three LLLS were performed during the study period. LLLS was a significantly cheaper operation compared with OLLS (P = 0.001, £3594.14 versus £5593.41). The median hospital stay was shorter in the laparoscopic group (P = 0.002, 3 versus 7 days). No difference was found in outcomes between a LLLS performed by a trainee or consultant (operating time, morbidity or R1 resection rate). The procedure length was significantly shorter during the later half of the study period [120 versus 129 min (P = 0.045)]. CONCLUSION LLLS is a significantly cost effective operation compared with an open approach with a reduction in hospital stay. In addition, it is suitable to use as a training operation.