Search

Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 ( P Wilcox = 0.0002) and day 7 ( P Wilcox = 2.7 × 10 -5 ), and the degree of elevation differed by the presence of grade 2 CRS ( P interaction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand., (© 2021 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.)

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Background/objectives: Dilatation of the pancreatic duct and common bile duct, known as double duct sign (DDS), suggests sinister pathology at the periampullary region. Non-jaundiced patients with incidental DDS and otherwise normal cross-sectional imaging present a diagnostic dilemma to the multidisciplinary team (MDT). The primary aim of this review was to assess the diagnostic yield of endoscopic ultrasound (EUS) in detecting causal pathology in this patient population., Methods: A systematic literature search (Medline, EMBASE, Google Scholar, Cochrane database and PROSPERO) was performed to identify original studies that reported EUS findings in patients with incidental DDS. Primary outcome was detection of a periampullary tumour. Secondary outcome was detection of benign causal pathology. Meta-analysis was used to calculate an absolute measure (pooled proportion) of pathology detection., Results: Four studies (177 patients) were included. EUS detection rate for a periampullary tumour was 5% (95% CI, 0-10%) including both adenocarcinomas and adenomas. EUS detection rate for benign causal pathology was 22% (95% CI, 10-34%), the most common being chronic pancreatitis CONCLUSION: Non-jaundiced patients with incidental DDS on cross-sectional imaging have a 5% risk of a periampullary tumour that can be detected by EUS., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Ten percent of cirrhotic patients are known to have a high risk of postoperative complications. Ninety percent of bariatric patients suffer from non-alcoholic fatty liver disease (NAFLD), and 50% of them may develop non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis. The aim of this study was to assess whether the presence of cirrhosis at the time of bariatric surgery is associated with an increased rate and severity of short- and long-term cirrhotic complications., Methods: A cohort of 110 bariatric patients, between May 2003 and February 2018, who had undergone liver biopsy at the time of bariatric surgery were reassessed for histological outcome and divided into two groups based on the presence (C, n = 26) or absence (NC, n = 84) of cirrhosis. The NC group consisted of NASH (n = 49), NAFLD (n = 24) and non-NAFLD (n = 11) liver histology. Medical notes were retrospectively assessed for patient characteristics, development of 30-day postoperative complications, severity of complications (Clavien-Dindo (CD) classification) and length of stay. The C group was further assessed for long-term cirrhosis-related outcomes., Results: The C group was older (52 years vs 43 years) and had lower BMI (46 kg/m 2 vs 52 kg/m 2 ) and weight (126 kg vs 145 kg) compared to the NC group (p < 0.05). The C group had significantly higher overall complication rate (10/26 vs 14/84, p < 0.05) and severity of complications (CD class ≥ III, 12% vs 7%, p < 0.05) when compared to the NC group. The length of stay was similar between the two groups (5 days vs 4 days). The C group had significant improvement in model end-stage liver disease scores (7 vs 6, p < 0.01) with median follow-up of 4.5 years (range 2-11 years). There were no long-term cirrhosis-related complications or mortality in our studied cohort (0/26)., Conclusion: Bariatric surgery in cirrhotic patients has a higher risk of immediate postoperative complications. Long-term cirrhosis-related complications or mortality was not increased in this small cohort. Preoperative identification of liver cirrhosis may be useful for risk stratification, optimisation and informed consent. Bariatric surgery in well-compensated cirrhotic patients may be used as an aid to improve long-term outcome.

Background: In bariatric surgery, preoperative very low-calorie diets (VLCD) may better meet the technical demands of surgery by shrinking the liver. However, diets may affect tissue healing and influence bowel anastomosis in an as-yet-undefined manner., Objective: This randomized controlled trial aimed to examine the effect on collagen deposition in wounds in patients on a 4-week VLCD before laparoscopic gastric bypass., Setting: University hospital., Methods: The trial was undertaken in patients undergoing laparoscopic Roux-en-Y gastric bypass, with a control group (n = 10) on normal diet and an intervention group (n = 10) on VLCD (800 kcal) for 4 weeks. The primary outcome measured was expression of collagen I and III in skin wounds, with biopsies taken before and after the diet and 7 days postoperatively as a surrogate of anastomotic healing. Secondary outcome measures included liver volume and fibrosis score, body composition, operating time, blood loss, hospital stay, and complications., Results: Patients in both groups were similar in age, sex, body mass index (53.4 versus 52.8 kg/m 2 ), co-morbidities, liver volume, and body composition. Expression of mature collagen type I was significantly decreased in diet patients compared with controls after 4 weeks of diet and 7 days after surgery. This was significant decrease in liver volume (23% versus 2%, P = .03) but no difference in operating times (129 versus 139 min, P = .16), blood loss, length of stay, or incidence of complications., Conclusions: Preoperative diets shrink liver volume and decrease expression of mature collagen in wounds after surgery. Whether the latter has a detrimental effect on clinical outcomes requires further evaluation., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Intensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT)., Materials and Methods: Ten adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = [D5% - D95%]/[D mean ] × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing., Results: IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half., Conclusion: This manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted., (© 2018 The Authors.)

Objective: Evaluate prevalence and pattern of occipital pneumatization (OP)., Patients: Individuals with imaging evidence of OP on computed tomography (CT)., Intervention(s): High resolution CT scans of the temporal bone., Main Outcome Measure: The prevalence and pattern of OP on 1000 CT scans performed at a large academic healthcare system., Results: OP had a prevalence of 11.8% (n = 118) while occipital condyle pneumatization occurred in only 0.3%. Occipital air cells were right-sided in 27.1% (n = 32), left-sided in 51.7% (n = 61), and bilateral in 21.2% (n = 25), and OP was contiguous with the occipitomastoid suture. In cases of unilateral OP, the contralateral jugular foramen demonstrated relative enlargement (p = 0.006), but a direct association could not be established., Conclusions: The occipital bone is an accessory site of skull base pneumatization in 11.8% of the population undergoing temporal bone CT, while air cell extension into the occipital condyle occurs more rarely. These occipital air cells have a left-sided predilection and are always in direct proximity to the occipitomastoid suture, suggesting developmental egress from the mastoid. OP is a normal variant and lacks features of craniocervical pneumatization, which is a rare disorder.

Background: Obesity surgery mortality risk scoring system (OS-MRS) classifies patients into high, intermediate and low risk, based on age, body mass index, sex and other comorbidities such as hypertension and history of pulmonary embolism. High-risk patients not only have a higher mortality but are more likely to develop post-operative complications necessitating intervention or prolonged hospital stay following bariatric surgery. Endoscopically placed duodenal-jejunal bypass sleeve (Endobarrier) has been designed to achieve weight loss and improve glycaemic control in morbidly obese patients with clinically proven effectiveness. The aim of this study was to assess if pre-operative insertion of endobarrier in high-risk patients can decrease morbidity and length of stay after bariatric surgery., Materials and Methods: Between 2012 and 2014, a cohort of 11 high-risk patients had an Endobarrier inserted (E&BS group) for 1 year prior to definitive bariatric surgery. These patients were compared against a similar group undergoing primary bariatric surgery (PBS group) during same duration. The two groups were matched for age, gender, body mass index, comorbidities, surgical procedure and OS-MRS using propensity score matching. Outcome measures included operative time, morbidity, length of stay, intensive therapy unit (ITU) stay, readmission rate, percentage excess weight loss (%EWL) and percentage total weight loss (%TWL)., Results: Patient characteristics and OS-MRS were similar in both groups (match tolerance 0.1). There was no significant difference in total length of stay, readmission rate, %EWL and %TWL. Operative time, ITU stay, post-operative complications and severity of complications were significantly less in the E&BS group (p < 0.05) with significant likelihood of planned ITU admissions in the PBS group (p < 0.05)., Conclusion: Endobarrier could be considered as a pre bariatric surgical intervention in high-risk patients. It may result in improved post-operative outcomes in high-risk bariatric patients.

Introduction: Laparoscopy is increasingly utilised as a diagnostic tool in management of abdominal trauma; however its role in therapeutic intervention remains unexplored. The aim of this study is to compare laparoscopy with laparotomy in the treatment of abdominal trauma in haemodynamically stable patients., Methods: A review of patients undergoing surgery for abdominal trauma between January 2004-2014 identified 25 patients who underwent laparoscopy for therapeutic intervention (TL). This group was matched with 25 similar patients undergoing laparotomy (LT). Matching of the two cohorts was based on patient characteristics, severity of injuries, haemodynamic compromise and radiological findings. Peri-operative outcomes were compared., Discussion: Patient characteristics were similar in TL and LT patients for age (median 33 vs. 26 years), gender distribution and clinical presentation. Injury severity score was also similar with a median of 16 in both groups (major trauma = ISS>15, normal range 0-75). Types of injuries included; hollow viscus [bowel repair = 10 (TL) vs. 16 (LT)] and solid organs [5(TL) vs. 2 (LT)]. Median operating time was similar in both groups; 105(TL) compared to 98 (LT) minutes. Post-operative complications (1 vs. 10, p = 0.02), analgesia requirements, specifically opiate use (34 vs. 136 morphine equivalents, p = 0.002) and hospital stay (4 vs. 9 days, p = 0.03) were significantly lower in the laparoscopy group., Conclusions: Abdominal trauma in haemodynamically stable patients can be managed effectively and safely with laparoscopy by experienced surgeons. Major benefits may include lower morbidity, reduced pain, and shorter length of hospital stay., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Background: Staple line bleeding (SLB) is a common intraoperative complication following resection in laparoscopic sleeve gastrectomy (SG). Opinion is divided on the best measure to deal with SLB which includes expensive reinforcement strategies, suturing the staple line or diathermy. Tranexemic acid is a relatively inexpensive drug known to reduce bleeding in trauma and surgery. The aim of this study was to evaluate whether intraoperative tranexemic acid reduces staple line bleeding., Methods: In this prospective matched comparative study of SG, one cohort of patients was administered tranexemic acid (1 g) after induction and compared to a control group. The primary outcome compared the number of staple line bleeding points requiring intervention intra-operatively. Secondary outcomes included estimated blood loss and operating time. The anaesthetic and thromboprophylaxis protocols were uniform. Operative technique and stapling equipment were identical in all patients., Results: Twenty-five patients were allocated to both the control and treatment arms. Patient characteristics in both groups were similar in age (median 34 vs 43 years), body mass index (median 54.7 vs 52 kg/m(2)), gender distribution (female:male = 20:5) and co-morbidities. The treatment group receiving tranexemic acid, required significantly less number of haemostatic stitches for staple line bleeding (19 vs 46, p < 0.05), incurred less intraoperative blood loss (p < 0.01) and had quicker operating times (median 66 vs 80 min, p < 0.05). There was no difference in morbidity or mortality in both groups., Conclusion: Intraoperative prophylactic tranexemic acid use is a simple and economical option for effectively reducing staple line bleeds leading to significant decrease in operating times.

Background: Bile acids (BA) modulate lipid and glucose metabolism in a feedback loop through production of fibroblast growth factor (FGF) 19 in the terminal ileum. Changes in BA after bariatric surgery may lead to improvements in the metabolic syndrome, including fatty liver disease. This study investigated the relationship between BA and metabolic and inflammatory profiles after laparoscopic sleeve gastrectomy (LSG)., Methods: Patients undergoing LSG had fasting blood samples taken pre-operatively and 6 months post-surgery. Liver injury was measured using cytokeratin (CK) 18 fragments. BA were measured using liquid chromatography tandem-mass spectrometry. FGF-19 was measured using enzyme-linked immunosorbent assay., Results: The study included 18 patients (12 females), with mean age 46.3 years (SEM ± 2.9) and BMI 60.1 kg/m(2) (±2.6). After 6 months, patients lost 39.8 kg (±3.1; p < 0.001). Fourteen patients (78 %) had steatosis. FGF-19 increased from median 128.1 (IQR 89.4-210.1) to 177.1 (121.8-288.9, p = 0.045) at 6 months. Although total BA did not change, primary glycine- and taurine-conjugated BA, cholic acid decreased, and secondary BA, glycine-conjugated urodeoxycholic acid increased over the study period. These changes are associated with reduction in insulin resistance, pro-inflammatory cytokines and CK-18 levels., Conclusions: The profile of individual BA is altered after LSG. These changes occur in the presence of reductions in inflammatory cytokines and markers of liver injury. This study supports evidence from recent animal models that LSG may have an effect on fatty liver through changes in BA metabolism.

Background: The combination of pneumoperitoneum and intraoperative retraction of the left lobe of the liver leads to hepatocellular injury during laparoscopic gastric surgery. Fatty livers are more susceptible to ischaemic insults. This trial investigated whether the antioxidant N-acetylcysteine (NAC) reduced liver injury during laparoscopic sleeve gastrectomy (LSG)., Methods: Patients undergoing LSG were randomised (single blinded) to receive intraoperative NAC infusion or standard anaesthetic treatment. Blood samples were taken before and after surgery (days 0 to 4). Primary endpoints included serum aminotransferases. Secondary measures were C-reactive protein, weight cell count (WCC), cytokines (interleukin 6 and 10) and cytokeratin-18 as markers of apoptosis. Intraoperative liver biopsy samples were assessed using a locally developed injury score., Results: Twenty patients (14 females, mean age 44.5 (SEM ± 2.9) years, mean BMI 60.8 (SEM ± 2.4) kg/m(2)) were recruited (NAC n = 10, control n = 10). The trial was stopped early after a planned interim analysis. Baseline liver function was similar. The peak rise in liver enzymes was on day 1, but levels were not significantly different between the groups. Rates of complications and length of stay were not significantly different. Secondary outcome measures, including white cell count (WCC), cytokines and cytokeratin (CK)-18 fragments, were not different between groups. Liver injury scores did not differ significantly., Conclusions: NAC did not reduce intraoperative liver injury in this small number of patients. The heterogenous nature of the study population, with differences in co-morbidities, body mass index and intraabdominal anatomy, leads to a varied post-operative inflammatory response. Significant hepatocyte injury occurs through both necrosis and apoptosis.

Background: Obesity-related dyslipidaemia comprises hypercholesterolaemia, hypertriglyceridaemia, low HDL-cholesterol and normal to raised LDL-cholesterol levels. 40% of morbidly obese surgical patients have dyslipidaemia. Roux-en-Y gastric bypass (RYGB) surgery has many beneficial metabolic effects, but the full impact on plasma lipids has not been clearly defined., Methods: A systematic review of electronic databases (Ovid; Medline; PubMed; Embase) between 1960 and March 2012 was performed using search terms including the following: obesity surgery, bariatric surgery, gastric bypass, cholesterol, lipids, triglycerides and non-esterified fatty acids. A total of 2442 manuscripts were screened. Papers with paired plasma lipid levels around RYGB surgery were included. Exclusions included the following: editorials, dual publications, n < 10, resulting in 75 papers of relevance. A meta-analysis was performed of the effect of RYGB surgery upon plasma lipids at different time points up to 4 years following surgery, using a random effects model., Results: Paired data were available for 7815 subjects around RYGB surgery for morbid obesity with a baseline BMI 48 kg/m(2) (n = 2331). There was a reduction in plasma total cholesterol and LDL-C from 1 month up to 4 years post-RYGB (p < 0.00001, p < 0.00001). Following RYGB, HDL-C increased from 1 year onwards (p < 0.00001), and triglyceride levels were reduced postoperatively from 3 months up to 4 years (p < 0.00001). NEFA levels were increased at 1 month postoperatively (p = 0.003), but from 3 months onwards did not differ from preoperative levels (p = 0.07)., Conclusions: RYGB surgery reverses the dyslipidaemia of obesity. These findings support the use of RYGB in the management of high cardiovascular risk lipid profiles in morbid obesity.

Unlabelled: The aim of the study was to perform a comprehensive analysis of patients with a benign final histology after pancreaticoduodenectomies (PD) for suspected pancreatic and periampullary cancer., Material and Methods: We searched the pathology database at the King's College Hospital for negative PD specimens submitted between January 2004-December 2010. Clinical, diagnostic, surgical,histopathological and outcome data were collected retrospectively. Pathology specimens and imaging results have been re-evaluated. A literature review was performed to identify factors affecting the incidence across centres., Results: 469 PD were performed for presumed cancer. The incidence of benign disease encountered in this group was 7.25% (34/469). Autoimmune pancreatitis (AIP) was a finding in 26.47% (9/34) of cases. 17.65% of PD were complicated by a pancreatic leak and the overall mortality rate was 8.82%(3/34). Radiologists revised over 75% of pre-operative diagnoses. The incidence of benign disease was correlated with the overall centre experience and utilisation of CT imaging, but not ERCP or EUS., Conclusions: It is impossible with current diagnostics to entirely avoid cases of benign disease inpatients undergoing PD for suspected cancer. The mortality rate is higher in this group, but it is possible to avoid unnecessary procedures in experienced centres. AIP represents an important diagnostic entity, which should be actively pursued pre-operatively.

Single-incision surgery in the morbidly obese patient has not been widely adopted, but remains a popular choice amongst patients. In the bariatric patient, it presents its own surgical challenges with hepatomegaly and increased abdominal adiposity. Here, we present our experience of 275 single-incision laparoscopic gastric bands.Between June 2009 and April 2013, 275 obese patients underwent single-incision laparoscopic adjustable gastric banding through a single incision using a multichannel single port and via a pars flaccida approach. Prospective data collection was undertaken including operating time, additional ports and additional procedures undertaken.In this series, median operative time was 60 (range 34-170) min. An additional port was placed in 15 patients (5%), including two conversions to four-port technique (0.7%). Of these patients (n = 15), the majority were male (p < 0.0001). Reasons for additional port placement included bleeding and anatomical abnormalities. Additional port placement occurred more often within the first 50 cases (5/50, 10% vs 10/225, 4%). An umbilical incision resulted in more wound-related complications than a transverse incision in the upper abdomen (p < 0.001). There were no 30-day mortality and minimal morbidity with two wound infections resulting in band removal.Single-incision laparoscopic adjustable gastric banding can be performed safely with minimal morbidity in the morbidly obese patient, and our technique has a high rate of success for all BMIs. Following 275 single-incision band insertions additional port placements were more commonly required in male patients, BMI >45 and earlier in the learning curve.

Background: Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery., Methods: Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m2, n = 7), adjustable gastric banding (n = 6), Roux-en-Y gastric bypass (RYGB, n = 7) and biliopancreatic diversion with duodenal switch (DS, n = 5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h D-xylose, L-rhamnose and lactulose test (intestinal absorption and permeability)., Results: Age and gender were not different but BMI differed between groups (p = 0.001). No difference in oro-caecal transit time (p = 0.935) or functional enterocyte mass (p = 0.819) was detected. FCp was elevated post-RYGB vs. obese (p = 0.016) and FE-1 was reduced post-RYGB vs. obese (p = 0.002). Faecal fat concentrations were increased post-DS vs. obese (p = 0.038) and RYGB (p = 0.024) and were also higher post-RYGB vs. obese (p = 0.033). Urinary excretion of D-xylose and L-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs. other groups (all p < 0.02), suggesting increased intestinal permeability., Conclusions: Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.

Background: Rhabdomyolysis (RML) is a rare complication of bariatric surgery. A systematic review was performed to identify risk factors and patient outcomes in morbidly obese patients undergoing bariatric surgery who develop RML., Methods: A comprehensive search was performed between January 1990 and March 2012 using relevant MeSH terms. Studies were chosen based on predefined inclusion criteria. RML was defined as a creatine kinase of more than 1,000 IU/L. The parameters assessed included patient characteristics of the RML population, type of bariatric surgery performed, operating time, complications, presentation and diagnosis of RML., Results: Twenty-two studies were analysed which included 11 case reports, two case series, six prospective and three retrospective comparative studies. Overall 145 patients with RML were reported following bariatric surgery. Acute renal failure was found in 20 patients (14 %) and was significantly more likely to occur in patients with postoperative muscle pain (p < 0.05). The mortality rate after renal failure was 25 % (n = 5). In the comparative studies, 87 RML patients were compared with 325 non-RML patients. The RML patients were more likely to be male, had a greater mean body mass index (BMI) (52 vs 48 kg/m(2), p < 0.01) and underwent a longer operation (255 vs 207 min, p < 0.01) compared to non-RML patients., Conclusions: Risk factors of developing RML following bariatric surgery include male gender, elevated BMI and prolonged operating time. Patients with a biochemical diagnosis of RML and postoperative myalgia after bariatric surgery are at increased risk of developing acute renal failure and mortality. These patients must be identified and treated promptly.

Background and Purpose: The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists)., Methods: The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects' CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects' CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement., Results: Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively)., Conclusions: In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00623350.

Background: As single incision surgery increases in popularity, the feasibility of offering this approach in bariatric surgery is further progression of this surgical technique. With the technical challenges that both operating on the morbidly obese patient and single incision surgery present, we describe our initial experience undertaking 111 single-incision gastric band insertions., Methods: From June 2009 to October 2010, 111 obese patients underwent single-incision laparoscopic adjustable gastric banding through a single transverse incision using a multichannel single port and a pars flaccida technique. Prospective data collection was undertaken, including visual analog scores., Results: In this initial series, the median operative time was 65 minutes (range 34-165). There was 1 conversion to a 5-port laparoscopic technique (.9%), and an additional port was placed in 7 patients (6%). Male patients were more likely to require an additional port (P < .05). The single-incision size ranged from 26 to 45 mm (median 35). At 23 hours postoperatively, the median pain score was 2.5 on a 0-10 visual analog score. On multivariate analysis, pain was found to increase with operation time (P < .001). The median length of stay was 24 hours (range 5.5-48). There was no mortality and minimal morbidity, with 1 wound infection necessitating band removal., Conclusions: Single-incision laparoscopic adjustable gastric banding can be performed safely with minimal morbidity and mortality in the morbidly obese patient, and our technique has a high rate of success. The benefits compared with the traditional laparoscopic approach and long-term outcomes are yet to be established. However, if the intra-abdominal operative time is >60 minutes, one should consider the placement of an additional port, especially in male patients., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Single incision laparoscopic bariatric surgery has developed over the last few years, with single incision laparoscopic adjustable gastric banding (SILS-AGB) being performed most commonly. However, there are no randomised controlled trials and few matched studies comparing SILS-AGB to conventional laparoscopic multi-port multiport adjustable gastric banding (LAGB). Our aim was to study any differences in outcome and analgesic requirements between two matched groups of gastric band patients (SILS-AGB and LAGB)., Methods: Between June 2009 and September 2010, 111 patients underwent SILS-AGB and 99 patients underwent LAGB performed by a single surgeon (AGP). Patients were matched for age, sex, weight, BMI and co-morbidities. Forty six SILS-AGB and LAGB patients were included for analysis. Their outcomes were compared for operating times, conversions, analgesia requirements, morbidity and mortality., Results: Patients characteristics between the SILS-AGB and LAGB groups were similar with no differences in their median age (44 vs 47 years), sex (m:f; 7:39 vs 4:42), body mass index (43.1 vs 44.4 kg/m(2)) or co morbidities respectively. In the SILS-AGB group the median operating time (70 min) was not significantly longer than in LAGB group (61.5 min, p = 0.07). However, SILS-AGB patients used less opiates (p < 0.01) than the LAGB patients. There was no difference in morbidity, mortality or readmission rates., Conclusion: SILS-AGB is a safe and feasible option and is comparable with LAGB. Post operative demand for analgesia was significantly less in the SILS-AGB group. Further comparisons of post operative pain and long term outcomes are required; however preliminary results are promising.

Obesity increases the risk of progression of chronic kidney disease (CKD) towards kidney failure and may preclude access to kidney transplantation. Weight loss surgery remains relatively novel in obese patients with CKD, with several studies reporting results using Roux-en-Y bypass and adjustable gastric banding. However, in obese patients with CKD, kidney failure after bypass surgery and gastric band erosion after kidney transplantation have been reported. We present the first report of laparoscopic sleeve gastrectomy (LSG) performed for the treatment of obesity in patients with CKD. Weight loss, blood pressure and lipids, estimated kidney function, surgical complications and adverse events were studied. Nine obese patients with CKD (five of whom were undergoing haemodialysis treatment) underwent LSG, with median body mass index decrease of 8.4 kg/m(2) and excess weight loss of 43.0% after 6 months. Four of the five patients on haemodialysis were added to the kidney transplantation waiting list as a result of weight loss achieved with LSG. Adverse events occurred in three patients: myocardial infarction (one patient), acute kidney injury secondary to dehydration (one patient) and compromised dialysis access (one patient). There was one complication-a gastric leak, detected 7 months after LSG, requiring further surgical intervention and nasojejunal feeding, and no mortality. Our preliminary evidence suggests that LSG is an effective treatment for obesity in patients with CKD. However, there may be additional risk associated with the procedure in patients with CKD, requiring further study.

Background: An increasing number of techniques are emerging in the literature describing single-incision laparoscopic cholecystectomy (SILC). The advent of a new surgical approach is a reminder of the increase in bile duct injuries in the past when laparoscopic cholecystectomy was first introduced. With this in mind, the authors describe a safe and reproducible approach to SILC., Methods: Between August 2008 and August 2009, 20 patients with symptomatic gallbladder disease underwent SILC using a totally transumbilical fundus-first approach with an intraoperative cholangiogram. Data including pain scores were collected prospectively., Results: In this initial series, the median operative time was 103 min (range, 55-177 min), including the time for two patients undergoing additional procedures at the time of surgery. Intraoperative cholangiograms were completed for 18 of 19 patients. Additional ports were required in four patients for safe completion of the procedure. The mean pain score 12 h postoperatively was 2.5 on a visual analogue scale with a range of 0-10. There was no morbidity or mortality., Conclusion: According to the findings, SILC with an intraoperative cholangiogram can be performed safely using a fundus-first approach. However, for SILC to become the operation of choice for the treatment of gallbladder disease, evidence is required to demonstrate its advantage over laparoscopic cholecystectomy.

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported and discuss the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate-related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other.

Background: Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively., Methods: 2 groups of Wistar rats underwent sham and BPD surgery. Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken., Results: Animals in the BPD group had significant reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P<0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham., Conclusions: In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery.

Objective: To study the effect of bariatric surgery on the entero-hypothalamic endocrine axis of humans and rodents., Background: Bariatric surgery is the most effective obesity treatment as it achieves substantial and sustained weight loss. Glycemic control and enhanced satiation improve before substantial weight loss occurs. Gut peptides, acting both peripherally and centrally, contribute to glycemic control and regulate food intake., Methods: We examined meal-stimulated responses of insulin, ghrelin, peptide YY (PYY), glucagon-like-peptide-1 (GLP-1), and pancreatic polypeptide (PP) in humans and rodents following different bariatric surgical techniques., Results: Compared with lean and obese controls, patients following Roux-en-Y gastric bypass (RYGB) had increased postprandial plasma PYY and GLP-1 favoring enhanced satiety. Furthermore, RYGB patients had early and exaggerated insulin responses, potentially mediating improved glycemic control. None of these effects were observed in patients losing equivalent weight through gastric banding. Leptin, ghrelin, and PP were similar in both the surgical groups. Using a rodent model of jejuno-intestinal bypass (JIB), we showed elevated PYY and GLP-1 in JIB rats compared with sham-operated rats. Moreover, exogenous PYY reduced food intake and blockade of endogenous PYY increased food intake. Thus, higher plasma PYY following JIB may contribute to reduced food intake and contribute to weight loss., Conclusions: Following RYGB and JIB, a pleiotropic endocrine response may contribute to the improved glycemic control, appetite reduction, and long-term changes in body weight.

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans., Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity. A longitudinal study was performed to assess the effect of bariatric surgery induced weight loss on these parameters. 73 healthy subjects across a wide range of body mass were recruited; of these, 8 underwent bariatric surgery (median BMI 52.2 kg/m2, interquartile range 50.355.9). Endothelial dependent vasodilatation was measured using the brachial artery vasodilatory response to forearm hyperemia assessed using highresolution ultrasonography., Results: Obese subjects were characterised by a complex collection of abnormalities, with hypertension, impaired glucose homeostasis, systemic inflammation and reduced FMD. BMI < or =25 kg/m2 (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30 kg/m2 (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects. A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from 5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01., Conclusions: Even moderate obesity leads to endothelial dysfunction. In severely obese subjects, FMD is normalized by weight loss. This improvement in FMD is associated with a decline in inflammatory markers, blood pressure and insulin. The improvement in FMD occurred despite patients remaining significantly obese. These results suggest that an integrated approach to improving endothelial function in obese humans may be necessary.

Aim: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients., Methods: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality., Results: The operative mortality in the series was 3.95%. This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Post-operative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117) or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery., Conclusion: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.

Background: Obesity surgery has been shown to result not only in sustained weight loss, but also in improvements in psychological morbidity and quality of life. The present study aimed to explore the mechanisms behind the success of surgery and to examine how it might bring about such changes in patients' health status., Methods: Both quantitative and qualitative methods were used. A questionnaire was completed by patients who had undergone bariatric surgery in the past 4 years (n=22) and a matched-group of waiting list controls (n=39). In depth interviews were then carried out with 15 surgical patients., Results: The quantitative study showed that the surgical group weighed less, had more negative experiences of eating and yet reported improved subjective health status using a range of validated tools. The qualitative study provided some insights into this improved health status, with the surgical patients reporting improved energy and self-esteem. The patients also reported a fundamental shift in their relationship with food. In particular, they described changes in their eating behavior and stated that they had a new experience of fullness and a reduction in their hunger. Furthermore, they described how food now had a reduced role in their lives and that the operation had made them feel more in control of their food intake., Conclusion: Post-surgical improvements in health status may not only be a result of the non-specific consequences of surgery brought about by weight loss, but also a result of the specific impact of the surgical procedure itself. By enforcing a reduction in the amount of food that can be eaten, restrictive surgery seems to generate changes in the individuals' relationship to food and may help to re-establish a perception of control over eating behavior.