Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: Clinical outcome and cost-effectiveness analyses.

BACKGROUND: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT). METHODS AND FINDINGS: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change. CONCLUSIONS: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

The first consensus statement on revisional bariatric surgery using a modified Delphi approach.

BACKGROUND: Revisional bariatric surgery (RBS) constitutes a possible solution for patients who experience an inadequate response following bariatric surgery or significant weight regain following an initial satisfactory response. This paper reports results from the first modified Delphi consensus-building exercise on RBS. METHODS: We created a committee of 22 recognised opinion-makers with a special interest in RBS. The committee invited 70 RBS experts from 27 countries to vote on 39 statements concerning RBS. An agreement amongst ≥ 70.0% experts was regarded as a consensus. RESULTS: Seventy experts from twenty-seven countries took part. There was a consensus that the decision for RBS should be individualised (100.0%) and multi-disciplinary (92.8%). Experts recommended a preoperative nutritional (95.7%) and psychological evaluation (85.7%), endoscopy (97.1%), and a contrast series (94.3%). Experts agreed that Roux-Y gastric bypass (RYGB) (94.3%), One anastomosis gastric bypass (OAGB) (82.8%), and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) (71.4%) were acceptable RBS options after gastric banding (84.3%). OAGB (84.3%), bilio-pancreatic diversion/duodenal switch (BPD/DS) (81.4%), and SADI-S (88.5%) were agreed as consensus RBS options after sleeve gastrectomy. lengthening of bilio-pancreatic limb was the only consensus RBS option after RYGB (94.3%) and OAGB (72.8%). CONCLUSION: Experts achieved consensus on a number of aspects of RBS. Though expert opinion can only be regarded as low-quality evidence, the findings of this exercise should help improve the outcomes of RBS while we develop robust evidence to inform future practice.

Single-stage conversions from failed gastric band to sleeve gastrectomy versus Roux-en-Y gastric bypass: results from the United Kingdom National Bariatric Surgical Registry.

BACKGROUND: For patients in whom laparoscopic adjustable gastric band has failed, conversion to Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy are both options for further surgical treatment. There are limited data comparing these 2 procedures. The National Bariatric Surgery Registry is a comprehensive United Kingdom-wide database of bariatric procedures, in which preoperative demographic characteristics and clinical outcomes are prospectively recorded. OBJECTIVES: To compare perioperative complication rate and short-term outcomes of patients undergoing single-stage conversion of gastric band to Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy. SETTING: United Kingdom national bariatric surgery database. METHODS: From the National Bariatric Surgical Registry data set, we identified 141 patients undergoing single-stage conversion from gastric band to either gastric bypass (113) or sleeve gastrectomy (28) between 2009 and 2014, and analyzed their clinical outcomes. RESULTS: With respect to perioperative outcomes gastric bypass was associated with a higher incidence of readmission or reintervention postoperatively (16 versus 0; P = .04). There was no difference in percentage excess weight loss between sleeve gastrectomy and gastric bypass at final follow-up at 1 year (52.1% versus 57.1% respectively; P = .4). CONCLUSIONS: Conversion from band to sleeve or bypass give comparable good early excess weight loss; however, conversion to sleeve is associated with a better perioperative safety profile.

The Laparoscopic Management of Median Arcuate Ligament Syndrome and Its Long-Term Outcomes.

BACKGROUND: Case reports and small series of the surgical and radiological management of median arcuate ligament syndrome (MALS) have been described, however, long-term outcome data are lacking. The purpose of this study was to review our experience of the laparoscopic management of MALS, and describe the long-term outcomes after surgical intervention. METHODS: Data were collected between 2005 and 2016 in a single U.K. institution. All patients with MALS who underwent laparoscopic decompression of the celiac artery were included. Surgical outcomes were recorded from a prospectively collected database. Long-term outcomes were determined by outpatient review and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Six patients were included. Five were female with a median age of 30 years (22.3-48.3). All six presented with abdominal pain and a bruit. Length of symptoms on presentation was 41 months (19-69). Duplex ultrasonography indicated celiac trunk stenosis in each case, with an elevated peak velocity flow in the celiac trunk of 230 cm/s (210-287.5). All six underwent successful laparoscopic decompression of the celiac artery with no conversions to open. Operating time was 137.3 minutes (95.6-166.3) and intraoperative blood loss was 110 mL (65-225). Length of stay was one day (1-2.3), with no postoperative complications or mortality. Median follow-up was 109.5 months (78-113.5). At this point, all patients remained symptom free with an overall GIQLI score of 129/144 (123.8-134.5). CONCLUSIONS: MALS is a rare condition. Laparoscopic decompression of the median arcuate ligament is safe and offers long-term resolution of symptoms, and improvement in patient quality of life.

Obesity surgery makes patients healthier and more functional: real world results from the United Kingdom National Bariatric Surgery Registry.

BACKGROUND: The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom. OBJECTIVES: Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare. SETTING: United Kingdom. METHODS: All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively. RESULTS: A total of 50,782 entries were analyzed. The patients were predominantly female (78%) and white European with a mean age of 45 ± 11 years and a mean body mass index of 48 ± 8 kg/m2. Over 5 years of follow-up, statistically significant reductions in the prevalence of type 2 diabetes, hypertension, dyslipidemia, sleep apnea, asthma, functional impairment, arthritis, and gastroesophageal reflux disease were observed. The "remission" of these co-morbidities was evident 1 year postoperatively and reached a plateau 2 to 5 years after surgery. Obesity surgery was particularly effective on functional impairment and diabetes, almost doubling the proportion of patients able to climb 3 flights of stairs and halving the proportion of patients with diabetes related hyperglycemia compared with preoperatively. Surgery was safe with a morbidity of 3.1% and in-hospital mortality of .07% and a reduced median inpatient stay of 2 days, despite an increasingly sick patient population. CONCLUSIONS: Obesity surgery in the U.K. results not only in weight loss, but also in substantial improvements in obesity-related co-morbidities. Appropriate support and funding will help improve the quality of the NBSR data set even further, thus enabling its use to inform healthcare policy.

Open and laparoscopically assisted oesophagectomy: a prospective comparative study.

OBJECTIVES: Although a number of studies have examined minimally invasive approaches for oesophagectomy, these procedures have typically been offered only to selected patients with the limited long-term follow-up data. The purpose of this prospective study was to assess the feasibility of performing laparoscopically assisted oesophagectomy (LAO) for all-comers and to compare the short- and long-term clinical outcomes of this surgical strategy with a matched cohort of patients who had undergone open surgery. METHODS: From November 2009, all patients referred for trans-thoracic resection of an oesophageal cancer underwent a two-stage laparoscopically assisted Ivor-Lewis oesophagectomy. This consisted of laparoscopic mobilization of the stomach and distal oesophagus, followed by open thoracotomy, thoracic lymphadectomy and intrathoracic anastomosis. The clinical and oncological outcomes of the first 39 consecutive LAO patients were compared with those of the preceding 31 consecutive patients who had undergone open surgery. RESULTS: Of the 39 LAO cases, 37 cases were completed laparoscopically and 2 were converted to an open surgery. LAO was associated with a decreased incidence of postoperative complications (specifically cardiac and infectious complications) when compared with open surgery (54 vs 77%, P = 0.04). In addition, the initial intensive care unit stay (2 vs 4 days; P = 0.04) and overall length of hospital stay (14 vs 18 days; P = 0.02) were shorter in the LAO group. In terms of pathological outcomes, the lymph node yield and R0 resection rate of the LAO and open groups were comparable, as were the 1-year survival rates (62 vs 61%, P = 0.97). CONCLUSIONS: LAO can be offered to an unselected cohort of all-comers with a reduced postoperative complication rate and comparable oncological and long-term survival outcomes when compared with open surgery.

Long-term outcomes of extended proximal gastrectomy for oesophagogastric junctional tumours.

BACKGROUND: There is no consensus on the optimum approach for resection of oesophagogastric junctional (OGJ) tumours. We prospectively evaluated the efficacy of transabdominal radical extended proximal gastrectomy with oesophagogastric anastomosis (EPGOG) for selected tumours of the OGJ. METHODS: Between 1998 and 2007, 66 selected consecutive patients with tumours of the OGJ underwent successful EPGOG. Selection was limited to tumours where the maximal proximal extent was 36 cm ab oral. Pre-, peri-, and postoperative outcomes together with long-term survival data for these patients were prospectively collected. RESULTS: Median theatre time was 242 min (range = 120-480), with a median blood loss of 300 ml (range = 50-1720). Eighty-nine percent of patients were extubated in theatre; major complications occurred in 9 (14%) patients, with an overall in-hospital mortality rate of 8%. Thirty-five (53%) patients had nodal disease and the median lymph node yield was 13 (range = 4-36), with an R0 resection rate of 80%. In terms of long-term outcomes, the 2- and 5-year actuarial survival rates were 54 ± 6% and 41 ± 6%. CONCLUSION: Extended radical proximal gastrectomy with oesophagogastric anastomosis for selected junctional tumours is a feasible technique which does not compromise oncological principles as evidenced by an excellent long-term survival rate.

A double-blind, randomised, controlled trial to study the effects of an enteral feed supplemented with glutamine, arginine, and omega-3 fatty acid in predicted acute severe pancreatitis.

CONTEXT: Current best evidence is in favour of early institution of enteral feeding in acute severe pancreatitis with promising results from trials in immunonutrition on other patient groups. OBJECTIVE: To identify which groups of patients and products are associated with benefit, we investigated immunonutrition in patients with predicted acute severe pancreatitis. DESIGN: A randomised trial of a study feed containing glutamine, arginine, tributyrin and antioxidants versus an isocaloric isonitrogenous control feed was undertaken. PATIENTS: Thirty-one patients with a diagnosis of acute pancreatitis predicted to develop severe disease: 15 study feeds and 16 control feeds. INTERVENTIONS: Enteral feeding via nasojejunal tube for 3 days. If patients required further feeding the study was continued up to 15 days. MAIN OUTCOME MEASURES: Reduction in C-reactive protein (CRP) by 40 mg/L after 3 days of enteral feeding was the primary endpoint. Carboxypeptidase B activation peptide (CAPAP) levels were taken at regular intervals. RESULTS: After 3 days of feeding, in the study group 2/15 (13%) of patients had reduced their CRP by 40 mg/L or more. In the control group 6/16 (38%) of patients had reduced their CRP by this amount. This difference was found to be near the statistical significant limit (P=0.220). CONCLUSIONS: The cause of the unexpectedly higher CRP values in the study group is unclear. The rise in CRP was without a commensurate rise in CAPAP or outcome measures so there was no evidence that this represented pancreatic necrosis. The contrast between the CRP and CAPAP results is of interest and we believe that specific pancreatic indices such as CAPAP should be considered in larger future studies.

Cancer cell adaptation to chemotherapy.

BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. RESULTS: In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIalpha (TOPOIIalpha). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIalpha in 6/7 colorectal tumors and 8/10 ovarian tumors. CONCLUSION: This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

Rapid up-regulation of cyclooxygenase-2 by 5-fluorouracil in human solid tumors.

Inhibition of cyclooxygenase (COX)-2 has been associated with reduced growth of malignant cells. Current therapy of gastrointestinal carcinomas involves the use of 5-fluorouracil (5-FU)-based chemotherapy and we have therefore studied the effect of this agent on the expression of COX-2. COX-2 expression was measured by quantitative RT-PCR in biopsies from a series of 14 esophageal carcinomas, six of which had paired samples taken before and after chemotherapy, and in tumor-derived cells exposed to 5-FU in vitro from a series of 44 tumors, including breast, ovarian, esophageal and colonic carcinomas. COX-2 expression was increased by exposure to 5-FU or 5-FU combination chemotherapy in all the tumor types studied, whether measured in biopsies taken before and after 5-FU-based chemotherapy (4-fold increase, p<0.015) or in primary cells exposed to drugs in vitro (24-fold increase, p<0.001). A modest increase of COX-2 mRNA was also seen after in vitro treatment of cells with cisplatin. In contrast, doxorubicin and paclitaxel caused no up-regulation in vitro, while irinotecan caused inhibition of COX-2 (2.7-fold decrease, p<0.01). These data provide a molecular rationale for clinical trials of combination chemotherapy with COX-2 inhibitors.

Heterogeneity of chemosensitivity of esophageal and gastric carcinoma.

Esophageal and gastric cancer have a poor prognosis, and chemotherapy is rarely of long-term benefit. This may be related in part to heterogeneity of chemosensitivity and to constitutive resistance to individual cytotoxic drugs. This study aimed to demonstrate the degree of heterogeneity of chemosensitivity between tumors. We have examined the heterogeneity of chemosensitivity in esophageal and gastric cancer specimens (n=85) using an ex vivo ATP-based chemosensitivity assay (ATP-TCA). A variety of chemotherapeutic agents were tested. Sixty-four specimens were endoscopic biopsy samples; the remainder were from resection specimens. Cells were obtained from 62 specimens (73%). Eight assays were infected due to contamination/infection of the biopsy material, giving an evaluability rate of 87%. Analysis of the data showed considerable heterogeneity of chemosensitivity. The most active single agents identified by the assay were mitomycin C (56% sensitivity) and 5-fluorouracil (5-FU; 42% sensitivity). Exposure of tumor cells to combinations of drugs showed ECF (epirubicin, cisplatin, 5-FU) and mitomycin C+5-FU to be moderately active regimens. Other experimental drug combinations showed greater activity. There is a marked heterogeneity of chemosensitivity in esophageal and gastric cancers. The degree of heterogeneity observed suggests that the ATP-TCA could be used to individualize chemotherapy by selecting agents for particular patients. This approach provides the rationale for a trial of ATP-TCA-directed therapy to determine whether individualization of chemotherapy might improve patient response and survival.

Angelchik prosthesis revisited.

There are few long-term follow-up reports of the Angelchik prosthesis (AP). We report the longest follow-up series (66-192 months, average 145 months) to date. Between October 1983 and January 1994, 65 patients (45 men and 20 women) aged between 29 and 84 years (mean 52 years) had an AP inserted for gastro-oesophageal reflux (GOR) with or without hiatus hernia (HH). Clinical, radiological, endoscopy, and operative details were reviewed. Postoperative complications, investigations, and follow-up details were critically analyzed. All living patients (n = 53) with an AP in situ were interviewed and symptomatic assessment was carried out using a modified Visick system (I-IV). The average duration of the GOR symptoms before the operation was 5.7 years (range 10 months to 20 years). The average hospital stay was 8 days (range 5-15 days). Postoperatively, five patients developed chest infection/atelectasis, four had superficial wound infection, two had deep vein thrombosis (one with pulmonary embolism), one had urinary retention, and four developed an incisional hernia. Six patients (three with an AP in situ) died of other medical conditions. Ten (15%) patients had removal of the prosthesis. Eight (12%) and 11 (17%) had transient and persistent dysphagia, respectively. Thirteen (20%) and five (8%) patients had distal slippage and proximal migration of the prosthesis, respectively. One patient had erosion of the AP into the stomach, while in another patient, the straps of the prosthesis ruptured. Of the 53 living patients with an AP in situ, 28 (53%) were Visick I, 11 (20%) were Visick II, 11 (20%) were Visick III, and 3 (7%) were Visick IV. We conclude that the AP has poor long-term results, with only 66% attaining Visick I and II, and a prosthesis removal rate of 15% (10/65). Patients with preoperative dysphagia, hypothyroidism, and diabetes tend to do worse with an AP. Obese patients and those with failed previous fundoplication seemed to fare well with an AP. In view of poor long-term results and high incidence of complications as compared to other conventional operations for GOR, we cannot recommend the continued use of the AP.