Erik N. Hansen

The Importance of Caloric Restriction in the Early Improvements in Insulin Sensitivity After Roux-en-Y Gastric Bypass Surgery

OBJECTIVE Many of the metabolic benefits of Roux-en-Y gastric bypass (RYGB) occur before weight loss. In this study we investigated the influence of caloric restriction on the improvements in the metabolic responses that occur within the 1st week after RYGB. RESEARCH METHODS AND DESIGN A mixed meal was administered to nine subjects before and after RYGB (average 4 ± 0.5 days) and to nine matched, obese subjects before and after 4 days of the post-RYGB diet. RESULTS Weight loss in both groups was minimal; the RYGB subjects lost 1.4 ± 5.3 kg (P = 0.46) vs. 2.2 ± 1.0 kg (P = 0.004) in the calorically restricted group. Insulin resistance (homeostasis model assessment of insulin resistance) improved with both RYGB (5.0 ± 3.1 to 3.3 ± 2.1; P = 0.03) and caloric restriction (4.8 ± 4.1 to 3.6 ± 4.1; P = 0.004). The insulin response to a mixed meal was blunted in both the RYGB and caloric restriction groups (113 ± 67 to 65 ± 33 and 85 ± 59 to 65 ± 56 nmol · l−1 · min−1, respectively; P < 0.05) without a change in the glucose response. Glucagon-like peptide 1 levels increased (9.2 ± 8.6 to 12.2 ± 5.5 pg · l−1 · min−1; P = 0.04) and peaked higher (45.2 ± 37.3 to 84.8 ± 33.0 pg/ml; P = 0.01) in response to a mixed meal after RYGB, but incretin responses were not altered after caloric restriction. CONCLUSIONS These data suggest that an improvement in insulin resistance in the 1st week after RYGB is primarily due to caloric restriction, and the enhanced incretin response after RYGB does not improve postprandial glucose homeostasis during this time.

Estradiol is associated with mortality in critically ill trauma and surgical patients

Objective:Sexual dimorphism (variation in outcome related to sex) after trauma–hemorrhage and sepsis is well documented in animals, with the pro-estrus state being proinflammatory and associated with a survival advantage. Although some observational studies confirm this pattern in humans, others demonstrate no difference in mortality. Estrogens are important modulators of the inflammatory response and insulin resistance in humans and have been linked to increased mortality during sepsis. Our objective was to determine whether sex hormone levels were associated with outcomes in critically ill surgical patients. Design:Prospective cohort. Patients:A total of 301 adult critically ill or injured surgical patients remaining in the intensive care unit for ≥48 hrs at two academic medical centers. Interventions:None. Measurements:Blood was collected 48 hrs after intensive care unit admission and assayed for sex hormones (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor necrosis factor-&agr; and interleukin-1, -2, -4, -6, -8, and -10). Demographic and outcome data were also collected. Main Results:Estradiol was significantly higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol demonstrated greater than a three-fold increase in the mortality rate for the highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with an odds ratio for death of 4.60 (95% confidence interval, 1.56–13.0) compared with a reference estradiol level of 45 pg/mL. Conclusions:We conclude that serum estradiol correlates with mortality in critically ill and injured surgical patients and discuss potential mechanisms for this observation.

Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery

Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.

Pentobarbital coma for refractory intra-cranial hypertension after severe traumatic brain injury: mortality predictions and one-year outcomes in 55 patients

OBJECTIVE To identify predictors of mortality and long-term outcomes in survivors after pentobarbital coma (PBC) in patients failing current treatment standards for severe traumatic brain injuries (TBI). This is a retrospective cohort study of severe TBI patients receiving PBC at Level I Trauma Center and tertiary university hospital. METHODS Four thousand nine hundred thirty-four patients were admitted to the trauma intensive care unit with severe TBI (head Abbreviated Injury Scale >or= 3) between April 1998 and December 2004. Six hundred eleven received intracranial pressure (ICP) monitoring and 58 received PBC. Three patients underwent craniotomy for intracranial mass lesion and were excluded. The study group received standardized medical management for severe TBI including opiates, benzodiazepines, elevation of the head of bed, avoidance of hypotension and hypercapnia and hyperosmolar therapy (HOsmRx). In addition, 31 of 55 patients (56%) underwent placement of intraventricular catheters for cerebrospinal fluid drainage. If routine medical management and cerebrospinal fluid diversion failed to control ICP, then the patient was determined to have refractory intracranial hypertension (RICH) and PBC treatment was initiated. PBC was performed with pentobarbital infusion with continuous electroencephalogram monitoring to ensure adequate burst suppression. The measurements include serum sodium (Na) and osmolality (Osm) were assessed as indicators for initiation of PBC and to estimate the 50% mortality cut-points when controlling for ICP. Follow-up functional outcomes were assessed using the Glasgow Outcome Scale and stratified according to admission Glasgow Coma Scale score and Marshall computed tomography classification. Of the 55 PBC patients, 22 (40%) survived at discharge. 19 of 22 had long-term follow-up (1 year or more) available. Of these, 13 (68%) were normal or functionally independent (Glasgow Outcome Scale score 4 or 5). Serum Na and Osm were associated with death (p < 0.05) when controlling for ICP. The 50% mortality cut-points were Na of 160 mEq/L and Osm of 330 mOsm/kg H2O. Median minimum cerebral perfusion pressure after PBC was 42 mm Hg in survivors and 34 mm Hg in nonsurvivors (p = 0.013). CONCLUSIONS In patients with severe TBI and RICH, survival at discharge of 40% with good functional outcomes in 68% of survivors at 1 year or more can be achieved with PBC after failure of HOsmRx. Based on 50% mortality cut-points, analysis suggests the limits of HOsmRx to be Na of 160 mEq/L and Osm of 330 mOsm/Kg H2O. Maintenance of higher cerebral perfusion pressure after PBC is associated with survival. PBC treatment of RIH may be even more important when other treatments of RIH, such as decompressive craniectomy, are not available.

Single incision laparoscopic splenectomy in a 5-year-old with hereditary spherocytosis.

Laparoscopic splenectomy in a pediatric patient was performed through a single umbilical incision by using 3 ports.

Wilms tumor survival in Kenya

PURPOSE Survival from Wilms Tumor (WT) exceeds 90% at 5 years in developed nations, whereas at last report, 2-year event-free survival (EFS) in Kenya reached only 35%. To clarify factors linked to these poor outcomes in Kenya, we established a comprehensive web-based WT registry, comprised of patients from the four primary hospitals treating childhood cancers. MATERIALS AND METHODS WT patients diagnosed between January 2008 and January 2012 were identified. Files were abstracted for demographic characteristics, treatment regimens, and enrollment in the Kenyan National Hospital Insurance Fund (NHIF). Children under 15 years of age having both a primary kidney tumor on imaging and concordant histology consistent with WT were included. RESULTS Two-year event-free survival (EFS) was 52.7% for all patients (n=133), although loss to follow up (LTFU) was 50%. For the 33 patients who completed all scheduled standard therapy, 2-year EFS was 94%. Patients enrolled in NHIF tended to complete more standard therapy and had a lower hazard of death (Cox 0.192, p < 0.001). CONCLUSION Survival of Kenyan WT patients has increased slightly since last report. Notably, WT patients completing all phases of standard therapy experienced 2-year survival approaching the benchmarks of developed nations. Efforts in Kenya should be made to enhance compliance with WT treatment through NHIF enrollment.

Cholecystectomy using single-incision pediatric endosurgery: technique and initial experience in the first 25 cases.

BACKGROUND Laparoscopic cholecystectomy has become the standard, in most pediatric surgery centers. In the search for a less-invasive procedure, a single-incision laparoscopic approach has been reported in adults and very few children. OBJECTIVE The aim of this study was to present our initial experience of cholecystectomy, using single-incision pediatric endosurgery (SIPES), including the technique, the intraoperative challenges, and the outcome. METHODS All pediatric patients who underwent a SIPES cholecystectomy from March through September 2009 were prospectively evaluated. RESULTS Twenty-five children underwent a SIPES cholecystectomy. The most frequent indications were symptomatic cholelithiasis in 17 patients (68%) and biliary dyskinesia in 5 (20%). Five patients had sickle-cell anemia. The mean operative time was 73 minutes (range, 30-122). Median hospital stay was 1 day. In 17 patients (68%), a percutaneous 2-mm grasper was used to retract the gallbladder over the liver. No complications were noted, and no conversion to an open procedure was required. In 5 patients, additional trocars were added. On follow-up, 3 days to 2 months later, no complications were noted. No patients were readmitted, and there were no wound infections. CONCLUSIONS Cholecystectomy, when using the SIPES approach in children, is a safe, reasonable alternative to conventional laparoscopy, leaving an inconspicuous scar. Whether SIPES offers any further benefit to the patient, besides improved cosmesis, should be evaluated in future studies.

An evidence-based clinical protocol for diagnosis of acute appendicitis decreased the use of computed tomography in children

PURPOSE The increased use of computed tomography (CT) to diagnose appendicitis in children has led to a concern for the possibility of increased CT-related cancer morbidity. We designed a clinical protocol for the diagnosis and treatment of appendicitis in children in an attempt to decrease the use of CT scans at our institution. METHODS Patients who had surgical consultation for suspected appendicitis were placed on the clinical protocol. Data concerning diagnosis and treatment were collected prospectively. Retrospective data from patients admitted to our institution with acute appendicitis before the clinical protocol were collected as historical controls. RESULTS One hundred twelve patients were diagnosed and treated by our protocol between June and November 2009. Of these, 100 patients underwent an appendectomy for acute appendicitis. They were compared with 146 patients from 2007. In-house CT use decreased from 71.2% to 51.7% (P = .01). Preoperative ultrasound use increased from 2.7% to 21% (P < .001). The negative appendectomy rate increased (6.8% vs 11%, P = .25). CONCLUSIONS Our findings suggest that the implementation of an evidence-based clinical protocol for the diagnosis and treatment of acute appendicitis in children may safely decrease the use of CT scans and increase the use of ultrasound.

The Global Paediatric Surgery Network: A Model of Subspecialty Collaboration Within Global Surgery

Attention to surgical conditions in lowand middle-income countries (LMICs) has increased in recent years. Because half of the population in the world’s poorest countries are children [1], paediatric surgical conditions compose a significant proportion of the global burden of disease (BoD), and there are critical shortages in workforce and skills to treat these diseases in LMICs. Several populationbased studies have highlighted the magnitude of the need for paediatric surgery and the limited capacity, both in human resources and in infrastructure, to tackle the problem [2, 3]. Africa, in particular, has a grave shortage of paediatric surgeons. The number of fully trained paediatric surgeons ranges from 1 in Malawi (population 13 million) to 120 in Egypt (population of 80 million). In more than

Early experience in establishing and evaluating an ACGME-approved international general surgery rotation.

BACKGROUND In 2011, the Accreditation Council for Graduate Medical Education Surgery Residency Review Committee first provided guidelines for elective international general surgery rotations. The Vanderbilt general surgery residency program received Surgery Residency Review Committee approval for a fourth-year elective in Kenya beginning in the 2011-2012 academic year. Because this rotation would break ground culturally and geographically, and as an educational partnership, a briefing and debriefing process was developed for this ground-breaking year. OBJECTIVES Our objectives were to prepare residents to maximize the experience without competing for cases with local trainees or overburdening the host institution and to perform continuous quality assessment and improvement as each resident returned back. METHODS Briefing included health protection strategies, a procedures manual containing step-by-step preparation activities, and cultural-sensitivity training. Institutional Review Board exemption approval was obtained to administer a questionnaire created for returning residents concerning educational value, relations with local trainees, physical environment, and personal perceptions that would provide the scaffold for the debriefing conference. RESULTS The questionnaire coupled with the debriefing discussion for the first 9 participants revealed overall satisfaction with the rotation and the briefing process, good health, and no duty hours or days-off issues. Other findings include the following: (1) emotional effect of observing African families weigh cost in medical decision making; (2) satisfactory access to educational resources; (3) significant exposure to specialties such as urology and radiology; and (4) toleration of 4 weeks as a single and expressed need for leisure activity materials such as books, DVDs, or games. The responses triggered adjustments in the briefing sessions and travel preparation. The host institution invited the residents to return for the 2012-2013 year as well as 2013-2014. CONCLUSION Detailed preparation and the follow-up evaluation for assessment and improvement of this nascent international surgery experience are associated with resident satisfaction and the host institution has agreed to continue the rotation.