Paulina Salminen

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial

IMPORTANCE An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. OBJECTIVE To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. INTERVENTIONS Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. MAIN OUTCOMES AND MEASURES The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. RESULTS There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. CONCLUSIONS AND RELEVANCE Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01022567.

Comparison of Long-term Outcome of Laparoscopic and Conventional Nissen Fundoplication: A Prospective Randomized Study With an 11-Year Follow-up

Objective:The aim of this study was to compare the long-term objective and subjective outcomes of laparoscopic and open Nissen fundoplication in a randomized clinical trial with an 11-year follow-up. Summary Background Data:Laparoscopic Nissen fundoplication has become the method of choice in antireflux surgery, replacing its open counterpart despite the lack of long-term results from controlled clinical studies. Methods:Between April 1992 and June 1995, 110 consecutive patients were randomized to either laparoscopic (LAP) or conventional (open) Nissen fundoplication. The objective long-term follow-up consisted of an upper gastrointestinal endoscopy and a clinical assessment; the subjective long-term outcome was investigated by personal interviews using a structured questionnaire. Results:Forty-nine patients in the LAP group and 37 patients in the open group were available for evaluation. Late subjective results, including postoperative symptoms and evaluation of the surgical result, were similar in both groups. With the benefit of hindsight, 73.7% of the patients in the open group and 81.8% in the LAP group would again choose surgical treatment (P = 0.3042). In the LAP group, there were 5 (13.2%) partially or totally disrupted plications compared with the 14 (40.0%) disrupted plications in the open group (P = 0.0152). There were 10 incisional hernias in the open group compared with none in the LAP group (P < 0.001). Conclusions:At long-term follow-up, the open and LAP approaches for the Nissen fundoplication have similar long-term subjective symptomatic outcome despite the significantly higher incidence of incisional hernias and defective fundic wraps at endoscopy in the open group defining laparoscopic Nissen fundoplication as the procedure of choice in surgical management of gastroesophageal reflux disease.

Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity.

Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity.

Bile duct injuries during laparoscopic cholecystectomy: primary and long-term results from a single institution

BackgroundIatrogenic bile duct injury carries high morbidity. After the introduction of laparoscopic cholecystectomy the incidence of these injuries has at least doubled, and even after the learning curve, the incidence has plateaued at the level of 0.5%.MethodsA total of 32 patients sustained biliary tract injuries of the 3736 laparoscopic cholecystectomies performed in and around Turku University Central Hospital between January 1995 and April 2002. The data concerning primary treatment and long-term results were collected and analyzed retrospectively.ResultsThe overall incidence for bile duct injuries, including all the minor injuries (cystic duct leaks and bile duct strictures), was 0.86%; for major injuries alone the incidence was 0.38%. Nineteen percent of the injuries were detected intraoperatively. All the cystic duct leaks were treated endoscopically with a 90% success rate. Of the bile duct strictures 88% were treated successfully with endoscopic techniques. Ninety-three percent of the major injuries, including tangential lesions of common bile duct and total transections, were treated operatively. The operation of choice was either hepaticojejunostomy or cholangiojejunostomy in 69% of the cases; the rest were treated with simple suturing over a T-tube or an endoscopically placed stent. The long-term results, with a median follow-up period of 7.5 years, are good in 79% of the operated patients and in 84% of the whole study population. Mortality rate was 3% and acute or chronic cholangitis was seen in 13% of the patients during follow-up.ConclusionMost of the minor bile duct injuries, including cystic duct leaks and bile duct strictures, are well treatable with endoscopic techniques, whereas most of the major injuries require operative treatment, which at optimal circumstances gives good results.

Population‐based study of the surgical workload and economic impact of bowel obstruction caused by postoperative adhesions

Intestinal obstruction is the most severe consequence of adhesion formation. This study examined the annual surgical workload and costs of intestinal obstruction caused by postoperative intra‐abdominal adhesions.

Obesity Is Associated with Decreased μ-Opioid But Unaltered Dopamine D2 Receptor Availability in the Brain

Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased μ-opioid receptor (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m2] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [11C]carfentanil and [11C]raclopride, respectively. We also used quantitative meta-analytic techniques to pool previous evidence on the effects of obesity on altered D2R availability. Morbidly obese subjects had significantly lower MOR availability than control subjects in brain regions relevant for reward processing, including ventral striatum, insula, and thalamus. Moreover, in these areas, BMI correlated negatively with MOR availability. Striatal MOR availability was also negatively associated with self-reported food addiction and restrained eating patterns. There were no significant differences in D2R availability between obese and nonobese subjects in any brain region. Meta-analysis confirmed that current evidence for altered D2R availability in obesity is only modest. Obesity appears to have unique neurobiological underpinnings in the reward circuit, whereby it is more similar to opioid addiction than to other addictive disorders. The opioid system modulates motivation and reward processing, and low μ-opioid availability may promote overeating to compensate decreased hedonic responses in this system. Behavioral and pharmacological strategies for recovering opioidergic function might thus be critical to curb the obesity epidemic.

Linear Stapler Technique May Be Safer than Circular in Gastrojejunal Anastomosis for Laparoscopic Roux-en-Y Gastric Bypass: A Meta-analysis of Comparative Studies

The technique of choice for gastrojejunostomy (GJ) during laparoscopic Roux-en-Y gastric bypass (LRYGB) for morbid obesity is controversial. We performed a meta-analysis comparing linear versus circular stapler technique to evaluate this issue. A systematic literature search was performed. Primary outcomes were gastrojejunal leak and stricture. Secondary outcomes were operative time, length of hospital stay, post-operative bleeding, wound infection, marginal ulcers and estimated weight loss. Eight studies involving 1,321 patients were retrieved and included in the present study. A significantly decreased risk of GJ stricture was observed after using linear versus circular stapler (RR, 0.34; 95% CI, 0.12–0.93; p = 0.04). Wound infection risk (RR, 0.38; 95% CI, 0.22–0.67; p = 0.0008) and operative time (MD, −24.18; 95% CI, −35.31, −13.05; p < 0.0001) were significantly reduced by using linear stapling. No significant differences were observed in the other outcome end-points. The use of the linear stapler compared with circular stapler for GJ during LRYGB for morbid obesity may be associated with a reduced risk of anastomosis stricture and wound infection, as well as with a shorter operative time.

Effect of bariatric surgery on liver glucose metabolism in morbidly obese diabetic and non-diabetic patients

BACKGROUND & AIMS Bariatric surgery reduces weight and improves glucose metabolism in obese patients. We investigated the effects of bariatric surgery on hepatic insulin sensitivity. METHODS Twenty-three morbidly obese (nine diabetic and fourteen non-diabetic) patients and ten healthy, lean control subjects were studied using positron emission tomography to assess hepatic glucose uptake in the fasting state and during euglycemic hyperinsulinemia. Magnetic resonance spectroscopy was performed to measure liver fat content and magnetic resonance imaging to obtain liver volume. Obese patients were studied before bariatric surgery (either sleeve gastrectomy or Roux-en-Y gastric bypass) and six months after surgery. RESULTS Insulin-induced hepatic glucose uptake was increased by 33% in non-diabetic and by 36% in diabetic patients at follow-up compared with baseline, but not totally normalized. The liver fat content was reduced by 76%, liver volume by 26% and endogenous glucose production by 19% in non-diabetic patients. The respective changes in diabetic patients were 73%, 24%, and 25%. Postoperatively, liver fat content and endogenous glucose production were almost normalized to lean controls, but liver volume remained greater than in control subjects. CONCLUSIONS This study shows that bariatric surgery leads to a significant improvement in hepatic insulin sensitivity: insulin-stimulated hepatic glucose uptake was improved and endogenous glucose production reduced when measured, six-months, after surgery. These metabolic effects were accompanied by a marked reduction in hepatic volume and fat content. Overall, the gain in hepatic insulin sensitivity in diabetic patients was quite similar to non-diabetic patients for the same weight reduction.

Obesity is associated with white matter atrophy: A combined diffusion tensor imaging and voxel‐based morphometric study

Little is known about the mechanisms by which obesity influences brain structure. In this study, the obesity‐related changes in brain white and gray matter integrity were examined.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial

Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. Design, Setting, and Participants The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Interventions Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Results Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and Relevance Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins. Trial Registration clinicaltrials.gov Identifier: NCT00793143