Bariatric surgery in the treatment of morbid obesity : long term outcomes and comparison of laparoscopic sleeve gastrectomy with Roux-en-Y gastric bypass

Obesity is currently one of the greatest global health problems. It is associated with increased morbidity and mortality, worsened quality of life (QOL) and significant health care costs. For morbidly obese patients, bariatric surgery is the only effective treatment option showing good and sustainable long-term weight loss and remission or improvement of obesity related comorbidities. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard of bariatric surgery with demonstrated longterm efficacy. During the last years, laparoscopic sleeve gastrectomy (LSG) has become the most common bariatric procedure despite the lack of long-term followup results at that time. The main aim of this thesis was to compare the short and long-term outcomes on weight loss, obesity related co-morbidities, and QOL after LSG and LRYGB in the treatment of morbid obesity in a randomized clinical multicenter equivalence trial (SLEEVEPASS). In addition, this thesis aimed to assess the QOL improvement after laparoscopic gastric banding (LGB) and to compare it with the QOL of the general population. The operative time of LSG was shorter with no difference in early (30 days) overall morbidity between LSG and LRYGB. At 5-year follow-up, the primary endpoint of percent excess weight loss (%EWL) was 57% after LRYGB and 49% after LSG. The mean difference was not statistically significant based on the prespecified equivalence margins. At 5 years, there were no differences regarding the long-term resolution of type 2 diabetes or dyslipidemia, improvement of QOL, morbidity, and mortality, but hypertension resolution was superior after LRYGB. QOL improved significantly after LAGB and was maintained at five-year follow-up but did not reach the level of the general population.Bariatrinen kirurgia sairaalloisen lihavuuden hoidossa: pitkäaikaistulokset ja vertailu mahalaukun kavennusleikkauksen ja ohitusleikkauksen välillä Lihavuus on yksi suurimpia maailmanlaajuisia terveysongelmia. Siihen liittyy lisääntynyt sairastavuus ja kuolleisuus, huonontunut elämänlaatu sekä merkittäviä terveydenhuollon kustannuksia. Lihavuuskirurgia on ainoa hoitomuoto, jolla saavutetaan hyvät pitkäaikaistulokset painonlaskun sekä sairaalloiseen lihavuuteen liittyvien liitännäissairauksien paranemisen osalta. Mahalaukun ohitusleikkaus (bypass) on vakiintunut leikkausmenetelmä, jonka teho on osoitettu pitkäaikaisseurannassa. Viime vuosina mahalaukun kavennusleikkauksesta (sleeve) on tullut yleisin lihavuuskirurginen leikkausmenetelmä ilman käytettävissä olevia pitkäaikaistuloksia. Tämän väitöskirjatyön tarkoituksena oli vertailla mahalaukun kavennus- ja ohitusleikkauksen tuloksia painonlaskun, liitännäissairauksien paranemisen sekä elämänlaadun osalta satunnaistetussa kliinisessä monikeskus-ekvivalenssitutkimuksessa (SLEEVEPASS). Lisäksi tutkittiin mahapantaleikkauksen jälkeistä elämänlaadun paranemista ja vertailtiin sitä väestön yleiseen elämänlaatuun. Varhaisvaiheen tuloksissa kavennusleikkauksen leikkausaika oli lyhyempi, mutta komplikaatioiden määrässä ei ollut eroa ohitusleikkaukseen verrattuna. Tutkimuksen ensisijainen päätetapahtuma eli ylipaino-osuuden prosentuaalinen lasku (%EWL) viiden vuoden seurannassa oli ohitusleikkauksen jälkeen 57% ja kavennusleikkauksen jälkeen 49%. Keskimääräinen ero ei ollut tilastollisesti merkitsevä perustuen ennalta määriteltyihin ekvivalenssirajoihin. Leikkausmenetelmien välillä ei ollut eroa tyypin 2 diabeteksen, hyperkolesterolemian ja elämänlaadun paranemisessa, eikä sairastavuudessa ja kuolleisuudessa, mutta verenpainetauti parani useammin ohitusleikkauksen jälkeen. Mahapantaleikkauksen jälkeen elämänlaatu parani merkitsevästi viiden vuoden seuranta-aikana, mutta lihavuuskirurgisten potilaiden elämänlaatu oli vertailuväestöä huonompi

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes

OBJECTIVE We investigated fat distribution and tissue-specific insulin-stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. RESEARCH DESIGN AND METHODS A total of 23 obese patients (BMI 43.0 ± 3.6 kg/m2; 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [18F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. RESULTS At baseline, visceral fat GU was 30 ± 7% of muscle GU in control subjects and 57 ± 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (∼40%) more than subcutaneous fat (7%). Tissue-specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. CONCLUSIONS Bariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose

Validation of the individualized metabolic surgery score for bariatric procedure selection in the merged data of two randomized clinical trials (SLEEVEPASS and SM-BOSS).

Background: LSG and LRYGB are globally the most common bariatric procedures. IMS score categorizes T2D severity (mild, moderate, and severe) based on 4 independent preoperative predictors of long-term remission as follows: T2D duration, number of diabetes medications, insulin use, and glycemic control. IMS score has not been validated in a randomized patient cohort.Objectives: To assess the feasibility of individualized metabolic surgery (IMS) score in facilitating procedure selection between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) for patients with severe obesity and type 2 diabetes (T2D).Setting: Merged individual patient-level 5-year data of 2 large randomized clinical trials (SLEEVEPASS and SM-BOSS [Swiss Multicenter Bypass or Sleeve Study]).Methods: IMS score was calculated for study patients and its performance was analyzed.Results: One hundred thirty-nine out of 155 patients with T2D had available preoperative data to calculate IMS score as follows: mild stage (n = 41/139), moderate stage (n = 77/139), severe stage (n = 21/139). At 5 years, 135 (87.1%, 67 LSG/68 LRYGB) were available for follow-up and 121 patients had both pre- and postoperative data. Diabetes remission rates according to preoperative IMS score were as follows: mild stage 87.5% (n = 14/16) after LSG and 85.7% (n = 18/21) after LRYGB (P = .999), moderate stage 42.9% (n = 15/35) and 45.2% (n = 14/31) (P = .999), and severe stage 18.2% (n = 2/11) and 0% (n = 0/7) (P = .497), respectively. The T2D remission rate varied significantly between the stages as follows: mild versus moderate odds ratio (OR) 8.3 (95% CI, 2.8-24.0; P Conclusions: In our study, remission rates of T2D were not statistically different after LSG and LRYGB among all patients and among patients with mild, moderate, and severe diabetes stratified by the IMS score. However, the study may be underpowered to detect differences due to small number of patients in each subgroup. IMS score seemed to be useful in predicting long-term T2D remission after bariatric surgery.</p

Renal Sinus Fat Is Expanded in Patients with Obesity and/or Hypertension and Reduced by Bariatric Surgery Associated with Hypertension Remission

Renal sinus fat is a fat depot at the renal hilum. Because of its location around the renal artery, vein, and lymphatic vessels, an expanded renal sinus fat mass may have hemodynamic and renal implications. We studied whether renal sinus fat area (RSF) associates with hypertension and whether following bariatric surgery a decrease in RSF associates with improvement of hypertension. A total of 74 severely obese and 46 lean controls were studied with whole-body magnetic resonance imaging (MRI). A total of 42 obese subjects were re-studied six months after bariatric surgery. RSF was assessed by two independent researchers using sliceOmatic. Glomerular filtration rate (eGFR) was estimated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Patients with obesity accumulated more RSF compared to lean controls (2.3 [1.7-3.1] vs. 1.8 [1.4-2.5] cm(2), p = 0.03). Patients with hypertension (N = 36) had a larger RSF depot compared to normotensive subjects (2.6 [2.0-3.3] vs. 2.0 [1.4-2.5] cm(2), p = 0.0007) also after accounting for body mass index (BMI). In the pooled data, RSF was negatively associated with eGFR (r = -0.20, p = 0.03), whereas there was no association with systolic or diastolic blood pressure. Following bariatric surgery, RSF was reduced (1.6 [1.3-2.3] vs. 2.3 [1.7-3.1] cm(2), p = 0.03) along with other markers of adiposity. A total of 9/27 of patients achieved remission from hypertension. The remission was associated with a larger decrease in RSF, compared to patients who remained hypertensive (-0.68 [ -0.74 to -0.44] vs. -0.28 [ -0.59 to 0] cm(2), p = 0.009). The accumulation of RSF seems to be involved in the pathogenesis of hypertension in obesity. Following bariatric surgery, loss of RSF was associated with remission from hypertension

Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis : effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight

Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. Methods: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. Discussion: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors.Peer reviewe

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy : A Population-Based Nationwide Study in Finland

Background No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. Methods This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. Results A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. Conclusions This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.Peer reviewe

Preoperative hemoglobin count and prognosis of esophageal cancer, a population-based nationwide study in Finland

Publisher Copyright: © 2021Background: The prognostic value of preoperative hemoglobin in patients undergoing esophagectomy is unknown. The aim of this study was to examine whether preoperative hemoglobin is associated with prognosis in patients undergoing esophagectomy for cancer. Materials and methods: This was a population-based nationwide retrospective cohort study in Finland, using Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with available preoperative hemoglobin measurement were included. Multivariable cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period of surgery, age at surgery, sex, comorbidity (Charlson Comorbidity Index), tumor histology, tumor stage, neoadjuvant therapy, type of surgery (minimally invasive or open) and annual hospital volume. Results: Of the 1313 patients, 932 (71.0%) were men and 799 (60.9%) had esophageal adenocarcinoma. Overall all-cause mortality was significantly higher in the lowest hemoglobin count tertile (HR 1.26 (1.07–1.47)) compared to the highest tertile, but this association was attenuated after adjustment for confounding. No differences were found between the preoperative hemoglobin groups in the adjusted analyses of 90-day all-cause, 5-year all-cause, and 5-year cancer-specific mortality. Conclusion: In this population-based nationwide study, preoperative hemoglobin count had no independent prognostic significance in esophageal cancer.Peer reviewe

Physical Activity Associates with Muscle Insulin Sensitivity Postbariatric Surgery

PurposeBariatric surgery is considered as an effective therapeutic strategy for weight loss in severe obesity. Remission of type 2 diabetes is often achieved following the surgery. We investigated whether increase in self-reported habitual physical activity associates with improved skeletal muscle insulin sensitivity and reduction of fat depots after bariatric surgery.MethodsWe assessed self-reported habitual physical activity using Baecke questionnaire in 18 diabetic and 28 non-diabetic patients with morbid obesity (median age 46 years and BMI 42.0 kg·m-2) before and six months after bariatric surgery operation. Insulin-stimulated femoral muscle glucose uptake was measured using FDG PET -method during hyperinsulinaemia. In addition, abdominal subcutaneous and visceral fat masses were quantified using magnetic resonance imaging and liver fat content using magnetic resonance spectroscopy. Also, serum pro-inflammatory cytokines were measured.ResultsPatients lost on average 22.9% of weight during the follow-up period of six months (pConclusionSelf-reported physical activity is associated with reversal of skeletal muscle insulin resistance following bariatric surgery as well as with the loss of visceral fat content and improved postoperative metabolism in bariatric surgery patients.</p

Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight

Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk.Methods: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength.Discussion: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors

Preoperative Esophageal Stenting and 5-Year Survival in Patients Undergoing Esophagectomy for Esophageal Cancer : a Population-Based Nationwide Study from Finland

Background: Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. Methods: This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. Result: Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoperative stent with HRs of 1.29 (95% CI 1.00–1.65) and 1.25 (95% CI 0.97–1.62), respectively, compared to no stenting. The adjusted HR of 90-day mortality was 2.49 (95% CI 1.27–4.87) in model 1 and 2.49 (95% CI 1.25–4.99) in model 2. When including only neoadjuvant-treated patients, those with preoperative stent had a 5-year survival of 39.2% compared to 46.4% without stent (adjusted HR 1.34, 95% CI 1.00–1.80), and a 90-day mortality rate of 8.5% and 2.5% (adjusted HR 3.99, 95% CI 1.51–10.50). Discussion: This nationwide study reports worse 5-year and 90-day outcomes in patients with preoperative esophageal stent. Since residual confounding remains possible, observed difference could be only an association rather than the cause.publishedVersionPeer reviewe