The value of "diaphragmatic relaxing incision" for the durability of the crural repair in patients with paraesophageal hernia: a double blind randomized clinical trial.

Background: Surgical repair of paraesophageal hernias (PEHs) is burdened with high recurrence rates, and hitherto various techniques explored to enforce the traditional crural repair have not been successful. The hiatal reconstruction in PEH is exposed to significant tension, which may be minimized by adding a diaphragmatic relaxing incision to enhance the durability of the crural repair. Patients and methods: All individuals undergoing elective laparoscopic repair of a large PEH, irrespective of age, were considered eligible. PEHs were classified into types II-IV. The preoperative work-up program included multidetector computed tomography and symptom assessment questionnaires, which will be repeated during the postoperative follow-up. Patients were randomly divided into a control group with crural repair alone and an intervention group with the addition of a left-sided diaphragmatic relaxing incision at the edge of the upper pole of the spleen. The diaphragmatic defect was then covered by a synthetic mesh. Results: The primary endpoint of this trial was the rate of anatomical PEH recurrence at 1 year. Secondary endpoints included symptomatic gastroesophageal reflux disease, dysphagia, odynophagia, gas bloat, regurgitation, chest pain, abdominal pain, nausea, vomiting, postprandial pain, cardiovascular and pulmonary symptoms, and patient satisfaction in the immediate postoperative course (3 months) and at 1 year. Postoperative complications, morbidity, and disease burden were recorded for each patient. This was a double-blind study, meaning that the operation report was filed in a locked archive to keep the patient, staff, and clinical assessors blinded to the study group allocation. Blinding must not be broken during the follow-up unless required by any emergencies in the clinical management of the patient. Likewise, the patients must not be informed about the details of the operation. Trial Registration: ClinicalTrials.gov, identification number NCT04179578.

Tension-free mesh versus suture-alone cruroplasty in antireflux surgery: a randomized, double-blind clinical trial.

BACKGROUND: Antireflux surgery is effective for the treatment of gastro-oesophageal reflux disease (GORD) but recurrence of hiatal hernia remains a challenge. In other types of hernia repair, use of mesh is associated with reduced recurrence rates. The aim of this study was to compare the use of mesh versus sutures alone for the repair of hiatal hernia in laparoscopic antireflux surgery. METHODS: Patients undergoing laparoscopic Nissen fundoplication for GORD between January 2006 and December 2010 were allocated randomly to closure of the diaphragmatic hiatus with crural sutures or non-absorbable polytetrafluoroethylene mesh (CruraSoft®). The primary outcome was recurrence of hiatal hernia, as determined by barium swallow study 12 months after surgery. Secondary outcomes were: intraoperative and postoperative complications, use of antireflux medication, postoperative oesophageal acid exposure, quality of life, dysphagia and duration of hospital stay. RESULTS: Some 77 patients were randomized to the suture technique and 82 patients underwent mesh repair. At 1 year, the hiatal hernia had recurred in six of 64 patients (9 per cent) in the mesh group and two of 64 (3 per cent) in the suture group (P = 0·144). Reflux symptoms, use of proton pump inhibitors and oesophageal acid exposure did not differ between the groups. At 3 years, recurrence rates were 13 and 10 per cent in the mesh and suture groups respectively (P = 0·692). Dysphagia scores decreased in both groups, but more patients had dysphagia for solid food after mesh closure (P = 0·013). Quality-of-life scores were comparable between the groups. CONCLUSION: Tension-free crural repair with non-absorbable mesh does not reduce the incidence of recurrent hiatal hernia compared with use of sutures alone in patients undergoing laparoscopic fundoplication. NCT03730233 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía antirreflujo es efectiva para el tratamiento de la enfermedad por reflujo gastroesofágico (gastro-oesophageal reflux disease, GORD), pero la recidiva de la hernia de hiato sigue siendo un desafío. En otros tipos de reparación herniaria, la utilización de mallas se asocia con tasas reducidas de recidiva. El objetivo de este estudio fue comparar la utilización de una malla con suturas solo para la reparación de la hernia de hiato en cirugía antirreflujo laparoscópica. MÉTODOS: Pacientes sometidos a funduplicatura de Nissen por GORD entre enero 2006 y diciembre 2010 fueron asignados de forma aleatoria a cierre del hiato diafragmático con suturas de la crura o malla PTFE no absorbible (CruraSoft®). El resultado primario fue la recidiva de la hernia hiatal determinada mediante estudio radiológico con papilla de bario a los 12 meses de la cirugía. Los resultados secundarios fueron las complicaciones intra- y postoperatorias, utilización de medicación antirreflujo, exposición postoperatoria del esófago al reflujo ácido, calidad de vida, disfagia y duración de la estancia postoperatoria. RESULTADOS: Un total de 77 pacientes fueron aleatorizados a la técnica con suturas y 82 pacientes fueron sometidos a reparación con malla. Al año, se observó recidiva de la hernia de hiato en 6 de 64 pacientes en el grupo con malla (9%) y 2 de 64 pacientes (3%) en el grupo con suturas (P = 0,144). Los síntomas de reflujo, utilización de inhibidores de la bomba de protones (IBPs) y exposición del esófago al ácido no difirieron entre los grupos. A los 3 años, las tasas de recidiva fueron 13% y 10% para el grupo con malla y para el grupo con sutura, respectivamente (P = 0,692). Las puntuaciones de disfagia se redujeron en ambos grupos, pero más pacientes presentaron disfagia para sólidos tras el cierre con malla (P = 0,013). Las puntuaciones de calidad de vida posteriores fueron similares en ambos grupos. CONCLUSIÓN: En pacientes sometidos a funduplicatura laparoscópica, la reparación de la crura sin tensión con malla no absorbible no reduce la incidencia de recidiva de la hernia de hiato en comparación con el uso de suturas solo.

Adipose lipid turnover and long-term changes in body weight.

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.

Sustainability of the relationship between preoperative symptoms and postoperative improvement in quality of life after inguinal hernia repair.

PURPOSE: Chronic pain and discomfort are common before and after inguinal hernia repair (IHR) and pain is clearly linked to reduced quality of life (QoL). The long-term effect of IHR on QoL in relation to preoperative symptoms is incompletely described. METHODS: 309 men (18-75 years) undergoing IHR under local anesthesia and day care surgery were included. Pre- and postoperative symptoms, pain and QoL (SF-36) were measured before and up to 3 years after surgery. RESULTS: Before surgery, 197 patients (64%) reported pain (VAS 0.9-5.4) from their inguinal hernia. 102 patients (33%) had other inguinal symptoms, and 26% were asymptomatic. Patients with preoperative groin pain (P) scored their physical QoL (PCS) lower compared with controls (C) (median (IQR) 43.5 (34.7-50.3) vs. 53.9 (47.8-56.9, p < 0.001)), whereas patients with no pain (N) did not (53.0 (47.9-55.9), p = 0.57). Mental QoL was not affected before or after surgery. At 1, 2 and 3 years after surgery, 14, 12 and 7% of patients, respectively, reported groin pain. In P, PCS increased from 43.5 before surgery to 55.3 (p < 0.001) at 36 months, but was unchanged in N (53.0 vs 55.9, p = ns). CONCLUSIONS: The incidence of inguinal pain decreases over time after inguinal hernia repair. Both preoperative reduction and long-term improvement in physical QoL are strongly associated with the presence of preoperative groin pain. This supports, from a QoL perspective, that patients with preoperative pain are those who benefit the most from IHR, also from a long-term perspective.

Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study.

BACKGROUND: The cardiometabolic risk profile improves following bariatric surgery. However, the degree of improvement in relation to weight-stable control subjects is unknown. OBJECTIVES: To study the differences in cardiometabolic risk profile between formerly obese patients following Roux-en-Y gastric bypass (RYGB) surgery and control subjects. METHODS: Subjects undergoing RYGB and reaching a BMI <30 kg m-2 2 years postsurgery were matched with control subjects regarding age, sex and BMI. The following examinations were performed: insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, insulin clearance, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile, inflammatory marker levels, dual-energy X-ray absorptiometry and subcutaneous adipose tissue cellularity (fat cell size and number). RESULTS: Sixty-nine subjects undergoing RYGB were matched to a control subject. Insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, blood pressure, inflammatory status and glucose, triglyceride and HDL cholesterol levels were comparable to values of control subjects. However, HOMA-IR (1.0 ± 0.5 vs. 1.3 ± 0.7, P = 0.005), insulin clearance (0.38 ± 0.08 vs. 0.34 ± 0.08 µL m-2  min-1 , P < 0.0001) and circulating levels of insulin (31 ± 15 vs. 37 ± 17 pmol L-1 , P = 0.008), total cholesterol (4.1 ± 0.7 vs. 4.8 ± 0.9 mmol L-1 , P < 0.0001) and LDL cholesterol (2.1 ± 0.6 vs. 2.9 ± 0.8 mmol L-1 , P < 0.0001) were improved beyond the levels in matched control subjects. Furthermore, formerly obese subjects had higher lean and lower fat mass as well as a more benign type of adipose cellularity (hyperplasia with many small fat cells) compared to control subjects. CONCLUSIONS: Subjects who underwent RYGB and reached a postobese state demonstrated a beneficial body composition, slightly increased insulin sensitivity as indirectly measured by HOMA-IR and higher insulin clearance, lower atherogenic lipid/lipoprotein levels and benign adipocyte morphology compared with control subjects who had never been obese. In line with previous results, our findings may in part explain why RYGB confers long-term protection against metabolic complications.

Rates of and methods used at reoperation for recurrence after primary inguinal hernia repair with Prolene Hernia System and Lichtenstein.

INTRODUCTION: Since the introduction of tension-free mesh repair of inguinal hernia ad modum Lichtenstein (L), recurrence rates have been reduced to 1-2%. The bi-layer mesh Prolene Hernia System (PHS) is an alternative mesh with a theoretical potential to further reduce recurrence rates. However, a reoperation due to recurrence after PHS might be technically difficult since both the anterior and posterior space has been utilized. METHODS: Data on all males 18-75 years undergoing primary inguinal hernia repair (IHR) with PHS or L between January 1999 and October 2010 was collected from the Swedish Hernia Register (SHR). Moreover, data was collected for all operations due to recurrence after primary IHR with PHS or L between January 1st 1999 and December 31st 2014. RESULTS: A total of 1229 primary IHR with PHS and 78,230 with L was identified. Rates of reoperation for recurrence after PHS was significantly lower compared to L (1.5 vs. 2.7 %), [OR 0.38 (0.20-0.74)]. A medial recurrence was most common in both groups. At reoperation, an open anterior mesh repair was used in 74 % after PHS and a posterior mesh repair was performed in 58 % after L. Re-operating time was shorter, although not statistically significant in the PHS group (47 vs. 58 min, p = 0.29). Complication rates after surgery due to recurrence did not differ between groups. CONCLUSION: The findings from this dataset suggest that recurrence rates after primary IHR with PHS might be lower and that reoperation due to recurrence after PHS is not more complicated than after L.

The effect of diverting stoma on long-term morbidity and risk for permanent stoma after low anterior resection for rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is a severe complication after low anterior resection (LAR) in rectal cancer surgery. A diverting loop ileostomy has been reported to reduce early clinical AL and thereby decrease short-term morbidity. Less is known if long-term morbidity is affected by a loop ileostomy constructed at LAR. METHODS: At Ersta Hospital, Sweden, 287 consecutive patients were operated on with LAR, 2002-2011. Follow-up time was 3 years after LAR. Due to a shift in routines, 15% were diverted at LAR, 2002-2006 and 91%, 2007-2011. Data on long-term morbidity and permanent stoma in patients with or without a diversion at primary surgery were compared. RESULTS: During LAR, 139 patients were diverted (S+), 148 were not (S-). Total rate of AL, both early and late, was 26% in S+ and 30% in S-, p 0.25. Late AL (>30 days after LAR) was found in 6% and 15% were readmitted in the late postoperative period with no difference between the groups. Total length of hospital stay (30 days-3 years after LAR) was longer among S+ compared to S-, mean 7 vs. 4 days (p < 0.001). One out of six ended up with a permanent stoma (17% S+, 14% S-, p 0.47). Clinical AL was an independent risk factor and the most common cause for a permanent stoma in both groups. CONCLUSION: A diverting loop ileostomy at LAR did not reduce long-term morbidity but was associated with a longer total length of hospital stay during a 3-year follow up.

UltraPro Hernia System, Prolene Hernia System and Lichtenstein for primary inguinal hernia repair: 3-year outcomes of a prospective randomized controlled trial.

PURPOSE: Chronic pain and discomfort are common after inguinal hernia repair (IHR). In this study, results from a 3-year follow-up from a randomized controlled study comparing three different mesh repairs for postoperative pain, discomfort, Quality of Life (QoL) and patient satisfaction are reported. METHODS: Between November 1, 2006 and January 31, 2009, 309 men, who underwent day surgery for primary unilateral inguinal hernia under local anesthesia, were randomized to three different mesh repairs; UltraPro Hernia System (U), Prolene Hernia System (P) and Lichtenstein procedure (L). RESULTS: Preoperatively, there were no differences between groups regarding demographics, symptoms, inguinal pain or QoL (SF-36 and a hernia-specific questionnaire). Operating time, postoperative pain, complications and time to full recovery were similar. At 36 months, 21 patients indicated pain [L, n = 6, P, n = 6 and U, n = 9; VAS (median (IQR)): L 0.4 (0.2-1.7), P 0.2 (0.1-2.3) and U 1.6 (0.7-4.6), p = ns]. Physical QoL was reduced in all groups before surgery and was similarly increased to normal levels after 3 months without further changes throughout the study. Although 92 % of participants were satisfied, sixteen percent reported any discomfort from the groin (ns between groups). Five recurrences were reported (L, n = 2, P, n = 1 and U, n = 2, p = ns). CONCLUSIONS: After 3 years of follow-up, all three procedures provided equally good results regarding, pain, discomfort and QoL and could therefore be recommended for primary IHR in LA.

Guidelines for Perioperative Care in Bariatric Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations.

BACKGROUND: During the last two decades, an increasing number of bariatric surgical procedures have been performed worldwide. There is no consensus regarding optimal perioperative care in bariatric surgery. This review aims to present such a consensus and to provide graded recommendations for elements in an evidence-based "enhanced" perioperative protocol. METHODS: The English-language literature between January 1966 and January 2015 was searched, with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohort studies. Selected studies were examined, reviewed and graded. After critical appraisal of these studies, the group of authors reached a consensus recommendation. RESULTS: Although for some elements, recommendations are extrapolated from non-bariatric settings (mainly colorectal), most recommendations are based on good-quality trials or meta-analyses of good-quality trials. CONCLUSIONS: A comprehensive evidence-based consensus was reached and is presented in this review by the enhanced recovery after surgery (ERAS) Society. The guidelines were endorsed by the International Association for Surgical Metabolism and Nutrition (IASMEN) and based on the evidence available in the literature for each of the elements of the multimodal perioperative care pathway for patients undergoing bariatric surgery.

Impaired atrial natriuretic peptide-mediated lipolysis in obesity.

BACKGROUND: Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered. METHODS: Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis. RESULTS: In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men. CONCLUSIONS: ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD.

BACKGROUND: Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro-oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti-reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients. AIM: To perform a double-blind sham-controlled study in GERD patients who were chronic PPI users. METHODS: We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6-month follow-up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis. RESULTS: The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P < 0.001. After 6 months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised. CONCLUSION: Transoral incisionless fundoplication (TIF2) is effective in chronic PPI-dependent GERD patients when followed up for 6 months. Clinicaltrials.gov: CT01110811.

The effect of diverting stoma on postoperative morbidity after low anterior resection for rectal cancer in patients treated within an ERAS program.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after low anterior resection (LAR) with total mesorectal excision (TME) for rectal cancer. Whether the Enhanced Recovery After Surgery (ERAS)-protocol influences the risk of short-term morbidity in relation to the use of a diverting stoma is unclear. METHODS: Between 2002 and 2011, 287 consecutive patients underwent LAR with TME for rectal cancer at Ersta Hospital, Sweden. All patients were treated according to the ERAS program and thereby included. Between 2002 and 2006 15% had a diverting stoma compared to 91 %, 2007 to 2011. RESULTS: One hundred and thirty-nine patients were operated with a diverting stoma at primary surgery (S+), 148 patients were not (S-). The groups were comparable regarding pre- and peroperative data and patients' characteristics. Postoperative morbidity within 30 days after surgery (S+ 53% vs. S- 43%) and hospital stay (S+ 11 days vs. S- 9 days) did not differ. AL occurred in 22% of all patients. In a multivariate analysis, no significant difference in AL was found in relation to the use of a diverting stoma (S+ vs. S-, OR 0.64, 95% CI 0.34-1.19). Eleven patients (8%) in the S+ group underwent relaparotomy versus 22 (15%) in the S- group (p = 0.065). Total overall compliance to the ERAS program was 65%. Patients in S- had faster postoperative recovery. CONCLUSION: A diverting stoma did not affect postoperative morbidity in this large cohort of patients undergoing LAR within an ERAS program. However, the routine use of a diverting stoma could be expected to delay postoperative recovery.

The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes.

BACKGROUND/OBJECTIVES: Obese subjects have increased number of enlarged fat cells that are reduced in size but not in number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity. SUBJECTS/METHODS: Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined 2 years after gastric bypass surgery at a post-obese state (body mass index (BMI) 26±2 kg m(-2), mean±s.d.) and from 14 never-obese women (BMI 25±2 kg m(-2)). Gene expression was analyzed in subcutaneous adipose tissue from nine women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively. RESULTS: The average degree of DNA methylation of all analyzed CpG sites was lower in fat cells from post-obese as compared with never-obese women (P=0.014). A total of 8504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG islands and surrounding shores. The 8504 DMS mapped to 3717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of the genes linked to adipogenesis (that is, 35 of 130) displayed DMS (adjusted P=10(-8)) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared with never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women. CONCLUSIONS: Global CpG hypomethylation and over-representation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women.

Adipose tissue morphology predicts improved insulin sensitivity following moderate or pronounced weight loss.

BACKGROUND: Cross-sectional studies show that white adipose tissue hypertrophy (few, large adipocytes), in contrast to hyperplasia (many, small adipocytes), associates with insulin resistance and increased risk of developing type 2 diabetes. We investigated if baseline adipose cellularity could predict improvements in insulin sensitivity following weight loss. METHODS: Plasma samples and subcutaneous abdominal adipose biopsies were examined in 100 overweight or obese individuals before and 10 weeks after a hypocaloric diet (7±3% weight loss) and in 61 obese subjects before and 2 years after gastric by-pass surgery (33±9% weight loss). The degree of adipose tissue hypertrophy or hyperplasia (termed the morphology value) in each individual was calculated on the basis of the relationship between fat cell volume and total fat mass. Insulin sensitivity was determined by homeostasis model assessment-estimated insulin resistance (HOMAIR). RESULTS: In both cohorts at baseline, subjects with hypertrophy displayed significantly higher fasting plasma insulin and HOMAIR values than subjects with hyperplasia (P<0.0001), despite similar total fat mass. Plasma insulin and HOMAIR were normalized in both cohorts following weight loss. The improvement (delta insulin or delta HOMAIR) was more pronounced in individuals with hypertrophy, irrespective of whether adipose morphology was used as a continuous (P=0.0002-0.027) or nominal variable (P=0.002-0.047). Absolute adipocyte size associated (although weaker than morphology) with HOMAIR improvement only in the surgery cohort. Anthropometric measures at baseline (fat mass, body mass index, waist-to-hip ratio or waist circumference) showed no significant association with delta insulin or delta HOMAIR. CONCLUSIONS: In contrast to anthropometric variables or fat cell size, subcutaneous adipose morphology predicts improvement in insulin sensitivity following both moderate and pronounced weight loss in overweight/obese subjects.

Weight loss prior to bariatric surgery: an updated review of the literature.

BACKGROUND AND AIMS: Prior to bariatric surgery, a preoperative weight-reducing regimen is usually adhered to in most centers. The clinical effects of such a regimen are yet to be determined. MATERIAL AND METHODS: We reviewed the current literature by searching in PubMed for publications reporting clinical effects resulting from a preoperative weight loss regimen prior to bariatric surgery published from January 1, 1995 to April 30, 2014. RESULTS: In total, we identified 23 original publications and 2 review articles which met all inclusion criteria. These were included and fully analyzed with regard to effects of preoperative weight loss. In general, for parameters such as operating time and intraoperative complications including blood loss and recovery, inconsistent data were reported. Most studies included low number of patients and with heterogenic designs, and the results could not form the base for recommendations. However, for outcomes such as postoperative complications and weight development over time, data from large-scale studies and randomized controlled trials suggest beneficial effects following adherence to weight loss prior to bariatric surgery. CONCLUSION: Although a large amount of data in the current literature on the effects of weight loss prior to bariatric surgery are inconsistent for many outcome parameters, recently published results regarding effects on postoperative complications and weight development over time strongly suggest that such a regimen should be recommended. Whether a certain degree of weight loss should be mandatory before being accepted for bariatric surgery is, however, still controversial.

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects.

BACKGROUND: Cardiovascular disease is associated with multiple risk factors including stiff arteries and large adipocytes. Whether the latter two are interrelated is unknown. We aimed to determine whether arterial stiffness is associated with fat cell size and number in subcutaneous or visceral white adipose tissue (WAT). METHODS: A cross-sectional study of 120 obese subjects scheduled for bariatric surgery in whom WAT mass and distribution was assessed by dual-X-ray absorptiometry. Biopsies from visceral (greater omentum) and subcutaneous (abdominal) WAT were obtained to calculate fat cell volume and number. Arterial stiffness was determined as aortic pulse wave velocity (PWV). RESULTS: Visceral adipocyte volume, but not number, was strongly (P<0.0001) and positively correlated with PWV, explaining 20% of the inter-individual variations in this parameter. This relationship remained significant after correction for clinical confounders. PWV correlated positively (r=0.38, P<0.0001) with visceral (but not subcutaneous) WAT mass. Furthermore, PWV was also positively associated with subcutaneous adipocyte volume (r=0.20, P=0.031) and negatively with fat cell number (r=-0.26, P=0.006). However, the relationships between PWV and visceral WAT mass or subcutaneous fat cell size/number became non-significant when controlling for visceral fat cell volume. In a multiple regression analysis to determine the factors that explain variations in PWV, only visceral fat cell volume, age, pulse rate and diastolic blood pressure entered the model, together explaining 42% of the variation in PWV. CONCLUSIONS: Visceral fat cell volume was the only WAT parameter that constituted an independent and significant, positive regressor for arterial stiffness determined by PWV. Although a causal relationship is not established, visceral fat cell volume may explain the well-known correlation between central fat mass, arterial stiffness and cardiovascular risk, at least in severely/morbidly obese subjects.

Waist circumference to assess reversal of insulin resistance following weight reduction after bariatric surgery: cohort and cross-sectional studies.

OBJECTIVE: To validate the use of waist circumference to assess reversal of insulin resistance after weight loss induced by bariatric surgery. DESIGN: In cross-sectional studies, threshold values for insulin resistance were determined with homeostasis model assessment of insulin resistance (HOMA-IR) (algorithm based on fasting plasma glucose and insulin) in 1018 lean subjects and by hyperinsulinemic euglycemic clamp (clamp) in 26 lean women. In a cohort study on 211 patients scheduled for bariatric surgery, HOMA-IR and waist circumference were measured before and 1.5-3 years after weight reduction. In a subgroup of 53 women, insulin sensitivity was also measured using clamp. RESULTS: The threshold for insulin resistance (90th percentile) was 2.21 (mg dl(-1) fasting glucose × mU l(-1) fasting insulin divided by 405) for HOMA-IR and 6.118 (mg glucose per kg body weight per minute) for clamp. Two methods to assess reversal of insulin resistance by measuring waist circumference were used. A single cutoff value to <100 cm for waist circumference was associated with reversal of insulin resistance with an odds ratio (OR) of 49; 95% confidence interval (CI)=7-373 and P=0.0002. Also, a diagram based on initial and weight loss-induced changes in waist circumference in patients turning insulin sensitive predicted reversal of insulin resistance following bariatric surgery with a very high OR (32; 95% CI=4-245; P=0.0008). Results with the clamp cohort were similar as with HOMA-IR analyses. CONCLUSIONS: Reversal of insulin resistance could either be assessed by a diagram based on initial waist circumference and reduction of waist circumference, or by using 100 cm as a single cutoff for waist circumference after weight reduction induced by bariatric surgery.