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Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function of preadipocytes. The transcriptomic profile of visceral adipose tissue preadipocytes collected from Lean, Obese and Obese with T2D was assessed throughout in vitrodifferentiation using RNA sequencing. Reduced Representation Bisulfite Sequencing was used to establish the genome-wide DNA methylation profile of human preadipocytes and 3T3-L1 preadipocytes treated by the inflammatory cytokine Tumour Necrosis Factor-α (TNF-α) or palmitate. While preadipocytes from all obese subjects (Obese+Obese T2D), compared to those of Lean, were transcriptionally different in response to differentiation in culture, preadipocytes from Obese T2Dshowed impaired insulin signalling and a further transcriptomic shift towards altered adipocyte function. Cultures with a lower expression magnitude of adipogenic genes throughout differentiation (PLIN1, CIDEC, FABP4, ADIPOQ, LPL, PDK4, APOE, LIPE, FABP3, LEP, RBP4and CD36) were associated with DNA methylation remodelling at genes controlling insulin sensitivity and adipocytokine signalling pathways. Prior incubation of 3T3-L1 preadipocyteswith TNF-α or palmitate markedly altered insulin responsiveness and metabolic function in the differentiated adipocytes, and remodelled DNA methylation and gene expression at specific genes, notably related to PPAR signalling. Our findings that preadipocytes retain the memory of the donor in culture and can be reprogrammed by extracellular factors support a mechanism by which adipocyte precursors are epigenetically reprogrammed in vivo. Epigenetic reprogramming of preadipocytes represents a mechanism by which metabolic function of visceral adipose tissue may be affected in the long term by past exposure to obesity- or T2D-specific factors.

Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site.

Background: Transanal endoscopic microsurgery (TEM) represents a choice of treatment in patients with neoplastic lesions in the rectum. When TEM fails, completion total mesorectal excision (cTME) is often required. However, a concern is whether cTME increases the rate of abdominoperineal resections (APR) and is associated with higher risk of incomplete mesorectal fascia (MRF) resection. The aim of this study was to compare outcomes of cTME with primary TME (pTME) in patients with rectal cancer. Methods: This was a nationwide study on all patients with cTME from the Danish Colorectal Cancer Group database between 2005 and 2015. Patients with cTME were compared to patients with pTME after propensity score matching (matching ratio 1:2). Matching variables were age, gender, tumor distance from anal verge, American Society of Anesthesiologists (ASA) score and American Joint Committee on Cancer (AJCC) stage. Results: A total of 60 patients with cTME were compared with 120 patients with pTME. Patients with cTME experienced more intraoperative complications as compared to pTME patients (18.3% vs. 6.7%, p= 0.021). However, there was no difference in the rate of perforations at or near the tumor/previous TEM site (6.7% vs. 2.5%, p= 0.224), conversion to open surgery (p= 0.733) or 30-day morbidity (p= 0.86). On multivariate analysis, cTME was not a risk factor for APR (OR 2.49; 95% CI 0.95–6.56; p= 0.064) or incomplete MRF (OR 1.32; 95% CI 0.48–3.63; p= 0.596). There was no difference in the rate of local recurrence between cTME and pTME (5.2% vs. 4.3%, p= 0.1), distant metastases (6.8% vs. 6.8%, p= 1), or survival (p= 0.081). The mean follow-up time was 6 years. Conclusion: In our study, the largest so far on the subject, we find no difference in postoperative short- or long-term outcomes between cTME and pTME.

Background: A contralateral occult inguinal hernia is frequently observed in patients planned for a unilateral laparoscopic inguinal hernia repair. Surgical strategy for contralateral groin management in patients scheduled for an endo-laparoscopic unilateral inguinal hernia repair is controversial and based on questionable evidence. This study aimed to gather international opinion concerning the surgical strategy for the contralateral asymptomatic side when no hernia or lipoma is clinically evident at the preoperative examination or anamnesis.Methods: An international Internet-based questionnaire was sent to all the members of the European Hernia Society, the Americas Hernia Society, and the Asia Pacific Hernia Society. The clinical scenario for responders was a patient with a unilateral symptomatic inguinal hernia planned for endo-laparoscopic repair with no preoperative symptoms/lump on the contralateral side.Results: A total of 640 surgeons replied (response rate = 26%), of whom 506 were included for analysis. Most surgeons had performed > 300 repairs. The preferred surgical technique was evenly distributed between laparoscopic total extraperitoneal repair and laparoscopic transabdominal preperitoneal repair. In total, 54% preferred to implant a prophylactic mesh on the contralateral side when an occult hernia was found, 47% when a lipoma was found, and 6% when no occult hernia/lipoma was identified.Conclusions: Mesh implementation was preferred by half of the endo-laparoscopic hernia surgeons for a contralateral occult hernia and/or lipoma. Although not supported by strong evidence, mesh implantation on the asymptomatic contralateral side might be cost-effective and perhaps beneficial in the long term but could be offset by increased risk of chronic pain and sexual dysfunction.

Backgrounds: The optimal surgical strategy for the treatment of chronic pain after inguinal hernia repair is controversial and based on relatively weak evidence. The purpose of this study was to analyze pain-related functional impairment using a simplified clinical treatment algorithm for a standardized surgical treatment. The algorithm was predefined, and the indication to operate was based on strict criteria.Methods: This was a prospective, non-controlled, explorative study. The pain operation was either open triple neurectomy with total mesh removal or laparoscopic retroperitoneal triple neurectomy. A clinically relevant postoperative change was defined as ⩾25% change from the baseline level. Primary outcome was pain-related impairment of physical function using the Activity Assessment Scale. Secondary outcomes included Individual Patient-Reported Outcome Measures, Hospital Anxiety and Depression Scale, and PainDETECT Questionnaire.Results: A total of 240 patients were referred (2016–2019). Sixty-six patients were included for the analysis. A total of 25% of referred patients were offered a pain operation. Follow-up was a median 3 months (range: 3–13). Activity Assessment Scale scores were clinically relevant improved in 43 patients (68%), not clinically relevant different in 19 (30%), and clinically relevant worsened in one (2%). Secondary outcome scores were all significantly improved (P< 0.05) except for the risk of postoperative depression (P= 0.092). Fifty-one patients (77%) reported that chronic groin pain was reduced after the operation.Conclusions: Pain-related functional impairment was improved with clinical relevance in roughly 70% of patients through a simplified clinical algorithm for surgical treatment of severe chronic pain after an inguinal hernia repair.

Background and objective: Bariatric surgery is a major event associated with psychological changes such as improvements in self-esteem, increased autonomy, and better self-value. Such changes could affect the patient’s interpersonal relationships; however, little is known about the impact of bariatric surgery on changes in relationship status. In this paper, we aim to test the hypothesis that bariatric surgery is associated with changes in interpersonal relationships such as becoming single for those who were in a relationship or entering a relationship among those who were single before surgery. Methods: This register-based cohort study consisted of 12,493 patients undergoing bariatric surgery (95% gastric bypass) from 2005 to 2013 and a reference group of 15,101 individuals with obesity between the age of 18–63 with a body mass index between 32 and 60 kg/m2. Transitions between married, divorced, widowed, never-married single, and living with a partner without being married were analyzed by Poisson regression. Additionally, the outcome was dichotomized, and transitions between being single and being in a relationship were also analyzed. All analyses were weighted using inverse probability of treatment weighting based on propensity scores. Results: The overall incidence rate ratio (IRR) of changing status from being single to in a relationship was 2.03 (95% CI: 1.18–2.28), and the overall IRR of changing status from being in a relationship to single was 1.66 (95% CI: 1.50–1.83). Conclusion: Bariatric surgery is associated with a higher chance of finding a partner among single individuals, and a higher risk of separating from a partner among individuals in a relationship.

Duration of convalescence after inguinal hernia repair is of major socio-economic interest and an often reported outcome measure. The primary aim was to perform a critical analysis of duration of convalescence from work and activity and secondary to identify risk factors for unexpected prolonged convalescence after laparoscopic inguinal hernia repair. A qualitative systematic review was conducted. PubMed, Embase and the Cochrane database were searched for trials reporting convalescence after laparoscopic inguinal hernia repair in the period from January 1990 to January 2016. Furthermore, snowball search was performed in reference lists of identified articles. Randomized controlled trials and prospective comparative or non-comparative trials of high quality were included. Trials with ≥100 patients, >18 years of age and manuscripts in English were included. Scoring systems were used for assessment of quality. The literature search identified 1039 papers. Thirty-four trials were included in the final review including 14,273 patients. There was overall a large variation in duration of convalescence. Trials using non-restrictive recommendations of 1–2 days or “as soon as possible to return to all activities” reported overall a shorter duration of convalescence compared with trials not using recommendations for convalescence. Strenuous physical activity at work, strenuous leisure activity and patients with expectations of a prolonged period of convalescence may be risk factors for prolonged convalescence extending more than a few days after laparoscopic inguinal hernia repair. Patients should be recommended a duration of 1–2 days of convalescence after laparoscopic inguinal hernia repair. Short and non-restrictive recommendations may reduce duration of convalescence without increasing risk of pain, complications or recurrence rate.

Conventional laparoscopic cholecystectomy (CLC) is regarded as the gold standard for cholecystectomy. However, single-incision laparoscopic cholecystectomy (SLC) has been suggested to replace CLC. This study aimed at comparing long-term incidences of port-site hernia and chronic pain after SLC versus CLC. We conducted a matched cohort study based on prospective data (Jan 1, 2009–June 1, 2011) from the Danish Cholecystectomy Database with perioperative information and clinical follow-up. Consecutive patients undergoing elective SLC during the study period were included and matched 1:2 with patients subjected to CLC using pre-defined criteria. Follow-up data were obtained from the Danish National Patient Registry, mailed patient questionnaires, and clinical examination. A port-site hernia was defined as a repair for a port-site hernia or clinical hernia located at one or more port sites. In total, 699 patients were eligible and 147 patients were excluded from the analysis due to pre-defined criteria. The rate of returned questionnaires was 83%. Thus, 552 (SLC, n= 185; CLC, n= 367) patients were analyzed. The median observation time was 48 months (range 1–65) after SLC and 48 months (1–64) after CLC (P= 0.940). The total cumulated port-site hernia rate was 4 % and 6 % for SLC and CLC, respectively (P= 0.560). Incidences of moderate/severe chronic pain were 4 % and 5 % after SLC and CLC, respectively (P= 0.661). We found no difference in long-term incidence of port-site hernia or chronic pain after SLC versus CLC.

IMPORTANCE: In Denmark approximately 10 000 groin hernias are repaired annually, of which 2% to 4% are femoral hernias. Several methods for repair of femoral hernias are used including sutured repair and different types of mesh repair with either open or laparoscopic techniques. The use of many different approaches reflects a rather low level of evidence for the best method of repair. Randomized clinical trials are lacking. Large, prospective cohort studies are an alternative way of acquiring improved evidence regarding the best type of repair. OBJECTIVE: To investigate the reoperation rate after laparoscopic vs open femoral hernia repair, analyzing data from a nationwide database. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted. Data on femoral hernia repairs registered in the Danish Hernia Database from January 1998 until February 2012 were extracted and analyzed. All repairs were followed in the database and analyzed for reports of reoperation, which were used as a proxy for recurrence. Femoral hernia recurrence and inguinal hernia occurrence after the index repair were analyzed. EXPOSURE: Repair of a femoral hernia. MAIN OUTCOMES AND MEASURES: Reoperation for a femoral hernia. RESULTS: A total of 3970 primary femoral hernia repairs were analyzed; 27.3% occurred in men. There were 2413 elective repairs (60.8%) and 1557 emergency procedures (39.2%). In a multivariate analysis, laparoscopic repair was found to result in reduced risk of reoperation (hazard ratio, 0.33; 95% CI, 0.09-0.95) compared with open repair. The risk of reoperation was higher in women (hazard ratio, 1.95; 95% CI, 1.10-3.45). Furthermore, the laparoscopic approach seemed to reduce the risk of subsequent occurrence of an inguinal hernia in the same groin. CONCLUSIONS AND RELEVANCE: Laparoscopic repair of a femoral hernia reduces the risk of reoperation for a recurrence compared with open repair. The results from this study support the guidelines recommending the use of the laparoscopic approach for repair of femoral hernias.

Surgical outcome results after repair for parastomal hernia are sparsely reported and based on small-scale studies.

Preliminary studies have indicated clinical advantages of mesh fixation using fibrin glue in transabdominal preperitoneal groin hernia repair (TAPP)  compared with tack fixation. The aim of this randomized double-blinded, controlled, clinical trial is to compare fibrin glue with tacks fixation of mesh during TAPP.One hundred and twelve men with unilateral inguinal hernia were enrolled. Primary outcome was pain during coughing on postoperative day 1. Secondary outcomes were postoperative scores of pain at rest, discomfort, and fatigue (day 1 and cumulated day 0–3), incidence of moderate/severe nausea and/or vomiting, foreign-body sensation, and recurrence after 6 months. Outcome measures were assessed by visual analogue scale (VAS, 0–100 mm), verbal rating scale (no, light, moderate or severe) and numerical rating scales (NRS, 1–10).One hundred patients were available for analysis. The fibrin group (n= 50) had significantly less pain during coughing on day 1 compared with the tacks group (n= 50) [median 23 (range 0–80) vs 35 (2–100) mm] (p= 0.020). Moreover, day 1 scores and all cumulated scores of pain during rest, discomfort, and fatigue were significantly lower in the fibrin group compared with the tacks group (all p-values ≤ 0.02). There was no significant difference in the incidence of nausea and/or vomiting (p> 0.05) or recurrence (fibrin glue n= 2, tacks n= 0, p= 0.241). Incidence of foreign-body sensation was significantly lower in the fibrin group at 1 month (p= 0.006).Fibrin glue compared with tacks fixation improved the early postoperative outcome after TAPP. The trial was registered at clinicaltrials.gov NCT01000116.

Abstract: Background: Previous studies have shown different pain characteristics in different types of laparoscopic operations, but pain pattern has not been studied in detail after laparoscopic inguinal hernia repair. To optimise preoperative patient information and postoperative analgesic treatment the present study investigated postoperative pain in terms of time course, pain intensity and individual pain components during the first 4 days after transabdominal preperitoneal hernia repair (TAPP). Methods: The study was a single-centre prospective trial including 50 consecutive male patients with primary or recurrent inguinal and/or femoral hernia undergoing elective repair. Several pain components (visceral pain, incisional pain and shoulder pain) were studied as well as pain at the three different trocar incisions. Pain was recorded before operation and on a daily basis during the first four postoperative days using a visual analogue and a verbal rating scale. We used 1 × 12 and 2 × 5 mm trocars for TAPP. Results: A total of 46 patients were available for analyses (age median 58 years, range 27–69 years). Visceral pain dominated significantly compared with incisional pain (P < 0.01), which again dominated over shoulder pain intensity and incidence (P < 0.01). Pain intensity did not significantly differ between different trocar incisions (5 and 12 mm) (P > 0.05). The overall pain intensity (a conglomerate of the different pain components) was most intense 3 h after TAPP and declined to preoperative levels on day 3 (P > 0.5). Conclusion: Pain was most intense 3 h after the operation and declined to low levels within the first 3 days. Visceral pain was by far the dominating pain component compared with incisional and shoulder pain.

Abstract: Background: The risk of trocar site hernia (TSH) may be 0–22%, but no large scaled data with long-term follow-up are available. The purpose of this study was to estimate the long-term risk of TSH repair. Methods: All patients in Denmark who underwent a laparoscopic procedure in 1997 were identified using the Danish National Patient Register and followed during a 12-year period. Hospital records for patients with an incisional or umbilical hernia repair were tracked and manually analyzed for possible relationship between reoperation and the initial laparoscopy. Results: We included 7,626 patients. During follow-up, we identified 95 patients with TSH repair with a cumulative risk of 1.3% being lowest after minor gynecological procedures and appendectomy and highest after fundoplication, cholecystectomy, and oophorectomy. The TSH was mainly at the umbilicus site (n = 63, 66%), and 15 (16%) of the TSH repairs were performed as an emergency procedure. Conclusions: The long-term risk of TSH repair is low, but the risk of an emergency operation for TSH is relatively high, which suggests that all patients with a TSH should be offered elective repair.

The need for acquisition of specific laparoscopic skills has emphasized the role of a preclinical laboratory-training program. However, for laparoscopic inguinal hernia repair with a steep learning curve, especially for totally extraperitoneal repair, preclinical skill training remains a challenge. A standardized preclinical resident training program in endoscopic surgery is described. Also, a standardized clinical training program is proposed with systematic dissection in 10 different consecutive steps for totally extraperitoneal inguinal hernia repair. Continuous mentoring by an expert is an absolute prerequisite to the success of this training program. In this way, the learning period may be drastically reduced to approximately 30 procedures, in whom the resident progressively performs more and more of the different steps, and ultimately the complete procedure. Validation studies at different institutions are starting up to demonstrate the additional value of this training program.

Abstract: Background: Studies on the circadian variation in bodily functions and sleep are important for understanding the pathophysiological processes in the postoperative period. We aimed to investigate changes in the circadian variation in activity after minimally invasive surgery (laparoscopic cholecystectomy, LC) and major abdominal surgery (MAS) and if these changes correlated with postoperative subjective recovery measures. Methods: We examined 76 and 44 patients undergoing LC and MAS, respectively, for 4 days before and after surgery. Subjective recovery parameters were assessed by visual analogue scale (sleep quality, general well-being and pain) and fatigue was measured by a ten-point fatigue scale. The activity levels of the patients were monitored by actigraphy (a wrist-worn device measuring patient activity). Measures of circadian activity level [interday stability (IS), intraday variability (IV) and the amplitude (AMP)] were derived after nonparametric analysis of activity data. Results: IS was significantly reduced both after MAS (0.72 before surgery and 0.58 after surgery, p < 0.0001) and after LC (0.76 before surgery and 0.66 after surgery, p < 0.0001). The IS dropped significantly more following MAS surgery compared with following LC surgery (p < 0.001). The fragmentation of the rhythm IV increased and the amplitude dropped significantly after both LC and MAS surgery. Subjective recovery parameters were worse after MAS when compared with LC, and correlated significantly to the circadian activity parameters (IS, IV and AMP). Conclusion: Severely disturbed circadian activity parameters was found after both LC and MAS with worse changes after MAS. Measures of circadian activity pattern analyses correlated significantly with postoperative subjective recovery parameters.

Abstract: Background: Intravenous administration of dexamethasone 90 min before laparoscopic cholecystectomy improves surgical outcome but may be impractical. The objective of this study was to assess the clinical efficacy of oral self-administration of prednisone 2 h before ambulatory laparoscopic cholecystectomy. Methods: In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain 24 h after surgery and secondary outcomes were fatigue and malaise 24 h after surgery. Outcome parameters were registered before operation, on the day of operation, and the following two days. Analgesic and antiemetic requirements were registered, and nausea and vomiting were assessed twice within the first 24 h. Side-effects and 30-day follow-up for morbidity were registered. Results: Data from 184 patients were available for statistical analysis. There were no significant differences in side-effects or complications between the surgical groups (P > 0.05). No significant intergroup differences in 24-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion: There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy.

Conversion of laparoscopic cholecystectomy to laparotomy may increase postoperative complications and convalescence and should therefore be avoided when possible. The authors present three technical tips that may prevent unnecessary conversion to open procedure (suspension sutures in the gallbladder, use of the Endo Paddle Retract (United States Surgical Corp., Norwalk, CT, USA) to depress abdominal viscera, and subtotal cholecystectomy). These methods may be used in situations in which there is no operative risk for complications, such as bile duct injury, but technical aspects of the operation normally would have resulted in conversion to laparotomy.

Objective. Assessment of early postoperative activity is important in the documentation of improvements of peri-operative care. This study was designed to validate computerized activity-based monitoring of physical activity and sleep (actigraphy) in patients after abdominal surgery. Methods. The study included twelve hospitalized patients after major abdominal surgery studied on day 2 to 4 after operation and twelve unhospitalized healthy volunteers. Measurements were performed for 24 consecutive hours. The actigraphy measurements were compared with self-reported activity- and sleep registration. The actigraphy output was obtained by the zero-crossing mode (ZCM) and time-above-threshold mode (TATM). Results. The overall results showed comparable mean agreement between actigraphy and self-reported activity registrations for patients of 80% (SD 12%) and volunteers of 84% (SD 6%) (p = 0.15). In both study groups, all correlation coefficients between actigraphy measurements and self-reported activity data were statistically significant (rs values for patients 0.4 to 0.8 and volunteers 0.6 to 0.9). A higher mean agreement between automated actigraphy sleep detection and self-reported sleep registration were found in the volunteers (85%, SD 15%) compared with the patients (77%, SD 11%) (p < 0.05). The mean activity value awake was higher in the volunteers than in the patients (p < 0.05). Conclusion. Computerized activity monitoring by actigraphy is a reliable and easy method for monitoring physical activity and sleep-wake cycles after major abdominal surgery.

Objectives. This study investigated the velocity distribution across the natural mitral valve.