Melatonin decreases human adipose tissue insulin sensitivity.

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Full Laparoscopic Vascular Reconstruction for Portal Tumoral Invasion During a Right Hepatectomy Using the Caudal Approach.

BACKGROUND: Laparoscopic liver surgery has progressively evolved. Consequently, liver procedures are increasingly performed laparoscopically, particularly in experienced centers. However, vascular resection and reconstruction still are considered a limitation for laparoscopy1 due to the risk of bleeding and the technical difficulty. METHODS: A 72-year-old woman with a history of colorectal cancer had a 10 cm metastasis diagnosed in the right hemiliver with tumoral invasion of the right portal branch and tumor thrombus advancing to the portal confluence. After adjuvant chemotherapy and with stable disease, surgical resection was planned.2,3 Tips to avoid portal stenosis were carefully followed. RESULTS: The operation was performed with a fully laparoscopic procedure. To minimize manipulation, an in situ right hepatectomy was performed.4 The right hepatic artery was dissected and ligated. The liver transection was guided with a caudal approach of the middle hepatic vein.5 The right biliary duct was then divided, achieving an excellent exposure of the portal bifurcation. The main and left portal trunks were occluded with vascular clamps, and the right portal vein was sharply divided with scissors. The stump was sutured to minimize backflow bleeding and to cover the tumor thrombus. Then, the portal opening was transversally sutured with a 5/0 running suture. The clamps were released, and the authors observed no bleeding and an adequate caliber with no stenosis. The procedure was completed in the standard fashion. The postoperative course was uneventful, and the woman was discharged on postoperative day 3. No early or late complications were observed.6 CONCLUSIONS: In selected cases, patients who require vascular resection and reconstruction during hepatectomies can benefit from the advantages of a laparoscopic approach.

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

INTRODUCTION: rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. MATERIAL AND METHODS: this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.

Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients.

Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changes with age. SAT and VAT biopsies were obtained from obese individuals during gastric bypass surgeries [ n = 16; body mass index: 44.8 ± 11.4 kg/m2; age: 44 ± 9 yr (range: 30-58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase ( BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes ( P > 0.05). With increasing age, the circadian period decreased in mature adipocytes ( P = 0.005) (ß = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCN signaling.-Kolbe, I., Carrasco-Benso, M. P., López-Mínguez, J., Luján, J., Scheer, F. A. J. L., Oster, H., Garaulet, M. Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients.

Isoperistaltic versus antiperistaltic ileocolic anastomosis. Does it really matter? Results from a randomised clinical trial (ISOVANTI).

BACKGROUND: Right hemicolectomy is a very common surgery. Many studies compare different options for laparoscopic ileocolic anastomoses: intra- or extracorporeal; handsewn or stapled; side-to-side or end-to-side. However, there are no studies about the influence that peristalsis could have on this anastomosis. The aim of this study is to compare safety and feasibility of isoperistaltic and antiperistaltic anastomosis in terms of postoperative morbidity and mortality between both groups. The secondary endpoint is to compare long-term functional outcomes (chronic diarrhoea) and quality of life (GIQLI questionnaire) after a 1-year follow-up period. METHODS: A double-blind, randomised, prospective trial in patients undergoing scheduled surgery for right colon cancer with laparoscopic right hemicolectomy and isoperistaltic (ISO) or antiperistaltic (ANTI) ileocolic anastomoses. RESULTS: Hundred and eight patients were included in the study. Patients were randomised either to isoperistaltic or antiperistaltic configuration (54 ISO/ANTI). No significant differences in baseline variables were found. No differences in surgical time (130 [120-150] min ISO vs. 140 [127-160] ANTI, p = 0.481), nor in anastomotic time (19 [17-22] vs. 20 [16-25], p = 0.207) and nor in postoperative complications: 37.0% ISO versus 40.7% ANTI, (p = 0.693) were found. There were no differences in postoperative ileus (p = 0.112) nor in anastomotic leakage (3.7% vs. 5.56%, p = 1.00). Differences in "time to first flatus" and "time to first deposition" were found in favour of the antiperistaltic group (p = 0.004 and p = 0.017). Anastomotic configuration did not influence hospital stay (3 days [2-6] isoperistaltic vs. 3 [2-4] antiperistaltic, p = 0.236). During follow-up, there were no differences between the two groups at 1, 6 and 12 months (p = 0.154, p = 0.498 and p = 0.683), nor in chronic diarrhoea rates in GIQLI scores (24% ISO vs. 31.4% ANTI, p = 0.541). CONCLUSIONS: The isoperistaltic and antiperistaltic ileocolic anastomosis present similar results in terms of performance, safety and functionality. However, further studies must be carried out in order to assess relationship between postoperative ileus and anastomosis configuration. TRIAL REGISTRATION: Randomised Clinical trial (Identifier: NCT02309931).

Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P < 0.00001). Insulin sensitivity reached its maximum (acrophase) around noon, being 54% higher than during midnight (P = 0.009). The amplitude of the rhythm was positively correlated with in vivo sleep duration (r = 0.53; P = 0.023) and negatively correlated with in vivo bedtime (r = -0.54; P = 0.020). No circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

V-Y advancement flaps for extensive perianal defect repair. / El colgajo V-Y como método de reparación de defectos perianales extensos.

OBJECTIVES: Some perianal pathologies require aggressive surgery that will need techniques to allow to re-establish the integrity of the perianal region. The purpose is to analyze short and long term results after perineal reconstruction with V-Y flaps. METHODS: A retrospective review of prospectively collected database was conducted at Virgen de la Arrixaca's Hospital in Murcia (España) between January 2000 and December 2013. The study includes all patients who underwent a perineal reconstruction with V-Y flaps. Demographic and surgical data and short-/long- term morbidity was recorded. RESULTS: 10 patients were included, 6 males and 4 females. The average age was 58,1±17,4 years. Surgical indication included both malignant and benign pathologies. Operating time was 143,5±41,3min. R0 resection was performed in all cases although histopathological analysis showed involvement of the deeper margin in 3 cases. Length of hospital stay was 7,8±7,6 days. Regarding complications: 6 patients had partial dehiscence of the flap. None of the patients lost the flap completely. The most frequent late complication was anal stenosis (n=4). Follow up showed total continence in 7 patients. Two patients had variable fecal and/or flatus incontinence. A colostomy was made in one case due to severe incontinence. CONCLUSIONS: V-Y flaps are an effective and feasible technique to cover large perianal defects after aggressive surgeries. However, this technique is not free of postoperative morbidity.

Single-port Colectomy VS Multi-port Laparoscopic Colectomy. Systematic Review and Meta-analysis of More Than 2800 Procedures.

OBJECTIVE: Multiport laparoscopic surgery in colon pathology has been demonstrated as a safe and effective technique. Interest in reducing aggressiveness has led to other procedures being described, such as SILS. The aim of this meta-analysis is to evaluate feasibility and security of SILS technique in colonic surgery. MATERIAL AND METHODS: A meta-analysis of twenty 7 observational studies and one prospective randomized trial has been conducted by the use of random-effects models. RESULTS: A total amount of 2870 procedures was analyzed: 1119 SILS and 1751 MLC. We did not find statistically significant differences between SILS and MLC in age (WMD 0.28 [-1.13, 1.68]; P=.70), BMI (WMD -0.63 [-1.34, 0.08]; P=.08), ASA score (WMD -0.02 [-0.08, 0.04]; P=.51), length of incision (WMD -1.90 [-3.95, 0.14]; P=.07), operating time (WMD -2.69 (-18.33, 12.95]; P=.74), complications (OR=0.89 [0.69, 1.15]; P=.37), conversion to laparotomy (OR=0.59 [0.33, 1.04]; P=.07), mortality (OR=0.91 [0.36, 2.34]; P=.85) or number of lymph nodes harvested (WMD 0.13 [-2.52, 2.78]; P=.92). The blood loss was significantly lower in the SILS group (WMD -42.68 [-76.79, -8.57]; P=.01) and the length of hospital stay was also significantly lower in the SILS group (WMD -0.73 [-1.18, -0.28]; P=.001). CONCLUSION: Single-port laparoscopic colectomy is a safe and effective technique with additional subtle benefits compared to multiport laparoscopic colectomy. However, further prospective randomized studies are needed before single-port colectomy can be considered an alternative to multiport laparoscopic surgery of the colon.

The learning curve of laparoscopic treatment of rectal cancer does not increase morbidity.

INTRODUCTION: The treatment of rectal cancer via laparoscopy is controversial due to its technical complexity. Several randomized prospective studies have demonstrated clear advantages for the patient with similar oncological results to those of open surgery, although during the learning of this surgical technique there may be an increase in complications and a worse prognosis. OBJECTIVE: Our aim is to analyze how the learning curve for rectal cancer via laparoscopy influences intra- and postoperative results and oncological markers. A retrospective review was conducted of the first 120 patients undergoing laparoscopic surgery for rectal neoplasia. The operations were performed by the same surgical team with a wide experience in the treatment of open colorectal cancer and qualified to perform advanced laparoscopic surgery. We analyzed sex, ASA, tumour location, neoadjuvant treatment, surgical technique, operating time, conversion, postoperative complications, length of hospital stay, number of lymph nodes, stage and involvement of margins. RESULTS: Significant differences were observed with regard to surgical time (224 min in the first group, 204 min in the second group), with a higher rate of conversion in the first group (22.5%) than in the second (11.3%). No significant differences were noted for rate of conservative sphincter surgery, length of hospital stay, post-surgical complications, number of affected/isolated lymph nodes or affected circumferential and distal margins. CONCLUSIONS: It is possible to learn this complex surgical technique without compromising the patient's safety and oncological outcome.

Randomized prospective study to compare laparoscopic appendectomy versus umbilical single-incision appendectomy.

INTRODUCTION: The use of single-incision laparoscopic surgery may represent an improvement over conventional laparoscopic surgery. In recent years, more and more articles have been published demonstrating the feasibility of this approach. Hence, for this reason, we present this randomized prospective study to compare the 2 techniques. METHODS: Between September 2009 and December 2010, a total of 184 patients with a diagnosis of acute appendicitis and indicated for surgery were included in the study, of whom, 91 received an appendectomy via a single umbilical incision and 93 via conventional laparoscopy. The study protocol was approved by the ethical committee of the Virgen de la Arrixaca University Hospital (Murcia). The study was registered on ClinicalTrials.gov with inscription number NCT0151529. All the operations were performed by the same team of surgeons. RESULTS: As far as the demographical results of the study population are concerned, there were no significant differences between the 2 groups for age, weight, sex, body mass index, and removed appendix type. Operating time was longer with the single-port approach: 38.13 ± 13.49 versus 32.12 ± 12.44 minutes (P = 0.02). Significant differences were observed for postoperative pain, which was measured on the visual analog scale, with less pain reported in the single-incision group: 2.76 ± 1.64 versus 3.78 ± 1.76 (P < 0.001). There were no significant differences between the 2 groups for early and late complications and lengths of hospital stay measured in postoperative hours. CONCLUSIONS: The transumbilical single-port approach is seen as a feasible technique for performing appendectomy. It does not increase the rate of complications and represents a possible alternative to conventional laparoscopic appendectomy.

[Afferent loop stimulation prior to ileostomy closure]. / Estimulación del asa eferente previa al cierre de ileostomía.

There is a 17% complications rate after ileostomy closure, with paralytic ileus being the most common. With the aim of reducing this complication, stimulation via the afferent loop was performed daily for the 2 weeks prior to the stoma.

Habitual nappers and non-nappers differ in circadian rhythms of LIPE expression in abdominal adipose tissue explants.

Background and purpose: Napping is a widespread practice worldwide and has in recent years been linked to increased abdominal adiposity. Lipase E or LIPE encodes the protein hormone-sensitive lipase (HSL), an enzyme that plays an important role in lipid mobilization and exhibits a circadian expression rhythm in human adipose tissue. We hypothesized that habitual napping may impact the circadian expression pattern of LIPE, which in turn may attenuate lipid mobilization and induce abdominal fat accumulation. Methods: Abdominal adipose tissue explants from participants with obesity (n = 17) were cultured for a 24-h duration and analyzed every 4 h. Habitual nappers (n = 8) were selected to match non-nappers (n = 9) in age, sex, BMI, adiposity, and metabolic syndrome traits. Circadian LIPE expression rhythmicity was analyzed using the cosinor method. Results: Adipose tissue explants exhibited robust circadian rhythms in LIPE expression in non-nappers. In contrast, nappers had a flattened rhythm. LIPE amplitude was decreased in nappers as compared with non-nappers (71% lower). The decrease in amplitude among nappers was related to the frequency of napping (times per week) where a lower rhythm amplitude was associated with a higher napping frequency (r = -0.80; P = 0.018). Confirmatory analyses in the activity of LIPE's protein (i.e., HSL) also showed a significant rhythm in non-nappers, whereas significance in the activity of HSL was lost among nappers. Conclusion: Our results suggest that nappers display dysregulated circadian LIPE expression as well as dysregulated circadian HSL activity, which may alter lipid mobilization and contribute to increased abdominal obesity in habitual nappers.

Laparoscopic radical hepatectomy and lymphadenectomy for incidental gallbladder cancer. Surgical technique with ICG fluorescence enhancement.

BACKGROUND: Radical re-resection has been demonstrated beneficial in incidental gallbladder cancer (iGBC) stages ≥ pT1b [1]. Anatomical resection (AR) of segments IVb-V is recommended, particularly for iGBC and liver-sided tumors [2]. Laparoscopically, this is a challenging procedure, as well as the regional lymphadenectomy, since inflammation from previous surgery can hinder identification of extrahepatic bile ducts. This difficult minimally invasive procedure, facilitated with indocyanine green (ICG) fluorescence enhancement [3] is herein didactically demonstrated. METHODS: A 73 y. o. female patient underwent laparoscopic cholecystectomy for cholelithiasis. An iGBC -pT2b with positive cystic node-was found. Completion radical surgery was decided. Before surgery, 1.5mg of ICG was intravenously administered. A regional lymphadenectomy (stations 5-8-9-12-13) was safely performed: ICG allowed for bile duct visualization despite scarring from previous procedure. AR (IVb-V) was performed based on a glissonian-pedicle approach. After completing the procedure, a new dose of ICG was administered to discard ischemic areas in the remnant. RESULTS: Total operative time was 359 min. Intermittent Pringle maneuver resulted in <50 ml bleeding. Hospital stay was 3 days. Pathological examination revealed no residual tumor in the liver bed. Ten lymph nodes were resected; 3 of them (2 retroportal and 1 common hepatic artery) showing tumoral invasion. After surgery, 6 cycles of adjuvant chemotherapy (Gemcitabine-Oxaliplatin) was administered. CONCLUSIONS: Laparoscopic radical surgery (AR of segments IVb-V plus regional lymphadenectomy) for iGBC is feasible and safe [4]. ICG fluorescence can be of help to identify hilar structures and rule out areas of ischemia.

Factor Structure of the AUDIM-M Dimensional Self-Concept Questionnaire in Mexican Adolescents.

Self-concept is one of the most relevant variables in the field of personality, and a negative self-perception can pose a risk to the adolescent's development. The present study aimed to analyze the psychometric properties proposed by Aguirre and collaborators for the dimensional self-concept questionnaire (AUDIM-M). The total sample was 560 adolescents from the city of Chihuahua, Chihuahua, with a mean age of 12.96 ± 0.88 years. The factor structure of the questionnaire was analyzed using confirmatory factor analysis. The analyses show that a four-factor structure is viable and adequate (GFI 0.964; RMSEA 0.057; CFI 0.950). The four-factor structure (personal self-concept, physical self-concept, social self-concept, and academic self-concept), according to statistical and substantive criteria, shows adequate indicators of reliability and validity adjustment. The model obtained coincides with that proposed by Aguirre et al. Improving adolescents' self-concept undoubtedly contributes to their quality of life, hence the need for valid and reliable instruments for its measurement; this study could be a first approach for future research.