Publications by authors named "Silecchia Gianfranco"

114 Publications

Transhiatal Migration After Laparoscopic Sleeve Gastrectomy: Myth or Reality? A Multicenter, Retrospective Study on the Incidence and Clinical Impact.

Obes Surg 2021 Apr 9. Epub 2021 Apr 9.

Division of General Surgery & Bariatric Center of Excellence-IFSO EC, Department of Medico- Surgical Sciences and Biotechnologies, "La Sapienza" University of Rome, Rome, Italy.

Purpose: Only anecdotally reported, intrathoracic migration (ITM) represents an unacknowledged complication after sleeve gastrectomy (LSG) contributing to gastroesophageal reflux disease (GERD) development, both recurrent and de novo. The primary endpoint of this study was to evaluate the incidence of postoperative ITM ≥ 2 cm; the secondary endpoint was to determine the relationships between ITM, GERD, endoscopic findings, and percentage of patients requiring surgical revision.

Materials And Methods: A retrospective, multicenter study on prospective databases was conducted, analyzing LSGs performed between 2013 and 2018. Inclusion criteria consisted of primary operation; BMI ranging 35-60 kg/m; age 18-65 years; minimum follow-up 24 months; and postoperative UGIE, excluding concomitant hiatal hernia repair. Esophageal manometry and 24-h pH-metry were indicated, based on postoperative questionnaires and UGIE; patients with GERD due to ITM, and non-responders to medical therapy, were converted to R-en-Y gastric bypass (RYGB).

Results: An ITM ≥ 2cm was postoperatively diagnosed in 94 patients (7% of 1337 LSGs), after mean 24.16 ± 13.6 months. Postoperative esophagitis was found in 29 patients vs. 15 initially (p=0.001), while GERD was demonstrated in 75 (vs. 20 preoperatively, p< 0.001). Fifteen patients (16%) underwent revision to RYGB with posterior cruroplasty. Seventeen patients with severe GERD presented improvement of endoscopic findings and clinical symptoms as a result of conservative therapy.

Conclusions: ITM after LSG is not a negligible complication and represents an important pathogenic factor in the development or worsening of GERD. Postoperative UGIE plays a fundamental role in the diagnosis of esophageal mucosal lesions.
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http://dx.doi.org/10.1007/s11695-021-05340-xDOI Listing
April 2021

Telematics pre-operative psychological and nutritional assessment in candidates for bariatric surgery during COVID-19 phase 2: a pilot prospective observational study.

Minerva Surg 2021 Feb;76(1):57-61

Division of General Surgery and Bariatric Center of Excellence IFSO EC, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.

Background: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak.

Methods: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree.

Results: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment.

Conclusions: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.
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http://dx.doi.org/10.23736/S2724-5691.20.08706-4DOI Listing
February 2021

The relation between sexuality and obesity: the role of psychological factors in a sample of obese men undergoing bariatric surgery.

Int J Impot Res 2020 Dec 17. Epub 2020 Dec 17.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.

Obesity produces a significant deterioration in general and sexual health. The aim of this cross-sectional study was to investigate the impact of obesity on sexuality, illustrating the psychological constructs that may play a significant role in determining sexual functioning and satisfaction. During the psychological assessment for bariatric surgery eligibility, 171 obese men filled out a socio-demographic questionnaire, the International Index of Erectile Function (IIEF), the 20 Item-Toronto Alexithymia Scale, the Symptom Checklist-90-Revised, the Body Uneasiness Test, and the Obesity-related Disability test. A series of hierarchical multiple regression analyses highlighted how obese men sexual desire (F = 10.128, p < 0.001), erectile function (F = 63.578, p < 0.001), orgasmic function (F = 33.967, p < 0.001), intercourse satisfaction (F = 159.752, p < 0.001), and general satisfaction (F = 18.707, p < 0.001) were significantly associated with other IIEF sexual domains, difficulties in identifying feelings, psychopathological symptoms (such as depression and paranoid ideation), body image, and quality of life. Findings are useful for deepening understanding of obese male sexual response, and more generally, for analyzing the complex and multivariate relation between obesity and sexuality, supporting the need of a multidisciplinary approach to obesity care that includes professionals with specific training in sexology.
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http://dx.doi.org/10.1038/s41443-020-00388-2DOI Listing
December 2020

Granzyme B Expression in Visceral Adipose Tissue Associates With Local Inflammation and Glyco-Metabolic Alterations in Obesity.

Front Immunol 2020 18;11:589188. Epub 2020 Nov 18.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with "sick" fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases.
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http://dx.doi.org/10.3389/fimmu.2020.589188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708321PMC
November 2020

Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.

Int J Mol Sci 2020 Nov 29;21(23). Epub 2020 Nov 29.

Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ test) and with AUROC = 0.89 ( = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.
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http://dx.doi.org/10.3390/ijms21239091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730815PMC
November 2020

Current status on the adoption of high energy devices in Italy: An Italian Society for Endoscopic Surgery and New Technologies (SICE) national survey.

Surg Endosc 2020 Nov 5. Epub 2020 Nov 5.

Department of General Surgery, Ospedale Civile, Adria, Italy.

Background: In the past three decades, different High Energy Devices (HED) have been introduced in surgical practice to improve the efficiency of surgical procedures. HED allow vessel sealing, coagulation and transection as well as an efficient tissue dissection. This survey was designed to verify the current status on the adoption of HED in Italy.

Methods: A survey was conducted across Italian general surgery units. The questionnaire was composed of three sections (general information, elective surgery, emergency surgery) including 44 questions. Only one member per each surgery unit was allowed to complete the questionnaire. For elective procedures, the survey included questions on thyroid surgery, lower and upper GI surgery, proctologic surgery, adrenal gland surgery, pancreatic and hepatobiliary surgery, cholecystectomy, abdominal wall surgery and breast surgery. Appendectomy, cholecystectomy for acute cholecystitis and bowel obstruction due to adhesions were considered for emergency surgery. The list of alternatives for every single question included a percentage category as follows: " < 25%, 25-50%, 51-75% or > 75%", both for open and minimally-invasive surgery.

Results: A total of 113 surgical units completed the questionnaire. The reported use of HED was high both in open and minimally-invasive upper and lower GI surgery. Similarly, HED were widely used in minimally-invasive pancreatic and adrenal surgery. The use of HED was wider in minimally-invasive hepatic and biliary tree surgery compared to open surgery, whereas the majority of the respondents reported the use of any type of HED in less than 25% of elective cholecystectomies. HED were only rarely employed also in the majority of emergency open and laparoscopic procedures, including cholecystectomy, appendectomy, and adhesiolysis. Similarly, very few respondents declared to use HED in abdominal wall surgery and proctology. The distribution of the most used type of HED varied among the different surgical interventions. US HED were mostly used in thyroid, upper GI, and adrenal surgery. A relevant use of H-US/RF devices was reported in lower GI, pancreatic, hepatobiliary and breast surgery. RF HED were the preferred choice in proctology.

Conclusion: HED are extensively used in minimally-invasive elective surgery involving the upper and lower GI tract, liver, pancreas and adrenal gland. Nowadays, reasons for choosing a specific HED in clinical practice rely on several aspects, including surgeon's preference, economic features, and specific drawbacks of the energy employed.
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http://dx.doi.org/10.1007/s00464-020-08117-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644118PMC
November 2020

Concomitant hiatal hernia repair during bariatric surgery: does the reinforcement make the difference?

Minerva Surg 2021 Feb 2;76(1):33-42. Epub 2020 Oct 2.

Division of General Surgery and Bariatric Center of Excellence-IFSO EC, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.

Background: Hiatal hernia repair (HHR) is still controversial during bariatric procedures, especially in case of laparoscopic sleeve gastrectomy (LSG).

Aims: to report the long-term results of concomitant HHR, evaluating the safety and efficacy of posterior cruroplasty (PC), simple or reinforced with biosynthetic, absorbable Bio-A mesh (Gore, Flagstaff, AZ, USA). Primary endpoint: PC's failure, defined as symptomatic HH recurrence, nonresponding to medical treatment and requiring revisional surgery.

Methods: The prospective database of 1876 bariatric operations performed in a center of excellence between 2011-2019 was searched for concomitant HHR. Intraoperative measurement of the hiatal surface area (HSA) was performed routinely.

Results: A total of 250 patients undergone bariatric surgery and concomitant HHR (13%). Simple PC (group A, 151 patients) was performed during 130 LSG, 5 re-sleeves and 16 gastric bypasses; mean BMI 43.4±5.8 kg/m, HSA mean size 3.4±2 cm. Reinforced PC (group B) was performed in 99 cases: 62 primary LSG, 22 LGB and 15 revisions of LSG; mean BMI 44.6±7.7 kg/m2, HSA mean size 6.7±2 cm. PC's failure, with intrathoracic migration (ITM) of the LSG was encountered in 12 cases (8%) of simple vs. only 4 cases (4%) of reinforced PC (P=0.23); hence, a repeat, reinforced PC and R-en-Y gastric bypass (LRYGB) was performed laparoscopically in all cases. No mesh-related complications were registered perioperatively or after long-term follow-up (mean 50 months). One case of cardiac metaplasia without goblet cells was detected 4 years postoperatively; conversion to LRYGB, with reinforced redo of the PC was performed. The Cox hazard analysis showed that the use of more than four stitches for cruroplasty represents a negative factor on recurrence (HR=8; P<0.05).

Conclusions: An aggressive search for and repair of HH during any bariatric procedure seems advisable, allowing a low HH recurrence rates. Additional measures, like mesh reinforcement of crural closure with biosynthetic, absorbable mesh, seem to improve results on long term follow-up, especially in case of larger hiatal defects. In our experience, reinforcement of even smaller defects seems advisable in obese population.
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http://dx.doi.org/10.23736/S0026-4733.20.08503-XDOI Listing
February 2021

Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase.

Int J Mol Sci 2020 Sep 29;21(19). Epub 2020 Sep 29.

Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.

Angiopoietin-like protein 4 (ANGPTL4) regulates lipid partitioning by inhibiting circulating and tissue lipoprotein lipase (LPL); ANGPTL4 loss-of-function variants improve insulin sensitivity and reduce type 2 diabetes (T2D) risk with mechanisms partially unknown. This study was designed to explore metabolic implications of differential ANGPTL4 and LPL expression in human adipose tissue (AT). We recruited eighty-eight obese individuals, with and without abnormal glucose metabolism (AGM), undergoing bariatric surgery; visceral AT (VAT) fragments were obtained intra-operatively and analyzed by immunohistochemistry and mRNA by rt-PCR. Data on hepatic ANGPTL4 mRNA were available for 40 participants. VAT ANGPTL4 expression was higher in AGM individuals than in those with normal glucose tolerance (NGT) and associated with VAT inflammation, insulin resistance, and presence of adipocyte size heterogeneity. Increased ANGPTL4 was associated with AGM with OR = 5.1 (95% C.I.: 1.2-23; = 0.02) and AUROC = 0.76 (95% C.I.: 1.2-23; < 0.001). High LPL was associated with the detection of homogeneous adipocyte size, reduced microvessel density, and higher HIF-1α levels and inversely correlated to blood transaminases. In conclusion, in obese individuals, VAT ANGPTL4 levels are increased in the presence of local inflammation and AGM. Conversely, higher LPL expression describes a condition of increased lipid storage in adipocytes, which may serve as a protective mechanism against ectopic fat accumulation and related metabolic disease in obesity.
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http://dx.doi.org/10.3390/ijms21197197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582588PMC
September 2020

Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease.

J Endocrinol Invest 2021 May 27;44(5):979-988. Epub 2020 Aug 27.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Introduction: Dipeptidyl peptidase 4 (DPP4) levels are associated to metabolic and cardiovascular diseases in humans; initial evidence reported a relationship between DPP4 and chronic liver diseases. Aim of this study was to investigate hepatic and systemic DPP4 levels/activity in relation to NAFLD/NASH in individuals with and without metabolic disease.

Methods: We recruited fifty-two obese individuals undergoing bariatric surgery and intra-operative liver biopsy at Sapienza University, Rome, Italy. The association between DPP4 levels/activity and NAFLD was also evaluated in 126 non-obese individuals recruited in the same setting.

Results: NAFLD patients had significantly higher circulating DPP4 activity than no-NAFLD in both the obese and non-obese cohorts; plasma DPP4 activity and levels linearly correlated with steatosis grade and inflammation at the liver biopsy. Hepatic DPP4 mRNA was not associated to either its circulating levels/activity or NAFLD. In the multivariate logistic regression analysis on all the study participants (n = 178), higher circulating DPP4 activity was associated with NAFLD independently of potential confounders with OR (95% CI): 3.5 (1.2-10.21), p = 0.022.

Conclusions: This study demonstrates the coexistence of increased plasma DPP4 levels and activity in NAFLD. Circulating DPP4 measurement may represent a novel cost-effective strategy for NAFLD/NASH risk stratification and a potential tool for monitoring disease's progression in established NAFLD.
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http://dx.doi.org/10.1007/s40618-020-01392-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049937PMC
May 2021

Protocol of an interdisciplinary consensus project aiming to develop an AGREE II extension for guidelines in surgery.

BMJ Open 2020 08 11;10(8):e037107. Epub 2020 Aug 11.

Medical School, European University Cyprus, Nicosia, Cyprus.

Introduction: Appraisal of Guidelines for Research and Evaluation (AGREE II) is an instrument that informs development, reporting and assessment of clinical practice guidelines. Previous research has demonstrated the need for improvement in methodological and reporting quality of clinical practice guidelines specifically in surgery. We aimed to develop an AGREE II extension document for application in surgical guidelines.

Methods And Analysis: We have performed a structured literature review and assessment of guidelines in surgery using the AGREE II instrument. In exploratory analyses, we have identified factors associated with guideline quality. We have performed reliability and factor analyses to inform the development of an extension document. We will summarise this information and present it to a Delphi panel of stakeholders. We will perform iterative Delphi rounds and we will summarise the final results to develop the extension instrument in a dedicated consensus conference.

Ethics And Dissemination: Funding bodies will not be involved in the development of the instrument. Research ethics committee and Health Research Authority approval was waived, since this is a professional staff study only and no duty of care lies with the National Health Service to any of the participants. Conflicts of interest, if any, will be addressed by reassigning functions or replacing participants with relevant conflicts. The results will be disseminated through publication in peer reviewed journals, the funders' websites, social media and direct contact with guideline development organisations and peer-reviewed journals that publish guidelines.
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http://dx.doi.org/10.1136/bmjopen-2020-037107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418673PMC
August 2020

Updates in bariatric surgery guidelines: what's new?

Minerva Surg 2021 02 6;76(1):5-7. Epub 2020 Aug 6.

Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.23736/S0026-4733.20.08447-3DOI Listing
February 2021

Bariatric and metabolic surgery during COVID-19 outbreak phase 2 in Italy: why, when and how to restart.

Surg Obes Relat Dis 2020 10 24;16(10):1614-1618. Epub 2020 Jun 24.

Division of General Surgery & Bariatric Center of Excellence IFSO EC, Department of Medico-Surgical Sciences and Biothecnologies, Sapienza University of Rome, Latina, Italy. Electronic address:

In Italy elective bariatric and metabolic surgery was cancelled on February 21,2020 at the beginning of the so-called phase 1 of the SARS-CoV-2 outbreak. Gradually it was restarted on May 4,2020 at the beginning of the so-called phase 2, when epidemiological data showed containment of the infection. Before the outbreak in eight high-volume bariatric centers 840 patients were surgically treated developing a Covid-19 infection, during phase 1, in only 5 cases (0.6%) without mortality. The post-operative complication rate was similar when compared to the 836 subjects submitted to bariatric surgery the year before. Since the high prevalence of infection in subjects with BMI > 30, it was argued that early intervention on obesity during phase 2 could help to minimize the effects of the disease in the event of a possible reversion to a SARS-CoV-2 outbreak phase 1. At the same time a prospective observational study from July 1 till the WHO declaration of the end of the pandemic has started in the eight high volume centers to monitor the post-operative outcome and its effect on SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.soard.2020.06.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313526PMC
October 2020

Platelet-rich plasma PRP vs. absorbable mesh as cruroplasty reinforcement: a study on an animal model.

Minim Invasive Ther Allied Technol 2020 Jul 23:1-10. Epub 2020 Jul 23.

General Surgery and Bariatric Centre of Excellence IFSO-EC, AUSL LT-ICOT, Department of Medico-Surgical Sciences and Biotechnologies, University La Sapienza of Rome, Latina, Italy.

Background: Reinforcement of posterior cruroplasty has been proposed to minimize the failure of hiatal hernia repair (HHR). The applications of autologous platelet-rich plasma (PRP) and absorbable mesh are barely reported in this area.

Aims: To analyze local macroscopic and microscopic changes induced by mesh vs. PRP as reinforcement of HHR, using a reliable laparoscopic experimental porcine model.

Material And Methods: This prospective, comparative pilot study was conducted on 14 female pigs, aged four to six months. An iatrogenic hiatal defect was laparoscopically simulated and repaired, reinforced with Bio-A® mesh (group A) or PRP (group B). Specimen retrieval was performed after seven months for histopathological (HP) examination.

Results: No local or general complications were registered, with complete resorption of reinforcements, that determined inflammatory infiltrates with local collagen production and tissue neo-vascularization. Group A had an increased mean chronic inflammation score ( = .3061), showing significant sclerotic collagenizing process. PRP enhanced angiogenesis, collagenizing, myofibroblast recruitment and tissue ingrowth.

Conclusions: No residual materials or evidence of anatomical distortion were found. Animal model was safe and reliable. This is the first report of complete absorption of Bio-A positioned on crural area. HP results suggest the clinical application of PRP in HHR as a promising co-adjuvant to local remodeling and healing. ASA: American Society of Anesthesiologists; AB: Alcian Blue; PAS: Periodic Acid-Schiff; CP: platelet concentrate; fPC: filtered plasma concentrate; GERD: gastro-esophageal reflux disease; HSA: hiatal surface area; HHR: hiatal hernia repair; HP: histopathological; HH: hiatal hernia; HE: hematoxylin and eosin; HR: hiatus repair alone; HRM: hiatus repair and acellular dermal matrix; NM: Nicolae Manolesccu; LNF: laparoscopic Nissen fundoplication; PC: posterior cruroplasty; PPP: platelet-poor plasma; RP: platelet-rich plasma.
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http://dx.doi.org/10.1080/13645706.2020.1795686DOI Listing
July 2020

Italian multi-society modified Delphi consensus on the definition and management of anastomotic leakage in colorectal surgery.

Updates Surg 2020 Sep 1;72(3):781-792. Epub 2020 Jul 1.

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Introduction: The incidence of anastomotic leak (AL) has not decreased over the past decades and some important grey areas remain in its definition, prevention, and management. The aim of this study was to reach a national consensus on the definition of AL and to identify key points to be applied in clinical practice.

Methods: A 3-step modified Delphi method was used to establish consensus. Ten representative members of the major Italian surgical scientific societies with proven colorectal expertise were selected after a call to action. After a comprehensive literature search, each expert drew a list of evidence-based statements which were voted in round one by the scientific board. Panel members were asked to mark "totally disagree", "partially agree" or "totally agree" for each statement and provide comments. The same voting method was used for round 2. Round 3 consisted of a final face-to-face meeting.

Results: Thirty-three statements (clustered into 14 topics) were included in round 1. Following the third voting round, a final list of 16 items was formulated, which encompass the following 9 topics: AL definition, patient- and operative-related risk factors, prevention measures, bowel preparation, surgical technique, intraoperative assessment, early diagnosis, radiological diagnosis and management of specific patterns of AL. The overall response rate was 100% for all items in all the three rounds.

Conclusions: This Delphi survey identified items that expert colorectal surgeons agreed were important to be applied in the prevention, diagnosis, and management of AL. This represents the first consensus involving all relevant national scientific societies, defining important and shared concepts in the diagnosis and management of AL.
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http://dx.doi.org/10.1007/s13304-020-00837-zDOI Listing
September 2020

Acute cholecystitis during COVID-19 pandemic: a multisocietary position statement.

World J Emerg Surg 2020 06 8;15(1):38. Epub 2020 Jun 8.

Department of Mini-Invasive and General Surgery, Cristo Re Hospital, Rome, Italy.

Following the spread of the infection from the new SARS-CoV2 coronavirus in March 2020, several surgical societies have released their recommendations to manage the implications of the COVID-19 pandemic for the daily clinical practice. The recommendations on emergency surgery have fueled a debate among surgeons on an international level.We maintain that laparoscopic cholecystectomy remains the treatment of choice for acute cholecystitis, even in the COVID-19 era. Moreover, since laparoscopic cholecystectomy is not more likely to spread the COVID-19 infection than open cholecystectomy, it must be organized in such a way as to be carried out safely even in the present situation, to guarantee the patient with the best outcomes that minimally invasive surgery has shown to have.
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http://dx.doi.org/10.1186/s13017-020-00317-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278255PMC
June 2020

Relationship between hepatic and systemic angiopoietin-like 3, hepatic Vitamin D receptor expression and NAFLD in obesity.

Liver Int 2020 09 28;40(9):2139-2147. Epub 2020 Jun 28.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin-like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)-mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD-related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD-related gene expression in human obesity in relation to NAFLD.

Methods: We conducted a cross-sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT-PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay.

Results: Compared to non-NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders.

Conclusions: Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up-regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs-mediated ectopic fat accumulation and NAFLD development in obesity.
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http://dx.doi.org/10.1111/liv.14554DOI Listing
September 2020

Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease.

Diabetes Metab Res Rev 2021 Jan 1;37(1):e3358. Epub 2020 Jul 1.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Aims: Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity.

Methods: We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies.

Results: Within our study population, NAFLD was significantly associated with greater VAT CD68 macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco-metabolic profile.

Conclusions: In obese patients, NAFLD is associated in a dose-dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications.
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http://dx.doi.org/10.1002/dmrr.3358DOI Listing
January 2021

Obesity surgery and eating and weight disorders: a new topical collection of EWD.

Eat Weight Disord 2021 Apr 26;26(3):757-758. Epub 2020 May 26.

Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Corso della repubblica 79, 040100, Latina, Italy.

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http://dx.doi.org/10.1007/s40519-020-00937-0DOI Listing
April 2021

Weight Loss and Eating Pattern 7 Years After Sleeve Gastrectomy: Experience of a Bariatric Center of Excellence.

Obes Surg 2020 Oct;30(10):3747-3752

Department of Medical-Surgical Sciences and Biotechnologies, Division of General Surgery and Bariatric Centre of Excellence, University of Rome "La Sapienza", Rome, Italy.

Purpose: Report the analysis from a single center series of consecutive primary sleeve gastrectomy (SG) on the factors affecting weight loss at long term.

Materials And Methods: Patients submitted to primary SG with a follow-up of 7 years were screened. Weight loss was evaluated with %excess weight loss (%EWL) and %excess BMI loss (%BMIL). Weight regain (WR) was defined as in increase of 25% of the obtained %EWL and insufficient weight loss (IWL) as loss < 50% EWL. Eating behaviors were evaluated with 7 days record (7dR). All the variables potentially affecting the weight loss were cross-matched for correlation. The study population was divided in three groups: group A (WR), group B (IWL), and group C (sustained weight loss) for comparative analysis.

Results: A total of 86 patients (21 M/65 F) with a preoperative BMI of 47.08 ± 6.15 kg/m were evaluated. Cumulative 7 years weight loss was as follows: 61.66 ± 22.69% EWL and 32 ± 9% EBMIL. A total of 4.6% had an IWL while 27.9% a WR. The analysis showed a significant difference among the daily calories and fats consuming, number of meals, physical activity, grazing/sweet eating habits, and adherence to follow-up (p < 0.05) between groups A and C. Cox hazard demonstrated a significant risk (p < 0.05) to WR in case of adherence to follow-up shorter than 48 months, high daily calories, and fats intake (hazard ratio (HR) range 5-9). Eight patients (9.3%) had a surgical revision.

Conclusion: Our data demonstrated that long-term results (7 years) of SG are strongly related to eating habits and patient's behaviors.
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http://dx.doi.org/10.1007/s11695-020-04699-7DOI Listing
October 2020

Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP.

Surg Endosc 2020 06 23;34(6):2332-2358. Epub 2020 Apr 23.

Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background: Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery.

Methods: A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards.

Results: Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure.

Conclusion: This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions.
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http://dx.doi.org/10.1007/s00464-020-07555-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214495PMC
June 2020

Letter in Reply: Long-term Results After Laparoscopic Sleeve Gastrectomy with Concomitant Posterior Cruroplasty: Five-Year Follow-up.

J Gastrointest Surg 2020 06 30;24(6):1455-1457. Epub 2020 Mar 30.

Division of General Surgery & Bariatric Center of Excellence-IFSO EC, Department of Medico-Surgical Sciences and Biotechnologies, University La Sapienza of Rome, Via F. Faggiana, 1668, Latina, Italy.

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http://dx.doi.org/10.1007/s11605-020-04573-yDOI Listing
June 2020

Persistent Fistula after Sleeve Gastrectomy: A Chronic Dilemma.

Chirurgia (Bucur) 2019 Nov-Dec;114(6):790-797

There is no time limit for the occurrence of leaks after sleeve gastrectomy LSG, and very late ones might evolve versus persistent, chronic fistulas. The aim of this retrospective study was to analyze the incidence, treatment and outcomes of persistent, chronic fistulas occurred or treated in a bariatric Center of Excellence IFSO-EC (CoE) and to establish a standardized approach. Materials between 2011-2018, nine cases of postoperative leaks occurred on a total of 1365 LSG performed (0.65%), 7 of them having late presentations (onset over 10 days postoperative). Chronic, persistent fistulas were identified and analyzed, including one gastro-bronchial and one gastro-cutaneous fistulas. We present three peculiar cases of very late, chronic type III fistulas, with onset at 6-84 months after primary LSG and their management, including conservative, interventional radiology and endoscopy and surgical therapies. the management of late, chronic type III fistula is variable, with no standard algorithm to follow, but it should be planned based on the clinical evaluation, time of diagnosis, available resources, multidisciplinary approach and expertise. This emphasises again the necessity of a bariatric CoE that can guarantee a better diagnose and treatment, based on the use of wide, available resources, both professional and material.
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http://dx.doi.org/10.21614/chirurgia.114.6.790DOI Listing
January 2020

Noninvasive assessment of hepatic steatosis and fibrosis in patients with severe obesity.

Endocrine 2020 03 19;67(3):569-578. Epub 2019 Dec 19.

Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Santa Maria Goretti Hospital, Sapienza University of Rome, Via Guido Reni 1, 04100, Latina, Italy.

Purpose: In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population.

Methods: Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS).

Results: In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02).

Conclusions: In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.
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http://dx.doi.org/10.1007/s12020-019-02155-wDOI Listing
March 2020

Correction to: Laparoscopic right hemicolectomy: the SICE (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospectivetrial on 1225 cases comparing intra corporeal versus extra corporeal ileo‑colic side‑to‑side anastomosis.

Surg Endosc 2020 Nov;34(11):4801-4802

Department of Medical Surgical Science and Biotechnologies, Faculty Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.

Due to an error in production the members of SICE CoDIG (Colon Dx Italian Group) listed in the Acknowledgments were not tagged correctly as authors in the XML of this article. This listing is presented again here.
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http://dx.doi.org/10.1007/s00464-019-07322-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853029PMC
November 2020

Laparoscopic right hemicolectomy: the SICE (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospective trial on 1225 cases comparing intra corporeal versus extra corporeal ileo-colic side-to-side anastomosis.

Surg Endosc 2020 11 18;34(11):4788-4800. Epub 2019 Nov 18.

Department of Medical Surgical Science and Biotechnologies, Faculty Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.

Background: While laparoscopic approach for right hemicolectomy (LRH) is considered appropriate for the surgical treatment of both malignant and benign diseases of right colon, there is still debate about how to perform the ileo-colic anastomosis. The ColonDxItalianGroup (CoDIG) was designed as a cohort, observational, prospective, multi-center national study with the aims of evaluating the surgeons' attitude regarding the intracorporeal (ICA) or extra-corporeal (ECA) anastomotic technique and the related surgical outcomes.

Methods: One hundred and twenty-five Surgical Units experienced in colorectal and advanced laparoscopic surgery were invited and 85 of them joined the study. Each center was asked not to change its surgical habits. Data about demographic characteristics, surgical technique and postoperative outcomes were collected through the official SICE website database. One thousand two hundred and twenty-five patients were enrolled between March 2018 and September 2018.

Results: ICA was performed in 70.4% of cases, ECA in 29.6%. Isoperistaltic anastomosis was completed in 85.6%, stapled in 87.9%. Hand-sewn enterotomy closure was adopted in 86%. Postoperative complications were reported in 35.4% for ICA and 50.7% for ECA; no significant difference was found according to patients' characteristics and technologies used. Median hospital stay was significantly shorter for ICA (7.3 vs. 9 POD). Postoperative pain in patients not prescribed opioids was significantly lower in ICA group.

Conclusions: In our survey, a side-to-side isoperistaltic stapled ICA with hand-sewn enterotomy closure is the most frequently adopted technique to perform ileo-colic anastomosis after any indications for elective LRH. According to literature, our study confirmed better short-term outcomes for ICA, with reduction of hospital stay and postoperative pain.

Trial Registration: Clinical trial (Identifier: NCT03934151).
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http://dx.doi.org/10.1007/s00464-019-07255-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572335PMC
November 2020

Alcohol ingestion symptoms after sleeve gastrectomy: intoxication or drunkenness? A prospective study from a Bariatric Centre of Excellence.

Eat Weight Disord 2020 Dec 13;25(6):1719-1725. Epub 2019 Nov 13.

Division of General Surgery and Bariatric Centre of Excellence, Department of Medical-Surgical Sciences and Biotechnologies, University of Rome "La Sapienza", Rome, Italy.

Purpose: The aim of this original research is to evaluate the effect of SG on alcohol intake symptoms, blood alcohol content (BAC), and alcohol metabolite levels.

Methods: At 0-6-12 months after SG, BAC of patients was measured at 0, 15, 30, and 60 min, and then every 30 min, and urinary metabolite (ethanol and acetaldehyde) levels were measured 2 h after consuming a standard red wine drink. Symptoms perceived by patients were evaluated using symptom alcoholization post-obesity surgery scores.

Results: Thirty obese patients (12 men/18 women; mean body mass index, 44 ± 4 kg/m) who underwent SG were enrolled in this study. At 12 months after SG, no alcohol use disorder was observed and BAC tended to peak after 15 min, with alcohol intoxication symptoms (nausea/vomiting, flushing, and diaphoresis), and return to zero after 90 min of wine intake. Ethanol and acetaldehyde levels were significantly different at 12 months compared with the levels at time 0 (p < 0.05).

Conclusions: Following SG, patients exhibit a high BAC at 15 min after moderate alcohol consumption accompanied with increased metabolite excretion and intoxication symptoms.

Level Of Evidence: Level III obtained from well-designed cohort analytic study.
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http://dx.doi.org/10.1007/s40519-019-00813-6DOI Listing
December 2020

Insulin resistance, but not insulin response, during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD.

Nutr Metab Cardiovasc Dis 2020 01 10;30(1):106-113. Epub 2019 Aug 10.

Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address:

Background And Aim: Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage.

Methods And Results: We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC] x insulin [AUC]) during OGTT, insulin response as (insulin [dAUC]/glucose [dAUC] or Insulinogenic Index (IGI = (I-I)/(G-G)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis.

Conclusions: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.
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http://dx.doi.org/10.1016/j.numecd.2019.08.001DOI Listing
January 2020

Hiatal Surface Area's CT scan measurement is useful in hiatal hernia's treatment of bariatric patients.

Minim Invasive Ther Allied Technol 2021 Apr 31;30(2):86-93. Epub 2019 Oct 31.

Department of General Surgery and Bariatric Center of Excellence IFSO-EC, University La Sapienza of Rome, Latina, Italy.

Introduction: Hiatal surface area (HSA) measurement has been recently proposed as useful tool for tailored treatment of hiatal defects. Multidetector CT scan (MDCT) of the hiatal area was shown to be useful in hiatal hernia (HH) management.

Purpose: MDCT preoperative HSA measurements validation as a useful method in the surgical repair decision making process of hiatal defects in candidates to antireflux ± bariatric surgery.

Material And Methods: Twenty-five obese patients (group A), candidates to laparoscopic cruroplasty ± bariatric surgery, were prospectively evaluated preoperatively and after one year, using an original MDCT algorithm, compared with intraoperative HSA measurement. Twelve non-obese (group B) and 12 obese patients (group C), without GERD or HH, were used as control groups.

Results: Median preoperative HSA was 7.9 cm, (interquartile IQR 5.97-9.80) while intraoperative median HSA was 6 cm (6-9.5),  = .84. Postoperative median HSA was 3.8 cm (3.21-4.8), showing the efficacy of cruroplasty, comparable with HSA calculated in the control groups (3.98 for B and 3.69 cm for C,  = .8547). No statistically significant difference between MDCT preoperative measurement and intraoperative findings was observed.

Conclusions: Preliminary results demonstrate MDCT scan HSA measurements as a valid, non-invasive method to predict intraoperative findings. It allows the HSA monitoring in order to correlate the symptoms onset and failure of cruroplasty.
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http://dx.doi.org/10.1080/13645706.2019.1683033DOI Listing
April 2021

Correction to: SICE national survey: current state on the adoption of laparoscopic approach to the treatment of colorectal disease in Italy.

Updates Surg 2020 03;72(1):229

Department of Surgery, University Hospital "La Sapienza", Rome, Italy.

The surname and given name of author Riccardo Brachet Contul was incorrectly published.
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http://dx.doi.org/10.1007/s13304-019-00685-6DOI Listing
March 2020

Long-Term Results After Laparoscopic Sleeve Gastrectomy with Concomitant Posterior Cruroplasty: 5-Year Follow-up.

J Gastrointest Surg 2020 09 13;24(9):1962-1968. Epub 2019 Aug 13.

Division of General Surgery & Bariatric Center of Excellence-IFSO EC, Department of Medico-Surgical Sciences and Biotechnologies, University La Sapienza of Rome, Via F. Faggiana, 1668, Latina, Italy.

Background: Hiatal hernia (HH) repair during laparoscopic sleeve gastrectomy (LSG) has been advocated to reduce the incidence of postoperative gastroesophageal reflux disease (GERD) and/or intrathoracic migration (ITM). The necessity of intraoperative repair in asymptomatic patients is still controversial. Previous, mid-term results of a prospective, comparative study evaluating posterior cruroplasty concomitant with LSG (group A 48 patients with simple vs. group B 48 reinforced with bioabsorbable mesh) confirmed the safety and effectiveness of simultaneous procedures. Present aim was to report the 60 months follow-up update, evaluating GERD and esophageal lesions' incidence and HH's recurrence.

Results: Follow-up was completed in 87.5% of the patients. Recurrent GERD was registered in 6/38 (15.7%, group A) and in 9/46 (19.5%, group B) (p = 1.0000). Grade A esophagitis and GERD was shown in 2 patients (5.2%), respectively 2 (4.3%) of each group (p = 1.0000), and recurrent HH was confirmed subsequently by contrast study and CT scan. Neither Barrett's lesions nor de novo GERD was found in any patient. Failure of the cruroplasty with ITM was recorded in 7 patients from group A (18.4%) and 2 patients from group B (4.3%) p < 0.05; hence, a repeat posterior, reinforced cruroplasty was performed in all cases. A total of 12 patients (14.2%, 8 respective 4) were converted within 5 years for persistent/recurrent GERD, with only 1 case of de novo (group B).

Conclusions: Accurate patient selection and proper sleeve technique, combined with posterior cruroplasty (simple or reinforced) ensure effectiveness, with a rate of failure (HH recurrence) at 5 years of 10.7%.
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http://dx.doi.org/10.1007/s11605-019-04355-1DOI Listing
September 2020