Abdominal drainage after elective colorectal surgery: propensity score-matched retrospective analysis of an Italian cohort.

More than 100 years after the statements of Robert Lawson Tait ‘When in doubt, drain’ and of William Stewart Halsted ‘No drainage at all is better than the ignorant employment of it’ 1 , the assumption that the placement of peritoneal drains after elective colorectal surgery can provide diagnostic and therapeutic benefit through prevention and early detection of anastomotic leak or other intraperitoneal collections is debated 2 , 3 . Evidence suggests that drains can stimulate serous fluid production and may lead to an increased risk of surgical site infection (SSI) 4 and adhesions, and prolonged hospital length of stay (LOS), impacting on postoperative pain control, mobility 4 , 5 , increased perceived discomfort and anxiety 6 . The Enhanced Recovery After Surgery (ERAS) Society 7 , the American Society of Colon and Rectal Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons 8 , French 9 and Italian 10 guidelines, based on RCTs 11 , 12 , older 13 , 14 and more recent 15 , 16 meta-analyses or systematic reviews of RCTs, strongly recommend that pelvic and peritoneal drains should not be used routinely in colorectal surgery. However, this strong recommendation is based on moderate-quality evidence 8 , 17 (all the RCTs showed a bias of surgeon blinding, and some of them had a bias of allocation concealment and sequence randomization method 12 , systematic reviews/meta-analyses included a large number of infra-promontory anastomoses in which a pelvic drain is almost always placed) and mainly on data observed before the widespread application of minimally invasive surgery. Conversely, many surgeons, particularly in Europe and China 18 , still believe that prophylactic drainage may remove collected fluid, thus reducing the risk of intra-abdominal infection, favouring early detection of postoperative complications such as intra-abdominal bleeding or anastomotic leakage, and minimize their severity, possibly avoiding reoperation 19 , 20 . Despite the above-mentioned recommendations, recent large observational studies in Italy, Spain and Europe 21–25 report an abdominal drain placement rate after colorectal resection ranging from 40 to 70 per cent, reaching 90 per cent in a recent survey among German and Austrian surgeons 26 , whereas these rates are generally reported below 15 per cent in North America 27 , 28 . The aim of the present study was to address the existing gap in knowledge by evaluating the impact of the omission of abdominal drains on early adverse events in patients who underwent elective colorectal surgery. Data were used from two prospective open-label observational multicentre studies of the Italian ColoRectal Anastomotic Leakage (iCral) study group 24 , 25 .

This was a retrospective propensity score-matched analysis (PSMA) of patients who had undergone colorectal surgery for malignant and benign diseases enrolled in two consecutive studies upon explicit inclusion/exclusion criteria, in 78 surgical centres in Italy from January 2019 to September 2021: iCral2 24 and iCral3 25 . The inclusion criteria were: ASA class I, II or III; elective or delayed urgency setting (defined as >48 h from admission in iCral2 and >24 h from admission in iCral3); patient’s written informed consent for inclusion in the study and processing of sensitive data. The exclusion criteria were pregnancy, hyperthermic chemotherapy (HIPEC) for carcinomatosis and incomplete data. The iCral2 study excluded patients with a protective stoma proximal to the anastomosis; conversely, these patients were included in the iCral3 study. Both studies were conducted in accordance with the Declaration of Helsinki and guidelines for good clinical practice E6 (R2). The study protocols were approved by the ethics committee of the coordinating centre (Marche Regional Ethics Committee (CERM) 2018/334 released on 28 November, 2018 for iCral2 and 2020/192 released on 30 July, 2020 for iCral3) and registered at clinicaltrials.gov ( NCT03771456 for iCral2 and NCT04397627 for iCral3). Subsequently, all other centres were authorized to participate by their local ethics committees. Due to the retrospective nature of the current analysis, no specific authorization was requested. To control for data imbalance derived from several treatment confounders, the present PSMA study included 6157 patients (73.7 per cent) out of 8359 in the parent studies, based on explicit exclusion criteria: any anastomosis located <10 cm from the anal verge, any anastomosis protected by a proximal stoma, delayed urgency, neo-adjuvant therapy, perioperative steroids and dialysis ( Fig. 1 ). The variables and outcomes recorded in the PSMA study population are shown in Tables 1 and 2 . To optimize the effectiveness of PSMA by reducing the number of unmatched cases, continuous variables were categorized according to their median values. Study flow chart according to the reporting and guidelines in propensity score analysis 29 iCral, Italian ColoRectal Anastomotic Leakage study group; ERAS, enhanced recovery after surgery; SMD, standardized mean difference. Descriptive analysis of the variables considered in the 6157 patients evaluated by the Italian ColoRectal Anastomotic Leakage study group (iCral) Values are n (%) unless otherwise stated. *Chi square independence test with one degree of freedom; MNA-SF, Mini Nutritional Assessment—Short Form; IBD, inflammatory bowel disease; Intracorporeal, anastomosis performed under visual control through the scope; Extracorporeal, anastomosis performed under direct visual control through an open access; Met./ac., metropolitan/academic; BT, blood transfusion; ERAS, enhanced recovery after surgery items. All enrolled patients were followed up for 8 weeks after surgery by local investigators, who were left free to manage the perioperative interval according to their usual local criteria, including any additional exam and time to discharge. Any adverse event was recorded and graded according to Clavien–Dindo 30 and the Japanese Clinical Oncology Group (JCOG) extended criteria 31 as well as any reoperation, readmission or death. Anastomotic leakage (AL) was defined according to the international consensus 32 . All the outcomes were calculated at 60 days after surgery. The primary endpoint was the duration of postoperative hospital stay (LOS, inclusive of any readmission) either dichotomized according to its median value or considered as a continuous variable. The secondary endpoints were: superficial and/or deep surgical site infections (s-d-SSI), defined as drain-specific complications including purulent drainage from superficial incisions, positive culture of fluid or tissue from superficial incisions, pain or tenderness, localized swelling, redness, heat, and/or infections involving deep fascial and muscle layers without dehiscence 33 ; deep wound dehiscence; abdominal collection/abscess defined as intraperitoneal postoperative collections that altered the normal postoperative course, requiring either medical, radiological, endoscopic or surgical intervention 33 ; SSI defined as s-d-SSI plus abdominal collection/abscess plus deep wound dehiscence; infectious morbidity rate defined as SSI plus pulmonary infections plus urinary infections; AL; overall morbidity rate (any adverse event); major morbidity rate (any adverse event grade > II); reoperation (any unplanned operation) rates; mortality (any death) rates. This was a retrospective PSMA of two prospective cohorts, with sample sizes calculated and reported in the respective core papers 24 , 25 . Events per variable guideline were followed 34 . There were no missing data in the database of 6157 patients. The target of estimand was represented by the average treatment effect in the true population of interest (ATT). A propensity score-matching model 35 , 36 was used for the analysis ( Fig. 1 ). An adjusted logistic regression was used to estimate the propensity scores of the treatment and control groups. The exposure variable was a treatment that implied no abdominal drain(s) placement in elective colorectal surgery, and 21 covariates, potentially affecting the treatment 37 , were selected: age, sex, ASA class, BMI, diabetes, chronic renal failure, chronic liver disease, nutritional status measured through the Mini Nutritional Assessment—Short Form (MNA-SF) 38 , surgery for malignancy, centre volume, hospital type (academic/metropolitan versus local/regional), surgical unit type (general versus oncologic/colorectal), mini-invasive surgery, standard surgical procedure, operation length (minutes), intra- or extracorporeal anastomosis, stapled versus handsewn anastomosis, end-to-end anastomosis, preoperative blood transfusion(s), intra- and/or postoperative blood transfusion(s), and overall ERAS pathway adherence rates. To ensure that the treatment groups were balanced 39 , a PSMA using the software ‘R © ’ (Version 4.2.2, The R Foundation © for Statistical Computing, Vienna, Austria, 2022) was performed. A nearest neighbour approach with a logit distance metric and a caliper of 0.1 to minimize differences between the groups was used as well as adjusted logistic regression to estimate the association between the treatment variable and outcomes. Balance in the matched groups was assessed by calculating the standardized mean difference (SMD), using a threshold of 0.1 (an SMD less than 0.1 typically indicates a negligible difference between the means of the groups) and the general variance ratio (a variance ratio close to 1 indicates that variances are equal in the two groups). For outcome modelling, an adjusted logistic regression was performed based on a treatment variable represented by no abdominal drain placement in elective colorectal surgery and on the same 21 covariates selected for the PSMA 40 , presenting odds ratios (OR) and 95 per cent c.i. The eventual effect of any unobserved confounder was tested through a sensitivity analysis 41 , using the library ‘SensitivityR5’ of the software R © (Version 4.2.2, The R Foundation © for Statistical Computing, Vienna, Austria, 2022) and presenting the Γ values (each 0.1 increment of Γ values representing a 10 per cent odds of differential assignment to treatment due to any unobserved variable).

A total of 8359 patients who underwent colorectal resection with anastomosis were enrolled in two consecutive studies upon explicit inclusion/exclusion criteria, in 78 surgical centres in Italy from January 2019 to September 2021: iCral2 24 and iCral3 25 . The overall rate of abdominal drain placement after elective colorectal surgery was 64.8 per cent (3989 of 6157 patients). Tables 1 and 2 provide descriptions of the study covariates and, regarding univariable outcome analysis, drain omission was significantly associated with a lower risk of s-d-SSI, SSI, overall morbidity rate, mortality rate and LOS >6 days. The prevalence characteristics of the 3989 patients in whom abdominal drain(s) were placed are reported in Table 2 . Drain(s) placement was significantly prevalent in males, ASA III, BMI >25.25 kg/m 2 , diabetes, MNA-SF ≤12, surgery for benign disease open surgery, non-standard procedures (transverse colectomy, splenic flexure colectomy, Hartmann reversal, (sub) total colectomy, other) in comparison to standard procedures (right colectomy, left colectomy, anterior resection), extracorporeal anastomosis, handsewn anastomosis, end-to-end anastomosis, operation length >170 min, local/regional hospitals in comparison to metropolitan/academic hospitals, centre volume < 4 patients/month, intra/postoperative blood transfusion(s), overall ERAS adherence <75 per cent. Descriptive analysis of the outcomes considered in the 6157 patients evaluated by the Italian ColoRectal Anastomotic Leakage Values are n (%) unless otherwise stated. *Univariate ORs estimation with Wolf valuation of the c.i.; †Mean(s.d.). ‡Median (i.q.r.). s-d-SSI, superficial and/or deep surgical site infections; SSI, s-d-SSI plus deep wound dehiscence plus abdominal collection/abscess; Infectious morbidity rate, s-d-SSI plus deep wound dehiscence plus abdominal collection/abscess plus pulmonary infections plus urinary infections; LOS, length of postoperative hospital stay. For the PSMA, 3604 patients were included, and two groups of 1802 patients were generated ( Fig. 1 ): group A (no abdominal drain(s), true population of interest), and group B (abdominal drain(s), control population). This population of 3604 patients included data deriving from 77 (98.7 per cent) of the original 78 centres: group A included data deriving from 60 (77.9 per cent) centres and group B from 75 (97.4 per cent) centres. A good balance between the two groups was achieved, SMD within 0.1 ( Table 3 and Fig. 2 ), with a model variance ratio of 1.0843. Love plot of covariate standardized mean differences between treatment and control groups before and after matching; the vertical lines represent the interval of ± 0.1 within which balance is considered acceptable ERAS, enhanced recovery after surgery. Variables distribution in treatment and control groups before and after propensity score-matching *Student's test for proportions. SMD, standardized mean difference; MNA-SF, Mini Nutritional Assessment--Short Form; Intracorporeal, anastomosis performed under visual control through the scope; Extracorporeal, anastomosis performed under direct visual control through an open access; Met./ac., metropolitan/academic; Col/onc: colorectal/oncologic; BT, blood transfusion; ERAS, enhanced recovery after surgery items. Group A versus group B showed a significantly lower risk of LOS >6 days (408 (22.6 per cent) versus 575 (31.9 per cent) events; OR 0.60; 95 per cent c.i. 0.51–0.70; P < 0.001). Sensitivity analysis for LOS calculated a Γ of 1.5 ( P upper bound = 0.090), meaning that assuming the probabilities of assignment to the two treatment groups to be different because of unknown and/or unmeasured confounding variables, 50 per cent of patients should have been treated by drain(s) placement instead of omission to alter the significant association between drain(s) omission and LOS <6 days. The overall mean(standard deviation (s.d.)) LOS was 5.77(5.77) days in group A versus 6.63(5.70) days in group B ( P < 0.0001; two tailed Student’s t test with equal variances), with a mean difference of 0.86 days in favour of group A. No difference was recorded between the two groups regarding all the other endpoints: s-d-SSI (OR 0.98; 95 per cent c.i. 0.64–1.48; P = 0.900); deep wound dehiscence (OR 2.20; 95 per cent c.i. 0.52–9.30; P = 0.280); abdominal collection/abscess (OR 1.13; 95 per cent c.i. 0.64–1.99; P = 0.670); SSI (OR 1.15; 95 per cent c.i. 0.82–1.62; P = 0.420); infectious morbidity rate (OR 1.21; 95 per cent c.i. 0.90–1.62; P = 0.190); AL (OR 0.99; 95 per cent c.i. 0.67–1.46; P = 0.950); overall morbidity rate (OR 1.06; 95 per cent c.i. 0.90–1.24; P = 0.480); major morbidity rate (OR 1.11; 95 per cent c.i. 0.81–1.52; P = 0.500); reoperation rate (OR 1.19; 95 per cent c.i. 0.85–1.66; P = 0.300); mortality rate (OR 0.67; 95 per cent c.i. 0.27–1.68; P = 0.390).

This study presents data on a retrospective PSMA of a prospective multicentre database comparing drain(s) versus no drain(s) placement after elective colorectal surgery. This study involved 78 surgical centres, representing a snapshot of real-life clinical practice in Italy. Abdominal drain(s) placement after elective colorectal surgery was performed in 64.8 per cent of 6157 patients, and the univariable analysis of this population demonstrated a statistically significant association between drain(s) placement and a higher risk of s-d-SSI, SSI, overall morbidity rate, mortality rate and prolonged LOS, confirming the observations of previous studies 4 , 7 , 8 , 11–16 . Conversely, our PSMA showed that omission of drain(s) placement after elective colorectal surgery was significantly associated with a lower risk of LOS >6 days, albeit with a small and not clinically significant reduction of 0.86 days mean difference. No statistically significant association was detected for secondary outcomes. The main aim of the present analysis was to identify any reason supporting the use of drains by Italian (and European) surgeons following elective colorectal resections; there was no single reason to support their use. While LOS is an important outcome for hospital managers and for costs associated with the care of patients with colorectal diseases, it is of relatively little interest to patients and surgeons compared with other endpoints such as AL, major morbidity rate, reoperation rate and quality of life. This study did not demonstrate any difference in the risk of AL, major adverse events and reoperations. This disproves the possible role of abdominal drain(s) on earlier diagnosis and treatment of AL, for which we have highlighted the role of the joint use of clinical scores, C-reactive protein and procalcitonin 42 . The use of abdominal and pelvic drain(s) will continue to exist in a minority (for example, <20 per cent) of selected patients (low rectal anastomoses, immunocompromised and/or frail patients, heavily contaminated or dirty procedures, excessive blood loss and/or intraoperative complications). However, the routine placement is not supported 43 , and a progressive de-implementation strategy should be actively sought at organizational and surgeon levels 44 . A recent retrospective PSMA of a prospective international cohort 23 on the same topic used a ‘full matching’ model, which may result in bias as some observations may not have suitable matches. The main strength of this large sample size study is that it followed rigorous guidelines for applying PSMA 29 , 45 , being based on the following items: rigorous patient selection from the parent population, performed upon explicit criteria: to limit data imbalance, several potential confounders related to the surgical procedure (delayed urgency, operations without any abdominal incision/trans-anal procedures) or exclusively impacting on a subgroup of patients (anastomosis located <10 cm from the anal verge, neo-adjuvant therapy, proximal protective stoma, administration of perioperative steroids, patients treated by dialysis) were excluded; a reasoned inclusion of 21 conditioning variables (covariates): hospital type, surgical unit type and centre volume to account for the potential imbalance of multicentre, clustered data; adherence to the ERAS pathway items to account for the potential imbalance of medical, anaesthetic and surgical perioperative management; resections for benign and malignant diseases, mini-invasive or open surgery, standard and non-standard procedures 24 , intracorporeal (anastomosis performed under visual control through the scope) or extracorporeal (anastomosis performed under direct visual control through an open access) anastomoses, stapled or handsewn anastomoses, end-to-end or different fashion anastomoses, and operation length, in relation to the imbalance of the surgical treatment; pre- and intrapostoperative blood transfusion(s) to account for transfusion-related morbidity rate 46 ; age, sex, ASA class, body mass index, diabetes, chronic renal failure, chronic liver disease, and Mini Nutritional Assessment–Short Form, to account for patient imbalance; evaluation of the treatment effect through an adjusted multiple regression model including the same 21 covariates used for matching 40 ; a clear, sheer and restrictive balance algorithm ( Fig. 1 ); a sensitivity analysis for unmeasured confounders. Another strength of this study was the large number of enrolled patients in a well-defined time-lapse in a large number of centres, representing a very wide sample of surgical units performing colorectal resections in Italy. Although the multicentre nature of the considered data may be a definite source of clustering bias, it is undoubtedly representative of real-life data. However, this study has several limitations, and its results should be interpreted with caution. First, several controversial risk factors were not measured or recorded in the parent studies: single surgeon’s experience 47 , material, type and time to removal of drain(s) 48 , and indication (routine or selective) for drain(s) placement 23 . Second, although a sensitivity analysis of unmeasured confounders has been conducted, potential residual unknown factors and the inability to rule out potential measurement errors by the participating investigators, may have had an impact on the results. This study confirms that abdominal drain(s) placement after elective colorectal surgery is linked to a slightly prolonged non-clinically relevant LOS, without influencing anastomotic leakage, major morbidity rate and reoperation rate. Abdominal drains should not be routinely used in elective colorectal surgery.

Assistance with the study: iCral study group co-investigators: Stefano Mancini 26 , Gian Luca Baiocchi 27 , Roberto Santoro 28 , Walter Siquini 29 , Gianluca Guercioni 3 , Massimo Basti 30 , Corrado Pedrazzani 31 , Mauro Totis 32 , Alessandro Carrara 33 , Andrea Lucchi 34 , Maurizio Pavanello 35 , Andrea Muratore 36 , Stefano D’Ugo 37 , Alberto Di Leo 38 , Giusto Pignata 39 , Ugo Elmore 40 , Gabriele Anania 41 , Massimo Carlini 42 , Francesco Corcione 43 , Nereo Vettoretto 44 , Graziano Longo 45 , Mario Sorrentino 46 , Antonio Giuliani 47 , Giovanni Ferrari 48 , Lucio Taglietti 49 , Augusto Verzelli 50 , Mariantonietta Di Cosmo 51 , Davide Cavaliere 52 , Marco Milone 53 , Stefano Rausei 54 , Giovanni Ciaccio 55 , Giovanni Tebala 56 , Giuseppe Brisinda 57 , Stefano Berti 58 , Paolo Millo 59 , Luigi Boni 60 , Mario Guerrieri 61 , Roberto Persiani 62 , Dario Parini 63 , Antonino Spinelli 64 , Michele Genna 65 , Vincenzo Bottino 66 , Andrea Coratti 67 , Dario Scala 68 , Umberto Rivolta 69 , Micaela Piccoli 70 , Carlo Talarico 71 , Franco Roviello 72 , Alessandro Anastasi 73 , Giuseppe Maria Ettorre 74 , Mauro Montuori 75 , Pierpaolo Mariani 76 , Nicolò de Manzini 77 , Annibale Donini 78 , Mariano Fortunato Armellino 79 , Carlo Feo 80 , Silvio Guerriero 81 , Andrea Costanzi 82 , Federico Marchesi 83 , Moreno Cicetti 84 , Paolo Ciano 2 , Michele Benedetti 2 , Leonardo Antonio Montemurro 2 , Maria Sole Mattei 2 , Elena Belloni 2 , Daniela Apa 2 , Matteo Di Carlo 2 , Elisa Bertocchi 7 , Gaia Masini 7 Amedeo Altamura 8 , Francesco Rubichi 8 , Desirée Cianflocca 10 , Marco Migliore 10 , Diletta Cassini 11,12 , Lorenzo Pandolfini 13 , Alessandro Falsetto 13 , Antonio Sciuto 14 , Ugo Pace 15 , Andrea Fares Bucci 15 , Francesco Monari 16 , Grazia Maria Attinà 17 , Angela Maurizi 18 , Michele Simone 19 , Francesco Giudici 20 , Fabio Cianchi 20 , Bruno Sensi 21 , Alessandra Aprile 22 , Domenico Soriero 22 , Andrea Scarinci 23 , Gabriella Teresa Capolupo 24 , Valerio Sisti 25 , Marcella Lodovica Ricci 25 , Andrea Sagnotta 26 , Sarah Molfino 27 , Pietro Amodio 28 , Alessandro Cardinali 29 , Simone Cicconi 3 , Irene Marziali 3 , Diletta Frazzini 30 , Cristian Conti 31 , Nicolò Tamini 32 , Marco Braga 32 , Michele Motter 33 , Giuseppe Tirone 33 , Giacomo Martorelli 34 , Alban Cacurri 34 , Carlo Di Marco 35 , Patrizia Marsanic 36 , Nicoletta Sveva Pipitone Federico 36 , Marcello Spampinato 37 , Lorenzo Crepaz 38 , Jacopo Andreuccetti 39 , Ilaria Canfora 39 , Giulia Maggi 40 , Matteo Chiozza 41 , Domenico Spoletini 42 , Rosa Marcellinaro 42 , Umberto Bracale 43 , Roberto Peltrini 43 , Maria Michela Di Nuzzo 43 , Emanuele Botteri 44 , Simone Santoni 45 , Massimo Stefanoni 46 , Giovanni Del Vecchio 47 , Carmelo Magistro 48 , Silvia Ruggiero 49 , Arianna Birindelli 49 , Andrea Budassi 50 , Daniele Zigiotto 51 , Leonardo Solaini 52 , Giorgio Ercolani 52 , Giovanni Domenico De Palma 53 , Silvia Tenconi 54 , Paolo Locurto 55 , Antonio Di Cintio 56 , Maria Michela Chiarello 57 , Maria Cariati 57 , Andrea Gennai 58 , Manuela Grivon 59 , Elisa Cassinotti 60 , Monica Ortenzi 61 , Alberto Biondi 62 , Maurizio De Luca 63 , Francesco Carrano 64 , Francesca Fior 65 , Antonio Ferronetti 66 , Giuseppe Giuliani 67 , Graziella Marino 68 , Camillo Leonardo Bertoglio 69 , Francesca Pecchini 70 , Vincenzo Greco 71 , Roberto Piagnerelli 72 , Giuseppe Canonico 73 , Marco Colasanti 74 , Enrico Pinotti 75 , Roberta Carminati 76 , Edoardo Osenda 77 , Luigina Graziosi 78 , Ciro De Martino 79 , Giovanna Ioia 79 , Fioralba Pindozzi 80 , Lorenzo Organetti 81 , Michela Monteleone 82 , Giorgio Dalmonte 83 , Gabriele La Gioia 84 . From: 26 General & Oncologic Surgery Unit, San Filippo Neri Hospital, ASL Roma 1; 27 General Surgery Unit 3, Department of Clinical and Experimental Sciences, University of Brescia; 28 General Oncologic Surgery Unit, Belcolle Hospital, Viterbo; 29 General Surgery Unit, S. Lucia Hospital, Macerata; 30 General Surgery Unit, Spirito Santo Hospital, Pescara; 31 General & HPB Surgery Unit, University Hospital, Verona; 32 Colorectal Surgery Unit, San Gerardo Hospital, ASST Monza; 33 1st General Surgery Unit, S. Chiara Hospital, Trento; 34 General Surgery Unit, ‘Ceccarini’ Hospital, Riccione (RN); 35 General Surgery Unit, AULSS2 Marca Trevigiana, Conegliano Veneto (TV); 36 General Surgery Unit, ‘E. Agnelli’ Hospital, Pinerolo (TO); 37 General Surgery Unit, ‘V. Fazzi’ Hospital, Lecce; 38 General and Minimally Invasive Surgery Unit, San Camillo Hospital, Trento; 39 2nd General Surgery Unit 2, Spedali Civili di Brescia; 40 Gastroenterologic Surgery Unit, IRCCS S. Raffaele Hospital, Milano; 41 General & Laparoscopic Surgery Unit, University Hospital, Ferrara; 42 General Surgery Unit, S. Eugenio Hospital, ASL Roma 2; 43 General Oncologic and Mininvasive Surgery Unit, ‘Federico II’ University, Napoli; 44 General Surgery Unit, Spedali Civili of Brescia, Montichiari (BS); 45 General Surgery Unit, Policlinico Casilino, Roma; 46 General Surgery Unit, Latisana-Palmanova Hospital, Friuli Centrale University (UD); 47 General Surgery Unit, S. Carlo Hospital, Potenza; 48 General Oncologic and Mininvasive Surgery Unit, Great Metropolitan Niguarda Hospital, Milano; 49 General Surgery Unit, ASST Valcamonica, Esine (BS); 50 General Surgery Unit, Profili Hospital, Fabriano (AN); 51 General & Upper GI Surgery Unit, University Hospital, Verona; 52 General & Oncologic Surgery Unit, AUSL Romagna, Forlì (FC); 53 General & Endoscopic Surgery Unit, ‘Federico II’ University, Napoli; 54 General Surgery Unit, Gallarate Hospital (VA); 55 General Surgery Unit, S. Elia Hospital, Caltanissetta; 56 General Surgery Unit, S. Maria Hospital, Terni; 57 General Surgery Unit, San Giovanni di Dio Hospital, Crotone; 58 General Surgery Unit, ASL 5 Liguria POLL, La Spezia; 59 General Surgery Unit, ‘U. Parini’ Regional Hospital, Aosta; 60 General Surgery Unit, Fondazione IRCCS Ca’ Granda, Policlinico Maggiore Hospital, Milano; 61 Surgical Clinic, Torrette Hospital, University of Ancona; 62 General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma; 63 General Surgery Unit, S. Maria della Misericordia Hospital, Rovigo; 64 Colorectal Surgery Unit, Humanitas University, Rozzano (MI); 65 General & Bariatric Surgery Unit, University Hospital, Verona; 66 General & Oncologic Surgery Unit, Evangelico Betania Hospital, Napoli; 67 General Surgery Unit, Misericordia Hospital, Grosseto; 68 Abdominal Oncologic Surgery Unit, Basilicata Oncologic Hospital, Rionero in Vulture (PZ); 69 General Surgery Unit, Fornaroli Hospital, ASST Ovest Milanese, Magenta (MI); 70 General Surgery Unit, Civil Hospital, Baggiovara (MO); 71 General Surgery Unit, Villa dei Gerani Hospital, Vibo Valentia (VV); 72 Surgical Clinic, University of Siena; 73 General Surgery Unit, San Giovanni di Dio Hospital, Firenze; 74 General & Transplant Surgery Unit, San Camillo-Forlanini Hospital, Roma; 75 General & Mininvasive Surgery Unit, S. Pietro Hospital, Ponte San Pietro (BG); 76 General Surgery Unit, Pesenti Fenaroli Hospital, Alzano Lombardo (BG); 77 Surgical Clinic, University of Trieste; 78 General & Emergency Surgery Unit, University of Perugia; 79 General & Emergency Surgery Unit, S. Giovanni di Dio e Ruggi d’Aragona Hospital, Salerno; 80 General Surgery Unit, Delta Hospital, Lagosanto (FE); 81 General Surgery Unit, ‘F. Murri’ Hospital, Fermo; 82 General Surgery Unit, S. Leopoldo Hospital, Merate (LC); 83 Surgical Clinic, University of Parma; 84 General Surgery Unit, S. Maria della Misericordia Hospital, Urbino (PU); Italy.