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Background Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years, and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 came from Eastern countries. After 2015, only retrospective studies have been published, all with inconsistent results. Methods ADiGe (Abdominal Drain in Gastrectomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment. The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, and readmission rate. Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in the control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to the patient and caregivers. Discussion ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure. Trial registration Prospectively registered (last updated on 29 October 2020) at ClinicalTrials.gov with the identifier NCT04227951 .

Background Laparoscopic total mesorectal excision for low rectal cancer is not considered a gold standard treatment due to the high conversion rate and the long operation time. Methods A retrospective review examined a surgical series of 174 laparoscopic low rectal resections involving total mesorectal excision (1995–2006), with particular reference to technical points as well as surgical and oncologic outcomes. Miles operations and partial mesorectal excisions were excluded. Results The cancer affected the low rectum in 110 cases and the medium rectum in 64 cases. A total of 68 patients were subjected to neoadjuvant radiochemotherapy. The anastomosis was mechanical for 83.3% of the cases and intersphinteric through the perineum for 16.6% of the cases. Protective ileostomy was performed in 112 cases. The conversion rate was 4.6%. The mesorectum remained intact in 91.6% of the cases and was partially interrupted in 15 of the cases. In no case was it totally discontinued. The postoperative morbidity rate was 16.7%, and the mortality rate was 0.57%. The incidence of anastomotic fistulas was 14.4%. The percentage was higher for males (18.6 vs 8.3%) and correlated with the low distance of the tumor from the anal verge (18.2 vs 7.8%) and the absence of a protection ileostomy (20.9 vs 10.7%). After an average follow-up period of 48.6 months (range, 24–149 months), six patients (3.44%) experienced a pelvic recurrence. The 5-year overall survival rate was 75.4%, and the disease-free survival rate was 61.9%. Conclusion Laparoscopic total mesorectal excision for low rectal cancer is safe and effective, allowing surgical and oncologic outcomes similar to those reported for open surgery.

Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.

Background Diverting ileostomy is a common procedure in rectal cancer surgery, but it is sometimes associated with a nonnegligible rate of complications. The primary aim of this study was to analyze the incidence and types of stoma-related complications for ileostomy creation after rectal cancer resection. The secondary aims were to report the indications, the technical details, and the efficacy of stoma care provided by ostomy nurses. Methods From 15 February to 31 December 2022, consecutive patients who underwent protective ileostomy after anterior rectal cancer resection were enrolled for prospective data collection at 45 Italian colorectal surgery centers. Univariate and multivariate analyses were performed to evaluate factors that influenced the occurrence of stoma-related complications. Results In all, 287 patients were enrolled in the analysis. The short- and long-term postoperative stoma-related morbidity rates were 33.8% and 29.62%, respectively. The most frequent complications were dehydration (17.77%), peristomal skin dermatitis (13.59%), mucocutaneous separation (8.36%), and stoma retraction (4.18%). At the end of follow-up (median time 9 months), the overall stoma closure rate was 83.97% (241 patients), with a median time to stoma closure of 146 days (range 9–483 days). On multivariate analysis, the presence of a stoma nurse was a significant protective factor against stoma-related complications. Conclusions This study demonstrated that the creation of a protective ileostomy is associated to a nonnegligible rate of short-term and long-term postoperative stoma-related morbidity, higher than 25%. The most frequent complication is dehydration, and the presence of stoma-specialized nurses seems to be a protective factor for stoma-related complications. Moreover, more than 15% of protective stomas were not closed at the end of follow-up.

BackgroundHDV depends on HBsAg for its infectivity. HBsAg can derive from cccDNA and also from the integration of the so-called linear HBV-DNA in the genome of infected hepatocytes. Here, we elucidate the contribution of HBsAg production from linear HBV-DNA integration in sustaining HDV activity and its pathogenetic potential.Material and Methods70 liver biopsies from eAg-negative individuals (74% NUC-treated) were included: 35 with CHB and 35 with CHD. Droplet-digital PCR was used to quantify intrahepatic levels of cccDNA, pgRNA, HDV-RNA and HBs transcripts from cccDNA and from integrated HBV-DNA (Grudda, 2022). Next-generation sequencing by Illumina was applied to assess the integration of linear HBV-DNA in hepatocytes’ genome (in 22 CHB and 32 CHD).ResultsIndividuals with CHD and CHB had comparable age and NUC-treatment duration. CHD was characterized by lower cccDNA and pgRNA than CHB (median [IQR]: 1 [0.02–12] vs 24 [8–93] copies (cps)/1000 cells and 8 [1–147] vs 518 [57–3,894] cps/1000cells, P<0.0001 for both). In CHD, no correlation was observed between cccDNA and intrahepatic HDV-RNA, supporting that HDV replicative activity is not strictly related to the extent of HBV reservoir.At least 1 event of linear HBV-DNA integration was observed in 100% and 78.1% (25/32) of individuals with CHB and CHD (total number of unique HBV-integration events: 847 in CHB and 427 in CHD). Furthermore, in both CHB and CHD, a comparable production of HBs transcripts was observed, with >99% of them from integrated HBV-DNA (median [IQR] cps/1000cells: 12,776 [4,570–55,977] in CHB and 6,041 [323–29,446] in CHD).Among the 427 HBV-integration events observed in CHD, 180 involved coding regions of the hepatocytes’ genome, corresponding to a median (IQR) number of 5 (2–10) unique events per patient. Notably, the number of HBV-integration events in coding regions showed a positive correlation with the amount of integration-derived HBsAg transcripts and with serum HBsAg (Rho=0.54 and 0.64, P<0.01 for both). Even more, HBV-integration events were significantly more frequent in individuals with CHD characterized by higher serum HBsAg levels (median [IQR] number of unique HBV-integration events: 10 [7–16] in people with vs 2 [1–7] in people without serum HBsAg >4 logIU/ml; P=0.01).In 19/25 individuals with CHD characterized by >1 HBV-integration event, HBV-DNA integrants localised in human genes regulating cell proliferation. Among the 60 genes identified, 40 genes are already known to be specifically involved in hepatocarcinogenesis.ConclusionsHDV persistence is independent from the intrahepatic HBV reservoir and is sustained by HBsAg production from integrated HBV-DNA. Higher HBsAg levels (>4logIU/ml) can reflect an enrichment of HBV-DNA integration events in coding regions of hepatocytes’ genome.Localization of HBV integrants suggests that these events may potentially induce hepatocytes proliferation, paving the way for carcinogenesis.

BackgroundLimited information is available on the extent of HDV genetic diversification in ribozyme (critical for HDV replication) and HDAg domains (crucial for viral morphogenesis and containing cytotoxic T lymphocytes epitopes [CTLE]) and their correlation with virological and biochemical parameters.Methods103 individuals with chronic HDV infection were included. Full-length HDV genome sequences were obtained by Illumina (median [IQR] reads/seq: 62045[30460–91899]). Sub-genotypes 1 were defined by phylogenetic analysis. Amino acid (aa) residues were defined conserved if not mutated in 99% of sequences. HDAg domains and CTLE (N=18) were defined according to Pascarella 2010 and Kohsar 2021.ResultsIndividuals were mostly males with a median age of 54 (44–60) years, mainly from Eastern Europe (EE,51%) and Italy (IT,44.8%). Serum HDV-RNA and ALT were 5.6 (4.9–6.2)logIU/ml and 94 (65–152)U/L. Sub-genotypes 1c and 1e were the most prevalent (47.1% and 45.2%): 1c predominated in individuals from EE(77.6% vs 22.4%,P<0.001) while 1e in IT(77.5% vs 22.5%,P<0.001).HDV ribozyme was characterised by a high degree of genetic conservation. An opposite scenario was observed for HDAg in which the number of conserved aa in HDAg dropped to 36.7% (79/214), with 18.2% in coiled coil sequence (CCS), 27.3% RNA binding domain (RDB)2, 30.8% in RBD1, 33.3% in nuclear localization sequence (NLS), 40% in virus assembly signal (VAS) and 63.3% in RBD3. The degree of genetic conservation of CTLEs ranges from 11.1% in CTLEs 46–54 and 43–51 to 60.0% in 140–149.Notably, CTLE 170–179 from individuals with HDV-RNA >5logIU/ml (70% of conserved aa with vs 20% without HDV-RNA <5 logIU/ml, P=0.025) showed lower genetic conservation, suggesting that an enrichment of mutations in this CTLE can enhance viral replication.Finally, despite a comparable degree of genetic conservation between sub-genotypes 1e and 1c, they were characterized by divergent genetic pathways. In particular, sub-genotype 1c was significantly associated with the selection of 7 specific mutations (I16T/V, N22S, D47E, R112K, T180A, A202S, prevalence ranging from 26.5% to 44.9% vs 0% in 1e, P<0.001). Conversely, sub-genotype 1e was significantly associated with the selection of 6 specific mutations (D29E, D46E, K113R, R131K, M171L, I188V prevalence ranging from 23.9% to 43.5% vs 0% in 1c, P<0.009). Notably, in sub-genotype 1c, the co-presence of I16V/T+D47E+A202S correlated with ALT>3ULN (100% vs 27.5%, P=0.001)ConclusionSub-genotypes 1 are characterized by a conspicuous degree of genetic diversification in HDAg that has contributed to the selection of divergent genetic signatures. The enrichment of mutations in specific CTL epitopes could potentially hamper HDV recognition by immune response and in turn enhancing viral replication.Overall, the role of the high degree of genetic variability in affecting the proper HDV detection by the currently available diagnostic assays deserves further investigation.

Background and AimsHepatitis D virus (HDV) infection is often underdiagnosed, despite the severity of the related liver disease. Here, we investigate the rates of HDV screening, HDV seroprevalence and the rate of HDV RNA positivity among antiHDV+ individuals in routine care across Europe and parts of the Middle East, as well as the characteristics of individuals with active HDV infection.MethodWe collected data from 15,200 HBsAg+ people attending 16 tertiary centres during 2021–2023: Northwestern Europe (NWE: UK, Switzerland, Luxembourg, Germany, Sweden; N=3596, 23.6%), Southern Europe (SE: Spain, Italy, Slovenia, Croatia; N=3203, 21.1%), and Eastern Europe (EE: Romania, Serbia, Slovakia; N=4136, 27.2%) and the Middle-East (ME: Israel, Turkey; N=4265, 28.1%).ResultsParticipants were predominantly males (59.5%), HBeAg-negative (90.7%) with a median (IQR) age of 49 (39–60) years and only 28.6% were receiving nucleos(t)ide analog treatment. The rate of HDV screening varied widely across regions: 23.9%, EE; 59.3%, NWE; 71.5%, ME; 79.1%, SE.Overall, HDV seroprevalence was 5.9% (523/8801) with the highest rate of anti-HDV positivity in EE (9.9%), followed by ME (7.0%), NWE (5.8%) and SE (3.3%). By country, anti-HDV positivity peaked in Romania (10.4%), Turkey (8.7%), Germany (7.9%) and Italy (6.8%).Compared to individuals with HBV infection, anti-HDV+ people had significantly higher HBsAg levels (median [IQR]: 3225 [591–9784] vs 2568 [242–11163] IU/ml, p<0.001), lower HBV-DNA (3.1 [2.2–3.9] vs 2.4 [1.6–3.7] log IU/ml, p<0.001) and a more advanced liver disease (Ishak score >4: 25.7% vs 4.6%, HCC: 5.9% vs 1%, p<0.001 for both). HIV coinfection was also more common (10.8% vs 4.1%, p< 0.001).Overall, among 523 individuals with anti-HDV positivity, 82.6% were tested for HDV-RNA and 46.9% showed an active HDV infection with a median (IQR) HDV-RNA of 5.7 (4.2–7.1) log IU/ml and ALT of 92 (58–171) U/L. Strikingly, large regional variations were noted in both HDV-RNA detection (ME: 39.6%, NWE: 40%, SE: 56.1% and EE: 71.6%, p= 0.0002) and HDV-RNA levels (median [IQR] log IU/ml: 6.4 [4.9–7.2] in ME, 5.4 [3.9–6.7] in EE, 5.4 [4.0–7.4] in NWE and 4.0 [3.2–4.7] in SE, p=0.001).Remarkably, among 344 participants tested for HDV-RNA despite anti-HDV negativity, a total of 7 (2%) from EE (N=5), SE (N=1) and Africa (N=1) had detectable HDV-RNA with median levels of 5.4 (5–6) log10 IU/ml.ConclusionsDespite the substantial burden of HDV infection and related liver disease, significant gaps in HDV screening still remain across Europe, particularly in specific regions. Notably, we observed a small but appreciable proportion with HDV RNA despite lack of anti-HDV, underscoring the need for greater standardisation of HDV diagnostics. Overall, the data supports the urgent need to improve and harmonize HDV screening measures and promote the access to antiviral treatment at pan-European level.

In 2011, our regional district adopted an experimental system for fast referral (within 72 h) by general practitioners to several outpatient specialist evaluations including hepatology. The aim of this study was to assess the characteristics and appropriateness of urgent hepatology visits. Retrospective study. Hospital-based study in Italy. A total of 192 subjects referred to our outpatient hepatology clinic classified as 'urgent' were compared with 397 patients evaluated with standard referral. A comparison with 200 patients visited just before the adoption of the new system was also included. Patients' features and appropriateness of referral in urgent and non-urgent groups using the new system. Increase in liver enzymes was the main factor that leads to specialist hepatology consultation and was more frequent in the urgent group (37% vs. 27.1%, P < 0.001). Liver malignancies were identified in 2.6% of patients in the urgent group, whereas this percentage was 10 times lower in the non-urgent group (P = 0.01). Urgent patients required inpatient admission more frequently compared with non-urgent patients (4.2% vs. 0.5%; P = 0.003). Inappropriate referral was recorded in 41% of cases in the urgent group (no reason for urgency 27%; condition not attributable to liver 13.5%). In the non-urgent group, consultations were inappropriate in 20.1% of cases (condition not attributable to liver). In comparison with the old system, the new one allocated >85% of patients with serious illness to urgent group. This strategy is helpful in selecting patients with more serious hepatic conditions. Appropriateness of referral represents a crucial issue.

BackgroundWhile 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.MethodsOne 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.ResultsICA 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.ConclusionsIn 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 registrationClinical trial (Identifier: NCT03934151).

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.