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A relevant number of adenomas can be missed during colonoscopy.Assess the current status of colonoscopy procedures in Italian centers.A prospective observational study involving 17 hospitals (34 endoscopists) included consecutive patients undergoing standard colonoscopy. In the first phase, endoscopists performed consecutive colonoscopies. In the second phase, retraining via an online learning platform was planned, while in the third phase data were collected analogously to phase 1.A total of 3,504 patients were enrolled. Overall, a BBPS score ≥6 was obtained in 95.6% of cases (94.8% and 96.9% in the pre- and post-training phases, respectively). 88.4% of colonoscopies had a withdrawal time ≥6 min (88.2% and 88.7% in the pre- and post-training phases). Median adenoma detection rate (ADR) was 39.1%, with no significant differences between the pre- and post-training phases (40.1% vs 36.9%; P = 0.83). In total, 81% of endoscopists had a ADR performance above the 25% threshold.High colonoscopy quality standards are achieved by the Italian hospitals involved. Quality improvement initiatives and repeated module-based colonoscopy-training have been promoted in Italy during the last decade, which appear to have had a significant impact on quality colonoscopy metrics together with the activation of colorectal cancer screening programs.

Near-infrared (NIR) imaging with Indocyanine green (ICG) has been recently proposed for the sentinel lymph node (SLN) and lymphatic out-flow detection in several tumors. Nowadays its application in primary and secondary liver (LCs) and biliary cancers (BTCs) remains uninvestigated. A proof-of-concept prospective observational study including 18 patients underwent surgery for LCs and BTCs from September 2021 to November 2021 was carried out. The intraoperative NIR imaging with ICG was detected at predefined temporary intervals in order to identify the main lymphatic out-flow and the SLN. In 14 patients (77.8%) the lymphatic outflow pathway was visualized with a median time of 3 min after ICG injection (IQR 3-10). The SLN was detected and confirmed at the histological examination in 12 patients (66.7%). Intraoperative NIR imaging with ICG is a safe and feasible method to identify the lymphatic out-flow and SLN in LCs and BTCs.

Three-dimensional visualization technology (3DVT) has been recently introduced to achieve a precise preoperative planning of liver surgery. The aim of this observational study was to assess the accuracy of 3DVT for complex liver resections. 3DVT with hyper accuracy three-dimensional (HA3D™) technology was introduced at our institution on February 2020. Anatomical characteristics were collected from two-dimensional imaging (2DI) and 3DVT, while intraoperative and postoperative outcomes were recorded prospectively. A total of 62 patients were enrolled into the study. 3DVT was able to study tumor extension and liver anatomy, identifying at least one vascular variation in 37 patients (59.7%). Future remnant liver volume (FRLV) was measured using 2DI and 3DVT. The paired samples t test assessed positive correlation between the two methods (p Graphical abstract

Introduction The selection of the most informative quality of care indicator for laparoscopic liver surgery (LLS) is still debated; among those proposed, textbook outcome (TO) seems to provide a compositive measure of the outcomes of surgery. The aim of this study was to investigate the factors related with the TO in a cohort of patients who underwent LLS. Methods Patients who underwent LLS from 2014 to 2021 were included. TO for LLS (TOLLS) was defined as: R0 resection, absence of intraoperative incidents, severe complications, reintervention, 30-day readmission and in-hospital mortality. When also considering no prolonged length of hospital stay (LOS), the outcome was called TOLLS+. Results Four hundred twenty-one patients were included; TOLLS was achieved in 80.5%, TOLLS+ in 60.8% cases. R0 resection was obtained in 90.2% cases, intraoperative incidents occurred in 7.8%, severe complications in 5.0%, reintervention in 0.7%, readmission in 1.4% and in-hospital mortality in 0.2%. 32.5% of patients showed prolonged LOS. After univariate and multivariate analysis, factors influencing TOLLS were age (OR 0.967; p=0.003), concomitant surgery (OR 0.380; p=0.003), operative time (OR 0.996; p=0.008) and blood loss (OR 0.241; p<0.001); factors influencing TOLLS+ were ASA-score (OR 0.533; p=0.008), tumour histology (OR 0.421; p=0.021), concomitant surgery (OR 0.293; p<0.001), operative time (OR 0.997; p=0.016) and blood loss (OR 0.361; p=0.003). Conclusions TOLLS can be achieved in most patients undergoing LLR, and it seems to be influenced mostly by surgery-related factors; conversely, TOLLS+ is achieved less frequently and seems to be influenced also by patient- and tumour-related factors.

Introduction In the last decade, several difficulty scoring systems (DSS) have been proposed to predict technical difficulty in laparoscopic liver resections (LLR). The present study aimed to investigate the ability of four DSS for LLR to predict operative, short-term, and textbook outcomes. Methods Patients who underwent LLR at a single tertiary referral center from January 2014 to June 2020 were included in the present study. Four DSS for LLR (Halls, Hasegawa, Kawaguchi, and Iwate) were investigated to test their ability to predict operative and postoperative complications. Machine learning algorithms were used to identify the most important DSS associated with operative and short-term outcomes. Results A total of 346 patients were included in the analysis, 28 (8.1%) patients were converted to open surgery. A total of 13 patients (3.7%) had severe (Clavien–Dindo ≥ 3) complications; the incidence of prolonged length of stay (> 5 days) was 39.3% (n = 136). No patients died within 90 days after the surgery. According to Halls, Hasegawa, Kawaguchi, and Iwate scores, 65 (18.8%), 59 (17.1%), 57 (16.5%), and 112 (32.4%) patients underwent high difficulty LLR, respectively. In accordance with a random forest algorithm, the Kawaguchi DSS predicted prolonged length of stay, high blood loss, and conversions and was the best performing DSS in predicting postoperative outcomes. Iwate DSS was the most important variable associated with operative time, while Halls score was the most important DSS predicting textbook outcomes. No one of the DSS investigated was associated with the occurrence of complication. Conclusions According to our results DDS are significantly related to surgical complexity and short-term outcomes, Kawaguchi and Iwate DSS showed the best performance in predicting operative outcomes, while Halls score was the most important variable in predicting textbook outcome. Interestingly, none of the DSS showed any correlation with or importance in predicting overall and severe postoperative complications. Graphical abstract

Purpose:Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection.Experimental Design:We identified patients who underwent initial CLM resection during 2007–2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models.Results:Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P = 0.858 and 0.729, respectively).Conclusions:RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.

Supplementary Figure 3. Overall survival (OS) and recurrence-free survival (RFS) by RAS mutation status.

Supplementary Figure description

Supplementary Figure 1. Patient selection

Supplementary Figure 4. Overall survival (OS) by RAS, TP53, and SMAD4 mutation status in 313 patients with unresectable colorectal metastases.

Supplementary Table 1. Genes and codon tested for adequate amplicons Supplementary Table 2. Multivariable hazard ratios (HRs) for OS and RFS by RAS mutation status in 507 patients Supplementary Table 3. Demographic and clinicopathologic characteristics of 313 patients with unresectable colorectal metastases.

Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis.

Background: The evaluation of surgical margins in resected perihilar cholangiocarcinoma (PHCC) remains a challenging issue. Both ductal (DM) and radial margin (RM) should be considered to define true radical resections (R0). Although DM status is routinely described in pathological reports, RM status is often overlooked. Therefore, the frequency of true R0 and its impact on survival might be biased. Objective: To improve the evaluation of RM status and investigate the impact of true R0 on survival. Methods: From 2014 to 2020, 90 patients underwent curative surgery for PHCC at Verona University Hospital, Verona, Italy. Both DM (proximal and distal biliary margin) and RM (hepatic, periductal, and vascular margin) status were evaluated by expert hepatobiliary pathologists. Patients with lymph-node metastases or positive surgical margins (R1) were candidates for adjuvant treatment. Clinicopathological and survival data were retrieved from an institutional database. Results: True R0 were 46% (41) and overall R1 were 54% (49). RM positivity resulted in being higher than DM positivity (48% versus 27%). Overall survival was better in patients with true R0 than in patients with R1 (median survival time: 53 vs. 28 months; p = 0.016). Likewise, the best recurrence-free survival was observed in R0 compared with R1 (median survival time: 32 vs. 15 months; p = 0.006). Multivariable analysis identified residual disease status as an independent prognostic factor of both OS (p = 0.009, HR = 2.68, 95% CI = 1.27–5.63) and RFS (p = 0.009, HR = 2.14, 95% CI = 1.20–3.83). Conclusion: Excellent survival was observed in true R0 patients. The improved evaluation of RM status is mandatory to properly stratify prognosis and select patients for adjuvant treatment.

The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.

Background Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. Methods This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 – 2008 (derivation cohort) and 2009 – 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. Results 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 – 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 – 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 – 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Conclusions Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

The aim of this study was to analyze the risk factors for surgical infectious complications and the outcomes of patients undergoing surgery for perihilar cholangiocarcinoma according to the microbiological examinations.Patients who underwent surgery for perihilar cholangiocarcinoma in the last decade were enrolled, and all clinical and microbiological data were collected from a retrospective monocentric database. Univariate and multivariate analyses were performed distinguishing patients who developed at least 1 surgical infectious complication (surgical site infections, acute bacterial cholangitis, bacteremia).A total of 98 patients were included. Among patients who developed surgical infectious complications (51%), many preoperative characteristics were significantly more frequent: American Society of Anesthesiologists score ≥3 (P = .026), neutrophil-to-lymphocyte ratio ≥3.4 (P = .001), endoscopic sphincterotomy (P = .032), ≥2 biliary drainage procedures (P = .013), acute cholangitis (P = .012), multidrug resistant (P = .009), and ≥3 microorganisms' detection (P = .042); whereas during the postoperative period, surgical infectious complications were associated to increased incidence of intensive care unit readmission (P = .031), major complications (P.001), posthepatectomy liver failure (P = .005), ascites (P = .008), biliary leakage (P = .008), 90-day readmission (P = .003), and prolonged length of hospital stay (P.001). At the multivariate analysis 3 independent preoperative risk factors for surgical infectious complications were identified: neutrophil-to-lymphocyte ratio ≥3.4 (P = .004), endoscopic sphincterotomy (P = .009), and acute cholangitis (P = .013). The presence of multidrug-resistance in the perioperative biliary cultures was related to postoperative multidrug-resistant species from all cultures (P.001) and organ/space and incisional-surgical site infections (P ≤ .044).Infective complications after surgery for perihilar cholangiocarcinoma worsen the short-term outcomes. A careful microbiological surveillance should be carried out in all cases to prevent and promptly treat surgical infectious complications.

Identify the factors related to failure ablation after percutaneous ultrasound guided single electrode radiofrequency ablation (RFA) for hepatocarcinoma (HCC) and propose a score for improving patient selection and treatment allocation.From 2010 to 2020 585 HCC nodules treated with RFA were prospectively collected. Ablation Difficulty Score (ADS) was built-up according to clinical and radiological factors related to failure ablation identified by Cox-logistic regression analysis. The study population was stratified in low risk (ADS 0), intermediate risk (ADS 1), and high risk (ADS ≥ 2) of failure ablation.Overall ablation success rate was 85.5%. Morbidity and mortality rates were 3.5% and 0.0%. According to per nodule analysis the following factors resulted related to failure ablation: size 20 mm (p = 0.002), sub-capsular location (p = 0.008), perivascular location (p = 0.024), isoechoic appearance (p = 0.008), and non-cirrhotic liver (p = 0.009). The ablation success rate was 93.5% in ADS 0, 85.8% in ADS 1 and 71.3% in ADS ≥ 2 (p 0.001). The 1-year local tumor progression (LTP) free survival was 90.2% in ADS 0, 80.6% in ADS 1, and 72.3% in ADS ≥ 2 (p = 0.009). Nodule's size 20 mm (p = 0.014), isoechoic appearance (p = 0.012), perivascular location (p = 0.012) resulted related to lower LTP free survival.Ablation Difficulty Score could be a simple and useful tool for guiding the treatment decision making of HCC. RFA in high risk nodules (ADS ≥ 2) should be carefully evaluated and reserved for patients not suitable for surgery or liver transplantation.

Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings.

The relationship between immune-nutritional status and tumor growth, biological aggressiveness and survival, is still debated. Therefore, this study aimed to evaluate the prognostic performance of different inflammatory and immune-nutritional markers in patients who underwent surgery for biliary tract cancer (BTC). The prognostic role of the following inflammatory and immune-nutritional markers were investigated: Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Neutrophil to Lymphocyte ratio (NLR), Platelet to Lymphocyte ratio (PLR), Lymphocyte to Monocyte ratio (LMR), Prognostic Nutritional Index (PNI). A total of 282 patients undergoing surgery for BTC were included. According to Cox regression and ROC curves analysis for survival, LMR had the best prognostic performances, with hazard ratio (HR) of 1.656 (p = 0.005) and AUC of 0.652. Multivariable survival analysis identified the following independent prognostic factors: type of BTC (p = 0.002), T stage (p = 0.014), N stage (p &lt, 0.001), histological grading (p = 0.045), and LMR (p = 0.025). Conversely, PNI was related to higher risk of severe morbidity (p &lt, 0.001) and postoperative mortality (p = 0.005). In conclusion, LMR appears an independent prognostic factor of long-term survival, whilst PNI seems associated with worse short-term outcomes.

Purpose We retrospectively evaluated outcomes of a new sequential treatment strategy for patients with multiple colorectal liver metastases (CLM): planned incomplete resection and postoperative percutaneous completion ablation for intentionally-untreated lesions under cross-sectional imaging guidance. Methods Patients with CLM who underwent curative-intent hepatectomy and ablation during 2007–2018 were analyzed. Complications, local tumor progression (LTP) rates at ablation site(s), and overall survival (OS) estimated using the Kaplan-Meier method were compared between patients who underwent CLM resection and postoperative percutaneous ablation for intentionally-untreated lesions (completion ablation) and patients who underwent CLM resection and concomitant intraoperative CLM ablation under ultrasound guidance. Results Number and largest diameter of CLM and liver resection complexity did not differ significantly between the completion ablation (n = 23) and intraoperative ablation (n = 92) groups. Microwave (versus radiofrequency) ablation was used more frequently in the completion ablation group than in the intraoperative ablation group (61% [14/23] vs. 6% [6/92], P = 0.001). The complication rate after hepatectomy and ablation was significantly lower in the completion ablation group (21% [5/23] versus 48% [44/92], P = 0.033). No death was observed in either group. The 5-year LTP cumulative incidence was significantly lower in the completion ablation group (31.7% versus 62.4%, P = 0.030). The 5-year OS rate did not differ significantly between groups (53%, completion ablation; 42%, intraoperative ablation; P = 0.407). Conclusions Resection and postoperative percutaneous completion ablation under cross-sectional imaging guidance may be a safe and effective treatment pathway in patients with CLM in whom liver resection alone cannot achieve R0 resection.

INTRODUCTION Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions

Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000–2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3–T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49–3.13, P

Background The refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery. Methods The institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used. Results Perioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality. Conclusions A multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.

Hilar biliary strictures (HBS) are difficult to diagnose and treat, because their etiology is not always ascertained by all the available diagnostic tests. If a diagnosis cannot be made, HBS are classified as indeterminate. In recent years, both new imaging and endoscopic techniques, and a better understanding of hepato-biliary diseases have significantly reduced the number of patients diagnosed with indeterminate HBS. A complete work-up of these patients is mandatory to exclude malignancy and is based on laboratory tests, radiological imaging, and endoscopic procedures. Briefly, a decision-making process for the diagnosis of patients with HBS is discussed and a diagnostic algorithm is proposed.

Background Current evidence supports the curative resection of colorectal cancer and synchronous liver and lung metastases in selected patients.1,2 This video shows simultaneous left colectomy, bilobar liver resection, and lung metastasectomy via a transdiaphragmatic approach for stage IV colorectal cancer.3 PATIENT: A 57-year-old man with a stage IV colonic adenocarcinoma was considered for simultaneous resection of primary, liver, and lung metastases without thoracic incision. The tumor mutational status was KRAS, NRAS, and BRAF wild-type, and the patient underwent preoperative chemotherapy. Technique After performing a midline laparotomy, atypical liver resection of segments 8/4a was performed under the guidance of intraoperative ultrasonography and intermittent Pringle maneuver using the two-surgeon's technique. A small capsular lesion in segment 3 also was intraoperatively detected and resected. Lung metastasectomy of the right lower lobe was performed via a transdiaphragmatic approach using an endoscopic stapler. Sigmoid colectomy with transanal circular-stapled anastomosis was performed. Duration of surgery and blood loss were 358 min and 400 ml, respectively. Histopathological examination showed metastatic colonic adenocarcinoma with negative surgical margins and final stage was T3N2aM1b. The patient was discharged on postoperative day 6 without complication. He was alive and free of disease at 90-day follow-up. Conclusions Simultaneous colon, liver, and lung resection via a transdiaphragmatic approach is a feasible and safe surgical strategy in selected patients with peripheral lung metastases and favorable tumor biology.4 This surgical strategy avoids thoracic incision, multiple operations, and may reduce the healthcare costs and the recovery time to early implement postoperative therapy.

Hepatopancreatoduodenectomy is performed to achieve curative resection of malignant biliary tumors.1 However, the morbidity and mortality associated with this challenging surgical procedure remain high, and optimal indications remain unclear.2–4 Biliary papillomatosis (BP) is a precursor lesion of cholangiocarcinoma. This video shows hepatopancreatoduodenecomy for multifocal cholangiocarcinoma in the setting of BP. A 75-year-old man with a medical history of cholecystectomy presented with obstructive jaundice. Magnetic resonance colangiopancreatography and computed tomography scan showed diffuse biliary dilation with mild enhancing nodularities in the whole extrahepatic bile duct. Cholangioscopy with biopsies proved cholangiocarcinoma arising from BP at the prepapillary common bile duct (CBD) and the biliary confluence. The second-order right ducts were free of disease. The patient underwent nasobiliary drainage and was considered for hepatopancreatoduodenecomy. A right subcostal incision was performed. Intraoperative ultrasound showed BP of the intrapancreatic CBD spreading only to the left bile duct. En bloc resection of the left liver, caudate lobe, and CBD was performed together with pylorus-preserving pancreatoduodenectomy. The reconstruction phase was performed on a single-loop by duct-to-mucosa pancreatojejunostomy, two-duct biliojejunostomy with mucosa-to-mucosa alignment, and duodenojejunostomy. Transanastomotic external stents were used for biliary and pancreatic drainage. Histopathologic examination confirmed foci of cholangiocarcinoma arising from BP. Resection margins were negative. Lymph node metastasis, microvascular invasion, perineural invasion, and mucin secretion were absent. The patient was discharged on postoperative day 14 without complications. At the 2-year follow-up assessment, he was alive and free of disease. Cholangiocarcinoma arising from BP is a proper indication for hepatopancreatoduodenectomy. The long-term oncologic benefits might outweigh the possible perioperative complications.5,6

Purpose: Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection. Experimental Design: We identified patients who underwent initial CLM resection during 2007–2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models. Results: Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P = 0.858 and 0.729, respectively). Conclusions: RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.

Hepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood.Patients who underwent hepatectomy for HCC between 1998-2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm).Of 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis.Patients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.

Background Patients with prior colorectal cancer (CRC) are at slightly increased risk of metachronous colorectal neoplasms, therefore endoscopic surveillance is indicated. Current recommendations of repeating examinations at 1, 3 and 5 years after surgery, are not tailored according to risk stratification. Our aim was to find predictive factors of colorectal neoplasms to build a predictive model, to spare colonoscopies for low-risk patients. Methods Multicenter retrospective study including patients with colon carcinoma surgically resected from 2001 to 2008 (training cohort) and from 2009 to 2013 (validation cohort). A predictive model for neoplasms occurrence at second surveillance colonoscopy was developed and externally validated. Results 396 and 131 patients were included in training and validation cohort respectively. Patients with ≥1 adenoma at the 2nd surveillance colonoscopy were 113/396 (28.5%) and 21/131 (16.5%) in the two groups. In the validation cohort, 3 cancers were found. Four variables were associated with higher risk of metachronous colorectal adenomas at 2nd surveillance colonoscopy on multivariate analysis: age >65 years old, left colectomy, ≥1 advanced adenoma at basal colonoscopy and ≥1 adenoma at first surveillance colonoscopy (table 1). The predictive model showed fair discrimination, with an area under the ROC curve of 0.69 and 0.64, in training and validation cohort respectively. In validation group, If patients with a low-risk profile (i.e. none of the risk factors) skip the 2nd surveillance colonoscopy, 25/131 (19.1%) exams would be saved while missing 2/21 (9.5%) patients with ≥1 adenoma; no cancer would be missed. Conclusions We provided a risk-stratification tool for adenoma occurrence after colon surgery, which could prove cost-effective to select patients who could skip the second surveillance colonoscopy.

Background and aims A split-dose regimen for colonoscopy is recommended by international guidelines, but its adoption is still suboptimal. Our aim was to assess whether a Plan-Do-Study-Act approach (PDSA), a scientific method promoting quality improvement, would be able to improve adherence to a split-dose regimen, and to identify factors influencing its adoption. Methods This study consisted of three phases: Cycle 1: a cross-sectional assessment of split-dose adherence in consecutive outpatients/inpatients undergoing colonoscopies in 74 Italian centers; Educational intervention: regional meetings with literature review, analysis of Cycle 1 data, and discussion on corrective measures; local diffusion of educational material and tools for improvement; Cycle 2: reassessment of split-dose adherence after spontaneous local interventions. Demographic, clinical, and procedural variables were systematically collected. Multivariate logistic regression was used to identify predictors of split-dose adoption. Results In total, 8213 patients (mean age = 60.29 years (SD = 13.58), men = 54 %, outpatients = 88.4 %) were enrolled between 2013 and 2016 (Cycle 1 = 4189 patients and Cycle 2 = 4024 patients). Split-dose adoption rose from 29.1 % in Cycle 1 to 51.1 % in Cycle 2 (P Conclusions An educational intervention with observation-driven corrections through a PDSA approach was able to substantially increase the adoption of a split-dose regimen.

Background and aim: The safety of endoscopic resection of large colorectal lesions (LCLs) (≥20 mm) is clinically relevant. The aim of the present study was to assess the rate of post-resection adverse events (AEs) in a real-life setting. Patients and methods: In a prospective, multicentre, observational study, data from consecutive resections of LCLs over a 6-month period were collected in 24 centres. Patients were followed up at 15 days from resection for AEs. The primary endpoint was intra-procedural bleeding according to lesion morphology. Secondary endpoints were delayed bleeding and perforation. Patient and polyp characteristics, and polypectomy techniques were analysed with respect to the bleeding events. Results: In total, 1504 patients (female/male: 633/871, mean age, 66.1) with 1648 LCLs (29.1% pedunculated and 70.9% non-pedunculated lesions) were included. Overall, 168 (11.2%) patients had post-resection bleeding (8.5 and 2.0% immediate and delayed, respectively), while 15 (1.0%) cases of perforation occurred. Independent predictors of immediate bleeding for pedunculated lesions were bleeding prophylaxis (odds ratio (OR) 0.28, 95% confidence interval (CI) 0.13–0.62), simple polypectomy (versus endoscopic mucosal resection, OR 0.38, 95% CI 0.17–0.88) and inpatient setting (OR 2.21, 95% CI 1.07–5.08), while bleeding prophylaxis (OR 0.37, 95% CI 0.30–0.98), academic setting (OR 0.27, 95% CI 0.12–0.54) and size (OR 1.03, 95% CI 1.00–1.05) were predictors for those non-pedunculated. Indication for colonoscopy (screening versus diagnostic (OR 0.33, 95% CI 0.12–0.86)), antithrombotic therapy (OR 3.12, 95% CI 1.54–6.39) and size (OR 2.34, 95% CI 1.12–4.87) independently predicted delayed bleeding. Conclusions: A low rate of post-resection AEs was observed in a real-life setting, reassuring as to the safety of endoscopic resection of ≥2 cm colorectal lesions. Bleeding prophylaxis reduced the intra-procedural bleeding risk, while antithrombotic therapy increased delayed bleeding. CLINICALTRIAL: (NCT02694120).

Background: Laparoscopic Incisional and Ventral Hernia Repair (LIVHR) is a safe and worldwide accepted procedure performed using absorbable tacks. The aim of the study was to evaluate recurrence rate in a long term follow-up and whether the results of laparoscopic IVH repair in the elderly (≥65 years old) are different with respect to results obtained in younger patients. Methods: One hundred and twenty-nine consecutive patients (74 women and 55 men, median age 67 years, range = 30-87 years) with ventral (N = 42, 32.5%) or post incisional (N = 87, 67.5%) hernia were enrolled in the study. Patients were divided into two groups according to their age: group A (N = 55, 42.6%) aged Results: The mean operative time was not significantly different between groups (66.7 ± 37 vs. 74 ± 48.4 min, p = 0.4). To the end of 2016, seven recurrences had occurred (group A = 3, group B = 4, p = 1). Complications occurred in 8 (16%) patients in group A and 21 (28.3%) patients in group B. Conclusion: In conclusion, our results confirm that the use of absorbable tacks does not increase recurrence frequency and laparoscopic incisional and ventral repair is a safety procedure also in elderly patients.

Irreversible electroporation is a new ablation modality. Our purpose was to describe the MRI findings after irreversible electroporation treatment of hepatocellular carcinoma (HCC).In an 18-month period, we treated 24 HCC lesions in 20 patients who were not candidates for surgery. MRI was performed before and 1 month after irreversible electroporation. We used the liver-specific contrast medium gadoxetic acid. We evaluated the size, shape, signal intensity (T1-weighted, T2-weighted, and diffusion-weighted imaging), dynamic contrast enhancement pattern, and signal behavior during the liver-specific phase. Changes in the perilesional parenchyma, perfusion abnormalities, and complications were also recorded.According to the modified Response Evaluation Criteria in Solid Tumors system, 22 of 24 lesions had a complete response, and two lesions showed a partial response and were retreated. The lesions showed a mean size increase of 10%, with a round or oval shape. On the T1-weighted images, we observed a hyperintense core and a hypointense rim. On the T2-weighted sequences, the signal was heterogeneously hypointense. On diffusion-weighted images, 83% of lesions showed restricted diffusion, with b values of 0-800 s/mm(2), whereas in 17% of the lesions, the signal was not clearly discernible for different b values. The apparent diffusion coefficient values did not show statistically significant differences between the baseline (800-1020 × 10(-3) mm(2)/s) and the reassessment after 1 month (900-1100 × 10(-3) mm(2)/s). The necrotic area did not show a signal increase after contrast material injection. Perfusion abnormalities, such as areas of transient hepatic intensity difference, were present in the tissue adjacent to six treated lesions. In two patients, a reduced or absent concentration of the contrast medium was observed during the liver-specific phase around the ablation zone. One patient had an arteriovenous shunt and another had biliary duct dilatation.MRI detects characteristic morphologic and functional changes after irreversible electroporation treatment.

The majority of currently available oesophageal metal stents are partially covered to reduce migration risk. Preliminary experiences with fully covered stents seem to indicate an increased risk of migration in patients treated for malignant dysphagia. The aim of our study was to determine, in this setting, the safety and efficacy of a new, recently introduced stent with anti-migration proprieties.We designed a prospective, multicentre, non-randomized, follow-up study in nine tertiary referral centres. Eighty-two patients with dysphagia due to inoperable or metastatic oesophageal cancer were included. In all of them the fully covered WallFlex(®) stent was placed. Main outcome measurements included functional outcome, recurrent dysphagia, complications, and mortality.Dysphagia score improved from a median of 3, before stenting, to 1 at 4 weeks after stent placement (P0.001). Perforation occurred in 1 patient after 39 days, while bleeding was reported in 3. In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (N=10, 12.2%), tissue overgrowth (N=7; 8.5%), and food impaction (N=2; 2.4%).Placement of the fully covered WallFlex(®) stent resulted in safe and effective palliation of malignant dysphagia, with migration and tissue overgrowth rates comparable to previously reported data on partially covered stents.