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There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013–2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42–56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p&nbsp

Simple Summary The treatment of peri-hilar (h-CCA) and intrahepatic (i-CCA) cholangiocarcinoma is an evolving field in hepato-pancreato-biliary surgery. Continuous development of radiological and surgical techniques currently offers different treatment strategies, ranging from traditional hepatectomies to complex approaches involving preoperative portal vein embolization or associating liver partition and portal vein ligation for staged hepatectomy. Recent advances in perioperative chemo-radiotherapy have improved patient survival and have been incorporated into transplant protocols, yielding excellent results. We report a comprehensive review of current surgical and multimodal approaches to h-CCA and i-CCA treatment. Abstract Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Background: The benefits of pure laparoscopic and robot-assisted liver resections (LLR and RALR) are known in comparison to open surgery. The aim of the present retrospective comparative study is to investigate the role of RALR and LLR according to different levels of difficulty. Methods: The institutional databases of six high-volume hepatobiliary centers were retrospectively reviewed. The study population was divided in two groups: LLR and RALR. The procedures were stratified for difficulty levels accordingly to three classifications. A propensity score matching was implemented to mitigate selection bias. Short-term outcomes were the object of comparison. Results: Nine hundred and thirty-six LLR and 403 RALR were collected. RALR exhibited fewer cases of intraoperative blood loss, lower transfusion and conversion rates (especially for oncological radicality) than LLR in the setting of highly difficult operations, whereas LLR had lower postoperative morbidity and fewer low-grade complications. For intermediate and low-difficulty resections, the intraoperative advantages of RALR gradually decreased to nonsignificant results and LLR remained associated with lower postoperative morbidity. Conclusion: Robot-assisted liver resections do not show operative nor clinically significant benefits over LLR for low- and intermediate-difficulty resections. By reducing conversion rates, RALR can favour the operative feasibility of difficult resections possibly extending the indications of minimally invasive approaches for liver resection.

Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.

Introduction No definitive data describing associations between cases of Open Abdomen (OA) and Entero-atmospheric fistulae (EAF) exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) thus analyzed the International Register of Open Abdomen (IROA) to assess this question. Material and methods A prospective analysis of adult patients enrolled in the IROA. Results Among 649 adult patients with OA 58 (8.9%) developed EAF. Indications for OA were peritonitis (51.2%) and traumatic-injury (16.8%). The most frequently utilized temporary abdominal closure techniques were Commercial-NPWT (46.8%) and Bogota-bag (21.9%). Mean OA days were 7.9 ± 18.22. Overall mortality rate was 29.7%, with EAF having no impact on mortality. Multivariate analysis associated cancer (p = 0.018), days of OA (p = 0.003) and time to provision-of-nutrition (p = 0.016) with EAF occurrence. Conclusion Entero-atmospheric fistulas are influenced by the duration of open abdomen treatment and by the nutritional status of the patient. Peritonitis, intestinal anastomosis, negative pressure and oral or enteral nutrition were not risk factors for EAF during OA treatment.

To date, the improvements in survival of patients with liver metastases and advances in technology allowed the surgical indications to be extended. In complex cases, however, the possibility of performing a curative hepatic resection collides with the need to preserve a sufficient liver volume to avoid a postoperative hepatic failure. Currently postoperative liver failure is the major cause of death for these patients. In the attempt to overcome this limit in the last decades, we tried to introduce new measures and develop new surgical techniques. From the introduction by Makuuchi in the 1980s of the preoperative portal embolization, many surgical techniques have been proposed and perfected. The aim of this chapter is to describe the new surgical techniques for the approach of complex hepatic metastases.

The article by Matthews and colleagues (1) emphasizes the potential impending consequences of underreporting secondary endpoints in studies addressing surgical site infection rates. Generally speaking, this may be a very crucial question about clinical trial methodology and rigor.

Introduction The safety and the protective role of stenting the pancreato-jejunal anastomosis on the occurrence of pancreatic fistula is debated. Aim of this study was to evaluate the outcome of patients who received internal stenting during pancreatoduodenectomy and to review the literature on the related complications. Methods From 2007 to 2014 we performed 207 pancreatoduodenectomies with endto-side duct-to-mucosa pancreato-jejunal anastomosis. We retrospectively analyzed the outcome of 38 high-risk patients with an internal stent through the pancreato-jejunal anastomosis. The occurrence and severity of pancreatic fistula were defined according to International Study Group of Pancreatic Fistula classification. We evaluated the fate and complications of the stents by radiological and clinical follow-up. A literature review was performed through web-search. Results No patients had stent-related symptoms or complications. Seven patients (18.4%) developed clinically relevant pancreatic fistula. We had a mean of 1.9±0.9 (SD) postoperative imaging exams for 33 patients. The median time of follow-up was 3 months (range 1-62). The stent was no longer visible in 17 patients (51.5%); in 8 cases (24.2%) it was in the pancreatic duct, in 7 (21.2%) migrated in the jejunal limb and in 1 patient into the colon. By literature review we retrieved 13 papers reporting on long-term outcomes of internal pancreato-jejunal stenting. Discussion Internal stenting does not seem to be associated with major long-term morbidity, but the short follow-up does not allow definitive judgment on the fate of the stents still in place or dislocated into the jejunal limb. Literature describes a low rate of complications, mainly hepato-biliary infections due to stent migration

In surgical patients, malnutrition is an important risk factor for post-operative complications. In undernourished patients undergoing major gastrointestinal procedures, preoperative enteral nutrition (EN) should be preferred whenever feasible. It may be given either orally or by feeding tubes, depending on patient compliance. Early oral intake after surgery should be encouraged, but if an insufficient postoperative oral intake is anticipated, tube feeding should be initiated as soon as possible. The use of immunomodulating formulas offers significant advantages when compared to standard feeds and the positive results on postoperative complications seem independent from the baseline nutritional status. In malnourished patients, the optimal timing and dose of immunonutrition is unclear, but consistent data suggest that they should be treated peri-operatively for at least two weeks. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

Purpose: Surgical site infections (SSIs) are the most common infections in colorectal surgery. Although some studies suggest that rectal surgery differs from colon surgery for SSI incidence and risk factors, the National Nosocomial Infection Surveillance system categorizes all colorectal surgeries into only one group. The aim of this study was to determine incidence, characteristics, and risk factors of SSIs according to the subclassification of colorectal surgery into right colon surgery (RCS), left colon surgery (LCS), and rectum surgery (RS). Methods: From November 2005 to July 2009, all patients requiring colorectal resectioning were enrolled into our program. The outcome of interest was an SSI diagnosis. Univariate and multivariate analyses were performed to determine SSI predictors in each group. Results: Two hundred seventy-seven consecutive colorectal resections were analyzed. SSI rates were 8% in RCS, 18.4% in LCS, and 17.6% in RS. LCS and RS showed significantly higher SSI incidences (p∈=∈0.022) and greater rates of organ/space infections compared to RCS (p∈=∈0.029). Predictors of SSI were steroid use among RCS, age greater than 70 years, multiple comorbidities, steroid use, non-neoplastic colonic disease, urgent operation, ostomy creation, postoperative intensive care among LCS, preoperative chemoradiation, heart disease, and prolonged operation among RS patients. On multivariate analysis, the coupled LCS and RS groups showed an increased risk for SSI compared to RCS (OR, 2.57). Conclusions: SSI incidences, characteristics, and risk factors seem to be different among RCS, LCS, and RS. A tailored SSI surveillance program should be applied for each of the three groups, leading to a more competent SSI recognition and reduction of SSI incidence and related costs. © 2010 Springer-Verlag.

OBJECTIVE: To identify predictive risk factors for conversion to open splenectomy and postoperative complications in patients undergoing elective laparoscopic splenectomy. BACKGROUND: The laparoscopic approach represents the "gold standard" for splenectomy, but its use in the treatment of splenomegaly and malignant disease is controversial. Factors that influence immediate outcome are clinical, anatomic, and pathologic. METHODS: Univariate and multivariate analyses of data from the Italian Registry of Laparoscopic Surgery of the Spleen, a multicenter database supported by 25 referral centers. Analysis of data (1993-2007) was performed on a series of patients (n = 676) undergoing elective laparoscopic splenectomy. Demographic data, the operative indications, the surgical technique applied, and any intra- and/or postoperative complications with respect to the patients were assessed. Records were analyzed retrospectively using the Student t test, the chi test, and logistic regression. RESULTS: Conversion to open splenectomy was necessary in 39 cases (5.8%). Perioperative deaths occurred in 3 cases (0.4%). There were no complications in 560 patients (82.8%), with a mean hospital stay of 5 days (range, 2-54). Overall, morbidity occurred in 116 patients (17.2%). Multivariate analysis found that the body mass index (P = 0.01) and the presence of hematologic malignancy (P < 0.001) were independent predictors for intraoperative complications and surgical conversion. Spleen longitudinal diameter (P = 0.001) and surgical conversion (P = 0.001) were independent predictors for the occurrence of postoperative complications. CONCLUSIONS: This large multicenter study provides evidence for the significance of predictive risk factors for intra- and postoperative complications in laparoscopic splenic surgery. Besides splenic dimensions, other factors like the patient's habitus and the specific underlying hematologic pathology should be recognized by the surgeon to reduce complications and initiate adequate treatment.

PURPOSE: In literature, few papers compare different hemostatic devices in laparoscopic adrenalectomy. This sequential cohort study analyzes the outcomes of laparoscopic adrenalectomy performed by different hemostatic instruments, to evaluate if any of them has any advantage over the other and as secondary endpoints, the impact of body mass index (BMI) and tumor size on the indication, and the outcome of laparoscopic adrenalectomy. METHODS: Forty-six patients, aged 54.6 +/- 46 years, underwent laparoscopic adrenalectomy over 5 years. Mean BMI was 27 +/- 4.8 kg/m(2). Twenty-four patients had a left tumor, and 22 had a right one. Patients were divided into two groups according to the hemostatic device: Ultracision was used in 26 patients, and Ligasure was used in 20. Groups were well matched for histology, tumor size and site, BMI, gender, and age. RESULTS: Mean operating time was 126.5 +/- 52 min, blood losses were 101 +/- 169 mm, conversion rate was 6.5%, morbidity was 26%, and hospitalization was 5.3 +/- 2.5 days. Groups did not differ for surgical time, blood losses, complications, and conversion rate; BMI and length of surgery were not related. Tumor side and size did not affect surgical time, regardless of the hemostatic tool. Patients submitted to left adrenalectomy bled more (p = 0.007) and had more complications (p = 0.016) than those undergone operation on the right side. CONCLUSIONS: Obesity (BMI > 30) and large masses do not contraindicate laparoscopic adrenalectomy. Left adrenalectomies bleed more and have a higher morbidity. Hemostatic device choice is up to surgeon's preference.

Assessment of the severity of acute pancreatitis (AP), together with the patient's nutritional status is crucial in the decision making process that determines the need for artificial nutrition. Both should be done on admission and at frequent intervals thereafter. The indication for nutritional support in AP is actual or anticipated inadequate oral intake for 5-7 days. This period may be shorter in those with pre-existing malnutrition. Substrate metabolism in severe AP is similar to that in severe sepsis or trauma. Parenteral amino acids, glucose and lipid infusion do not affect pancreatic secretion and function. If lipids are administered, serum triglycerides must be monitored regularly. The use of intravenous lipids as part of parenteral nutrition (PN) is safe and feasible when hypertriglyceridemia is avoided. PN is indicated only in those patients who are unable to tolerate targeted requirements by the enteral route. As rates of EN tolerance increase then volumes of PN should be decreased. When PN is administered, particular attention should be given to avoid overfeeding. When PN is indicated, a parenteral glutamine supplementation should be considered. In chronic pancreatitis PN may, on rare occasions, be indicated in patients with gastric outlet obstruction secondary to duodenal stenosis or those with complex fistulation, and in occasional malnourished patients prior to surgery. © 2009 European Society for Clinical Nutrition and Metabolism.

Purpose: New hemostatic technologies (NT) are often employed in thyroid surgery in the effort to reduce operating time and complications. The aim of this study is to compare three different hemostatic techniques. Methods: This is a prospective randomized study. There were 150 patients, aged 56±14 years, randomized for total thyroidectomy with conventional technique (CT), Ligasure vessel sealing system (LI) or Harmonic Scalpel (HS) at the university surgical department. One hundred thirty-five patients had benign diseases; 15 had malignancies. Results: Mean postoperative hospital stay was 2.6 days. Mean operation time was 113±31 min; in HS patients, it was significantly shorter (p

BACKGROUND& AIMS: Perioperative nutrition with specialized enteral diets improves outcome when compared with standard formulas. A post-hoc analysis suggested preoperative administration as the most important period. Thus, we designed a study to understand prospectively whether preoperative supplementation could be as efficacious as the perioperative approach and superior to a conventional treatment (no artificial nutrition) in reducing postoperative infections and length of hospital stay. METHODS: A total of 305 patients with preoperative weight loss

L’adenocarcinoma pancreatico e’ una delle neoplasie con piu’ alta mortalita’ nei paesi occidentali, con una sopravvivenza media di 6 mesi e una percentuale estremamente bassa di sopravvivenza a lungo termine. L’evento principale nello sviluppo dell’adenocarcinoma pancreatico e’ la mutazione del gene KRAS, che tuttavia e’ particolarmente difficile da colpire a livello molecolare. Strategie terapeutiche piu’ efficaci per l’adenocarcinoma pancreatico possono derivare dall’impiego di terapie molecolari. L'obiettivo di questo lavoro e’ quello di identificare nuovi meccanismi e molecolari e strategie terapeutiche per l’adenocarcinoma pancreatico attraverso l’uso modelli cellulari e murini KRAS mutati. Metodi Abbiamo analizzato i risultatiti dello screening di 50 molecole su piu’ di 500 linee cellulari tumorali (incluso 46 di adenocarcinoma pancreatico). Abbiamo disegnato due strategie differenti incluso: 1) un inibitore di JAK2 che inibisce funzionalmente STAT3 e 2) un inibitore di MEK1/2 (AZD-6244), in monoterapia o in combinazione con un inibitore di PI3K (BKM-120 e GDC-0941), in un modello murino KRAS mutato che ricapitola la progressione istopatologica dell’adenocarcinoma pancreatico. Risultati 1) JAK2: lo screening su larga scala di linee cellulari con un inibitore di JAK2 ha mostrato che l’adenocarcinoma pancreatico mostra una sensitivita’ aumentata ( fino a >30 volte) per questa molecola. La sensitivita’ correla con il livello di espressione di pSTAT3 e gp130, un recettore a monte della cascata di STAT3. Abbiamo inoltre osservato che il sottogruppo di adenocarcinoma pancreatico con alti livelli di STAT3 mostra una attivazione costante del pathway IL6/LIF-gp130. Per definire la funzione di STAT3 nell’adenocarcinoma pancreatico, abbiamo quindi sviluppato un modello murino condizionale per STAT3. STAT3 e’ necessario precocemente per lo sviluppo the di lesioni pre-neoplastiche come PanIN (Neoplasia pancretica intraepiteliale) e ADM (Metaplasia acino-duttale). In aggiunta, l’inattivazione di STAT3 blocca lo sviluppo dell’adenocarcinoma pancreatico in un modello ortotopico. I nostri risultati dimostrano che STAT3 ha un ruolo critico nella inizio e progressione dell’adenocarcinoma pancreatico, indicando che la sua inibizione possa essere una strategia terapeutica efficace. Inoltre dimostra che l’espressione di gp130 e pSTAT3 possa essere un biomarker efficace per predire la risposta a un inbitore di JAK2. 2) MEK/PI3K: un altro dato emerso dal nostro screening cellulare e’ che l’adenocarcionoma pancreatico e’ relativamente resistente a monoterapie. Il profilo dell’inibitore di MEK1/2. AZD-6244, ha mostrato una alta efficacia per l’adenocarcinoma pancreatico. Abbiamo tuttavia notato che per indurre apoptosi era necessario associare un inibitore di PI3K (BKM-120 o GDC-0941). Abbiamo testato questa combinazione in modelli murini di adenocarcinoma pacreatico e comparato con trattamento in monoterapia, agenti tradizionali e placebo. La combinazione di MEK e PI3K ha mostrato di ritardare l’insorgenza dei tumori e di aumentare la soopravvivenza in tumori avanzati, sebbene i tumori tendessero a ricorrere nel lungo termine. Conclusioni Questo lavoro dimostra che 1)JAK2 e’ un target molecolare per il trattamento dell’adenocarcinoma pancreatico, in particolare in tumori con alti livelli di GP130; 2) MEK e PI3K sono essenziali nella progressione dell’adenocarcinoma pancreatico e la loro inibizione combinata potrebbe rappresentare una efficace strategia terapeutica. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging. As new targeted agents are becoming available for clinical trial we aimed to design improved therapeutic approaches for the treatment of pancreatic ductal adenocarcinoma by means of in vitro and in vivo models of pancreatic adenocarcinoma. Methods We analyzed the results of a high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically-relevant compounds. We designed two different strategies including 1) a JAK2 inhibitor that blocks STAT3 function and 2) a MEK1/2 inhibitor, AZD-6244, for efficacy alone or in combination with the PI3K inhibitors, BKM-120 or GDC-0941, in a KRASG12D-driven GEMM that recapitulates the multi-step pathogenesis of human PDAC. Results 1) JAK2 inhibitor: Large-scale screening of cancer cell lines with a JAK2 inhibitor that blocks STAT3 function revealed a >30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. To define functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC. We showed that STAT3 is required for the development of the earliest pre-malignant pancreatic lesions, acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Moreover, acute STAT3 inactivation blocked PDAC initiation in a second in vivo model. Our results demonstrate that STAT3 has critical roles throughout the course of PDAC pathogenesis, supporting the development of therapeutic approaches targeting this pathway. Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors. 2) MEK1/2/PI3K inhibitors: In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD-6244, was an outlier, showing the highest selective efficacy in PDAC. While MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM-120 or GDC-0941). When tested in a PDAC GEMM and compared to the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Conclusions: Our studies point to 1)JAK2 as a therapeutic target in GP130 high pancreatic cancers and 2) important contributions of MEK and PI3K signaling to PDAC pathogenesis suggesting that dual targeting of these pathways may provide benefit in some PDAC patients.

Background: Duodenal stump fistula (DSF) is a severe complication of gastrectomy. Although nonsurgical therapy is preferred, surgery is still mandatory in one third of DSF patients. The aim of this article is to analyze the surgical management of DSF and factors related to its outcome. Methods: We performed a retrospective multicenter study using data from January 1990 to November 2011 in 16 Italian surgery centers. We collected 8,268 elective gastrectomies for malignancies, 7,987 by the laparotomic and 281 by the laparoscopic approach. Two hundred five patients developed a DSF, 75 of whom underwent surgery for DSF. We analyzed mortality and DSF healing time as well as the impact of clinical, oncological, and surgical characteristics. Results: The laparoscopic approach increased the risk of DSF development (odds ratio 5.6, 95% confidence interval 2.7–10.6, P&nbsp