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Background: Several registries focus on patients undergoing minimally invasive liver surgery (MILS). This study compared transatlantic registries focusing on the variables collected and differences in baseline characteristics, indications, and treatment in patients undergoing MILS. Furthermore, key variables were identified. Methods: The five registries for liver surgery from North America (ACS-NSQIP), Italy, Norway, the Netherlands, and Europe were compared. A set of key variables were established by consensus expert opinion and compared between the registries. Anonymized data of all MILS procedures were collected (January 2014–December 2019). To summarize differences for all patient characteristics, treatment, and outcome, the relative and absolute largest differences (RLD, ALD) between the smallest and largest outcome per variable among the registries are presented. Results: In total, 13,571 patients after MILS were included. Both 30- and 90-day mortality after MILS were below 1.1% in all registries. The largest differences in baseline characteristics were seen in ASA grade 3–4 (RLD 3.0, ALD 46.1%) and the presence of liver cirrhosis (RLD 6.4, ALD 21.2%). The largest difference in treatment was the use of neoadjuvant chemotherapy (RLD 4.3, ALD 20.6%). The number of variables collected per registry varied from 28 to 303. From the 46 key variables, 34 were missing in at least one of the registries. Conclusion: Despite considerable variation in baseline characteristics, indications, and treatment of patients undergoing MILS in the five transatlantic registries, overall mortality after MILS was consistently below 1.1%. The registries should be harmonized to facilitate future collaborative research on MILS for which the identified 46 key variables will be instrumental.

We aimed to evaluate the usefulness of C-reactive protein (CRP) and procalcitonin (PCT) as markers of infection, sepsis and as predictors of antibiotic response after non-emergency major abdominal surgery. We enrolled, from June 2015 to June 2019, all patients who underwent surgery due to abdominal infection (peritoneal abscess, peritonitis) or having sepsis episode after surgical procedures (i.e. hepatectomy, bowel perforation, pancreaticoduodenectomy (PD), segmental resection of the duodenum (SRD) or biliary reconstruction in a Tertiary Care Hospital. Serum CRP (cut-off value < 5 mg/L) and PCT (cut-off value < 0.1mcg/L) were measured in the day when fever was present or within 24 h after abdominal surgery. Both markers were assessed every 48 h to follow-up antibiotic response and disease evolution up to disease resolution. We enrolled a total of 260 patients underwent non-emergency major abdominal surgery and being infected or developing infection after surgical procedure with one or more microbes (55% mixed Gram-negative infection including Klebsiella KPC, 35% Gram-positive infection, 10% with Candida infection), 58% of patients had ICU admission for at least 96 h, 42% of patients had fast track ICU (48 h). In our group of patients, we found that PCT had a trend to increase after surgical procedure; particularly, those undergoing liver surgery had higher PCT than those underwent different abdominal surgery (U Mann-Whitney p < 0.05). CRP rapidly increase after surgery in those developing infection and showed a statistical significant decrease within 48 h in those subject being responsive to antibiotic treatment and having a clinical response within 10 days independently form the pathogens (bacterial or fungal). Further we found that those having CRP higher than 250 mg/L had a reduced percentage of success treatment at 10 days compared to those < 250 mg/mL (U Mann-Whitney p < 0.05). PCT did not show any variation according to treatment response. CRP in our cohort seems to be a useful marker to predict antibiotic response in those undergoing non-emergency abdominal surgery, while PCT seem to be increased in those having major liver surgery, probably due to hepatic production of cytokines.

The most common anesthetic approach in hepato-pancreatic-biliary (HPB) surgery is general anesthesia (GA), but it may result in increased morbidity and mortality and peri-operative risks especially in frail patients. The aim of this study was to assess the safety and effectiveness of neuraxial anesthesia (NA) in HPB in a pilot clinical series. This analysis was conducted on 46 consecutive patients undergoing HPB surgery in an Italian Tertial referral center. Data were prospectively collected and retrospectively analyzed. continuous spinal anesthesia (CSA), combined spino-epidural anesthesia (CSEA) and peridural anesthesia (PA) were used in major and minor hepatectomies and bilio-pancreatic surgery instead of GA. NA was evaluated by analyzing the surgical and anesthesiological short-term outcomes. 46 patients were considered eligible for the study between February 2018 and May 2020. The average age was 69.07 (± 9.95) years. 22 were males and 24 were females. According to the ASA score, 19 (41.30%) patients had ASA II, 22 (47.83%) had ASA III and 5 (10.87%) had ASA IV. 22 (47.83%) patients underwent CSA, 20 (43.48%) CSEA and 4 (8.69%) PA. We performed 8 major and 19 minor hepatectomies, 7 bilio-digestive derivations, 5 Whipple procedures, 4 iatrogenic biliary duct injuries, 2 splenopancreatectomies and 1 hepatic cyst fenestration. Clavien-Dindo ≥ 3 was observed in 3 patients. The conversion rate to endotracheal intubation occurring in 3 of 46 (6.52%) patients. After surgery, no local or pulmonary complications and delirium were reported in our series. The present study demonstrates that NA is a safe and feasible option in selected patients, if performed in referral centers by well-trained anaesthesiologists and surgeons.

Background: Liver metastases are a leading cause of cancer-associated deaths in patients affected by colorectal cancer (CRC). The multidisciplinary strategy to treat CRC is more effective when the radiological diagnosis is accurate and early. Despite the evolving technologies in radiological accuracy, the radiological diagnosis of Colorectal Cancer Liver Metastases (CRCLM) is still a key point. The aim of our study was to define a new patient representation different by Artificial Intelligence models, using Formal Methods (FMs), to help clinicians to predict the presence of liver metastasis when still undetectable using the standard protocols. Methods: We retrospectively reviewed from 2013 to 2020 the CT scan of nine patients affected by CRC who would develop liver lesions within 4 months and 8 years. Seven patients developed liver metastases after primary staging before any liver surgery, and two patients were enrolled after R0 liver resection. Twenty-one patients were enrolled as the case control group (CCG). Regions of Interest (ROIs) were identified through manual segmentation on the medical images including only liver parenchyma and eventual benign lesions, avoiding major vessels and biliary ducts. Our predictive model was built based on formally verified radiomic features. Results: The precision of our methods is 100%, scheduling patients as positive only if they will be affected by CRCLM, showing a 93.3% overall accuracy. Recall was 77.8%. Conclusion: FMs can provide an effective early detection of CRCLM before clinical diagnosis only through non-invasive radiomic features even in very heterogeneous and small clinical samples.

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15–25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients’ selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

Background: Pancreaticoduodenectomy is the only possible choice of treatment for peri-ampoullar neoplasms. Morbidity in pancreatic surgery is mainly related to the development of a postoperative pancreatic fistula (POPF). According to International Study Group on Pancreatic Fistula it is possible to grade POPF based on clinical variables. Three main different surgical strategies have been proposed to deal with the pancreatic stump following pancreaticoduodenectomy: pancreatojejunostomy, pancreatogastrostomy and pancreatic duct occlusion, but none of them has been clearly demonstrated to be superior to the others. The aim of our study is to evaluate the feasibility of duct occlusion and its correlations with postoperative pancreatic fistula, “brittle diabetes” and overall survival in a low volume centre. We decided to review our previous experience in the light of the recent Covid pandemic where, in our country, it has been forced in many regions to displace treatment of oncological patients in low volume hospitals with limited experienceMethods: We retrospectively reviewed 56 consecutive patients, from a prospective maintained database, who underwent Whipple’s procedure from January 2007 to December 2014 in a tertiary Hepatobiliary Surgery and Liver Transplant Unit with a low volume of pancreatic resections. The mean follow-up was 24.5 months. Results: The overall incidence of postoperative pancreatic fistula was 66.6%: 15 patients had a Grade A (31.25%), 13 a Grade B fistula (27.03%), and 4 (8.3%) suffered from a life-threatening Grade C fistula. At the last follow-up, 24 of the 28 patients who were alive (85.6%) habitually used substitutive pancreatic enzyme. Conclusion: Duct occlusion can be a safe alternative to pancreatic anastomosis especially in low volume centres and for those patients (age >75 years, obese, hard pancreatic texture, small pancreatic duct) at higher risk of clinically relevant POPF.Trial registration: 'retrospectively registered'

This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry.LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment.A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis.Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales.Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Background In general surgery residency, hepatobiliary training varies significantly across the world. The aim of this study was to establish an international consensus among hepatobiliary surgeons on components of a hepatobiliary curriculum for general surgery residents. Methods A three-round modified Delphi technique was employed. Fifty-two hepatobiliary surgeons involved in general surgery training programs were invited. An initial questionnaire was developed by a group of experts in hepatobiliary and educational research after a systematic literature review. It comprised 90 statements about knowledge, technical skills, attitudes, and postoperative care. Panelists could add or alter items. The survey was delivered electronically and the panel was instructed to score the items based on 5-point Likert scale. Consensus was reached when at least 80% of panelists agreed on a statement with Cronbach's alpha value >0.8. Results Forty-one (79%) experts have participated. Sixteen panelists are based in Asia, 14 in Europe, and 11 in the Americas. Eighty percent of all proposed skills (81/101) were considered fundamental including knowledge (39/43), technical skills (16/32), attitude (15/15), and postoperative care (11/11). Conclusion An international consensus was achieved on components of a hepatobiliary curriculum. Acquiring broad knowledge is fundamental during residency. Advanced liver resection techniques require specialized hepatobiliary training.

Objective: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC) is one of the most important indications for the minimally invasive approach. Our study aims to analyze the experience of the Italian Group of Minimally Invasive Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor location and how it affects morbidity and mortality. Methods: 38 centers participated in this study; 372 cases of LLR for HCC were prospectively enrolled. Patients were divided into two groups according to the HCC nodule location. Group 1 favorable location and group 2 unfavorable location. Perioperative outcomes were compared between the two groups before and after a propensity score match (PS) 1:1. Results: Before PS in group 2 surgical time was longer; conversion rate was higher; postoperative transfusion and comprehensive complication index were also higher. PS was performed with a cohort of 298 patients (from 18 centers), with 66 and 232 patients with HCC in unfavorable and favorable locations, respectively. After PS matching, 62 patients from group 1 and group 2 each were compared. Operative and postoperative course were similar in patients with HCC in favorable and unfavorable LLR locations. Surgical margins were found to be identical before and after PS. Conclusions: These results show that LLR in patients with HCC can be safely performed in all segments because of the extensive experience of all surgeons from multiple centers in performing traditional open liver surgery as well as laparoscopic surgery.

The aim of this study was to evaluate safety, feasibility and short-term outcomes of our first 70 consecutive patients treated by robotic-assisted liver resection after a reversal proctoring between a high HPB volume centre and our well-trained center in minimally invasive General Surgery. Six surgeons were involved in this HubSpoke learning program.From September 2012 to December 2016, 70 patients underwent robotic-assisted liver resections (RALR). We treated 18 patients affected by colorectal and gastric cancer with synchronous liver lesions suspected for metastases in a one-stage robotic-assisted procedure. For the first 20 procedures we had a tutor in the operatory room, who was present also in the next most difficult procedures.The 30- and 90-day mortality rate was zero with an overall morbidity rate of 10.1%. Associated surgical procedures were performed in about 65,7% of patients. The observed conversion rate was 10%. The results of the first 20 cases were similar to the next 50 showing a shortned learning curve.Minimally invasive robot-assisted liver resection is a safe technique; it allows overcoming many limits of conventional laparoscopy. This innovative, time-enduring HubSpoke may allow patients to undergo a proper standard of care also for complex surgical procedures, without the need of reaching referral centres.

Background Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. Results Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC. Conclusions RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows.

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 × 109 viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.

The present case report describes imaging findings (CT and MRI features) of a primary malignant fibrous hystiocitoma, presenting as a dual stage lesion, completely exophytic along liver surface with surgical and histological correlations. Imaging characteristics suggested the nature of the lesion (mesenchymal) and the behavior (expansile growth pattern) which addressed surgeons to a conservative excision.

Importance The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. Objectives To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. Design, Setting, and Participants Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. Main Outcome and Measures Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. Results One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). Conclusions and Relevance An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

Carcinoid tumours arise from neuroendocrine cells and may develop in almost any organ. These type of tumours actually are correctly termed neuroendocrine tumours. Hepatic neuroendocrine carcinomas rarely arise as primary tumour; in fact on 100 cases reported in literature just a few of these are of primary nature. We report the case of a giant hepatic neuroendocrine carcinoma in a 55-year-old man. The symptoms were only recurrent hypoglycemia and an abdominal mass. Diagnosis was performed by blood analysis, ultrasonography, TC scan and In111-DTPA-octreotide scan. Surgical treatment occurred by an en bloc removal of the mass and a wide resection with free margins. Histological examination confirmed diagnosis. Clinical and instrumental diagnostic follow-up show the patient still alive, in very good conditions and disease free two years after surgery.

Background: Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive liver transplant and are subsequently immunosuppressed. As further follow-up of previously reported patients (Di Nicuolo et al. 2005), an assessment of PERV infection was made in the same patient population pharmacologically immunosuppressed for several years after BAL treatment and in healthcare workers (HCWs) involved in the clinical trial at that time. Methods: Plasma and peripheral blood mononuclear cells (PBMCs) from eight patients treated with the Academic Medical Center-BAL (AMC-BAL), who survived to transplant, and 13 HCWs, who were involved in the trial, were assessed to detect PERV infection. A novel quantitative real-time polymerase chain reaction assay has been used. Results: Eight patients who received a liver transplant after AMC-BAL treatment are still alive under long-term pharmacological immunosuppression. The current clinical follow-up ranges from 5.6 to 8.7 yr after BAL treatment. A new q-real-time PCR assay has been developed and validated to detect PERV infection. The limit of quantification of PERV DNA was >= 5 copies per 1 x 105 PBMCs. The linear dynamic range was from 5 x 100 to 5 x 106 copies. In both patients and HCWs, neither PERV DNA in PBMCs nor PERV RNA in plasma and PBMC samples have been found. Conclusion: Up to 8.7 yr after exposure to treatment with porcine liver cell-based BAL, no PERV infection has been found in long-term immunosuppressed patients and in HCWs by a new highly sensitive and specific q-real-time PCR assay

Background: Brain dead patients are the main source of organs for transplants. Brain death causes changes in peripheral organs. We define modifications of gene expression in specific pathways occurring in donor livers and their influence on gene expression profile of livers after transplant. Methods: We compared gene expression profile of both deceased donor livers and transplanted livers to gene expression data of liver tissue, retrieved from Array Express database, used as control. All expression data were obtained by microarray analysis. Results: The expression of about 33,000 genes has been compared in liver samples from three groups: deceased donor livers, transplanted livers two hours after reperfusion, and control livers. We found that about 900 genes are dysregulated in deceased donor versus control livers. Up-regulated genes are mainly involved in apoptosis, immune response and inflammation. Down-regulated genes are mostly involved in metabolism and electron transport. We also re-evaluated a group of genes that in a previous study were found dysregulated in transplanted livers when compared to donor livers. Most of these genes, but not all, were dysregulated also when compared to control livers. Moreover 317 additional genes, dysregulated after liver transplant, were identified in this study; they were undetectable in the previous study because they had the same dysregulation both in donor and in transplanted livers. Conclusions: Understanding molecular mechanisms that in the donor compromise graft function is crucial in order to discriminate between basal graft damages and ischemia-reperfusion injuries and therefore to identify therapeutic targets aiming to improve liver transplantation performances.

Nowadays, the respective approach to hepatic resections (for malignant or benign liver lesions) is oriented toward minimal parenchymal resection. This surgical behavior is sustained by several observations that surgical margin width is not correlated with recurrence of malignancies. Parenchymal-sparing resection reduces morbidity without changing long-term results and allows the possibility of re-do liver resection in case of recurrence. Minimally invasive liver surgery (MILS) is performed worldwide and is considered a standard of care for many surgical procedures. MILS is associated with less blood loss, less analgesic requirements, and shorter length of hospital with a better quality of life. One of the more frequent criticisms to MILS is that it represents a more challenging approach for anatomical segmentectomies and that in most cases a non-anatomical resection could be performed with thinner resection margins compared with open surgery. But even in the presence of reduced surgical margins, oncological results in the short- and long-term follow-up seem to be the same such as open surgery. The purpose of this review is to try to understand whether chasing at any cost laparoscopic anatomical segmentectomies is still necessary whereas non-anatomical resections, with a parenchymal-sparing behavior, are feasible and overall recommended also in a laparoscopic approach. The message coming from this review is that MILS is opening more and more new frontiers that are still need to be supported by further experience.

Cystic and polycystic diseases are genetic and congenital disorders in which cysts occur in the liver (simple cysts and autosomal dominant polycystic liver disease) or in combination with cysts in the kidneys (autosomal dominant polycystic kidney disease). Women have a higher prevalence with a female-to-male ratio of 1.5:1. Most of the patients are asymptomatic and can be managed conservatively. Severe symptoms can affect 20 % of patients who develop massive hepatomegaly with possible compression of surrounding organs. Rarely (

It is a great pleasure for us to introduce this special issue of Updates in Surgery focused on ‘‘Minimally Invasive Surgery of the Liver’’ (MILS). Indeed, this area has recently developed and grown thanks both to advances in new technologies and to efforts done by a new generation of surgeons: in 2015, minimally invasive liver surgery has proved its safety and efficacy when performed by teams with good experience in both laparoscopic and hepatic surgery, allowing a significant reduction of intraoperative blood loss, need for portal clamping, postoperative morbidity and shortening postoperative hospitalization, as a result of a more rapid functional recovery. Initial skepticisms regarding technical challenges and oncological adequacy have been overcome, and great enthusiasm has been raised in this newborn field. In 2014, the 2nd consensus conference on MILS was held in Morioka, Japan, and recommendations based on the strength of scientific evidences have been provided. Many training opportunities are now available for surgeons who want to get specific experience. Overall, the future of MILS seems to be promising. Despite this, many topics still deserve in-depth study: this monographic volume tries to reply to many open issues and to certify and codify what has already been acknowledged in clinical practice; we are witnesses of a dramatic change in the way of approaching many liver diseases and have the duty of offer the best available treatment to our patients. We have the honor of including an Editorial from Professor Wakabayashi who describes current trends of laparoscopic liver surgery and its evolution from Louisville to Morioka. The volume is then structured into two sessions, thanks to the contribution of Italian and international authors: in the first one, four review articles are provided, focusing on hot topics like HCC surgery, definition of segmentectomies, robotic approach and difficulty scores; in the second part, by means of original articles, contributions are provided to scientific knowledge on issues that are still debated, such as indications and contraindications of major resections, resections of posterosuperior segments, outcomes of metastases resection, MILS in highand low-volume Italian centers, advantages and limitations of robotic approach, learning curve and accuracy of laparoscopic ultrasound. We therefore wish to thank all the authors for their effort in providing a better insight into the present and future time of this revolutionary approach to liver surgery. We do hope that this editorial effort may help Italian and foreign colleagues willing to develop their activity in minimally invasive MILS according to the principles of scientific knowledge and evidence-based medicine. Luca Aldrighetti Fulvio Calise

Laparoscopic liver surgery has not yet gained widespread acceptance among liver surgeons. Some questions remain regarding indications to surgery and health related quality of life (HRQOL) after surgery, especially for the treatment of benign lesions, has so far not yet been investigated. The aim of this study is to evaluate HRQOL at 1 month, 6 months and 1 year after surgery in two groups of patients undergoing liver resections for benign liver lesions either by laparoscopic or open surgery. From January 2004 to September 2010 75 patients underwent surgery (29 laparoscopic, 46 open) for benign liver lesions. We retrospectively compared surgical results of the two groups and evaluated HRQOL with the SF-36 test. A personal or telephonic interview was administrated for the assessment of HRQOL before surgical treatment and at 1 month, 6 months and 1 year after surgery. Sixty six patients (88%) were available for the study. The length of stay (4.7 vs. 8.2 days, p = 0.0002), the reprisal of oral intake (II post-op vs. III post-op, p = 0.02) the number of transfused patients (2 vs. 8, p = 0.1) and the overall rate of morbidity (p = 0.06) were lower in the laparoscopic group. HRQOL was significantly better in the laparoscopic group in the first year after surgery. Surgical treatment for benign liver lesions, when indicated, should be laparoscopic. This approach shows a lower rate of surgical complications with a better quality of life after surgery and a faster reprisal of social and job activities.

These prophetic words, written and sung by Bob Dylan almost 50 years ago, may well apply to the (relatively) new field of minimally invasive surgery of the liver (MISL). Nowadays the open approach to liver surgery (OLS) quickly falls behind in comparison with MISL. Older surgeons still have ringing in their ears the repeated warnings concerning risks related to laparoscopic cholecystectomy (LC). Prominent remarks included a possible increased risk of bile duct injuries [1], a prolonged learning curve [2], and the need for young surgeons to have well-established training in OLS before starting to perform LC. None of these alarms has overcome the tide of LC diffusion, and none of them proved to be effectively true. Thanks to many training modalities, such as dry lab, wet lab, simulators, virtual realities, and practice in large animals (pig), young surgeons directly enter into liver surgery using the laparoscopic approach, and open cholecystectomy is almost always and everywhere an embarrassing memory.

Postoperative complications directly due to liver resection are hepatic failure and abdominal fluid collections due to bleeding or biliary leaks from the resection plane. The decrease in complication rates is due to technological advances and the widespread use of anatomically oriented resection techniques that significantly minimize liver-tissue necrosis. Hepatic parenchyma has in fact a complex, high-density framework of vascular and biliary structures, and even the most meticulous and appropriate approach to resection does not exclude the risk of postoperative bleeding and/or biliary leaks.

In 2009, the most comprehensive review of published series of minimally invasive liver resection (MILR) reported nearly 3,000 cases performed worldwide, emphasizing an exponential growth in the application of this technique by surgeons experienced with both hepatic and laparoscopic surgery [1]. The goal of our survey was to provide an overview of the spread of the minimally invasive approach to liver resections in Italy.

Although some liver resections may now be safely performed without vascular clamping, blood saving remains an important concern in hepatobiliary surgery, especially in patients with liver tumors, as blood loss seems to directly affect early and late outcome.

The liver is one of the most frequently injured abdominal organs in trauma (about 35–45% of blunt abdominal trauma, 40% of stab wounds, and 30% of gunshot wounds); about 80% occur in men between 20 and 40 years of age [1]. Liver trauma is classified according to the Liver Injury Scale from the American Association for the Surgery of Trauma (AAST), which lists six grades with progressive severity depending above all on two parameters: depth of parenchyma laceration, and the area of hematoma with or without vascular involvement. The diagnostic and therapeutic approach to abdominal and liver trauma has evolved in recent decades, leading to a reduction in deaths [1, 2].

Shall we see through a camera better than with our eyes? The question, still appropriate at the present time, dates back to the seventeenth century. It seemsthat Vermeer, and then Canaletto some decades later, introduced in their paintings the use of the camera obscura, or optic camera (Figs. 14.1, 14.2). The simplest arrangement, with a lens fastened in the pinhole, projected an inversed and reversed image on a vertical screen opposite the aperture. A variation on this employed a translucent screen, allowing the viewer to see the image from the other side, thereby correcting the left-to-right reversal. These two types of cameras projected the image directly and could be combined in one device. The optical camera obscura ushered in a new approach to optics, opening up new views of the visible world and shaping a new understanding of vision itself.

In 1957, Couinaud published his fundamental paper on the surgical anatomy of the liver [1], describing the eight segments, everyone with its pedicle: artery, portal vein, and bile duct. Since then, every liver surgeon has referred to it as a bible to be followed during routine surgical practice. Only with the experience with liver transplantation in the mid-1990s was splitting segment 1 into two sections suggested, identifying the portion of segment 1 on the right side of the caval vein as segment 9 [2]. This was only a minor modification of the original classification. Since the rapid spread of liver surgery in the 1970s, several authors have suggested technical tricks to remove the entire segment by sectioning the tributary pedicle [3–5].

Portal vein ligation (PVL) is a standard procedure for achieving resectability in patients with an inadequate future remnant liver (FRL) prior to planning subsequent major hepatectomy. Its role in inducing FRL hypertrophy prior to major liver resection is clear [1]. Actually, PVL is the first step in a two-stage hepatectomy for treating initially unresectable liver metastases [1]. As reported in the literature, this procedure can be achieved safely without causing mortality [2]. Capussotti et al. showed how PVL is as effective as PV embolization in inducing hypertrophy of the remnant liver volume [2]. The possibility of using a laparoscopic approach seems to be favorable, even for achieving lower patient morbidity rates, particularly in the case of synchronous colorectal metastasis, avoiding the need to perform a further procedure (laparotomy/portal embolisation) [3,4]. Finally, in a planned two-stage hepatectomy, laparoscopic PVL (LPVL) greatly reduces the presence of adhesions when it is time to perform the second surgical step [5].

Background & Aims: The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma