Transatlantic registries for minimally invasive liver surgery: towards harmonization.

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.

Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation. METHODS: This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later. RESULTS: Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores. CONCLUSIONS: The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.

Robotic versus open resection for colorectal liver metastases in a "referral centre Hub&Spoke learning program". A multicenter propensity score matching analysis of perioperative outcomes.

Background: Surgical resection is still considered the optimal treatment for colorectal liver metastasis (CRLM). Although laparoscopic and robotic surgery demonstrated their reliability especially in referral centers, the comparison between perioperative outcomes of robotic liver resection (RLR) and open (OLR) liver resection are still debated when performed in referral centers for robotic surgery, not dedicated to HPB. Our study aimed to verify the efficacy and safety of perioperative outcomes after RLR and OLR for CRLM in an HUB&Spoke learning program (H&S) between a high volume center for liver surgery and high volume center for robotic surgery. Methods: We analyzed prospective databases of Pineta Grande Hospital (Castel Volturno) and Robotic Surgical Units (Foligno-Spoleto and Arezzo) from 2011 to 2021. A 1:1 propensity score matching (PSM) was performed according to baseline characteristics of patients, solitary/multiple CRLM, anterolateral/posterosuperior location. Results: 383 patients accepted to be part of the study (268 ORL and 115 RLR). After PSM, 45 patients from each group were included. Conversion rate was 8.89 %. RLR group had a significantly lower blood loss (226 vs. 321 ml; p=0.0001), and fewer major complications (13.33 % vs. 17.78 %; p=0.7722). R0 resection was obtained in 100% of OLR (vs.95.55%, p =0.4944. Hospital stay was 8.8 days in RLR (vs. 15; p=0.0001).Conclusion: H&S represents a safe and effective program to train general surgeons also in Hepatobiliary surgery providing R0 resection rate, blood loss volume and morbidity rate superimposable to referral centers. Furthermore, H&S allow a reduction of health mobility with consequent money saving for patients and institutions.

Long-term effectiveness of resection and radiofrequency ablation for single hepatocellular carcinoma ≤3 cm. Results of a multicenter Italian survey.

BACKGROUND & AIMS: The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma ≤3 cm and compensated cirrhosis. METHODS: The study involved 544 Child-Pugh A cirrhotic patients (246 in the resection group and 298 in the radiofrequency group) observed in 15 Italian centers. Overall survival and tumor recurrence rates were analyzed using the Kaplan Meier method before and after propensity score matching. Cox regression models were used to identify factors associated with overall survival and tumor recurrence. RESULTS: Two cases of perioperative mortality were observed in the resection group and the rate of major complications was 4.5% in the resection group and 2.0% in the radiofrequency group (p=0.101). Four-year overall survival rates were 74.4% in the resection group and 66.2% in the radiofrequency group (p=0.353). Four-year cumulative HCC recurrence rates were 56% in the resection group and 57.1% in the radiofrequency group (p=0.765). Local tumor progression was detected in 20.5% of ablated patients and in one resected patient (p<0.001). After propensity score matching, both survival and tumor recurrence were still not significantly different although a trend towards lower recurrence was observed in resected patients. Older age and higher alpha-fetoprotein levels were independent predictors of poor overall survival while older age and higher alanine-aminotransferase levels resulted to be independent factors associated with higher recurrence rate. CONCLUSIONS: In spite of a higher rate of local tumor progression, radiofrequency ablation can provide results comparable to liver resection in the treatment of single hepatocellular carcinoma ≤3 cm occurring in compensated cirrhosis.

Neuraxial anesthesia in hepato-pancreatic-bilio surgery: a first western pilot study of 46 patients.

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.

Survival after locoregional treatments for hepatocellular carcinoma: a cohort study in real-world patients.

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79-1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64-1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66-1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.

Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma.

BACKGROUND: The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC). OBJECTIVE: To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC. METHODS: In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990-2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata. RESULTS: After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not. CONCLUSIONS: The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.

Postoperative Outcomes Analysis After Pancreatic Duct Occlusion: A Safe Option to Treat the Pancreatic Stump After Pancreaticoduodenectomy in Low-Volume Centers.

Background: Surgical resection is the only possible choice of treatment in several pancreatic disorders that included periampullar neoplasms. The development of a postoperative pancreatic fistula (POPF) is the main complication. Despite three different surgical strategies that have been proposed-pancreatojejunostomy (PJ), pancreatogastrostomy (PG), and pancreatic duct occlusion (DO)-none of them has been clearly validated to be superior. The aim of this study was to analyse the postoperative outcomes after DO. Methods: We retrospectively reviewed 56 consecutive patients who underwent Whipple's procedure from January 2007 to December 2014 in a tertiary Hepatobiliary Surgery and Liver Transplant Unit. After pancreatic resection in open surgery, we performed DO of the Wirsung duct with Cyanoacrylate glue independently from the stump characteristics. The mean follow-up was 24.5 months. Results: In total, 29 (60.4%) were men and 19 were (39.6%) women with a mean age of 62.79 (SD ± 10.02) years. Surgical indications were in 95% of cases malignant diseases. The incidence of POPF after DO was 31 (64.5%): 10 (20.8%) patients had a Grade A fistula, 18 (37.5%) Grade B fistula, and 3 (6.2%) Grade C fistula. No statistical differences were demonstrated in the development of POPF according to pancreatic duct diameter groups (p = 0.2145). Nevertheless, the POPF rate was significantly higher in the soft pancreatic group (p = 0.0164). The mean operative time was 358.12 min (SD ± 77.03, range: 221-480 min). Hospital stay was significantly longer in patients who developed POPF (p < 0.001). According to the Clavien-Dindo (CD) classification, seven of 48 (14.58%) patients were classified as CD III-IV. At the last follow-up, 27 of the 31 (87%) patients were alive. Conclusions: Duct occlusion could be proposed as a safe alternative to pancreatic anastomosis especially in low-/medium-volume centers in selected cases at higher risk of clinically relevant POPF.

Early Diagnosis of Liver Metastases from Colorectal Cancer through CT Radiomics and Formal Methods: A Pilot Study.

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.

The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology.

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.

Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver.

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 × 10(5) PBMCs. The linear dynamic range was from 5 × 10(0) to 5 × 10(6) 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.

Surgical Management of Hepatic Benign Disease: Have the Number of Liver Resections Increased in the Era of Minimally Invasive Approach? Analysis from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry.

BACKGROUND: Increased expertise with minimally invasive liver surgery (MILS) could cause an unjustified extension of indications to resect liver benign disease (BD). The aim of this study was to evaluate the operative risk of MILS for BD and if implementation and diffusion of MILS have widened indications for BD resection. METHODS: A prospective study including centers with > 6 MILS for BD, enrolled in the I Go MILS registry from January 2015 to October 2016. Cysts fenestrations were excluded. RESULTS: Eight hundred eighteen MILS were performed in 15 centers. One hundred seventy-three of these (21.1%) were for BD: conversion rate was 6.9%, postoperative mortality and morbidity rates were 0 and 13.9%. During the same period, 3713 liver resections (open + MILS) were performed and 407 (11.0%) were for BD. A time-trend analysis showed that the total number of MILS and the number of MILS for malignant disease significantly increased, but this increasing trend was not documented for the number of MILS for BD, which remained stable during the study period of time. This trend was confirmed for the overall rate of resected BD (open + MILS) that remained stable. DISCUSSION: BD represents a valid indication for MILS. For BD, 21.1% of MILS was performed, rate significantly lower than that previously reported in Italy. Although an evident growth of the use of MILS was observed during the time period analysis in Italy, this trend did not correspond to an increased number of MILS for BD, and the overall rate of resected BD was comparable to that reported in previous large open series.

MRI and CT findings of a primary malignant fibrous hystiocitoma presenting as a huge glissonian mass; imaging findings with surgical and histological correlations.

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.

Robot-assisted liver surgery in a general surgery unit with a "Referral Centre Hub&Spoke Learning Program". Early outcomes after our first 70 consecutive patients.

BACKGROUND: 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 Hub&Spoke learning program. METHODS: 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. RESULTS: 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. CONCLUSIONS: Minimally invasive robot-assisted liver resection is a safe technique; it allows overcoming many limits of conventional laparoscopy. This innovative, time-enduring Hub&Spoke may allow patients to undergo a proper standard of care also for complex surgical procedures, without the need of reaching referral centres.

Correction to: Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry.

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

Hepaticojejunostomy in the treatment of iatrogenic biliary lesions following laparoscopic cholecystectomy. A retrospective study on 51 cases.

BACKGROUND/AIMS: Laparoscopic cholecystectomy is characterized by a higher incidence of iatrogenic biliary lesions. The Authors evaluate the role of hepaticojejunostomy in the treatment of iatrogenic biliary lesions following laparoscopic cholecystectomy in 51 patients observed in the Campania region, Italy from 1991 to 2003. METHODOLOGY: The Authors report the data of a retrospective multicentric study of 51 patients -39 women (76.47%), 12 men (13.53%)-reoperated on for major biliary lesions following laparoscopic cholecystectomy. Hepaticojejunostomy in 20 cases (39.21%) and T-Tube plasty in 20 cases (39.21%) were performed. RESULTS: The mean follow-up was 25.01 months. The mean hospital stay was 25.7 days. 1/51 patients (1.9%) died from intraoperative incontrollable hemorrhage while cumulative postoperative mortality was 9.8% (5/51 patients). Therapeutic success rate of hepaticojejunostomy was 70% with a T-Tube plasty success rate of 65%. 9/51 patients (17.64%) were reoperated while in 4/51 (7.84%) a biliary stent was positioned. In 1/51 patients (1.9%) a biliary cirrhosis and in 3/51 (5.7%) a bioumoral cholestasis was observed. CONCLUSIONS: Laparoscopic cholecystectomy causes a higher incidence of iatrogenic biliary lesions. Hepaticojejunostomy gives better long-term results and lower morbidity compared to T-Tube plasty. Management of septic complications in patients with iatrogenic biliary lesions represents the first therapeutic step.