Publications by authors named "Fabrizio Di Benedetto"

163 Publications

Pure laparoscopic versus robotic liver resections: Multicentric propensity score-based analysis with stratification according to difficulty scores.

J Hepatobiliary Pancreat Sci 2021 Jul 22. Epub 2021 Jul 22.

Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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.
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http://dx.doi.org/10.1002/jhbp.1022DOI Listing
July 2021

Proximal splenic artery embolization to treat refractory ascites in a cirrhotic patient.

Hepatology 2021 Jul 4. Epub 2021 Jul 4.

Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy.

Since the early 1970s several studies have reported distal splenic artery embolization, better known as partial spleen embolization (PSE), as an efficacious treatment of portal hypertensive variceal bleeding and hypersplenism in cirrhosis [1,2]. However, the effect of PSE on portal pressure is secondary to the induction of spleen infarction. Depending both on the infarct volume and possible infection, PSE can induce serious complications including death [2,3]. On the other hand, proximal splenic artery embolization (PSAE), which mimics surgical splenic artery ligation, prevents large infarction of the spleen favoring collateral perfusion of its intact distal vasculature [3]. For this, PSAE has been extensively preferred to PSE for reducing portal hyperflow and treating refractory ascites (RA) after whole or partial liver transplantation (LT) [3,4].
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http://dx.doi.org/10.1002/hep.32037DOI Listing
July 2021

Laparoscopic surgery versus radiofrequency ablation for the treatment of single hepatocellular carcinoma ≤3 cm in the elderly: a propensity score matching analysis.

HPB (Oxford) 2021 Jun 8. Epub 2021 Jun 8.

Division of Hepato-Pancreato-Biliary Surgery, "F. Miulli" General Hospital, Acquaviva delle Fonti, Bari, Italy. Electronic address:

Background: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients.

Methods: A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019.

Results: After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03).

Conclusion: Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.
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http://dx.doi.org/10.1016/j.hpb.2021.05.008DOI Listing
June 2021

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

Updates Surg 2021 Jun 5. Epub 2021 Jun 5.

Department of Surgery, Regional Hospital of Treviso, Treviso, Italy.

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.
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http://dx.doi.org/10.1007/s13304-021-01100-9DOI Listing
June 2021

Radiofrequency ablation surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria.

World J Gastroenterol 2021 May;27(18):2205-2218

Unit of Hepato-Pancreatic-Biliary Surgery, "F. Miulli" General Regional Hospital, Acquaviva delle Fonti 70021, Italy.

Background: Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria.

Aim: To evaluate short- and long-term outcome in elderly patients (> 70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA.

Methods: The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression.

Results: After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively ( = 0.001). Disease-free survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group ( = 0.001).Postoperative Clavien-Dindo III-IV complications were lower in the RFA group (1% 11%, = 0.001) in association with a shorter length of stay (2 d 7 d, = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (> 10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (> 1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (> 10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate.

Conclusion: Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (> 70 years) with HCC in Milan criteria.
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http://dx.doi.org/10.3748/wjg.v27.i18.2205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117730PMC
May 2021

Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation.

Liver Int 2021 07 22;41(7):1629-1640. Epub 2021 Apr 22.

General Surgery and Transplant Unit, San Camillo Hospital, Rome, Italy.

Background & Aims: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility.

Methods: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232).

Results: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model . According to the model, one extra point of MELDNa was added for each 0.5 cm /m reduction of total psoas area (TPA) < 6.0 cm /m . At external validation, the Sarco-Model showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model . As for the futility threshold, transplanted patients with TPA < 6.0 cm /m and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%).

Conclusions: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.
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http://dx.doi.org/10.1111/liv.14889DOI Listing
July 2021

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

Updates Surg 2021 Apr 1. Epub 2021 Apr 1.

Liver-Kidney Transplantation Unit, Department of Medicine, University of Udine, Udine, Italy.

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.
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http://dx.doi.org/10.1007/s13304-021-01019-1DOI Listing
April 2021

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study.

Transpl Infect Dis 2021 Mar 26:e13608. Epub 2021 Mar 26.

Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Objective: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM).

Methods: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis.

Results: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06).

Conclusions: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.
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http://dx.doi.org/10.1111/tid.13608DOI Listing
March 2021

Trauma and donation after circulatory death: a case series from a major trauma center.

J Int Med Res 2021 Mar;49(3):3000605211000519

Department of Intensive Care Anesthesia and Trauma Division, Cesena, Italy.

Even with encouraging recipient outcomes, transplantation using donation after circulatory death (DCD) is still limited. A major barrier to this type of transplantation is the consequences of warm ischemia on graft survival; however, preservation techniques may reduce the consequences of cardiac arrest and provide better organ conservation. Furthermore, DCD in trauma patients could further expand organ donation. We present five cases in which organs were retrieved and transplanted successfully using normothermic regional perfusion (NRP) in trauma patients. Prompt critical care support and surgical treatment allowed us to overcome the acute phase. Unfortunately, owing to the severity of their injuries, all of the donors died. However, the advanced and continuous organ-specific supportive treatment allowed the maintenance of general clinical stability and organ preservation. Consequently, it was possible to retrieve and transplant the donors' organs. Death was ascertained in accordance with cardio-circulatory criteria, which was followed by NRP. We consider that DCD in trauma patients may represent an important source of organs.
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http://dx.doi.org/10.1177/03000605211000519DOI Listing
March 2021

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion.

Transplantation 2021 Jan 7. Epub 2021 Jan 7.

1. Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 2. Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 5. UO Chirurgia Generale e dei Trapianti, AOU Sant'Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. 6. Division of Liver Transplantation, AO Papa Giovanni XXIII, Bergamo, Italy. 7. General Surgery 2U, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. 8. Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplant Unit, Padua University, Padua, Italy. 9. Abdominal Surgery and Organ Transplantation Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS - ISMETT), Palermo, Italy 10. Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy 11. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

Background: Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE).

Methods: We coordinated a multicenter retrospective Italian cohort study with 44 controlled DCD donors, who underwent NRP, to present transplant characteristics and results. To rank our results according to the high donor risk, we matched and compared a subgroup of 37 controlled DCD livers, preserved with NRP and D-HOPE, with static-preserved controlled DCD transplants from an established European program.

Results: In the Italian cohort, D-HOPE was used in 84% of cases, and the primary nonfunction rate was 5%. Compared to the matched comparator group, the NRP+D-HOPE-group showed a lower incidence of moderate and severe acute kidney injury (stage 2: 8% vs 27% and stage 3: 3% vs 27%, P=0.001). Ischemic cholangiopathy remained low (2-year proportion free: 97% vs 92%, P=0.317), despite the high-risk profile resulting from the longer donor warm ischemia in Italy (40 vs 18min, P<0.001).

Conclusions: These data suggest that NRP and D-HOPE yield good results in DCD livers with prolonged warm ischemia.
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http://dx.doi.org/10.1097/TP.0000000000003595DOI Listing
January 2021

Total robotic ALPPS approach for hepatocellular carcinoma in cirrhotic liver.

Int J Med Robot 2021 Jun 1;17(3):e2238. Epub 2021 Mar 1.

Hepatopancreatobiliary Surgery and Transplant, Modena University Hospital, Modena, Italy.

Background: Hepatocellular carcinoma (HCC) is a common indication for associating liver partition with portal vein ligation for staged hepatectomy (ALPPS). Robotic liver resection has been done for HCC, but robotic ALPPS is a rare procedure.

Methods: To present three cases of totally robotic ALPPS in cirrhotic patients with HCC.

Results: Three cirrhotic male patients with HCC underwent ALPPS; the mean age was 54.3 years. MELD score was ≤9 and tumour size between 90 and 140 mm. The mean hypertrophy of the future liver remnant after the first stage was 77.5% and no postoperative liver failure was reported. Mean operative time of stage 1 was 7:30 h and of stage 2 was 4:37 h, without blood transfusion. The mean hospital stay for the first stage was 10 days and for the second stage was 9.3 days. No postoperative complication was recorded.

Conclusions: Robotic ALPPS in cirrhotic patients with HCC is safe and feasible.
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http://dx.doi.org/10.1002/rcs.2238DOI Listing
June 2021

Major robotic hepatectomies: technical considerations.

Updates Surg 2021 Jun 7;73(3):989-997. Epub 2021 Jan 7.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, 41124, Modena, Italy.

Robotic approach to the liver may allow to perform difficult resections with a minimally invasive strategy in an easier way as compared to standard laparoscopy. The aim of this study is to review our experience with robotic major hepatectomies, reporting technical considerations, and describing the outcomes of patients that underwent either left (LRH) or right robotic hepatectomy (RRH). Our prospectively maintained database was screened to identify all patients that received a major liver resection for benign or malignant disease. Preoperative data and postoperative short-term and long-term outcomes were reported. 261 robotic procedures were performed in our Center between May 2014 and October 2020. 12 patients underwent robotic left hepatectomy (RLH) and 10 patients were treated by robotic right hepatectomy (RRH). In the RLH group, median operative time (OT) was 383 min, median estimated blood loss (EBL) was 300 ml, and median in-hospital stay was of 3 days. In the RRH group, median OT was 490 min, median EBL 725 ml, and median hospital stay was 5 days. Although one of the advantages of minimally invasive surgery is to obtain radical resections with parenchyma sparing strategies, patients that need a major hepatectomy may benefit of a robotic resection with good postoperative outcomes. Team learning curve and growth instead of personal progression is crucial to expand the limits of novel surgical techniques.
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http://dx.doi.org/10.1007/s13304-020-00940-1DOI Listing
June 2021

Common bile duct lesions - how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct: A case report.

World J Gastrointest Endosc 2020 Dec;12(12):555-559

Endoscopy Unit, Azienda Ospedaliero-Universitaria di Modena, Modena 41121, MO, Italy.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree, with morphological variations and occasional invasion.

Case Summary: We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography. Using the SpyGlass DS II technology, we were able to define tumor extension and obtain targeted Spy-byte biopsies. After multidisciplinary evaluation, the patient was scheduled for surgical resection of the tumor, which was radically removed.

Conclusion: Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.
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http://dx.doi.org/10.4253/wjge.v12.i12.555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739144PMC
December 2020

The COVID-19 second wave risk and liver transplantation: lesson from the recent past and the unavoidable need of living donors.

Transpl Int 2021 03 9;34(3):585-587. Epub 2021 Feb 9.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1111/tri.13803DOI Listing
March 2021

Robotic vs open distal pancreatectomy: A multi-institutional matched comparison analysis.

J Hepatobiliary Pancreat Sci 2020 Dec 12. Epub 2020 Dec 12.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy.

Background: Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR-POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: We collected data from five high-volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed.

Results: Two hundred and forty-six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR-POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively.

Conclusions: Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high-volume and proficient centers.
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http://dx.doi.org/10.1002/jhbp.881DOI Listing
December 2020

Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation.

World J Transplant 2020 Nov;10(11):345-355

Surgery Department, Hepato-Pancreato-Biliary Surgery, Surgical Oncology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria di Modena, University of Modena and Reggio Emilia, Modena 41125, Italy.

Background: Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients. Early postoperative portal vein thrombosis (PVT, incidence 2%-2.6%) and early hepatic artery thrombosis (HAT, incidence 3%-5%) have a poor prognosis in transplant patients, having impacts on graft and patient survival. In the present study, we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.

Aim: To investigate whether intraoperative thromboelastography (TEG) is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation (LT).

Methods: We retrospectively collected thromboelastographic traces, in addition to known risk factors (cold ischemic time, intraoperative requirement for red blood cells and fresh-frozen plasma transfusion, prolonged operating time), in 27 patients, selected among 530 patients (≥ 18 years old), who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT (case group). Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion. We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications (1:1 match) (control group). The chosen matching parameters were: Patient graft and donor characteristics [age, sex, body mass index (BMI)], indication for transplantation, procedure details, United Network for Organ Sharing classification, BMI, warm ischemia time (WIT), cold ischemia time (CIT), the volume of blood products transfused, and conventional laboratory coagulation analysis. Normally distributed continuous data are reported as the mean ± SD and compared using one-way Analysis of Variance (ANOVA). Non-normally distributed continuous data are reported as the median (interquartile range) and compared using the Mann-Whitney test. Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher's exact test depending on best applicability. IBM SPSS Statistics version 24 (SPSS Inc., Chicago, IL, United States) was employed for statistical analysis. Statistical significance was set at < 0.05.

Results: Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively. The incidence of early hepatic artery occlusion was 3.02%, whereas the incidence of PVT was 2.07%. A comparison between the case and control groups showed some differences in the duration of surgery, which was longer in the case group ( = 0.032), whereas transfusion of blood products, red blood cells, fresh frozen plasma, and platelets, was similar between the two study groups. Thromboelastographic parameters did not show any statistically significant difference between the two groups, except for the G value measured at basal and 120' postreperfusion time. It was higher, although within the reference range, in the case group than in the control group ( = 0.001 and < 0.001, respectively). In addition, clot lysis at 60 min (LY60) measured at 120' postreperfusion time was lower in the case group than in the control group ( = 0.035). This parameter is representative of a fibrinolysis shutdown (LY60 = 0%-0.80%) in 85% of patients who experienced a thrombotic complication, resulting in a statistical correlation with HAT and PVT.

Conclusion: The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT, suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.
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http://dx.doi.org/10.5500/wjt.v10.i11.345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708883PMC
November 2020

Robotic Liver Resection Versus Percutaneous Ablation for Early HCC: Short- and Long-Term Results.

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Background: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting.

Methods: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short- and long-term outcomes to define the best approach in this specific cohort.

Results: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively.

Conclusions: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.
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http://dx.doi.org/10.3390/cancers12123578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761404PMC
November 2020

Laparoscopic versus open right posterior sectionectomy: an international, multicenter, propensity score-matched evaluation.

Surg Endosc 2020 Nov 2. Epub 2020 Nov 2.

Department of Surgery, Southampton University Hospital, Southampton, UK.

Background: Although laparoscopic liver resection has become the standard for minor resections, evidence is lacking for more complex resections such as the right posterior sectionectomy (RPS). We aimed to compare surgical outcomes between laparoscopic (LRPS) and open right posterior sectionectomy (ORPS).

Methods: An international multicenter retrospective study comparing patients undergoing LRPS or ORPS (January 2007-December 2018) was performed. Patients were matched based on propensity scores in a 1:1 ratio. Primary endpoint was major complication rate defined as Accordion ≥ 3 grade. Secondary endpoints included blood loss, length of hospital stay (LOS) and resection status. A sensitivity analysis was done excluding the first 10 LRPS patients of each center to correct for the learning curve. Additionally, possible risk factors were explored for operative time, blood loss and LOS.

Results: Overall, 399 patients were included from 9 centers from 6 European countries of which 150 LRPS could be matched to 150 ORPS. LRPS was associated with a shorter operative time [235 (195-285) vs. 247 min (195-315) p = 0.004], less blood loss [260 (188-400) vs. 400 mL (280-550) p = 0.009] and a shorter LOS [5 (4-7) vs. 8 days (6-10), p = 0.002]. Major complication rate [n = 8 (5.3%) vs. n = 9 (6.0%) p = 1.00] and R0 resection rate [144 (96.0%) vs. 141 (94.0%), p = 0.607] did not differ between LRPS and ORPS, respectively. The sensitivity analysis showed similar findings in the previous mentioned outcomes. In multivariable regression analysis blood loss was significantly associated with the open approach, higher ASA classification and malignancy as diagnosis. For LOS this was the open approach and a malignancy.

Conclusion: This international multicenter propensity score-matched study showed an advantage in favor of LRPS in selected patients as compared to ORPS in terms of operative time, blood loss and LOS without differences in major complications and R0 resection rate.
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http://dx.doi.org/10.1007/s00464-020-08109-yDOI Listing
November 2020

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant.

JAMA Surg 2020 12 16;155(12):e204095. Epub 2020 Dec 16.

S. Orsola-Malpighi University Hospital, Bologna, Italy.

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015.

Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant.

Design, Setting, And Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017.

Main Outcomes And Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant.

Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk.

Conclusions And Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.
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http://dx.doi.org/10.1001/jamasurg.2020.4095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593884PMC
December 2020

Temporal Trends and Outcomes in Liver Transplantation for Recipients With HIV Infection in Europe and United States.

Transplantation 2020 10;104(10):2078-2086

Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection.

Methods: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined.

Results: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss.

Conclusions: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.
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http://dx.doi.org/10.1097/TP.0000000000003107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919403PMC
October 2020

Minimally Invasive Stage 1 to Protect Against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry.

J Laparoendosc Adv Surg Tech A 2020 Oct 9;30(10):1082-1089. Epub 2020 Sep 9.

Department of General Surgery, Azienda Ospedaliero-Universitaria di Bologna, Maggiore Hospital, Bologna, Italy.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI- versus open-ALPPS for HCC, with specific focus on PHLF. Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%,  < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days,  < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05,  = .040) and partial parenchymal transection (OR = 0.04,  = .027) were protective against PHLF. This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.
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http://dx.doi.org/10.1089/lap.2020.0563DOI Listing
October 2020

Hepatocellular carcinoma and liver transplant: beyond the Milan criteria and the risk of "short-blanket" syndrome.

Hepatobiliary Surg Nutr 2020 Aug;9(4):518-521

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, AOU di Modena and University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.21037/hbsn.2019.11.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423555PMC
August 2020

Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis.

Int J Surg 2020 Oct 12;82:210-228. Epub 2020 Aug 12.

Background: Minimally invasive surgery (MIS) has been increasingly used in the treatment of gastric cancer (GC). Laparoscopic gastrectomy (LG) has shown several advantages over open surgery in dealing with GC, although it is still considered a demanding procedure. Robotic gastrectomy (RG) is now being employed with increased frequency worldwide and has been reported to overcome some limitations of conventional LG. The aim of this updated meta-analysis is to compare surgical and oncological outcomes of RG versus LG for gastric cancer.

Materials And Methods: A systematic review and meta-analysis was conducted using the PubMed, MEDLINE and Cochrane library database of published studies comparing RG and LG up to March 2020. The evaluated end-points were intra-operative, post-operative and oncological outcomes. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI), and a random-effect model was always applied.

Results: Forty retrospective studies describing 17,712 patients met the inclusion criteria. With respect to surgical outcomes, robotic compared with laparoscopic gastrectomy was associated with higher operating time [MD 44.73, (95%CI 36.01, 53.45) p < 0.00001] and less intraoperative blood loss [MD -18.24, (95%CI -25.21, -11.26) p < 0.00001] and lower rate of surgical complication in terms of Dindo-Clavien ≥ 3 classification [OR 0.66, (95%CI 0.49, 0.88) p = 0.005]. With respect to oncological outcomes, the RG group showed a significantly increased mean number of retrieved lymph nodes [MD 1.84, (95%CI 0.84, 2.84) p = 0.0003], but mean proximal and distal resection margin distance and the recurrence rate were not significantly different between the two approaches.

Conclusions: With respect to safety, technical feasibility and oncological adequacy, robotic and laparoscopic groups were comparable, although the robotic approach seems to achieve better short-term surgical outcomes. Moreover, a higher rate of retrieved lymph nodes was observed in the RG group.
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http://dx.doi.org/10.1016/j.ijsu.2020.07.053DOI Listing
October 2020

Laparoscopic major hepatectomy for hepatocellular carcinoma in elderly patients: a multicentric propensity score‑based analysis.

Surg Endosc 2021 Jul 3;35(7):3642-3652. Epub 2020 Aug 3.

Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Acquaviva delle Fonti, Bari, Italy.

Background: Considering the increase in overall life expectancy and the rising incidence of hepatocellular carcinoma (HCC), more elderly patients are considered for hepatic resection. Traditionally, major hepatectomy has not been proposed to the elderly due to severe comorbidities. Indeed, only a few case series are reported in the literature. The present study aimed to compare short-term and long-term outcomes between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients with HCC using propensity score matching (PSM).

Methods: We performed a multicentric retrospective study including 184 consecutive cases of HCC major liver resection in patients aged ≥ 70 years in _8 European Hospital Centers. Patients were divided into LMH and OMH groups, and perioperative and long-term outcomes were compared between the 2 groups.

Results: After propensity score matching, 122 patients were enrolled, 38 in the LMH group and 84 in the OMH group. Postoperative overall complications were lower in the LMH than in the OMH group (18 vs. 46%, p < 0.001). Hospital stay was shorter in the LMH group than in the OMH group (5 vs. 7 days, p = 0.01). Mortality at 90 days was comparable between the two groups. There were no significant differences between the two groups in terms of overall survival (OS) and disease-free survival (DFS) at 1, 3, and 5 years.

Conclusion: LMH for HCC is associated with appropriate short-term outcomes in patients aged ≥ 70 years as compared to OMH. LMH is safe and feasible in elderly patients with HCC.
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http://dx.doi.org/10.1007/s00464-020-07843-7DOI Listing
July 2021

ASO Author Reflections: Robotic ALPPS: The Future is Coming.

Ann Surg Oncol 2020 Dec 13;27(Suppl 3):836-837. Epub 2020 Jul 13.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, MO, Italy.

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http://dx.doi.org/10.1245/s10434-020-08855-2DOI Listing
December 2020

Liver resection in Cirrhotic liver: Are there any limits?

Int J Surg 2020 Oct 9;82S:109-114. Epub 2020 Jul 9.

Chairman of HPB Surgical Division. Miguel Servet University Hospital. Zaragoza, Spain.

Liver resection remains one of the most technically challenging surgical procedure in abdominal surgery due to the complex anatomical arrangement in the liver and its rich blood supply that constitutes about 20% of the cardiac output per cycle. The challenge for resection in cirrhotic livers is even higher because of the impact of surgical stress and trauma imposed on borderline liver function and the impaired ability for liver regeneration in cirrhotic livers. Nonetheless, evolution and advancement in surgical techniques as well as knowledge in perioperative management of liver resection has led to a substantial improvement in surgical outcome in recent decade. The objective of this article was to provide updated information on the recent developments in liver surgery, from preoperative evaluation, to technicality of resection, future liver remnant augmentation and finally, postoperative management of complications.
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http://dx.doi.org/10.1016/j.ijsu.2020.06.050DOI Listing
October 2020

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure for cholangiocarcinoma.

Int J Surg 2020 Oct 7;82S:97-102. Epub 2020 Jul 7.

Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Perihilar cholangiocarcinoma (PHCC) has been a great challenge for surgeons, requiring advanced skills and expertise and was often associated with high morbidity and mortality. Resectability rates are up to 75% even in experienced centers. In patients with PHCC, radical liver and bile duct resection aiming R0 surgical margins offers the best long-term survival. Therefore, extensive resections with low FLR are commonly needed and PVE is offered to induce remnant liver hypertrophy for a long period. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) is considered a promising approach inducing rapid remnant hypertrophy to prevent dropouts due to complications or tumor progression and increase resectability. Although poor results were reported initially, refinements in technique and risk adjustment of patient selection improved outcomes. The procedure is still under debate for the indication of PHCC. This article reviews the current literature on ALPPS in treatment of perihilar and intrahepatic cholangiocarcinoma.
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http://dx.doi.org/10.1016/j.ijsu.2020.06.045DOI Listing
October 2020

First Case of Full Robotic ALPPS for Intrahepatic Cholangiocarcinoma.

Ann Surg Oncol 2021 Feb 7;28(2):865. Epub 2020 Jul 7.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, MO, Italy.

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for intrahepatic cholangiocarcinoma (ICC) demonstrated good long-term outcomes1 and can increase the rate of resectability in locally advanced ICC;2 however, the rates of postoperative complications (Clavien-Dindo grade III) and mortality range between 13.6 and 44% and 0 and 29%, respectively.3 Minimally invasive strategies may reduce the risk of postoperative morbidity, with the same oncologic outcomes.4,5 We report the first case of full robotic ALPPS for advanced ICC.

Methods: The patient was a 61-year-old male diagnosed with a 6.5 cm ICC involving segments IV, V, and VIII. The total clean liver volume was 1553 cc, with a future liver remnant (FLR) volume of 21.6% (segments I, II, and III: 337 cc). The procedure was performed by a senior hepato-pancreato-biliary (HPB) surgeon at the robotic console and a junior HPB surgeon at the table side.

Results: Computed tomography scan on postoperative day (POD) 9 after stage 1 showed that FLR increased up to 38%. The indocyanine green clearance test showed a plasma disappearance rate of 19.8%/min and a retention rate at 15 min of 5.1%; complete blood tests are available at the end of the video. ALPPS was completed on POD 14, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 5. Final pathology showed a 6 cm ICC, G3, R0 margin (10 mm), T2-N0-M0. The patient started adjuvant capecitabine, and after 6 months was in good general condition without signs of local or systemic recurrence.

Conclusions: Robotic ALPPS combines the opportunity to perform a curative resection in patients presenting with insufficient FLR with the advantages of a minimally invasive approach. It is feasible and oncologically accurate for ICC when performed in fully trained HPB centers.
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http://dx.doi.org/10.1245/s10434-020-08794-yDOI Listing
February 2021

Efficient T-Cell Compartment in HIV-Positive Patients Receiving Orthotopic Liver Transplant and Immunosuppressive Therapy.

J Infect Dis 2021 Feb;223(3):482-493

Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Background: In patients undergoing orthotopic liver transplant (OLT), immunosuppressive treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T-cell phenotype and polyfunctionality in human immunodeficiency virus-positive (HIV+) and -negative (HIV-) patients undergoing immunosuppressive treatment after OLT.

Methods: We studied peripheral blood mononuclear cells from 108 subjects divided into 4 groups of 27: HIV+ transplanted patients, HIV- transplanted patients, HIV+ nontransplanted patients, and healthy subjects. T-cell activation, differentiation, and cytokine production were analyzed by flow cytometry.

Results: Median age was 55 years (interquartile range, 52-59 years); the median CD4 count in HIV+ patients was 567 cells/mL, and all had undetectable viral load. CD4+ and CD8+ T-cell subpopulations showed different distributions between HIV+ and HIV- OLT patients. A cluster representing effector cells expressing PD1 was abundant in HIV- transplanted patients and they were characterized by higher levels of CD4+ T cells able to produce interferon-γ and tumor necrosis factor-α.

Conclusions: HIV- transplanted patients have more exhausted or inflammatory T cells compared to HIV+ transplanted patients, suggesting that patients who have already experienced a form of immunosuppression due to HIV infection respond differently to anti-rejection therapy.
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http://dx.doi.org/10.1093/infdis/jiaa395DOI Listing
February 2021

Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study.

Eur J Intern Med 2020 09 30;79:70-75. Epub 2020 Jun 30.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.
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http://dx.doi.org/10.1016/j.ejim.2020.05.041DOI Listing
September 2020
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