Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. RESULTS: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. CONCLUSIONS: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.

Bile duct anatomical variations: Relevance for liver division and preparing left split liver grafts for pediatric transplantation: Cohort study.

BACKGROUND: liver lateral section graft is the most common graft type used for transplantation in children worldwide. Compared to whole liver grafts, a higher rate of biliary complications has been described. Historically, 2 techniques have been described for transection of liver - trans-hilar or trans-umbilical parenchymal transection. Though these techniques allow dividing the biliary system at two distinct positions, the usual surgical strategies do not take advantage of this advantage. MATERIAL AND METHODS: A retrospective study was conducted on 40 candidates who volunteered for donation of their left lateral liver section for transplantation, between October 2017 and April 2019. Preoperative imaging was analyzed to depict the arterial and biliary anatomy of the liver and their variations, with a dedicated attention to the left liver (segments 2, 3 and 4). Anatomy of the biliary system was taken into account for defining the optimal surgical strategy - either through a trans-hilar or a trans-umbilical parenchymal transection. RESULTS: In 26/40 patients, arterial or biliary variations were much relevant for decision-making on the optimal plane of liver division (trans-umbilical (N = 14) and trans-hilar (N = 26)). This resulted in 23 grafts with a single artery and bile duct, 6 grafts with double arteries and a single bile duct, and 9 grafts with double bile ducts and a single artery; only two grafts had complex anatomy. There was no arterial complication and the overall incidence of biliary problems was 14.7%. All grafts are functioning well at a mean follow-up of 19.6 ± 8.5 months. CONCLUSIONS: Anatomical variations are frequent and their knowledge is relevant for procurement of lateral section liver graft. Knowledge of these variation, or -better- preoperative biliary imaging is helpful in guiding parenchymal transection at procurement and preparing optimal liver grafts.

Case report: Trans-papillary free stenting of the cystic duct and of the common bile duct in a double biliary ducts anastomoses of a right lobe living donor transplantation.

BACKGROUND: One of the major issues related to the living donor liver transplantation recipient outcome is still the high rate of biliary complication, especially when multiple biliary ducts are present and multiple anastomoses have to be performed. CASE PRESENTATION AND CONCLUSION: We report a case of adult-to-adult right lobe living donor liver transplantation performed for a recipient affected by alcohol-related cirrhosis with MELD score of 17. End-stage liver disease was complicated by refractory ascites, portal hypertension, small esophageal varices and portal gastropathy, hypersplenism, and abundant right pleural effusion. Here in the attached video we described the adult-to-adult LDLT procedures, where a right lobe with two biliary ducts draining respectively the right anterior and the right posterior segments has been transplanted. LDLT required a biliary reconstruction using the native cystic and common bile ducts stented trans-papillary with two 5- French 6 cm long soft silastic catheter. None major complications were detected during post-operative clinical courses. Actually, the donor and the recipient are alive and well. The technique we describe in the video, allow to keep the biliary anastomoses protected and patent without having the risk of creating cholestasis and the need of invasive additional procedure. No living donor right lobe transplantation should be refused because of the presence of multiple biliary ducts.

Vitamin D levels in liver transplantation recipients and early postoperative outcomes: Prospective observational DLiverX study.

BACKGROUND & AIMS: In critically ill patients with liver disease, vitamin D deficiency is associated with higher disease severity, increased frequency of infections, and worse outcomes. This study sought to describe the trend of vitamin D in orthotopic liver transplantation (OLT) recipients and its association with outcomes. METHODS: Prospective observational study of 67 consecutive OLT recipients enrolled between September, 2016 and August, 2017 at IRCCS-ISMETT, Palermo (Italy). Trend of vitamin D levels and potential factors influencing it levels were evaluated through a generalized linear mixed regression model. RESULTS: Sixty-four (95.5%) recipients were vitamin D deficient (<20 ng/ml), with a median value of 8.8 ng/ml [6.2-12.9], and forty-seven of these (70.1%) showed severe deficiency (<12 ng/ml) at baseline, 7.9 ng/ml [5.4-8.9]. The baseline vitamin D showed an inverse correlation with liver disease severity: Child-Pugh, MELD score, bilirubin, INR, and organ failure (p < 0.01) at baseline. Vitamin D increased on postoperative day (POD) 28 compared with POD1: +4.5 ng/ml, C.I. 95% 3.6-5.3 ng/ml, p < 0.01. Lower baseline vitamin D, donor age, transfusion of fresh frozen plasma (negative impact, all p < 0.05), and intra-operative bypass (positive impact at POD 28, p < 0.01) were associated with variation of vitamin D levels after transplantation. Incomplete graft recovery was associated with lower vitamin D on POD28: 8.2 ± 4.4 versus 13.8 ± 9.4 ng/ml, p < 0.01; the odds ratio (OR) was 0.84; CI 95% 0.73-0.97, p = 0.014. The OR for infections within POD 28 was inversely associated with baseline vitamin D: 0.87; CI 95% 0.79-0.98, p = 0.02, and with vitamin D level at baseline <12 ng/ml: OR 6.44; CI 95% 1.66-24.94; p < 0.01. CONCLUSIONS: Preoperative Vitamin D is correlated with disease severity, and was highly associated with invasive infection in the first 28 PODs. After OLT, the value on POD 28 had a strong association with graft function.

ERAS Protocol for Perioperative Care of Patients Treated with Laparoscopic Nonanatomic Liver Resection for Hepatocellular Carcinoma: The ISMETT Experience.

Background: Liver resection (LR) remains the best therapeutic option for patients with early-stage hepatocellular carcinoma (HCC) with preserved hepatic function and who are not eligible for liver transplantation. After its inception, the enhanced recovery after surgery (ERAS) protocol was widely used for treating patients with liver cancer, although there are still no clear indications for improving upon it in both open and laparoscopic surgery. Objective: This study aims to describe our institute's experience in the application of the ERAS protocol in a cohort of HCC patients, and to explore possible factors that could have an impact on postoperative outcomes. Materials and Methods: We retrospectively analyzed our experience with LR performed from September 2017 to January 2020 in patients treated with ERAS protocol, focusing on describing impact on postoperative nutrition, analgesic requirements, and length of hospitalization. Demographics, operative factors, and postoperative complications of patients were reviewed. Results: During the study period, 89 HCC patients were eligible for LR, and 75% of patients presented with liver cirrhosis. The most prevalent among etiologic factors was hepatitis C virus infection (53 patients out of 89, 60%), followed by nonalcoholic steatohepatitis (18 patients, 20%). The median age was 70 years. Liver cirrhosis did not have an impact on postoperative course of patients. Patients who underwent laparoscopic surgery and nonanatomic LR experienced low complication rates, shorter length of stay, and shorter time of intravenous analgesic requirements. Conclusions: Continual refinement with ERAS protocol for treating HCC patients based on perioperative counseling and surgical decision-making is crucial to guarantee low complication rates, and reduce patient morbidity and time for recovery.

Impact of Italian Score for Organ Allocation System on Deceased Donor Liver Transplantation: A Monocentric Competing Risk Time-to-Event Analysis.

BACKGROUND: Liver transplantation (LT) is the only definitive and curative treatment for patients with end-stage liver disease and hepatocellular carcinoma. We aimed to evaluate the impact of the Italian score for organ allocation (ISO) in terms of the waiting-list mortality, probability of LT, and patient survival after LT. PATIENT AND METHODS: All of the adult patients on the waiting list for LT at our institute from January 2014 to December 2017 were included in the study. The probabilities of death while on the waiting list, dropout from the list, and LT were compared by means of cumulative incidence functions, in a competing risk time-to-event analysis setting. Uni- and multivariable logistic regression models were used to estimate and compare the probability of death and to find potential risk factors for waiting-list death. RESULTS: There were 286 patients on the waiting list for LT during the study period, 122 of whom entered the waiting list prior to the implementation of ISO (Group A) and 164 afterward (Group B). Group A had 62 transplants, and Group B had 116 transplants. Group B showed a lesser probability of death (P = .005) and a greater probability of transplant (P < .001) compared to Group A. In the 2 groups, post-transplant survival was similar. CONCLUSION: Based on preliminary clinical experience from a single transplant center, the ISO allocation system demonstrated an overall reduced probability of patient death while on the waiting list without impairing post-LT survival, suggesting that the ISO system might represent an improved method of organ allocation, with a more beneficial distribution of livers.

Enhanced Recovery after Implementation of Surgery Protocol in Living Kidney Donors: The ISMETT Experience.

INTRODUCTION: Laparoscopic living donor nephrectomy (LLDN) has become the standard procedure for living kidney transplantation. Enhanced recovery after surgery (ERAS) is a multimodal perioperative management aimed at facilitating rapid patient recovery after major surgery by modifying the response to stress induced by exposure to surgery. This association can further reduce hospital stay, surgical stress, and perioperative morbidity of living kidney donors. MATERIAL AND METHODS: In this retrospective analysis conducted at our institute, we compared the first 21 patients who underwent LLDN enrolled with the ERAS protocol with 55 patients who underwent LLDN with the fast-track protocol in the 5 years prior to ERAS protocol implementation. RESULTS: We evaluated 76 consecutive patients. After ERAS protocol implementation, elderly living donors had a shorter hospital stay and a faster return to normal life compared with the same age group of patients in the previous period. There were no major differences in median postoperative hospital stay and no meaningful differences in the percentage of complications after surgery and hospital readmissions. CONCLUSIONS: The introduction of the ERAS protocol for patients undergoing LLDN compared with the traditional protocol led to a reduction in postoperative hospitalization in elder donors, without determining a raise in the number of hospital complications and readmissions.

Crucial Role of Extended Criteria Donors in Deceased Donor Single Kidney Transplantation to Face Chronic Shortage in the Heart of the Mediterranean Basin: A Single-Center Experience.

BACKGROUND: The gap between organ availability and patients on the waiting list for deceased donor kidney transplants has resulted in the wide use of extended criteria donors (ECDs).We aimed to compare the surgical outcomes of single kidney transplantation (KT) performed at our institute with standard criteria donor (SCD) or ECD grafts, according to the Organ Procurement and Transplantation Network definition. PATIENTS AND METHODS: Our retrospective analysis studied 115 adult recipients of KT from January 2016 to July 2018, with kidney grafts procured from adult donors after brain or circulatory death, performed at our institute. Among the 2 recipients' groups, we compared the incidence of early graft loss, delayed graft function, hospitalization, and surgical complications. We compared the evaluation of time to early graft loss with Kaplan-Meier estimators and curves; the hypothesis of no difference in time to graft loss between the 2 groups was tested using the log-rank statistics. RESULTS: Of the 103 deceased donor kidney transplants during the study period, 129 grafts were used after the regional network sharing allocation. More frequently, ECDs had a greater body mass index than SCDs (25.2 ± 3.9 vs 27.7 ± 5.0, P = .005) and type II diabetes mellitus (0% vs 18%, P = .002). KT recipients who received an ECD graft (73, 63.5%) were older (59.8 ± 9.8 vs 45.2 ± 15.4, P < .001) and presented a higher rate of delayed graft function (56% vs 24%, P = .001). Post-transplant graft loss did not differ among the 2 groups. CONCLUSION: Based on clinical experience in a single transplant center, ECD use for KTs is crucial in facing the organ shortage, without impairing post-deceased donor kidney transplant outcomes.

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study.

BACKGROUND: Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. PATIENT AND METHODS: We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. DISCUSSION: This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. TRIAL REGISTRATION: ISRCTN27083228 .

Preliminary Report on Introduction of Enhanced Recovery After Surgery Protocol for Laparoscopic Rectal Resection: A Single-Center Experience.

INTRODUCTION: Laparoscopic rectal surgery seems to improve postoperative recovery of patients who undergo surgery for rectal cancer. The aim of this study was to evaluate preliminary results of implementation of enhanced recovery after surgery (ERAS) protocol for laparoscopic rectal resection (LRR) for cancer at our institute. MATERIALS AND METHODS: We conducted a retrospective analysis of prospectively collected data. Patients who underwent LRR for cancer at our institute after introduction of enhanced recovery protocol were compared with a control group of patients who previously underwent surgery with traditional protocol. Primary endpoints evaluated were length of stay (LOS) and rates of complications and readmissions. RESULTS: We studied 150 consecutive patients, 56 operated with the traditional approach and 94 according to ERAS protocol. The mean (range) LOS was 10 (4-27) days for patients in control group versus 8.5 (3-32) days for patients in the ERAS group (P = .0823). No evidence of a different rate (P = .227) of complications was registered between the two groups. One patient in each group was readmitted. CONCLUSIONS: The introduction of the ERAS protocol in LRR for cancer at our institute led to an initial reduction in hospital LOS, without increase in morbidity or readmission rate compared with our previous experience with traditional protocol.

Evolution of Technique in Laparoscopic Donor Nephrectomy: A Single Center Experience.

BACKGROUND: Renal transplantation is the most successful therapy for improving survival and quality of life for end-stage renal disease (ESRD). Living donor kidney transplantation (LDKTx) has been used as an alternative to reduce the stay on the waiting list of patients with ESRD. Laparoscopic donor nephrectomy (LDN) has become the standard procedure for LDKTx. OBJECTIVE: This study aims to describe evolution of surgical technique with LDN at our institute. MATERIALS AND METHODS: We retrospectively analyzed our experience with LDN performed from January, 2003 to November, 2016, focusing on describing modifications of the surgical technique and devices made during those years. Demographics, operative factors, and postoperative complications of donors were reviewed. RESULTS: From the beginning of our experience with LDKTx we have performed 185 cases. From 2003 to 2016, 144 LDN were performed. Modifying our technique in response to the learning curve, complications encountered, and technological advancements, we experienced low complication rates. CONCLUSIONS: Continual refinement with LDN techniques based on intraoperative observations and technological advances is necessary to keep complication rates low and reduce donor morbidity and time for recovery.

Laparoscopic Approach for Thermoablation Microwave in the Treatment of Hepatocellular Carcinoma: A Single Center Experience.

BACKGROUND: The surgical therapy of choice for hepatocellular carcinoma (HCC) is liver transplantation (LT) or hepatic resection, although only a small percentage of patients can undergo these procedures. Microwave thermal ablation (MWTA) can be an effective alternative treatment for HCC that complicates a cirrhotic liver disease, either as a final procedure or for downstaging patients on the waiting list for LT, or in combination with resective surgery to achieve oncological radicality. OBJECTIVE: The purpose of this retrospective study was to evaluate experience with the laparoscopic approach of MWTA at our center. MATERIALS AND METHODS: In a cohort of 35 consecutive patients undergoing MWTA with laparoscopic approach between January, 2013 and May, 2016, we reviewed the demographic data, the Barcelona clinic liver cancer stage, the severity of cirrhotic liver disease, the size of the ablated lesion, the duration of the procedure, and complications occurring within 90 days of surgery. RESULTS: MWTA was performed by applying one to three hepatic parenchymal insertions (mean 1.8) per patient. The mean duration of surgery was 163 ± 18 minutes. There was no blood loss in any of the procedures. Complete necrosis on CT scan was achieved in 26/35 patients (75%). The mean hospital stay was 4.6 (range 2-7) days; major complications were postablation syndrome in 2/35 (5.7%), peritoneal fluid in 4/35 (11.4%), and transient jaundice in 1/35 (2.8%) patients. There was no mortality. CONCLUSIONS: Laparoscopic MTWA is a safe and effective treatment for unresectable HCC and when a percutaneous procedure is not feasible.

Successful Portal Vein Stent Placement in a Child with Cavernomatous Replacement of the Portal Vein After Partial Liver Transplantation: The Importance of a Recognizable Portal Vein Remnant.

Late portal vein thrombosis with cavernomatous replacement has been reported in 4.5% of pediatric patients who have undergone partial liver transplantation. In such cases, minimally invasive radiological treatments have a high failure rate. We report a successful case of percutaneous recanalization of the portal vein remnant, and subsequent stent placement, in a pediatric patient who underwent left lateral split liver transplantation with cavernomatous replacement of the portal vein.

Internal sphincterotomy reduces postoperative pain after Milligan Morgan haemorrhoidectomy.

BACKGROUND: Over the last few years, there has been increasing attention on surgical procedures to treat haemorrhoids. The Milligan-Morgan haemorrhoidectomy is still one of the most popular surgical treatments of haemorrhoids. The aim of the present work is to assess postoperative pain, together with other early and late complications, after Milligan-Morgan haemorrhoidectomy as we could observe in our experience before and after performing an internal sphincterotomy. METHODS: from January 1980 to May 2007, we operated 850 patients, but only 699 patients (median age 53) were included in the present study because they satisfied our inclusion criteria. The patients were divided into two groups: all the patients operated on before 1995 (group A); all the patients operated on after 1995 (group B). Since 1995 an internal sphincterotomy of about 1 cm has been performed at the end of the procedure. The data concerning the complications of these two groups were compared. All the patients received a check-up at one and six months after operation and a telephone questionnaire three years after operation to evalue medium and long term results. RESULTS: after one month 507 patients (72.5%) did not have any postoperative complication. Only 192 patients (27.46%) out of 699 presented postoperative complication and the most frequent one (23.03%) was pain. The number of patients who suffered from postoperative pain decreased significantly when performing internal sphincterotomy, going from 28.8% down to 10.45% (chi(2): 10,880; p = 0,0001); 95% Confidence Interval (CI) 24.7 to 28.9 (group A) and 10.17 to 10.72 (group B). In 51 cases (7.29%) urinary retention was registered. Six cases of bleeding (0.85%) were registered. Medium and long term follow up did not show any difference among the two groups. CONCLUSION: internal sphincterotomy: reduces significantly pain only in the first postoperative period, but not in the medium-long term follow up; does not increase the incidence of continence impairment when performed; does not influence the incidence of the other postoperative complications especially as regard medium and long term results.