Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications: a multicentre observational cohort and propensity score-matched analysis.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation. METHODS: Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared. RESULTS: Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870). CONCLUSION: In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.

Lay Summary Patients with liver cancer may be treated with transarterial chemoembolization (TACE) during the period on the transplant waiting list. With TACE, chemotherapeutic coils are injected directly into the small arteries supplying the tumour, after which these vessels are closed. The aim of this therapy is to decrease the tumour size and slow down tumour growth. However, concerns are raised that manipulation of the main hepatic artery by TACE may cause damage to the artery itself. If this would result in problems during or after liver transplantation when the artery is connected to the artery supplying the donor liver, this may endanger the donor liver graft survival. The present study shows no increased risk in problems to connect the artery during liver transplantation after TACE treatment. Also, arterial complications after liver transplantation did not occur more frequently if patients had received TACE treatment. The authors therefore conclude that TACE treatment before liver transplantation could be considered a safe approach.

Infrarenal versus supraceliac aorto-hepatic arterial revascularisation in adult liver transplantation: multicentre retrospective study.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (≤ 30 days) HAT was in 6.2% (4/64) in the SC-AHAR and 10.7% (6/56) IR-AHAR group (p = 0.512) whilst incidence of late HAT was significantly lower in the SC-AHAR group (4.7% (3/64) vs 19.6% (11/56) - p = 0.024). IR-AHAR was the only independent risk factor for HAT (exp[B] = 3.915; 95% CI 1.400-10.951; p = 0.009). When AHAR is necessary at liver transplantation, the use of the supraceliac aorta significantly reduces the incidence of hepatic artery thrombosis and should therefore be recommended whenever possible.

Transplant Surgeon Burnout and Marital Distress in the Sandwich Generation: The Call for Organizational Support in Family Life.

Burnout (emotional exhaustion, depersonalization, and low personal accomplishment) is the enervation an individual experiences from a chronically taxing work environment. Little research has examined the demands of the sandwich generation (both children and older adults in the home) on burnout and marital satisfaction. METHODS: This is a cross-sectional survey of American and European transplant surgeons on the effects of sandwich generation-related demands on burnout and marital satisfaction, covarying for transplant surgeon age. RESULTS: A total of 286 married or partnered transplant surgeons were included. Presence (vs absence) of children in the home did not impact burnout, but those with children who reported difficulties with flexible childcare reported greater emotional exhaustion (P = .03) and depersonalization (P = .02) than those without difficulties. A total of 38.5% of married transplant surgeons reported marital distress. European transplant surgeons reported lower marital satisfaction than those from the United States (P < .01). Having an older adult in the home may also negatively impact transplant surgeons' marital satisfaction (P = .048). DISCUSSION: As health care organizations move forward with programs aimed at creating a sustainable workforce, providing professional environments supportive of important family-related demands is imperative.

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection.

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

Modified Sugiura Operation for Idiopathic Portal Hypertension with Bleeding Oesophageal Varices. A Case Report.

A case of a 36 years old man presenting massive upper GI bleeding due to oesophageal varices developed in the context of an idiopathic portal cavernoma and extensive porto-splenic thrombosis is discussed. He underwent a successful modified Sugiura operation (oesophago-gastric devascularisation and splenectomy [OGDS]) completed with interventional endoscopic treatment of residual oesophageal varices. The benefit of the modified Sugiura procedure proposed for the treatment of upper GI variceal bleeding developed in the context of splanchnic venous thrombosis is discussed. The procedure is a valid therapy in the treatment of symptomatic extra-hepatic hypertension when other options are inapplicable.

Leiomyosarcoma of the Inferior Vena Cava Level II Including Both Renal Veins : Surgical Approach.

A 66 years old male developping an acute lower right limb oedema due to an extended venous thrombosis of the common femoral and iliac veins was diagnosed to have a leiomyosarcoma of the inferior vena cava (IVC) involving both renal veins. The characteristics and management of this level II IVC leiomyosarcoma are discussed with particular attention to the renal vein reconstruction and neo-adjuvant therapy.

Leiomyosarcoma of the Inferior Vena Cava Level II Including Both Renal Veins: Surgical Approach.

A 66 years old male developping an acute lower right limb oedema due to an extended venous thrombosis of the common femoral and iliac veins was diagnosed to have a leiomyosarcoma of the inferior vena cava (IVC) involving both renal veins. The characteristics and management of this level II IVC leiomyosarcoma are discussed with particular attention to the renal vein reconstruction and neo-adjuvant therapy.

Allograft inflow - concern in liver transplantation after intraoperative radiotherapy for cholangiocarcinoma.

UNLABELLED: Patients who underwent local radiotherapy during surgical resection for cholangiocarcinoma are at increased risk of developing extensive thrombosis of splanchnic vessels and secondary biliary cirrhosis on the remnant liver; hence they become liver transplantation candidates. In these recipients, adequate graft inflow cannot be provided by conventional liver transplantation procedures. Cavoportal hemitransposition and renoportal anastomosis alongside complex arterial reconstructions are innovative techniques to restore allograft inflow in such cases. We report two cases of hilar cholangiocarcinoma formerly treated by left hepatectomy-Whipple en Bloc and intraoperative radiotherapy that developed late secondary biliary cirrhosis requiring liver transplantation. During transplant procedure, concern has been raised by the previous radiation-induced peritoneal injury with extended splanchnicthrombosis. Cavoportal hemitransposition and renoportal anastomosis were performed respectively, beside arterial graft reconstructions. Patients survived 57 and 18 days respectively, after transplantation. Cavoportal hemitransposition and renoportal anastomosis likewise complex arterial reconstructions are life-saving procedures to secure allograft inflow in the setting of radiation-induced extensive splanchnic thrombosis. However,this condition adversely affects patient and graft survival owing to high rates of early vascular and biliary complications, so these patients are not good liver transplantation candidates. ABBREVIATIONS: CCA - cholangiocarcinoma, CPHT - cavoportal hemitrans position, Ct - celiac trunk, DSVT - diffusesplanchnic vein thrombosis, HA - hepatic artery, IVC - inferior vena cava, LRV - left renal vein, LT - liver transplantation, PV- portal vein, PVT - portal vein thrombosis, RISC -radiation induced sclerosing cholangitis, RISC-BC - radiationinduced sclerosing with biliary cirrhosis, RPA - renoportal anastomosis.

Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis.

We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased.We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r = -0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta-analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that "reduced tacrolimus" trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 [0.38-0.69]), with no significant influence on acute rejection (RR = 0.92 [0.65-1.31]) compared to "conventional tacrolimus" trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6-10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.

Impact of steroid-avoidance immunosuppression on long-term outcome after liver transplantation for HCV cirrhosis: the need for well documented long-term follow-up.

AIM: study impact of steroid avoidance on HCV recurrence after transplantation. METHODS AND MATERIAL: 35 HCV pats, being part of prospective, randomized, double-blind, placebo-controlled study comparing Tacrolimus (TAC)-Placebo (PLAC) (n = 14) to TAC-short-term (2 mo) low-dose steroid (STER) (n = 21), had 5 years follow-up. Primary endpoint was 1 and 5 years survival; secondary (composite) endpoint comprised HCV related cirrhosis, re-transplantation (re-LT) and death. RESULTS: 1 and 5-years survival were 93% and 75% in TAC-PLAC group; 91% and 66% in TAC-STER group (p 0.38). Two (14.3%) TAC-PLAC pats died due to HCV cirrhosis at 54 and 72 mo; 7 (33%) TAC-STER pats died due to cholestatic hepatitis at 5.8 and 9 mo, to cirrhosis at 18, 22, 34, 73 and 79 mo (p 0.20). Composite endpoint at 5 years didn't show advantage in favor of TAC-PLAC patients (5/14 [35.7%] vs. 9/21 [42.8%] pts, p.0.69). Early biopsies seemed more favorable in TAC-PLAC pats; at 5 years results were identical for both groups. Only 1 (7.1%) TAC-PLAC and 2 (9.5%) TAC-STER pats needed rejection treatment. CONCLUSION: immunosuppression using steroid avoidance or short-term use had similar outcomes. Well documented long-term follow-up, including biopsies, is necessary in order to make conclusions in relation to impact of steroid use on outcome of HCV liver recipients.

Liver transplantation or Starzl's legacy. A look backward, a look forward.

Since the first successful liver transplantation (LT) in 1963 by Starzl, enormous progresses have been made in this field of medicine. The author looks back at the recommendations put forward at the 1983 NIH Consensus conference on liver transplantation in order to show the enormous progresses that have been made in his field during the last four decades. Today almost none of the original indications and contraindications remain in place. Despite the extension of indications, results of LT continuously improved. The attention of the transplant physicians should from now onwards be focused on the achievement of an immunosuppressive free (or tolerant) status in order to further consolidate the excellent obtained long-term results.

Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia.

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Endoscopic retroperitoneal neurectomy for chronic pain after groin surgery.

BACKGROUND: Chronic postoperative pain after inguinal surgery remains a difficult problem. The role of minimally invasive surgery in this complex setting is still unexplored. METHODS: Between January 1997 and January 2007, 34 men and five women with a mean(s.d.) age of 47(16) years underwent endoscopic retroperitoneal neurectomy (ERN) for chronic neuropathic groin pain due to genitofemoral nerve with or without ilioinguinal nerve entrapment. Follow-up data were obtained 1 and 12 months after surgery. RESULTS: At both timepoints after ERN, the severity of chronic postoperative groin pain at rest and during daily activities, and the rate of occupational disability, were significantly decreased in 27 of the 39 patients compared with preoperative values (all P < 0.001). CONCLUSION: ERN for chronic postoperative genitofemoral nerve entrapment neuropathy was successful in the majority of patients selected for the procedure. This minimally invasive approach allows simultaneous neurectomy of genitofemoral and ilioinguinal nerves.