Gastrointestinal perforation in liver transplantation recipients: risk factors analysis from a 10-year retrospective study with an international multicenter survey about management strategies.

Risk factors for gastrointestinal (GI) perforations in adult liver transplantation (LT) recipients have never been deeply investigated, as well as their management. The aim of this study is to report a single-center 10 years' experience about GI perforations after LT, focusing on risk factors and management strategies according to an international survey involving expert transplant surgeons. Data regarding all consecutive patients undergoing liver transplantations from January 2009 until December 2019 in a single institution were retrospectively collected. Risk factors for GI perforation were investigated. A web survey about the management of gastrointestinal perforations was conducted among worldwide transplantation centers. On 699 adult liver transplantations performed in our center, 20 cases of GI perforations were found, with an incidence of 2.8%. A previous abdominal surgery was found to be the only risk factor (p = 0.01). Ninety-day mortality was 75%. According to the survey, a more conservative treatment was suggested in case of gastric and duodenal perforations (consisting in a direct suture or an external drain), while a more aggressive treatment was adopted for ileal or colic perforation (stoma with or without resection). The W value for inter-personal agreement was 0.41. Despite rare, GI perforations in LT recipients can represent a life-threatening complication. Surgical management can be challenging and depends on both the site of perforation and the clinical conditions of the patient.

Duct-to-duct biliary reconstruction with or without an intraductal removable stent in liver transplantation: The BILIDRAIN-T multicentric randomised trial.

Background & Aims: Biliary complications (BC) following liver transplantation (LT) are responsible for significant morbidity. No technical procedure during reconstruction has been associated with a risk reduction of BC. The placement of an intraductal removable stent (IRS) during reconstruction followed by its endoscopic removal showed feasibility and safety in a preliminary study. This multicentric randomised controlled trial aimed at evaluating the impact of an IRS on BC following LT. Methods: This multicentric randomised controlled trial was conducted in 7 centres from April 2015 to February 2019. Randomisation was done during LT when a duct-to-duct anastomosis was confirmed with at least 1 of the stump diameters ≤7 mm. In the IRS group, a custom-made segment of a T-tube was placed into the bile duct to act as a stake during healing and was removed endoscopically 4 to 6 months post LT. The primary endpoint was the incidence of BC (fistulae and strictures) within 6 months post LT. The secondary criteria were complications related to the IRS placement or extraction, including endoscopic retrograde cholangio-pancreatography (ERCP)-related complications. Results: In total, 235 patients were randomised: 117 in the IRS group and 118 in the control group. BC occurred in 31 patients (26.5%) in the IRS group vs. 24 (20.3%) in the control group (p = 0.27), including 16 (13.8%) and 15 (12.8%) strictures, respectively. IRS migration occurred in 24 patients (20.5%), cholangitis in 1 (0.9%), acute pancreatitis in 2 (1.8%), and difficulty during endoscopic extraction in 19 (19.4%). No predictive factor for BC was identified. Conclusions: IRS does not prevent BC after LT and may require specific endoscopic expertise for removal. Trial registration number ClinicalTrialsgov: NCT02356939 (https://clinicaltrials.gov/ct2/show/NCT02356939?term=NCT02356939&draw=2&rank=1). Lay summary: Liver transplantation is a life-saving treatment for many patients with end-stage liver disease. However, it can be associated with complications involving the bile duct reconstruction. Herein, the placement of a specific stent called an intraductal removable stent was trialled as a way of reducing bile duct complications in patients undergoing liver transplantation. Unfortunately, it did not help preventing such complications.

Indocyanine green fluorescence angiography during liver and pancreas transplantation: a tool to integrate perfusion statement's evaluation.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making during surgical procedures, in particular to assess organs perfusion. METHODS: We used the ICG fluorescence during liver transplantations in six cirrhotic patients to help assessing the graft biliary duct perfusion in order to identify the appropriate level to perform the anastomosis. We also used ICG fluorescence also in five patients receiving kidney-pancreas transplantation to evaluate the perfusion levels of the duodenal stump of the pancreas graft. RESULTS: Follow-up period for the patients was 12 months. The perioperative period was uneventful, no biliary complications such as leaks or stenosis were reported after liver transplantation, no complications of the entero-enteric anastomoses occurred after pancreatic transplantation. CONCLUSIONS: ICG fluorescence seems to safely provide important objectifiable perfusion information during organ transplantation procedures that can integrate surgeon's expertise. In fact, detecting intra-operatively perfusion defects, it allows real time modifications on technical strategies potentially useful to reduce the feared risk of anastomotic leakage and consequent severe complications.

Early Hepatic Artery Thrombosis After Liver Transplantation: What is the Impact of the Arterial Reconstruction Type?

OBJECTIVE: Hepatic artery thrombosis (HAT) is the most severe vascular complication occurring after liver transplantation, with an incidence ranging from 2 to 9% in adults. Although the ideal arterial reconstruction is often described as a short and non-redundant anastomosis fashioned between the recipient and donor hepatic arteries, there is no strong evidence about this ideal reconstruction in the literature. The aim of this study was to assess the impact of the type of arterial reconstruction on early HAT after primary liver transplantation. METHODS: We retrospectively reviewed a contemporary MELD era cohort of 282 patients who underwent deceased donor primary liver transplantation from 2007 to 2012. Graft artery was classified as "short" when the section was located at the proper/common hepatic artery or "long" when the celiac trunk was used for anastomosis. Recipient arterial sites for arterial anastomosis were classified in three sites: (1) "distal" (proper hepatic artery or common hepatic artery/gastro-duodenal bifurcation), (2) "intermediate" (common hepatic artery) and (3) "proximal" (celiac trunk-splenic artery-aorta). We used univariate and multivariate analyses to assess the impact of different types of arterial reconstruction on early HAT. RESULTS: Of 282 primary liver transplantations, 17 patients (6%) developed early HAT. Patients with and without early HAT had comparable demographic and operative data. The main anastomotic combination was short graft artery on the recipient-common hepatic artery (n = 111, 39%). A long graft artery was used in 91 patients (32%) and was associated with hepatic artery variations (56%; n = 51; p = 0.001). Arterial reconstructions using a long graft artery (p = 0.003), a recipient proximal site as celiac trunk-splenic artery-aorta (p = 0.02) and the combination of a long graft artery on the recipient distal hepatic artery (p = 0.02) were significantly associated with early HAT. The early HAT rate in patients with a long graft artery was not significantly different between patients with or without donor arterial variation (respectively, 12% (n = 6/51) vs. 12% (n = 5/40); p = 1). In multivariate analysis, the use of a long graft artery, whatever the recipient anastomosis site, was an independent risk factor of early HAT (OR 3.2; 95% CI 1.2-9; p = 0.02). CONCLUSION: The type of arterial reconstruction used for arterial anastomosis during primary liver transplantation has an impact on the occurrence of early HAT. The use of a long graft artery is an independent risk factor of early HAT. Thereby, we recommend the use of a short graft artery with a direct path when feasible to reduce the occurrence of early HAT after primary liver transplantation.

Vena cava encirclement predicts difficult native hepatectomy.

Recipient hepatectomy is a challenging liver transplantation (LT) procedure that has life-threatening complications. The current predictive mortality clinic-biological scores (Child/Model for End-Stage Liver Disease [MELD]) do not take into consideration the recipient's liver anatomy. The aim of this study was to evaluate the impact of the dorsal sector anatomy of a cirrhotic liver on the morbidity/mortality rates of hepatectomy. A multicenter retrospective study (clinic-biological and morphologic) was performed from 2013 to 2014. The degree of encirclement of the inferior vena cava (IVC) by the dorsal sector of the liver was measured. The study population included 320 patients. Seventy-four (23%) patients had complete IVC encirclement. A correlation (P = 0.01) has been reported between the existence of a circular dorsal sector and the number of transfusions during LT (4 packed red blood cell [PRBC] transfusions in the group without IVC versus 7 PRBC transfusions in the other group). The existence of such anatomy increases the relative risk of early reoperation for IVC bleeding by 31% (P = 0.05). There is a correlation between alcoholic cirrhosis and dorsal-sector hypertrophy (126 cc versus 147.5 cc; P = 0.05). Concerning surgical time, we found no significant between-group differences. Compared to the severity of cirrhosis, an inverse correlation was observed between the MELD and Child scores and the dorsal sector hypertrophy (P < 0.001). No significant difference in terms of transfusion was found between the temporary portocaval shunt group (n = 168) and the other group (n = 152). The presence of a circular sector is associated with an increased risk of hemorrhage during hepatectomy, as well as an immediate postoperative risk of reoperation. Liver Transplantation 22 906-913 2016 AASLD.

Risk factors for postoperative bile leakage: a retrospective single-center analysis of 411 hepatectomies.

BACKGROUND: The primary focus of the study was to analyze the risk factors for bile leakage after hepatectomy for benign or malignant tumors. METHODS: A total of 411 patients who had undergone hepatectomy between December 2006 and December 2011 were retrospectively analyzed. The severity of bile leakage was graded according to the ISGLS classification. Twenty-eight pre- and postoperative parameters were analyzed. RESULTS: The overall bile leakage incidence was 10.2% (42/411). The severity of the leakage was classified according to the ISGLS classification. Bile leakage was detected early in case of abdominal drainage (11.4% vs 1.9%, P=0.034). It prolonged the time of hospitalization (16 vs 9 days, P=0.001). In all patients, wedge resection was associated with a higher incidence of bile leakage in contrast to anatomical resections (25.6% vs 4.1%, P<0.0001) regardless of the underlying liver disease. Furthermore, total vascular exclusion increased risk of bile leakage (P=0.008). CONCLUSIONS: Bile leakage as a major issue after hepatic resection is related to the postoperative morbidity and the hospitalization time. It is associated with non-anatomical resection and a total vascular exclusion.

Omental flap for hepatic artery coverage during liver transplantation.

In 1994, a technique of omental flap interposition to cover the celiac and mesenteric vessels after pancreaticoduodenectomy was described. It aimed to isolate the pancreatic anastomosis from the vessels dissected during pancreaticoduodenectomy. In liver transplantation (LT), the omental flap was initially used to reduce the risk of hepatic artery (HA) kinking. Currently, we use this technique to cover the dissected HA, reducing the consequences of postoperative biliary fistula (BF), particularly the risk of postoperative complications (thrombosis/bleeding). We describe this technique adding a simple modification consisting of covering the HA with an omental flap after completion of the biliary anastomosis. We performed LT with an omental flap to cover the HA vessels in 62 (55 %) of the 112 consecutive patients who underwent LT between January 2012 and July 2013. No postoperative deaths occurred. The rate of BF was 9.7 % (six cases). In the omental flap series, no postoperative thrombosis, HA pseudoaneurysm, or complications occurred. In the six cases of BF, the dissected HAs were completely isolated from the biloma. This simple technique has no specific morbidity; it isolates the HA from the biliary anastomosis and therefore may reduce the risk of severe postoperative HA complications after LT.

Reversed saphenous bypass for hepatic artery pseudoaneurysm after liver transplantation.

BACKGROUND: Hepatic artery pseudoaneurysm (HAP) is found in 1-2% of liver transplantation (LT) patients. The mortality associated with pseudoaneurysm formation after orthotopic LT is reported to be as high as 75%. Because of the rarity of complications, particularly when considered individually, much of the direction for the management of complications is anecdotal. This article discusses the presentation, etiology, types, treatment indications, and vascular procedures used to manage complications with LT. METHODS: Between January 2004 and December 2011, 464 LTs were performed at our institution. Of these, 9 (1.9%) consecutive patients underwent surgical treatment of HAP (8 men and 1 woman; median age, 58.4 years [range, 46-67 years]). Four patients underwent transarterial chemoembolization before LT for hepatocellular carcinoma. In all cases, revascularization with a reversed autologous saphenous vein bypass was performed. RESULTS: Four patients had ruptured pseudoaneurysms, and the others were diagnosed as having asymptomatic pseudoaneurysms during the follow-up period. The median delay between LT and the diagnosis of HAP was 39.6 days (range, 22-92 days). All were anatomically extrahepatic. The median diameter was 15.3 mm (range, 9-30 mm). Four patients had a T-tube. In 6 cases, biliary leakage was associated with the LT and, in the remaining 3, mycosis was recorded. After surgery, 1 patient underwent retransplantation because of ischemic cholangitis. Five years later, 5 patients had normal arterial anatomy, and the other 3 patients had stenosis that was successfully treated by stents. All of the patients had normal liver function at follow-up. One patient died 16 months later because of a heart attack. CONCLUSIONS: HAP with massive intraperitoneal bleeding is a rare but serious life-threatening complication when it occurs after LT. The majority of HAP cases are associated with bile leakage and mycosis; therefore, surgery must be the treatment of choice. Our conclusions support surgical revascularization with reversed saphenous grafts as a feasible and efficient treatment in cases of HAP.

Double arterial anastomosis in liver transplantation: is two better than one?

Arterial revascularization during liver transplantation is normally achieved by anastomosing the graft hepatic artery to the largest artery available at the recipient pedicle--either the common hepatic artery (CHA) or an accessory right hepatic artery (RHA) originating from the superior mesenteric artery (SMA). When a small caliber RHA is present, the artery is ligated and a single anastomosis with the CHA is performed. In the absence of a vascular reconstruction of the graft, the gastroduodenal artery is usually ligated as well. In this article, we describe a new type of arterial anastomosis in the case of a small accessory RHA and/or severe graft hepatic artery atherosclerosis that is commonly seen in elderly donors. To our knowledge, these are the first cases reported in the literature. This technique can be easily performed without increasing the arterial revascularization time or increasing the risk of complications associated with arteriosclerotic arteries. A 12-month follow-up revealed excellent function of the liver grafts.

Hepatic artery kinking during liver transplantation: survey and prospective intraoperative flow measurement.

BACKGROUND: Hepatic artery thrombosis (HAT) represents the most common vascular complication occurring after liver transplantation (LT). Herein, we report the results of a prospective study of hepatic artery flow (HAF) measurement during abdominal wall closure after LT along with the results of an international survey of procedures adopted, in order to avoid the arterial kinking (AK) in case of long artery. METHODS: Sixty-four surgeons were asked regarding the different procedures used to avoid AK in the presence of long artery. We prospectively assessed the HAF during three phases of LT in 26 consecutive LT performed in patients with a long HA: after completion of the biliary anastomosis (M0), and partial abdominal wall closure with (M1w) or without (M1w/o) hepatic artery anti-kinking method (HAAK). RESULTS: Sixty (93.7 %) surgeons replied to the survey: 44 (73.3 %) surgeons cut the artery as short as possible, of whom 38 (86.3 %) interposed an oxidized polymer or the omentum, and six (13.7 %) used other systems. Fourteen (23.3 %) surgeons did not use any interposition methods. The remaining two (3.3 %) surgeons left a long artery without HAAK. In our cohort we obtained the following HAF measures: M0 152 mL/min (89-205), M1 without HAAK 114 (66-168) and M1 with HAAK procedure 158 (91-219) (p = 0.002). CONCLUSIONS: Our survey confirms that no consensus is currently available regarding the most effective method for avoiding AK. Kinking occurs most probably when the liver is released in its final position. The utilization of an interposition method could ensure the maintenance of a correct HAF.

Excessive alcohol consumption after liver transplantation impacts on long-term survival, whatever the primary indication.

BACKGROUND & AIMS: Beyond 5 years, poorer survival, related to alcohol relapse, is observed in patients with liver transplant for alcohol-related liver disease (ALD). However, alcohol consumption has been significantly understudied in non-ALD transplant recipients. We aimed at analyzing the impact of alcohol consumption on long-term survival irrespective of the indication for transplantation. METHODS: This observational study included consecutive adult recipients of a primary liver graft between 1991 and 2007 in our hospital, who survived >6 months. Patients without ALD as primary indication, but with a history of excessive alcohol consumption before transplantation, were classified as secondary indication ALD. We studied the impact on survival of excessive consumption of alcohol after transplantation and several other variables. RESULTS: The 441 patients had mean follow-up of 81.7 months. Among the 281 patients with excessive alcohol consumption before transplantation, 206 had ALD as primary indication. After transplantation, alcohol consumption was reported by 32.3% of the study population, 43.7% in primary indication ALD, and 24.3% in non-ALD patients. Survival was 82% at 5 years and 49% at 10 years for patients with excessive alcohol relapse, compared with 86% and 75%, respectively, for patients without persistent excessive alcohol relapse. By multivariable analysis, the independent risk factors of death were: excessive alcohol relapse, age >51 years, post-transplantation diabetes mellitus, cyclosporine-based immunosuppression, and non-hepatic cancer. CONCLUSIONS: Excessive alcohol consumption has a negative impact on long-term survival after liver transplant, irrespective of the primary indication. Death is mainly due to recurrence of liver disease and non-hepatic cancer.

Liver transplantation and spontaneous neovascularization after arterial thrombosis: "the neovascularized liver".

The only arterial pathway available after liver transplantation is the hepatic artery. Therefore, hepatic artery thrombosis can result in graft loss necessitating re-transplantation. Herein, we present evidence of neovascularization at long-term follow-up in a series of transplant patients with hepatic artery thrombosis. We termed this phenomenon "neovascularized liver". Hepatic artery thrombosis was noted in 30/407 cases (7.37%), and occurred early in 13 patients (43.3%) and late (>30 days) in 17 (56.7%) patients. At the time of this study, 11 (36.7%) patients had a neovascularized liver. Those patients with neovascularized liver and normal liver function were closely followed. Of these patients, 10 (91%) showed evidence of neovascularized liver by imaging, and an echo-Doppler arterial signal was recorded in all patients. The mean interval between the diagnosis of hepatic artery thrombosis and neovascularized liver was 4.1 months (range of 3-5.5 months). Liver histology showed an arterial structure in 4 (36.4%) patients. Four factors were associated with development of neovascularized liver: late hepatic artery thrombosis, early hepatic artery stenosis, site of thrombosis, and Roux-en-Y anastomosis. The overall survival rate at 54 months was 90.9%. In conclusion, a late hepatic artery thrombosis may be quite uneventful and should not automatically lead to re-transplantation.

Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans.

RATIONALE: Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. OBJECTIVES: To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. METHODS: Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains). MEASUREMENTS AND MAIN RESULTS: TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 µm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. CONCLUSIONS: Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.

Long-term outcomes of liver transplantation: diabetes mellitus.

1. Despite methodological problems in estimating the true incidence of new-onset diabetes (NODM), it is generally accepted that this is a common complication of liver transplantation (LT), with the mean reported incidence varying between 7% and 30%. 2. The main predictors of post-LT NODM are ethnicity, a family history of diabetes, age > 45 years, glucose intolerance prior to LT, central obesity, metabolic syndrome, use of corticosteroids over a long period, use of tacrolimus, and hepatitis C infection. 3. NODM is associated with impaired long-term graft function and reduced survival. Diabetes is among the main risk factors for coronary heart disease, cerebrovascular disease, and peripheral occlusive arterial disease in transplant recipients. 4. The management of NODM includes the therapeutic and preventive steps taken in patients with type 2 diabetes. Little information exists on the use of antidiabetic compounds in transplant recipients. Some studies have suggested that LT recipients with NODM may benefit from a conversion to cyclosporine through improved glucose metabolism.