Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Early Postoperative Serum Phosphate Drop Predicts Sufficient Hypertrophy After Liver Surgery.

OBJECTIVE: The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD). BACKGROUND: Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia. METHODS: Serum phosphate changes within the first 7 postoperative days after ALPPS (n=61) and LLD (n=54) were prospectively assessed and correlated with standardized volumetry after 1 week. In a translational approach, postoperative phosphate changes were investigated in mice and in vitro . RESULTS: After ALPPS stage 1 and LLD, serum phosphate levels significantly dropped from a preoperative median of 1.08 mmol/L [interquartile range (IQR) 0.92-1.23] and 1.07 mmol/L (IQR 0.91-1.21) to a postoperative median nadir of 0.68 and 0.52 mmol/L, respectively. A pronounced phosphate drop correlated well with increased liver hypertrophy ( P <0.001). Patients with a low drop of phosphate showed a higher incidence of posthepatectomy liver failure after ALPPS (7% vs 31%, P =0.041). Like in humans, phosphate drop correlated significantly with degree of hypertrophy in murine ALPPS and hepatectomy models ( P <0.001). Blocking phosphate transporter (Slc20a1) inhibited cellular phosphate uptake and hepatocyte proliferation in vitro. CONCLUSION: Phosphate drop after hepatectomy is a direct surrogate marker for liver hypertrophy. Perioperative implementation of serum phosphate analysis has the potential to detect patients with insufficient regenerative capacity at an early stage.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Uses of a dedicated 3D reconstruction software with augmented and mixed reality in planning and performing advanced liver surgery and living donor liver transplantation (with videos).

The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics, virtual surgery simulation and using the created scenarios in real-time surgery using mixed reality. In this article, we described our experience on developing a dedicated 3 dimensional visualization and reconstruction software for surgeons to be used in advanced liver surgery and living donor liver transplantation. Furthermore, we shared the recent developments in the field by explaining the outreach of the software from virtual reality to augmented reality and mixed reality.

Comparison of Anatomic and Non-Anatomic Liver Resection for Hepatocellular Carcinoma: A Retrospective Cohort Study.

Background and Objectives: The survival benefit of anatomical liver resection for hepatocellular carcinoma has not been elucidated yet. In this study, we aimed to investigate the effects of anatomic and non-anatomic liver resection on surgical outcomes in patients with hepatocellular carcinoma. Materials and Methods: A retrospective analysis of patients undergoing anatomic or non-anatomic resections due to hepatocellular carcinoma between March 2006 and October 2019 was conducted. Demographics, preoperative laboratory assessments, treatment strategies, and postoperative outcomes were analyzed. Results: The total cohort consisted of 94 patients, with a mean age of 63.1 ± 8.9 years, and 74.5% were male. A total of 41 patients underwent anatomic liver resection, and 53 patients underwent non-anatomic resection. The overall survival rates were found to be similar (5-year overall survival was 49.3% for anatomic resection and 44.5% for non-anatomic resection). Estimated median overall survival times were 58.5 months and 57.3 months, respectively (p = 0.777). Recurrence-free 1-, 3-, and 5-year survival rates were found to be 73.6%, 39.1%, and 32.8% in the non-anatomic resection group and 48.8%, 22.7%, and 22.7% in the anatomic resection group, respectively. Grade three or higher complication rates were found to be similar among the groups. Conclusions: This study did not find a difference between two surgical methods, in terms of survival. A tailored selection of the resection method should be made, with the aim of complete removal of tumoral lesions and leaving a suitable functional liver reserve, according to the parenchymal quality and volume of the liver remnant.

Stage I-laparoscopy partial ALPPS procedure for perihilar cholangiocarcinoma.

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.

Hepatic vein in living donor liver transplantation.

Right lobe living donor liver transplantation (LDLT) is a major development in adult LDLT that has significantly increased the donor pool by providing larger graft size and by decreasing risk of small-for-size graft syndrome. However, right lobe anatomy is complex, not only from the inflow but also from the outflow perspective. Outflow reconstruction is one of the key requirements of a successful LDLT and venous drainage of the liver graft is just as important as hepatic inflow for the integrity of graft function. Outflow complications may cause acute graft failure which is not always easy to diagnose. The right lobe graft consists of two sections and three hepatic venous routes for drainage that require reconstruction. In order to obtain a congestion free graft, several types of vascular conduits and postoperative interventions are needed to assure an adequate venous allograft drainage. This review described the anatomy, functional basis and the evolution of outflow reconstruction in right lobe LDLT.

Extended left hepatectomy for intrahepatic cholangiocarcinoma: hepatic vein reconstruction with in-situ hypothermic perfusion and extracorporeal membrane oxygenation.

BACKGROUND: Liver resection for intrahepatic cholangiocarcinoma (ICC) with invasion of the inferior vena cava (IVC) and hepatic veins (HV) is a challenging procedure. CASE PRESENTATION: We report a case of a 63-year-old woman with a 6-cm, centrally located liver mass. Her biochemistry results were normal except for a Ca19-9 level of 1199 U/ml. The liver biopsy was consistent with ICC and 60% macrosteatosis. Abdominal CT scans revealed a large central mass invading the left HV, middle HV and right HV, infringing on their junction with the vena cava. An operation was planned using a 3-dimensional (3D) computer simulation model using dedicated software. We also describe a novel veno-portal-venous extracorporeal membrane oxygenation (VPV-ECMO) support with in-situ hypothermic perfusion (IHP) during this procedure. We aimed to perform an extended left hepatectomy and reconstruct 3 right HV orifices with an interposition jump graft to the IVC with total vascular exclusion (TVE) and IHP A supplemental video describing the preoperative planning, the operative procedure with the postoperative follow-up in detail is presented. After the patient was discharged, she developed a hepatic venous outflow obstruction 3 months postoperatively, which was effectively managed with hepatic venous stenting by interventional radiology. She is currently symptom free and without tumour recurrence at the 1-year follow-up. CONCLUSIONS: This report demonstrates that extended left hepatectomy for IHC with IHP and VPV-ECMO is safe and feasible under the supervision of a highly experienced team.

Outcomes of Laparoscopic Versus Open Liver Resection: A Case-control Study With Propensity Score Matching.

BACKGROUND: This study aimed to evaluate the perioperative outcomes of patients with benign and malignant liver lesions scheduled for laparoscopic and open surgery using a propensity score-matched approach to analyze additional cofactors influencing outcomes. PATIENTS AND METHODS: In this study, we retrospectively reviewed 270 patients who underwent laparoscopic or open liver resection at our institute between October 2016 and November 2021. Patients were divided into open and laparoscopic liver resection groups and compared according to the intention to treat principle. In the purification process for the nonrandom nature of the study, a matching analysis was performed at a 1:1 case-control ratio. The PS model included selected data on body mass index, additional data on the American Society of Anesthesiology score, cirrhosis, lesion <2 cm from the hilum, lesion <2 cm from the hepatic vein or inferior vena cava, and type of neoadjuvant chemotherapy. RESULTS: The operation time and 30- and 90-day mortality rates were similar between the groups. The average length of hospital stay was 11 days in the open surgery group and 9 days in the laparoscopic surgery group after matching ( P =0.011). The 30-day morbidity rate was statistically different between the groups before and after matching, favoring the laparoscopic group ( P =0.001 and 0.006, respectively). After the propensity score-matched approch, the open group's Pringle time was shorter than that of the laparoscopic group. The total operative time was longer in the laparoscopic than in the open surgery group. This did not change after matching (300 vs. 240 min). CONCLUSIONS: Laparoscopic surgery is a feasible and safe treatment option for patients with liver tumors, with promising results in terms of morbidity and hospital stay.

Revival of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma: An international multicenter study with promising outcomes.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma has been considered to be contraindicated due to the initial poor results. Given the recent reports of improved outcomes, we aimed to collect the recent experiences of different centers performing associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma to analyze factors related to improved outcomes. METHODS: This proof-of-concept study collected contemporary cases of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma and analyzed for morbidity, short and long-term survival, and factors associated with outcomes. RESULTS: In total, 39 patients from 8 centers underwent associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma from 2010 to 2020. The median preoperative future liver remnant volume was 323 mL (155-460 mL). The median future liver remnant increase was 58.7% (8.9% -264.5%) with a median interstage interval of 13 days (6-60 days). Post-stage 1 and post-stage 2 biliary leaks occurred in 2 (7.7%) and 4 (15%) patients. Six patients (23%) after stage 1 and 6 (23%) after stage 2 experienced grade 3 or higher complications. Two patients (7.7%) died within 90 days after stage 2. The 1-, 3-, and 5-year survival was 92%, 69%, and 55%, respectively. A subgroup analysis revealed poor survival for patients undergoing additional vascular resection and lymph node positivity. Lymph node-negative patients showed excellent survival demonstrated by 1-, 3-, and 5-year survival of 86%, 86%, and 86%. CONCLUSION: This study highlights that the critical attitude toward associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma needs to be revised. In selected patients with perihilar cholangiocarcinoma, associating liver partition and portal vein ligation for staged hepatectomy can achieve favorable survival that compares to the outcome of established surgical treatment strategies reported in benchmark studies for perihilar cholangiocarcinoma including 1-stage hepatectomy and liver transplantation.

Early period intensive care follow-up after liver transplantation in children: a single center experience.

BACKGROUND: Liver transplantation (LT) is a well-established, life-saving treatment for children with irreversible acute and chronic liver failure (LF). We aimed to evaluate the factors associated with morbidity and mortality in the early period of LT in children by reviewing our pediatric intensive care unit (PICU) experience. METHODS: We reviewed children`s medical records followed in the PICU after LT between May 2015-August 2021, including demographic parameters, indications for LT, operative variables, respiratory and circulatory support requirements, LT-related complications and survival. RESULTS: During this period, 40 pediatric patients who underwent LT were evaluated. LT was performed in 35 (87.5%) cases of chronic liver disease and 5 (12.5%) cases of acute liver failure. Twenty-four patients had chronic liver failure due to cholestatic liver disease. The patients` Pediatric Risk of Mortality (PRISM) III score was 18.82±SD (2-58) at PICU admission. 1-year survival was 87.5%, and overall survival was 85%. Younger age, low body weight, preoperative pediatric end-stage liver disease (PELD), and model for end-stage liver disease (MELD) values of 20 and higher were important risk factors for unfavorable outcomes after living donor liver transplantation (LDLT). These risk factors are both associated with technically more challenging vascular and bile duct reconstruction and higher complication rates, and increased mortality during the early period after LT. CONCLUSIONS: The early period of optimum PICU management in pediatric LT recipients is crucial for successful outcomes, which is also related to the patients` characteristics, disease severity scores, and surgical procedures.

Reducing Risk for Acute Kidney Injury After Living Donor Hepatectomy by Protocolized Fluid Restriction: Single-Center Experience.

BACKGROUND: Acute kidney injury (AKI) is a potential complication after restricted fluid therapy for major surgery. The aim of this study was to evaluate the incidence of AKI for living liver donor hepatectomy in which applied intraoperative protocolized fluid restriction was used targeting a low central venous pressure (CVP) level with high pulse pressure variation (PPV) and systolic pressure variation (SPV). MATERIAL AND METHODS: Living liver donors were admitted for this retrospective observational study. Low CVP <5 mm Hg with high PPV<20% and SPV<15% were the targets of the clinical protocol to reduce intraoperative blood loss via protocolized fluid management until the end of the hepatic parenchymal division. KDIGO criteria were used for AKI definition. The SPSS version 11.5 program was used for statistical analysis. RESULTS: The study included 130 patients, 79 (60.8%) men and 51 (39.2%) women, with from 18 to 58 years of age. Donors underwent right and left lobe hepatectomies (116 and 14, respectively). The baseline CVP, the lowest CVP of hepatectomy, and the highest CVP measured after hepatectomy were 7.45 ± 2.41, 4.28 ± 1.12, 7.67 ± 2.09 mm Hg, respectively. Only 4 patients with right lobe hepatectomy developed AKI stage I (3.1%) in the first 24 hours. The 4 patients were recovered at 48 hours postoperatively. CONCLUSION: This study demonstrated that a CVP target of <5 mm Hg and high PPV/SPV via a simple fluid management modality with protocolized-fluid restriction until the procurement may not cause AKI in living liver donors in a closed follow-up anesthesia approach.

Living liver donor hilar anatomical variations and impact of variant anatomy on transplant outcomes.

Donor anatomy is an essential part of donor selection and operative planning in living donor liver transplantation. In this study, variations of hilar structures, and the effects of variant anatomy on donor and recipient outcomes were evaluated. Living donor liver transplantations in a single center between January 2013 and December 2020 were retrospectively reviewed. In total, 203 liver transplantations were analyzed. Type 1 arterial anatomy, type 1 portal vein anatomy and type 1 bile duct anatomy were observed in 144 (70.9%), 173 (85.2%), and 129 (63.5%) donors, respectively. Variant biliary anatomy was observed more frequent in donors with variant portal vein branching than in those with type 1 portal anatomy (60.0% vs 32.3%, P = .004). The overall survival rates calculated for each hilar structure were similar between recipients receiving grafts with type 1 anatomy and those receiving grafts with variant anatomy. When donors with variant anatomy and donors with type 1 anatomy were compared in terms of hilar structure, no significant difference was observed in the frequency of complications and the frequency of serious complications. Biliary variations are more common in individuals with variant portal vein anatomy. Donor anatomic variations are not risk factors for inferior results of recipient survival or donor morbidity.

Outcomes of Surgical Strategies for Living Donor Liver Transplantation in Patients With Portal Vein Thrombosis: A Cohort Study.

BACKGROUND: Adequate portal flow to the liver graft is the requirement of a successful liver transplant (LT). Historically, portal vein thrombosis (PVT) was a contraindication for LT, especially for living donor LT (LDLT), demanding technically more difficult operations and advanced technique. In this study, the outcomes of patients with and without PVT after LDLT were compared. METHODS: Adult LDLTs performed by 2 centers (n = 335) between 2013 and 2020 were included into this large cohort study. PVT was classified based on Yerdel classification grade 1 to 4. RESULTS: Sixty-two patients with PVT constituted 19% of the study cohort of 335 recipients. While mean platelet count was found to be lower (P = .011) in the PVT group, patient age (P = .035), operation duration (P = .001), and amount of intraoperative blood transfusion (P = .010) were found to be higher. Incidence of PVT was higher in female patients than males (22.7% vs 16.1%, P = .037). There was no significant difference in survival between patients with and without PVT on 30-day (P = .285), 90-day (P = .565), 1-year (P = .777), and overall survival (P = .917). Early thrombosis did not show a better survival rate than Grades 2, 3, or 4 PVT. Thrombosis limited to portal vein was not found to bring a survival advantage compared with Grade 3 and 4 thromboses. Eversion thrombectomy was the most common procedure (66%) to overcome PVT intraoperatively. CONCLUSION: Although technically more challenging, PVT is not a contraindication of LDLT. Similar outcomes can be achieved in LDLT in patients with PVT after proper restoration of portal flow, which eliminates the default survival disadvantage of patients with PVT.

3D-reconstruction and heterotopic implantation of reduced size monosegment or left lateral segment grafts in small infants: A new technique in pediatric living donor liver transplantation to overcome large-for-size syndrome.

BACKGROUND: Monosegmental grafts and reduced left lateral segment grafts have been introduced to overcome the problems of large-for-size grafts in pediatric living donor liver transplantation. Here, we introduce a new method of reduced size monosegment or left lateral segment grafts transplanted in the right diaphragmatic fossa heterotopically in small infants. METHODS: There were 4 infants who underwent living donor liver transplantation with heterotopically implanted reduced monosegmental or left lateral segment grafts at our center. The demographic, operative, postoperative, and follow-up data of these infants were collected from our prospectively designed database and reviewed. Technical details of the donor and recipient operation are shared and a supplemental provided. RESULTS: The mean recipient age was 7.5 ± 0.9 months (range: 5-10 months), and body weight was 5.9 ± 0.7 kg (range: 4.6-7.8). Primary diagnoses of the recipients were biliary atresia (n:3) and progressive familial intrahepatic cholestasis (n:1). Mean graft-recipient weight ratio was 3.3 ± 0.2. Reduced monosegment III grafts were used in 2 cases, and reduced left lateral segment grafts were used in the other 2 patients. Bile duct reconstruction was done by Roux-en-Y hepaticojejunostomy in 3 patients and duct-to-duct anastomosis in the remaining patient. All patients recovered from the liver transplantation operation and are doing well at a mean follow-up of 8 months. CONCLUSION: Living donor liver transplantation with heterotopically implanted reduced monosegmental or left lateral segment seems feasible for the treatment of neonates and extremely small infants. Further accumulation of cases and long-term follow-up are necessary to collect data for the establishment of this treatment modality.

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

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.

Acute arterial occlusion due to vascular closure device: A report of two cases.

Vascular closure devices are frequently used after percutaneous arterial interventions to achieve hemostasis at the puncture site and facilitate early ambulation. Occasionally, complications have been reported with closure devices, such as hematoma, infection, arteriovenous fistula, pseudoaneurysm, and ischemia. This is a report of 2 cases of severe, acute-onset arterial occlusion and critical limb ischemia, one of which occurred in the upper limb following the use of a vascular closure device, and the required surgical treatment.

The use of porcine acellular dermal matrix for management of gastrocutaneous fistula after laparoscopic sleeve gastrectomy.

Sleeve gastrectomy is an effective and single stand-alone surgical procedure for the treatment of morbid obesity. One of the most frequent and serious complications of this procedure is staple-line leak. It can usually be treated with self-expandable stents. If this process results in failure and gastrocutaneous fistula occurs, a challenging period starts for the patient and the surgeon. We describe a new, relatively simple and quick endoscopic technique for closing a chronic gastrocutaneous fistula. A plug prepared with porcine acellular dermal matrix was used for this purpose. Gastrocutaneous fistula following an obesity surgery can be successfully treated endoscopically with this technique. This method can prevent the need for aggressive reconstructive surgery following a gastrocutaneous fistula and can prompt rapid improvement while decreasing the average hospital stay for this condition.