An Elbow Patch Reconstruction Technique for Narrowed Remnant Portal Veins during Right Lobe Living Donor Hepatectomy: A Rescue Surgery.

Background: Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction technique" to correct the narrowed remnant portal vein just or late after right lobe living donor hepatectomy. Methods: Demographic and clinical data of 12 living liver donors with narrowed remnant portal veins and treated with the "elbow patch reconstruction technique" were prospectively collected and retrospectively evaluated. Anatomic variation of the portal vein was defined in accordance with the Nakamura classification; six of the living liver donors had type A, three had type B, and the remaining three had type C. In eight of the living liver donors with a narrowed remnant portal vein, diagnosis was detected by intraoperative Doppler ultrasonography and visual inspection by experienced transplant surgeons in the living donor hepatectomy procedure. In the remaining four living liver donors, diagnosis was performed postoperatively when elevation of liver enzymes was noticed during the routine liver function test and Doppler US. The diagnosis was confirmed by multidetector computed tomography. Results: Data from nine males and three females aged 18 to 54 years were analyzed. All of the living liver donors were followed up for a median of 1710 days (min-max: 1178-4447 days; IQR: 1516 days), and none of the living liver donors had any structural or functional complications in the portal vein. Conclusions: Narrowing remnant portal veins are rare, but they are a life-threatening complication in living liver donors, and this condition requires urgent management. Image guided interventions and narrowed segment resection with end-to-end anastomosis using a vascular graft carried a potential risk for thrombosis and restenosis. To avoid these complications, we shared a technique named "elbow patch reconstruction technique". This technique can be very effective in relieving the narrowing of the remnant portal vein after right lobe living donor hepatectomy.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

BACKGROUND/AIMS: The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. MATERIALS AND METHODS: The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. RESULTS: The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter >4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules >4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. CONCLUSIONS: In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Evaluation of Bone Mineral Metabolism After Liver Transplantation by Bone Mineral Densitometry and Biochemical Markers.

AIM: This study aimed to evaluate the course of bone and mineral metabolism after liver transplantation (LT) in patients with chronic liver disease. METHODS: One hundred four patients who had undergone LT and had a minimum of 6 months of follow-up after LT were included in this prospective cohort study. The following parameters were evaluated for each patient: preoperative and postoperative (postoperative day [POD]30, POD90, POD180) osteocalcin, bone-specific alkaline phosphatase (BALP), type 1 collagen, beta-C-terminal end telopeptide (ß-CTx), vitamin D, parathyroid hormone (PTH), ALP, calcium, phosphate, sedimentation, and bone mineral densitometer scores (L2, L4, L total, and F total). The parameters were compared in terms of sex, presence of liver tumor (hepatocellular carcinoma [HCC; n = 19] vs non-HCC [n = 85]), and presence of autoimmune liver disease (autoimmune liver disease [ALD; n = 8] vs non-ALD [n = 96]). RESULTS: The median age of the patients (n = 81 men and n = 23 women) was 52 years (95% CI, 50-56). There was a significant change in the defined time intervals in parameters such as osteocalcin (P < .001), BALP (P < .001), ß-CTx (P < .001), vitamin D (P < .001), PTH (P < .001), ALP (P = .001), calcium (P < .001), phosphate (P = .001), L2 (P = .038), L total (P = .026), and F total (P < .001) scores. There was a significant difference in POD90 ALP (P = .033), POD180 calcium (P = .011), POD180 phosphate (P = .011), preoperative sedimentation (P = .032), and POD180 F total (P = .013) scores between both sexes. There was a significant difference in POD180 osteocalcin (P = .023), POD180 ß-CTx (P = .017), and preOP calcium (P = .003) among the HCC and non-HCC groups. Furthermore, we found significant differences in preoperative ALP (P = .008), preoperative sedimentation (P = .019), POD90 (P = .037) and POD180 L2 (P = .005) scores, preoperative (P = .049) and POD180 L4 (P = .017), and POD180 L total (P = .010) and F total (P = .022) scores between the patients with and without ALD. CONCLUSION: This study shows that the bone and mineral metabolism of the LT recipients was negatively affected after LT. In addition, we showed that bone and mineral metabolism was more prominent in patients with HCC, and bone mineral density scores were higher in patients with ALD.

Immunosuppressive Medication Adherence in Patients With Hepatocellular Cancer Who Have Undergo Liver Transplantation: A Case Control Study.

BACKGROUND: We aimed to compare the adherence to immunosuppressive medication use in patients who underwent liver transplantation (LT) due to hepatocellular carcinoma (HCC) and non-HCC reasons. METHODS: The study population was determined as 242 patients with HCC and 1290 patients with non-HCC who had LT performed in our institute between March 2002 and November 2021; all these patients were contacted by phone in March 2022. The sample size was calculated using the MedCalc software program, and the number of patients required in each group was determined as 111 patients. Furthermore, we used the sample.int function, a random integer generator in the R (version 4.1.2) software program. Whereas demographic and clinical parameters were determined as independent variables, the immunosuppressive medication adherence scale (IMAS) score was determined as a dependent variable. Patients were evaluated by the IMAS. This 11-item IMAS scale evaluates the lowest compliance score as 11 and the highest as 55. RESULTS: Out of a total number of 221 patients, 161 (72%) were men and 60 (27.1%) were women, with a median age of 58 years (IQR: 14); one patient in the non-HCC group was excluded due to lack of data. Among the HCC and non-HCC groups, significant differences were found in terms of the variables of age (P = .003), IMAS score (P < .001), sex (P = .001), working status (P = .004), chronic diseases (P = .008), tacrolimus alone (P < .001), tacrolimus plus everolimus (P < .001), and often medication changes (P < .001). A statistically significant correlation was found between the IMAS score and whether the patients had HCC (P < .001) and frequently changing immunosuppressive drugs (P = .023). CONCLUSION: This study showed that patients with frequent drug changes or non-HCC etiology had better adherence to immunosuppressive drug use.

Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. METHODS: Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. RESULTS: Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. CONCLUSION: It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.

Primary Hepatic Actinomycosis Mimicking Neuroendocrine Tumor.

INTRODUCTION: The Actinomyces species is a fastidious, gram-positive, non-spore-forming bacteria that thrive in microareophilic and anaerobic conditions. Infection in the liver, an organ rarely affected by this pathogen, is presumed to be caused by hematogenous spread through the portal vein from a mucosal injury or other abdominal injury or a focus of infection. CASE DESCRIPTION:  A 60-year-old male patient has a mass lesion of 15 × 10 cm in the left lobe on computed tomography. A tru-cut biopsy was performed with USG, and fragmented tissue pieces were obtained. In histopathological examination, these samples were reported as tumors with neuroendocrine differentiation. The biopsy sample contains a large amount of tumor neighborhood, and tumoral area is quite small. And, therefore, a clear diagnosis could not be found. A mass lesion with mildly increased Ga 68 DOTATATE uptake was observed in the left lobe of the liver (SUVmax value 3.8) and was interpreted in favor of the primary neuroendocrine tumor of the liver. DISCUSSION: Actinomyces cases are very rare and their diagnosis is usually delayed due to its slow and insidious course, and lack of specific clinical and radiological findings. It is difficult to make a correct diagnosis even in microbiological examinations and biopsy materials obtained in the presence of imaging methods. It can mimic tumors of abdominopelvic structures. CONCLUSION: Actinomyces should be kept in mind in cases with liver masses accompanied by previous abdominal surgery, abdominal trauma, high fever, and leukocytosis.

Techniques of hepatic arterial reconstruction in liver transplantation.

BACKGROUND: Hepatic artery reconstruction is an essential part of liver transplantation. This difficult stage of the operation is even more demanding in living donor liver transplantation than in deceased donor liver transplantation. One of the most important advances in hepatic artery reconstruction for living liver grafts was the introduction of microsurgical techniques involving an operative microscope or surgical loupe. Many surgical reconstruction techniques have been used in this field. PURPOSE: In this article, first, we will talk about the hepatic artery reconstruction techniques that are frequently used in deceased donor liver transplantation, and afterward, we will talk about the hepatic artery reconstruction techniques used in living donor liver transplantation, which include the hepatic artery reconstruction technique we use and call "one stay corner suture technique". CONCLUSIONS: We think high-volume transplant centers should tend to develop a standardized technique for doing hepatic artery reconstruction with their teams. We think the "one stay corner suture technique" can be easily applied in centers that perform LDLT.

Median arcuate ligament syndrome noticed during pancreaticoduodenectomy.

Median arcuate ligament syndrome (MALS) occurs as a result of compression of the celiac artery by a fibrous band called the median ligament, which originates from the diaphragmatic crus. The prevalence of MALS has been reported as 10-24% among patients. The etiology is not clear. The components of the clinical triad are a chronic post-prandial pain, epigastric murmur and weight loss. Diagnosis is based on clinical and radiological findings. MALS has been reported in a small portion of patients undergoing pancreaticoduodenectomy. Most of the patients have been diagnosed prior to surgery.

The Effect of Pre-transplant Lipid Profile on Post-transplant Hepatocellular Carcinoma Recurrence: Retrospective Single-Center Analysis.

BACKGROUND: Plasma lipids have been shown to relate to tumor biology. We aimed to analyze the effect of pre-transplant plasma lipid profiles on post-transplant tumor recurrence in patients with hepatocellular carcinoma and to identify any possible relationship between the pre-transplant lipid profile with maximum tumor diameter, number of tumor nodules, tumor differentiation, portal vein invasion, or serum biomarker levels. METHODS: Patients with hepatocellular carcinoma who underwent liver transplants between 2006 and 2021 had data collected pro- spectively and were analyzed retrospectively. Patients who did not have lipid profile data before transplant and whose post-transplant follow-up period was <90 days were excluded. Patients who had pre-transplant plasma lipid data and whose post-transplant follow-up period was >90 days were included in this study (n = 254). RESULTS: Lower high-density lipoprotein cholesterol levels were found to be significantly associated with post-Tx recurrence (38 vs 29.5, P < .001) and were also significantly associated with macroscopic portal vein thrombosis (39 vs 30.4, P < .021). There was no significant association between plasma lipids and tumor differentiation. Higher high-density lipoprotein cholesterol levels were significantly asso- ciated with good overall and disease-free survivals (P = .024 and P = .001). CONCLUSION: Pre-transplant low plasma high-density lipoprotein cholesterol levels were significantly associated with portal vein throm- bosis and poor post-transplant overall and disease-free survivals.

Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma.

BACKGROUND: Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. METHODS: We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. RESULTS: HCCs with 1, 2, or ≥ 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. CONCLUSIONS: MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival.

De Novo Malignancies After Liver Transplantation: Experience of a High-Volume Center.

PURPOSE: Patient care, newer immunosuppressive medications, and advances in surgical technique, have resulted in significant prolongation of survival after liver transplantation in recent years. However, as life expectancy increased and the early mortality rates have decreased, different problems have evolved due to chronic immunosuppressive therapy. The aim of the present study is to evaluate patients who were transplanted and then developed de novo malignancies, in terms of the type of malignancies and the follow-up period. METHODS: The study was conducted on 2814 patients who received liver transplantation between 2008 and 2020 in Inonu University Liver Transplant Institute. In total, the data of 23 patients were evaluated retrospectively. RESULTS: Non-melanoma skin cancer was the most common de novo malignancy (21.7%), followed by gynecological cancers (17.3%). The interval between the time of transplantation until the development of de novo malignancy was 36 (6-75) months. The median follow-up period after the diagnoses of the de novo malignancies was 4.11 years. One, 3-, 5-year survival rates of patients after the diagnoses of de novo malignancies were 69.6%, 56.5%, and 41.9%; respectively. CONCLUSION: Non-melanotic skin cancers were the most common de novo cancers in liver transplant recipients. A strict surveillance program is very important in the follow-up of liver transplant recipients.

Portal vein reconstruction with cryopreserved vascular grafts: A two-edged sword.

BACKGROUND: Portal vein anastomotic complications related to size discrepancy are important causes of morbidity and mortality in pediatric liver transplantation. Interposed vascular grafts in portal vein anastomosis can solve this problem. The aim of this study is to evaluate the results of pediatric liver transplantations performed using cryopreserved interposed vascular grafts between graft portal vein and superior mesenteric vein (SMV)-splenic vein (SpV) confluence. METHODS: Twenty-nine pediatric patients received liver transplantation using cryopreserved venous grafts in our Liver Transplant Institute between 2013 and 2020 were included in this study. Demographic, clinical, and operative characteristics and postoperative follow-up were analyzed. RESULTS: Sixteen patients (55.2%) had portal hypoplasia and five patients (17.2%) had portal vein thrombosis. In total, six patients (20.6%) suffered portal vein thrombosis in the early postoperative period. Three patients (10.3%) experienced portal vein thrombosis in the late postoperative period. Late portal vein thrombosis rate was significantly higher in patients with early portal vein thrombosis (3/6 patients [50%] versus 0/23 patients [0%]; p = .034). Lack of portal flow was significantly higher in patients with both early (50% versus 0%; p = .002) and late portal vein thrombosis (66.7% versus 6.7%; p = .03). CONCLUSION: Preoperative portal vein thrombosis and insufficient flow are important factors affecting success of liver transplant in children. The use of interposed vein grafts in problematic portal anastomoses can overcome portal flow problems.

Incidental Hepatocellular Carcinoma after Liver Transplantation: Clinicopathologic Features and Prognosis.

Background: The prognostic impact and clinicopathologic features of incidental hepatocellular carcinoma (iHCC) detected in explanted livers of patients undergoing liver transplantation (LT) has been a controversial issue in previous studies when compared with patients who are diagnosed with hepatocellular carcinoma (pdHCC) before LT. We aimed to review and compare these patient groups in a high-volume LT center. Methods: The present study involves a retrospective analysis of 406 HCC patients who received LT between January 2002 and April 2022. Among these patients, demographic data, histopathologic features and prognosis for iHCC and pdHCC were evaluated. Results: In our series, 406 patients' final diagnosis was HCC after they had received LT, nevertheless 54 patients in this HCC group were diagnosed incidentally after the pathological evaluation of the explanted livers. The etiology of the underlying liver disease between pdHCC (n = 352) and iHCC (n = 54) groups had some differences in our study population. Most of the patients in the pdHCC group had moderately differentiated tumors (45.7%). On the other hand, most of the patients in the iHCC group had well differentiated tumors (79.6%). There were 158 (44%) patients who met the Milan criteria in the pdHCC group while there were 48 (92%) patients in the iHCC group (p < 0.001). IHCC patients had statistically better 1, 3, 5 and 10 years disease-free and overall survival rates when compared with pdHCC patients. There was only 1 (1.8%) patient who had tumor recurrence in the iHCC group while 76 (21%) patients had tumor recurrence in the pdHCC group (p = 0.001). There is no disease free and overall survival difference when iHCC patients are compared with pdHCC patients who met the Milan criteria. Conclusion: It is the first study to show that iHCC patients may differ from pdHCC patients in terms of etiological features. IHCC tumors show better histopathologic features than pdHCC with low recurrence rate and iHCC patients have better survival rates than pdHCC patients.

A simple 2-parameter blood test alert for the presence of small hepatocellular carcinomas.

OBJECTIVES: The majority of HCCs present at an advanced stage in which potentially curative therapies cannot be used. Surveillance ultrasound has been found to increase the numbers of patients diagnosed with small tumors, but it is often not used. We aimed to try to identify widely-available and cheap potential serum markers for use in patients at risk for HCC. MATERIAL AND METHODS: A comparison was made of the complete blood count and liver function tests in a group of patients (n=114) with proven small HCCs (≤ 2 cm) and patients without HCC (n=506), all of whom were treated by liver transplantation in our Liver Transplantation Institute. RESULTS: Significant differences were found for blood levels of WBC, lymphocytes, total bilirubin and transaminases. Several 2-parameter combinations were assessed, but only the combination of total bilirubin and lymphocytes was found to be significantly different between patients with small HCCs and no HCC. Multivariate regression analysis showed significance only for total bilirubin levels and lymphocyte counts. The results were confirmed using a separate small cohort of non-transplant patients. CONCLUSION: The combination of elevated levels of total bilirubin and lymphocyte counts holds promise for identification of patients with chronic liver disease who are at risk for HCC.

A Combination of Blood Lymphocytes and AST Levels Distinguishes Patients with Small Hepatocellular Carcinomas from Non-cancer Patients.

PURPOSE: HCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically available and cheap potential blood tests as biomarkers for screening patients at risk for HCC. METHODS: A comparison was made of commonly used blood count and liver function parameters in a group of patients (n = 101) with small HCCs (≤ 3 cm) or without HCC (n = 275), who presented for liver transplantation in our institute. RESULTS: Significant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein among the tumor characteristics were found to be significantly different among the 2 HCC groups, as well as levels of blood total bilirubin, ALKP, and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients. CONCLUSION: The combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.

Diagnostic and therapeutic management algorithm for biliary complications in living liver donors.

This study aimed to demonstrate the efficacy of our diagnostic and therapeutic management algorithm and catheter-assisted (percutaneous transhepatic biliary tract drainage [PTBD] or transanastomotic feeding tube) hepaticojejunostomy (HJ) procedures in living liver donors (LLDs) with biliary complications. Living donor hepatectomy (LDH) was performed between September 2005 and April 2021 in 2 489 LLDs. Biliary complications developed in 220 LLDs (8.8%), 136 of which were male, and the median age was 29 (interquartile range [IQR]: 12) years. Endoscopic sphincterotomy ± stenting was performed in 132 LLDs, which was unsuccessful in 9 LLDs and required HJ. Overall, 142 LLDs underwent interventional radiologic procedures. Fifteen LLDs with biliary complications underwent HJ (PTBD catheter = 6 and transanastomotic feeding tube = 9) at a median of 44 days (IQR: 82). Following HJ, 14 LLDs did not have any complications throughout the median follow-up period of 1619 days (IQR: 1454). However, percutaneous dilation for HJ anastomotic stricture was performed in one patient. Biliary complications are very common following LDH; therefore, surgeons in the field should have a low threshold to perform HJ for biliary complications that persist after other treatments. Our catheter-assisted HJ techniques demonstrated a high success rate and aided HJ in a hostile abdomen during revisional surgery.

CRP is a superior and prognostically significant inflammation biomarker for hepatocellular cancer patients treated by liver transplantation.

BACKGROUND: Inflammation and its markers are considered prognostically important for many cancers, including Hepatocellular Carcinoma (HCC). However, it is not really clear which markers are the best. AIMS: To assess in a cohort of prospectively-evaluated HCC patients who were treated with liver transplant and whose survival was known, multiple commonly used inflammatory markers in relation to survival and to both clinical and tumor aggressiveness parameters. RESULTS: Amongst 330 transplanted HCC patients, CRP was found to be the only significant inflammatory marker for survival, on multivariate Cox regression analysis. NLR, PLR, GGT, AST, ALT and the Glasgow inflammation score were also found to be significant, but on univariate analysis only. CRP was significant in patients with both small (< 5 cm) and large HCCs and in patients with elevated or low Alpha-Fetoprotein (AFP) levels. Comparison of HCC patients with high (>2.5 mg/ dL) compared low serum CRP levels showed significant differences for blood levels of NLR, LMR, Hb, total bilirubin and liver transaminases, as well as Maximum Tumor Diameter (MTD) and percent of patients with Portal Vein Thrombosis (PVT). CONCLUSIONS: Elevated serum CRP levels were associated with significantly increased MTD and percent of patients with PVT and significantly worse overall survival in HCC patients who were treated by liver transplantation.