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.

Management of Biliary Complications in Liver Transplant Recipients with Duct-To-Duct Anastomosis: A Single-Center Experience.

BACKGROUND: The aims of this study were to investigate biliary complications in liver transplant recipients with choledochocholedocho stomy anastomosis, to identify the risk factors for the development of such complications, and to evaluate the success of endoscopic approaches in liver transplant recipients. METHODS: Between January 2013 and May 2021, a total of 238 patients with liver diseases underwent liver transplantation: 174 recipients undergoing choledochocholedochostomy anastomosis were included in the analysis. RESULTS: Their median age was 54.0 years. The median posttransplant follow-up period was 29 months. Hepatitis B virus infection (33%) was the most common indication for liver transplantation. Most patients (87%) received living donor liver transplantation. The overall prevalence of posttransplant biliary complications was 31%. Anastomotic biliary strictures were the most common biliary complications (72%), followed by biliary leakage (13%). The median time between endoscopic retrograde cholangiography and liver transplantation was 4 months, with a mean of 3 ± 1.6 sessions. Endoscopic retrograde cholangiography-guided drainage and balloon dilation with or without stent placement was the most common treatment modalities for recipients with biliary strictures. The overall success rate of endoscopic treatment modalities was 83.3%, with 65% of the recipients exhibiting complete biochemical and endoscopic responses. The response did not differ significantly between living donor liver transplantation and cadaveric donor liver transplant recipients (P > .05). Three recipients required revision surgery for biliary complication repair. Six patients died due to biliary sepsis. CONCLUSION: Biliary stricture and leakages were the most common biliary complications after liver transplantation. Endoscopic treatment was successful in most recipients.

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.

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.

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.

Live Donor Assessment Tool (LDAT): A Turkish validity and reliability study.

BACKGROUND/AIMS: Psychosocial and psychiatric evaluations are crucial components of the assessment of a live donor candidate. The Live Donor Assessment Tool (LDAT) was developed for this purpose. This study aims to evaluate the validity and reliability of the Turkish version of LDAT. MATERIALS AND METHODS: 132 live kidney or liver donor were referred to assess their psychosocial/psychiatric appropriateness for donation and were randomized for clinical evaluation as usual or with LDAT. The internal consistency of LDAT was measured by Chronbach's alpha coefficient. Inter-rater reliability was measured by using Spearman's correlation coefficient. The potential validity of LDAT was assessed by comparing LDAT scores to clinical decisions. The Mann-Whitney U test was used to compare LDAT scores across two clinically classified groups (acceptable/declined). Logistic regression was performed using LDAT scores to predict the clinical decision. RESULTS: The Turkish version of LDAT items demonstrate good internal consistency (α=0.773). Inter-rater reliability of LDAT demonstrated strong correlation (ICC=0.72). LDAT scores differentiated the accepted/declined groups, and strongly predicted the clinical decision. With a cut-off score of 60.5, LDAT was found to have high sensitivity and specificity. CONCLUSION: The Turkish version of LDAT was found to be a valid and reliable tool. LDAT could be an appropriate tool to assess live donor candidates.

Allogeneic hematopoietic stem cell and liver transplantation in a young girl with dedicator of cytokinesis 8 protein deficiency.

DOCK8 deficiency is a rare inherited combined immunodeficiency, caused by mutations in the DOCK8 gene. We describe a case with DOCK8 deficiency associated with severe CLD in whom orthotopic LT was performed successfully after allogeneic HSCT. A 5 year-old girl with DOCK8 deficiency presented with mild direct hyperbilirubinemia and abnormal GGT level and without a previous history of jaundice. She had severe growth retardation, hepatosplenomegaly and generalized eczema. Progressive worsening of CLD was observed within 4 months. Investigations for etiology of liver disease were negative. Liver biopsy showed bridging necrosis, cholestasis and, cirrhosis. Recurrent immune hemolytic crisis and several viral infections developed in follow-up. She underwent whole cadaveric LT for end-stage liver disease (ESLD) 1 year after allogenic HSCT from a full matched related donor. The postoperative course was uneventful. The patient is alive with normal liver function and moderate skin graft versus host disease for 36 months after LT. In conclusion DOCK8 deficiency can be associated with severe CLD. Successful LT following HSCT is possible in patients with ESLD in DOCK8 deficiency. The timing of LT is challenging in patients requiring both HSCT and LT since conditioning regimens for HSCT can be highly hepatotoxic and the patients with suboptimal liver function can become decompensated during HSCT.

Prevention and acute management of biliary injuries during laparoscopic cholecystectomy: Expert consensus statement.

Gallstone disease is very common and laparoscopic cholecystectomy is one of the most common surgical procedures all over the world. Parallel to the increase in the number of laparoscopic cholecystectomies, bile duct injuries also increased. The reported incidence of bile duct injuries ranges from 0.3% to 1.4%. Many of the bile duct injuries during laparoscopic cholecystectomy are not due to inexperience, but are the result of basic technical failures and misinterpretations. A working group of expert hepatopancreatobiliary surgeons, an endoscopist, and a specialist of forensic medicine study searched and analyzed the publications on safe cholecystectomy and biliary injuries complicating laparoscopic cholecystectomy under the organization of Turkish Hepatopancreatobiliary Surgery Association. After a series of e-mail communications and two conferences, the expert panel developed consensus statements for safe cholecystectomy, management of biliary injuries and medicolegal issues. The panel concluded that iatrogenic biliary injury is an overwhelming complication of laparoscopic cholecystectomy and an important issue in malpractice claims. Misidentification of the biliary system is the major cause of biliary injuries. To avoid this, the "critical view of safety" technique should be employed in all the cases. If biliary injury is identified intraoperatively, reconstruction should only be performed by experienced hepatobiliary surgeons. In the postoperative period, any deviation from the expected clinical course of recovery should alert the surgeon about the possibility of biliary injury.

Five right hepatic vein reconstructions using the autologous saphenous vein in the right lobe living-donor liver transplant: a case report.

In living-donor liver transplant, hepatic venous anomalies are not rare. Despite numerous techniques developed over the years, the best way of establishing a patent and durable hepatic drainage system remains controversial. We present a case where we successfully reconstructed 5 hepatic venous structures with a combination of direct anastomosis and saphenous vein interposition. Careful planning before surgery, and a customized approach for the patient on the back table, brought about successful results.

Outcomes of laparoscopic versus open splenectomy.

PURPOSE: Laparoscopic techniques have gained wide clinical acceptance in surgical practice today. The laparoscopic approach has been established as the technique of choice for elective splenectomies performed on normal sized spleens. The purpose of this study was to evaluate the outcome of patients undergoing laparoscopic splenectomy (LS) at the TOBB University of Economics and Technology (ETU) Hospital and Kecioren Training and Research Hospital. METHODS: One hundred and thirty-five patients underwent splenectomy between January 2000 and July 2010. For comparison, the records of 130 patients undergoing splenectomy were evaluated for age, gender, hospital stay, time to start of diet, conversion rate, operation time and wound infection. RESULTS: Mean operation time means the time interval between surgeon commencing operation to end of operation. Mean operation time in patients treated by LS was 132 minutes and 121 minutes in open splenectomy (OS). Mean hospital stay was 5.65 days in patients undergoing LS and starting of diet was 1.21 days. In patients treated by OS, mean hospital stay was 9.17 days, starting of diet was 2.37 days. Four patients were converted to open surgery. Conversion rate was 6.4 percent. In the early post operative period (within 10 days of surgery) 9.2%, LS group had lower incidences of wound infection rate after surgery than OS group (4.8%, 7.4%, respectively; P = 0.06). CONCLUSION: LS is a safe and effective alternative to OS for treatment of splenic diseases in patients of all ages.

Incidental gallbladder cancer diagnosed during or after laparoscopic cholecystectomy in members of the Turkish population with gallstone disease.

BACKGROUND/AIMS: Gallbladder cancer is a rare neoplasm. We report our experience with gallbladder cancer that was incidentally diagnosed during or after laparoscopic cholecystectomy performed for gallstone disease. MATERIAL AND METHODS: This study included all laparoscopic cholecystectomies due to gallstone disease undertaken from May 1999 to June 2010. Exclusion criteria were suspicion of malignancy and/or existence of gallbladder polyps detected with ultrasonography preoperatively. Patients with incidentally diagnosed gallbladder cancer were recorded, and the clinical and demographic characteristics of these patients were reviewed. RESULTS: Of 5,382 patients in whom laparoscopic cholecystectomy was attempted, 5,164 were included in this study. Incidental gallbladder cancer was found in five patients, with a mean age of 66.2 years. The histological tumor stages were adenocarcinoma in situ in one patient, pT1b in one patient, pT2 in one patient, and pT3 in two patients. Two patients who underwent laparoscopic cholecystectomy alone underwent no additional surgery because of the low stage of the tumors. The three remaining patients, whose laparoscopic cholecystectomies were converted to open surgeries, underwent cholecystectomy, excision of the liver bed and lymph node dissection. The overall median survival time was 32 months. CONCLUSION: The incidence of incidental gallbladder cancer has been reported to vary, up to 2.85%. In this single-center study, the rate of incidental gallbladder cancer was found to be 0.09%. Female gender and advanced age are demographic risk factors for gallbladder carcinoma. Although gallbladder cancer is well known for its poor prognosis, tumors that are incidentally diagnosed are often found at an early stage and have a better prognosis.

Ciliated foregut cyst of the gallbladder: report of a case and review of literature.

Cystic lesions of the gallbladder are very rare and they are generally lined by single columnar or mucinous epithelium. A ciliated cyst of foregut origin is extremely rare in gallbladder. To our knowledge, only five cases have been reported so far. Here, we present the sixth case found incidentally in ultrasonographic examination in a 41-year-old woman suffering from chronic right upper quadrant pain. Laparoscopic cholecystectomy was performed for the gallstones and a benign appearing cyst in ultrasonography. Macroscopically, a submucosal unilocular cyst was located in the neck of the gallbladder. There was no communication with the lumen. Histologically, the cyst was lined by pseudostratified ciliated epithelium containing goblet cells and had a muscular wall. The postoperative course was uneventful. Patient was discharged on the second day of the operation and was well after 2 months.

Aflatoxin exposure in viral hepatitis patients in Turkey.

BACKGROUND/AIMS: Hepatocellular carcinoma is the fifth most common cancer and a major public health problem worldwide. Differences in distribution of hepatocellular carcinoma incidence are probably due to different levels of exposure to hepatocellular carcinoma risk factors: chronic infections with hepatitis B virus (HBV) and aflatoxin exposure in developing countries, and smoking and alcohol abuse in developed countries. Aflatoxin is one of the most important of the environmental toxins that contribute to the pathogenesis of hepatocellular carcinoma, especially in the regions where dietary foodstuffs (peanuts, corn, Brazil nuts, pistachios, spices and figs) are highly contaminated. High aflatoxin levels have been shown in the foodstuffs that are produced in our country. The specific aim of this study was to assess the rate of aflatoxin exposure and to determine some clues about aflatoxin metabolism by measuring and comparing the levels of carcinogenic forms in healthy subjects, in different stages of viral disease, and in different viral hepatitis types. METHODS: This was a cross-sectional observational, single-center study. A total of 203 (male/female: 119/84) viral hepatitis patients who were consecutively admitted to Ankara University, School of Medicine, Gastroenterology Clinic, between January 2006 and June 2007 were enrolled into the study. Sixty-two healthy subjects (male/female: 33/29) with normal blood chemistry and negative viral serology served as controls. Chemical forms AFB1, AFB2, AFG1, and AFG2 were assessed in plasma of study participants by high-performance liquid chromatography. RESULTS: AFB1, AFB2, AFG1, and AFG2 were detected in 24.6%, 17.2%, 22.7%, 18.2% of the 203 patients, respectively, and were significantly higher than in the control group for all chemical forms. Percentage of AFB1-positive patients was significantly higher than in the control group irrespective of disease stage. There was no significant difference between chronic infected patients, cirrhotic patients and patients with Hepatocellular carcinoma with respect to percentage of aflatoxin-positive individuals. CONCLUSIONS: With this study, we have documented that in viral hepatitis patients, aflatoxin exposure is significantly higher than in healthy subjects in Turkey and it may play an important role in the development of hepatocellular carcinoma. Thus, large studies exploring the relation between aflatoxin exposure, viral hepatitis status, and risk of hepatocellular carcinoma development are needed.

PPAR-alpha L162V polymorphism in human hepatocellular carcinoma.

BACKGROUND/AIMS: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. METHODS: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. RESULTS: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. CONCLUSIONS: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced hepatocellular carcinoma and is absent in HCV-related hepatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.

Solid pseudopapillary tumor of the pancreas: emphasis on differential diagnosis from aggressive tumors of the pancreas.

Solid pseudopapillary tumor is an unusual primary tumor of the pancreas with a low potential for malignancy and unknown cell origin, seen mostly in young women. Although it is discussed among pancreatic epithelial tumors, many cases do not express cytokeratin but show neuroendocrine differentiation. Three cases (2 female, 1 male, aged 24, 45 and 50 years, respectively) of solid pseudopapillary tumor localized in the pancreas are presented. All cases displayed a well-circumscribed tumor, with an average diameter of 6 cm and a red-brown colored, hemorrhagic, cystic cut surface. Microscopically they were encapsulated with large areas composed of thin papillary formations and solid areas focally. Tumor cells were dyscohesive with small, round- to-oval, central nuclei, and vacuolated, clear or eosinophilic cytoplasm without mitotic activity. NSE, vimentin, synaptophysin, ER, PR, Ki-67, S-100, Pan CK, a1-antitrypsin, a2-antichymotrypsin, and antibodies were used in the immunohistochemical study. Vimentin, synaptophysin, NSE, PR, and a1-antitrypsin showed expression in all cases, while Pan-CK was expressed in two cases. Ki-67 expression was below 1% in all cases. Morphologic features of solid pseudopapillary tumor may be confused with pancreatic endocrine neoplasm and ductal adenocarcinoma. All cases showed features of histiocytic and neuroendocrine differentiation. Epithelial differentiation was identified in two cases. We conclude that immunohistochemistry is incapable of giving additional information for the diagnosis of solid pseudopapillary tumor due to different lines of differentiation of tumor cells. We believe that macroscopic and microscopic features (using hematoxylin and eosin stain) are more important for the diagnosis and differential diagnosis of this tumor.

Effects of peritoneal lavage with scolicidal agents on survival and adhesion formation in rats.

Intraoperative irrigation of the peritoneal cavity with scolicidal agents is frequently recommended when dealing with traumatic or spontaneous rupture of hydatid cysts. The present experimental study was designed to examine the influence of various scolicidal agents on adhesion formation and survival. A total of 149 rats were randomly allocated to nine groups. Peritoneal lavage through a median laparotomy was performed with the following scolicidal agents. Group 1 (0.9% saline: controls), group 2 (20% hypertonic saline), group 3 (0.04% chlorhexidine gluconate), group 4 (3% hydrogen peroxide), group 5 (0.5% silver nitrate), group 6 (1% polyvinylpyrrolidone-iodine, or PVP-I ), group 7 (5% PVP-I), group 8 (0.5% cetrimide/0.05% chlorhexidine), and group 9 (10% PVP-I). The surviving animals were sacrificed on postoperative day 15. Adhesion formation was macroscopically graded by the Nair criteria. The severity of adhesion formation was evaluated microscopically using the fibrosing scoring criteria and the strain test. Group 9 (10% PVP-I) was excluded from the adhesion evaluation because all of the rats died in this group. The mortality rate was significantly higher in groups 5 and 7 than in groups 1, 2, 3, 4, 6, and 8. Adhesion scores were significantly lower in groups 1, 2, 3, and 4 than in groups 5, 6, 7, and 8. The lowest adhesion score was found in group 3 and the highest in the group 7. These results indicate that 0.04% chlorhexidine gluconate, the most potent scolicidal agent in vitro and in vivo, was associated with the lowest adhesion formation and mortality among various scolicidal agents in this experimental study.