Analysis of outcomes and renal recovery after adult living-donor liver transplantation among recipients with hepatorenal syndrome.

When timely access to deceased-donor livers is not feasible, living-donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single-center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non-HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post-LT renal recovery. The HRS group had a higher death rate than the non-HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post-LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non-recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post-LT sepsis (p < 0.001) and non-recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre-LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post-LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post-LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post-LT renal recovery.

Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells.

Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Hypothermic perfusion hepatectomy for unresectable liver cancer: A single-center experience.

BACKGROUND: The resection of liver tumors that involve the hepatic veins adjacent to the vena cava or hepatic hilum is technically challenging. We present our surgical techniques and the long-term outcome of five patients with conventionally unresectable tumors. METHODS: Five patients with conventionally unresectable tumors were successfully treated by "ex-situ liver resection" and "in-situ and ante-situm hypothermic liver perfusion" under total vascular exclusion and venovenous bypass. RESULTS: These approaches allowed complete tumor removal with vascular reconstruction under a bloodless surgical field, while minimizing hepatic ischemic injury and preserving liver function. No perioperative mortalities occurred, and postoperative complications were minimal. The postoperative survival periods were limited due to the advanced malignancies in our patients, but the survival benefit was encouraging. The median postoperative survival time was 29.1 months, with the longest survival period being nearly 10 years. These approaches improved the quality of life and provided an opportunity for additional treatment. CONCLUSIONS: Hypothermic perfusion hepatectomy is a realistic option for achieving surgical cure or significantly improved survival and quality of life in patients with tumors deemed unresectable using conventional normothermic hepatectomy. These approaches can overcome the limitations of the liver's restricted normothermic ischemia tolerance or inaccessible tumor locations.

Can heme oxygenase-1 be a prognostic factor in patients with hepatocellular carcinoma?

Heme oxygenase-1 (HO-1) is an important catalytic enzyme in heme degradation, which increases during stressful conditions. It plays a major role in antioxidative and antiapoptotic processes and is associated with tumor growth and metastasis.This study aimed to evaluate the degree of HO-1 expressions in hepatocellular carcinoma (HCC) surgical specimens and the correlation between HO-1 expression and patient prognosis. Formalin-fixed, paraffin-embedded HCC tissue samples (n = 96) were included in the analysis, and the expression of HO-1 was evaluated by immunohistochemical staining. We reviewed clinical features of patients and evaluated the prognostic role of HO-1 in patient survival and recurrence.Positive HO-1 expression was identified in 43 cases (44.8%) and was frequently found in patients with advanced histology (Edmondson-Steiner [E-S] grade 2, 3, 4), α-fetoprotein (AFP) level of more than 200 IU/mL, and the presence of microvascular and capsular invasion (P < .05). In the univariate analysis, the overall survival (OS) and disease-free survival (DFS) of patients with HO-1-positive HCC were not statistically different from those with HO-1-negative HCC. Moreover, HO-1 expression was not associated with patient survival and recurrence based on the multivariate analysis. In the subgroup analysis of patients without preoperative transarterial chemoembolization (TACE) (n = 61), HO-1 was not also associated with tumor recurrence (P = .681).The clinical implication of HO-1 activity is controversial in various malignancies. However, HO-1 expression did not seem to influence the prognosis of HCC patients.

Multidisciplinary approach for treatment of primary hepatic choriocarcinoma in adult male patient.

Choriocarcinoma is a rare malignant germ cell tumor and it usually occurs in the gonads (ovary or testis) and uterus. Primary hepatic choriocarcinoma (PHC) is a variant of choriocarcinoma featuring sole liver presentation without any evidence of gonodal involvements. Adult male patients with PHC carry dismal prognosis and their median survival period was less than 5 months. We herein present a first Korean case of a 54-year-old male patient with adult PHC, who was treated by surgical resection and chemotherapy through a multidisciplinary approach.

Angiogenesis in the Transplanted Donor Graft After Living-Donor Liver Transplantation.

BACKGROUND: There is no direct evidence for the role of angiogenesis in liver regeneration in humans. This study aimed to determine whether angiogenesis is involved in the regeneration of transplanted donor grafts in human living-donor liver transplantation (LDLT) and to examine the impact of donor graft volume on angiogenesis. METHODS: Clinical data and liver tissue characteristics were analyzed in 4 patients who received adult-to-adult LDLT with dual left lobe grafts from 2 living donors. Liver tissues from transplanted donor grafts were obtained and immunohistochemically examined at 3 to 4 weeks after transplantation using the endothelial marker Ki67+ and CD31+. RESULTS: All recipients showed recovery of normal liver function and a significant increase in the volume of engrafted left lobes after transplantation. Immunohistochemistry showed a remarkable increase in Ki67+ single hepatocyte proliferation, implying the role of hepatocytes in liver reconstitution, and a high density of blood vessels and proliferative endothelium, suggesting in vivo angiogenesis. Furthermore, we found that Ki67+ nuclei in CD31+ sinusoidal endothelial cells were higher in recipients with smaller donor grafts than in those with larger donor grafts. CONCLUSIONS: Our results suggested that angiogenesis is involved in the regeneration of transplanted liver in humans in inverse proportion to the donor graft volume.

Placement of an Aortohepatic Conduit as an Alternative to Standard Arterial Anastomosis in Liver Transplantation.

BACKGROUND The aim of this study was to assess the impact of placement of an aortohepatic conduit on graft and patient survival after liver transplantation (LT) in selected patients with an inadequate recipient hepatic artery (HA) for a standard arterial anastomosis. MATERIAL AND METHODS Of 331 patients who underwent deceased donor LT, 25 (7.6%) who received placement of an aortohepatic conduit at the time of transplantation were included. Clinical characteristics and outcomes, including postoperative complications, conduit patency, and graft and patient survival rates, were analyzed. RESULTS All 25 patients included in this study presented a high preoperative Model for End-stage Liver Disease score (25.4±8.6; range, 6-42) and high rates of retransplantation (n=11, 44%) or previous abdominal - pelvic surgery (n=5, 20%). The observed postoperative vascular complications were portal vein thrombosis in 3 cases (12%) and anastomosis-site bleeding of the aortohepatic conduit in 1 case (4%); there was no HA thrombosis or stenosis in our analysis. With a median follow-up of 37 months (range, 0-69 months), all aortohepatic conduits were patent, and the graft and patient survival rates were 84% and 68%, respectively. The causes of death were graft failure (n=4), pneumonia (n=3), and cerebrovascular accidents (n=1). CONCLUSIONS Our results indicate that placement of an aortohepatic conduit is a feasible alternative to a standard arterial anastomosis in selected patients whose HA and surrounding potential inflow arteries are not suitable for standard arterial anastomosis.

Incidental gallbladder cancer after routine cholecystectomy: when should we suspect it preoperatively and what are predictors of patient survival?

PURPOSE: In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. METHODS: Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. RESULTS: The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). CONCLUSION: Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.

A Concurrence of Adenocarcinoma with Micropapillary Features and Composite Glandular-Endocrine Cell Carcinoma in the Stomach.

We report a unique case of synchronous double primary gastric cancer consisting of adenocarcinoma components with micropapillary features and composite glandular-endocrine cell carcinoma components. The patient was a 53-year-old man presenting with a 6-month history of epigastric pain and diarrhea. A subtotal gastrectomy was performed. Histologically, one tumor was composed of micropapillary carcinoma components (50%) with tight clusters of micropapillary aggregates lying in the empty spaces, admixed with moderately differentiated adenocarcinoma components. MUC-1 was expressed at the stromal edge of the micropapillary component. The other tumor was composed of atypical carcinoid-like neuroendocrine carcinoma (50%), adenocarcinoid (30%), and adenocarcinoma components (20%). The neuroendocrine components were positive for CD56, synaptophysin, chromogranin, and creatine kinase. The adenocarcinoid components were positive for both carcinoembryonic antigen and neuroendocrine markers (amphicrine differentiation). This case is unique, due to the peculiar histologic micropapillary pattern and the histologic spectrum of adenocarcinoma adenocarcinoid-neuroendocrine carcinoma of the synchronous composite tumor.

Uncomplicated jejunal diverticulosis with pneumoperitoneum.

Small bowel diverticulosis is a rare finding within all bowel diverticuloses and jejunal diverticulosis is even rarer. Their relative clinical rarity and varied presentation may make diagnosis both delayed and difficult. We experienced a case of jejunal diverticulosis, which was diagnosed intraoperatively. A 55-year-old woman was admitted to Emergency Department with pneumoperitoneum on plain chest and abdominal film from a local clinic. She was hemodynamically stable with minimal tenderness on the left upper quadrant of the abdomen but no rebound tenderness. At surgery, small bowel torsion and jejunal diverticulosis were confirmed. Over 30 variable sized small bowel diverticula were noted on the mesenteric side of the proximal jejunum. The affected segment of the jejunum was about 180 cm. On exploration, we could not find any perforation site. No postoperative complications were observed, and the patient made a full recovery. Jejunal diverticulosis is rare, but it should not be regarded as insignificant.

Pneumatosis intestinalis after adult living donor liver transplantation: report of three cases and collective literature review.

BACKGROUNDS/AIMS: Pneumatosis intestinalis (PI) is a condition in which multiple gas-filled mural cysts develop in the gastrointestinal tract. Although its exact etiology remains obscure, PI is rarely observed in liver transplant (LT) recipients. METHODS: In 317 cases of adult living donor LT (LDLT) performed during 2011, PI developed in three patients during the 3 year follow-up. RESULTS: Of these three patients, the two who demonstrated PI at 6 weeks and 2 months after LT, respectively, were asymptomatic and showed no signs of secondary complications. Diagnosis was made incidentally using abdominal radiographs and computed tomography (CT) scans. PI was identified in the right ascending colon with concomitant pneumoperitoneum. These two patients received supportive care and maintained a regular diet. Follow-up CT scans demonstrated spontaneous resolution of PI with no complications. The third patient was admitted to the emergency room 30 months after LDLT. His symptoms included poor oral intake and intermittent abdominal pain with no passage of gas. Abdominal radiography and CT scans demonstrated PI in the entire small bowel, with small bowel dilatation, pneumoperitoneum, and pneumoretroperitoneum, but no peritonitis. Physical examination revealed abdominal distension but no tenderness or rebound tenderness. After 1 week of conservative treatment, including bowel rest and antibiotics therapy, PI and pneumoperitoneum resolved spontaneously without complications. CONCLUSIONS: We suggest that adult LDLT recipients who develop asymptomatic or symptomatic PI with no signs of secondary complications can be successfully managed with conservative treatment.

Systemic capillary leak syndrome (Clarkson's disease) during elective pylorus-preserving pancreaticoduodenectomy: case report.

Systemic capillary leak syndrome (SCLS), also called Clarkson's disease is rare and life-threatening disorder of unknown etiology, which is a characteristic triad of hypovolemic shock, hemoconcentration, and hypoalbuminemia. Unexplained capillary leakage from the intravascular to the interstitial space, which has been estimated up to 70% of the intravascular volume, is the proposed mechanism. Because the pathogenesis is unknown, it is diagnosed clinically after exclusion of other diseases that cause systemic capillary leak and no efficacious pharmacological treatment has been clearly established. The mortality rate ranges from 30% to 76%. In Korea, four cases of SCLS (5 cases in adult and 1 case in child) were reported by 2012. We describe a case of severe SCLS that suddenly occurred and rapidly progressed during pylorus preserving pancreaticoduodenectomy and review the literature.

Non-typhoid salmonella septic arthritis in dual living liver transplant recipient: a case report.

Non-typhoid salmonellosis is an infectious disease caused by Salmonella species other than Salmonella typhi. Although the usual clinical course of non-typhoid salmonellosis is a benign self-limiting gastroenteritis, these bacteria are especially problematic in immunocompromised individuals, including patients with malignancies, human immunodeficiency virus, or diabetes, and those receiving corticosteroids or other immunotherapy agents. In addition to enteric symptoms, Salmonella species give rise to extra-intestinal complications, including self-limiting arthritis, which appears 1 to 3 weeks after the onset of infection and lasts from a few weeks to several months. In some patients, however, this arthritis spears to be chronic in nature. We describe herein a living-donor liver transplant recipient who experienced non-typhoid Salmonella-triggered arthritis in the left hip. The patient recovered uneventfully after 6-month-long antibiotics treatment. Clinicians involved in transplantation should be aware of the possibility that transplant recipients, like other immunocompromised individuals, are at risk of salmonellosis and therefore require careful clinical and microbiological evaluation, with the goals of prevention and early recognition of infection.

A comparative study regarding the effect of an intraperitoneal anti-adhesive agent application in left-liver living donors.

BACKGROUNDS/AIMS: After left-sided hepatectomy due to a living donor, the stomach can become adhered to the hepatic cut surface. An unwanted gastric stasis can occur. For prevention of such gastric adhesion and laparotomy-associated adhesive ileus, some anti-adhesive agents have been developed for intra-abdominal application. The purpose of this study is to evaluate the effect of an intraperitoneal anti-adhesive agent application compared with a historical control group. METHODS: The study group consisted of 220 consecutive living donors who donated a left-liver graft during the time period between January 2006 and December 2011. The anti-adhesive agent which was used was composed of sodium hyaluronate and sodium carboxymethyl cellulose. The historical control group which used no anti-adhesive agent included 220 consecutive left-liver donors during the time period between January 1998 and December 2004. RESULTS: An overt gastric stasis which required fasting was observed in 5 subjects (2.3%) in the study group and in 7 subjects (3.2%) in the control group (p=0.77). An additional work-up to determine gastric stasis or prolonged ileus was performed in 17 (7.7%) and 22 (10%) donors, respectively (p=0.51). Only one donor in the control group underwent a laparotomy for an intestinal obstruction. No clinical factors such as patient age, sex, body mass index, remnant right liver proportion, shape of skin incision, and duration of surgery were significant risk factors of gastric stasis or prolonged ileus. No harmful side-effects of the anti-adhesive agent were identified. CONCLUSIONS: As a result of this study, the application of an anti-adhesive agent could not be proved as to be effective for prevention of gastric stasis and postoperative ileus. A further randomized and controlled study will be required to demonstrate the real benefits of an anti-adhesive application in left-liver living donors.

Section 6. Management of extensive nontumorous portal vein thrombosis in adult living donor liver transplantation.

BACKGROUND: Patent portal vein (PV) and adequate portal inflow is essential for successful living donor liver transplantation (LDLT). In extensive portal vein thrombosis (PVT) patients, however, complete PV thrombectomy is not feasible particularly at intrapancreatic portion, and subsequently portal flow steal through preexisting sizable collaterals or rethrombosis can occur. To overcome those problems, we introduced interruption of sizable collaterals and intraoperative cine-portogram (IOP), which is useful for diagnosis and treatment of residual PVT and sizable collaterals. METHODS: Fourteen percent of adult LDLT (188/1399) had PVT from February 2008 to December 2012 and were subdivided into Yerdel's grades 1, 2, 3, and 4 based on preoperative imaging and operative findings. Considering the severity of PVT and presence of sizable collaterals, the managements were as follows: thrombectomy alone, additional PV plasty, PV stenting, interposition graft, or additional interruption of collaterals. RESULTS: The Yerdel's grade of PVT patients were 1 (42%), 2 (54%), 3 (3%), and 4 (1%). One hundred one (77%) patients underwent interruption of sizable collaterals. The most common management for PVT was thrombectomy alone in grades 1 and 2, thrombectomy plus PV stenting and/or ballooning in grade 3, and interposition graft in grade 4. In LDLT for PVT patients, 1-year mortality was 9%, and PV-related complication occurred in 5%. The severity of PVT made no difference in the outcome. CONCLUSION: Multi-disciplinary approaches including surgical correction of PVT, IOP, and interruption of sizable collaterals resulted in excellent outcome, and it was not affected by the severity of PVT.

Effectiveness of external drainage of the bile duct in pancreaticoduodenectomy: a single surgeon's experience.

BACKGROUNDS/AIMS: The rates of surgery-related complications during and after pancreaticoduodenectomy (PD) remain very high, reaching up to 41%. They were primarily caused by leakage of pancreatic juice. We evaluated the effectiveness of external drainage of the bile duct using a pigtail drain to prevent pancreatic leakage in patients undergoing PD. METHODS: We evaluated 79 patients who underwent PD using a single-layer continuous suture between the pancreatic parenchyma and jejunum after duct-to-mucosa anastomosis by a single surgeon from April 2005 to December 2008. Of the 79, 44 underwent external drainage (ED) of the bile duct using a pigtail drain, performed in the intraoperative field via a retrograde transhepatic approach, whereas 35 did not undergo ED. RESULTS: Age, sex distribution, number of total complications, pancreatic duct size, pancreatic texture and duration of hospital stay did not differ between patients who did and did not undergo ED. In groups with or without ED, 0 and 4 patients, respectively, showed leakage of pancreatic juice and the difference was statistically significant (p=0.02). CONCLUSIONS: The fact that none of the patients who underwent external drainage experienced pancreatic leakage, suggests that external drainage of the bile duct with a pigtail drain to decompress the jejunum and to drain pancreatic and bile juice is useful in preventing the complications of pancreatic leakage.