ABO Incompatible Living Donor Liver Transplantation: A Single Center Experience / 대한이식학회지

BACKGROUND: This study examined the outcomes of ABO incompatible living donor liver transplantation (LDLT). The changes in the immunologic factors that might help predict the long term outcomes were also studied. METHODS: Twenty-three patients, who underwent ABO incompatible LDLT from 2010 to 2015, were reviewed retrospectively. The protocol was the same as for ABO compatible LDLT except for the administration of rituximab and plasma exchange. The clinical outcomes and immunologic factors, such as isoagglutinin titer and cluster of differentiation 20+ (CD20+) lymphocyte levels were reviewed. RESULTS: The center showed a 3-year survival of 64% with no case of antibody-mediated rejection. When transplantation-unrelated mortalities (for example, traffic accidents and myocardial infarction) were removed from statistical analysis, the 3-year survival was 77.8%. Although isoagglutinin titers continued to remain at low levels, the CD20+ lymphocyte levels recovered to the pre-Rituximab levels at postoperative one year. CONCLUSIONS: As donor shortages continue, ABO incompatible liver transplantation is a feasible method to expand the donor pool. On the other hand, caution is still needed until more long-term outcomes are reported. Because CD20+ lymphocytes are recovered with time, more immunologic studies will be needed in the future.

Human Leukocyte Antigen-C Genotype and Killer Immunoglobulin-like Receptor-Ligand Matching in Korean Living Donor Liver Transplantation

BACKGROUND: The interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts. METHODS: One hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes. RESULTS: Homozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival. CONCLUSIONS: This study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.

A novel pancreaticogastrostomy method using only two transpancreatic sutures: early postoperative surgical results compared with conventional pancreaticojejunostomy

PURPOSE: To evaluate the surgical outcomes of pancreaticogastrostomy (PG) using two transpancreatic sutures with a buttress method through an anterior gastrostomy (PGt), and compare these results with our previous experience with pancreaticojejunostomy (PJ) including the dunking and duct to mucosa methods after pancreaticoduodenectomy (PD). METHODS: In this study, 171 patients who had undergone PD between January 2005 and April 2013 were classified into three groups according to the method of the pancreaticoenteric anastomosis: dunking PJ (PJu group; n = 67, 39.1%), duct to mucosa PJ (PJm group; n = 41, 23.9%), and PGt (PGt group; n = 63, 36.8%). We retrospectively analyzed patient characteristics, perioperative outcomes, and surgical results. RESULTS: Both groups had comparable demographics and pathology, and there were no significant differences in operative time, estimated blood loss, or postoperative hospital stay. Within the two groups, morbidities occurred in 49 cases (10.7%), and were not significantly different between the two groups, excepting postoperative pancreatic fistula (POPF). The PGt group had a lower rate of POPF (18/63, 28.6%) than the PJu and PJm groups (21/67, 31.3% and 19/41, 46.3%; P = 0.048), especially in terms of grades B and C POPF (4/63 [6.3%] in the PGt group vs. 7/67 [10.4%] in the PJu group and 9/41 [22.0%] in the PJm group, P = 0.049). CONCLUSION: The PGt method showed feasible outcomes for POPF and had advantages over dunking PJ and duct to mucosa PJ with respect to immediate postoperative results. PGt may be a promising technique for pancreaticoenteric anastomosis after PD.

Dual-incision laparoscopic spleen-preserving distal pancreatectomy

Laparoscopic spleen-preserving distal pancreatectomy has been widely performed for benign and borderline malignancy in the body or tail of the pancreas when there are not oncologic indications for splenectomy. As the need for minimally invasive procedures to reduce postoperative morbidity and improve the quality of life is increasing, many surgeons have attempted to reduce the number of trocars and incision size to minimize access trauma and scarring. Single-port laparoscopic spleen-preserving distal pancreatectomy is the result of these efforts; however it has many limitations such as technical difficulty and prolonged operation time. In this article, we report the first case of dual-incision laparoscopic spleen-preserving distal pancreatectomy, proving that it can be a safe and feasible minimally invasive procedure for benign or borderline malignant tumors in the body or tail of the pancreas.

De novo hepatitis B virus infection developing after liver transplantation using a graft positive for hepatitis B core antibody

PURPOSE: The use of hepatitis B core antibody (HBcAb)-positive grafts is increasing, especially where hepatitis B is endemic. However, this remains controversial because of the risk of development of de novo HBV infection. METHODS: We collected information obtained between January 2000 and December 2012 and retrospectively analyzed data on 187 HBsAg-negative donors and recipients were analyzed retrospectively. De novo HBV infection was defined as development of HBsAg positivity with or without detection of HBV DNA. RESULTS: Forty patients (21.4%) received HBcAb-positive grafts. Survival rate did not differ by donor HBcAb status (P = 0.466). De novo HBV infection occurred in five patients (12.5%) who were not treated with anti-HBV prophylaxis, and was significantly more prevalent in hepatitis B surface antibody (HBsAb)- and HBcAb-negative than HBsAb- and HBcAb-positive recipients (50% vs. 4.2%, P = 0.049). All patients except one were treated with entecavir with/without antihepatitis B immunoglobulin and four were negative in terms of HBV DNA seroconversion. No patient died. CONCLUSION: HBcAb-positive grafts are safe without survival difference. However, the risk of de novo hepatitis B virus infection was significantly increased in HBsAb- and HBcAb-negative recipients. All patients were successfully treated even after recurrence.

Clinical significance of single-port laparoscopic splenectomy: comparison of single-port and multiport laparoscopic procedure

PURPOSE: Single-port laparoscopic splenectomy has been performed sporadically. The aim of this study is to assess our experience with single-port laparoscopic splenectomy compared to conventional multiport laparoscopic surgery for the usual treatment modality for various kinds of splenic disease. METHODS: Between October 2008 to February 2014, 29 patients underwent single-port laparoscopic splenectomy and 32 patients received multiport laparoscopic splenectomy. We retrospectively analyzed the clinical outcomes of single-port group and multiport group. RESULTS: The body mass index and disease profiles of the both groups were similar. The operative times of single-port and multiport group were 113.6 +/- 39.9 and 95.9 +/- 38.9 minutes, respectively (P = 0.946). The operative blood loss of the two groups were 295.8 +/- 301.3 and 322.5 +/- 254.5 mL (P = 0.582). Postoperative retrieved splenic weight of the single-port and multiport groups were 283.9 +/- 300.7 and 362.3 +/- 471.8 g, respectively (P = 0.261). One single-port partial splenectomy and 6 multiport partial splenectomies were performed in this study. There was one intraoperative gastric wall injury. It occurred in single-port group, which was successfully managed during the operation. Each case was converted to laparotomy in both groups due to bleeding. There was one mortality case in the multiport laparoscopic splenectomy group, which was not related to the splenectomy. Mean hospital stay of the single-port and multiport group was 5.8 +/- 2.5 and 7.3 +/- 5.2 days respectively (P = 0.140). CONCLUSION: Single-port laparoscopic splenectomy seems to be a feasible approach for various kinds of splenic disease compared to multiport laparoscopic surgery.

Culture with Growth Factor Supplements Improves the Viability and Function of Rat Hepatocytes / 대한이식학회지

BACKGROUND: To identify the optimum culture conditions by investigating isolated rat hepatocytes cultured in medium containing different growth factors. METHODS: Hepatocytes were isolated from rats using a two-step perfusion technique and divided into the following four groups cultured in medium containing different growth factors: control, epidermal growth factor (EGF), insulin, and EGF+insulin. The viability of the cultured rat hepatocytes and liver function parameters, including albumin, ammonia, and urea in the culture medium, were measured. Hepatocyte morphology was examined by staining with hematoxylin and eosin, and albumin receptor expression was confirmed by immunofluorescence. RESULTS: Slightly higher viability was observed in the growth factor groups than in the control group, although without significance (P=0.073). The levels of albumin (P=0.001), ammonia (P<0.001), and urea (P=0.041) differed significantly among the four groups. The functional parameters in the growth factor groups, particularly the EGF+insulin group, were significantly superior to those in the control group. The morphology of the hepatocytes in all growth factor groups was well maintained at 10 days. However, the control group showed deterioration in cell morphology by day 7. CONCLUSIONS: Morphological and functional assessment indicated that the presence of growth factors, particularly EGF+insulin, provided culture conditions superior to those of non-supplemented medium.

Effects of glucose concentration in the medium on rat hepatocyte culture

PURPOSE: To determine the optimum culture conditions by investigating isolated rat hepatocytes cultured in medium containing different glucose concentrations. METHODS: Hepatocytes were isolated from rats using a two-step perfusion technique and divided into the following two groups cultured in medium containing different glucose concentrations: (1) low-glucose group and (2) high-glucose group. Total cell count and viability of cultured rat hepatocytes and liver function parameters (i.e., concentrations of albumin, ammonia, and urea in the culture medium) were measured. The morphology of cultured rat hepatocytes was examined by staining with hematoxylin and eosin, and albumin receptor expression was confirmed by immunofluorescence. RESULTS: Total cell count and viability showed smaller increases in the low-glucose group than the high-glucose group, although the difference was not statistically significant (P = 0.112 and P = 0.147, respectively). The levels of albumin (P = 0.943), ammonia (P = 0.744), and urea (P = 0.709) were not significantly different between the two groups. In both groups, the function of cultured hepatocytes decreased significantly over time. The morphology of hepatocytes was well maintained in both groups at 3 days. On day 7, the cytoplasm was transformed into a spindle shape. On day 10, these changes were exaggerated, and were more prominent in the high-glucose group. CONCLUSION: Morphological assessment indicated that low-glucose culture medium is better than high-glucose culture medium for culturing of hepatocytes, although there was not significantly different in functional assessment. The cultured hepatocytes with low-glucose culture medium could be maintained for 7 days.

Outcomes of living donor liver transplantation using elderly donors

PURPOSE: Living donor liver transplantation (LDLT) using elderly donors is increasing in frequency in response to organ shortage. However, elderly donor graft has been reported to negatively affect graft patency and patient survival. METHODS: We retrospectively reviewed the medical records of 604 patients who underwent LDLT at Seoul St. Mary's Hospital, The Catholic University of Korea between May 1999 and September 2012. Elderly donors were defined as those > or =55 years of age. Here, we evaluate the survival differences and causes of death of recipients of elderly donor grafts. RESULTS: The overall mortality rate of the recipients was significantly higher in the elderly donor group (group A) than in the younger donor group (group B: 46.2% vs. 18.1%, P = 0.004). The survival length of group A was significantly shorter than that of group B (31.2 +/- 31.3 and 51.4 +/- 40.8 months, P = 0.014). The significantly common causes of death in group A were biliary (41.7%) and arterial complication (16.7%), and it was higher than those in group B (P = 0.000 and P = 0.043, respectively). CONCLUSION: LDLT using elderly donors could induce more serious complications and higher mortality rates than those at using younger donors. As such, careful donor selection is needed, especially with regard to assessing the condition of potential elderly donor livers. Furthermore, a large-volume and multicenter study of complications and outcomes of LDLT using elderly donor liver is required.

Relation of the E-cadherin Expression and the Lauren Classification in Stomach Cancer according to the Tumor Location

PURPOSE: E-cadherin (ECD) plays a pivotal role in integrating the normal tissue architecture and the suppression of cancer invasion, including stomach cancer. The epidemiology of stomach cancers is noticeably different according to the site of the index tumor, even though the stomach cancers all have similar gross shapes. In this study, the relation between the expression of ECD, along with the clinicopathologic parameters and recurrence or survival, were investigated for patients with gastric adenocarcinoma according to the tumor location. METHODS: We examined formalin-fixed, paraffin-embedded archival tissues from 50 surgically resectable gastric adenocarcinomas, which were grouped by the index tumor site as follows: distal (antrum) versus proximal (mid and upper body). To elucidate the correlation between the ECD expression and the site of the stomach cancer with the other clinicopathologic factors, we examined the ECD tissue status via performing immunohistochemistry. To compare the rates of recurrence and survival among subgroups, the patients were followed up for an average of 42 months. RESULTS: Among the 50 tumors examined, 28 (56%) tumors showed various degrees of a ECD expression. The gender, age, size, depth of invasion, lymph node metastasis, stage, lymphatic invasion and vascular invasion were not related with the ECD expression. The Lauren classification was cor-related with the ECD expression in the mid and upper body stomach cancer, but not in the antral stomach cancer (P=0.042). The expression of ECD was not related with the survival rate (P=0.223). There was no significant difference in the recurrence rate between the subgroups with and without an abnormal expression of ECD (P=0.588). CONCLUSION: For the mid and upper body stomach cancer, the expression of E-cadherin correlated with the diffuse type of cancer, according to the Lauren classification, but not with the survival rate.

Clinical Analysis of Recurrent Gastrointestinal Stromal Tumor (GIST) Patients

PURPOSE: Gastrointestinal stromal tumors (GISTs) are of a mesenchymal origin, and they arise predominantly from the gastrointestinal tract. This study aims to aid the post operative management of GIST patients by analyzing the clinical and immunopathological features of recurrent GISTs. METHODS: We enrolled 98 GIST patients who had been operated on for their primary tumor from 1987 to 2001 at the Catholic Medical Center. Among them, 28 patients had clinical and radiological features that were proved to be recurrence, and the patients' survival rates were compared according to the treatment modalities. RESULTS: When the maximum length of tumor was shorter and the mitotic index lower, then these patients had higher disease free survival rates and lower recurrence rates. The Ki-67 negative group had lower recurrence rates than their Ki-67 positive counterparts. Recurrence was mostly observed as liver metastasis. The mean length of time to recur was 22.96 months. Fifteen patients received additional treatments such as surgery, chemotherapy and radiation therapy, but there was no significant difference in survival rates when they were compared to the 13 patients who did not receive further treatments. CONCLUSION: Of the patients diagnosed with GIST after surgery, those with worse prognostic factors, i.e. a bigger tumor size and higher mitotic index, require more meticulous surveillance for tumor recurrence, and especially for liver recurrence, which was the most common recurrence site, during the follow up exams. In addition, although there have not been any remarkably effective treatments for the recurrent GIST patients, further researches for new therapy such as STI-571 is mandated.