Clinical Analysis of Stercoral Perforation without Mortality.

AIMS: This study was designed to review the clinical features of stercoral colonic perforation and to evaluate the appropriate intraoperative procedures and postoperative management to achieve the best surgical outcomes. METHODS: Between January 2009 and December 2015, 12 patients with stercoral perforation confirmed surgically and pathologically were included in this study, and their medical records were reviewed retrospectively. RESULTS: The enrolled patients included 2 men and 10 women; their mean age was 73.8 years. Abdomino-pelvic CT was an important diagnostic tool, which revealed fecalomas, extraluminal air and pericolic fat stranding in all patients. Hartmann's operation was performed in all patients, with a mean operation time of 239.3 min. Perforation site was in the left colon, mainly in the sigmoid colon. Intraoperative hypotension developed in 8 cases (66.7%). Postoperatively, all patients needed intensive care for 6.5 days and 6 patients needed the administration of inotropic agents for 3.0 days postoperatively. Disseminated intravascular coagulation developed in 10 cases (83.3%). There was no surgical mortality. CONCLUSION: Colorectal surgeons should be aware of the possibility of stercoral perforation, despite its rare incidence. Deep understanding of this potentially fatal disease by surgeons could reduce surgical mortality and improve postoperative outcomes.

Advances in endoscopic management of biliary complications after living donor liver transplantation: Comprehensive review of the literature.

Apart from noticeable improvements in surgical techniques and immunosuppressive agents, biliary complications remain the major causes of morbidity and mortality after living donor liver transplantation (LDLT). Bile leakage and stricture are the predominant complications. The reported incidence of biliary complications is 15%-40%, and these are known to occur more frequently in living donors than in deceased donors. Despite the absence of a confirmed therapeutic algorithm, many approaches have been used for treatment, including surgical, endoscopic, and percutaneous transhepatic techniques. In recent years, nonsurgical approaches have largely replaced reoperation. Among these, the endoscopic approach is currently the preferred initial treatment for patients who undergo duct-to-duct biliary reconstruction. Previously, endoscopic management was achieved most optimally through balloon dilatation and single or multiple stents placement. Recently, there have been significant developments in endoscopic devices, such as novel biliary stents, as well as advances in endoscopic technologies, including deep enteroscopy, the rendezvous technique, magnetic compression anastomosis, and direct cholangioscopy. These developments have resulted in almost all patients being managed by the endoscopic approach. Multiple recent publications suggest superior long-term results, with overall success rates ranging from 58% to 75%. This article summarizes the advances in endoscopic management of patients with biliary complications after LDLT.

De Novo Hepatitis B Infection From Hepatitis B Core Antibody-Positive Donors During Hepatitis B Immunoglobulin Prophylaxis.

De novo hepatitis B infection in patients receiving liver transplants from hepatitis B core antibody-positive donors is well known, but the effective prevention strategy has not been well established. In our hospital, recipients receive hepatitis B immunoglobulin monotherapy if they are hepatitis B surface antigen negative at the time of transplant and are receiving a liver from a hepatitis B core antibody-positive donor. Since August 2006, we have had 4 patients who were naïve to hepatitis B virus and received a hepatitis B core antibody-positive graft. Two patients died of other causes, and 2 patients, who had liver transplant in October 2006 and October 2009, developed de novo hepatitis B. Both patients were tested annually for serum hepatitis B surface antigen as part of routine visit. Tests were negative; however, both patients recently became hepatitis B surface antigen positive. Other laboratory results, including liver function test, were unremarkable, except HBsAb titer was undetectable even though hepatitis B immunoglobulin monotherapy had been administrated 2 months previously in both patients. The patients had hepatitis B virus DNA levels of 3.07E+08 copies/mL and 1.51E+08 copies/mL. We suggest that additional prophylactic therapies above hepatitis B immunoglobulin monotherapy are needed for these recipients.

Section 10. Endoscopic management of biliary complications in adult living donor liver transplantation.

Living donor liver transplantation (LDLT) has become an accepted therapeutic option for patients with end-stage liver disease. However, biliary complications remain the major causes of morbidity and mortality for LDLT recipients. Although there are currently no reports of a clear therapeutic algorithm, many approaches have been developed to treat biliary complications, including surgical, endoscopic, and percutaneous transhepatic techniques. Endoscopic treatment is currently the preferred initial treatment for patients that have previously undergone duct-to-duct biliary reconstruction. This article discusses aspects of endoscopic management of biliary complications that occur in adult LDLT.

A new technique for complete portal vein and superior mesenteric vein thrombosis in a liver transplant recipient.

We describe a deceased-donor liver transplant recipient with grade 3 complete portal vein and superior mesenteric vein thromboses, which was successfully managed with an extensive thrombectomy through the venotomy site of superior mesenteric vein. In this case report, we suggest our method as an option for grade 3 portal vein thromboses, and discuss other options available for recipients with portal vein thromboses.

Serial ImmuKnow assay in stable kidney transplant recipients.

OBJECTIVES: The ImmuKnow assay (cylex Inc., Columbia, MD) has been reported to measure the global immune monitoring tool for organ transplantation recipients. We assess immuKnow ATP values in stable kidney transplant patients. MATERIAL AND METHODS: Patients who were kidney transplanted between September 2008 and May 2011 were enrolled in the prospective serial ImmuKnow assay study. The criteria of inclusion were living donor kidney transplantation (KT), no evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and PRA less than 50%. ImmuKnow assay monitoring was performed at one day before operation, post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. We excluded patients who had undergone infectious syndrome or rejection episodes during the follow-up period. RESULTS: Among 71 patients who were enrolled in prospective serial ImmuKnow assay monitoring, 37 patients were proven to stable KT patients during the follow-up period. Two hundred and twenty-four samples from 37 patients were collected. ImmuKnow value and immunosuppression drug level were compared in post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. The value of ImmuKnow assay was significantly different depending on the length of time after transplant (p = 0.038). Interestingly, the pre-transplant ImmuKnow values were lower than those of the immediate post-transplant period. CONCLUSIONS: The ImmuKnow value of stable KT recipients is different according to "time after transplant". Therefore, "time after transplant" should be considered when applying an ImmuKnow assay in clinical practice.

The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation.

Liver transplantation (LT) is performed in patients with hepatocellular carcinoma (HCC), but recurrent HCC after LT remains a problem. We retrospectively reviewed the data from 63 patients with recurrent HCC who underwent LT at a single institution between September 1996 and March 2011 to determine the prognosis of patients with recurrent HCC after LT. A survival analysis was performed with the preoperative data, histological findings, patterns of recurrence, and treatment methods. Univariate and multivariate analyses were performed to determine the factors associated with early (<1 yr) cancer-related death. The independent prognostic factors, according to the multivariate analysis, were recurrence within six months (hazards ratio [HR] = 4.557, p = 0.021) and initial multiple-organ involvement (HR = 5.494, p = 0.015). The survival rates of patients differed according to the treatment type. The combined treatment with local and systemic treatment resulted in increased survival even in patients with HCC recurrences involving multiple organs.

Antiviral treatment for hepatitis B virus recurrence following liver transplantation.

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV-related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty-seven LTs were performed for HBsAg-positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow-up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 10(5) IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV-recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre-transplant HBV viremia and an effective post-transplant HBV prophylaxis.

Enhanced significance of donor-recipient age gradient as a prognostic factor of graft outcome in living donor kidney transplantation.

BACKGROUND: Successful kidney transplantation (KT) increases survival and improves quality of life for patients with end-stage renal disease. Donor age is an important factor influencing graft outcomes. We evaluated the relationship between the donor-recipient age gradient (DRAG) and graft outcomes after living-donor kidney transplantation (LDKT). Additionally, we analyzed graft survival in patients receiving kidneys from age-mismatched donors. METHODS: From February 1995 to March 2011, a series of 968 consecutive adult LDKT recipients were enrolled in our study. Graft survival and laboratory data for each patient were retrospectively collected. DRAG values were divided into four groups: ≤-21, -20 to -1, 0-20, and ≥ 21 years. RESULTS: Higher DRAG had negative effects on graft rejection episodes and serum creatinine levels beyond the first month post-transplantation. A DRAG of more than 20 years was significantly correlated with worse 10-year graft survival. Kidneys from donors older than 55 years of age showed significantly compromised graft outcomes when transplanted into recipients younger than 30 years of age, but not in older recipients. Graft survival in transplants using old-to-old allocation was not different from that of young-to-young allocation. In cases of older donors, a lower DRAG between older donors and older recipients showed more favorable graft outcomes than a higher DRAG between older donors and younger recipients. CONCLUSIONS: This study demonstrated that DRAG may serve as a prognostic factor for predicting graft outcomes after LDKT. Additionally, we showed that transplantation of older donor kidneys via living donation is justified in appropriately chosen age-matched recipients.

Significance of true-positive and false-positive pretransplantation lymphocytotoxic crossmatch in primary liver allograft outcomes.

BACKGROUND: At the time of transplantation, a recipient's serum is tested against the prospective donor's lymphocytes to identify specific reactivity and to look for a donor-specific crossmatch (CXM). Here, we investigated the relationship between the pretransplantation lymphocytotoxic CXM results and the long-term outcome of liver transplantation at a single center. METHODS: From October 1998 to April 2011, medical records, laboratory data, and pretransplantation lymphocytotoxic CXM results were collected from 1133 consecutive liver transplant recipients. RESULTS: We performed liver transplantations on 80 (7.1%) patients after a true-positive CXM (t+CXM). The t+CXM group exhibited higher initial aminotransferase levels immediately after transplantation compared with a negative CXM group. However, no significant differences in rejection, biliary or vascular complications, viral disease recurrence, or de novo malignancies were found. Although overall graft and patient survival did not differ between the groups, liver-specific graft survival was inferior in the t+CXM group. It was also found that, in 42 (3.7%) recipients, initially positive results converted to final negative results after the elimination of immunoglobulin M autoantibodies. We defined this subpopulation as a false-positive CXM. Significantly decreased posttransplantation aminotransferase levels with a higher incidence of de novo malignancies were observed in this group compared with negative controls. CONCLUSION: Our findings demonstrate that t+CXM transplants show increased aspartate aminotransferase and alanine aminotransferase peak immediately after transplantation, which influences liver-specific graft outcomes. Additionally, the presence of circulating immunoglobulin M autoantibodies against recipients' own antigens may be protective in liver grafts. However, this may be a predisposing factor for de novo malignancies.

Expression and functional significance of the erythropoietin receptor in hepatocellular carcinoma.

BACKGROUND: Erythropoietin, through its specific receptor (EpoR), may induce responses in a variety of non-haematopoietic tissues including malignant cells. The purpose of this study was to examine the expression of EpoR in hepatocellular carcinoma (HCC) and to correlate the levels of EpoR expression with the clinicopathological properties of HCC and tumour recurrence. METHODS: The study included 134 patients who underwent curative hepatectomy for hepatitis B virus (HBV)-related primary HCC. The clinical, laboratory and pathological data from these patients were retrospectively collected. The expression of EpoR mRNA and protein were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. RESULTS: Expression of EpoR mRNA in the cirrhotic liver was positively correlated with tumour cell differentiation and 1-year disease-free survival (74.8% in the high expression group versus 46.9% in the low expression group; P = 0.001), as it was for EpoR mRNA expression in HCC (64.4% in the high expression group versus 52.7% in the low expression group; P = 0.044). Tumour recurrence showed stronger dependence on the expression of EpoR protein in non-malignant cirrhotic livers than in HCC. CONCLUSION: In HBV-related HCC, the levels of EpoR mRNA and protein in non-tumour cirrhotic livers were positively correlated with tumour cell differentiation, which is a favourable predictor of disease-specific survival.

The different etiology of fulminant hepatic failure (FHF) in Korea and prognostic factors in patients undergoing liver transplantation for FHF.

BACKGROUND: The prognosis of fulminant hepatic failure (FHF) depends on the etiology and reversibility. In this study, we identified the etiological difference of FHF in Korea and analyzed the prognostic factors after liver transplantation (LT) for FHF. METHODS: We retrospectively reviewed 42 patients with FHF who underwent LT from April 1999 to April 2011 at Samsung Medical Center, Seoul, Korea. The patients were categorized into two groups according to the short-term result of LT, and perioperative profiles were compared to identify the short-term poor prognostic factors. RESULTS: Unlike Western countries, there was no paracetamol-related FHF but herbal/folk medicines were the most frequent causes of FHF (26.2%). HAV-related FHF increased significantly and comprised the main portion of FHF with Herbal/folk medicines after 2005. Encephalopathy grade, onset time, pre-transplantation need of renal replacement, and ventilator treatment were significantly different between groups in univariate analysis. In multivariate analysis, pre-transplantation renal replacement treatment and hepatic encephalopathy grade IV were the independent prognostic factors after LT. CONCLUSIONS: The etiologies of FHF in Korea were different compared with Western reports. The requirement of renal replacement treatment and hepatic encephalopathy grade IV were identified as independent poor prognostic factors after LT for FHF in this study.

Risk factors of peritoneal recurrence and outcome of resected peritoneal recurrence after liver resection in hepatocellular carcinoma: review of 1222 cases of hepatectomy in a tertiary institution.

BACKGROUND: Reports on the risk factors of peritoneal recurrence (PR) after liver resection for hepatocellular carcinoma are lacking. We examined the risk factors of PR after hepatectomy and the outcome of resected PR at our institution. METHODS: We retrospectively reviewed the data from 1,222 patients who underwent hepatectomies for hepatocellular carcinoma in Samsung Medical Center from January 2006 to August 2010. We identified patients with PR and studied the risk factors and outcomes of resected PR. RESULTS: The rate of PR was 3.0% (n=36). The mean±SD age of patients was 54.0±10.2 years. Among those with PR, 23 patients (63.9%) had unresectable disease and 13 patients (36.1%) had resectable disease. Multivariate analysis found that tumor size>50 mm, presence of microvascular invasion, bile duct invasion, and positive margins were significant risk factors of PR after liver resection. The median overall survival (OS) for resectable PR was 33.0 (28.0-61.6) months compared to 14.0 (6.8-21.2) months for unresectable PR (P=0.009). Cox regression analysis demonstrated that resected PR [hazard ratio (HR) 0.042, P = 0.001] and interval between hepatectomy and PR (>6 months) (HR 0.195, P=0.016) were positive prognostic factors for OS, while alfa-fetoprotein>200 ng/dl at detection of PR (HR 11.321, P=0.015) and serosal involvement of primary hepatocellular carcinoma (HR 25.616, P=0.007) were negative prognostic factors for OS. CONCLUSIONS: We found that tumor size>50 mm, presence of microvascular invasion, bile duct invasion, and positive resection margins were significant risk factors of PR after liver resection. Selected patients with resected PR had significantly better OS.

Donor morbidity including biliary complications in living-donor liver transplantation: single-center analysis of 827 cases.

BACKGROUND: Because of the shortage of deceased-donor livers for transplantation, living-donor liver transplantation (LDLT) has become an indispensible treatment strategy for end-stage liver disease. The critical prerequisite for LDLT is the maximal safety of healthy donors. METHODS: From June 1996 to November 2010, a total of 827 completed donor hepatectomies were performed in our center. We analyzed donor morbidity associated with LDLT. RESULTS: There was no donor mortality. No complications were observed in 744 (90.0%) donors, and 83 (10.0%) donors experienced complications. Wound complications were most common, occurring in 48 (5.8%) patients. According to a modified Clavien classification, grade I, grade II, grade IIIa, and grade IIIb complications were experienced in 56 (67.5%), 2 (2.4%), 15 (18.1%), and 10 (12.0%) donors, respectively. Surgical or interventional management was successful in all grade IIIa and grade IIIb donors. The incidence of biliary complications was significantly higher in younger donors. Donor morbidity did not decrease below the attained level even after time had passed. CONCLUSIONS: This study demonstrates the safety of donor hepatectomy. Complications were relatively minor and easily controlled. The incidence of biliary complications and donor age was inversely correlated. The procedural experience of the surgeons was not associated with the donor complication rate.

Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) from several tissues have immunomodulatory properties that involve various immunosuppressive molecules. An example is human leukocyte antigen (HLA)-G, a non-classical major histocompatibility complex (MHC) class I molecule that induces tolerance via interactions with inhibitory receptors present on major immune effector cells. Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression have come under investigation. Our goal was to determine whether HLA-G plays a crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can be used as a tool for biologic immunosuppression with HLA-G in transplantation. METHODS: MSC were characterized by fluorescence-activated cell sorting (FACS) analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining for differentiation. The immunogenicity and immunomodulatory effects of MSC were monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC was done using a lentiviral system. Results. MSC from different tissues had similar morphology, immunophenotypic characters and differentiation potential. We also found that the immunosuppressive effect of MSC was monitored along with their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1 appeared to enhance the immunosuppressive effect of hAT MSC, and the function of HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC proliferation assays. CONCLUSIONS: Although the HLA-G molecule is not the sole factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G plays an important role in immunosuppression and that hAT MSC can be used as a tool for biologic immunosuppression during transplantation procedures.

Effect of early enteral nutrition after hepatectomy in hepatocellular carcinoma patients.

BACKGROUNDS/AIMS: To evaluate the effect of early enteral nutrition after hepatectomy in hepatocellular carcinoma (HCC) patients on postoperative gastrointestinal motility recovery and admission days, liver function and nutrition recovery, and postoperative complication. METHODS: From August 2010 to July 2011, 102 patients with primary HCC underwent hepatectomy. Forty two patients took a sip of water (SOW) at postoperative day (POD)#1, soft blended diet (SBD) at POD#2 (early diet group, ED group), otherwise 60 patients took a SOW at POD#3, SBD at POD#4 (conventional diet group, CD group). Postoperative flatus-pass day, stool-pass day, nausea, vomiting, admission days, immediate postoperative (POD#0) and POD#1, 3, 5, 7 profiles of albumin, prothrombin time (PT) INR, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), white blood cell (WBC), and POD#1, 3, 5, 7 profiles of C-reactive protein (CRP), and postoperative complications cases were compared between ED group and CD group. All clinical data were compared retrospectively. RESULTS: Flatus-pass days (p<0.01), stool-pass days (p<0.01) and postoperative admission days (p=0.012) were shorter in ED group. Total bilirubin levels were higher at POD#0, 1, 3 but lower or similar at POD#5, 7 in ED group. AST, ALT levels were higher at POD#0 but lower at POD#1, 3, 5. There were no significant differences in albumin, PT INR, WBC, CRP and postoperative complication rates. CONCLUSIONS: ED group had no difference in nutritional recovery and postoperative complication rates compared to CD group but it has better gastrointestinal motility recovery, liver function recovery, and shorter postoperative admission days.

ABO Incompatible Kidney Transplantation-Current Status and Uncertainties.

In the past, ABO blood group incompatibility was considered an absolute contraindication for kidney transplantation. Progress in defined desensitization practice and immunologic understanding has allowed increasingly successful ABO incompatible transplantation during recent years. This paper focused on the history, disserted outcomes, desensitization modalities and protocols, posttransplant immunologic surveillance, and antibody-mediated rejection in transplantation with an ABO incompatible kidney allograft. The mechanism underlying accommodation and antibody-mediated injury was also described.

Graft-versus-host disease after kidney transplantation.

Graft-versus-host disease (GVHD) is a rare complication after kidney transplantation. We describe a 62-year-old female with end-stage renal disease due to hypertension. She received a kidney with 4 mismatched human leukocyte antigen (HLA) out of 6 HLA - A, B, DR from a deceased donor. After the procedure, the patient showed watery diarrhea on postoperative day (POD) 45. An endoscopic biopsy of the colon revealed some apoptotic cells consistent with GVHD. Thrombocytopenia was gradually developed on POD 54. She received steroid pulse therapy, and thrombocytopenia did not progress. However, pneumonia, renal failure, and cardiac failure occurred. She died due to multiple organ failure. We must consider GVHD in renal transplant recipients without homozygous or identical HLA, who had only watery diarrhea without other typical GVHD symptoms such as skin rash and fever, although GVHD is rare in renal transplant recipients.

Cardiac tamponade caused by tuberculosis pericarditis in renal transplant recipients.

A 50-year-old male, renal transplant recipient, was admitted with fever and chest discomfort. At admission, chest radiologic finding was negative and echocardiography showed minimal pericardial effusion. After 2 days of admission, chest pain worsened and blood pressure fell to 60/40 mmHg. Emergency echocardiography showed a large amount of pericardial effusion compressing the entire heart. Pericardiocentesis was performed immediately. Mycobacterium tuberculosis was isolated from pericardial fluid. Tuberculosis pericarditis should be considered as the cause of cardiac tamponade in renal transplant recipients, even with the absence of pericardial effusion in the initial study or suggestive history.

Is cytomegalovirus infection dangerous in cytomegalovirus-seropositive recipients after liver transplantation?

Cytomegalovirus (CMV) infections contracted after liver transplantation put patients at an increased risk of morbidity and mortality. We analyzed the effects of CMV infection by time of onset, mortality, and graft failure risk factors in liver recipients who were CMV donor-positive/recipient-positive (D+/R+). We reviewed 618 medical records for consecutive adult liver transplant cases. CMV pp65 antigenemia assays to determine patient CMV status were administered monthly. The incidences of CMV infection and disease were 55.7% (344 of 618 records) and 5.5% (34 of 618 records), respectively. The differences in patient survival and graft failure rates for CMV-infected and CMV-uninfected patients were not significant (P = 0.707 and P = 0.973), but the rates were lower in patients with CMV disease than in CMV-uninfected patients (P = 0.005 and P = 0.030, respectively). The recurrence of hepatitis B virus and hepatocellular carcinoma, hepatic dysfunction, infection, numerous pp65-staining cells, and CMV disease were found to be the risk factors for mortality and graft failure in CMV D+/R+ adult liver transplant patients. In conclusion, the occurrence of CMV disease, and not asymptomatic CMV infection, was a risk factor for mortality and graft failure in adult liver transplant recipients with CMV D+/R+.