Living Donor Liver Transplantation to a Survivor of LiverResection for Hepatocellular Carcinoma with Major Portal Vein Invasion

We present a case of living donor liver transplantation to a 3-year disease-free survivor of liver resection for hepatocellular carcinoma (HCC) with major portal vein invasion. A 48-year-old man had HCC in the right lobe with a portal venous tumor thrombus extending into the left portal vein. An extended right lobectomy with thrombectomy was performed to remove the thrombus. Three years after liver resection, the patient experienced liver failure, with massive ascites and jaundice due to the formation of a thrombus in the main and left portal veins. During the 3 years after liver resection, no metastasis or recurrence of HCC had been detected, and tumor markers had been within normal ranges. The portal venous thrombus did not show any arterial enhancement under contrast-enhanced computed tomography, suggesting that the co-existence of any HCC component in the portal venous thrombus may have been negative. Based on these findings, living donor liver transplantation was performed using a right lobe graft from the patientʼs son. The patient is alive at 87 months after the transplantation, with no evidence of HCC recurrence

Surgical Outcome of Patients Undergoing Pancreaticoduodenectomy: Analysis of a 17-Year Experience at a Single Center

The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patientsʼ clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75 and 15.8 , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p＜0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p＜0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PDʼs clinical outcomes

The Outcome of Complex Hepato-Pancreato-Biliary Surgery for Elderly Patients: A Propensity Score Matching Analysis

Background/Aims: Postoperative mortality and morbidity rates after hepato-pancreato-biliary (HPB) surgery remain high, and the number of elderly patients requiring such surgery has been increasing. This study aimed to investigate postoperative outcomes of complex HPB surgery for elderly patients. Methods: We retrospectively reviewed perioperative data of 721 patients who underwent complex HPB surgery between 2010 and 2015. The patients were divided into 2 groups: elderly (≥75 years) and non-elderly (< 75 years). Surgical outcomes of both groups were compared after propensity score-matching analysis. Subsequently, risk factors for serious postoperative morbidity were identified by multivariate analysis. Results: Before matching, the elderly group (n = 170) had more comorbidities, such as cardiovascular and renal disease, than the non-elderly group (n = 551). Matching yielded elderly (n = 170) and non-elderly groups (n = 170) with similar preoperative backgrounds. The mortality and morbidity rates did not differ significantly between the groups. In multivariate analyses, operative time (OR 1.79; p = 0.005) and blood loss (OR 1.66; p = 0.03) were identified as independent risk factors for serious postoperative morbidity, whereas older age did not have a predictive impact (OR 1.16; p = 0.52). Conclusions: Although elderly ­patients had more comorbidities and higher incidences of postoperative mortality and several complications before matching, their postoperative outcomes were equivalent to those of non-elderly patients after matching

Prognostic Factors for Pediatric Living Donor Liver Transplantation: Impact of Zero-mortality Transplant for Cholestatic Diseases

Living donor liver transplantation (LDLT) is the final therapeutic arm for pediatric end-stage liver diseases. Toward the goal of achieving further improvement in LDLT survival, we investigated factors affecting recipient survival. We evaluated the prognostic factors of 60 pediatric recipients (< 16 years old) who underwent LDLT between 1997 and 2015. In a univariate analysis, non-cholestatic (NCS) disease, graft/recipient body weight ratio, cold and warm ischemic times, and intraoperative blood loss were significant factors impacting survival. In a multivariate analysis, NCS disease was the only significant factor worsening survival (p=0.0021). One-and 5-year survival rates for the cholestatic disease (CS, n=43) and NCS (n=17) groups were 100% vs. 70.6% and 97.4% vs. 58.8% (p=0.004, log-rank). Intergroup comparisons revealed that CS was significantly associated with operation time, cold ischemia, hepatomegaly of the native liver, and portal plasty. These data suggest that a cirrhotic, swollen, artery-dominant liver did not increase graft size-related risks despite the surgical complexity of preceding operations. The NCS group’s poorer survival originated from recurrence of the primary disease and liver manifestation of systemic disease untreatable by transplantation. Improving the survival of pediatric recipients requires intensive efforts to prevent primary disease relapse and more rapid diagnoses to exclude contraindications from NCS disease

Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy

Antigen-specific cancer immunotherapy is a promising strategy for improving cancer treatment. Recently, many tumor-associated antigens and their epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the density of endogenously presented antigen-derived peptides on tumor cells is generally sparse, resulting in the inability of antigen-specific CTLs to work effectively. We hypothesize that increasing the density of an antigen-derived peptide would enhance antigen-specific cancer immunotherapy. Here, we demonstrated that intratumoral peptide injection leads to additional peptide loading onto major histocompatibility complex class I molecules of tumor cells, enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, human leukocyte antigen (HLA)-A*02:01-restricted glypican-3(144-152) (FVGEFFTDV) and cytomegalovirus(495-503) (NLVPMVATV) peptide-specific CTLs showed strong activity against all peptide-pulsed cell lines, regardless of whether the tumor cells expressed the antigen. In in vivo studies using immunodeficient mice, glypican-3(144-152) and cytomegalovirus(495-503) peptides injected into a solid mass were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of ovalbumin(257-264) peptide (SIINFEKL) was effective for tumor growth inhibition and survival against ovalbumin-negative tumors without adverse reactions. Moreover, we demonstrated an antigen-spreading effect that occurred after intratumoral peptide injection. Intratumoral peptide injection enhances tumor cell antigenicity and may be a useful option for improvement in antigen-specific cancer immunotherapy against solid tumors

Sarcopenia and American Society of Anesthesiologists Physical Status in the Assessment of Outcomes of Hepatocellular Carcinoma Patients Undergoing Hepatectomy

Sarcopenia following liver surgery has been reported as a predictor of poor prognosis. Here we investigated predictors of outcomes in patients with hepatocellular carcinoma (HCC) and attempted to establish a new comprehensive preoperative assessment protocol. We retrospectively analyzed the cases of 254 patients who underwent curative hepatectomy for HCC with Child-Pugh classification A at our hospital between January 2007 and December 2013. Sarcopenia was evaluated by computed tomography measurement. The influence of sarcopenia on outcomes was evaluated. We used multivariate analyses to assess the impact of prognostic factors associated with outcomes, including sarcopenia. Of the 254 patients, 118 (46.5%) met the criteria for sarcopenia, and 32 had an American Society of Anesthesiologists (ASA) physical status &ge;3. The sarcopenic group had a significantly lower 5-year overall survival rate than the non-sarcopenic group (58.2% vs. 82.4% , p＝0.0002). In multivariate analyses of prognostic factors, sarcopenia was an independent predictor of poor survival (hazard ratio [HR]＝2.28, p＝0.002) and poor ASA status (HR＝3.17, p＝0.001). Sarcopenia and poor ASA status are independent preoperative predictors for poor outcomes after hepatectomy. The preoperative identification of sarcopenia and ASA status might enable the development of comprehensive approaches to assess surgical eligibility

Hepatitis C Virus-specific T-cell Response Correlates with Hepatitis Activity and Donor IL28B Genotype Early after Liver Transplantation

It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At＞3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect

Predictive Factors for Successful Vaccination Against Hepatitis B Surface Antigen in Patients Who Have Undergone Orthotopic Liver Transplantation

Post-orthotopic liver transplantation (OLT) hepatitis B recurrence is well-controlled with a nucleos(t)ide analogue and hepatitis B immunoglobulin (HBIG) combination, but the high cost and the potential risk of unknown infection associated with HBIG remain unresolved issues. Low-cost recombinant hepatitis B virus (HBV) vaccine administration is a potential solution to these problems. We retrospectively analyzed the rate and predictive factors of HBV vaccine success in 49 post-OLT patients: liver cirrhosis-type B (LC-B), n=28 patients; acute liver failure-type B (ALF-B), n=8; and non-HBV-related end-stage liver disease (non-B ESLD) who received a liver from anti-hepatitis B core antibody-positive donors, n=13. A positive anti-hepatitis B surface antibody response was achieved in 29% (8/28) of the LC-B group, 88% (7/8) of the ALF-B group, and 44% (4/9) of the adult non-B ESLD group. All four non-B ESLD infants showed vaccine success. The predictive factors for a good response in LC-B were young age, marital donor, and high donor age. ALF-B and non-B ESLD infants are thus good vaccination candidates. LC-B patients with marital donors are also good candidates, perhaps because the donated liver maintains an efficient immune memory to HBV, as the donors had already been infected in adulthood and showed adequate anti-HBV immune responses

Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Liver Transplantation

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an extremely rare cause of hyponatremia post-liver transplantation. A 15-year-old Japanese girl with recurrent cholangitis after Kasai surgery for biliary atresia underwent successful living donor liver transplantation. Peritonitis due to gastrointestinal perforation occurred. Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia’s cause as SIADH. We suspected that tacrolimus was the disease’s cause, so we used cyclosporine instead, plus hypertonic sodium plus water intake restriction, which improved the hyponatremia. Symptomatic hyponatremia manifested by SIADH is a rare, serious complication post-liver transplantation