Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer.

BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

Higher human lymphocyte antigen class I expression in early-stage cancer cells leads to high sensitivity for cytotoxic T lymphocytes.

Human lymphocyte antigen (HLA) class I molecules play a central role in cytotoxic T lymphocytes (CTL)-based antitumor immunity. However, the expression rate of HLA class I in cancer cells remains a topic of discussion. We compared HLA class I expression levels between cancer cells and surrounding non-tumorous hepatocytes in 20 early-stage hepatocellular carcinoma (HCC) patients by immunohistochemistry using EMR 8-5. The expression levels of HLA class I were classified as negative, incomplete positive or complete positive. Similarly, for various types of solid cancers, HLA class I expression was examined. For the HLA class I expression in cancer cells, among 20 HCC patients, 13 were complete positive, 3 were incomplete positive, and 4 were negative. In addition, 15 (75.0%) had higher expression levels of HLA class I in cancer cells compared with that in surrounding non-tumorous hepatocytes. An interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay indicated that cancer cells with positive expression of HLA class I had strong sensitivity to antigen-specific CTL. We suggested that HLA class I expression in cancer cells could be involved in the clinical prognosis of HCC patients. Similarly, 66.7%, 100.0%, 66.7% and 62.5% of patients with early-stage pancreatic, gallbladder, esophageal and breast cancers, respectively, had higher expression levels of HLA class I in cancer cells than in surrounding normal tissue cells. We suggest that in several early-stage solid cancers, including HCC, HLA class I expression levels in cancer cells are higher than that in surrounding normal tissue cells, which could result in the anti-tumor effect of CTL-based cancer immunotherapy.

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.

Risk Analysis for Invasive Fungal Infection after Living Donor Liver Transplantation: Which Patient Needs Potent Prophylaxis?

BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality after living donor liver transplant (LDLT). The aim of this study was to identify the risk factors for post-LDLT IFI for early diagnosis and improvement of antifungal treatment outcome. METHODS: Risk analysis data were available for all 153 patients who underwent LDLT between January 2005 and April 2012. RESULTS: During the follow-up period (1,553 ± 73 days, range 20-2,946 days), 15 patients (9.8%) developed IFI classified as "proven" (n = 8) and "probable" (n = 7) with fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p = 0.0026). Multivariate analysis identified model for end-stage liver disease score of ≥26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI. CONCLUSION: Preoperative recipients' status and postoperative kidney dysfunction can affect an occurrence of post-transplant IFI. These risk factors would be taken into consideration for designation of proper antifungal therapy.

Preoperative Controlling Nutritional Status Score Predicts Mortality after Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Preoperative nutritional status is reportedly associated with postoperative outcomes in patients with hepatocellular carcinoma. This study aimed to investigate the significance of the controlling nutritional status (CONUT) score and the prognostic nutritional index (PNI) as predictors of postoperative outcomes. METHODS: We retrospectively reviewed data from 331 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2015. Patients were divided into 2 groups based on their CONUT score and the PNI. We evaluated the effect of the CONUT score and PNI on perioperative outcomes. Multivariate analysis was performed to identify independent predictors of in-hospital mortality after hepatectomy. -Results: The high CONUT group had a significantly higher -incidence of 30-day mortality (p < 0.001), in-hospital mortality (p = 0.002), ascites (p = 0.006), liver failure (p = 0.02), sepsis (p = 0.01), and enteritis (p < 0.001). The low PNI group was also significantly associated with 30-day mortality (p < 0.001), in-hospital mortality (p = 0.003), liver failure (p < 0.001), sepsis (p = 0.02), enteritis (p = 0.02), and hospital stay (p = 0.01). In multivariate analyses, a high CONUT score was an independent predictor of in-hospital mortality after hepatectomy (hazard ratio [HR] 9.41, p = 0.038), but the PNI was not (HR 5.86, p = 0.08). CONCLUSIONS: Preoperative assessment of the CONUT score is helpful for evaluating patients' nutritional status and mortality risk after liver surgery.

Effect of an enhanced recovery after surgery protocol in patients undergoing pancreaticoduodenectomy: A randomized controlled trial.

BACKGROUND & AIMS: Evidence of the advantages of enhanced recovery after surgery (ERAS) protocols following pancreaticoduodenectomy (PD) is limited. The aim of this study was to examine the efficiency of ERAS protocols in patients following PD. METHODS: Between June 2014 and October 2016, patients undergoing PD were randomly assigned to receive ERAS protocols or standard care. The primary endpoint was the postoperative length of stay. Secondary endpoints included postoperative complications, postoperative quality-of-life (QoR-40J), readmission, and medical cost. RESULTS: Of 80 eligible patients, 74 were analyzed in intention-to-treat principles: 37 in the control group and 37 in the ERAS group. The mean length of stay in the ERAS group was significantly shorter than that in the control group (20.1 ± 5.4 vs 26.9 ± 13.5 days, P < 0.001). The ERAS group had a significantly lower percentage of postoperative complications (32.4% vs 56.8%, P = 0.034) and readmissions (0% vs 8.1%, P = 0.038). Quality-of-life was also significantly better in the ERAS group (184 ± 12.4 vs 177 ± 14.5, P = 0.022). The total medical cost was lower in the ERAS group, but not significantly ($25,445 ± 5065 vs $28,384 ± 9999, P = 0.085). CONCLUSIONS: The optimization of ERAS protocols in patients undergoing PD is safe and accelerates perioperative recovery and quality-of-life, thereby reducing the length of stay. Morbidity was significantly decreased in the ERAS group without compromising surgical outcome. REGISTRATION NUMBER: UMIN000014068.

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.

A subclinical high tricuspid regurgitation pressure gradient independent of the mean pulmonary artery pressure is a risk factor for the survival after living donor liver transplantation.

BACKGROUND: Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT). METHODS: We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG; n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO20.6 (mPAP-FIO20.6) was also assessed. Patients exhibiting pO2 < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO2) ≥ 15 mmHg were categorized as potentially having HPS (subclinical HPS; n = 29). The clinical course after LDLT was investigated according to subclinical high TRPG. RESULTS: A subclinical high TRPG (p = 0.012) and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO20.6 was expected to correlate with a worse survival, a high mPAP-FIO20.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt. CONCLUSION: In cirrhosis patients, mPAP-FIO20.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation.

Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

A novel intestinal rotation method for digestive reconstruction after combined pancreaticoduodenectomy and extended right hemicolectomy: A case report and surgical technique.

INTRODUCTION: Pancreaticoduodenectomy (PD) combined with extended right hemicolectomy (RH) is a challenging procedure for locally advanced malignancies. However, information concerning the reconstruction method of the digestive system is limited. Here, we present a case and surgical technique of a novel intestinal rotation method for digestive reconstruction after PD combined with RH. PRESENTATION OF CASE: A 62-year-old man with locally advanced pancreatic cancer received conversion surgery combined with PD and RH after preoperative chemotherapy. With respect to the reconstruction of the digestive system, the entire intestinal mesentery was rotated 180° forward counterclockwise around the axis of the superior mesenteric artery, and then the reconstruction, according to Child's method, was performed. The patient recovered without problems in gastroenterological functions after the operation. DISCUSSION: With respect to the reconstruction of the digestive system in patients undergoing combined PD and RH, practitioners should pay close attention to twisting of the intestinal mesentery when bringing up the proximal jejunum for pancreatojejunostomy and hepatojejunostomy and the distal ileum for ileocolic anastomosis. This intestinal rotation method enables a smooth and uneventful reconstruction of the digestive system. CONCLUSION: This is the first detailed description of an intestinal rotation method for digestive reconstruction after combined PD and extended RH. The intestinal rotation method can be an alternative and helpful technical option for digestive reconstruction in patients with combined PD and RH.

Primary pancreatic-type acinar cell carcinoma of the jejunum with tumor thrombus extending into the mesenteric venous system: a case report and literature review.

BACKGROUND: Although ectopic pancreatic tissue is common in the upper gastrointestinal tract, the incidence of ectopic pancreatic tissue in the jejunum is low, and malignant transformation in ectopic pancreatic tissue is rare. Furthermore, pancreatic-type acinar cell carcinoma (ACC) developing in the jejunum and ACC accompanied by tumor thrombus are extremely rare. CASE PRESENTATION: A 78-year-old-woman presented with melena. Abdominal computed tomography images and endoscopic examination revealed a submucosal jejunal mass with tumor thrombus extending into a jejunal vein. The patient underwent a curative resection combined with a partial jejunectomy and partial pancreatectomy. Histopathological examination of the resected tissue showed tumor cells with a homogeneous acinar architecture identical to pancreatic-type ACC and tumor thrombus. Postoperatively, she was followed for 10 months and had no recurrence. CONCLUSION: We present an extremely rare case of pancreatic-type ACC in the jejunum with extensive tumor thrombus invading into the mesenteric venous system. This type of cancer has not been reported previously but should be considered in the differential diagnosis of a jejunal mass.

Radiographic sarcopenia predicts postoperative infectious complications in patients undergoing pancreaticoduodenectomy.

BACKGROUND: Recently, skeletal muscle depletion (sarcopenia) has been reported to influence postoperative outcomes after certain procedures. This study investigated the impact of sarcopenia on postoperative outcomes following pancreaticoduodenectomy (PD). METHODS: We performed a retrospective study of consecutive patients (n = 219) who underwent PD at our institution between January 2007 and May 2013. Sarcopenia was evaluated using preoperative computed tomography. We evaluated postoperative outcomes and the influence of sarcopenia on short-term outcomes, especially infectious complications. Subsequently, multivariate analysis was used to assess the impact of prognostic factors (including sarcopenia) on postoperative infections. RESULTS: The mortality, major complication, and infectious complication rates for all patients were 1.4%, 16.4%, and 47.0%, respectively. Fifty-five patients met the criteria for sarcopenia. Sarcopenia was significantly associated with a higher incidence of in-hospital mortality (P = 0.004) and infectious complications (P < 0.001). In multivariate analyses, sarcopenia (odds ratio = 3.43; P < 0.001), preoperative biliary drainage (odds ratio = 2.20; P = 0.014), blood loss (odds ratio = 1.92; P = 0.048), and soft pancreatic texture (odds ratio = 3.71; P < 0.001) were independent predictors of postoperative infections. CONCLUSIONS: Sarcopenia is an independent preoperative predictor of infectious complications after PD. Clinical assessment combined with sarcopenia may be helpful for understanding the risk of postoperative outcomes and determining perioperative management strategies.

Preoperative Controlling Nutritional Status (CONUT) Score for Assessment of Prognosis Following Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Immune-nutritional status has been recently reported as a prognostic factor in hepatocellular carcinoma (HCC). The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to investigate the efficacy of the CONUT score as a prognostic factor in patients undergoing hepatectomy for HCC. METHODS: A total of 295 patients who underwent curative hepatectomy for HCC between January 2007 and December 2014 were retrospectively analyzed. Patients were divided into two groups according to the CONUT score. The impact of the CONUT score on clinicopathological, surgical, and long-term outcomes was evaluated. Subsequently, the impact of prognostic factors, including the CONUT score, associated with outcomes was assessed using multivariate analyses. RESULTS: Of 295 patients, 118 (40%) belonged to the high CONUT group (CONUT score ≥ 3). The high CONUT group had a significantly lower 5-year recurrence-free survival rate than the low CONUT group (27.9 vs. 41.4%, p = 0.011) and a significantly lower 5-year overall survival rate (61.9 vs. 74.9%, p = 0.006). In multivariate analyses of prognostic factors, the CONUT score was an independent predictor of recurrence-free survival (hazard ratio = 1.64, p = 0.006) and overall survival (hazard ratio = 2.50, p = 0.001). CONCLUSIONS: The CONUT score is a valuable preoperative predictor of survival in patients undergoing hepatectomy for HCC.

Early Chimerism After Liver Transplantation Reflects the Clinical Course of Recurrent Hepatitis C.

BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

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.

Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma.

Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface protein overexpressed in hepatocellular carcinoma(HCC), and its overexpression is associated with poor prognosis. The diagnostic potential of GPC3 as a serum marker has been reported. In the present study, we evaluated the usefulness of plasma GPC3 as a predictor for recurrence after surgical resection in stage I HCC patients by newly developed an enzyme-linked immunosorbent assay (ELISA) system. Current study demonstrated that high levels of preoperative plasma GPC3 patients tended to experience postoperative recurrence. On the other hand, pre- and postoperative plasma GPC3 positivity of non-recurrence patients was very low. Moreover, even after surgery, approximately half of patients who experienced recurrence were positive for plasma GPC3. Postoperative plasma GPC3 positivity was significantly correlated with worse recurrence-free survival. Immuohistochemical analysis also showed positive rate of GPC3-expression in HCC was higher in recurrence patients than in non-recurrence patients. These results suggested that both pre- and postoperative plasma GPC3 levels may be accurate predictors for recurrence after curative resection of early-stage HCC. It should be noted that the current study only examined a small number of cases; thus, a larger sample size is necessary to validate GPC3 as a predictor for HCC recurrence.

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 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.

Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients.

The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.

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 patients' 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 PD's clinical outcomes.