Keinosuke Ishido

L1 Cell adhesion molecule (L1CAM) expression at the cancer invasive front is a novel prognostic marker of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most extremely aggressive cancers with a poor prognosis after curative resection. L1 cell adhesion molecule (L1CAM) is a 200–220 kDa type I transmembrane glycoprotein of the immunoglobulin superfamily, which has been shown to affect the prognosis of several cancers. No clinicopathological significance of L1CAM expression has been examined at the invasive front of PDAC. In this study, we examined the relationship between L1CAM expression and clinicopathological features in PDAC by immunohistochemistry.

Hepatic venous outflow obstruction in living donor liver transplantation: balloon angioplasty or stent placement?

BACKGROUND The incidence of hepatic venous outflow obstruction (HVOO) has been reported to be 5%-13% when a partial graft is used for orthotopic liver transplantation (OLT). HVOO leads to graft congestion, portal hypertension, and finally cirrhosis, which jeopardizes both graft and recipient survivals. In this study, we sought to identify perioperative factors influencing HVOO and to investigate conditions that require stent placement. PATIENTS AND METHODS From February 1994 to December 2010, we performed 40 living donor liver transplantations (LDLT). HVOO occurred in 5 cases (12.5%), all of which were left lobe grafts. Because HVOO was not observed in patients with body weight (BW) <30 kg, we investigated the other 28 cases with BW >30 kg. RESULTS There was no difference from unaffected subjects except for cold ischemic time (CIT), which was significantly longer: 86.2 ± 10.4 minutes vs 46.0 ± 4.8 minutes (P = .001). Balloon angioplasty, which was selected as the initial treatment for all stricture patients, improved 2 patients after 1 and 5 treatments, respectively, but 3 subjects underwent repeated HVOO, finally being treated with self-expandable metallic stents at 9, 6, and 10 years after LDLT, respectively. All patients finally resolved their strictures. CONCLUSION HVOO reflects intimal hyperplasia and fibrosis at the anastomotic sites or compression and twisting of the anastomosis caused by graft regeneration. In addition, progression of chronic rejection and fibrosis are possibly responsible for late-onset HVOO. Longer CIT possibly reflects difficulties in the venoplasty before anastomosis. No bleeding or thrombosis complications were observed during dilatation among our cases. The selection of the stent size for each case and careful stent deployment are important to prevent complications. Stent placement should be considered in patients with chronic rejection who are refractory to several balloon angioplasties with early-onset or late-onset HVOO.

Carriers for enzymatic attachment of glycosaminoglycan chains to peptide

In the previous study, we have found that the endo-beta-xylosidase from Patinopecten had the attachment activities of glycosaminoglycan (GAG) chains to peptide. As artificial carrier substrates for this reaction, synthesis of various GAG chains having the linkage region tetrasaccharide, GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl, between GAG chain and core protein of proteoglycan was investigated. Hyaluronic acid (HA), chondroitin (Ch), chondroitin 4-sulfate (Ch4S), chondroitin 6-sulfate (Ch6S), and desulfated dermatan sulfate (desulfated DS) as donors and the 4-metylumbelliferone (MU)-labeled hexasaccharide having the linkage region tetrasaccharide at its reducing terminals (MU-hexasaccharide) as an acceptor were subjected to a transglycosylation reaction of testicular hyaluronidase. The products were analyzed by high-performance liquid chromatography and enzyme digestion, and the results indicated that HA, Ch, Ch4S, Ch6S, and desulfated DS chains elongated by the addition of disaccharide units to the nonreducing terminal of MU-hexasaccharide. It was possible to custom-synthesize various GAG chains having the linkage region tetrasaccharide as carrier substrates for enzymatic attachment of GAG chains to peptide.

Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors

Background: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. Methods: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. Jamess University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. Results: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90‐day mortality (2.5% vs 13.6%, respectively), disease‐specific 5‐year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. Conclusion: Disease‐specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long‐term survival.

Liver Transplantation for Wilson's Disease in Pediatric Patients: Decision Making and Timing

Transplantation for Wilsons disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilsons disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilsons index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilsons disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention.

Enzymatic Attachment of Glycosaminoglycan Chain to Peptide Using the Sugar Chain Transfer Reaction with Endo-β-xylosidase

Endo-β-xylosidase from the mid-gut gland of the molluscus Patinopecten is an endo-type glycosidase that hydrolyzes the xylosyl serine linkage between a core protein and a glycosaminoglycan (GAG) chain, releasing the intact GAG chain from proteoglycan. In this study, we investigated GAG chain transfer activity of this enzyme, in order to develop a method for attaching GAG chains to peptide. Peptidochondroitin sulfate (molecular mass of sugar chain, 30 kDa) from bovine tracheal cartilage as a donor and butyloxycarbonyl-leucyl-seryl-threonyl-arginine-(4-methylcoumaryl-7-amide) as an acceptor were incubated with endo-β-xylosidase. As a result, a reaction product with the same fluorescence as the acceptor peptide was observed. High pressure liquid chromatography analysis, cellulose acetate membrane electrophoresis, and enzymatic digestion showed that this reaction product had the chondroitin sulfate (ChS) from the donor. Furthermore, the acceptor peptide was released from this reaction product after hydrolysis by endo-β-xylosidase. Therefore, it was confirmed that the ChS chain released from the donor was transferred to the acceptor peptide by the GAG chain transfer reaction of endo-β-xylosidase. The optimal pH for hydrolysis by this enzyme was found to be about 4.0, whereas that for this reaction was about 3.0. Not only the ChS but also the dermatan sulfate and the heparan sulfate were transferred to the acceptor peptide by this reaction. By using this reaction, the GAG chain could be attached to the peptide in one step. The GAG chain transfer reaction of endo-β-xylosidase should be a significant glycotechnological tool for the artificial synthesis of proteoglycan.

Liver transplantation versus conservative treatment for adult-onset type II citrullinemia: our experience and a review of the literature.

Adult-onset type II citrullinemia (CTLN2), an autosomal recessive disorder caused by a mutation in the SLC25A13 gene, is characterized by increased serum citrulline and ammonia levels. Patients with CTLN2 also display various neuropsychiatric symptoms. Many individuals with CTLN2 are fond of protein-rich and/or lipid-rich foods with an aversion to carbohydrate-rich foods. We herein report two cases of CTLN2 treated with living donor liver transplantation (LDLT) and provide a review of the pertinent literature. Case 1 was a 43-year-old man admitted to our hospital for repetitive episodes of consciousness disturbance. Case 2 was a 37-year-old man admitted to our hospital because of abnormal behavior associated with hyperammonemia. A definitive diagnosis of CTLN2 was accomplished by DNA analysis in both patients, who successfully underwent LDLT using liver segments from donor siblings with confirmed heterozygous gene expression. Case 2 also underwent conservative therapy with arginine and a high-fat, carbohydrate-restricted diet prior to LDLT. Postoperative recovery was uneventful and food was unrestricted in both patients. We also identified 77 cases of CTLN2 in the literature and reviewed them in terms of outcome of both liver transplantation and conservative therapy. The survival rate in patients treated by liver transplantation was 100%, whereas that in patients treated by conservative treatment showed improvement from 39.5% to 76.5% over the years. Liver transplantation is a practical treatment that fundamentally improves patient quality of life after transplantation. However, recent studies have suggested that arginine and sodium pyruvate administration combined with intensive nutritional support is also an effective therapy for CTLN2. Further development of conservative therapy may provide a safer, more affordable alternative to liver transplantation in the near future.

Donor Quality of Life After Living Donor Liver Transplantation: Single-Institute Experience

AIM Living donor liver transplantation (LDLT) has been widely accepted because of the severe shortage of hepatic grafts. However, the healthy donor is exposed to risks of morbidity and mortality. In this study, we analyzed medical, functional, and psychological outcomes of donors after hepatectomy for liver donation. PATIENTS AND METHODS Among 41 donor hepatectomy cases for LDLT performed in our institute from January 1994 to May 2011, we reviewed the medical records (liver function tests, complications, etc) of 27 subjects who donated to recipients older than 12 years. We also performed a questionnaire survey based on the Japanese Short Form-36 version 2 Health Survey scales as a measure of physical and mental health, to which 31 subjects responded. RESULTS Six of the 27 donors experienced prolonged jaundice. Their ratios of graft volume/standard donor liver volume (GV/SDLV) were higher than those of the 21 donors without prolonged jaundice (60.0% vs 41.5%). According to the questionnaires, social functioning among those having undergone emergency hepatectomy as well as general health perceptions declined in those with postoperative complications. Physical component summary declined among those having undergone emergency hepatectomy and with postoperative complications. CONCLUSION In liver donation from a living donor, massive hepatectomy should be avoided. A ratio of GV/SDLV around 50% seems reasonable. Donors with emergency transplantations or postoperative complications must be more carefully followed after donor hepatectomy.

Combination therapy with gemcitabine and nab‑paclitaxel for locally advanced unresectable pancreatic cancer

The aim of the present study was to investigate the early treatment outcomes of combined gemcitabine and nab-paclitaxel treatment for locally advanced unresectable pancreatic cancer (LURPC). The subjects comprised 7 patients with LURPC receiving the abovementioned combination therapy at the Hirosaki University Hospital (Hirosaki, Japan) between January and September, 2015. The clinicopathological factors, adverse events and response to treatment were investigated. To determine whether the cases were unresectable, the National Comprehensive Cancer Network guidelines, version 2. 201,) were applied. The patients underwent a median of 4 (range, 2-7) courses of treatment. The response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors. The subjects included 1 male and 6 female LURPC patients, with a median age of 71 years (range, 59-78 years). The tumor was located in the head and body of the pancreas in 6 and 1 patients, respectively. No patients achieved a complete response, 5 achieved a partial response, 2 had stable disease, and none exhibited progressive disease. The response rate was 71%. The mean tumor diameter decreased significantly from 35 mm (range, 24-60 mm) prior to treatment to 22 mm (range, 20-35 mm) following treatment. Two patients were downstaged. The mean carbohydrate antigen (CA) 19-9 values decreased significantly from 767 U/ml (range, 14-1,977 U/ml) prior to treatment to 35 U/ml (range, 14-123 U/ml) following treatment. Adverse events classified as grade ≥3 occurred in 4 patients (57%): 3 patients (43%) suffered from neutropenia and 1 patient (14%) developed bilateral cellulitis of the lower extremities. No patients experienced an increase in disease severity, and all were able to continue treatment following temporary withdrawal or dosage reduction. Therefore, combined treatment with gemcitabine and nab-paclitaxel had favorable tumor-reducing effects and was not associated with severe adverse events, suggesting that this is a useful therapeutic strategy for patients with LURPC.

Ex vivo application of endocytoscopy for determining the longitudinal extent of bile duct cancer: a pathological analysis of 28 resected cases

The aim was to examine the diagnostic ability of an endocytoscope system (ECS) for detecting the longitudinal extent of bile duct cancer.