Norihisa Kimura

Adenoma of the Nipple in an Adolescent

We recently treated a 14-year-old girl with a clinically and histologically diagnosed with adenoma of the nipple. Enucleation of a mass preserving the nipple was successfully performed. Adenoma of the nipple is a rare disease which is often mistaken clinically for Paget’s disease. About 200 cases of the tumors have been reported worldwide so far. The most common symptom is erosion of the nipple and nipple discharge. Our case had erosion of the nipple but no discharge. Adenoma of the nipple is a benign lesion which can be successfully treated by a simple surgery.

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.

Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy

BACKGROUND & AIMS To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model. METHODS Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested at 0, 1, 3, and 7 days for microarray analysis, quantitative real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry to examine the expression of multidrug resistance protein 4 (Mrp4), bile salt export pump (Bsep), and sodium-dependent taurocholate cotransporting polypeptide (Ntcp). RESULTS Persistently elevated levels of serum bile acids were observed at days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased at day 3. The expression of Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. The levels of Bsep, an export pump localized to the canalicular membrane, were unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, at days 3 and 7, Ntcp was localized in the cytoplasm and was hardly detected in the basolateral membrane. CONCLUSIONS These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seem to be responsible for the high blood bile acids levels after massive hepatectomy.

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.

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.

A case of pancreatoblastoma prenatally diagnosed as intraperitoneal cyst

Pancreatoblastoma in childhood is a very rare malignant tumor, but is considered to have a relatively good prognosis because of its low metastatic potential. We report 1-day-old female infant who was recently found to have an intraabdominal cyst on prenatal ultrasound examination. The tumor was a unilocular, cystic mass without invasion or metastasis to other organs, allowing total resection. It was diagnosed postnatally with pancreatoblastoma.

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.

Gene expression of ATP-binding cassette transporters during liver regeneration after 90% hepatectomy in rats

Liver damage with hyperbilirubinemia during regeneration of the small liver is the major hurdle to expand the indications of adult living donor liver transplantation. We performed a large-scale gene expression analysis of the regenerating liver after a 90% hepatectomy in rats, and analyzed the changes in the gene expression patterns related to the ATP-binding cassette (ABC) transporters. RNAs were prepared from 3 rat livers at 0, 24, 72 and 168 h after a 90% hepatectomy. The gene expression profile was analyzed by the Rat Genome 230 2.0 array with special references to the ABC transporters. Among 31,042 probes, 1,587 reported genes were identified as either upregulated or downregulated more than 2-fold. Among 20 ABC transporter genes, multidrug resistance protein (MRP) 2 and organic anion transporting polypeptide (OATP) 1 were significantly downregulated, while MRP1 and MRP3 tended to be expressed. These genetic changes were confirmed by real-time PCR. A microarray analysis demonstrated not only an extensive gene expression profile in the regenerating liver but more specific molecular events related to bilirubin transport at the same time. Changes in the expression pattern of the ABC transporters, therefore, seem to be the key event in liver failure during liver regeneration.

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.