Masanobu Hyodo

Regulatory SNP in the RBP4 Gene Modified the Expression in Adipocytes and Associated With BMI

Retinol‐binding protein 4 (RBP4) is a recently identified adipokine that was involved in insulin resistance. RBP4 is predominantly expressed from the liver in normal metabolic state to transport retinoids throughout the body, but the exact physiological function and the regulatory mechanisms of adipocyte‐derived RBP4 have not been revealed. We conducted the genetic analysis about metabolic parameters in Japanese and Mongolian; the minor allele carriers of regulatory single‐nucleotide polymorphism (SNP −803G>A) showed significantly higher BMI in Japanese men (P = 0.009) and women (P = 0.017), and in Mongolian women (P = 0.009). Relative quantification of RBP4 transcripts in −803GA heterozygotes showed that the minor allele–linked haplotype‐derived mRNA was significantly more abundant than the transcript from major allele. RBP4 promoter assay in 3T3L1 adipocytes revealed that the minor allele increased the promoter activity double to triple and the administration of 9‐cis‐retinoic acid (RA) and 8‐bromo‐cyclic adenosine monophosphate (8‐Br‐cAMP) enhanced the activity. Multiple alignment analysis of human, mouse, rat, and cattle RBP4 promoter suggested conserved seven transcription factor binding motifs. Electrophoretic mobility shift assay showed the −803G>A SNP modulate the affinity against unidentified DNA‐binding factor, which was assumed to be a suppressive factor. These results collectively suggested that the minor allele of RBP4 regulatory SNP enhanced the expression in adipocytes, which may be associated with the adipogenesis.

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

PurposeOur purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC).MethodsThe study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC.ResultsWe studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC.ConclusionsThe possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.

Diagnosis and treatment of pediatric patients with late-onset portal vein stenosis after living donor liver transplantation.

Portal vein stenosis (PVS) after living donor liver transplantation (LDLT) is a serious complication that can lead to graft failure. Few studies of the diagnosis and treatment of late‐onset (≥3 months after liver transplantation) PVS have been reported. One hundred thirty‐three pediatric (median age 7.6 years, range 1.3–26.8 years) LDLT recipients were studied. The patients were followed by Doppler ultrasound (every 3 months) and multidetector helical computed tomography (once a year). Twelve patients were diagnosed with late‐onset PVS 0.5–6.9 years after LDLT. All cases were successfully treated with balloon dilatation. Five cases required multiple treatments. Early diagnosis of late‐onset PVS and interventional radiology therapy treatment may prevent graft loss.

Rendezvous penetration method using double-balloon endoscopy for complete anastomosis obstruction of hepaticojejunostomy after pediatric living donor liver transplantation

A 12-year-old boy underwent a living donor liver transplantation at another facility in March 2006 after undergoing a failed Kasai operation. The left lobe from his mother was used for the graft with a single-orifice bile duct 4 mm in diameter. The biliary reconstruction was performed via a Roux-en-Y hepaticojejunostomy with an interrupted 6-0 absorbable monofilament suture material without a biliary stent. The patient was treated with tacrolimusand methylprednisolone-based immunosuppression. The postoperative course was uneventful, except for an episode of postoperative diabetes requiring a subcutaneous insulin injection. In September 2006, he was referred to our department because of intrahepatic bile duct dilatation. Image findings and laboratory data revealed biliary stricture with liver dysfunction. A percutaneous transhepatic cholangiodrainage (PTCD) was performed, with placement of a 7-French PTCD tube. Complete obstruction of the anastomosis was observed on cholangiography 2 weeks later. The PTCD tube was changed from a 7-French tube to a 9-French tube in order to observe the anastomosis with a 2.8-mm-diameter cholangioscope (CHF-CB30S, Olympus, Tokyo, Japan). This proved ineffective, however, as the guide wire could not be passed through the anastomosis. Because in our experience double-balloon endoscopy (DBE) can reveal the outline of a complete obstruction of hepaticojejunostomy, we were compelled to apply the rendezvous penetration method using DBE. RENDEZVOUS PENETRATION METHOD USING DBE

Alternate-day oral therapy with TS-1 for advanced gastric cancer.

BackgroundTS-1 (1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyrimidine-1 M potassium oxonate) has a high single-agent response rate, of more than 40%, for gastric cancer; however, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effects. The alternate-day dosage of pyrimidine fluoride anticancer drugs could reduce their adverse effects without compromising their effects. We attempted an alternate-day therapy with TS-1 aiming at the avoidance of adverse effects and significantly longer duration of administration.MethodsWe observed patients for clinical effects and adverse effects under alternate-day dosage of TS-1, and determined blood 5-fluorouracil (FU) levels. The judgment of clinical effects was based on the New Guidelines to Evaluate the Response to Treatment in Solid Tumors (RECIST), whereas the evaluation of adverse effects was based on the National Cancer Institute NCI-common toxicity criteria (CTC).ResultsIn 72 (78%) of 92 patients, the TS-1 regimen was converted to the alternate-day dosage because of adverse effects. Twenty patients were treated with the alternate-day dosage regimen from the start because of the fear of adverse effects. The alternate-day dosage was clinically effective, as 28 of 34 patients after relatively curative resection remained alive and free from recurrence. The median survival time of 58 patients after noncurative resection or with unresectable or recurrent cancer was 332 days. Fifty-three percent of these 58 patients achieved partial response and stable disease of more than 12 weeks’ duration. We followed time-dependent changes in blood 5-FU levels in 36 of the patients on alternate-day therapy, in whom TS-1 had been administered daily before being administered every other day. The trough level was significantly lower when TS-1 was administered on alternate days, and blood 5-FU reached a peak at sufficiently effective levels at 2 h even after administration on the alternate-day basis.ConclusionThis study demonstrated that, compared with daily administration, alternate-day administration of TS-1 reduces adverse effects, and simultaneously ensures effective blood levels and provides sufficient clinical effects.

Double-balloon enteroscopy for bilioenteric anastomotic stricture after pediatric living donor liver transplantation.

Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double‐balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture.

Living Donor Liver Transplantation for Neonates Using Segment 2 Monosubsegment Graft

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13–27 days, 2.59–2.84 kg, respectively. S2 or reduced S2 grafts (93–98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min–15 h 27 min and 200–395 mL, respectively. The graft‐to‐recipient weight ratio was 3.3–3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.

Minimum Leakage Rate (0.5%) of Stapled Esophagojejunostomy with Sacrifice of a Small Part of the Jejunum after Total Gastrectomy in 390 Consecutive Patients

Background: The development of new surgical instruments and devices has facilitated the performance of esophagojejunostomy after total gastrectomy. However, total prevention of dehiscence of anastomoses remains difficult. We introduced a new procedure for esophagojejunostomy using a circular stapler, requiring sacrifice of only a small part of the jejunum. Methods: The study group comprised 390 consecutive patients who underwent reconstruction by Roux-en-Y esophagojejunostomy, performed with a circular stapler, sacrificing a small part of the jejunum after total gastrectomy. We assessed anastomotic leakage and anastomotic stenosis after surgery. Results: Only 2 patients (0.5%) had leakage and 4 (1.0%) had anastomotic stenosis after reconstruction. All the patients were cured by conservative therapy. Conclusions: Esophagojejunostomy performed with a circular stapler after total gastrectomy, with sacrifice of only a small part of the jejunum, is a useful and easy procedure, with a leakage rate of 0.5%.

Hand-assisted laparoscopic distal gastrectomy with abdominal wall-lift method.

We performed a hand-assisted laparoscopic resection of the distal stomach for treatment of gastric cancer with use of an abdominal wall-lift method. The surgeons left hand, which was inserted through a right lower quadrant incision, was extremely useful in accomplishing D2 lymph node dissection, application of a pursestring instrument, and approximation of a circular stapler to carry out a Billroth I anastomosis. Abdominal wall-lift enabled us to perform the gastrectomy without any concern about gas leakage. The combination of the wall-lift method and hand assistance seems to further enlarge the possibilities of laparoscopic procedures, especially in gastrointestinal surgery.

Living-Donor Liver Transplantation in 126 Patients with Biliary Atresia: Single-Center Experience

OBJECTIVES To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation. PATIENTS AND METHODS Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death. CONCLUSIONS Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.