Hideki Sasanuma

Simultaneous colorectal and liver resections for synchronous colorectal metastases.

Background: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. Subjects and Methods: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. Results: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75–11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. Conclusion: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.

The impact of rituximab in ABO‐incompatible pediatric living donor liver transplantation: The experience of a single center

Previous studies have demonstrated the safety of ABO‐incompatible pediatric LDLT using preoperative plasmapheresis and rituximab; however, no reports have described the timing and dosage of rituximab administration for pediatric LDLT. This study aimed to describe a safe and effective dosage and timing of rituximab for patients undergoing pediatric ABO‐incompatible LDLT based on the experience of our single center. A total of 192 LDLTs in 187 patients were examined. These cases included 29 ABO‐incompatible LDLTs in 28 patients. Rituximab was used beginning in January 2004 in recipients older than two yr of age (first period: 375 mg/m2 in two cases; second period: 50 mg/m2 in two cases; and 200 mg/m2 in eight cases). Two patients who received 375 mg/m2 rituximab died of Pneumocystis carinii pneumonia and hemophagocytic syndrome. One patient who received 50 mg/m2 rituximab required retransplantation as a consequence of antibody‐mediated complications. All eight patients administered 200 mg/m2 survived, and the mean CD20+ lymphocyte count was 0.1% at the time of LDLT. In the preoperative management of patients undergoing pediatric ABO‐incompatible LDLT, the administration of 200 mg/m2 rituximab three wk prior to LDLT was safe and effective.

Effects of anastrozole on lipid metabolism compared with tamoxifen in rats.

AbstractBackground. Anastrozole, a new aromatase inhibitor, has been used to treat postmenopausal metastatic breast cancer, and several clinical trials of adjuvant treatment using this agent are ongoing. However, the effects of anastrozole on lipid metabolism are unknown. The aim of this study was to evaluate the effect of anastrozole on lipid metabolism, especially lipoprotein lipase (LPL) activity, compared with tamoxifen in rats. Methods. Ovariectomized female rats were divided into six groups: C, controls; T, tamoxifen treatment; A, anastrozole treatment; CAT, combined anastrozole/tamoxifen treatment; NAT, no treatment after tamoxifen; and AAT, anastrozole treatment after tamoxifen. The agents were orally administered for 3 weeks. Serum total cholesterol, triglycerides, and LPL activity in postheparin plasma were measured at the end of the experiment. Results. Serum cholesterol levels were significantly lower in the T and CAT groups than in controls (P < 0.001). Serum triglyceride levels were significantly higher in the T group than in the other groups (P < 0.001). LPL activity was significantly lower in T and AAT groups (P < 0.01). There was no significant difference in any parameters in group A. Conclusions. Anastrozole does not affect lipid metabolism including LPL activity. There was little effect on lipid profiles during combination treatment or following treatment with tamoxifen. In a clinical setting, therefore, anastrozole might be safe for patients with abnormal triglyceride profiles during tamoxifen treatment.

Selection of living donor liver grafts for patients weighing 6kg or less

In the field of pediatric living donor liver transplantation (LDLT), physicians sometimes must reduce the volume of left lateral segment (LLS) grafts to prevent large‐for‐size syndrome. There are 2 established methods for decreasing the size of an LLS graft: the use of a segment 2 (S2) monosegment graft and the use of a reduced LLS graft. However, no procedure for selecting the proper graft type has been established. In this study, we conducted a retrospective investigation of LDLT and examined the strategy of graft selection for patients weighing ≤6 kg. LDLT was conducted 225 times between May 2001 and December 2012, and 15 of the procedures were performed in patients weighing ≤6 kg. We selected S2 monosegment grafts and reduced LLS grafts if the preoperative computed tomography (CT)–volumetry value of the LLS graft was >5% and 4% to 5% of the graft/recipient weight ratio, respectively. We used LLS grafts in 7 recipients, S2 monosegment grafts in 4 recipients, reduced S2 monosegment grafts in 3 recipients, and a reduced LLS graft in 1 recipient. The reduction rate of S2 monosegment grafts for use as LLS grafts was 48.3%. The overall recipient and graft survival rates were both 93.3%, and 1 patient died of a brain hemorrhage. Major surgical complications included hepatic artery thrombosis in 2 recipients, bilioenteric anastomotic strictures in 2 recipients, and portal vein thrombosis in 1 recipient. In conclusion, our graft selection strategy based on preoperative CT‐volumetry is highly useful in patients weighing ≤6 kg. S2 monosegment grafts are effective and safe in very small infants particularly neonates. Liver Transpl 21:233‐238, 2015.

Immunoglobulin G4–Related Sclerosing Cholangitis Mimicking Hilar Cholangiocarcinoma Diagnosed With Following Bile Duct Resection: Report of a Case

We report a rare case of immunoglobulin G4 (IgG4)–related sclerosing cholangitis without other organ involvement. A 69-year-old-man was referred for the evaluation of jaundice. Computed tomography revealed thickening of the bile duct wall, compressing the right portal vein. Endoscopic retrograde cholangiopancreatography showed a lesion extending from the proximal confluence of the common bile duct to the left and right hepatic ducts. Intraductal ultrasonography showed a bile duct mass invading the portal vein. Hilar bile duct cancer was initially diagnosed and percutaneous transhepatic portal vein embolization was performed, preceding a planned right hepatectomy. Strictures persisted despite steroid therapy. Therefore, partial resection of the common bile duct following choledochojejunostomy was performed. Histologic examination showed diffuse and severe lymphoplasmacytic infiltration, and abundant plasma cells, which stained positive for anti-IgG4 antibody. The final diagnosis was IgG4 sclerosing cholangitis. Types 3 and 4 IgG4 sclerosing cholangitis remains a challenge to differentiate from cholangiocarcinoma. A histopathologic diagnosis obtained with a less invasive approach avoided unnecessary hepatectomy.

The natural history of liver regeneration in rats: Description of an animal model for liver regeneration studies

BACKGROUND Rodent models have been used to evaluate aspects of liver regeneration. The aim of the present study was to investigate the natural history of liver regeneration in healthy rats. METHODS A 70% partial hepatectomy was performed in 64 rats. The animals were randomised into 8 groups and evaluated on postoperative days one to eight. Hepatocyte proliferation was evaluated by immunohistochemistry using unbiased stereological principles. RESULTS The mean rat body weight was 238 g (211-287). The mean weight of the resected liver was 6.3 g (5.2-7.3) and the estimated mean total liver weight was 8.9 g (7.4-10.4). Both liver weight analysis and regeneration rate showed an ascending curve, with a maximum slope on postoperative days 1-4, reaching a steady state on days 5-8. Hepatocyte proliferation (positive Ki-67 cell profiles pr. mm(2)) was high (250 cell profiles/mm(2)) on postoperative days 1-3 and tapered off on day 5. CONCLUSION Seventy percent partial hepatectomy in healthy rats induces a rapid regenerative response and PODs 2, 4 and 8 seems optimal for assessing hepatic growth in future studies.

Experimental system for in-situ measurement of temperature rise in animal tissue under exposure to acoustic radiation force impulse

PurposeAcoustic radiation force impulse (ARFI) has recently been used for tissue elasticity measurement and imaging. On the other hand, it is predicted that a rise in temperature occurs. In-situ measurement of temperature rise in animal experiments is important, yet measurement using thermocouples has some problems such as position mismatch of the temperature measuring junction of the thermocouple and the focal point of ultrasound. Therefore, an in-situ measurement system for solving the above problems was developed in this study.MethodsThe developed system is composed mainly of an ultrasound irradiation unit including a custom-made focused transducer with a through hole for inserting a thin-wire thermocouple, and a temperature measurement unit including the thermocouple.ResultsThe feasibility of the developed system was evaluated by means of experiments using a tissue-mimicking material (TMM), a TMM containing a bone model or a chicken bone, and an extracted porcine liver. The similarity between the experimental results and the results of simulation using a finite element method (FEM) implied the reasonableness of in-situ temperature rise measured by the developed system.ConclusionThe developed system will become a useful tool for measuring in-situ temperature rise in animal experiments and obtaining findings with respect to the relationship between ultrasound irradiation conditions and in-situ temperature rise.

Sorafenib inhibits liver regeneration in rats

BACKGROUND Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated. METHODS Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling. RESULTS Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8. CONCLUSION In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation.

Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation

PURPOSE Cytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs. PATIENTS AND METHODS Of 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection. RESULT Positive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody-negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody-positive donors. CONCLUSION In CMV infection after pediatric liver transplantation, cases with CMV antibody-positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody-negative donors are considered low risk.

Recurrent Cholangitis by Biliary Stasis Due to Non-Obstructive Afferent Loop Syndrome After Pylorus-Preserving Pancreatoduodenectomy: Report of a Case

We report a 71-year-old man who had undergone pylorus-preserving pancreatoduodenectomy (PPPD) using PPPD-IV reconstruction for cholangiocarcinoma. For 6 years thereafter, he had suffered recurrent cholangitis, and also a right liver abscess (S5/8), which required percutaneous drainage at 9 years after PPPD. At 16 years after PPPD, he had been admitted to the other hospital because of acute purulent cholangitis. Although medical treatment resolved the cholangitis, the patient was referred to our hospital because of dilatation of the intrahepatic biliary duct (B2). Peroral double-balloon enteroscopy revealed that the diameter of the hepaticojejunostomy anastomosis was 12 mm, and cholangiography detected intrahepatic stones. Lithotripsy was performed using a basket catheter. At 1 year after lithotripsy procedure, the patient is doing well. Hepatobiliary scintigraphy at 60 minutes after intravenous injection demonstrated that deposit of the tracer still remained in the upper afferent loop jejunum. Therefore, we considered that the recurrent cholangitis, liver abscess, and intrahepatic lithiasis have been caused by biliary stasis due to nonobstructive afferent loop syndrome. Biliary retention due to nonobstructive afferent loop syndrome may cause recurrent cholangitis or liver abscess after hepaticojejunostomy, and double-balloon enteroscopy and hepatobiliary scintigraphy are useful for the diagnosis of nonobstructive afferent loop syndrome.