Transition of Spleen Volume Long After Pediatric Living Donor Liver Transplantation for Biliary Atresia.

PURPOSE: After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS: Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS: Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS: Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation.

INTRODUCTION: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. OBJECTIVES: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. METHODS: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. RESULTS: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. CONCLUSIONS: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.

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.

Case report of FLT3-ITD-positive AML patient 11 years after living donor liver transplantation.

With the increasing number of long-term survivors of living donor liver transplantation, the occurrence of secondary cancer is sometimes reported. Solid tumors such as lymphomas are mainly observed. However, only 8 cases of leukemia have been reported so far. For patients younger than 15 years old, leukemia developed in 4 within 3 years after the liver transplantation, whereas acute lymphoblastic leukemia developed in only 1 patient. This is the first case report of a patient in whom FLT3-ITD-positive acute myeloid leukemia (AML) developed more than 10 years after living donor liver transplantation for congenital biliary atresia. AML developed in a 14-year-old boy 11 years after living donor liver transplantation from his father. The patient received the transplant at the age of 3 years and was treated with tacrolimus and methylprednisolone for transplant rejection. Eleven years posttransplantation, he visited the hospital with general malaise and anemia. Blood tests revealed an elevated white blood cell count of 60,100/µL, and the patient was diagnosed with AML. Chromosome analysis revealed a t(6; 9) (p23 q34) translocation; moreover, genetic testing revealed a FLT3-ITD-positive mutation. We started treatment in accordance with the Tokyo Children's Cancer Study Group AML99 protocol. With chemotherapy treatment, the patient achieved complete remission. After chemotherapy, we performed stem cell transplantation from his father. Other patients were reported in relatively early stages after liver transplantation, but our case was more than 10 years posttransplantation. The association with the onset of congenital bile duct atresia and leukemia is still not clear, but we consider the possibility that long-term immunosuppressive drugs contribute to developing leukemia.

Splenic artery embolization before laparoscopic splenectomy in children.

BACKGROUND: This study assessed the safety and utility of preoperative splenic artery embolization before laparoscopic splenectomy in children. METHODS: Five young girls with a mean age of 13.2 years underwent laparoscopic splenectomies at the authors' institution from August 1998 to April 2003. Three of the patients had idiopathic thrombocytopenic purpura, and two had hereditary spherocytosis. Preoperative splenic artery embolization was performed the day before the surgery in all cases. The laparoscopic splenectomy was performed using traditional laparoscopic procedures and standard laparoscopic instruments with the patient in the right semilateral position. RESULTS: The mean spleen weight was 252.6 g, and the mean length was 11.6 cm. All the patients reported postembolic pain, but not to a level unmanageable by intravascular narcotics. There were no severe complications in the splenic artery embolization. The laparoscopic splenectomies were completed in a mean of 211 min, with a mean estimated blood loss of 9 ml. None of the operations required conversion to traditional open laparotomy, and none of the patients died or experienced operative complications. CONCLUSION: The authors concluded that splenic artery embolization is safe and useful as an adjuvant procedure performed before elective laparoscopic splenectomy in children.

Genetic polymorphisms of aldehyde dehydrogenase 2, cytochrome p450 2E1 for liver cancer risk in HCV antibody-positive japanese patients and the variations of CYP2E1 mRNA expression levels in the liver due to its polymorphism.

BACKGROUND: Hepatocellular carcinoma (HCC) in persons with liver cirrhosis (LC) arises following hepatitis virus infection. Alcohol may accelerate the risk of development of LC and HCC. Cytochrome p450 2E1 (CYP2E1) oxidizes ethanol to form acetaldehyde and aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, which is carcinogenic in humans, and both alcohol-metabolizing enzymes show the genetic polymorphisms in a Japanese population. METHODS: Using polymorphism analysis, we studied the frequency of ALDH2 functional deletion due to the G to A single-bp mutation in exon 12 and CYP2E1 polymorphism in the transcriptional region, both associated with higher levels of acetaldehyde, in 135 patients with LC and/or HCC, including 99 with HCC, and 135 non-cancer controls. The mRNA expression levels of CYP2E1 in the liver were also examined in 55 surgical specimens. RESULTS: The allelic frequency of the homozygous ALDH2 2-2 genotype, coding for the enzyme deletion, was significantly higher compared to that of the homozygous or heterozygous ALDH2 1-1 genotypes in cases with HCC (OR = 5.4, 95% CI 2.1-14.0). There were no differences in the frequencies of specific genotypes of CYP2E1 in cases of HCC, but combined analysis of ALDH2 and CYP2E1 revealed that the odds ratio of occurrence of the C1/C1 homozygosity of CYP2E1 and the ALDH2 2-2 homozygosity was as high as 23.0 (2.9-182). The mRNA levels of CYP2E1 were higher in the liver of patients with the C1/C1 homozygosity of CYP2E1 than in those with other genotypes (P < 0.05). CONCLUSIONS: ALDH2 and CYP2E1 polymorphisms may modify the risk of development of HCC against the background of LC in the Japanese. Polymorphism analysis of alcohol-metabolizing enzymes using molecular techniques may be useful in the risk assessment of liver cancer in patients with hepatitis C virus infection.

Hand-assisted laparoscopic hepatectomy after partial splenic embolization.

The case of a patient with hepatocellular carcinoma and thrombocytopenia secondary to liver cirrhosis who underwent successful hand-assisted laparoscopic hepatectomy after partial splenic embolization is described. A 67-year-old man with severe liver cirrhosis was admitted for treatment of hepatocellular carcinoma. His early phase of hepatic angiography showed two hypervascular tumors in segment 6. The patients liver function was poor, with the indocyanine green retention at 15 min of 49.5%, a total serum bilirubin concentration of 2.0 mg/dl, an albumin concentration of 2.8 g/dl, and an hyaluronic acid concentration of 649 ng/ml. The platelet count was 3.0 x 10(4)/microl secondary to hypersplenism. Partial splenic embolization decreased the splenic volume by 50% preoperatively. At 2 months later, the platelet count was 6.0 x 10(4)/microl, and hand-assisted laparoscopic partial hepatectomy was performed uneventfully. The patients postoperative course was unremarkable, and he was discharged on postoperative day 12.

Combined endoscopic and radiologic intervention to treat esophageal varices.

BACKGROUND/AIMS: In patients with esophageal varices, we investigated the impact on long-term outcome of combining interventional radiologic procedures with endoscopic therapy. METHODOLOGY: Of 133 patients with esophageal varices, 86 were treated with endoscopic therapy alone and 47 underwent endoscopic therapy in addition to interventional radiologic procedures. End-points considered during 5-years of follow-up included recurrent bleeding and retreatment. RESULTS: Bleeding rates were 24.4% in the endoscopy group and 25.4% in the combined therapy group. Retreatment rates at 1, 3, and 5 years for the endoscopy group versus the combined therapy group were 40.7% versus 30.3%, 72.0% versus 67.5%, and 88.2% versus 80.5%, respectively, representing no significant difference between two groups. However, cumulative retreatment rates in Child's class C cases were significantly lower in the combined therapy group than in the endoscopy group (P = 0.025). Patients who had combined therapy which included all embolizing techniques showed significantly lower retreatment rates than patients treated with endoscopy alone (P = 0.05). CONCLUSIONS: In combination, interventional radiologic and endoscopic therapies are highly effective and can improve long-term outcome in patients with esophageal varices, especially those with poor liver function and those who undergo embolization by all techniques.

Liver cell adenoma in a 26-year-old man.

This is a report of a case of liver cell adenoma (LCA) in a 26-year-old man with no prior history of liver disease or glycogen storage disease and no record of hormonal therapy. He was found to have an asymptomatic hepatic mass during a routine medical examination. The physical findings were unremarkable, and the results of routine laboratory studies were all within normal limits. Selective hepatic arteriography showed a hypervascular mass within the right lobe of the liver. Despite the radiological examination, the nature of the mass was unknown, and preoperative biopsy was unadvisable because of the risk of bleeding. Because of the difficulty of determining the malignancy of the hepatic tumor preoperatively, elective laparotomy for diagnosis and hepatectomy as treatment appeared to be the best available approach. Pathological examination of the surgical specimen resulted in a diagnosis of LCA. A review of the literature revealed that LCA unassociated with the use of oral contraceptives is rare.

Celiac artery aneurysm: a case evaluated preoperatively with three-dimensional computed tomographic angiography.

In a 63-year-old woman computed tomography (CT) incidentally detected a celiac artery aneurysm approximately 3 cm in diameter. While conventional angiography suggested that the splenic artery and common hepatic artery arose from the celiac artery aneurysm, three-dimensional CT angiography indicated that the aneurysm involved only the mid portion of the celiac artery. Considering the risk of eventual aneurysm rupture, surgery was performed. Aneurysmectomy and devascularization of hepatic, splenic, and celiac arteries were carried out following complete cross-clamping of the celiac artery. The distal segment of the celiac artery was directly anastomosed to the proximal segment in an end-to-end fashion. Histologically, the aneurysm wall showed atheromatous changes. Contrast-enhanced abdominal CT confirmed complete removal of the celiac artery aneurysm, and postoperative angiography confirmed good arterial flow. The patient recovered uneventfully after surgery, with normalization of transiently abnormal hepatic function parameters. In this case of celiac artery aneurysm, three-dimensional CT angiography was found to be valuable in determining the relationships of the aneurysms to important arterial branches.

Hypersplenism induced by hepatectomy.

BACKGROUND/AIMS: We encountered a case of posthepatectomy splenic enlargement and hypersplenism followed by disseminated intravascular coagulopathy with airway hemorrhage causing death. METHODOLOGY: We, therefore, retrospectively investigated postoperative splenic enlargement, hypersplenism and disseminated intravascular coagulopathy by computed tomography and laboratory data in 57 hepatectomized patients with a malignant or benign disease in the postoperative period. RESULTS: Of 32 patients with hepatocellular carcinoma or biliary tract carcinoma (group A), 12 with metastatic hepatic lesions (group B), and 13 with benign liver disease (group C); remarkable (20%) splenic enlargement was noted in 8 patients in group A, 2 in group B, and 2 in group C. Seven of the 12 patients were associated with liver cirrhosis, 5 with preoperative splenomegaly, and 8 had undergone major hepatectomy. Postoperative hypersplenism developed in 5 patients in group A, and one patient in group C. All of them were associated with liver cirrhosis or chronic hepatitis and preoperative splenomegaly, and five had undergone hepatic lobectomy or more extensive resections. All except for the disseminated intravascular coagulopathy case recovered. Statistically, splenic enlargement was significantly related to the extent of hepatectomy; lobectomy versus segmentectomy = 28.3 +/- 28.5% (n = 14) versus 12.4 +/- 13.8% (n = 20), (unpaired Student's t test, P = 0.037). Platelet counts of the patients with liver cirrhosis or chronic hepatitis is lower than those without the diseases, both pre- and postoperatively (14.0 +/- 6.0 x 10(4)/mm3 vs. 21.5 +/- 6.2 x 10(4)/mm3, P = 0.0001). CONCLUSIONS: Postoperative hypersplenism was noted only in the patients with liver cirrhosis or chronic hepatitis and preoperative splenomegaly, and developed more frequently after larger hepatectomies than after smaller hepatectomies; 5 (45%) of 11 versus 1 (7%) of 14, chi 2 test, P = 0.026).

Acute cholecystitis caused by a cholesterol polyp.

A 39-year-old man hospitalized with upper abdominal pain had been found to have a 3mm polyp in the body of the gallbladder 3 years previously. Laboratory tests on admission showed mild liver dysfunction. Ultrasonography depicted a dilated gallbladder with increased wall thickness; the polyp could no longer be seen. Computed tomography with drip infusion cholangiography again showed a dilated gallbladder, and also stenosis of the distal cystic duct. The resected specimen obtained by laparoscopic cholecystectomy showed disappearance of the polyp from the body of the gallbladder. A cholesterol stone was incarcerated in the cystic duct, representing an impacted detached cholesterol polyp causing acute cholecystitis. Spontaneous detachment of a cholesterol polyp from the gallbladder mucosa, then, can result in acute cholecystitis.

Interventional radiology and endoscopic therapy for recurrent esophageal varices.

BACKGROUND/AIMS: We investigated the impact long-term prognosis of combined interventional radiology and endoscopic therapy in patients with esophageal varices. METHODOLOGY: Patients with recurrent esophageal varices underwent treatment as follows: 54 were treated with endoscopic therapy alone and 32 underwent endoscopic therapy plus interventional radiologic procedures. Primary endpoints during 5-year follow-up included recurrent bleeding, second retreatment, and death. RESULTS: The bleeding rates were 11.1% in the endoscopy group, and 9.4% in the combined therapy group. Second retreatment rates at 1 year, 3 years, and 5 years in the endoscopy group and combined therapy group were 25.4% and 17.2%, 70.2% and 39.3%, and 85.0% and 69.6%, respectively. The second retreatment rates in the combined therapy group were significantly reduced compared to the endoscopy alone group (P = 0.05). Cumulative retreatment rates in Child's class C cases were significantly lower in the combined therapy group than in the endoscopy group (P = 0.01). Survival at 3 years was 97.1% in the endoscopy group and 92.0% in the combined therapy group, and 5-year survival was 79.1% and 83.6%, respectively. CONCLUSIONS: The combination of interventional radiologic and endoscopic therapy is highly effective and improves long-term prognosis in patients with recurrent esophageal varices.

Spontaneous disappearance of a hepatic cyst.

The spontaneous disappearance of a hepatic cyst is described. A 62-year-old woman presented with symptoms of general fatigue in August 1992. Her past medical history was significant for chronic hepatitis, which was diagnosed in 1990 but not treated. Initial laboratory tests revealed mild liver dysfunction with a positive serologic test for hepatitis C. In August 1992, ultrasonography and computed tomography disclosed a cystic lesion along the middle hepatic vein in the right anterior segment of the liver, which was 40 mm in diameter. Repeat radiologic studies in June 1994 demonstrated that the size of the cyst was unchanged. In May 1995, the cyst was only 25 mm in diameter, and it continued to decrease in size thereafter, to 10 mm in September 1995 and 7 mm in September 1996. No hepatic cyst was visualized in December 1996, though the region in which the cyst existed was hyperechoic. Laboratory data were essentially unchanged from August 1992 to December 1996. Clinically the patient remained asymptomatic.

Rupture of a hepatic metastasis from renal cell carcinoma.

We describe a rare case of spontaneous rupture of a hepatic metastasis from renal cell carcinoma that was treated successfully by hepatic arterial embolization. A 65-year-old woman, who had been undergoing immunotherapy for inoperably disseminated renal carcinoma and lung metastases, presented with severe abdominal pain in a state of hypovolemic shock. Computed tomography revealed a highly attenuated mass lesion in the right lobe of the liver and massive intraperitoneal hemorrhage. Subsequent hepatic angiography showed extravasation from the feeding right hepatic artery. Transcatheter embolization of the right hepatic artery was subsequently performed, and the patient made an uneventful recovery. Although hepatic rupture due to metastatic cancer is extremely rare, transcatheter arterial embolization (TAE) is an appropriate and useful treatment for massive hemorrhage caused by spontaneous rupture of liver metastasis.