Takeshi Urabe

Clinical Pilot Study of Intrahepatic Arterial Chemotherapy with Methotrexate, 5-Fluorouracil, Cisplatin and Subcutaneous Interferon-Alpha-2b for Patients with Locally Advanced Hepatocellular Carcinoma

To evaluate the efficacy of methotrexate (MTX)-5-fluorouracil (5-FU), cisplatin (CDDP), and interferon-α-2b(IFNα-2b) combination therapy, we conducted a clinical pilot study in patients with locally advanced hepatocellular carcinoma (HCC). Sixteen patients, who had received no prior treatment for the HCC, with portal tumor thrombosis in the main trunk or in the major branch were enrolled in the study. IFNα-2b (3 × 106 units) was injected subcutaneously 3 times per week. After a bolus administration of MTX (30 mg/m2), CDDP (75 mg/m2) and thereafter 5-FU (750 mg/m2) were given weekly by intrahepatic arterial infusion. In 15 eligible patients, there were 1 complete response (CR) and 6 partial responses (PR) with a response rate of 46.7%. Median survival of the 15 patients was 7 months, and the 2-year survival rate of CR and PR patients was 57.1%. There was severe transient hematologic toxicity. More than grade 2 nausea/vomiting was noted in >50%. In conclusion, the IFNα-2b combination chemotherapy demonstrated good response in patients with locally advanced HCC. This treatment should be tried in a controlled study.

Transjugular intrahepatic portosystemic shunt after previous recanalization of a chronically thrombosed portal vein via a transmesenteric approach

We report a cirrhotic patient with complete occlusion of the portal vein with marked cavernous transformation due to chronic thrombosis in whom a transjugular intrahepatic portosystemic shunt (TIPS) was success-fully created after direct minilaparotomy mesenteric vein catheterization, lysis and aspiration of the thrombus, and stenting in the portal vein. The methods used, we believe, provide a new technique for performing TIPS in chronically thrombosed portal veins in which previously no effective surgical therapeutic options were available.

Combination Chemotherapy for Advanced Hepatocellular Carcinoma Complicated by Major Portal Vein Thrombosis

Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis, and the development of new therapeutic strategies is necessary. Here we report the efficacy of combination chemotherapy in our biochemical modulation. Synergistic effects of interferon-alpha-2b on 5-fluorouracil or cisplatin were demonstrated in Huh7 cells. The efficacy of methotrexate-5-fluorouracil, cisplatin, and interferon-alpha-2b combination therapy was demonstrated in 34 patients with HCC complicated by major portal vein thrombosis. Among the 29 patients eligible for the study, there were 3 complete responders and 10 partial responders with an overall response rate of 45%. The 2-year survival of the 34 patients was 15%, and the median survival of complete and partial responders was 11 months. There was severe transient hematological toxicity. Eight patients suffered from renal insufficiency, and 4 of them underwent hemodialysis. Although a control study is clearly necessary, our combination therapy induced a good response in the patients with advanced HCC. On the basis of our results, intensive chemotherapy should be attempted in advanced HCC complicated by major portal vein invasion.

Adenomyomatosis of the Papilla of Vater: A Case Illustrating Diagnostic Difficulties

Aim: To describe the extremely rare case of an adenomyoma of the papilla of Vater. Case Report: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. Conclusion: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.

Gastrointestinal amyloidosis secondary to hypersensitivity vasculitis presenting with intestinal pseudoobstruction

Hypersensitivity vasculitis is characterized byinflammation and necrosis of small blood vesselssecondary to allergic or hypersensitivity mechanisms (1,2). Gastrointestinal involvement with edema and bleeding also has been reported (3-5).Long-standing inflammation, such as rheumatic disease,infectious disease, inflammatory bowel disease, familialMediterranean fever, and malignancy, may lead tosystemic amyloidosis (6). Gastrointestinal involvementmay induce anorexia, nausea and vomiting, diarrhea,constipation, bleeding, malabsorption, andpseudoobstruction (6, 10-12). In this report we discussa patient with hypersensitivity vasculitis with severeintestinal bleeding who developed systemic amyloidosiswith intestinal pseudoobstruction 29 months after onset.Secondary amyloidosis due to hypersensitivity vasculitis has not been previously reported,and the causal relationship is discussed in thisreport.

Evaluation of Esophago‐gastric Varices with Endoscopic Ultrasonography

Esophago‐gastric varices of 22 patients were studied using a newly developed method of endoscopic ultrasonography (EUS). During the observation, the esophagus was filled with de‐aerated water, and reflux of the water was prevented using a balloon placed 7 cm proximal to the tip of the endoscope. Thirteen of 22 patients received endoscopic sclerotherapy (EIS) for their esophago‐gastric varices, and sequential changes of the varices were observed mith EUS.

Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines

Abstract: We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIα, DNA topoisomerase IIβ, and glutathione-S-transferase π gene (GST-π) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-α (IFN-α) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIα, and topoisomerase IIβ genes in HepG2 were weakened when IFN-α was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-α decreased the signals, and the signals of GST-π were decreased by IFN-α plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-α may modulate the mechanism of resistance to CDDP in liver cancer.

Duct-narrowing chronic pancreatitis without immunoserologic abnormality: comparison with duct-narrowing chronic pancreatitis with positive serological evidence and its clinical management.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

Development of a Sol Particle Homogeneous Immunoassay for Measuring Full‐Length Selenoprotein P in Human Serum

Selenoprotein P (SeP), a selenium‐rich extracellular glycoprotein, is the primary selenoprotein in the plasma. SeP plays an important role in the maintenance of selenium levels in the peripheral tissues. We developed a new sol particle homogeneous immunoassay (SPIA) for measuring full‐length SeP (FL‐SeP) levels in the human serum.

Importance of achieving complete necrosis during the first treatment for hepatocellular carcinoma to prevent bone metastasis: A prospective study

Background and Aims: Recent advances in the treatment of hepatocellular carcinoma (HCC) have changed the importance of bone metastasis during the follow up of such patients. In the present study, we investigated risk factors for bone metastasis after treatment for HCC.