Clinical efficacy of combination therapy with ME3738 and pegylated interferon-alpha-2a in patients with hepatitis C virus genotype 1.

AIM: ME3738, a derivative of soyasapogenol B, enhances the anti-hepatitis C virus (HCV) effect of interferon in an in vitro replication system and an in vivo mouse model of HCV infection. ME3738 plus pegylated interferon (PEG IFN)-α-2a treatment for 12 weeks decreased HCV RNA levels in enrolled late virus responder (LVR) patients with relapsed HCV. Half of the patients reached undetectable HCV RNA level. The present clinical study of ME3738 was conducted in naïve chronic hepatitis C patients to investigate the sustained virological response (SVR) and safety of 48-week treatment with ME3738 plus PEG IFN-α-2a. METHODS: Subjects (n = 135) with genotype 1b chronic hepatitis C with high viral loads were divided into three groups (ME3738 50 mg b.i.d., 200 mg b.i.d. or 800 mg b.i.d.). ME3738 was administrated p.o. and PEG IFN-α-2a (180 µg/week) s.c. for 48 weeks, and SVR was assessed at 24 weeks of treatment-free follow up. RESULTS: The viral disappearance rates at 12 and 48 weeks were 23.0% and 48.9%, respectively. SVR was seen in 5.9% of subjects. ME3738 did not worsen the adverse reactions generally seen with PEG IFN-α-2a treatment, and any adverse reactions specific to ME3738 were not observed. CONCLUSION: ME3738 plus PEG IFN-α-2a treatment to naïve chronic hepatitis C patients showed an antiviral effect and a good safety profile up to 48 weeks. However, HCV RNA was again detected in many subjects after treatment termination. Even though ME3738 is not enough to suppress HCV reproduction in this treatment. ME3738 was concurrently used with PEG IFN-α-2a treatment; however, a clear additional effect on SVR was not confirmed.

Etiology and prognosis of fulminant hepatitis and late-onset hepatic failure in Japan: Summary of the annual nationwide survey between 2004 and 2009.

AIM: To summarize the annual nationwide survey on fulminant hepatitis (FH) and late-onset hepatic failure (LOHF) between 2004 and 2009 in Japan. METHODS: The annual survey was performed in a two-step questionnaire process to detail the clinical profile and prognosis of patients in special hospitals. RESULTS: Four hundred and sixty (n = 227 acute type; n = 233 subacute type) patients had FH and 28 patients had LOHF. The mean age of patients with FH and LOHF were 51.1 ± 17.0 and 58.0 ± 14.4 years, respectively. The causes of FH were hepatitis A virus in 3.0%, hepatitis B virus (HBV) in 40.2%, other viruses in 2.0%, autoimmune hepatitis in 8.3%, drug allergy-induced in 14.6% and indeterminate etiology in 29.6% of patients. HBV reactivation due to immunosuppressive therapy was observed in 6.8% of FH patients. The short-term survival rates of patients without liver transplantation (LT) were 48.7% and 24.2% for the acute and subacute type, respectively, and 13.0% for LOHF. The prognosis was poor in patients with HBV reactivation. The implementation rate for LT in FH patients was equivalent to that in the previous survey. The short-term survival rates of total patients, including LT patients, were 54.2% and 40.8% for the acute and subacute type, respectively, and 28.6% for LOHF. CONCLUSION: The demographic features and etiology of FH patients has gradually changed. HBV reactivation due to immunosuppressive therapy is problematic. Despite advances in therapeutic approaches, the prognosis of patients without LT has not improved.

A novel and comprehensive mouse model of human non-alcoholic steatohepatitis with the full range of dysmetabolic and histological abnormalities induced by gold thioglucose and a high-fat diet.

BACKGROUND: The search for effective treatments of non-alcoholic steatohepatitis (NASH), now the most common chronic liver disease in affluent countries, is hindered by a lack of animal models having the range of anthropometric and pathophysiological features as human NASH. AIMS: To examine if mice treated with gold thioglucose (GTG) - known to induce lesions in the ventromedial hypothalamus, leading to hyperphagia and obesity - and then fed a high-fat diet (HF) had a comprehensive histological and dysmetabolic phenotype resembling human NASH. METHODS: C57BL/6 mice were injected intraperitoneally with GTG and then fed HF for 12 weeks (GTG+HF). The extent of abdominal adiposity was assayed by CT scanning. A glucose tolerance test and an insulin tolerance test were performed to evaluate insulin resistance (IR). Histological, molecular and biochemical analyses were also performed. RESULTS: Gold thioglucose+HF induced dysmetabolism, with hyperphagia, obesity with increased abdominal adiposity, IR and consequent steatohepatitis, with hepatocyte ballooning, Mallory-Denk bodies, perivenular and pericellular fibrosis as seen in adult NASH, paralleled by an increased expression of the profibrogenic factors, transforming growth factor-ß1 and TIMP-1. Plasma adiponectin and the expression of adiponectin receptor 1 and receptor 2 were decreased, while PPAR-γ and FAS were increased in the livers of GTG+HF mice. In addition, GTG+HF mice showed glucose intolerance and severe IR. CONCLUSIONS: Treatment with GTG and HF diet induce, in mice, a comprehensive model of human NASH, with the full range of dysmetabolic and histological abnormalities.

Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis.

OBJECTIVES: Non-alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non-alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non-alcoholic steatohepatitis. METHODS: The seed extract was given in the drinking water to fats being fed a methionine-choline-deficient diet for 15 weeks. KEY FINDINGS: Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet-only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal was lower in the rats given the seed extract than in the diet-only group. In the former, liver tissue levels of transforming growth factor-beta and collagen were also decreased. CONCLUSIONS: Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non-alcoholic steatohepatitis.

Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease.

BACKGROUND: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function. OBJECTIVE: To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO. METHODS: Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers. RESULTS: Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD. CONCLUSIONS: KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.

A comparison of magnifying chromoendoscopy versus histopathology of forceps biopsy specimen in the diagnosis of minute flat adenoma of the colon.

Having noted a discrepancy between endoscopic and histopathological diagnoses in cases of minute adenomas of the colon, a prospective study was designed to clarify which is appropriate, magnifying chromoendoscopy or histopathology of a specimen obtained by biopsy forceps. A total of 208 patients comprised the study population. The endoscopic diagnoses were performed with magnifying colonoscopies. We separated the detected lesions with type III(L) pit pattern following Kudo's classification into two groups at random: in group A (n = 104) resected specimens were fixed with 20% buffered formalin without being flattened, whereas in group B (n = 104) the resected specimens were flattened using forceps before fixation and the specimens were cut under observation of their surface structure with stereomicroscopy. Comparison of the initial diagnoses between groups A and B showed that a total of 84.6% (88/104) of the lesions were diagnosed to be tubular adenomas histopathologically in group A, compared with 100% (104/104) in group B (P < 0.0001). Results for comparison of the secondary diagnoses between group A and group B showed that 14 of the 16 lesions were diagnosed as tubular adenomas histopathologically. Thereafter, 98.1% (102/104) of the lesions were diagnosed to be tubular adenomas histopathologically in group A (P = 0.4976). In conclusion, high-resolution magnifying chromoendoscopy is an appropriate procedure for the diagnosis of minute adenomas in comparison with histopathology of specimens obtained by biopsy forceps in this prospective study.

Carbonic anhydrase inhibitors. Cloning, characterization and inhibition studies of the cytosolic isozyme III with anions.

The cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isozyme III (hCA III) has been cloned and purified by the GST-fusion protein method. Recombinant pure hCA III had the following kinetic parameters for the CO(2) hydration reaction at 20 degrees C and pH 7.5: k(cat) of 1.3 x 10(4) s(- 1) and k(cat)/K(M) of 2.5.10(5) M(- 1) s(- 1). The first detailed inhibition study of this enzyme with anions is reported. Inhibition data of the cytosolic isozymes hCA I - hCA III with a large number of anions (halides, pseudohalides, bicarbonate, carbonate, nitrate, nitrite, hydrosulfide, sulfate, sulfamic acid, sulfamide, etc.), were determined and these values are comparatively discussed for these three cytosolic isoforms. Fluoride, nitrate, nitrite, phenylboronic acid and phenylarsonic acid (as anions) were weak hCA III inhibitors (K(I)s of 21-78.5 mM), whereas bicarbonate, chloride, bromide, sulfate and several other simple anions showed K(I)s around 1 mM. The best hCA III inhibitors were carbonate, cyanide, thiocyanate, azide and hydrogensulfide, which showed K(I)s in the range of 10-90 microM. It is difficult to explain the inhibitory activity of carbonate (K(I) of 10 microM) against hCA III, also considering the fact that this ion has an affinity of 15-73 mM for hCA I and II and is in equilibrium with one of the substrates of this enzyme, i.e., bicarbonate, which is a much weaker inhibitor (K(I) of 0.74 mM against hCA III, of 12 mM against hCA I and of 85 mM against hCA II).

Total pancreatectomy for multiple neuroendocrine tumors of the pancreas in a patient with von Hippel-Lindau disease.

Von Hippel-Lindau disease (VHLD) is an autosomal dominant familial syndrome associated with multiple neoplasms. Medical management of pancreatic lesions is still controversial, especially for pancreatic neuroendocrine tumors (NET). We report an experience of total pancreatectomy for multiple pancreatic neuroendocrine tumors in a VHLD patient, and discuss the indication of surgical treatment. The patient was a 33-year-old Japanese female with a medical history of VHLD-associated tumors. At 27 years of age, abdominal computed tomography revealed a number of strongly enhanced round tumors throughout the pancreas. She underwent total pancreatectomy with portal vein resection because of back pain and an increase of tumor size. Pathological examination reconfirmed the diagnosis of multiple pancreatic NET invading the portal vein. She has been well with intensive insulin therapy and has shown no recurrence of NET for more than one year. This is a rare case of total pancreatectomy with portal vein resection for treatment of pancreatic NET in a VHLD patient. Total pancreatectomy is a viable option for treatment of multi-centric or extensive pancreatic NET because of a favorable prognosis of NET after radical surgical treatment.

Cloning, polymorphism, and inhibition of beta-carbonic anhydrase of Helicobacter pylori.

BACKGROUND: Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2) to bicarbonate and a proton, and alpha-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpalphaCA). The purpose of this study was to characterize the beta-class CA of H. pylori (hpbetaCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy. METHODS: We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpalphaCA and hpbetaCA, was studied with an in vitro killing assay. RESULTS: DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 microg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin. CONCLUSIONS: Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of alpha-and beta-class CAs could be applied as alternative therapy for eradication of H. pylori.

A long-survived case with solitary splenic metastasis from ovarian carcinoma.

A61-year-old postmenopausal woman with ovarian carcinoma was treated with two surgical operations and a series of platinum-based chemotherapy. A solitary metastasis into the splenic parenchyma was identified 33 months after the second surgery by abdominal computed tomography with an increased serum level of CA-125. She underwent a pancreaticosplenectomy and received platinum-based adjuvant chemotherapy continuously for 2 years. Her serum CA-125 level decreased to a normal range and she has lived without any recurrence for more than 10 years after the splenectomy. Solitary metastases from ovarian cancer into the splenic parenchyma are extremely rare. Among 18 cases previously reported, this present case shows the longest disease-free survival. Because these cases show favorable prognosis after splenectomy, surgical treatment should be considered along with adjuvant chemotherapy.

Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND AND AIMS: Most patients with hepatocellular carcinoma (HCC) have underlying liver cirrhosis that is frequently associated with a state of protein energy malnutrition. The aim of this study was to evaluate the clinical benefit of perioperative supplementation of a branched-chain amino acid-enriched nutrient-mixture for patients undergoing liver resection for HCC. METHODS: A total of 112 patients with HCC who underwent hepatic resection were enrolled in this study. These patients were divided into two groups: 40 patients received perioperative supplementation of branched-chain amino acid-enriched nutrient-mixture (AEN group) and 72 patients did not (control group). Laboratory data, postoperative complications, duration of hospitalization, and survival were assessed for each group and compared. RESULTS: The overall incidence of postoperative complications was lower in the AEN group (17.5%) than in the control group (44.4%) (P = 0.01). Among the postoperative complications, surgical site infection and bile leakage was observed in 5% of patients in the AEN group and in 15.3% and 12.5% of patients in the control group, respectively. Ascites appeared after the surgery in 7.5% of patients in the AEN group and in 16.7% of patients in the control group. The duration of hospitalization was significantly shorter in the AEN group was than in the control group (P < 0.05). CONCLUSIONS: This study strongly suggests that perioperative supplementation of a branched-chain amino acid-enriched nutrient-mixture is clinically beneficial in reducing the morbidity associated with postoperative complications and in shortening the duration of hospitalization of patients with chronic liver disease who undergo liver resection for HCC.

Long-term effects of multimodal treatment for patients with resectable carcinoma of the pancreas.

The treatment of pancreatic carcinoma remains one of the most formidable challenges in oncology. Curative resection, currently the only available treatment option, provides no significant impact on long-term survival. The recent development of multimodal treatment options for pancreatic cancer has provided clinical benefits and improved patient survival. In this study, we retrospectively evaluated our experiences with multimodal therapy, including radiotherapy and chemotherapy with gemcitabine, for the treatment of resectable pancreatic cancer. Fifty-eight patients with ordinary pancreatic carcinoma who underwent surgical resection at Kochi Medical School were studied. The clinical and pathological factors and multimodal treatment for pancreatic carcinoma that influenced patient survival were analyzed. Cumulative 1-, 3- and 5-year survival rates after surgery for ordinary pancreatic carcinoma were 62.2, 20.3 and 20.3%, respectively. The overall 4-year survival rate of patients subjected to adjuvant chemotherapy with gemcitabine after curative resection for ordinary pancreatic carcinoma is 39.1%. Adjuvant chemotherapy with gemcitabine provided a significantly better prognosis for patients following curative surgical resection than curative surgical resection alone (P=0.035). Although the rate of survival was greater for patients who underwent radiotherapy than those who did not, the difference was not statistically significant (P=0.054). Postoperative local recurrence around the nerve plexus of celiac and superior mesenteric arteries was better controlled in patients who underwent radiotherapy than those who did not. Adjuvant chemotherapy with gemcitabine after curative resection provides a significant survival benefit for patients with pancreatic carcinoma. Our results suggest that the postoperative recurrence of ordinary pancreatic carcinoma will be reduced by multimodal treatment using radiotherapy and adjuvant chemotherapy with gemcitabine.

Morphogenesis of a colorectal neoplasm with a type IIIS pit pattern inferred from isolated crypts.

BACKGROUND: The goal of this study was to clarify morphogenetic development in colorectal neoplasms with depressions by examining isolated crypts and their pit patterns. METHODS: Twelve colorectal neoplasms with depressions were examined endoscopically, stereomicroscopically, and histopathologically. The pit pattern was defined according to Kudo's classification. The HCl digestion method was used to isolate the crypts. For scanning electron microscopy observations of the surface structure, specimens were mounted on brass stubs, coated with gold, and then observed. RESULTS: In isolated crypts with bifurcation extending to the middle or all the way to the lesion surface, the crypt orifice was round with a type IIIS pit pattern. In those with bifurcations extending up to the upper portion, the crypt orifice was oval with a type IIIS pit pattern. Some crypts were almost completely separated into two. The orifice diameter of a nonbifurcated crypt was 95.1 +/- 28.1 microm, whereas the diameters of crypts with bifurcations extending to the middle or the upper part were 114.7 +/- 40.8 and 208.1 +/- 71.4 microm, respectively. Thus, the orifice diameter of a crypt with the bifurcation reaching the upper part was about twice that of orifices of nonbifurcated crypts or those with bifurcations extending to the middle. CONCLUSIONS: Our results indicate that colorectal neoplasms with depressions may enlarge by a process of crypt bifurcation in which a single crypt divides into two crypts.

The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study.

AIM: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. METHODS: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). RESULTS: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. CONCLUSION: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis.

Evaluation of the depth score of type V pit patterns in crypt orifices of colorectal neoplastic lesions.

BACKGROUND: We developed and evaluated the clinical usefulness of a scoring system that subclassified type VI: pit patterns. METHODS: We studied 119 colon cancer lesions (pTis, n = 26; pT1, n = 93) and 22 tubular adenoma lesions with severe atypia in which a type VI: pit pattern was visible under a stereomicroscope. Four type VI: pit pattern formation appearances (existing pits, marginal irregularities of the gland duct, narrowing of the gland duct lumen, and unclear outline of the gland duct) were defined, and the relationship between each appearance and the invasive depth of the cancer was evaluated. RESULTS: When the four type VI: pit pattern appearances were considered in a logistic regression analysis, the odds of a more invasive submucosal cancer were significantly increased by the appearance of marginal irregularities, a narrowed lumen, and an unclear outline. In the logistic regression analysis results, when 0.63 was used as the cutoff score for prediction of a more invasive submucosal cancer, 80 cases in the less invasive group were classified correctly (specificity, 1.0), whereas 53 (86.9%) of the 61 cases in the more invasive group were classified correctly (sensitivity, 0.869). CONCLUSIONS: It is important first to understand the usability and limitations of objective scoring of type V pit pattern findings and then to apply this score to the determination of cancer depth in order to accurately identify lesions suitable for endoscopic treatment.

The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel drug targets.

Helicobacter pylori (H. pylori) successfully resides in the human stomach in highly acidic conditions, causing a variety of gastroduodenal lesions, including gastric ulcer, gastric cancer and MALT lymphoma. For acid acclimation of H. pylori, two types of enzymes, urease and carbonic anhydrase (CA), play a central role. They cooperatively function to maintain neutral pH in the bacterial cytoplasm and periplasm. The genome project of H. pylori identified two different classes of CA with different subcellular localization: a periplasmic alpha-class CA (hp alphaCA) and a cytoplasmic beta-class CA (hp betaCA). These two CAs are catalytically efficient with almost identical activity to that of the human isoform CA I for the CO(2) hydration reaction, and highly inhibited by many sulfonamides/sulfamates, including acetazolamide, ethoxzolamide, topiramate and sulpiride, all clinically used drugs. Furthermore, certain CA inhibitors, such as acetazolamide and methazolamide, were shown to inhibit the bacterial growth in vitro. Since the efficacy of eradication therapies currently employed has been decreasing due to drug resistance and side effects of the commonly used drugs, the dual inhibition of alpha- and/or beta-CAs of H. pylori could be applied as an alternative therapy in patients with H. pylori infection or for the prevention of gastroduodenal diseases provoked by this widespread pathogen.

Clinicopathologic features of adenocarcinoma at the gastric cardia: is it different from distal cancer of the stomach?

BACKGROUND: Although the incidence of gastric cardia cancer is considerably less than more distal gastric cancer, the rate of occurrence is now increasing. The objective of this study was to evaluate and compare the clinicopathologic findings of gastric cardia and more distal stomach adenocarcinoma. STUDY DESIGN: Patients included in our study were those who underwent operations for gastric adenocarcinoma in our institute from 1981 to 2006, and who had undergone complete medical history, including history of daily alcohol consumption; smoking; body mass index; and pathologic examinations. A total of 843 patients were included in our study, and were divided into cardia and noncardia cancer groups. RESULTS: Among the 843 patients, 23 (2.8%) had gastric cardia cancer. There were no substantial differences in age, gender, body mass index, smoking, or alcohol consumption between the two groups. Mean size of cardia tumors was larger than noncardia tumors. Although noncardia cancer was often detected at an early stage, gastric cardia cancer was most often diagnosed at an advanced stage. Pathologically, cardia cancer was more invasive and had more lymphatic permeation and lymph node metastasis than noncardia cancer. CONCLUSIONS: Gastric cardia cancer occurs at a low incidence of only 2.8% of resected gastric cancers. Unlike cases of gastric cardia cancer in Western populations, body mass index is not associated with occurrence of gastric cardia cancer in our study. Because gastric cardia cancer appears more aggressive than noncardia gastric cancer, early diagnosis and intervention are important.

Clinicopathological features and medical management of early gastric cancer.

BACKGROUND: The detection of early gastric carcinoma (EGC) has increased worldwide due to advances in endoscopic techniques and equipment. The aim of the current study was to compare the clinicopathological findings of patients with and without lymph node metastasis. METHODS: A total of 440 cases of early gastric carcinoma in patients who underwent surgical procedures between 1981 and 2002 at Kochi Medical School were studied. RESULTS: Lymph node metastasis was observed in 38 patients (8.6%) with EGC. Multivariate analysis identified 4 independent risk factors of lymph node metastasis: (1) submucosal invasion; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. CONCLUSION: For patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation is demonstrated.

Review of diagnostic criteria for autoimmune pancreatitis; for establishment of international criteria.

Along with worldwide expansion of the disease concept of autoimmune pancreatitis (AIP), the necessity of international diagnostic criteria for the disease is increasing. Since the first diagnostic criteria for AIP by the Japan Pancreas Society was proposed in 2002, certain groups in several countries have reported criteria for AIP. We reviewed the criteria proposed to date. Among three systematic criteria from Japan, the Mayo Clinic and Korea, there is no fundamental difference in the three major diagnostic categories: findings on pancreatic imaging, laboratory and histological studies. Notable differences are that typical imaging findings are essential for the diagnosis in Japanese and Korean criteria, but not in the Mayo criteria, while, the Mayo criteria emphasize the histological findings as a gold standard for the diagnosis. The critical differences between the Japanese and the other two criteria are the use of the diagnostic factors "other organ involvement" and "steroid responsiveness." Employment of these factors in clinical diagnostic criteria for general physicians possibly confuses the disease concept and definitely increases the risk for treating patients with pancreatic or biliary malignancies with steroids. Even if the sensitivity of criteria goes down, their use might be limited to certain kinds of specific criteria, such as that for epidemiological study, patient selection for research purposes, or use in expert hospitals. The disease entity of AIP postulated in Europe includes two histological types of pancreatitis with different clinical phenotypes, suggesting two syndromic spectra of autoimmune-related chronic pancreatitis.

Pancreatic transection using a sharp hook-shaped ultrasonically activated scalpel.

BACKGROUND AND AIMS: The operative mortality and morbidity associated with pancreatic surgery has been decreasing; however, pancreatic fistula remains a major cause of a potentially fatal complication. Although different devices and techniques have been proposed to reduce of the postoperative pancreatic fistula, none has gained unanimous acceptance. We herein describe a new technique for pancreatic transection using a sharp hook-shaped ultrasonically activated scalpel (UAS). MATERIALS AND METHODS: Between December 2004 and June 2006, 32 patients who had undergone pancreatectomies performed using the sharp hook-shaped UAS (Ethicon Endo-Surgery, Cincinnati, OH, USA) were studied. RESULTS: The incidence of pancreatic fistula in these patients was 6.3% (2/32). Both cases underwent a distal pancreatectomy. No patient had systemic organ failure induced by postoperative pancreatic fistula, and conservative drainage management improved the pancreatic fistula. No pancreatic fistulas developed in patients who underwent pancreaticoduodenectomy with a duct-to-mucosa anastomosis pancreaticojejunostomy after pancreatic transection using the sharp hook-shaped UAS. CONCLUSION: Pancreatic transection using the sharp hook-shaped UAS is an easy and useful method that facilitates detection of the main pancreatic duct with minimal blood loss. It may contribute to lower morbidity and mortality after pancreatic resection.