Rikiya Fujita

Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists

BACKGROUND There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan. METHODS Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis. FINDINGS For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important. INTERPRETATION In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries.

Hemoclipping for postpolypectomy and postbiopsy colonic bleeding

BACKGROUND Obtaining colonoscopic biopsies and polypectomy can result in hemorrhage. The most effective management of this complication has not been determined. The objective of this study was to evaluate the endoscopic hemoclip in postprocedural colonic bleeding. METHODS Among 9555 consecutive colonoscopies, cases of postprocedural colonic bleeding (postpolypectomy and postbiopsy) requiring treatment were retrospectively reviewed. Endoscopic hemoclipping was initially attempted in each case; the rate of hemostasis after hemoclipping, use of additional hemostatic methods, and clinical outcome (need for transfusion/hospitalization) were analyzed. RESULTS There were 72 cases of bleeding in which treatment was required (45 immediate postpolypectomy, 18 delayed postpolypectomy and 9 postbiopsy). Endoscopic hemostasis was achieved in all cases of immediate postpolypectomy and postbiopsy bleeding and in all but one of the cases with delayed postpolypectomy bleeding. A detachable snare was used in addition to hemoclips in 3 cases of delayed postpolypectomy bleeding. There were no episodes of recurrent bleeding, deaths or need for surgery related to bleeding. CONCLUSION Early endoscopic management of postprocedural bleeding by hemoclipping provides hemostasis in the great majority of cases.

Diagnosis of submucosal tumor of the upper GI tract by endoscopic resection

BACKGROUND Submucosal tumors are frequent findings during endoscopy, although definitive diagnosis based on histologic confirmation presents some difficulties. The aim of this study was to evaluate the efficacy and safety of endoscopic resection based on endoscopic ultrasonography (EUS) findings to reach a definitive diagnosis of submucosal tumor. METHODS Fifty-four submucosal tumors of the upper gastrointestinal (GI) tract were included in this study. EUS was performed to determine the layer of origin and location of the lesion and to rule out malignancy. En bloc resection was attempted for lesions originating in the muscularis mucosa or submucosa. For tumors originating in the muscularis propria, we performed partial resection limited to the covering mucosa to expose the lesion and obtained a sample with standard biopsy forceps. RESULTS Sufficient samples were obtained in all 54 cases. There was no perforation. Bleeding occurred in only 5 cases (9%) and was easily managed with endoscopic hemostatic methods. EUS and pathologic findings coincided in 74.1% of cases (40 of 54). Benign lesions (leiomyoma, aberrant pancreas, and others) were predominant (52 of 54), although 2 small lesions were confirmed at pathologic study to be malignant (leiomyosarcoma and leiomyoblastoma). CONCLUSIONS Endoscopic resection based on EUS findings proved to be an effective and safe method to confirm the histologic diagnosis of submucosal tumor of the upper GI tract. Endoscopic resection should be considered a valuable choice for definitive management of benign submucosal tumors originating in the superficial layers.

Treatment strategy for rectal carcinoids: a clinicopathological analysis of 229 cases at a single cancer institution.

Background and Aim:  A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis.

Interferon and cyclosporin A in the treatment of fulminant viral hepatitis

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 × 104U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the Kings College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.

Chronic hepatitis A with persistent viral replication

Hepatitis A virus (HAV) usually causes an acute self‐limited illness. This report describes a patient with hepatitis A whose serum aminotransferase activities remained above normal and whose serum was persistently positive for immunoglobulin (Ig) M class anti‐hepatitis A 31 months after the onset of hepatitis. Liver biopsy carried out 11 months after the onset of hepatitis showed histological changes consistent with chronic hepatitis of moderate severity. HAV RNA was detected by polymerase chain reaction (PCR) in feces collected at the time of the liver biopsy. Furthermore, the patient developed esophageal varices 25 months after the onset of hepatitis. We believe this to be the first reported case in which persistent replication of HAV is implicated in chronic hepatitis with the potential to develop into liver cirrhosis.

Hepatic subcapsular hematoma after extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones.

Abstract: We present a patient with complication of huge hepatic subcapsular hematoma after extracorporeal shock wave lithotripsy (ESWL) for pancreatic lithotripsy. The hematoma measured 78–110 mm. Angiography showed a subcapsular hematoma, rather than a hematoma in the liver. In the arterial phase, the distal end of the small vessel showed spotty opacification similar to microaneurysma, suggesting that it was an injury caused by separation of the liver and its capsule, caused by the shock waves. The portal vein and hepatic vein were normal. After 8 weeks of conservative therapy, the hematoma was gradually absorbed and the patient was discharged. Eight months after the accident, the hematoma had decreased to 40 mm in size. After 20 months, it was completely absorbed. The reported rate of renal subcapsular hematoma after ESWL for renal or ureter stones is 0.1%–0.7%. To date, however, only five cases of hepatic subcapsular hematoma after right renal stone disintegration have been reported. This is the first report of hepatic subcapsular hematoma after ESWL for pancreatic stones.

CASE REPORT: Primary hepatic lymphoma associated with chronic liver disease

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle‐aged males. Presenting symptoms and physical findings were non‐specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

A new technique for removal of bile duct stones with an expandable metallic stent

BACKGROUND Endoscopic sphincterotomy is used routinely for extraction of bile duct stones. Also, endoscopic papillary dilation is a safe and effective technique that significantly reduces the need for papillotomy. However, extraction of large and/or multiple stones after endoscopic papillary dilation can be difficult. A new technique, endoscopic metallic stent-lithotripsy, for treatment of bile duct stones without endoscopic sphincterotomy or endoscopic papillary dilation is described. METHODS A self-expandable metallic stent was used to dilate the major duodenal papilla to allow lithotripsy and removal of bile duct stones in 38 patients. RESULTS The bile duct was successfully cleared of stones in 36 cases (95%). Complications included one episode of mild pancreatitis and one of cholangitis. CONCLUSIONS Although the number of patients who underwent successful expanding metallic stent-lithotripsy was small, the method is promising as an alternative to endoscopic sphincterotomy and endoscopic papillary dilation.

Familial adenomatous polyposis associated with multiple endocrine neoplasia type 1-related tumors and thyroid carcinoma: a case report with clinicopathologic and molecular analyses.

We describe a sporadic case with familial adenomatous polyposis, multiple endocrine neoplasia type 1 (MEN1)-related tumors (an endocrine cell tumor of the pancreas and bilateral parathyroid tumors), and a papillary thyroid carcinoma. To clarify how mutations of the adenomatous polyposis coli (APC) gene and the MEN1 gene, responsible for familial adenomatous polyposis and MEN1, respectively, might have contributed to tumorigenesis in this case, we studied germline mutations in both genes and loss of heterozygosity at their genetic loci in multiple lesions. In addition, we performed immunohistochemistry for &bgr;-catenin, associated with the function of the APC gene. A germline mutation was found in the APC gene but not in the MEN1 gene. Normal allelic loss at the APC gene locus was observed in bilateral parathyroid tumors. Immunohistochemical staining of &bgr;-catenin demonstrated accumulation in the cytoplasm in addition to membrane staining in all analyzed tumors and a strong nuclear reaction in the endocrine cell tumor of the pancreas. The presence of normal allelic deletions of the APC gene in bilateral parathyroid tumors and nuclear staining of &bgr;-catenin in the pancreatic tumor in addition to the germline mutations suggests that functional loss of the APC gene played an important role not only in familial adenomatous polyposis but also in the MEN1-related tumors in this case.