bluuebunny/crossref_metadata_2025 huggingface dataset:
Chylous ascites caused by portal vein thrombosis treated with octreotide
Authors: LEONG RUPERT WL , HOUSE ANTHONY K , JEFFREY GARY P
Published: September 2003

Abstract  Chylous ascites is an uncommon entity with variable causes and rarely arises from portal vein thrombosis. This is a case report of chylous ascites caused by idiopathic portal vein thrombosis that was refractory to medical therapy and shunt surgery, which showed an impressive response to treatment with subcutaneous octreotide. We review the literature on chylous ascites with particular reference to the role of somatostatin analogs in the management of this rare condition.
Clinical significance of SEN‐virus on interferon response in chronic hepatitis C patients
Authors: LIN JIUN‐GUEY , GOTO TAKASHI , NAKANE KUNIO , MIURA KOUICHI , MIKAMI KEN‐ICHIRO , OHSHIMA SHIGETOSHI , YONEYAMA KAZUO , WATANABE SUMIO
Published: September 2003

Background and Aim:  A novel virus, SEN‐virus (SENV), was recently discovered. It has been reported as a candidate for a non‐A–E hepatitis virus. However, much is still unknown about the clinical significance of SENV. The aim of the present study was to clarify the clinical significance of SENV in patients coinfected with SENV and hepatitis C virus (HCV).

Methods:  The 52 subjects had chronic hepatitis C and had undergone interferon (IFN) therapy. SEN virus DNA was investigated by using polymerase chain reaction with SENV‐specific primers, which we designed to detect all strains of SENV. Additionally, SENV‐D and ‐H were detected by consensus primers.

Results:  Thirty‐five patients were SENV‐DNA positive and 22 patients were SENV‐D‐ or ‐H‐positive before IFN therapy. After IFN therapy, in the HCV‐RNA eradication group, all cases normalized their serum alanine aminotransferase (ALT). However, in the no eradication group, the ALT no‐response rate was 68.7%. In contrast, in the SENV eradication group, the ALT no‐response rate was 51.9%, and in the no eradication group, it was 37.5%. Also, in the SENV‐D and ‐H eradication group, the ALT no‐response rate was 54.5%, and in the no eradication group, it was 36.4%. The changes in ALT after IFN therapy were significantly correlated with the changes in HCV RNA, but no correlation was found with the SENV DNA presence.

Conclusions:  Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and SENV appears to primarily be caused by HCV, and is less attributable to SENV.
Clinical outcome of endoscopically removed early colorectal cancer
Authors: TUNG SHUI‐YI , WU CHENG‐SHYONG
Published: September 2003

Background and Aim:  Endoscopic resection is widely adopted for early colorectal cancer. Most studies examining the effectiveness of endoscopic treatment of early colorectal cancer are from Japan, and little is known about the success of this treatment in other areas of the world. The authors performed this study to investigate the effectiveness of endoscopic treatment of early colorectal cancer.

Methods:  The medical records of patients with histologically proven early colorectal cancer and who were treated by endoscopic resection between January 1985 and December 2000 were reviewed retrospectively. Information regarding the demographic data of patients, clinicopathological characteristics of the tumors, and follow‐up events were recorded and analyzed.

Results:  Altogether 91 patients, including 73 with mucosal cancers and 18 with submucosal invasive cancers, were enrolled. Nineteen patients (eight with mucosal cancers and 11 with submucosal invasive cancers) underwent subsequent surgical colectomy. Larger tumors, and those with sessile or flat depressed morphology, and deep submucosal invasion were more difficult to remove completely through endoscopic resection alone. Five patients had local recurrent tumors, occurring between 4 and 12 months after endoscopic resection, and were treated surgically. Furthermore, two patients died of unrelated diseases, one at 1 month and one at 3 years after treatment. All the other patients were well after an average follow‐up interval of 40.9 months (range 18–189 months).

Conclusions:  Endoscopic resection safely and effectively removed most early colorectal cancers. Careful histological examinations of resected specimens to determine the indications of subsequent surgical colectomy, and close post‐treatment surveillance would improve the outcome and life quality for these patients.
Cellular distribution of telomerase reverse transcriptase in human hepatocellular carcinoma
Authors: ONISHI TORU , NOUSO KAZUHIRO , HIGASHI TOSHIHIRO , TOSHIKUNI NOBUYUKI , NAKATSUKASA HARUSHIGE , KOBAYASHI YOSHIYUKI , UEMURA MASAYUKI , YUMOTO EIICHIRO , FUJIWARA KEISHI , SATO SHUICHIRO , NAKAMURA SHINICHIRO , YOKOYAMA JUNKO , HANAFUSA TADASHI , SHIRATORI YASUSHI
Published: September 2003

Background and Aim:  Telomerase is the enzyme that synthesizes telomeric DNA, and the activation of telomerase is closely related to cellular immortality. Telomerase activity has been reported in many human cancer tissues and is regulated by the expression of human telomerase reverse transcriptase (hTERT). The aim of the present study was to identify hTERT‐expressing cells in human liver tissues and evaluate the feasibility of the hTERT promoter for gene therapy of hepatocellular carcinoma (HCC).

Methods:  The authors examined the cellular distribution of hTERT transcripts in surgically resected HCC by in situ hybridization.

Results:  Among 20 samples, hTERT expression was observed in 15 HCC. Transcripts of hTERT were homogenously distributed in the cytoplasm of HCC cells in nine of 15 cases; six of 15 cases displayed a heterogeneous staining pattern. All poorly differentiated HCC that expressed hTERT showed a homogenous pattern of staining. None of the non‐cancerous hepatocytes were positive for the transcripts, but infiltrating lymphocytes were faintly stained. The homogenous expression of hTERT was also observed in the vascular invasion of HCC.

Conclusions:  The results indicate that most HCC cells express hTERT RNA and that the promoter is a good candidate as a target for gene therapy. However, careful consideration must be taken concerning the potential effects on lymphocytes.
Prevalence of Helicobacter pylori resistance to clarithromycin and metronidazole determined by 23S ribosomal RNA and rdxA gene analyses in Hiroshima, Japan
Authors: HIYAMA TORU , TANAKA SHINJI , MASUDA HIROSHI , SHIMA HIDEYUKI , KOSE KAZUHIRO , TUNCEL HANDAN , ITO MASANORI , KITADAI YASUHIKO , SUMII MASAHARU , UEMURA NAOMI , YOSHIHARA MASAHARU , SHIMAMOTO FUMIO , HARUMA KEN , CHAYAMA KAZUAKI
Published: September 2003

Background and Aims:  Resistance to antibiotics in Helicobacter pylori is increasing and becoming a serious problem in eradication treatment of H. pylori. The prevalence of H. pylori infections that are resistant to clarithromycin, metronidazole, or both were determined in H. pylori isolates in Hiroshima, Japan.

Methods:  Sixty Japanese patients with H. pylori infection were collected between 1999 and 2000. To detect the resistance to clarithromycin and metronidazole, mutations of the 23S ribosomal RNA (rRNA) and rdxA genes that are responsible for resistance in H. pylori, were examined by direct sequencing analysis.

Results:  Resistance to clarithromycin and metronidazole was detected in 12 (20.0%) and nine (15.0%) of the patients, respectively. Dual resistance to clarithromycin and metronidazole was detected in five (8.3%) patients.

Conclusion:  These results indicate that the relatively high prevalence of the dual resistance in H. pylori isolates may need special attention and new therapeutic approaches in Japan.
Value of regional cerebral blood flow in the evaluation of chronic liver disease and subclinical hepatic encephalopathy
Authors: YAZGAN YUSUF , NARIN YAVUZ , DEMIRTURK LEVENT , SARACOGLU MEHMET , ERCAN MUSTAFA , AKYATAN NEVZAT , DALKANAT NAGEHAN , OZEL A MELIH , CETIN MESUT
Published: September 2003

Aims:  Regional changes in cerebral blood flow in patients with chronic hepatitis, cirrhosis and subclinical hepatic encephalopathy were investigated in the present study using single photon emission computed tomography (SPECT).

Methods:  Twenty patients with cirrhosis, 11 patients with chronic hepatitis, and nine healthy controls were included in the study. Cerebral SPECT were obtained for all patients. The percentages of cerebral blood flow of 14 regions to the cerebellar blood flow were determined. Only the patients with cirrhosis underwent psychometric evaluation: visual evoked potentials (VEP) measurements and electroencephalogram (EEG) recordings along with blood levels of albumin, bilirubin, and ammonia were measured and prothrombin time was determined in cirrhotic patients. These patients were classified according to the Child–Pugh classification.

Results:  Among cirrhotic patients, six had abnormal results in VEP studies, 11 in psychometric tests and with six in EEG evaluation. Any abnormality in psychometric tests and/or VEP studies is taken as the main criterion; subclinical hepatic encephalopathy was detected in 12 of 20 patients. According to SPECT results in patients with subclinical encephalopathy, a statistically significant decrease in cerebral blood flow in right thalamus and nearly significant decrease in left thalamus were observed. Regional blood flow was significantly higher in the frontal lobes of patients with cirrhosis when compared with healthy controls. Similarly, cerebral blood flow in frontal and cingulate regions was significantly higher in patients with chronic hepatitis than in healthy controls. There was no relationship between cerebral blood flow and blood levels of ammonia or Child–Pugh score, in cirrhotic patients.

Conclusion:  Significant changes in cerebral blood flow may be present in chronic liver diseases and the authors suggest that the measurement of changes in cerebral blood flow might be useful in detecting subclinical hepatic encephalopathy.
Contribution of capsaicin‐sensitive afferent nerves to rapid recovery from ethanol‐induced gastric epithelial damage in rats
Authors: SOBUE MASASHI , JOH TAKASHI , OSHIMA TADAYUKI , SUZUKI HIDEO , SENO KYOJI , KASUGAI KUNIO , NOMURA TOMOYUKI , OHARA HIROTAKA , YOKOYAMA YOSHIFUMI , ITOH MAKOTO
Published: September 2003

Background and Aim:  It is well known that capsaicin‐sensitive nerve signaling acts as a protective factor against various ulcerogens. However, the contribution of topical capsaicin‐sensitive nerves within the stomach to rapid restitution has not been fully investigated. The present study was therefore conducted focusing on recovery from gastric mucosal damage induced by ethanol in vivo.

Methods:  Male Sprague‐Dawley rats were fasted and anesthetized. 51Cr‐EDTA was administered intravenously and gastric mucosal integrity was continuously monitored by measuring the blood to lumen 51Cr‐EDTA clearance. Capsaicin or vehicle was irrigated before, together with or after the perfusion of 20% ethanol, followed by perfusion with saline. In another experiment, ruthenium red, a capsaicin‐sensitive cation antagonist, was given before the ethanol‐capsaicin perfusion. Furthermore, this study was verified using lafutidine, a histamine H2‐receptor antagonist, which has a gastric mucosal protective action through the capsaicin‐sensitive afferent nerves.

Results:  When capsaicin was administered before ethanol treatment, mucosal damage was significantly reduced and recovery was significantly rapid compared to the control. When capsaicin (160 µM) and ethanol were administered simultaneously, the mucosal damage was exacerbated but recovery was nevertheless more rapid than the control group. With a lower dose of capsaicin (80 µM), mucosal damage was not exacerbated and recovery was enhanced. When capsaicin or lafutidine was administered after the induction of ethanol injury no change was detected regarding the damage. However, recovery was significantly accelerated. Ruthenium red reversed the action of post‐treatment with capsaicin on restitution.

Conclusions:  These results indicate that luminal administration of capsaicin exerts protection against and accelerates restitution from gastric damage in the very early phase after ethanol injury. This action is probably due to activation of topical capsaicin‐sensitive afferent nerves in the rat.
Plasma erythropoietin level in patients with cirrhosis and its relationship to the severity of cirrhosis and renal function
Authors: YANG YING‐YING , LIN HAN‐CHIEH , LEE WUI‐CHIANG , HUANG YI‐TSAU , HOU MING‐CHIH , LEE FA‐YAUH , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: September 2003

Background and Aim:  The level of plasma erythropoietin (EPO) in patients with cirrhosis is controversial. It is known that overproduction of nitric oxide (NO) plays, in part, a role for the development of peripheral arterial vasodilatation in cirrhosis with portal hypertension. It has also been hypothesized that a possible interaction is noted between endogenous EPO and NO production. The current study was undertaken to evaluate the relationship between plasma EPO levels and the severity of liver disease, hemodynamic values, renal functions, and plasma nitrate/nitrite levels in patients with cirrhosis.

Methods:  The authors measured the biochemistry, plasma EPO and nitrate/nitrite levels in 67 patients with cirrhosis (Child–Pugh class A in 23 and Child–Pugh class B and C in 44) and compared their values with those in 34 healthy subjects. Systemic and splanchnic hemodynamic measurements and effective renal plasma flow were obtained from cirrhotic patients.

Results:  Plasma EPO and nitrate/nitrite levels were significantly increased in patients with cirrhosis compared with healthy subjects. Additionally, plasma EPO values were higher in cirrhotic patients with ascites or with anemia than in those without ascites or without anemia, respectively. Plasma EPO levels were positively correlated to the hepatic venous pressure gradient (HVPG) and Child–Pugh score, negatively correlated to the renal and hepatic blood flows, but were not correlated to nitrate/nitrite level and systemic vascular resistance in cirrhotic patients. Multiple regression analysis showed that HVPG and renal plasma flow were independent predictors for the elevated EPO level in cirrhotic patients.

Conclusions:  Plasma EPO levels were increased in patients with cirrhosis compared with those in healthy subjects. The increase in plasma EPO levels is related to the degree of portal hypertension, the severity of cirrhosis and the renal plasma flow. In contrast, the EPO levels had no correlation to the nitrate/nitrite levels and systemic vascular resistance in patients with cirrhosis.
Identification of a novel pre‐S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen
Authors: YEH CHAU‐TING , CHANG MEI‐HUI , LAI HSIN‐YU , CHANG MING‐LING , CHU CHIA‐MING , LIAW YUN‐FAN
Published: September 2003

Background and Aim:  The aim of the present study was to investigate whether spontaneous seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B could be attributed to the presence of pre‐S/S gene mutations.

Methods:  Of 34 hepatitis B virus (HBV) carriers who experienced spontaneous seroclearance of HBsAg, 30 were still seropositive for HBV DNA. The serum samples of these carriers were subjected to sequence analysis.

Results:  A novel pre‐S2 mutation, G149R, was found in nine (group I) but not in 17 (group II) patients carrying HBV DNA with intact pre‐S/S reading frames. In the remaining four patients (group III), only aberrant pre‐S/S transcripts were found in their sera. Distinct patterns of amino acid substitutions specific to group I and II patients were identified. Superinfection by hepatitis C or D virus occurred predominantly in group II patients (P = 0.019). Superinfection by HBV of a different genotype occurred predominantly in patients without hepatitis C or D virus superinfection (P = 0.013). Site‐directed mutagenesis experiments showed that secretion of HBsAg was not defective in the pre‐S2 G149R mutant.

Conclusions:  In a particular subgroup (group I) of patients, seroclearance of HBsAg was not caused by superinfection of other hepatitis viruses, nor was it caused by failure of HBsAg secretion or detection. Instead, a yet unrecognized mechanism associated with emergence of a novel pre‐S2 mutation is responsible.
Novel diagnostic method of testing for Helicobacter pylori infection using the rapid leukocyte strip test, Leukostix
Authors: MATSUDA MITSURU , NODA YATSUGI , TAKEMORI YASUHIRO
Published: September 2003

Background and Aim:  A characteristic of gastric mucosa infected with Helicobacter pylori is infiltration of inflammatory cells, mainly consisting of neutrophils. The present study aimed to detect neutrophils in homogenates of biopsied gastric mucosa semiquantitatively using the rapid leukocyte strip test, Leukostix. The authors then investigated the association of these results with H. pylori status.

Methods:  The authors studied 342 patients undergoing endoscopy. Of these, 160 were treated for eradication of H. pylori infection and were reassessed after treatment. For the definitive diagnosis of H. pylori infection, quantitative culture, the rapid urease test and immunohistostaining were performed. Additionally, serum antibody against H. pylori was determined at the initial examination, and the 13C‐urea breath test was performed after treatment. With the use of Leukostix, homogenates of biopsied gastric mucosa were spotted onto strips and judged 2 min later.

Results:  There was a significant correlation between the positive reaction of Leukostix and the number of neutrophils in gastric tissues determined by microscopic observation. The sensitivity and specificity of Leukostix at the initial examination were 97.9% and 76.9%, respectively, while those after eradication treatment were 100% and 97.2%, respectively. There was a significant positive correlation between the degree of reaction of Leukostix and the amount of H. pylori determined by quantitative culture.

Conclusions:  The Leukostix test, using biopsied samples of gastric mucosa, was excellent for quantitative determination of neutrophils and useful for diagnosis of H. pylori infection and early assessment of treatment efficacy. Positive gradations of Leukostix results corresponded closely with the amount of H. pylori in gastric tissues.
Effects of aspirin and indomethacin on endothelial cell proliferationin vitro
Authors: PEARCE HR , KALIA N , BARDHAN KD , BROWN NJ
Published: September 2003

Background and Aim: Non‐steroidal anti‐inflammatory drugs (NSAID) are associated with delayed peptic ulcer healing. Ulcer healing is dependent on angiogenesis, which requires endothelial cell (EC) proliferation. The present study aimed to determine whether NSAID and prostaglandin E2(PGE2) inhibited EC proliferationin vitro.

Methods: Effects of 50 µL aspirin (10 µM‐1 mM), indomethacin (10 µM‐1 mM) and PGE2(1 µM‐0.1 mM) on the proliferation, viability and cell cycle of human dermal microvascular (HuDMEC) and human umbilical vein (HUVEC) EC were assessed using dual staining cell viability, 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide and flow cytometry assays.

Results: Proliferation of HuDMEC and HUVEC was significantly inhibited by 0.1 mM/1 mM indomethacin, 1 mM aspirin and 100 µM PGE2, with a significant (P < 0.05) increase in EC necrosis with 1 mM indomethacin and 100 µM PGE2. No effects on cell cycle were demonstrated.

Conclusions: High concentrations of NSAID inhibit both HuDMEC and HUVEC proliferationin vitroby cytotoxic (indomethacin) or cytostatic (aspirin and indomethacin) mechanisms.Interestingly, PGE2was also antiproliferative. Inhibition of EC proliferation may prevent angiogenesis at the ulcer site, which may in part explain the delayed ulcer healing associated with NSAID.
Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis: Association with disease severity
Authors: SELMI CARLO , ZUIN MASSIMO , BIONDI MARIA LUISA , INVERNIZZI PIETRO , BATTEZZATI PIER MARIA , BERNINI MARA , MEDA FRANCESCA , GERSHWIN M ERIC , PODDA MAURO
Published: September 2003

Background and Aims:  Primary biliary cirrhosis (PBC) presents a wide spectrum of clinical manifestations. In experimental models of liver cirrhosis and cholestasis it has been suggested that altered nitric oxide production is involved in liver injury and portal hypertension development. The present study investigated endothelial nitric oxide synthase (eNOS) genetic polymorphisms (894G/T, −786T/C) in patients with PBC and in controls to verify whether disease susceptibility and progression are associated with a particular genotype.

Methods:  Genomic DNA from 109 Italian PBC patients (65 with advanced disease, i.e. liver transplantation or histological stage III–IV) was obtained and polymorphisms determined by fluorescent probe analysis. Healthy subjects (n = 242) were used as a control group.

Results:  The allelic frequencies of both polymorphisms did not differ significantly between PBC patients and controls. When the association between genotypes and disease severity was addressed, both the 894T and the −786T alleles were more frequently found in the 22 patients with progressing disease (894T, frequency 0.455 compared with 0.240; P = 0.032; −786T, frequency 0.682 compared with 0.460; P = 0.038). Patients with 894TT presented higher Mayo score values (6.1 ± 1.2 compared with 5.4 ± 1.3 in 894G/G patients; P = 0.030) but similar age and disease duration values.

Conclusions:  The authors suggest that genetic variants of eNOS are not associated with susceptibility to PBC, although the genotypes may lead to differences in disease severity and progression.
Transforming growth factor‐beta‐1 genetic polymorphism in Japanese patients with chronic hepatitis C virus infection
Authors: SUZUKI SEIJI , TANAKA YASUHITO , ORITO ETSURO , SUGAUCHI FUMINAKA , HASEGAWA IZUMI , SAKURAI MAYUMI , FUJIWARA KEI , OHNO TOMOYOSHI , UEDA RYUZO , MIZOKAMI MASASHI
Published: September 2003

Background and Aim:  Transforming growth factor beta‐1 (TGF‐β1) is one of the most dominant fibrogenic cytokines in hepatic fibrosis. The aim of the present study was to examine the effects of TGF‐β1 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection and in healthy control subjects.

Methods:  The TGF‐β1 genotypes at codon 10 and codon 25 were determined in 206 Japanese patients with chronic HCV infection and in 101 Japanese healthy control subjects. Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) was used for the detection of these polymorphisms. The degree of hepatic fibrosis was assessed by liver biopsy and graded according to the New Inuyama Classification for chronic hepatitis graded F0–4.

Results:  The authors found no significant differences in genotype distributions and allele frequency between the HCV patients and the healthy control subjects. The frequencies of the TT, TC, and CC genotypes of codon 10 were 24%, 42% and 35%, respectively, among the patients of the F0–2 group, and 31%, 40% and 29%, respectively, among those of the F3–4 group. No significant differences were shown between the TGF‐β1 polymorphism at codon 10 and the stage of hepatic fibrosis. In contrast, no genetic alteration of codon 25 was found in healthy controls and patients with chronic HCV infection.

Conclusion:  These results suggest that there may not be a significant relationship between polymorphism at codon 10 and the development of progressive hepatic fibrosis in the Japanese population.
Epidemiology of autoimmune liver disease
Authors: FELD JJ , HEATHCOTE EJ
Published: September 2003

Primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are chronic liver diseases that likely have an autoimmune basis to their pathogenesis. Although significant strides have been made in the clinical management of these conditions, their pathogenesis remains obscure. Understanding of various epidemiological factors may shed light on predisposing or causative factors for these diseases. Most is known about the epidemiology of PBC, with only minimal information on that of PSC and AIH. In this review, the current data on the epidemiology of PBC, AIH and PSC are summarized and suggestions are made for future work in this important area.
Retroperitoneal kaposiform hemangioendothelioma with tufted angioma‐like features in an infant with Kasabach–Merritt syndrome
Authors: Brasanac Dimitrije , Janic Dragana , Boricic Ivan , Jovanovic Nada , Dokmanovic Lidija
Published: September 2003

Kasabach–Merritt syndrome denotes profound thrombocytopenia and coagulopathy in an infant with a vascular tumor. A retroperitoneal vascular tumor with an unusual combination of histopathological features is reported, and compared with vascular lesions described in the reported cases of Kasabach–Merritt syndrome in the literature. A large retroperitoneal tumor that had expanded through the sigmoid mesocolon into the sigmoid colon wall was resected from an 8‐month‐old infant with fully developed Kasabach–Merritt syndrome. Histological examination revealed a combination of venous (cavernous) malformation, kaposiform hemangioendothelioma and tufted angioma‐like areas. Cellular tumor components (especially tufted angioma‐like parts) infiltrated the wall of the sigmoid colon to the submucosal level. Immunohistochemical staining with antibodies to the Ki‐67 antigen and proliferating cell nuclear antigen showed a low proliferative activity, whereas the antiapoptotic bcl‐2 protein was expressed diffusely in tumor cells. This is the first reported case of a vascular tumor with tufted angioma‐like elements found in the retroperitoneum, and the first reported in combin‐ation with kaposiform hemangioendothelioma and venous malformation in the same lesion. Considering the immu‐nohistochemical results and overlapping histological features, it may be considered that tufted angioma and kaposiform hemangioendothelioma represent different growth patterns or stages in the development of a single type of hemangioma.
Malignant glomus tumor of the lung
Authors: Hishida Tomoyuki , Hasegawa Tadashi , Asamura Hisao , Kusumoto Masahiko , Maeshima Arafumi , Matsuno Yoshihiro , Suzuki Kenji , Kondo Haruhiko , Tsuchiya Ryosuke
Published: September 2003

Primary malignant glomus tumors of the lung are extremely rare, and to our knowledge, only three cases have been described to date. We report one such case in a 53‐year‐old man who presented with a persistent dry cough. Chest computed tomography scans demonstrated an irregularly shaped mass in the right lower lobe of the lung. Many small nodules were distributed from the main tumor to the periphery, along with bronchovascular bundles. Right lower lobectomy was performed under the diagnosis of lung tumor. The tumor was located in the proximal portion of the right lower lobe and extended along the pulmonary arteries. Histologi‐cal examination revealed a sheet‐like proliferation of epithelioid glomus cells and fascicles of spindle cells. The presence of increased mitotic activity, tumor necrosis and prominent intravascular invasion suggested malignancy. The tumor cells were immunoreactive for vimentin, calponin, h‐caldesmon, and α‐smooth muscle actin, which indicated definitive smooth muscle differentiation. We believe that this is the fourth reported case of malignant glomus tumor of the lung.
Fatal infectious mononucleosis with evidence suggestive of the development of B cell lymphoma
Authors: Hiroshima Kenzo , Iyoda Akira , Isobe Kouichi , Ishii Genichiro , Toyozaki Tetsuya , Shibuya Kiyoshi , Shimamura Fumihiko , Haga Yukiko , Okimoto Yuri , Horie Hiroshi , Harigaya Kenichi , Ohwada Hidemi
Published: September 2003

A 4‐year‐old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein–Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV‐associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen‐positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma.
Genetic analysis of cutaneous squamous cell carcinomas arising from different areas
Authors: Hayashi Masahiro , Tamura Gen , Kato Noriko , Ansai Shin‐ichi , Kondo Shigeo , Motoyama Teiichi
Published: September 2003

Although cutaneous squamous cell carcinomas (SCC) occur most frequently in sun‐exposed areas of the skin, they can also arise in non‐sun‐exposed areas. Some risk factors for cutaneous SCC, such as ultraviolet (UV) light, are well known. However, the major factor for carcinogenesis may depend on the site of the tumor as well as the ethnicity of the patient. In this study we examined 41 Japanese cutaneous SCC cases, focusing on the area of appearance and the presence of genetic alteration, with 27 cases from sun‐exposed areas, 10 from non‐sun‐exposed areas (excluding genital areas), and four from burn scars from sun‐exposed areas. Squamous cell carcinomas arising in sun‐exposed areas showed less frequent p53 gene mutations compared to SCC arising in non‐sun‐exposed areas. Ultraviolet light‐specific mutations were found in only two cases of SCC from sun‐exposed areas. Human papilloma virus (HPV) DNA was detected in two cases (7.4%) of the sun‐exposed areas and none of the non‐sun‐exposed or scar areas. The frequency of loss of heterozygosity on D5S178 in non‐sun‐exposed SCC was significantly higher than in sun‐exposed SCC. Furthermore, the incidence of fractional allelic loss (FAL) was significantly higher in non‐sun‐exposed SCC than in sun‐exposed SCC. Our findings suggest that sun‐exposed SCC in Japan may be relatively less involved with p53 mutation, and that non‐sun‐exposed SCC acquire more genetic alterations than sun‐exposed SCC.
Myxoid endometrial stromal sarcoma of the uterus
Authors: Kasashima Satomi , Kobayashi Masako , Yamada Mitsuoki , Oda Yoshio
Published: September 2003

A rare case of a myxoid type of endometrial stromal sarcoma of the uterus in a 41‐year‐old woman is reported. A tumor was found in the myometrium and was well circumscribed, measuring 9 × 7 × 7 cm in size. The tumor was mainly composed of a hypocellular area with tumor cells separated by prominent myxoid stroma. The tumor cells were spindle‐shaped and resembled endometrial stromal cells. Numerous small thin‐walled vessels were seen throughout the tumor. Immunohistochemically, the tumor cells were diffusely stained for estrogen and progesterone receptors and CD10, and focally and weakly for HHF35, α‐smooth muscle actin and desmin, but not stained for h‐caldesmon. These results indicated that the tumor originated from endometrial stromal cells. The tumor had an increased mitotic activity (MIB‐1 labeling index: 1–10%), and focally showed nuclear pleomorphism. Thus, this tumor had a malignant potential and was diagnosed as a myxoid type of low‐grade endometrial stromal sarcoma. The patient is currently well with no evidence of local recurrence or metastasis 21 months after the operation. This case indicates a wide morphological spectrum of endometrial stromal tumor. A myxoid endometrial stromal sarcoma should be considered in the different diagnosis of the intramural myxoid tumors in the uterus.
Pseudoinvasion of the colorectal polypoid tumors: Serial section study of problematic cases
Authors: Tanizawa Tohru , Seki Takayuki , Nakano Makoto , Kamiyama Ryuichi
Published: September 2003

Ten cases of endoscopically removed colorectal polypoid tumors exhibiting lobular growth patterns in the submucosa without prominent desmoplastic changes in the interstitium were investigated using serial sections, and four cases were confirmed to be pseudoinvasion. The growth pattern of these four cases (pseudoinvasive tumors) was morphologically compared with the other six tumors (microinvasive tumors) in which obviously infiltrating foci were seen in minimal ranges. In the pseudoinvasive tumors, intramucosal tumor tissue spread into the submucosa through the narrow gap of the muscularis mucosae and formed a lobulated nodule larger than the gap of the muscularis mucosae. This suggested that squeezing of the herniated tumor tissue by muscularis mucosae at the gap was crucial to forming a typical feature of pseudoinvasion. The maximum diameters of the gap of the muscularis mucosae (G) and the submucosal tumor nodule (N) were measured under a microscope and compared between both groups. The mean N/G ratio of the pseudoinvasive tumors (1.73 ± 0.46) indicated a significantly higher value than that of the microinvasive tumors (1.04 ± 0.06; P < 0.01). The N/G ratio could be one of the indices used to distinguish a pseudoinvasive tumor from a microinvasive tumor in colorectal polypoid tumors.
Different immunophenotypes in Buerger's disease
Authors: Kurata Atsushi , Machinami Rikuo , Schulz Andreas , Fukayama Masashi , Franke Folker Ernst
Published: September 2003

Recently, we reviewed the morphology of 31 specimens of thromboangiitis obliterans (TAO, Buerger's disease) in a multivariate analysis and showed that certain novel features of the affected vessels are different from arteriosclerosis obliterans (ASO) and thromboembolism. However, the pathogenic concept of TAO is still controversial. We applied immunohistochemistry to 58 amputated lower extremities and five autopsy controls. At specific sites of the diseased vessels, different cellular components were immunotyped by CD3, CD4, CD20, CD31, CD68, actin and desmin. These results were carefully compared among different diagnostic groups of vasoocclusive lesions by statistical methods. Some unique characteristics of TAO were identified when compared with ASO or thromboembolism. Consistent with a primary inflammatory and immunogenic lesion, lymphocytes and especially CD4+ T cells emerged significantly in TAO vessels and their adventitia. In the subset of definite TAO cases defined by all clinical criteria, the linear arrangement of macrophages, and B‐ and T‐lymphocytes along vascular elastic fibers was the most striking additional finding, suggesting elastic fibers are an important immunogen. However, this feature was not apparent in closely related cases, otherwise similar to TAO and different from ASO and thromboembolism. Thus, our results indicate a heterogeneous group of TAO diseases, suggesting that damage to elastic fibers may be a secondary change to primary inflammation.
Localized pleural malignant mesothelioma
Authors: Hirano Hiroshi , Takeda Shinichi , Sawabata Yoshinori , Okumura Yoshitomo , Maeda Hajime , Hanibuchi Masaki , Ito Masami , Nakagawa Masaru , Uematsu Kunio
Published: September 2003

The occurrence of pleural malignant mesothelioma (MM) is unusual and the cases that appear as a localized tumor are extremely rare. A case of localized pleural MM including immunohistochemical findings is presented. A 70‐year‐old man had an abnormal shadow found during a routine roentgenogram at an annual health checkup and was admitted to Toneyama National Hospital (Toyonaka, Osaka, Japan) for detailed examinations. Chest X‐rays showed a 2 × 5 cm‐sized nodule with relatively smooth margins in the right segment three. Computed tomography (CT) showed an extrapleural mass with a smooth surface and a thickened parietal pleura, and results of a biopsy performed under CT scanning yielded MM. Systematic examinations did not show any metastasis and the patient underwent surgery for removal of the mass. The resected tumor, measuring 3.2 × 3.1 cm, was firm, partially encapsulated, and irregularly shaped. Pathological examinations revealed that it consisted of large polygonal cells, partially showing myxoid patterns, which led to a diagnosis of localized pleural MM. Tumor recurrence was seen, and the duration between initial symptoms and death was 29 months. This case suggests that localized pleural MM has a high proliferative potential and aggressive course, and is considered an early stage of diffuse pleural MM.
Thyroid nodular lesion: Analysis of cancer risk based on Kuma Hospital experience
Authors: Mori Ichiro , Miyauchi Akira , Kuma Seiji , Tang Weihua , Kakudo Kennichi
Published: September 2003

It is a difficult question, whether it is malignant or not, when you follow up patients with thyroid nodular lesions. Cytological examination helps to solve this issue more accurately but a cancer risk still exists in patients with a negative cytology, non‐diagnostic or suspicious follicular neoplasms. Analysis of cancer risk in patients with benign thyroid nodular lesions was carried out among 1044 cases who underwent thyroid surgery at Kuma Hospital, Kobe, Japan, in 2000. The purpose of this study was to provide evidence of cancer risk in those patients in Japan. Among the 356 cases with benign nodular lesions, 99 cases of papillary carcinoma were found in the thyroid parenchyma. Seventy‐nine of the 99 cases were clinical cancer and were found preoperatively by cytology, while 20 out of 277 (7.22%) cases were found postoperatively as incidental carcinoma. The incidence of follicular carcinoma of a minimally invasive type in the index nodule was 22 out of 279 (7.89%) cases in patients who were surgically treated.
Amylin in pancreatic islets and pancreatic endocrine neoplasms
Authors: Tomita Tatsuo
Published: September 2003

Amylin is a chief constituent of the amyloid present in insulinomas, and is colocalized in beta islet cells. By immunocytochemical staining, all four islet cells including insulin, glucagon, somatostatin (SRIF) and pancreatic polypeptide (PP) cells were positively stained for amylin. The strongly insulin‐positive cells corresponded with the strongly amylin‐positive cells, and glucagon cells appeared to be strongly positive for amylin, whereas SRIF and PP cells were weakly positive for amylin. Among 37 cases of pancreatic endocrine neoplasms, insulinomas were more stronger stained for amylin than other islet cell tumors; however, amylin staining was the same or weaker than insulin staining. Glucagonomas and PP‐omas were weakly positive for amylin, whereas six of 11 gastrinomas were weakly positive for amylin. It is concluded that three orthoendocrine tumors including insulinomas, glucagonomas and PP‐omas were all positive for amylin, whereas ectopic hormone secreting gastrinomas were positive for amylin in six of 11 cases (55%). This colocalization of amylin with insulin, glucagon and PP may support a structure–function relationship of amylin and pancreatic hormones. The lesser immunoreactive amylin in pancreatic endocrine neoplasms than in normal islet cells may contribute to autonomous hypersecretion of hormones by pancreatic endocrine neoplasms.
Prevalence, Clinical Correlates, and Treatment of Migraine in Bipolar Disorder
Authors: Low Nancy C. P. , Du Fort Guillaume Galbaud , Cervantes Pablo
Published: September 2003

Objective.—To investigate the prevalence, clinical correlates, and treatment of migraine in bipolar disorder.

Background.—The relationship between migraine and mood disorders has been of long‐standing interest to researchers and clinicians. Although a strong association has been demonstrated consistently for migraine and major depression, there has been less systematic research on the links between migraine and bipolar disorder.

Methods.—A migraine questionnaire (based on International Headache Society criteria) was administered to 108 outpatients with bipolar disorder. Information on the clinical course of bipolar illness was also collected.

Results.—The overall lifetime prevalence of migraine was 39.8% (43.8% among women and 31.4% among men). In the subgroup of patients with bipolar II disorder, the lifetime prevalence of migraine was 64.7%. The bipolar with migraine group was younger, tended to be more educated, was more likely to be employed or studying, and had fewer psychiatric hospitalizations. Their initial presentation for psychiatric treatment was more often for symptoms of depression, rather than hypomania or mania. They were more likely to have a family history of migraine and psychiatric disorders, and a greater number of affected relatives. They were less likely to use mood stabilizers, and more likely to use atypical antidepressants. Migraine was assessed by a neurologist in only 16% of affected patients. The prevalence of the use of specific antimigraine medications (triptans) was 27.9%.

Conclusions.—This study confirms the higher prevalence of migraine among those with bipolar disorder compared to the general population. Migraine in patients with bipolar disorder is underdiagnosed and undertreated. Bipolar disorder with migraine is associated with differences in the clinical course of bipolar disorder, and may represent a subtype of bipolar disorder.
Factors Associated With Migraine‐Related Quality of Life and Disability in Adolescents: A Preliminary Investigation
Authors: Tkachuk Gregg A. , Cottrell Constance K. , Gibson Jessica S. , O'Donnell Francis J. , Holroyd Kenneth A.
Published: September 2003

Objectives.—This study examined factors associated with impaired quality of life and functioning in a sample of treatment‐seeking adolescent migraineurs.

Subjects.—The 37 participants were 51.4% female, and averaged 14.3 years of age and 4.1 migraines per month for the previous 36 months.

Procedure.—The Migraine‐Specific Quality of Life Questionnaire, questionnaire items inquiring about missed activities, and headache diary recordings of missed and impaired activity time served as dependent measures. Variables studied were age; gender; migraine frequency, duration, and severity; presence of nausea, photophobia, or phonophobia; and number of visits to an emergency department in the previous year.

Results.—Three hierarchical forward regressions and one logistic regression, controlling for age and gender, revealed that the presence of nausea and at least one emergency department visit predicted poorer quality of life and a greater number of missed activities in these adolescent migraineurs. The presence of migraine‐related missed activity hours from headache diaries was predicted by being male, having higher combined photophobia and phonophobia sensitivity scores, as well as more frequent and severe migraines. Greater impairment was predicted by having longer average duration attacks.

Conclusions.—These preliminary findings suggest that the continued development of effective treatment approaches to alleviate pain, suffering, and disability in adolescent migraineurs is required. In particular, evidence for the impact of nausea and sensitivities suggests that they may be important targets for treatment. As well, adolescent migraineurs with a history of a visit to an emergency department in the previous year likely experience greater individual and family distress, more disability, and poorer quality of life that require thoughtful, comprehensive treatment to prevent the development of more severe headache difficulties.
Cervicogenic Headache: Locus of Control and Success of Treatment
Authors: Stanton W. R. , Jull G. A.
Published: September 2003

Background.—A number of extraneous factors have been implicated in the effectiveness of treatment of headache, including patient beliefs about aspects of the treatment or persons delivering the treatment.

Objective.—The concept of external locus of control for headaches refers to patients with a high level of belief that headache and relief are influenced primarily by health care professionals. The aim of this study was to examine whether external locus of control is associated with a reduction in frequency of cervicogenic headaches among patients treated by a physiotherapist.

Design.—A recent randomized controlled trial of the effectiveness of physiotherapy among 200 patients with headache enabled a test of this relationship. Treatment consisted of manipulative therapy, therapeutic exercise, or a combination of the 2. Analysis of relative change in headache frequency was conducted after 6 weeks of treatment and at 3‐ and 12‐month follow‐up appointments.

Results.—Results of the analysis indicated that participants with relatively high external Headache‐Specific Locus of Control scores were more likely to achieve a reduction in headache frequency if they received the combined manipulative therapy and exercise therapy, compared with those who received no treatment. This was not determined for the group who received manipulative therapy, which is a treatment received passively by the patient.

Conclusions.—The interpretation of these findings is considered in the context of nongeneralization to the other physiotherapy treatment groups and sustained reduction in headache frequency following withdrawal of treatment. The pattern of findings suggests that characteristics of the therapy were more pertinent than characteristics of the therapist.
Tolerability and Safety of Eletriptan in the Treatment of Migraine: A Comprehensive Review
Authors: Mathew Ninan T. , Hettiarachchi Jayasena , Alderman Jeffrey
Published: September 2003

Objective.—To provide a comprehensive review of the tolerability and safety of eletriptan.

Background.—Eletriptan is a potent and selective 5‐HT1B/1D agonist that has demonstrated significant efficacy in the acute treatment of migraine in doses of 20 mg, 40 mg, and 80 mg.

Design.—This review reports the tolerability and safety of eletriptan across a broad spectrum of preclinical studies and clinical trials that collectively included treatment of more than 11 000 subjects and more than 74 000 migraine attacks.

Results.—In clinical trials, eletriptan was well tolerated and safe across its dosing range of 20 mg to 80 mg. The adverse event profile of eletriptan 20 mg was similar to placebo, while the most commonly used dose, eletriptan 40 mg, has an adverse event profile that is only marginally higher than placebo. Eletriptan was safe and well tolerated regardless of age or gender, and for both short‐ and long‐term treatment. Eletriptan is metabolized primarily by the CYP3A4 enzyme. Coadministration of potent CYP3A4 inhibitors was not associated with clinically meaningful change in eletriptan tolerability or safety in the population included in these clinical trials. The margin of cardiovascular safety for eletriptan was also confirmed by a well‐controlled clinical study in which intravenous eletriptan in excess of an 80‐mg dose was rapidly infused in patients undergoing coronary angiography; nonetheless, it is recommended that eletriptan not be coadministered with a limited list of 7 potent CYP3A4 inhibitors; in addition, the triptan class in general (including eletriptan) is contraindicated in patients with symptoms or findings consistent with ischemic heart disease or other significant underlying cardiovascular disease.

Conclusions.—This comprehensive review found that eletriptan is safe and well tolerated, and that relatively large changes in dose and plasma concentration result in minimal changes in tolerability.