Noninvasive assessment of liver fibrosis via spleen stiffness measurement using acoustic radiation force impulse sonoelastography in patients with chronic hepatitis B or C.

Portal hypertension and splenomegaly are common in patients with cirrhosis. However, there is limited previous in vivo research on the correlation between spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating characteristic curves estimated the diagnostic performance of SSM, with multiple linear regression models for LSM and SSM determining the significance of explanatory factors. Results indicated significant correlation between LSM and SSM (R(2) = 0.574, P < 0.0001). Using SSM to classify METAVIR fibrosis (METAVIR F) scores, the areas under curves were 0.839 (95% CI: 0.780-0.898) for METAVIR F1 vs F2-4, 0.936 (95% CI: 0.898-0.975) for F1-2 vs F3-4 and 0.932 (95% CI: 0.893-0.971) for F1-3 vs F4, all P < 0.001. Multiple linear regression models identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine aminotransferase, international normalized ratio of prothrombin time, sodium and platelet count as significant independent explanatory factors for liver stiffness (adjusted R(2) = 0.724, P < 0.001). Male gender, liver stiffness, METAVIR F2, F3 and F4 also significantly and independently explained spleen stiffness (adjusted R(2) = 0.647, P < 0.001). ARFI SSM is potentially useful as a single or adjunct predictor of stages of liver fibrosis.

Expression profile of metastasis-related genes in invasive oral cancers.

We used suppression subtractive hybridization (SSH) and oligonucleotide microarray to differentiate expression profiles of metastasis-related genes and to evaluate their clinical significance in patients with invasive oral cancer (OCa). Overexpression of the specific genes was confirmed by reverse transcription-PCR (RT-PCR). Cells expressing the gene were identified by immunohistochemistry in pathology specimens. Clinical correlation and significance were analyzed statistically. Using these methods, we detected increased expressions of MMP-1, -3, -7, -9, -10 and interleukin (IL)-8 in invasive OCa. Moreover, our data showed that overexpressions of MMP-1, -3, -7, -10 and IL-8 were associated with reduced survival.

Expression of short-form oncostatin M receptor as a decoy receptor in lung adenocarcinomas.

Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines, and binds to the OSM receptor (OSMR) to inhibit cancer growth. Four forms of OSMR have been identified: leukemia inhibitory factor receptor (LIFR), OSMR beta, short-form OSMR (OSMRs) and soluble OSMR (sOSMR). In this study, we examined the type and expression of OSMR in lung adenocarcinomas (LADCs). Expression of OSMR was determined by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy (CIM). Our results showed that, among the four forms of OSMR, OSMRs was mainly expressed in LADC, and expression level of OSMRs correlated with patient survival. CIM revealed that OSMRs was localized on the cell membrane of LADC cell lines in vitro. OSMRs acts as a decoy receptor by reducing the inhibitory effect of OSM on cell growth. Decrease in OSMRs expression by siRNA increased cell sensitivity to OSM, and ectopic expression of OSMRs reduced cell sensitivity to OSM. These results suggest that expression of OSMRs, which operates as a decoy receptor for OSM, is correlated with disease progression and adverse prognosis in patients with LADC.

Cortactin overexpression in the esophageal squamous cell carcinoma and its involvement in the carcinogenesis.

The aim of this study is to examine whether dysregulated expression of cortactin occurs in esophageal squamous cell carcinoma (ESCC) and is involved in the development of ESCCs. An immunohistochemistry study for cortactin expression was performed on 46 pairs of surgically resected non-tumor and ESCC tumor tissues and murine tumors of esophagi induced by a carcinogen. The results show increased cortactin expression in 20 and in 22 to a lesser extent, out of a total 46 ESCC tumor tissues. Increased cortactin was also detected in the premalignant lesions, the early stage dysplasia and carcinoma in situ, of ESCC tumor tissues. Differential polymerase chain reaction results showed slight increases in the EMS1 gene only in two of 10 ESCC tumor tissues, suggesting that EMS1 gene amplification is not the only mechanism for cortactin overexpression. In the mouse model induced by treatment with 4-nitroquinoline 1-oxide and arecoline, increased cortactin was detected in the epithelia with hyperkeratosis, papillomas, and ESCCs with invasion into the submucosa, respectively. Overall, we observed cortactin overexpression in early and late stages of human ESCCs and carcinogen-induced murine ESCCs, suggesting a role for cortactin in esophageal carcinogenesis.

Eosinophilic granuloma with acute epidural hematoma: a case report.

The most common symptoms of eosinophilic granuloma are local tenderness and an enlarged skull mass. The presence of epidural hematoma is a very rare symptom of eosinophilic granuloma. To our knowledge, this is only the second reported case of eosinophilic granuloma with epidural hematoma. A 2-year-old boy with a soft tumor on the occipital scalp, palpable at the age of 3 months, yet with no obvious history of trauma, was admitted due to a sudden onset of loss of consciousness. A brain computed tomography scan showed a lytic lesion on the occipital skull with a large epidural and subcutaneous hematoma, causing brain compression. He underwent an emergency craniectomy with removal of both the tumor and hematoma. The patient regained consciousness and had no residual neurological damage. Pathological reports showed abnormal proliferation of Langerhans' cells, eosinophilic cells and multinucleated cells. A whole-body bone nuclide scan revealed no other bone lesions. The patient was discharged uneventfully. The causes of hematomas are not very clear. They may be due to tumor necrosis or minor trauma. In our presented case, the cause of the epidural hematoma may have been tumor bleeding which ruptured into the epidural space. A solitary eosinophilic granuloma of the skull with acute epidural hematoma and loss of consciousness is extremely uncommon. Craniectomy with removal of the tumor and hematoma decompression may produce good results.

Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach.

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori-independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti-H pylori therapy in stage I(E) high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I(E) gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (+/- endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pylori dependence in early-stage MALT lymphomas of the stomach.

T cell lymphoproliferative disorder following bone marrow transplantation for severe aplastic anemia.

Post-transplant lymphoproliferative disorder (PTLD) is uncommonly of T cell origin, especially following BMT. We describe a 13-year-old boy with severe aplastic anemia (SAA) and no evidence of Fanconi's anemia who underwent BMT at 11 years of age using CY 10 mg/kg once daily i.v. on days -5, -4, antilymphocyte globulin (ALG) 30 mg/kg once daily i.v. on days -5 approximately -3 and CsA from day -1 as conditioning. The BMT failed and he received a further peripheral blood stem cell transplant (PBSCT) 240 days after BMT. Conditioning was with CY 50 mg/kg once daily i.v. on days -5 approximately -2, and ALG 15 mg/kg once daily i.v. on days -4 approximately -2. GVHD prophylaxis included CsA and MTX. Engraftment was later confirmed by cytogenetic studies. Desquamation and ulcers of the oral mucosa and mouth angle developed in the 13th month post PBSCT. A buccal mucosa biopsy on day +524 revealed only plasmacytosis. Immunosuppressants were discontinued at that point. Generalized lymphadenopathy, prolonged fever (waxing and waning) and facial swelling developed in the 18th month post PBSCT. A neck lymph node biopsy on day +601 showed T cell lymphoma of diffuse large cell type with monoclonal TCR gamma-chain gene rearrangement. A FISH study showed that the malignant T cells were of recipient origin. EBV in situ hybridization was negative. He did not receive further treatment apart from discontinuation of immunosuppressants. He was followed up in our out-patient clinic and showed good performance 1170 days post PBSCT. We speculate that a different mechanism was operating in the pathogenesis of T cell lymphoma in this case. Risk factors include SAA and two transplants, conditioned with CY and ALG, long term use of CsA and treatment with azathioprine.

Chemotherapy alone versus surgery followed by chemotherapy for stage I/IIE large-cell lymphoma of the stomach.

The optimal treatment of localized large-cell lymphoma of the stomach remains controversial. In particular, the role of surgical resection of the primary tumor needs to be clearly defined. We have reviewed all patients with a diagnosis of gastric lymphoma and treated in our institutions between 1988 and 1998. Patients fulfilling the following criteria were included in this study: (1) histologically proven large-cell lymphoma of the stomach; (2) adequate pathological materials and complete clinical information for analysis; (3) clinical stage I/II disease according to the Musshoff modification of Ann Arbor system; and (4) received primary chemotherapy alone with anthracycline- or anthracenedione-containing regimens (group A) or curative surgery followed by adjuvant chemotherapy (group B). There were 38 and 21 patients in group A and group B, respectively. All pertinent clinicopathologic features were similar between the two groups of patients, except that patients of group A had significantly more stage II-2 disease (P = 0.004). Of group A, among 36 patients who could be evaluated for response to chemotherapy, there were 29 complete and 1 partial responses, with an overall response rate of 83.3% (95% CI, 71.1-95.5%). The projected 5-year relapse-free survival (RFS) and overall survival (OS) were 86.0% (95% CI, 73.3-98.7%) and 72.6% (95% CI, 57.0-88.2%), respectively. On the other hand, the projected 5-year RFS and OS of group B were 77.9% (95% CI, 58.0-97.8%) and 77.8% (95% CI, 57.9-97. 7%), respectively, not significantly different from that of group A. Our data suggest that systemic chemotherapy alone may be a reasonable alternative treatment for stage I/II large-cell lymphoma of the stomach. Resection of the primary tumor before systemic chemotherapy does not appear to improve the cure rate of this group of patients.

T-cell malignant lymphoma with conjunctival involvement.

PURPOSE: To report a rare case of T-cell malignant lymphoma involving the conjunctiva. METHODS: A 63-year-old woman had rapid onset of bilateral perilimbal congestion and chemosis. Perilimbal thickening with corneal infiltration developed 20 days later. Computed tomography incidentally disclosed a right maxillary sinus mass. Biopsy specimens from the maxillary sinus mass and the left limbus were subjected to histopathologic examination and immunohistochemical study. RESULTS: T-cell malignant lymphoma of diffuse large cell type, stage IV, was diagnosed. The patient was treated with combination chemotherapy plus 13-cis-retinoic acid and remained in remission 1 1/2 years after diagnosis. CONCLUSION: Conjunctival involvement with T-cell lymphoma may present as episcleritis and chemosis.

Radiographic and computed tomographic findings of gastric mucosa-associated lymphoid tissue lymphomas.

The purpose of this retrospective study was to evaluate the detection of gastric mucosa-associated lymphoid tissue (MALT) lymphoma lesions by upper gastrointestinal (UGI) radiography and computed tomography (CT). Fifteen patients with endoscopic biopsy-proven MALT lymphoma were included. Fourteen of these patients underwent double-contrast UGI radiography and 14 were examined with CT of the upper abdomen; 13 underwent both procedures. UGI radiography identified 88% (30/34) of lesions detected by endoscopy, including 12 of 13 enlarged rugal folds and 15 of the 17 multinodular lesions, but failed to identify two of the three ulcerative lesions. UGI radiography identified the only submucosal lesion demonstrated by endoscopy, as well as one at the gastric antrum that had been missed by endoscopy. CT demonstrated nine of 30 endoscopically proven MALT lymphoma lesions, three with focal thickening of the gastric wall and six with a lobulated inner gastric wall. CT failed to demonstrate two fundal and 19 antral or gastric body lesions. Our findings suggest that the predominant UGI features of gastric MALT lymphoma are enlarged folds and multinodular lesions. Although UGI radiography does not reveal all MALT lymphoma lesions, it may find lesions that are not detected by endoscopy. Mucosal lesions of gastric MALT lymphoma are usually not detected by CT.

Clonal disease of natural killer large granular lymphocytes in Taiwan.

Lymphoproliferative diseases of large granular lymphocytes (LDGL) may arise from either CD3+ T cells or CD3- natural killer (NK) cells. LDGL with clonal proliferation of large granular lymphocytes (LGL) is defined as LGL leukaemia. The number of patients with NK-LGL leukaemia reported is limited and the pathogenesis of the disease is not yet clear. From 1991 to 1998 six patients with cytogenetically proved clonal disease of NK-LGL were identified in our institute. All were seropositive for Epstein-Barr virus (EBV). EBV RNA or DNA could be detected in LGL from four patients by EBV in situ hybridization or Southern blot analysis. Most patients ran an aggressive clinical course and five died of the disease. Nonrandom clonal chromosomal abnormalities, including duplication of 1q, rearrangement at 3q and loss of chromosomes Y, 13 or 10, were noted in the six patients from this study and in eight from the literature. The implications of these recurrent cytogenetic aberrations in the development and progression of the disease deserve further studies.

Angioimmunoblastic lymphadenopathy with dysproteinemia--lack of a prognostic value of clear cell morphology.

It has been suggested that angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is closely related to peripheral T cell lymphoma (PTCL). However, the clinical course of AILD-like PTCL is notoriously unpredictable. A minor portion of patients enjoyed prolonged remission with steroid-only treatments (indolent AILD) while most others died rapidly despite the use of intensive chemotherapy (aggressive AILD). Recently, it has been suggested that histological features such as the presence or absence of clear cells and convoluted cells are of high prognostic value. The validity of this observation was addressed in this study. Eighteen patients who presented between 1977 and 1994 at the National Taiwan University Hospital were retrospectively studied. There were 11 men and 7 women, with a median age of 47 years. Twelve patients had received various regimens of systemic chemotherapy, and the other 3 patients had been treated with steroids alone. Eight patients had indolent AILD and 6 aggressive AILD. The follow-up period in 4 patients was too short to be analyzed. The histopathology of these cases was divided, according to the criteria of Aozasa et al., into group I (neither cells), 4 patients; group II (only convoluted cells), 1 patient, and group III (clear cells with or without convoluted cells), 13 patients. Contrary to others, our data revealed that group III patients were doing better than group I patients. Univariate analysis of other pertinent clinical features, including sex, age, lymphadenopathy, B symptoms, hepatosplenomegaly, hypergammaglobulinemia, elevated serum lactate dehydrogenase, and treatment regimens, revealed none of them to be prognostically relevant. However, patients who had achieved complete remission by steroids or other systemic chemotherapy had a significantly better prognosis than those who had not. Together, these preliminary data suggested that (1) the presence or absence of clear cells and convoluted cells failed to predict the clinical behavior, and (2) induction of complete remission by steroids or other chemotherapeutic agents is an important prognostic index.

Endobronchial lesions in a non-AIDS patient with disseminated Mycobacterium avium-intracellulare infection.

A 34 year old female developed Mycobacterium avium-intracellulare infection with generalized lymphadenopathy, hepatosplenomegaly, pulmonary infiltration, pleural effusion and endobronchial polypoid lesions. M. avium-intracellulare was identified by means of sputum cultures, pleural effusion culture and lymph node culture. The anti-human immunodeficiency virus (HIV) antibody was negative. The CD4+ cell count was normal. Bronchoscopic examination revealed multiple polypoid lesions, which had nearly occluded the right main bronchus, right middle lobe and left lower lobe bronchi. Neodymium yttrium aluminium garnet (Nd-YAG) laser and antimycobacterial therapy were used effectively to relieve the airway obstruction. The clinical symptoms and signs responded favourably to antimycobacterial therapy.

Ultrasonographic examination of the posterior tibial tendon.

The posterior tibial tendons (PTTs) of 16 patients with PTT dysfunction and 10 age-matched healthy subjects were examined ultrasonographically, using a 10-MHz linear-array transducer. Normal PTTs appeared hyperechoic (more echogenic) and oval, with an average diameter of 7.8 mm x 3.7 mm at the medial malleolar level. Degenerated PTTs appeared hypoechoic (less echogenic) and swollen (9.8 mm x 5.0 mm). Peritendinitis presented as a hypoechoic rim on the longitudinal sonogram (along the long axis of the tendon) and a "target sign" (hyperechoic central structure with a hypoechoic halo) on the transverse sonogram (at the right angle to the long axis of the tendon). Complete rupture of the PTT revealed an empty tibial groove at the level of the medial malleolus on the transverse sonogram and a wavy fibril pattern over the distal end on the longitudinal sonogram. Compared with the operative findings or the results of the magnetic resonance imaging, ultrasonography was sensitive and specific in diagnosing tenosynovitis and complete rupture of the PTT.

Churg-Strauss syndrome presented as multiple intracerebral hemorrhage.

Intracerebral hemorrhage is an uncommon sequel of Churg-Strauss syndrome. We describe a 27 y old Taiwanese male patient who was clinicopathologically diagnosed as Churg-Strauss syndrome. The patient experienced a sudden onset of blurring of vision and slowness of motion and speech. Magnetic resonance imaging of the brain revealed lobar hemorrhage on right parieto-occipital and left parietal areas. The cause of cerebral hemorrhage was probably due to poorly controlled high blood pressure and vasculitis. He received pulse therapy of methylprednisolone and cyclophosphamide followed by oral prednisolone. His neurological symptoms responded well to such a regimen. Cerebral hemorrhage is a major cause of morbidity and death in patients with Churg-Strauss syndrome. Uncontrolled high blood pressure may cause cerebral hemorrhage. Careful monitor of blood pressure is critical for the management of Churg-Strauss syndrome patients.

Glutathione-S-transferase induces murine dermatitis that resembles human atopic dermatitis.

BACKGROUND: The molecular and functional basis of allergen-induced inflammation seen in atopic dermatitis (AD) remains undefined. OBJECTIVE: The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD. METHODS: An inbred strain of mice, BALB/c, when injected peritoneally with 30 micrograms of recombinant Sj26 protein (rSj26), a glutathione-S-transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by serum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen-specific late phase response. RESULTS: Significant responses of rSj26-specific IgE were detected 2 weeks after immunization, and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26-specific positive skin test and epicutaneous patch test could be demonstrated in rSj26-sensitized mice. CONCLUSIONS: These results suggest that rSj26 is capable of eliciting atopic dermatitis-like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen-induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue: clinicopathologic analysis of 19 cases.

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue type (MALToma) is a recently recognized disease entity. We report the clinicopathologic features of 19 patients with MALToma in Taiwan. The 19 patients included eight men and 11 women, ranging in age from 26 to 77 years, with a mean age of 58.8 years. Most complained of abdominal pain or gastrointestinal bleeding. The endoscopic and gross features of the gastric lesions revealed erosion (flat type), ulceration (depressed type), cobblestone appearance or abnormal gastric folds (elevated type), mimicking chronic gastritis, ulcer or early gastric carcinoma. Typical histopathologic features included lymphoepithelial lesion and extensive mucosal infiltration of centrocyte-like cells in all cases. Clonality analysis of the variable-diversity-joining region of the immunoglobulin gene by semi-nested polymerase chain reaction demonstrated monoclonality in 72% of the cases. Helicobacter pylori bacilli (H. pylori) could be identified on histologic sections in 15 cases (78.9%); the serologic test for H. pylori was positive in 12 of 13 patients tested (92%). In six patients receiving triple therapy (amoxicillin, bismuth subcitrate and metronidazole), five showed significant histologic regression with eradication of H. pylori 4 to 6 months after the start of treatment; one patient showed persistent lesions and presence of H. pylori. However, persistence of residual lymphoid cells and monoclonality of the immunoglobulin gene, could still be demonstrated in four cases. Of nine patients treated with surgery or chemotherapy, two died: one due to concomitant gastric carcinoma and the other one due to sudden apnea. No recurrence was observed in the remaining seven patients. The remaining four patients were lost to follow-up. Our experience confirmed that gastric MALToma is a low-grade neoplastic process. The dramatic response of gastric MALToma to anti-H. pylori treatment suggests that H. pylori infection is closely related to the pathogenesis of low-grade gastric MALToma. However, long-term follow-up is mandatory due to the persistence of the monoclonality of the immunoglobulin gene in the residual lymphoid cells after treatment.