Demographic and serological characteristics of Asian Americans with hepatitis B infection diagnosed at community screenings.

There is limited information regarding follow-up and hepatitis B serological status of Asian Americans diagnosed with chronic hepatitis B (CHB) through community screening. The aims of this study were to evaluate the prevalence and characterize CHB among Asians living in Los Angeles, assess follow-up of individuals with CHB diagnosed at screening and compare with patients with CHB followed by community gastroenterologists. Between October 2007 and May 2010, 7387 Asians were tested for HBV. HBsAg positive individuals (CHB) underwent additional testing for ALT, HBeAg/anti-HBe and HBV DNA. Patients with CHB were contacted 6 months later to determine whether they received follow-up care. We compared serological patterns of these individuals with CHB to patients with CHB who were seen for the first time (treatment naïve) by community gastroenterologists during the study period. Prevalence of CHB was 5.2%. About 99% patients with CHB were foreign-born, and only 27% could read/write English. 297 (77%) patients with CHB could be reached 6 months after diagnosis; 43% did not receive follow-up care, mostly because of lack of medical insurance. Patients with CHB followed by gastroenterologists were more likely to have insurance (69% vs 26%, P < 0.0001). 90% patients with CHB at screening were HBeAg negative/anti-HBe positive with 62% having inactive disease compared to only 30% of patients seen by gastroenterologists (P < 0.0001). Among CHB participants, 13% met criteria for treatment compared to 51% of patients with CHB (P < 0.0001). Only a small number of CHB screening participants require antiviral therapy. Lack of medical insurance is the main reason for most patients with CHB not seeking follow-up care after screening.

Abnormal distribution of O-alkyl groups in the neutral glycerolipids from human hepatocellular carcinomas.

The direct comparison of O-alkylglycerol composition in the neutral lipids fractions prepared from human hepatocellular carcinomas with that in corresponding preparations from nonneoplastic liver is reported. Tumor-bearing liver and noncancerous liver specimens were obtained either during surgery or at autopsy. Thirty different tissue specimens obtained from 18 cases were analyzed. Representative samples from each specimen were examined microscopically to confirm the pathological diagnosis. Gas chromatographic analysis of alkylglycerol derivatives showed that hexadecylglycerol, octadecylglycerol, and octadecenylglycerol were the principal components. Compared to the noncancerous liver, hepatocellular carcinomas contained higher proportions of hexadecylglycerol and lower proportions of both C18-glyceryl ethers. Associated with this change was an increase in the proportion of saturated to monoenic alkylglycerols. These abnormalities appeared to be more severe in the necrotic areas of the tumors. Higher concentrations of neutral alkyl glycerolipids and of cholesterol were found in the tumors; no differences between the two groups could be found in the levels of ether-linked phosphoglycerides, triglycerides, and lipid phosphorus.

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer.

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Treatment outcome and prognostic factors for primary nasal lymphoma.

PURPOSE: To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS: From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS: Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION: Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.

Acute intravascular hemolysis indicating thrombosis of Bjork-Shiley aortic prosthesis.

A patient with a Bjork-Shiley aortic prosthesis inserted two years and four months prior to receiving adequate anticoagulant therapy suddenly had severe intravascular hemolysis develop as a result of thrombosis of her aortic prosthesis. There was no notable hemodynamic compromise. The mechanism of the intravascular hemolysis is discussed.

Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells.

Tumors of the follicular dendritic cell are uncommon, and most occur as primary lymph node tumors. We report a case of primary follicular dendritic cell tumor of the liver that was initially reported as an inflammatory pseudotumor. The neoplasm recurred as two separate tumor masses 30 months after complete resection of the "hepatic inflammatory pseudotumor." It showed a wide spectrum of morphologic features ranging from areas with fascicles of very bland spindle cells amidst a background population of lymphocytes, reminiscent of inflammatory pseudotumor, to areas of dispersed sheets of highly pleomorphic tumor cells with a relative paucity of reactive inflammatory cells. The diagnosis was confirmed by positive immunohistochemical staining with CD21, CD35, R4/23, and Ki-M4 and by ultrastructural demonstration of convoluted interdigitating cell processes joined by desmosomes. The background lymphocytes were oligoclonal, CD8-positive T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in the tumor cells in the original and recurrent tumors. More importantly, the cells showed identical episomal clonal EBV on Southern blot analysis, implying that the initial and recurrent tumors are due to clonal proliferation of EBV-positive neoplastic follicular dendritic cells. The tumor cells expressed latent membrane protein but not EBV-encoded nuclear antigen 2 (EBNA2) or ZEBRA. Such gene expression is very similar to that of Hodgkin's disease and nasopharyngeal carcinoma. The strong expression of latent membrane protein restricted to the tumor cells and the clonality of the EBV suggest that the virus may be involved in the pathogenesis of this tumor and not present merely as a "bystander."

Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology.

A workshop jointly sponsored by the University of Hong Kong and the Society for Hematopathology explored the definition, differential diagnosis, and epidemiology of angiocentric lymphomas presenting in the nose and other extranodal sites. The participants concluded that nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity highly associated with Epstein-Barr virus (EBV). In situ hybridization for EBV an be very valuable in early diagnosis, especially if tissue is sparse. The cytologic spectrum is broad, ranging from small or medium-sized cells to large transformed cells. Histologic progression often occurs with time. Necrosis is nearly always present, and angioinvasion by tumor cells is seen in most cases. Nasal T/NK cell lymphoma has a characteristic immunophenotype: CD2-positive, CD56-positive, but usually negative for surface CD3. Cytoplasmic CD3 can be detected in paraffin sections. Clonal T-cell receptor gene rearrangement is not found. Tumors with an identical phenotype and genotype occur in other extranodal sites, most commonly in the skin, subcutis, and gastrointestinal tract, and should be referred to as nasal-type T/NK cell lymphomas. The differential diagnosis includes lymphomatoid granulomatosis, blastic or monomorphic NK cell lymphoma/leukemia, CD56-positive peripheral T-cell lymphoma, and enteropathy-associated T-cell lymphoma.

Differences in T-cell-receptor gene rearrangement and transcription in nasal lymphomas of natural killer and T-cell types: implications on cellular origin.

Although nasal lymphomas showing midfacial destructive lesions had been classified as T-cell lymphomas, their exact cellular origin is still unclear. Although they usually express a restricted number of T-cell-related antigens, namely, CD2, CD43, and CD45RO, other pan-T or subset-T-lineage antigens, such as CD3 (membrane), CD5, CD4, CD8, and CD7, are frequently absent. Conversely, they often express a natural killer (NK) cell-associated antigen, CD56, but lack other mature NK markets. To study their cellular origin further, the authors analyzed T-cell receptor (TCR) gene transcription in three cases of nasal lymphomas and correlated the findings with the phenotype and gene rearrangement data. Two cases of nasal lymphomas with CD2+CD3(Leu4)-CD19-CD56+ phenotype were shown to express truncated 1.0-kb Tbeta and multiple unrearranged Tdelta transcripts with germline TCR beta, gamma, delta, and immunoglobulin heavy-chain joining region (JH) genes, consistent with NK cell lineage. In contrast, one case of nasal lymphoma with CD2+CD3(Leu4)+CD8+CD19-CD56+ phenotype expressed full-length Talpha, Tbeta, and Tgamma transcripts rearranged TCR beta, gamma, and deleted TCR delta genes, indicating T-lineage, These results support the view that nasal lymphomas can separated into NK-cell and T-cell neoplasms, based on differences genotypic characteristics. The possibility of these tumors being derived from a putative common precursor cell merits further investigation.

Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases.

Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions.

An unusual lethal complication associated with Starr-Edwards prosthetic aortic valve holder.

This is the first report of an unusual fatal complication associated with the Starr-Edwards prosthetic aortic valve holder. The patient died 51 days after replacement of his aortic valve with a Starr-Edwards prosthetic aortic valve. The cause of death was coronary arterial embolus caused by a fragment broken off of the prosthetic aortic valve holder.

Latent sites of Epstein-Barr virus infection.

Epstein-Barr virus (EBV) has been detected in a wide spectrum of tumors. This study investigates the detection rate of EBV-DNA by Southern blot hybridization analysis (SOBH) and polymerase chain reaction (PCR) in different tissues from persons without apparent EBV-related diseases. Of 20 tonsillectomy specimens studied, SOBH indicated positivity for EBV-DNA in 1 case, and PCR indicated positivity in 10. In autopsies performed on patients with no apparent evidence of EBV-related diseases, the viral DNA was only detected by PCR in the following: parotid gland (7/15), submandibular gland (8/20), nasopharynx (8/10), tonsil (8/10), larynx (5/6), lung (5/9), cervical lymph node (7/10), mediastinal lymph node (7/10), abdominal lymph node (4/10), spleen (6/10), thyroid (5/10), liver (1/10), pancreas (1/4), kidney (4/10), uterine cervix (1/4), ovary (1/5) and testis (1/3). These results provide a baseline for interpreting the role of EBV in carcinogenesis.

Detection of trisomy 3 in primary gastric B-cell lymphoma by using chromosome in situ hybridization on paraffin sections.

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.

Lack of correlation between expression of Epstein-Barr virus (EBV) latent membrane protein and bcl-2 oncoprotein in vivo.

AIMS: To evaluate whether there is any correlation between the expression of Epstein-Barr virus (EBV) latent membrane protein (LMP) and oncoprotein bcl-2 in the lymph node biopsy specimens of a Chinese patient with EBV-related reactive lymphoproliferation who later developed T cell lymphoma after a short period of time. METHODS: Immunohistochemistry, with a standard alkaline phosphatase antialkaline phosphatase (APAAP) method and New Fuchsin as a chromogen, was used for single staining of bcl-2 or LMP. Double immunostaining combining APAAP and indirect immunofluorescence was performed for dual labelling of LMP and bcl-2. RESULTS: bcl-2 was expressed in 10-30% of cells in the first lymph node biopsy specimen (EBV-associated lymphoproliferative disorder) and 30-50% of cells in the second lymph node biopsy specimen (T cell lymphoma). LMP was expressed in the first biopsy specimen but not in the second. Double immunostaining results showed that around 78% of LMP positive cells were bcl-2 negative and 94% bcl-2 positive cells were LMP negative. Among the very small fraction of LMP and bcl-2 double positive cells, the intensity of bcl-2 staining was heterogeneous and was not always stronger than that observed in LMP negative bcl-2 positive cells. CONCLUSIONS: The expression of bcl-2 protein is independent of LMP protein status in vivo. Several mechanisms may be involved in EBV associated lymphomagenesis, and bcl-2 induction may occur independently of LMP expression.

Immunohistochemical demonstration of c-erbB-2 oncoprotein in gastric adenocarcinoma: comparison of cryostat and paraffin wax sections and effect of fixation.

AIMS: To investigate the effects of fixation on the immunohistochemical demonstration of c-erbB-2 oncoprotein using paraffin wax and cryostat sections; to compare c-erbB-2 expression in non-neoplastic and neoplastic gastric tissues. METHODS: Adjacent blocks of tumour and non-neoplastic tissue from four gastrectomy specimens were put into a panel of 10 fixatives including acetone, B5, Bouin's fluid, Carnoy's fluid, buffered formalin, formol dichromate, zinc formalin, 4% paraformaldehyde, periodate-lysine-paraformaldehyde (PLP) and periodate-lysine-paraformaldehyde-dichromate (PLPD) before embedding in paraffin wax for sectioning. Similar tissue blocks were snap frozen and cryostat sections were postfixed in these fixatives, either alone or in combination, before immunostaining. RESULTS: In paraffin wax embedded sections the best fixative was PLP, and in frozen tissues the best results were obtained after fixation of cryostat sections in buffered formalin followed by cold methanol and acetone. Applying these fixatives to samples from a further 16 gastrectomy specimens, strong membrane staining of c-erbB-2 protein was found in the tumour in eight of 16 cases (50%) using paraffin wax sections, and staining was stronger in the better differentiated carcinomas. For frozen tissues, positive membrane staining was found in all gastric adenocarcinomas, but differential staining intensity associated with tumour differentiation could not be detected. CONCLUSIONS: These results indicate that fixation and paraffin wax embedding affect the results of immunohistochemical demonstration of c-erbB-2 in gastric cancer. The choice of fixative is critical in the demonstration and evaluation of c-erbB-2 protein expression by immunohistochemistry in gastric carcinomas. Staining results also vary depending on whether frozen or paraffin wax embedded tissues are studied.

Improved double immunohistochemical staining method for cryostat and paraffin wax sections, combining alkaline phosphatase anti-alkaline phosphatase and indirect immunofluorescence.

AIMS: To develop and immunohistochemical staining method for cryostat and paraffin wax sections so that two different antigens in the same section of tissues could be detected by combining immunoenzyme and immunofluorescence techniques. METHODS: This double immunohistochemical staining method combines alkaline phosphatase-anti-alkaline phosphatase (APAAP) using New Fuchsin as a chromogen and indirect immunofluorescence. RESULTS: APAAP staining for one antigen of this double immunohistochemical staining method was observed under bright field conditions alternating with immunofluorescence for another antigen under ultraviolet light. The double exposed photograph of both easily identified the two signals within the same cell. CONCLUSIONS: This double immunohistochemical staining method can overcome the disadvantages of any masking effect of the double immunoenzymatic methods and the background problems of double immunofluorescence method especially when applied to paraffin wax sections. It also permits good morphological identification of the doubly stained cells which may be of crucial importance in studies on pathology specimens.

High incidence of BCL-6 gene rearrangement in diffuse large B-cell lymphoma of primary gastric origin.

The incidence of BCL-6 gene rearrangement was studied in 39 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary site of involvement was nodal in 18 cases and gastric in 21 cases. Clonal BCL-6 gene rearrangement was found in 17% of the patients with primary nodal and 48% with primary gastric lymphoma (p = 0.05). The clinical characteristics and treatment outcome of the 21 patients with primary gastric lymphoma were analyzed according to the BCL-6 status. Significantly more patients in the germline BCL-6 gene group had advanced stage (II, III and IV) of disease. Complete remission rate following primary therapy appeared to be higher for the positive rearrangement group (70% versus 36%), but it was not statistically significant. Those with a rearranged BCL-6 gene also appeared to have better survival at 5 years (58% versus 36%) but the difference was also not statistically significant. On the other hand, patients being classified as low risk according to the International Prognostic Index had significantly better survival at 5 years (89% versus 9%, p = 0.0001). We concluded that BCL-6 gene rearrangement was more commonly found in diffuse large B-cell lymphoma of primary gastric origin than its nodal counterpart and it may be playing a more important role in the pathogenesis of gastric large B-cell lymphoma. There was a trend that the BCL-6 gene rearrangement was associated with a more favorable outcome in patients with gastric large B-cell lymphoma but the difference was not statistically significant.

Intensive chemotherapy for adult lymphoblastic lymphomas.

A total of 20 adults patients presenting with previously untreated lymphoblastic lymphoma underwent an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. If the patients achieved a complete clinical remission (CR) after three courses, they were given intensive consolidation and maintenance chemotherapy based on a protocol that was modified from the L10/L17M regimen of the Memorial Sloan-Kettering group for acute lymphoblastic leukaemia and lymphoblastic lymphoma. Patients exhibiting localised areas of bulky disease were given additional involved-field radiotherapy. In all, 15 (75%) men and 5 (25%) women were entered in this study. Their median age was 28 years (mean, 30 years; range, 12-64 years). Overall, 3 (15%) had stage II disease, 3 (15%) had stage III disease and 14 (70%) had stage IV disease; 7 (35%) patients exhibited B symptoms and 4 (20%) had bulky disease. The overall (CR) rate was 10/20 (20%), and that following BACOP and m-BACOD therapy was 4/8 (50%) and 6/12 (50%), respectively. In all, 7 of the 10 complete responders (70%) relapsed. The disease-free survival of the ten who achieved a CR was 23% at 3 years. The overall survival of all 20 patients at 3 years was only 37%, and there were very few long-term survivors. More effective treatment for adult lymphoblastic lymphoma is required.

Anti-oral microbial activity of isoflavonoids in root bark of Ormosia monosperma.

From the root bark of Ormosia monosperma, 10 isoflavonoids including two new compounds 7,4'-dihydroxy-6",6"-dimethylpyrano-(2",3":5,6)-8-(3-methyl-1,3- butadienyl)isoflavone, named ormosidin, and dalbergion 4'-O-beta-D-glucopyranoside, were isolated. These structures were confirmed by spectroscopic analysis. 2,3-Dihydroauriculatin, one of the compounds isolated, showed moderate activities against oral-microbial organisms (Streptococcus mutans, Prophyromonas gingivalis and Actinomyces actinomycetemcomitans).

Immunohistological subtypes of non-Hodgkin's lymphoma in Hong Kong Chinese.

One hundred and four unselected cases of non-Hodgkin's lymphoma (NHL) in adult Chinese patients in Hong Kong were typed, using monoclonal and conventional antibodies, by immunoenzymatic labelling methods on cryostat sections or cell smears. The total included 69 cases (66%) of B-cell and 26 (25%) of T-cell tumours. The diffuse large cell (centroblastic or immunoblastic) types formed the largest proportion (44.9%) of B lymphomas. Of 26 cases of T-cell lymphoma 25 were of peripheral type; of these 25, the most frequent subtype (42.3%) was the immunoblastic lymphadenopathy-like lesion. Although there were 9 pleomorphic T-cell lymphomas, none of the patients presented with the adult T-cell leukemia/lymphoma syndrome. The incidence of T-cell lymphomas in our population is not markedly higher than that of western countries, but there are some interesting differences in the types of T-cell lymphomas that are commonly seen.

CEA tissue staining in colorectal cancer patients--correlation with plasma CEA, histology and staging.

To study the expression of tissue carcinoembryonic antigen (CEA) by immunoperoxidase staining in colorectal adenocarcinomas and its relation with preoperative serum CEA and clinicopathological parameters, we studied 85 unselected patients who underwent resective surgery for colorectal adenocarcinomas and were followed up for a mean of 66 mths. All tumors except 2 showed positive staining for CEA. The staining pattern was classifiable into 4 types: apical, cytoplasmic, basolateral and stromal, according to the predominant sites of staining. We found a significant positive correlation between tissue CEA staining pattern and preoperative plasma CEA. Plasma CEA levels were higher when tumor cell staining extended to basolateral regions of the cells and into stromal tissues rather than restricted to apical and cytoplasmic regions (p = 0.012). Furthermore, tissue CEA staining also correlated positively with vascular invasion by tumor cells (p = 0.046), with basolateral and stromal types associated with more frequent vascular invasion than apical and cytoplasmic types. This was in contrast to the preoperative CEA which did not correlate with vascular permeation. We speculate that tissue CEA staining is useful in indicating possible vascular invasion even at early stage whereas vascular invasion by a larger tumor bulk or even tumor metastases may be necessary to produce an increased plasma CEA level that is detectable. On the other hand, preoperative plasma CEA had a strong, positive relationship with tumor stage and mortality (p < 0.001 for both). Preoperative CEA was higher in tumors showing moderate and poor differentiation, although it did not reach statistical significance (p = 0.068), whereas tissue CEA staining had no correlation with tumor differention.(ABSTRACT TRUNCATED AT 250 WORDS)