Biomedical subjects

A Chott

Publications and source records attributed to A Chott.

At least 55 records · Page 3Linked to original sources

PubMed2000

Efficacy of standard treatment in patients with Hodgkin's disease--a single center experience.

Sixty-two consecutive patients with newly diagnosed Hodgkin's Disease (HD) were treated at our institution between 1991 and 1998 in accordance with protocols which we considered as optimal standard therapy. In patients with localised disease, extended field irradiation alone was used initially but short duration chemotherapy followed by involved field irradiation was given later. Initially, MOPP/ABV chemotherapy was considered the standard treatment regimen for advanced HD, subsequently it was replaced by ABVD treatment. At 5 years patients with localised HD have a projected overall survival of 95% and a failure-free survival of 72%. Relapses in patients treated with radiotherapy alone (6/16 cases) could be successfully managed with chemotherapy in most cases (5/6). In advanced HD, projected 5-year survival and failure-free survival are 100% and 80%, respectively. No treatment-related deaths or secondary malignancies were registered.

Adolescent↗

PubMed2000

Follicular lymphomas' BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation.

The human t(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between BCL-2 and D(H)/J(H) gene segments during V(D)J recombination in early B cells. De novo nucleotides are found inserted in most breakpoints and have been thus far interpreted as nontemplated N region additions. In this report, we have analyzed both direct (BCL-2/J(H)) and reciprocal (D(H)/BCL-2) breakpoints derived from 40 patients with follicular lymphoma with t(14;18). Surprisingly, we found that more than 30% of the breakpoint junctions contain a novel type of templated nucleotide insertions, consisting of short copies of the surrounding BCL-2, D(H), and J(H) sequences. The features of these templated nucleotides, including multiplicity of copies for 1 template and the occurrence of mismatches in the copies, suggest the presence of a short-patch DNA synthesis, templated and error-prone. In addition, our analysis clearly shows that t(14;18) occurs during a very restricted window of B-cell differentiation and involves 2 distinct mechanisms: V(D)J recombination, mediating the breaks on chromosome 14 during an attempted secondary D(H) to J(H) rearrangement, and an additional unidentified mechanism creating the initial breaks on chromosome 18. Altogether, these data suggest that the t(14;18) translocation is a more complex process than previously thought, involving the interaction and/or subversion of V(D)J recombination with multiple enzymatic machineries.

Base Sequence↗

PubMed2000

Expression of CD94/NKG2A and killer immunoglobulin-like receptors in NK cells and a subset of extranodal cytotoxic T-cell lymphomas.

Thirty-two natural killer (NK) and cytotoxic T-cell lymphomas and 14 noncytotoxic nodal T-cell lymphoma controls were immunostained with the use of monoclonal antibodies reactive against NK-cell receptor (NKR) molecules (CD94, NKG2A, p58.2, p58.1, p140, p70, p50.3). All NK-cell lymphomas (4 nasal/oral and 1 intestinal) expressed at least 1 NKR, the CD94/NKG2A complex. Two were positive for 1 or more killer immunoglobulin-like receptors. Of 15 extranodal cytotoxic T-cell lymphomas, 3 expressed CD94, including 2 intestinal and 1 hepatosplenic gammadelta T-cell lymphomas. In contrast, none of the nodal lymphomas were positive. Detection of NKRs may provide a useful tool to confirm the diagnosis of NK-cell lymphomas and to delineate a subgroup of cytotoxic T-cell lymphomas. Expression of NKRs only in extranodal cytotoxic T-cell lymphomas might reflect differences in the homing capabilities of cytotoxic T cells expressing NKRs in normal individuals and might be influenced in part by localized chronic immune reactions.

Adolescent↗

PubMed2000

Chemotherapy for the treatment of patients with primary high grade gastric B-cell lymphoma of modified Ann Arbor Stages IE and IIE.

BACKGROUND: Surgical intervention and combined modality treatment including radiation and chemotherapy have been studied widely in patients with high grade gastric B-cell lymphoma, whereas to the authors' knowledge the role of chemotherapy alone in patients with localized disease has not been investigated extensively. METHODS: Twenty-five consecutive patients with primary high grade gastric B-cell lymphoma of localized modified Ann Arbor Stages IE and IIE were studied prospectively at the study institution. Patients age < 75 years (n = 17; age range, 41-75 years) were given a standard regimen comprised of doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP), whereas patients age > 75 years (n = 8; age range, 82-93 years) were treated at a reduced dose. Restaging was performed after 3 and 6 cycles, followed by every 3 months for the first 2 years, and every 6 months thereafter. RESULTS: A total of 123 cycles were administered to the study patients, with the median number of 6 cycles per patient (range, 1-9 cycles). At a median follow-up of 24 months (range, 1.5-87+ months), 22 patients were alive without evidence of disease and 3 patients had died (1 patient death was treatment-related). Twenty-four patients who were considered evaluable achieved a complete remission, 21 patients after 3 cycles and the remaining 3 patients after 6 cycles of treatment. Side effects generally were manageable, with only one patient requiring premature discontinuation of treatment due to protracted thrombocytopenia after three courses of therapy, and tolerance was not different between the two age groups. No recurrences were observed at last follow-up. CONCLUSIONS: The authors believe that chemotherapy using the CHOP regimen is highly effective in the treatment of patients with localized primary high grade gastric lymphoma.

Adult↗

PubMed2000

Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease.

In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) can be found in a background of otherwise typical B-CLL. To test these HRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micromanipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in HRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from HRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein-Barr virus (EBV) was detected in the HRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL. There is evidence that HRS-like cells in B-CLL, like HRS cells in HD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the HRS-like cells, and in 1 of the EBV-positive HRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional. We speculate that the HRS-like cells in B-CLL represent potential precursors for HRS cells causing HD.

Aged↗

PubMed2000

Fas ligand is expressed in normal breast epithelial cells and is frequently up-regulated in breast cancer.

Fas (CD95/Apo-1) is a cell membrane receptor that upon binding by its ligand (FasL), triggers a signal resulting in apoptotic cell death. Fas is produced by breast epithelial cells, but its contribution to breast tissue homeostasis is unknown. This study investigated whether FasL is synthesized in the breast. By reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry, FasL expression was analysed in normal and malignant human breast epithelial cell lines, normal breast tissue, benign breast disease (fibrocystic changes, fibroadenoma), and breast cancer (ductal carcinoma in situ; invasive ductal, lobular, mucinous and medullary carcinomas). The results demonstrate expression of FasL by normal breast epithelial cells and show a marked increase of FasL protein in the majority of breast carcinomas, compared with normal breast tissue and benign breast disease. By western blot analysis, soluble FasL was detected in culture supernatants of one of three normal breast epithelial cell lines and in all four breast cancer cell lines tested. The expression of Fas protein was more heterogeneous in benign and malignant breast tissue, with expression levels ranging from weak to strong, but breast cancer cells frequently exhibited a weaker Fas expression than surrounding residual normal breast epithelial cells. In vitro, two out of three normal breast epithelial cell lines were sensitive to cell death induction by an agonistic anti-Fas antibody. Co-treatment with cycloheximide, an inhibitor of protein translation, rendered the resistant cell line sensitive. In contrast, two out of four breast cancer cell lines were resistant to the anti-Fas antibody and this resistance could not be reversed by cycloheximide. These results suggest that increased expression of FasL may confer an advantage on breast cancer cells, possibly by eliminating tumour-infiltrating immune cells, and/or by facilitating tissue destruction during invasion.

Adenocarcinoma↗

PubMed2000

Epstein-Barr virus is present in neoplastic cytotoxic T cells in extranodal, and predominantly in B cells in nodal T non-Hodgkin lymphomas.

Epstein-Barr virus (EBV)-positive T non-Hodgkin lymphomas (T-NHLs) have been described, but it is at present unknown how EBV infects T lymphocytes. It has been postulated that cytotoxic T cells (CTLs) or natural killer (NK) cells can be infected by EBV during the killing of an EBV-infected target cell. The objective of this study was therefore to determine whether the neoplastic cells in EBV-positive T-NHLs (n=221) of various locations have a cytotoxic phenotype. To identify EBV-harbouring cells, combinations were used of EBV-encoded RNA (EBER) in situ hybridization (RISH) and immunohistochemistry for T- and B-cell markers and the cytotoxic proteins TIA-1 and granzyme B. EBV was detected in the neoplastic cells of all nasal T-NHLs (n=9), 5/34 gastrointestinal (GI) T-NHLs, and 2/6 lung T-NHLs, but not in primary cutaneous T-NHLs (n=103). Moreover, EBV was found in the neoplastic cells of 2/48 nodal anaplastic large cell lymphomas (ALCLs), but not in neoplastic T cells of other nodal T-NHLs. However, 5/17 nodal peripheral T-NHLs not otherwise specified (PTCLs NOS) and 1/4 T-prolymphocytic leukaemias did contain EBV-positive non-T cells. Double staining revealed that in EBV-positive extranodal T-NHLs (n=16), the EBER-positive cells had a cytotoxic phenotype (TIA-1- and/or granzyme B-positive). In nodal non-ALCL T-NHLs, the EBER-positive cells were not positive for TIA-1 or granzyme B, nor did they express CD3, CD21 or HECA452. Instead, most of these cells expressed the B-cell marker CD20. These PTCLs NOS with EBER-positive cells showed features of AILD-like T-NHL. It is concluded that neoplastic cells of EBV-positive extranodal T-NHLs always have a cytotoxic phenotype, supporting the view that EBV can infect CTLs. In nodal non-ALCL T-NHL, EBV is only found in T-NHL with AILD-like features and is present in B cells, where it may contribute to the outgrowth of a malignant B-cell clone.

Antigens, CD20↗

PubMed2000

Fludarabine therapy in Waldenström's macroglobulinemia.

Seven patients with macroglobulinemia (six previously untreated, one with minimal pretreatment) were treated with fludarabine (25 mg/m2/day for 5 days, repeated every 4 weeks). The median age was 58 years. The time from diagnosis to treatment with fludarabine was 4.5 months to 175 months (median 32.6 months). The patients received six (n =5), five (n =1), and three (n = 1) courses of fludarabine. One patient showed only a slight decrease of immunoglobulin (Ig) M (from 5,750 mg/dl to 4,700 mg/dl) and no improvement of anemia. Therefore, treatment was stopped after three cycles. In the other six patients, a marked reduction of IgM levels (from 6,140 mg/dl to 1,220 mg/dl median), a normalization of hemoglobin (from 10.8 g/dl to 12.3 g/dl median), a reduction of lymphocyte count (from 1992/>microl to 652/microl median), and a reduction of beta2 microglobulin (from 2.3mg/l to 1.8 mg/l median) were achieved. A 50% IgM reduction was achieved 5.4 months (median) after the beginning of therapy, and the maximum response was observed 17.3 months (median) after the end of treatment. The responses were sustained without further therapy in six patients for 20.8-55.2 months. In one patient, disease progression was observed 12.5 months after the end of therapy. Fludarabine therapy was well tolerated with few side effects. In three patients, febrile episodes occurred. No opportunistic infections were recorded. We conclude that fludarabine is an effective treatment in previously untreated or in minimally pretreated patients with Waldenström's macroglobulinemia.

Adult↗

PubMed2000

Effects of interferon-alpha2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis.

Interferon (IFN)-alpha, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-alpha effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex-vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-alpha2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to > 1,400 ng/ml). PBMNCs were collected before and during IFN-alpha2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-alpha2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-alpha2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha2b. In summary, our data show that IFN-alpha2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment.

Adult↗

PubMed2000

Reciprocal translocation (3;5)(q26;q22) and possible BCHE gene involvement in an unusual myelogenous disorder with both myeloproliferative and dysplastic features.

We report on a 77-year-old male patient who presented with an unusual myelogenous disorder exhibiting both myeloproliferative and dysplastic features. The patient suffered from leukocytosis, eosinophilia, basophilia, transfusion dependent anemia, and rapidly progressing thrombocytopenia. Classical chromosome analysis and fluorescence in situ hybridization (FISH) revealed a reciprocal t(3;5)(q26;q22). Using yeast artificial chromosome (YAC) probes, the breakpoint on chromosome 3 was localized to the butyrylcholinesterase (BCHE) gene (3q26.1-q26.2). This gene has recently been implicated in the regulation of myeloid cells. Whether the BCHE gene was also involved in the deregulation of myelopoiesis, causing the unusual clinical picture in this case, remains unknown.

Aged↗

PubMed2000

New developments in extracutaneous lymphomas.

The recently proposed World Health Organization classification of neoplastic diseases of the lymphoid tissues is based on the principles of the Revised European-American Classification of Lymphoid Neoplasms introduced in 1994. Use of these classifications implies a new approach to lymphoma diagnosis, especially because of the inclusion of clinical data among which the site of involvement (nodal v extranodal) is very important. Recent technical advances allowing molecular biological investigations on the single cell level helped gain new insights into the cellular origin of B-cell lymphomas. Tumor cells of the majority of B-cell non-Hodgkin's lymphomas (NHL) harbor somatically mutated immunoglobulin variable region genes, and are therefore derived from germinal center B cells or their descendants. The same is true for Hodgkin's disease, which (at least in the majority of cases) is a germinal center derived B-cell lymphoma. Significant news on the molecular pathogenesis of NHL include the prognostically relevant dichotomy of B-CLL, the involvement of translocations affecting 3q27 in 20% to 40% of diffuse large B-cell lymphomas (DLBCL), the prognostical implication of the t(2;5) in anaplastic large cell lymphoma, and detection of the t(11;18) in gastric mucosa-associated lymphoid tissue (MALT)-type lymphoma. A major step forward with regard to gastric MALT-type lymphoma therapy was the discovery of a causal relationship between Helicobacter pylori infection and lymphomagenesis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy remains the golden standard for DLBCL treatment.

Antibodies, Monoclonal↗

PubMed2000

Platelet-derived growth factor-AA and -alpha receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma.

Platelet-derived growth factor (PDGF) is a major mitogen and chemotactic factor for mesenchymal cells such as fibroblasts, smooth muscle cells, and osteoblasts. PDGF exists as disulfide-linked homo- or heterodimers composed of two polypeptide chains encoded by distinct genes, designated PDGF-A and PDGF-B. Upon binding to its tyrosine kinase receptor PDGF-alpha, especially PDGF-AA stimulates the proliferation of osteoblastic cells and may exert autocrine and paracrine effects in regulating bone-forming processes. The purpose of this immunohistochemical study was to determine the expression of PDGF-AA and PDGF-alpha receptor in benign and malignant neoplastic bone lesions. Polyclonal antibodies to PDGF-AA and PDGF-alpha receptor were used on paraffin sections of 23 osteosarcomas and 17 osteoblastomas. Immunostaining was assessed quantitatively by evaluating the percentage of reactive tumor cells. In osteosarcomas, the mean expression of PDGF-AA and PDGF-alpha receptor was 33.97% (range, 2 to 80%; SD, 24.26%) and 27.13% (range, 3.2 to 72%; SD, 18.38%), respectively. Osteoblastomas showed significantly lower expression of PDGF-AA than osteosarcomas (mean, 15.71%; range, 5 to 34%; SD, 9.43%; P = .019). Although the mean expression of PDGF-alpha receptor in osteoblastomas was much lower than in osteosarcomas (mean, 17.55%; range, 3.6 to 26.8%; SD, 6.47%), the difference was not significant (P = .122). For osteosarcomas, Spearman correlation coefficient (two-tailed) revealed a significant correlation between the expression of PDGF-AA and PDGF-alpha receptor (r = .688), which was not the case for osteoblastomas (r = .267). These data suggest that in contrast to osteoblastoma, the growth of osteosarcoma may be supported by the coordinate expression of the potent mitogenic growth factor and its receptor that exert their functions by autocrine and paracrine mechanisms.

Autocrine Communication↗

PubMed2000

Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas.

The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.

Adult↗

PubMed2000

Cutaneous dendritic cells are main targets in acute HIV-1-infection.

Acute human immunodeficiency virus (HIV) infection is a transient illness that typically presents with mucocutaneous and constitutional symptoms. It is soon followed by seroconversion with the detection of anti-HIV antibodies in the peripheral blood. To better understand the pathogenetic events leading to this clinical picture, we sought to investigate the (immuno)histologic features of the skin rash occurring in an acutely infected person. A skin biopsy of an acutely infected person was investigated histologically and immunohistologically using paraffin-embedded tissue sections. Interface dermatitis with pronounced vacuolization of the basal keratinocytes was a prominent histological finding. The inflammatory infiltrate was composed of CD3+/CD8+ T cells with coexpression of Granzyme B7 and TIA-1, and CD68+ histiocytes/dendritic cells. CD1a+ intraepidermal Langerhans cells (LC) were significantly decreased and individual LC coexpressed HIV-p24 antigens as evidenced in double labeling experiments. HIV-infected LC were demonstrated in close apposition to cytotoxic T cells. This study provides the first definitive evidence for infection of LC at extramucosal sites in this very early stage of disease. Our findings emphasize the critical role of dendritic cells as a virus reservoir and the skin as a major site of HIV replication during the course of the disease.

Acute Disease↗

PubMed2000

Multiple myeloma with deletion of chromosome 13q is characterized by increased bone marrow neovascularization.

Anti-angiogenesis therapy with thalidomide has been reported to have marked activity in multiple myeloma (MM). As cytogenetics is an independent prognostic factor in MM, we analysed bone marrow (BM) angiogenesis and cytogenetic abnormalities in 34 patients with active MM. BM microvessel density (MVD), as determined by staining with anti-CD34, was significantly higher in MM (MVD: 221 +/- 94 per mm2) than in controls (80 +/- 36; P < 0.0001). In patients with the presence of at least one unfavourable cytogenetic abnormality (deletion of 13q14, deletion of 17p13, aberrations of 11q), a significantly increased BM MVD was observed (254 +/- 93 vs. 160 +/- 60 in patients with absence of these abnormalities; P = 0.0035). Further analyses indicated that increased BM MVD was significantly correlated with deletion of 13q14 (259 +/- 96 vs. 188 +/- 80; P = 0. 026), but not with other cytogenetic, clinical and laboratory MM parameters. We conclude that BM neovascularization is particularly high in MM with deletion of 13q14, which provides a rationale for use of anti-angiogenic strategies in the treatment of MM with high-risk cytogenetics.

Adult↗

PubMed2000

CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes.

Human T cells expressing CD161 and an invariant T-cell receptor (TCR) alpha-chain (Valpha24invt T cells) specifically recognize CD1d and appear to have immunoregulatory functions. However, the physiological target cells for this T-cell population, and whether alterations in CD1d expression contribute to the regulation of Valpha24invt T-cell responses, remain to be determined. A series of antibodies were generated to assess CD1d expression, structure and regulation on human lymphoid and myeloid cells. CD1d was expressed at high levels by human cortical thymocytes and immunoprecipitation analyses showed it to be a 48 000-MW glycosylated protein. However, after solubilization, the majority of the thymocyte CD1d protein, but not CD1d expressed by transfected cells, lost reactivity with monoclonal antibodies (mAbs) against native CD1d, indicating that it was alternatively processed. Moreover, thymocytes were not recognized by CD1d-reactive Valpha24invt T-cell clones. Medullary thymocytes and resting peripheral blood T cells were CD1d-, but low-level CD1d expression was induced on activated T cells. CD1d was expressed by B cells in peripheral blood and lymph node mantle zones, but germinal centres were CD1d-. Resting monocytes were CD1d+ but, in contrast to CD1a, b and c, their surface expression of CD1d was not up-regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) activation. These results demonstrate constitutive CD1d expression by human professional antigen-presenting cells and that post-translational processing of CD1d may contribute to regulation of the activity of CD1d-specific T cells.

Antibody Specificity↗

PubMed2000

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗

PubMed2000

Importance of extensive staging in patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma.

Lymphoma of the mucosa-associated lymphoid tissue (MALT) type usually arises in MALT acquired through chronic antigenic stimulation triggered by persistent infection and/or autoimmune processes. Due to specific ligand-receptor interactions between lymphoid cells and high-endothelial venules of MALT, both normal and neoplastic lymphoid cells display a pronounced homing tendency to MALT throughout the body. In the case of neoplastic disease these homing properties may be responsible for lymphoma dissemination among various MALT-sites. According to this concept, we have standardized staging procedures in all patients diagnosed with MALT-type lymphoma. All patients with MALT-type lymphoma underwent standardized staging procedures before treatment. Staging included ophthalmologic examination, otolaryngologic investigation, gastroscopy with multiple biopsies, endosonography of the upper gastrointestinal tract, enteroclysis, colonoscopy, computed tomography of thorax and abdomen and bone marrow biopsy. Biopsy was performed in all lesions suggestive for lymphomatous involvement, and evaluation of all biopsy specimens was performed by a reference pathologist. 35 consecutive patients with histologically verified MALT-type lymphoma were admitted to our department. Twenty-four patients (68%) had primary involvement of the stomach, five (15%) had lymphoma of the ocular adnexa, three (8.5%) had lymphoma of the parotid, and three (8,5%) of the lung. Lymph-node involvement corresponding to stage EII disease was found in 13 patients (37%), only one patient with primary gastric lymphoma had local and supradiaphragmatic lymph-node involvement (stage EIII). Bone marrow biopsies were negative in all patients. Overall, eight of 35 patients (23%) had simultaneous biopsy-proven involvement of two MALT-sites: one patient each had lymphoma of parotid and lacrimal gland, conjunctiva and hypopharynx, conjunctiva and skin, lacrimal gland and lung, stomach and colon, and stomach and lung. The remaining two patients had bilateral parotideal lymphoma. Staging work-up was negative for lymph-node involvement in all of these eight patients. The importance of extensive staging in MALT-type lymphoma is emphasized by the demonstration of multiorgan involvement in almost a quarter of patients. In addition, our data suggest that extra-gastrointestinal MALT-type lymphoma more frequently occurs simultaneously at different anatomic sites than MALT-type lymphoma involving the GI-tract.

Eye Neoplasms↗