Gastric non-Hodgkin Lymphoma Research Articles

High incidence of secondary myelodysplastic syndromes following PROMACE‐MOPP and involved field radiotherapy for localized gastric non‐Hodgkin's lymphomas

The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less than 10 per cent of secondary MDS are usually observed in patients treated for Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by modern chemotherapeutic regimens is needed. Between January 1985 and January 1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE) were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi-agent chemotherapy and involved-field irradiation. The mean age was 54 years (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28 months after therapy. Thirteen patients were followed up for at least 5 years. Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic analysis was performed in two cases and showed −7 and 18q− in one case, t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy should not be recommended in patients with localized gastric non-Hodgkin's lymphoma due to the high risk of developing secondary myelodysplastic syndromes. © 1996 John Wiley & Sons, Ltd.

Gastric non-Hodgkin lymphomas of mucosa-associated lymphoid tissue are not associated with more aggressive Helicobacter pylori strains as identified by CagA.

Primary gastric non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT-NHL) is strongly related to Helicobacter pylori (H pylori) infection. CagA positive H pylori strains appear to be more aggressive, as reflected by a greater degree of gastric inflammation and higher levels of Il-8 production. Using a polymerase chain reaction-based assay, cagA status was determined in H pylori strains of 12 patients with gastric MALT-NHL, 38 patients with peptic ulcer disease, and 39 patients with non-ulcer dyspepsia. CagA-positive H pylori strains were significantly more frequent in peptic ulcer disease than in non-ulcer dyspepsia (Fisher's exact test p <0.001). An increased frequency of CagA-positive strains was not identified in gastric MALT-NHL compared to non-ulcer dyspepsia patients (Fisher's exact test P <.3). Therefore, it can be concluded that infection with more aggressive strains is associated with the development of peptic ulcer disease, but plays a minor role, if any, in the development of gastric MALT-NHL.

Epidemiology of gastric non-Hodgkin's lymphoma patients: parallels with Helicobacter pylori.

The incidence of gastric non-Hodgkin's lymphoma (NHL) is increasing in the United States. However, little is known about the etiology of the disease. Some studies have shown an association between gastric NHL and Helicobacter pylori. No study has specifically delineated demographic features that distinguish gastric NHL patients from nongastric NHL patients. To obtain information about the differences between gastric and nongastric NHL patients, we conducted a hospital chart review study. We examined charts of all 25 cases of primary gastric NHL, as well as charts of 75 randomly selected nongastric NHL patients as controls. All patients were seen in the Division of Oncology at Stanford University Medical Center from 1972 to 1991. Demographic information was tabulated, and differences between the cases and controls were noted. The identified risk factors were determined by both univariate and logistic regression analyses. There was no difference between gastric NHL cases and nongastric controls with respect to age, gender, race, and family history of any cancer. However, in logistical regression, persons with gastric NHL were more likely than those with other forms of NHL to be born outside the United States (odds ratio = 12.8; 95% confidence interval = 2.9-56.0) and also to have a family history of stomach cancer (odds ratio = 18.4; 95% confidence interval 2.1-160.1). Gastric NHL is more likely than NHL at other sites to occur in persons with a family history of gastric cancer or in those born in developing countries. This epidemiological pattern supports the identified role of H. pylori in the development of gastric lymphoma.

Pantoprazole does not interact with diclofenac

Helicobacter pylori (H. pylori) has been found to be the major cause for gastroduodenal pathology, both in adults and children, a finding which resulted in a new understanding and approach of chronic active gastritis, duodenal ulcers, and, to a lesser degree, gastric ulcers. Very recently, H. pylori has also been described in association with gastric lymphoproliferative disease, more specifically low-grade B-cell lymphoma (MALToma) of the stomach, and even gastric non-Hodgkin lymphoma. We report the case of a 14-year-old girl presenting with severe cachexia, abdominal pain, and nausea, who was diagnosed with H. pylori chronic active gastritis and associated gastric lymphoproliferative disease of the low-grade MALT type (as defined by histology and typical gene rearrangements). The patient was treated only for the H. pylori infection (amoxicillin-bismuth-metronidazole triple therapy) without any adjuvant chemotherapy or surgery for her lymphoproliferative disease. The patient was subsequently followed for a period of 7 years with repeated esophago-gastroduodenoscopies with biopsies. There has been no histologic recurrence of H. pylori gastritis or lymphoproliferative disease. To our knowledge, this is the first report of an H. pylori associated gastric lymphoproliferative disorder in a pediatric patient who was exclusively treated for H. pylori infection and subsequently followed for a period of 7 years. Our observations suggest that H. pylori associated gastric lymphoproliferative disease can be completely cured by eradicating the organism. Therefore, this therapeutic approach, combined with close follow-up, should be the treatment of choice in children with this associated condition, before attempting more aggressive treatments, thus potentially avoiding chemotherapy and/or (partial) gastreetomy. PANTOPRAZOLE DOES NOT INTERACT WITH DICLOFENAC. H. Bliesath, R. Huber, .M. Hartmann, V.W. Steinijans, H.J. Koch, W. Wurst. Research Devision Byk Gulden, Konstanz, Germany

Clinical features of primary gastric non-Hodgkin's lymphoma (pgNHL) of the malt. Results of the prospective German-Australian multicenter trial: [formula omitted], M.-E. Kolve, K. Wilms for the Multicenter Study Group “Gastrointestinal lymphoma”. Dept. of Medicine, Aschaffenburg; Medizinische Poliklinik, Univ. of Würzburg, Würzburg, FRG

Clinical features of primary gastric non-Hodgkin's lymphoma (pgNHL) of the malt. Results of the prospective German-Australian multicenter trial: [formula omitted], M.-E. Kolve, K. Wilms for the Multicenter Study Group “Gastrointestinal lymphoma”. Dept. of Medicine, Aschaffenburg; Medizinische Poliklinik, Univ. of Würzburg, Würzburg, FRG

Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients.

Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0-189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n = 7) or secondary (n = 15) high-grade lymphomas; Musshoff stage IE was found in 29 and IIE in 12 cases. The median age at diagnosis was 61 years (range, 26-88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective analysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity.

Primary gastric lymphoma: a clinical and therapeutic evaluation of 82 patients.

Eighty-two patients with primary gastric (IE, II1E, and II2E) non-Hodgkin's lymphoma according to the Musshoff's staging system were treated with combined modality including surgery with/without radiotherapy between January 1985 and December 1991. According to the Updated Kiel classification 54 had high-grade histologic subtypes and 28 low-grade. The strategy throughout the study was to resect primary tumor: all patients underwent gastrectomy, 40 subtotal and 42 total gastrectomy. The resection permitted complete surgical staging utilizing three pathologic features: disease confined within or beyond the serosa, negative/positive regional lymph nodes, and negative/positive surgical margins. If there was no evidence of these pathologic factors, the patients who underwent surgery alone received no further radiotherapy. On the other hand, all patients who presented at least one of three pathologic factors were treated with adjuvant radiotherapy after the resection. All except 14 patients presented at least one of the pathologic features and 50 (61%) patients had involvement of the whole gastric wall. Radiotherapy included the gastric bed and para-aortic lymph nodes and, for the patients, who had positive regional lymph nodes in combination with the complete involvement of the gastric wall, the irradiation included the whole abdominal approach. The complete response rate was 97% and the 9-year disease-free survival was 93%. All but one of the 5 relapses occurred within 18 months stressing the need for more specific staging. Gastric resection with/without radiotherapy may still represent the primary therapeutic procedure in early stage gastric non-Hodgkin's lymphoma.

A retrospective analysis of treatment outcome in 106 cases of localized gastric non-Hodgkin lymphomas. Danish Lymphoma Study Group, LYFO.

197 cases of gastric lymphoma were reported to a population-based Danish registry of non-Hodgkin's lymphomas. 106 of these cases were localized, representing stages IE and II1E, and were analyzed retrospectively, using Cox regression analysis. 67 had surgical resection, 51 chemotherapy, and 55 radiotherapy, or combinations thereof. No type of treatment showed any superiority as regards survival (p = 0.13). Overall 5-year survival was 67%. The pretherapeutic presence of fever or S-LDH-elevation had a far more significant influence on survival than histology or any of the treatments or treatment combinations. Surgical resection was associated with a significantly higher risk of late complications than radiotherapy, suggesting that radiotherapy may be preferable to surgery as the primary treatment in localized gastric lymphoma. It could not be determined from the available data whether the addition of chemotherapy to the primary treatment provides any survival benefit.

Factors Influencing Lymph Node Infiltration in Primary Gastric Malignant Lymphoma of the Mucosa-associated Lymphoid Tissue

The spread of primary gastric non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT) to the perigastric lymph nodes is a very important step concerning the prognosis of these tumours. In order to evaluate the parameters that influence the infiltration of the lymph nodes we retrospectively investigated 145 surgical specimens with gastric MALT lymphoma. The involved factors, i.e. depth of infiltration, degree of malignancy, and largest tumour diameters were strongly intercorrelated and partly showed significant correlations with the lymph node infiltration as well. Further statistical analysis by means of logistic regression revealed that depth of infiltration was the only parameter that remained significantly correlated with lymph node infiltration. Our data further support the notion that the depth of infiltration is a very important prognostic factor in MALT lymphomas. This could contribute to the explanation as to why the so-called early lymphomas with an infiltration limited to mucosa and submucosa have a much better prognosis than more advanced tumours. Our data thus support the thesis that gastric MALT lymphomas show clinicopathologic similarities with gastric carcinomas. We suggest that the depth of infiltration should be included in the pathological reports concerning primary gastric lymphomas of the MALT.

Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group.

To evaluate incidence, time trends, geographic distribution, clinicopathologic presentation features, and prognostic factors for survival and relapse in gastrointestinal (GI) non-Hodgkin's lymphomas (NHLs). Over a 9-year period (1983 to 1991), 2,446 new NHL cases were recorded in a Danish population-based NHL registry (Danish Lymphoma Study Group [LYFO]). Of these, 306 (12.5%) were GI NHL (175 gastric, 109 intestinal, and 22 both sites). LYFO registry data were used for incidence rate (IR) assessment, and time-trend and geographic distribution analysis. Relative risk (RR) values for survival and relapse were identified by multivariate analysis. The mean annual, age-standardized IRs for gastric and intestinal NHL were 0.71/10(5) and 0.48/10(5) per year, respectively. Age-specific IRs for both localizations showed an exponential increase as a function of age. Time-trend analysis for the period 1983 to 1991 showed stable IRs for both localizations. Intestinal NHL was more frequent in males (male-to-female ratio, 2.0 v 1.3), and had a higher occurrence of disseminated disease, constitutional symptoms, high-grade histology, and T-cell phenotype (10% v 2%). Gastric NHL had more low-grade cases (38% v 19%), and almost all were of the mucosa-associated lymphoid tissue (MALT) type. The cause-specific 5-year survival rate was 63% for gastric NHL and 49% for intestinal NHL. The Musshoff staging system was an excellent discriminator between truly localized (stage I and II1) and disseminated cases (stage II2 to IV), particularly for gastric NHL, for which no survival difference was found between surgically and conservatively stage localized cases. (1) No increase in the incidence of GI NHL was found over a 9-year observation period; (2) nonrandom spatial distribution of new GI NHL cases was observed; (3) factors that significantly increased the risk of death in gastric cases were presence of B symptoms (RR = 3.3), clinical stage is more than II1 (RR = 3.0), age more than 72 years (RR = 2.4), and elevated serum lactate dehydrogenase (s-LDH) level (RR = 2.0); and factors that increased the risk of death in intestinal cases were presence of B symptoms (RR = 3.2), age more than 58 years (RR = 2.8), and clinical stage more than I (RR = 2.1); (4) factors that significantly increased the risk of relapse in gastric cases were male sex and no radiotherapy in primary treatment; and in intestinal cases were T-cell phenotype and no surgery in primary treatment; (5) surgical staging, as opposed to thorough noninvasive staging, did not improve staging accuracy and final outcome in localized gastric NHL.

Pointers to the diagnosis of gastric lymphoma on computed tomography

The computed tomographic features of 12 patients with primary gastric non-Hodgkin's lymphoma and a further seven patients with gastric involvement by disseminated non-Hodgkin's lymphoma have been reviewed. In eight of these 19 patients there were clefts within the area of gastric wall involved by lymphoma where oral contrast medium passed to within 2 mm of the serosal surface in and amongst areas of gastric wall thickening (maximal thickness ranging from 18 to 40 mm). In three of these patients some clefts extended beyond the expected margin of the stomach to enter into, and be contained by, a composite soft tissue mass of stomach, spleen and splenic hilar nodes. Awareness of these features, which are in keeping with the known range of macroscopic pathological appearances in non-Hodgkin's lymphoma, may help the radiologist to recognize this potentially curable disease.

Helicobacter pylori Infection and Gastric Lymphoma

Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma. This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay. Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0). Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

Evidence of a Malignant Cycle in Early Gastric Lymphoma

In order to investigate whether, by analogy with early gastric carcinomas, evidence of a malignant cycle could be found in early gastric non-Hodgkin's lymphomas (EGL), a study of 135 surgical specimens (46 gastrectomies, 80 aboral resections, nine local excisions) was performed. A malignant cycle was considered to have been shown when regenerative changes in the mucosa and fibrosis of the adjacent submucosa were detected. The depth of tumour infiltration was characterized using the UICC classification for gastric carcinomas. An EGL was found in 51.1% of cases (n = 69). The correlation between depth of infiltration and the histological classification of tumours proved statistically significant (p < 0.0001). Evidence of a malignant cycle was demonstrated in 72.5% of EGLs as compared with 27.3% in gastric lymphomas showing deeper infiltration (AL). The same held true for the histological classification of lymphomas. Findings consistent with a malignant cycle were found in 72.7% of low-grade compared with 37.7% of high-grade lymphomas. The difference in distribution proved to be statistically significant in both cases (p < 0.001). Most cases were localized in the antral region (53.6% of EGLs, 40.9% of ALs) and the lower third of the stomach (44.9% of EGLs and 33.3% of ALs). Detecting evidence of a malignant cycle, especially in EGL, has important diagnostic implications, requiring a careful search for minute lymphoma-associated irregularities in the neighbourhood of healed lesions, with the aim of determining the proper locations for a diagnostic biopsy.

Primary gastric CD30 (Ki-1)-positive large cell non-Hodgkin's lymphomas. A clinicopathologic analysis of six cases

The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and frequently involving the skin and other extranodal sites. In cutaneous large cell lymphomas, the CD30 expression was indicated as a favorable prognostic marker independently from cytology, anaplastic versus nonanaplastic. The stomach is the most common site of extranodal lymphomas in the adult population, but primary gastric CD30+ lymphomas have been reported rarely. The clinical, morphologic, and immunohistochemical features of six cases with primary CD30/Ki-1+ gastric large cell lymphomas were analyzed. The mean age of patients was 64 years with a prevalence of women (M:F ration = 1:2). Patients were assigned to Stage IE or IIE. Three of them died of disease, whereas the others are still alive (mean follow-up, 18 months). Three of six cases had ALCL morphology, whereas other cases had centroblastic, immunoblastic, and high-grade mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B-cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and a null, non-B, non-T phenotype in two of six cases. Within CD30+ primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic, did not affect clinical presentation and/or prognosis. The survival rate of the patients studied is in keeping with literature reports regarding prognosis of primary high-grade gastric NHL. The findings suggest that clinical behavior of this extranodal lymphoma is more closely related to clinical symptoms and initial stage of disease than to CD30 expression.

Combined surgery and chemotherapy in primary gastric non-Hodgkin's lymphoma: a retrospective study in sixty-six patients.

Sixty-six consecutive patients with primary gastric non-Hodgkin's lymphoma are reported. All patients underwent surgery which consisted of radical resection in 23 patients (36%) and partial or palliative excision in the remaining 43 cases (36 and 7 respectively). Three patients died before starting chemotherapy, two refused the treatment and 61 completed the postoperative chemotherapeutic programme. We analysed this group of patients in order to assess the efficacy of chemotherapy following surgery. Chemotherapy included either CVP or the original protocols from our institution. Excluding patients who underwent radical resection, postoperative chemotherapy induced complete remission in 87% of the remaining 39 patients. After a median follow-up of 84 months (range 6-216), the 10-year cause-specific survival was 90% with a stable curve plateau after about 25 months. The survival was only influenced by response to therapy (p < 0.0001). The disease-free survival for patients who were not radically resected was 93%. We encountered only two relapses after 15 and 32 months. One of these was local and the other systemic. Our results indicate that chemotherapy following surgery induces long-term remission and survival in primary gastric lymphoma and in particular improves remission and survival, in stage II. In our opinion, surgery may also be fundamental for the treatment of gastric lymphoma in the majority of cases.

The role of surgery in the management of the primary gastric non-hodgkin's lymphoma

The role of surgery in the management of the primary gastric non-hodgkin's lymphoma

胃悪性リンパ腫の生物学的悪性度および予後因子としてのＡｇＮＯＲｓの役割

胃悪性リンパ腫の生物学的悪性度および予後因子としてのＡｇＮＯＲｓの役割

Postoperative chemotherapy increases the disease-free survival rate in primary gastric lymphomas stage IE and IIE

We describe 53 patients with primary gastric non-Hodgkin's lymphoma (38 stage IE,15 stage IIE) treated with surgery as a primary procedure. According to the Working Formulation, 13 cases had low, 21 had intermediate and 19 had high grade malignancy. 34 patients considered at high risk received postoperative polychemotherapy. The overall 10-year disease-related survival is 91%. Median follow-up is 52 months. 7 patients relapsed (13%). The 10-year disease-free survival rate of the 19 patients initially treated with surgery is 60%, as compared with 92% in the patients who also received chemotherapy (P = 0.004). However, overall survival did not differ between the two groups, since two-thirds of the patients who relapsed after surgery alone were rescued with chemotherapy. Stage, age, sex and histology did not correlate with survival. In our experience, surgery was an adequate first step procedure; the addition of chemotherapy significantly reduced relapses and increased the disease-free survival rate in patients with unfavourable prognostic factors.

Gastric lymphoma in an 11‐year‐old boy: A case report

A child with prolonged abdominal symptoms was shown to have a concomitant gastric non-Hodgkin lymphoma and gastritis caused by Helicobacter pylori infection. After a course of antibiotics and 6 months of chemotherapy, the patient is disease free. The relationship of the microbial infection and tumor development is discussed. The case supports a hypothesis that local H. pylori infection may be a predisposing factor for gastric lymphoma.

Role of endosonography in the surgical management of non-Hodgkin's lymphoma of the stomach.

Ten patients with primary gastric non-Hodgkin's lymphoma (NHL) were preoperatively assessed by endoscopic ultrasonography (EUS). Tumor infiltration depth and lymph node involvement were assessed using the TNM classification system. EUS was 80% accurate in determining the TL stage and 90% in detecting lymph node metastases (NL stage). Based on the longitudinal tumor extent (antrum to fundus), as assessed by preoperative (n = 10) and additionally, intraoperative EUS (n = 3), partial gastric resection was performed in nine patients and total gastrectomy in one. All resection specimens had tumor-free resection margins (R0 resection rate 100%). These results were compared to those in 23 patients with gastric NHL operated on prior to the introduction of EUS in the hospital who were comparable with respect to tumor location and extent. In comparison with the ten cases where treatment was guided by EUS, the rate of total gastrectomy was higher (65% versus 10%) and the R0 resection rate lower (72% versus 100%) in this group of 23 patients. These results show that EUS may play a crucial role in the pre-surgical staging of gastric NHL.