Gastric Diffuse Large B-cell Lymphoma Research Articles

Synchronous primary gastric diffuse large B-cell lymphoma and multiple lung primary adenocarcinoma with pulmonary cryptococosis: a case report and literature review

BackgroundThe coexistence of non-Hodgkin’s lymphoma of the stomach and multiple primary lung adenocarcinomas with pulmonary cryptococcosis has rarely been reported.Case presentationWe herein present a 75-year-old man who was admitted to our hospital due to hematemesis. Gastroscopy and imaging revealed extensive stomach wall thickening and multiple lung lesions, including nodules and cavernous lesion. The patient was diagnosed with primary diffuse large B-cell lymphoma via gastroscopy and bilateral lung primary adenocarcinoma with cryptococcal infection via percutaneous CT-guided puncture biopsy. He subsequently underwent six cycles of R-CHOP regimen for gastric lymphoma, along with CT-guided radiofrequency ablation for the upper lobe of the right lung primary adenocarcinoma and radioactive particle implantation was performed on the lower lobe of the left lung primary adenocarcinoma, supplemented with antifungal therapy. After a definite diagnosis and systemic treatment, the patient was followed up for twenty-seven months with no tumor recurrence, progression or metastasis.ConclusionTo the best of our knowledge, the complex combination of multiple primary malignancies and pulmonary cryptococcal infection is extremely rare. The diagnosis is been confusing and challenging. CT-guided needle biopsy can help achieve pathological diagnosis, elucidate the type and stage of the tumor, and even change the clinical treatment strategy, which is necessary and beneficial.

Combined modality for localized gastric diffuse large B-cell lymphoma: Long-term outcomes of 50 patients.

7079 Background: R-CHOP is the primary treatment for gastric diffuse large B-cell lymphoma (GDLBCL); for localized disease, the role of consolidative radiation therapy (RT) after chemotherapy remains underexplored. This study focuses on localized GDLBCL undergoing a combined modality therapy of R-CHOP followed by gastric RT, comparing outcomes between those receiving short-course (3-4 cycles) and full-course (6 cycles) R-CHOP. Methods: A retrospective analysis identified 50 consecutive PGDLBCL pts treated with R-CHOP followed by RT between 1/2000-1/2021. Baseline characteristics and follow-up data were collected. Lugano PET criteria and endoscopy (EGD) assessed overall response rate. Kaplan-Meier and univariable cox regression models estimated overall survival (OS) and (PFS). Results: Of the 50 pts with localized (Stage I-II) disease, 34 (68%) received 3-4 cycles of R-CHOP and 16 (32%) received 6 cycles. Pre-RT disease evaluation varied, with 36 (72%) undergoing EGD and PET, 4 (8%) EGD and CT, and 6 (12%) PET alone. One pt (3%) exhibited active DLBCL post 3-4 cycle R-CHOP, while 5 (31%) did so after 6 cycles (p=0.1). Median time from last R-CHOP dose to RT start date was 1.2 months with a median 3060 cGy delivered dose for both groups (range 2340-3060 in the 3-4 cycle group, 3000-4500 in the 6-cycle group). Median follow-up time from RT end is 58 months. No in-field failures occurred post-complete response (CR); however, 1 pt did not achieve a CR following R-CHOP and RT, progressing in the stomach and subsequently at new, out-of-field (OOF) sites. 3 pts had OOF progression without relapses in the stomach in a median time of 21 months. Low-grade lymphoma in the stomach post-DLBCL CR was observed in 2 pts, 3 and 22 months from RT end, with 1 OOF marginal zone lymphoma 2 years-post RT. OS and PFS did not significantly differ between the 3-4 and 6 cycle groups (96-month OS 70% vs. 86%, p=0.8; 96-month PFS 76% vs. 86%, p=0.7). OS and DLBCL PFS were analyzed for pts with evidence of residual DLBCL pre-RT compared to those without evidence of disease after R-CHOP. The 24-month DLBCL PFS was 92% in the CR group and 67% for those with incomplete response (p=0.14), with 92% and 67% 24-month survival probability (p=0.11). On univariate analysis, pre-RT evidence of active DLBCL by PET and/or EGD, pre-RT PET FDG uptake, and achieving CR on first-post-RT imaging were not statistically significant for DLBCL PFS. Conclusions: Recognizing the limitations of a retrospective study, our study documents the effectiveness of short-course R-CHOP followed by RT in localized GDLBCL, with similar outcomes to the full 6-cycle regimen. Excellent disease control was observed, with few instances of DLBCL or low-grade lymphoma relapse. Further analysis will include a cohort receiving R-CHOP alone without consolidative RT. This analysis aims to contribute to the evolving standard of care for GDLBCL, providing insights for future treatment strategies.

Molecular Mechanisms and Treatment Strategies for Helicobacter pylori-Induced Gastric Carcinogenesis and Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Helicobacter pylori has been classified as a class I carcinogen by WHO because of its primary involvement in the development of gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. This review focuses on understanding the molecular pathophysiological mechanisms that operate within intracellular transduction pathways and their relevance in the treatment strategies for the two main diseases caused by H. pylori. H. pylori virulence factors such as cytotoxin-associated gene A and vacuolating cytotoxin A genotypes, inflammatory mediators, H. pylori-induced microRNA deregulation, alterations in autophagy proteins and regulators, and changes in DNA methylation are some of the molecular mechanisms that play essential roles in H. pylori infection and gastric carcinogenesis. The discovery of novel treatment strategies that target the deregulated intracellular transduction pathways in gastric carcinogenesis and MALT lymphoma is critical. H. pylori eradication (HPE) is not limited to H. pylori-dependent low-grade MALT lymphoma and may be used in patients with high-grade diffuse large B-cell lymphoma (DLBCL) (de novo or DLBCL-MALT lymphoma). The loss of H. pylori dependency and high-grade transformation appear to be distinct events in the progression of gastric lymphoma. Interestingly, patients with H. pylori-positive gastric DLBCL without histological evidence of MALT lymphoma (pure gastric DLBCL) may respond to HPE therapy.

Primary gastric diffuse large B-cell lymphoma: A multicentre retrospective study.

Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) accounts for the majority of extra-nodal DLBCL. Even so, literature is lacking on early, localised presentations. We studied a cohort of patients with stage I disease, diagnosed between 2006 and 2018, from six centres between Australia, Canada and Denmark. Our goal was to characterise outcomes, review treatmentand investigate the role of interim positron emission tomography (iPET). Thirty-seven eligible patients were identified. The median duration of follow-up was 42.2 months. All received chemoimmunotherapy with 91.9% (n = 34) given rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). 35.1% (n = 13) underwent consolidative radiotherapy. Eighteen patients were H. pylori positive and 11 had the documentation of H. pylori eradication therapy. The 4-year progression-free survival and overall survival of R-CHOP was 88% (95% CI: 71-95) and 91% (95% CI: 75-97) respectively. All patients who achieved a partial metabolic response or complete metabolic response on iPET went on to achieve complete response at the end of treatment. R-CHOP-based therapy with iPET assessment appears to offer favourable outcomes, with radiotherapy and H. pylori eradication therapy implemented on a case-by-case basis.

Awardee Summary of 2023 Taiwan Oncology Society Clinical Research Award Recipient: Persistent Endeavors on Research of Digestive Cancers for Three Decades

Abstract Objective: Digestive cancers account for five of the top ten cancer-related deaths in Taiwan. Our team has made persistent endeavors in translational research and clinical trials of digestive cancers for almost three decades. Data Sources and Study Selection: We enrolled relevant translational and clinical studies for digestive cancers published by our groups in the past three decades. Results: First, we developed a unique weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin regimen (HDFL) in 1992. HDFL exhibits satisfactory single-agent activity, minimal myelosuppression, and mild toxicity. A variety of HDFL-based doublet combinations (such as cisplatin-HDFL, oxaliplatin-HDFL, and paclitaxel-HDFL) have become cornerstone regimens for three decades for the treatment of gastric cancers, with high efficacy and manageable toxicity at our hospital. Second, we have made persistent efforts in translational research and clinical trials on early-stage gastric mucosa-associated lymphoid tissue lymphomas (MALTomas), gastric diffuse large B-cell lymphomas, colorectal cancers (CRCs), pancreatic cancers, and immuno-oncology. Third, on behalf of the Taiwan Oncology Society, we participated in and published the Pan-Asian adapted European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for locally advanced and metastatic CRC, gastric, and esophageal cancers, and the consensus meeting on tumor-agnostic indications of microsatellite instability-high (MSI-H) and NTRK. Conclusion: In the future, our team will make persistent endeavors in research on digestive cancers for immunotherapy and precision medicine to further improve treatment outcomes.

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Background/Objectives: Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Materials/Methods: 285 consecutive pts with PG lymphomas treated with RT between 1/2000-1/2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE v4.0. Results: Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 years (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-year OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Conclusion: Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

S4140 A Case Series of Primary Gastric Diffuse Large B-Cell Lymphomas Within the Hispanic Population: Underserved Is an Understatement

S4140 A Case Series of Primary Gastric Diffuse Large B-Cell Lymphomas Within the Hispanic Population: Underserved Is an Understatement

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Two hundred eighty-five consecutive pts with PG lymphomas treated with RT between January 2000 and January 2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE version 4.0. Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 yrs (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-yr OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

Helicobacter pylori eradication treatment for primary gastric diffuse large B-cell lymphoma: A single-center analysis.

Unlike the already established effect of Helicobacter pylori (H. pylori) eradication on gastric mucosa-associated lymphoid tissue (MALT) lymphoma, its therapeutic effect on primary gastric diffuse large B-cell lymphoma (DLBCL) is still unclear. To clarify the efficacy of H. pylori eradication treatment for primary gastric DLBCL. We reported on 3 new cases, and added them to 3 previously reported cases. We analyzed the usefulness of H. pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center. Of the 6 patients (27-90 years old, 3 males and 3 females), all 3 patients with single lesions (one transformed from MALT lymphoma) achieved complete remission (CR) after H. pylori eradication. Regarding the 2 newly reported cases, CR was maintained for more than 6 years with eradication treatment alone. In contrast, none of the 3 patients with 2 lesions achieved CR. In 1 newly reported case, endoscopic CR was achieved in one lesion, while stable disease was obtained in the other lesion. Two patients with progressive disease responded to standard chemotherapy ± radiation and remained in CR for more than 6 years. We believe it is worthwhile to attempt H. pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden.

A new nomogram for assessing complete response (CR) in gastric diffuse large B-cell lymphoma (DLBCL) patients after chemotherapy

PurposeAchieving complete response (CR) after first-line chemotherapy in gastric DLBCL patients often results in longer disease-free survival. We explored whether a model based on imaging features combined with clinicopathological factors could assess the CR to chemotherapy in patients with gastric DLBCL.MethodsUnivariate (P < 0.10) and multivariate (P < 0.05) analyses were used to identify factors associated with a CR to treatment. As a result, a system was developed to evaluate whether gastric DLBCL patients had a CR to chemotherapy. Evidence was found to support the model's ability to predict outcomes and demonstrate clinical value.ResultsWe retrospectively analysed 108 people who had been diagnosed gastric DLBCL; 53 were in CR. Patients were divided at random into a 5:4 training/testing dataset split. β2 microglobulin before and after chemotherapy and lesion length after chemotherapy were independent predictors of the CR of gastric DLBCL patients after chemotherapy. These factors were used in the predictive model construction. In the training dataset, the area under the curve (AUC) of the model was 0.929, the specificity was 0.806, and the sensitivity was 0.862. In the testing dataset, the model had an AUC of 0.957, specificity of 0.792, and sensitivity of 0.958. The AUC did not differ significantly between the training and testing dates (P > 0.05).ConclusionA model constructed using imaging features combined with clinicopathological factors could effectively evaluate the CR to chemotherapy in gastric DLBCL patients. The predictive model can facilitate the monitoring of patients and be used to adjust individualised treatment plans.

Outcome and patterns of relapse in primary gastric diffuse large B cell lymphoma treated with RCHOP

ABSTRACTObjectivesPatterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP).MethodsFrom 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS).Results64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6–185) months. The median time to progression or relapse was 9 months (range: 5–54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35–8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09–71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS.ConclusionTreatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.

Evaluation of clinical and prognostic factors for primary gastric diffuse large B-cell lymphoma: Single-center experience.

Primary gastric lymphomas, which make up the vast majority of extranodal non-Hodgkin lymphoma, are rare and the most common subtype is primary gastric diffuse large B-cell lymphoma (PG-DLBCL). In our study, we investigated the clinical and prognostic factors of this lymphoma type as a single-center experience. Between January 2001 and February 2021, 91 patients aged ≥18 years, registered with the diagnosis of primary gastric DLBCL, diagnosed histopathologically, and whose evaluation parameters were reached, were retrospectively scanned. The median age of 91 patients with a diagnosis of PG-DLBCL was 58 (20-81, minimum-maximum) years. Of the patients, 64.8% were men and 35.2% were women. While the number of patients with an International Prognostic Index (IPI) score of 0-2 (low-low-intermediate risk) was 54 (59.4%), the number of patients with an IPI score of 3 (high intermediate) was 19 (20.9%), and the number of patients with an IPI score of 4-5 (high risk) was 18 (19.8%). While 52.7% of the patients had a complete response, 20.9% had a partial response, 3.3% had stable disease, and 23.1% had progressive disease. The 10-year event-free survival (EFS) and overall survival (OS) rates for all patients, respectively, were 52.1% and 53.2%. We found factors affecting survival in univariate analysis; age groups (≤60/>60), ECOG groups (0-1/≥2), Lugano stage (I-II/III-IV), LDH level (normal/high), IPI risk groups (low/low-intermediate/high-intermediate/high) and radiotherapy (yes/no). In multivariate analysis, only; age groups (≤60/>60) and IPI risk groups (low/low-intermediate/high-intermediate/high) were found to be independent factors affecting survival. In addition, in our study, we determined that the division of the IPI intermediate risk group into low intermediate and high intermediate is one of the factors predicting prognosis. Few studies of PG-DLBCL have investigated the long-term survival rates of patients and primarily examined small patient groups because of the low incidence of the disease. In our study, we think that detailed evaluation of age and especially IPI risk groups play a role in predicting survival.

Exosomal PD‑L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B‑cell lymphoma.

Gastric diffuse large B‑cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death‑ligand 1 (PD‑L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD‑L1 in the supernatants of cultured diffuse large B‑cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with Tlymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD‑L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD‑L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD‑L1 promoted growth of tumors formed by DLBCL cells invivo and inhibited the proliferation of Tlymphocytes. Notably, the protein expression level of PD‑L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD‑L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD‑L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD‑L1 inhibited the proliferation of Tlymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD‑L1 may suggest a poor prognosis of GDLBCL, and exosomal PD‑L1 in plasma may be a new diagnostic indicator for GDLBCL.

A study on the prevention of hemorrhage and perforation in patients with primary gastric diffuse large-B cell lymphoma during treatment with immunochemotherapy.

Stomach hemorrhage and perforation are very severe and common complications in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL) during treatment with immunochemotherapy. However, no relevant clinical studies have been performed on the prevention of these serious complications. Patients diagnosed with PG-DLBCL were enrolled in this retrospective study. The prevention group received standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment without prednisone combined with antacids and anti-Helicobacter pylori (Hp) therapy. These patients received R-CHOP-based treatment until the complete recovery of gastric ulcers, as proven by gastroscopy. The control group received a standard R-CHOP regimen. Toxicity and survival were the main endpoints. A total of 52 patients received preventative treatment, while 146 patients did not. Among patients with stage I, II-1, and II-2 disease, the prevention group had a lower rate of hemorrhage and perforation (0/40) than the control group (10/78, p=0.044). At a median follow-up time of 25 months, the 5-year event-free survival (EFS) rates were 97.1% in the prevention group and 66.1% in the control group (p=0.025), and the 5-year overall survival (OS) rates were 100% and 72.0%, respectively (p=0.021). However, the differences in the 5-year EFS and OS of patients with disseminated disease were not statistically significant. Preventative treatment can decrease the risk of hemorrhage and perforation in patients with localized PG-DLBCL during immunochemotherapy, leading to better EFS and OS in these patients. However, preventative treatment failed to reduce the risk of gastric hemorrhage and perforation and did not improve survival (EFS and OS) in advanced-stage patients.

Diffuse large B-cell lymphoma and gastrointestinal Kaposi's sarcoma: a rare cause of upper gastrointestinal bleeding.

A 49-year-old man with a history of human immunodeficiency virus (HIV) infection, in a state of advanced immunosuppression and current antiretroviral therapy initiation. He was admitted to the hematology department after diagnosis of diffuse large B-cell lymphoma (DLBCL) associated with Epstein-Barr virus (EBV), disseminated cytomegalovirus (CMV) infection and cutaneous Kaposi's sarcoma (KS). During admission, he presented an episode of melena with anemization, so an urgent gastroscopy was performed. In the stomach there were multiple erythematous lesions, large and elevated, suggestive of subepithelial origin. Some of them presented an umbilicated center and other were ulcerated, covered with fibrin. The bulb and second duodenal portion showed similar involvement, large violaceous ulcerated lesions. Biopsies were taken and the anatomopathological diagnosis of the duodenal lesions was KS and of the gastric lesions KS and DLBCL associated with EBV. KS is an endothelial tumor associated with HIV. The stomach is the gastrointestinal organ most frequently affected and the typical endoscopic findings are nodular lesions. The stomach is the most common site of extranodal involvement in DLBCL. In both pathologies, the manifestation as upper gastrointestinal bleeding is exceptional and endoscopic biopsies can confirm the diagnosis.

Molecular and Genetic Study for Detection of Helicobacter pylori Virulence Genes among Patients with Diffuse Large B-Cell Lymphoma

Background: The bacteria Helicobacter pylori (Hp) has supposed to confirm an oncogenic consequence with the evolution of malignancy events in stomach, effectiveness of Hp consider a top risk factor of gastric-diffuse large B-cell lymphoma (DLBCL). Aims: the aim of this study was to observe the correlation between virulence factors, especially cytotoxin association gene A (CagA) and the progress of gastric DLBCL. Materials and Methods: Biopsy samples (50) involved in this study (28 were men, and 22 women, with a mean age up to 57.64 years), among gastric-DLBCL patients, with (25) control (were 14 men and 11 women) without DLBCL, tested at Medical City Teaching Hospital and Teaching Laboratories, study conducted from January 1st to September 30, 2022. Diagnosis was by molecular methods included DNA extraction for Hp by STR-Format kit (BIORON Diagnostics GmbHm In den Rauhweiden 20,67354 Germany), and “real-time polymerase chain reaction” methods using the (ABI PRISM 7700) Sequence Detection System, also applied the primers and probes, for Hp-CagA. Results: The mean of age was 55.7 ± 2 in DLBCL, while in control were 61.82 + 6, CagA +ve 66.66 + 2. In gastric DLBCL, the red blood cell count, white blood cell count, platelets count, and hemoglobin were all decline in DLBCL, not in the control group, lactate dehydrogenase levels in gastric DLBCL patients were rise (322 U/L), while less in control, while albumin (322g/dl) was less in gastric DLBCL patients. Hp 16S rRNA was detected relating to CagA variety, 66% (33/50) were CagA positive with highly significant in 23 patients with DLBCL (P = 0.004), and 10 in control patients. CagA gene expression was highly expression in gastric DLBCL patients with range up to (+), 8 (++), and 12 (+++), while in the control group was 5 (+), 2 (++), and 3 (+++), respectively. Conclusions: This present study fixed high frequency of CagA gene in gastric DLBCL patients. Moreover, confirmed this gene is significantly associated with gastric DLBCL in patients with Hp. Moreover, genotype EPIYA-ABC motif is related with the high risk of gastric DLBCL.

Primary gastric diffuse large B-cell lymphoma in a child

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A Novel Prognostic Model for Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common phenotype of extranodal non-Hodgkin's lymphoma (NHL). This research aims to identify a model for predicting overall survival (OS) and cancer-specific survival (CSS) in PG-DLBCL. A total of 1716 patients diagnosed with PG-DLBCL between 1975 and 2017 were obtained from the SEER database and further randomly divided into the training and validating cohorts at a ratio of 7 : 3. Univariate and multivariate cox analyses were conducted to determine significant variables for the construction of nomogram. The performance of the model was then assessed by the concordance index (C-index), the calibration plot, and the area under the receiver operating characteristic (ROC) curve (AUC). Multivariate analysis revealed that age, race, insurance status, Ann Arbor stage, marital status, chemotherapy, and radiation therapy all showed a significant association with OS and CSS. These characteristics were applied to build a nomogram. In the training cohort, the discrimination of nomogram for OS and CSS prediction was excellent (C-index = 0.764, 95% CI, 0.744-0.784 and C-index = 0.756, 95% CI, 0.732-0.780). The AUC of the nomogram for predicting 3- and 5-year OS was 0.779 and 0.784 and CSS was 0.765 and 0.772. Similar results were also observed in the internal validation set. We have successfully established a novel nomogram for predicting OS and CSS in PG-DLBCL patients with good accuracy, which can help physicians to quickly and accurately complete the evaluation of survival probability, risk stratification, and therapeutic strategy at diagnosis.

Early Primary Gastric Lymphoma with Adverse Prognosis Factors. Is it Benefit Adding Rituximab to CHOP-14?

Objective: Assess if the addition of rituximab to a dose-dense chemotherapy regimen in patients with primary gastric diffuse large B-cell lymphoma (PGL) in early stage, but, associated with worse prognostic factors. Patients and Methods: Patients with pathological diagnosis of PGL and early stages, but, with elevated levels of beta 2 microglobulin and lactic dehydrogenase, age &gt; 18 years age without upper limit, no gender differences, previously untreated, were recruit in an open label clinical trial, to received CHOP-14 (cyclophosphamide, vincristine, doxorubicin and prednisone, dose dense, every 14 days) and compare with patients that received R-CHOP14 (rituximab + CHOP-14). Results: Between March 2011 to December 2016, 141 patients were taken entry to the study: no statistical differences were observed in clinical and laboratory characteristics. Complete response (CR) was observed in 68 out of 72 (94.4%) patients in the CHOP-R14, and 67 out of 69 (95.1%) patients in the CHOP14 regimen. Actuarial curves at 5-years show that progression-free survival (PFS) was 89% (95%Confidence Interval (CI) in the CHOP-R14, that did not have statistical differences in the CHOP-14 arm: 92% (95%CI: 83% -97%) (p 0.887); the overall survival were: 90% (95% CI:86%-97%) and 93.4% (95% CI: 86% to 97%) (p 0,665). Toxicities were severe granulocytopenia and infection-related, but no dead were observed. Until now, late toxicities as acute leukemia, second neoplasms and cardiac damage has not been observed. Conclusion: The use of dose dense regimen (CHOP-14) confirm that is useful in the treatment of PGL associated to worse prognosis factors, the addition of rituximab did not show any benefit.

5-Hydroxymethylation alterations in cell-free DNA reflect molecular distinctions of diffuse large B cell lymphoma at different primary sites

Background5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almost any organ, but the prognosis of patients with DLBCL at different primary sites varies greatly. Previous studies have shown that 5hmC displays a tissue-specific atlas, but its role in DLBCLs at different primary sites remains unknown.ResultsWe found that primary gastric DLBCL (PG-DLBCL) and lymph node-involved DLBCL (LN-DLBCL) patients had a favorable prognosis, while primary central nervous system DLBCL (PCNS-DLBCL) patients faced the worst prognosis, followed by primary testicular DLBCL (PT-DLBCL) and primary intestinal DLBCL (PI-DLBCL) patients. Thus, we used hmC-CATCH, a bisulfite-free and cost-effective 5hmC detection technology, to first generate the 5hmC profiles from plasma cell-free DNA (cfDNA) of DLBCL patients at these five different primary sites. Specifically, we found robust cancer-associated features that could be used to distinguish healthy individuals from DLBCL patients and distinguish among different primary sites. Through functional enrichment analysis of the differentially 5hmC-enriched genes, almost all DLBCL patients were enriched in tumor-related pathways, and DLBCL patients at different primary sites had unique characteristics. Moreover, 5hmC-based biomarkers can also highly reflect clinical features.ConclusionsCollectively, we revealed the primary site differential 5hmC regions of DLBCL at different primary sites. This new strategy may help develop minimally invasive and effective methods to diagnose and determine the primary sites of DLBCL.