Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Optimal Initial Workup in Patients With Superficial Primary Gastric MALT Lymphoma.

The prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is favorable, especially in the absence of lymph node metastasis (LNM). We investigated LNM incidence and location in superficial type gastric MALT lymphoma. We performed a retrospective analysis of 450 patients newly diagnosed with gastric MALT lymphoma with tumor infiltration confined to the mucosa or submucosa as evidenced by endoscopic ultrasonography. LNM incidence and location were evaluated. Of the 450 patients, most patients (434, 96.4%) were initially LNM negative as confirmed by computed tomography (CT) scanning. Sixteen patients (3.6%) were LNM positive. There was no difference in clinical characteristics between the 2 groups except for the extent of lymphoma involvement and endoscopic findings. Among 41 patients undergoing abdominal/pelvic CT (APCT) only, LNM was detected in 1 (2.4%). There were 8 LNM cases among 238 patients undergoing both APCT and chest CT (3.4%). Among 171 patients undergoing APCT, chest CT, and neck CT, 7 cases of LNM were detected (4.1%). The detection rates for each CT were as follows: abdominal CT, 13/450 (2.9%); chest CT, 6/408 (1.5%); and neck CT, 1/171 (0.6%). Among 6 patients with chest CT-positive findings, 3 showed no evidence of LNM on APCT. LNM was an infrequent finding in gastric MALT lymphoma patients with tumor infiltration confined to the mucosa or submucosa. Besides endoscopy and endoscopic ultrasonography, APCT and chest CT are considered as optimal initial workup modalities in patients with assumed primary superficial gastric MALT lymphoma.

Dieulafoy disease with gastric MALT lymphoma

Rationale:Dieulafoy lesion (DL), a rare cause of gastrointestinal bleeding, is easily covered by blood scab formation on the mucous membrane for its small size, which makes it difficult to be identified under endoscope. In clinical practice, it is also very easy to miss gastric mucosa-associated lymphoid tissue (MALT) lymphoma that exhibits atypical early manifestations under gastroendoscope and is difficult to be diagnosed by routine superficial biopsy. Most patients only experience nonspecific dyspepsia symptoms.Patient concerns:A 68-year-old man suffering from repeated melena for 6 years arrived at our hospital. The patient had undergone gastroscopy and capsule endoscopy at other hospitals for several times and received symptomatic treatment, but his melena still continued to recur. At our hospital, the capsule endoscopy displayed that there existed large hemorrhage in the stomach, after which a gastrointestinal decompression tube was placed, so the bright red blood was drained. Subsequently, a sunken vascular malformation tissue in the anterior wall of the gastric fundus was observed under emergency endoscope. Pulsating blood flow appeared immediately after biopsy, and over-the-scope clip (OTSC) was quickly applied to stop the bleeding. Near the bleeding point, scar-like tissue that was surrounded by interrupted mucosa was discovered, and biopsy was performed at this site.Diagnosis:The diagnosis of DL and gastric MALT were determined by the digestive endoscopy and biopsy pathology.Interventions:With the diagnosis of DL and gastric MALT, the hemorrhagic spot was treated by OTSC. After the patient's condition was stable, anti-Helicobacter pylori treatment was performed.Outcomes:After the corresponding treatment, the 6-month follow-up revealed that the lymphoma was not completely cured, but no further bleeding occurred. There was no bleeding in the epigastric region and the patient was in good condition.Lessons:From endoscopy, it is easy to miss DL. When the hemostatic equipment is fully prepared, biopsy can be performed. After biopsy, pulsatile bleeding is convincing evidence for Dieulafoy disease. OTSC represents an effective and low-risk method for DL and it could replace surgery. Moreover, the mucosa surrounding Dieulafoy disease should be carefully observed to exclude coexisting diseases such as lymphoma or gastric cancer.

Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity.

Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world’s population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.

S2977 Incidental Finding of Helicobacter Heilmannii in Two Asymptomatic Individuals

INTRODUCTION: Helicobacter heilmannii previously known as Gastrospirillum hominis is commonly seen in animals and may have zoonotic potential. It contributes to about 5% of human gastric infections, resulting in chronic gastritis, peptic ulceration, and rarely gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. Most patients are symptomatic and present with dyspepsia, epigastric pain, or acid reflux. We report two cases in which incidental H.Heilmannii was found in the pathological report. CASE DESCRIPTION/METHODS: Both our patients had undergone esophagogastroduodenoscopy (EGD) in anticipation of bariatric surgery. One is a 22-year-old morbidly obese female without significant medical illness, who had mild patchy erythematous mucosa in the gastric antrum. Biopsy revealed moderate to severe chronic active gastritis. Both H.pylori and H.heilmannii organisms were identified on the Hematoxylin and eosin (H&E) stain. Next is a 25-year-old morbidly obese female with gastroesophageal reflux disease. Her EGD also revealed mild patchy erythematous mucosa in the gastric antrum and biopsy showed moderate inactive gastritis, reactive lymphoid follicles, and frequent long tightly coiled bacteria highlighted on H&E stain consistent with H.heilmannii. They were both treated with a 2-week course of amoxicillin, clarithromycin, and omeprazole. They remained asymptomatic during subsequent office visits and are scheduled for follow up EGD after their bariatric surgery. DISCUSSION: Gastric inflammation in humans infected with H.heilmannii is less severe and usually involves the gastric antrum like seen in our patients. Co-infection of H.heilmannii and H.pylori is often seen and is believed to have a higher prevalence of intestinal metaplasia than does infection with either strain alone. Studies have highlighted that H.heilmannii like H.pylori, is effectively eradicated with similar antimicrobial therapy. We are however unable to detect the presence or confirm eradication via ancillary tests such as urea breath test, serum antibody testing, or stool testing as with H.pylori. Whether in symptomatic patients or with incidental chronic gastritis findings, it is prudent to look for H.heilmannii in the absence of, or concomitant with H.pylori infection and treat them adequately to prevent further complications.Figure 1.: Antral mild chronic active gastritis - H&E stain, 10x.Figure 2.: Antral moderate chronic active gastritis - H&E stain, 10x.Figure 3.: Long tightly coiled organisms with corkscrew appearance, consistent with Helicobacter heilmannii - H&E stain, 100x, oil.

PRIMARY SJOGREN SYNDROME CAUSING PULMONARY EXTRANODAL MARGINAL CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extranodal marginal zone lymphoma (MZL) of the lung is a rare pulmonary lymphoid malignancy and World Health Organization (WHO) classifies Mucosa associated lymphoid tissue (MALT) lymphoma as a subtype of B-cell MZL. CASE PRESENTATION: 80 year old Caucasian male with past medical history of obstructive sleep apnea, chronic kidney disease stage III, type II diabetes mellitus, hypertension and tobacco abuse, was first seen in pulmonary clinic for asymptomatic innumerate bilateral pulmonary nodules noted on Computed Tomography (CT) scan of the chest. He complained of occasional chronic dry mouth on further questioning. Antibody testing was positive for Antinuclear antibodies (245 AU/ml) and SS Ro antibody (188 AU/ml). His dry mouth and lower lobe predominant cystic and nodular changes were concerning for lymphoid interstitial pneumonia associated with Sjogren's syndrome. He was referred to rheumatology then subsequently lost to follow up. He presented two years later with increased shortness of breath and progressive weight loss. Pulmonary function tests (PFTs) showed an isolated low diffusing capacity for carbon monoxide at 33% predicted (down from 75% prior). CT scan revealed progression of his bilateral lung nodules and cystic changes in the lower lungs bilaterally. He then underwent bronchoscopy and surgical lung biopsy. This showed a low-grade B- cell lymphoma with plasmacytic differentiation, most consistent with MALT stage 1E Extranodal marginal zone lymphoma. Patient was started on rituximab weekly for 4 weeks and reported some improvement in his sicca symptoms. DISCUSSION: Roughly 10 to 20 percent of SS patients have clinically significant lung disease defined by symptoms most commonly cough and dyspnea. Abnormal imaging and PFTs are common. Thin-walled lung cysts are detected with CT imaging in 12 to 46 percent of SS patients. Interstitial lung disease can occur in SS in several forms (1). In a series of thirteen patients with pulmonary MALT lymphoma performed by Yachoui et. al, 54% were positive for primary sjogren syndrome (PSS) (2). No difference in outcomes was noted on two large retrospectives studies involving different treatment modalities including surgery, chemotherapy or combined therapy. Asymptomatic patients should be observed with no treatment indicated initially. It is indicated for patients with a high burden of lymphadenopathy with splenomegaly, organ dysfunction, bone marrow suppression, and/or rapid disease progression (3). Series performed by Yachoui et. al demonstrated a favorable prognosis in all cases of pulmonary MALT lymphoma with all treatment modalities resulting in complete and sustained response (2). CONCLUSIONS: SS can have wide ranging organ involvement. Prompt referral to rheumatology and active monitoring is paramount. Further investigation is warranted to better understand pulmonary MALT pathogenesis, treatment, and outcomes in PSS. Reference #1: Stojan, G., et al. (2013). “Pulmonary manifestations of Sjögren's syndrome.” Current allergy and asthma reports 13(4): 354-360. Reference #2: Yachoui R, Leon C, Sitwala K, Kreidy M. Pulmonary MALT lymphoma in patients with Sjögren's syndrome. Clinical medicine & research. 2017;15(1-2):6-12. Reference #3: Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A, et al. Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leukemia & lymphoma. 1997;26(5-6):527-37

S1614 Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Isolated to the Colon

INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare non-Hodgkin B-cell lymphoma commonly seen in the stomach but can be found anywhere in the gastrointestinal tract. We present a patient found to have MALT lymphoma of the colon during a screening colonoscopy, which was initially thought to be a laterally spreading sessile serrated lesion. CASE DESCRIPTION/METHODS: A 56-year-old female presented for colorectal cancer screening. She reported having chronic abdominal pain and new increase in stool frequency in the setting of a rise in life stressors. The colonoscopy revealed a 4 cm Paris 0-IIa-IIc polyp of the transverse colon and the patient was referred for repeat exam with endoscopic mucosal resection of the lesion. During the colonoscopy, the polyp was lifted without issue but proved difficult to entrap in various polypectomy snares. A few small pieces of the polyp were eventually removed and collected while the rest of the lesion was left in situ and tattoos applied proximally and distally. Histology revealed marginal zone lymphoma. Computed tomography of the chest, abdomen, and pelvis was negative for metastatic disease and confirmed Stage 1 MALT lymphoma. H. pylori stool antigen test was positive and Strongyloides stercoralis IgG antibody was negative. A multi-disciplinary team decided that a transverse colectomy would be the best treatment strategy based on the patient’s wishes. The patient tolerated the transverse colectomy well. Her medical oncologist advised clinical follow up and imaging (as the lesion was visible on CT preoperatively) every six months for five years as well as repeat colonoscopy at 1 year from surgery. Finally, she was treated for H. pylori infection with quadruple therapy. DISCUSSION: MALT lymphoma of the colon is exceedingly rare. While treatment for gastric MALT lymphomas is well established, management of colonic MALT lymphoma is not. Treatment options can consist of surgical resection, chemotherapy, or radiation therapy based on staging. Although guidelines for Stage 1 colonic MALT lymphoma recommend surgical resection, a multi-disciplinary approach is essential. H. pylori infection is rarely associated with MALT lymphoma in the colon. Results are mixed regarding H. pylori treatment in these individuals, although there have been reports of lymphoma resolution following eradication therapy. Overall this case demonstrated the importance of a multidisciplinary approach in a rare case that was initially thought to be a lateral spreading lesion.Figure 1.: Paris 0-IIa-IIc polyp measuring 4.0 cm in the transverse colon.Figure 2.: Endoscopic mucosal resection (EMR) of the identified polyp.Figure 3.: H&E, ×400: High-power image of lymphoepithelial lesion, where neoplastic cells are invading the colonic epithelium.

Proteomic and transcriptomic studies of BGC823 cells stimulated with Helicobacter pylori isolates from gastric MALT lymphoma.

BackgroundThe correlation between the infection of H. pylori and the occurrence of gastric MALT lymphoma (GML) has been well documented. However, the mechanism of how GML is caused by this bacterium is not well understood, although some immunologic mechanisms are thought to be involved.Materials and methodsIn this study, we performed both transcriptomic and proteomic analyses on gastric cancer cells infected by H. pylori isolates from GML patients and the gastric ulcer strain 26695 to investigate the differentially expressed molecular signatures that were induced by GML isolates.ResultsTranscriptomic analyses revealed that the differentially expressed genes (DEGs) were mainly related to binding, catalytic activity, signal transducer activity, molecular transducer activity, nucleic acid binding transcription factor activity, and molecular function regulator. Fifteen pathways, including the Wnt signaling pathway, the mTOR signaling pathway, the NOD-like receptor signaling pathway and the Hippo signaling pathway, were revealed to be related to GML isolates. Proteomic analyses results showed that there were 116 differentially expressed proteins (DEPs). Most of these DEPs were associated with cancer, and 29 have been used as biomarkers for cancer diagnosis. We also found 63 upstream regulators that can inhibit or activate the expression of the DEPs. Combining the proteomic and transcriptomic analyses revealed 12 common pathways. This study provides novel insights into H. pylori-associated GML. The DEPs we found may be good candidates for GML diagnosis and treatment.ConclusionsThis study revealed specific pathways related to GML and potential biomarkers for GML diagnosis.

APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection

The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.

Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing.

Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma that can be classified as a mucosal-associated lymphoid tissue (MALT) lymphoma. Recently, second-generation or next-generation sequencing (NGS), which allows simultaneous sequencing of hundreds to billions of DNA strands, has been a focus of attention and is rapidly being adopted in various fields. In the present study, paraffin-embedded tissue samples of gastric MALT lymphoma (n=1) and small intestine MALT lymphoma (n=4) were selected, and DNA was extracted from the tissue samples. After performing quality control, NGS was performed using HemaSCAN™, a custom panel of 426 genes, including essential blood cancer genes. NGS revealed single nucleotide variations (SNVs), short insertions and deletions (InDels) and copy number variations (CNVs). These genomic variants were reported as annotated, known or novel variants. An annotated variant, an erb-b2 receptor tyrosine kinase 2 gene amplification, was observed in one patient. Known and novel variants, including SNVs of SET binding protein 6 (SETBP6), Runt-related transcription factor 1 and Kelch-like ECH-associated protein 1 genes, InDel of the marker of proliferation Ki-67 gene, and CNVs of the zinc finger protein 703 and NOTCH1 genes, were observed in ≥2 patients. Additionally, InDels with frameshift mutations were identified in the B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3 and mucin 2, oligomeric mucus/gel-forming genes in one patient. Since few NGS studies have been performed on MALT lymphoma, the current results were unable to determine if the different mutations that were identified are ‘actionable’ (that is, potentially responsive to a targeted therapy) Further studies are required to determine the associations between genetic mutations and the development of MALT lymphoma.

IBCL-344: Marginal Zone Lymphoma: Epidemiology and Outcomes in a Mexican Center

Context: Marginal zone lymphoma (MZL) is a rare entity, representing 5% of non-Hodgkin lymphomas with straightforward differences in presentation. The treatment is diverse and depends on the location and the medical practice of each center. There is no information in Mexico regarding its presentation and long-term results. Objective: To describe and analyze the epidemiology and the prognostic factors of MZL relating to treatment response and survival. Design: Retrospective observational analytical study. Setting: Instituto Nacional de Cancerologia, a hemato-oncological reference center. Patients: 113 diagnosed with MZL between 2008 and 2019. Interventions: No interventions. Main outcome measures: Descriptive statistics were used. Bivariate risk analysis with X2 and Fisher's exact test were utilized to search for prognostic factors for survival. OS and DFS were assessed with Kaplan Mayer and Log Rank curves. Results: Patients' average age was 57 and predominantly female (57.5%). The median follow-up was 44 months (1–141). MALT was the most common histological WHO variant (87.6%, 99), followed by nodal (8.8%, 10) and splenic (3.5%, 4) ones. For MALT, the most frequent location was conjunctiva and eye attachments (59.6%), followed by stomach (23.2%) and salivary glands (8.1%). H. Pylori was identified in 48% of stomach MALT. DHL was elevated in 8%. Most (108) received treatment: chemotherapy (46.9%) followed by RT (28%). The global response was 76%. The 8-year OS was 75% for the entire group. Regarding MALT, favorable prognostic factors for OS were complete response p = 0.043 (OR 1.4, 95% CI 0.89-2.2) and location of ocular annexes p = 0.009 (OR 0.49 (95% CI 0.32–0.76). The stomach location was the unfavorable one p = 0.01 (OR 1.76, 95% CI 1.09-2.86). The 5-year OS for gastric localization was 57.5%, with a median of 72 months. Other areas did not reach the median (log rank Conclusions: MZL has a heterogeneous presentation. In our series, conjunctival and ocular annexes MALT is found as the main variant–different from that reported in the international literature. The long-term prognosis is favorable, unlike in patients with gastric MALT lymphoma, in which it is less than what is described in other series.

Analysis of the response time to involved-field radiotherapy in primary gastrointestinal low-grade B-cell lymphoma

BackgroundEarly-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy.MethodsPatients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary’s Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up.ResultsA total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer.ConclusionsDelayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.

Analysis of clinical prognosis of 68 patients with gastric mucosa-associated lymphoid tissue lymphoma

Objective: To explore the clinical features and prognosis of gastric mucosa-associated lymphoid tissue lymphoma. Methods: The data of patients with gastric mucosa-associated lymphoid tissue lymphoma diagnosed and treated at Peking University Cancer Hospital from 2000 to 2019 were collected, and their clinical characteristics, treatment options and effects, and prognosis were retrospectively analyzed. Results: The median age of 68 patients was 56 years old, and the ratio of men to women was 0.6∶1.0. Early patients accounted for about 76% (52/68). The most commonly used treatment is Helicobacter pylori eradication, followed by radiotherapy and chemotherapy. The total effective rate is 94%, of which the complete remission rate is 72%. With a median follow-up of 44 months, the 5-year progression-free survival (PFS) rate was 73%, and the overall survival (OS) rate was 83%. Prognostic factor analysis showed that albumin level (P=0.011) and international prognostic index (IPI)(P=0.017) are independent prognostic indicators of PFS, The 5-year PFS rate of patients with normal and reduced albumin was 77% and 50%, respectively, and the 5-year PFS rate of patients with IPI score<2 points and IPI ≥ 2 points was 80% and 48%, respectively. Lactate dehydrogenase (LDH) (P=0.016) and albumin level (P=0.025) are independent prognostic indicators of OS, and the 5-year OS rates of patients with normal and elevated LDH were 87% and 67%, respectively. The 5-year OS rates of patients with normal albumin and reduced were 92% and 73%, respectively. Conclusions: Gastric mucosa-associated lymphoid tissue lymphoma is sensitive to treatment and has a good prognosis. The patient's albumin and lactate dehydrogenase levels are independent prognostic indicators.

Effectiveness and Safety of Subcutaneous Rituximab for Patients With Gastric MALT Lymphoma: A Case–Control Comparison With Intravenous Rituximab

IntroductionRituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case–control study. Patients and MethodsAll consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test. ResultsTwenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group. ConclusionIn a small case–control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group.

Radiotherapy in Early-stage Gastric MALT: Improved Survival Without Increased Cardiac Death.

Radiotherapy (RT) is an effective treatment for localized gastric mucosa-associated lymphoid tissue (MALT) lymphomas unresponsive to antibiotic therapy; however, irradiating the stomach can result in significant radiation to the heart, a risk factor for cardiac disease. We analyzed the Surveillance, Epidemiology, and End Results database to evaluate outcomes related to cardiac disease among patients treated with RT for stage I gastric MALT. We identified adult patients treated between 1993 and 2014. The relationship between treatment modality (RT, chemotherapy, combination, and no treatment) and overall survival (OS), mucosa-associated lymphoid tissue-specific survival (MSS), non-mucosa-associated lymphoid tissue-specific survival (non-MSS), and cardiac-specific survival (CSS) was assessed using the Kaplan-Meier estimator and Cox proportional hazards analyses. A total of 2996 patients (median follow-up, 5.6 y) were analyzed: 27.5% had received RT alone, 12.1% chemotherapy alone, 3.9% chemoradiotherapy, and 56.5% no/unknown treatment (including antibiotic therapy). Compared with RT alone, patients who received chemotherapy alone exhibited worse OS (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.32-2.10; P<0.001) and MSS (HR: 2.10; 95% CI: 1.36-3.23; P=0.001). Although CSS appeared worse in patients who received chemotherapy (HR: 1.56; 95% CI: 0.92-2.66; P=0.10), it was not statistically significant. When comparing orbital and gastric MALT patients, there was no significant difference in CSS (HR: 0.80; 95% CI: 0.49-1.31; P=0.38). RT improved survival among patients with stage I gastric MALT without increasing the risk of cardiac death. Those with gastric MALT exhibited similar CSS to those with orbital MALT. Although we cannot analyze nonfatal cardiac toxicity, these results suggest that, absent antibiotic therapy, RT should remain first-line treatment for early-stage gastric MALT.

A case of Barrett\u2019s esophageal cancer with gastric mucosa-associated lymphoma

BackgroundAlthough the first-line therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma is the eradication of Helicobacter pylori, the effect of eradication in Helicobacter pylori-negative cases is unclear. In this case report, we describe a surgical option for a case of Barrett’s esophageal cancer with concurrent gastric mucosa-associated lymphoid tissue lymphoma.Case presentationA 79-year-old man was admitted to our hospital with Barrett’s esophageal cancer and gastric mucosa-associated lymphoid tissue lymphoma. Initially, we performed endoscopic submucosal dissection for Barrett’s esophageal cancer. Since residual tumor was observed after the endoscopic submucosal dissection, we performed an esophagectomy with two-field lymph node dissection, which was followed by placement of a gastric conduit via the posterior mediastinal route. He was discharged 14 days after surgery. Although no additional treatment exists for mucosa-associated lymphoid tissue lymphoma, no recurrent disease has been detected to date.ConclusionAn option to use a portion of the stomach with low-grade malignant mucosa-associated lymphoid tissue lymphoma as a conduit after esophagectomy was suggested.

Is mucosa-associated lymphoid tissue lymphoma an infectious disease? Role of Helicobacter pylori and eradication antibiotic therapy (Review).

Mucosa-associated lymphoid tissue lymphoma (MALT) is seldom considered a diagnosis hypothesis in symptomatic patients. These lymphomas present as a main risk factor for chronic gastritis due to Helicobacter pylori infection. H. pylori leads to chronic inflammation, producing lymphoid tissue in the stomach mucosa (MALT) possibly leading to malignant transformation. Even though H. pylori remains one of the most important factors in the development of MALT lymphoma, it is not mandatory in the evolution of MALT lymphoma since high-grade lymphomas present a lower prevalence of H. pylori. The prevalence of H. pylori is indirectly proportional with the progression into the gastric wall. Mucosal and submucosal MALT lymphomas have a higher prevalence of the bacteria. However, genetic factors remain a risk factor especially if eradication treatment fails. Even though a low percentage of MALT lymphomas are H. pylori-negative, some respond to antibiotic eradication treatment. This can be explained either by the immunomodulatory effect of antibiotics or by other infectious sources such as Helicobacter heilmannii and Campylobacter jejuni (small bowel lymphoma). Treatment in MALT gastric lymphoma was a breakthrough since it was the first time in oncology where tumours were cured by antibiotic therapy, leading us to wonder if MALT lymphomas are infectious disease or not?

Helicobacter pylori Antigen But Not the Organism Is Occasionally Present Within Germinal Centers: Implications for Patient Management and Biology.

Helicobacter pylori infection is present in two thirds of the world's population and induces a myriad of human diseases, ranging from gastritis to gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Detection is critical for treatment and may require immunohistochemical (IHC) staining when organisms are not visible on hematoxylin and eosin. We have encountered cases in which IHC for Helicobacter pylori failed to demonstrate curvilinear or coccoid organisms, but did show a reticular pattern of immunoreactivity involving the underlying germinal centers. We performed a systematic retrospective evaluation of the frequency of H. pylori germinal center immunoreactivity over a 54-month period through evaluation of 367 gastric specimens. H. pylori germinal center immunoreactivity was observed in 5% of cases with germinal centers. Nine of 11 (81%) patients with H. pylori germinal center immunoreactivity had concurrent or recent H. pylori infection, in comparison to 36% of patients with germinal centers present but no immunoreactivity (n=9 of 25 patients, P=0.03). None of the patients with germinal center immunoreactivity developed mucosa-associated lymphoid tissue lymphoma. In situ hybridization for H. pylori performed on 3 cases with positive germinal center IHC was negative for H. pylori nucleic acids within those germinal centers, demonstrating that only the antigen is present. This work demonstrates that H. pylori antigen, but not viable organisms, is present in germinal centers in 5% of gastric specimens, and is associated with recent or concurrent H. pylori infection. We advocate for reporting of all H. pylori germinal center immunoreactivity with a recommendation for ancillary H. pylori testing.

Defining the Helicobacter pylori Disease-Specific Antigenic Repertoire.

The analysis of the interaction between Helicobacter pylori (HP) and the host in vivo is an extremely informative way to enlighten the molecular mechanisms behind the persistency/latency of the bacterium as well as in the progression of the infection. An important source of information is represented by circulating antibodies targeting the bacteria that define a specific “disease signature” with prospective diagnostic implications. The diagnosis of some of the HP induced diseases such as gastric cancer (GC), MALT lymphoma (MALT), and autoimmune gastritis (AIG) is not easy because patients do not show symptoms of illness in early-onset stages, at the same time they progress rapidly. The possibility of identifying markers able to provide an early diagnosis would be extremely beneficial since a late diagnosis results in a delay in undergoing active therapy and reduces the survival rate of patients. With the aim to identify the HP antigens recognized during the host immune-response to the infection and possibly disease progression, we applied a discovery-driven approach, that combines “phage display” and deep sequencing. The procedure is based on the selection of ORF phage libraries, specifically generated from the pathogen’s genome, with sera antibodies from patients with different HP-related diseases. To this end two phage display libraries have been constructed starting from genomic DNA from the reference HP 26695 and the pathogenic HP B128 strains; libraries were filtered for ORFs by using an ORF selection vector developed by our group (Di Niro et al., 2005; Soluri et al., 2018), selected with antibodies from patients affected by GC, MALT, and AIG and putative HP antigens/epitopes were identified after Sequencing and ranking. The results show that individual selection significantly reduced the library diversity and comparison of individual ranks for each condition allowed us to highlight a pattern of putative antigens specific for the different pathological outcomes or common for all of them. Within the putative antigens enriched after selection, we have validated protein CagY/Cag7 by ELISA assay as a marker of HP infection and progression. Overall, we have defined HP antigenic repertoire and identified a panel of putative specific antigens/epitopes for three different HP infection pathological outcomes that could be validated in the next future.

A Single Case Study of Treating H-Pyroli Infection with Coconut Oil

Helicobacter pylori (H-Pylori) are a Gram negative spiral organism in GI Tract. Final effect of H-pylori on the GI tract is variable and determined by microbial and host factors. The particular end result of H-Pylori varies from chronic gastritis to PUD, Gastric MALT Lymphoma. A case presented with chronic gastritis associated H-Pylori infection. Which showed resemblance with Clinical features of vatha –pitha Parinaamashoola (pain during digestion). It was intervened successfully with samanasnehapana (internal oleation therapy) of coconut oil. Coconut oil administered for 15 days. Helicobacter pylori immunoglobulin (IgG H-pylori) evaluated before and after the treatment. A positive H-pylori infection became negative after the treatment.

The Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma using Radiotherapy

The Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma using Radiotherapy