Progression of Primary Gastric Diffuse Large B-Cell Lymphoma after Helicobacter pylori Eradication.

In Helicobacter pylori-positive, localized primary gastric diffuse large B-cell lymphoma (DLBCL), an increasing number of reports have recently been published on the effectiveness of H. pylori eradication (HPE). However, HPE treatment strategies for gastric DLBCL, including its indications, have yet to be examined. No detailed report has been published on a case of gastric DLBCL unsuccessfully treated by HPE. A 64-year-old female and a 70-year-old male were pathologically diagnosed with chronic active gastritis and mucosa-associated lymphoid tissue lymphoma, respectively. Both patients were positive for H. pylori, so HPE was employed. The disease progressed within 1 year, and both patients were pathologically diagnosed with DLBCL by endoscopic biopsy. On reviewing the first pathology slide, both patients were diagnosed with DLBCL. That is, the 2 patients had primary gastric DLBCL; however, they exhibited progressive disease after HPE. This failure of HPE treatment may be due to the initial lymphomas being multiplex ulcerative lesions. In both cases, complete remission was achieved by chemotherapy (plus radiation therapy) without recurrence for more than 3 years.

ALK-positive anaplastic large cell lymphoma presenting multiple lymphomatous polyposis: A case report and literature review.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma that can be divided into two categories: anaplastic lymphoma kinase-positive (ALK+) and ALK-negative. Gastrointestinal ALK+ ALCL is rare. Multiple lymphomatous polyposis (MLP) is thought to be a representative form of gastrointestinal lesion in mantle cell lymphoma, and T-cell lymphomas seldom show this feature. Here, we report the first known case of ALK+ ALCL with gastroduodenal involvement to present with MLP. CASE SUMMARY: The patient was a 43-year-old man who was complained of a mass in the left inguinal area and was performed open biopsy. ALK+ ALCL was diagnosed pathologically. Computed tomography scan demonstrated multiple lymph node lesions in the abdomen - pelvis/inguinal region, and scattered nodular lesions in both lung fields. He did not complain of gastrointestinal symptoms. While, esophagogastroduodenoscopy identified MLP lesions from the antrum of the stomach to the descending portion of the duodenum and mild thickened folds on the corpus of the stomach, and biopsy showed invasion of ALK+ ALCL. We treated this patient with six cycles of CHOEP (Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, and Prednisone) chemotherapy. At the conclusion of treatment, there was complete remission. Numerous white scars were found on the stomach, endoscopically consistent with a remission image of lymphoma. The endoscopic features of this case were thought to be similar to those of MCL. CONCLUSION: The macroscopic/endoscopic features of gastrointestinal ALK+ ALCL may be more similar to those of B-cell lymphomas rather than T-cell lymphomas.

Successful Treatment of Gastrosplenic Fistula Arising from Diffuse Large B-Cell Lymphoma with Chemotherapy: Two Case Reports.

Gastrosplenic fistula (GSF) is a rare condition arising from gastric or splenic lymphomas. Surgical resection is the most common treatment, as described in previous reports. We report two cases of GSF in diffuse large B-cell lymphoma (DLBCL) patients that were successfully treated with chemotherapy and irradiation without surgical resection. Case 1 was of a 63-year-old man who had primary gastric DLBCL with a large lesion outside the stomach wall, leading to a spontaneous fistula in the spleen. Case 2 was of a 59-year-old man who had primary splenic DLBCL, which proliferated and infiltrated directly into the stomach. In both cases, chemotherapy comprising rituximab + dose-adjusted EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) was administered. Case 1 had significant bleeding from the lesion of the stomach during the treatment cycle; however, endoscopic hemostasis was achieved. Case 2 developed a fistula between the stomach and the spleen following therapeutic chemotherapy; however, no complications related to the fistula were observed thereafter. In both cases, irradiation was administered, and complete remission was achieved.

Coexistence of primary colorectal follicular lymphoma and multiple myeloma: a case report.

Colorectal follicular lymphoma (FL) occurs less frequently than duodenal-type FL, which is an established entity, and primary multiple FL only involving the colon is rare. Furthermore, the coexistence of lymphoma and multiple myeloma (MM) within the same patient is rare and the current study reports such a case. The patient was an asymptomatic 62-year-old man. He underwent colonoscopy screening, which revealed at least five polypoid tumors from the cecum to the rectum. Biopsy samples stained positive for CD20 and B-cell lymphoma 2 (BCL2) but stained negative for CD10, and fluorescence in situ hybridization analysis identified IGH/BCL2 in 95.2% of the tumor cells. Based on these findings, the patient was diagnosed with FL. On the bone marrow aspirate, the plasma cell count was 30% of all nucleated cells. Bence-Jones κ-type protein was detected by protein electrophoresis in serum and urine. The serum-free light chain κ/λ level was significantly elevated (484.3). Thus, the patient was also diagnosed with MM. Both FL and MM were targeted therapeutically; rituximab and bendamustine were effective for FL, and lenalidomide and low-dose dexamethasone were effective for MM. The patient was treated for 3 years and 7 months and, until now, was off-treatment for 4 years without rapid progression of the two malignancies. Although both diseases are still present, the patient has maintained stable disease. Our findings suggest that lymphoma and MM should be targeted separately as independent hematological malignancies when they occur concurrently.

Late duodenal metastasis from renal cell carcinoma with newly developed malignant lymphoma: A case report.

Duodenal metastasis from renal cell carcinoma (RCC) is rare. The current case report presents a very rare case of late duodenal metastasis from RCC with newly developed malignant lymphoma (diffuse large B-cell lymphoma: DLBCL) at the same time. A 64-year-old man with systemic lymph nodes swelling who had undergone left nephrectomy for RCC 25 years previously, was admitted to the present hospital. Inguinal lymph node biopsy was performed, leading to a diagnosis of DLBCL. fluorine-18-fluorodeoxy-glucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) revealed multiple lymph nodes, spleen, and ileocecal lesions. CT revealed an obvious hypervascular tumor involving the duodenum/pancreatic head. The tumor was false-negative on 18F-FDG-PET/CT. On esophagogastroduodenoscopy, the tumor was detected in the descending portion of the duodenum and was observed to be consistent with the submucosal tumor with a central ulcer, resembling those of ulcer-forming DLBCL. A biopsy was then performed carefully, and a clear cell RCC-derived metastatic cancer was diagnosed. Ileocolonoscopy revealed mucosal thickening of the terminal ileum, and led to a diagnosis of DLBCL infiltration with biopsy. To the best of the author's knowledge, this is the first case report of the coexistence of metastatic cancer from RCC and malignant lymphoma in the small intestine simultaneously. It was necessary to make a careful differential diagnosis in the imaging studies.

Management consideration for patient with a large solitary fibrous tumor occupying the infratemporal fossa: A case report.

The solitary fibrous tumor (SFT) was first described as a mesenchymal tumor of fibroblastic type, present in the pleura. The head and neck area is the third most common site of SFT occurrence. Numb chin syndrome (NCS) is a rare neurological symptom. The current report describes the case of a 39-year-old female patient referred to the present hospital with NCS, which was later observed to be due to a large SFT in the infratemporal fossa. Computed tomography and magnetic resonance images were taken and subsequent examination of these images revealed a space occupying mass (52×50×40 mm) in the infratemporal fossa. An open biopsy was performed on the lower part of the right auricula following angiography assisted vascular embolization of the maxillary artery. Pathological diagnosis was verified as SFT. Despite the tumor size and anatomical site, the SFT was successfully reduced in size by treatment with intensity modulated radiation therapy (IMRT) alone, with no recurrence. IMRT treatment of SFT may be effective as a future potential option for locally advanced head and neck SFT.

¹8F-FDG PET/CT imaging for a gastrointestinal mantle cell lymphoma with multiple lymphomatous polyposis.

Multiple lymphomatous polyposis (MLP) is an uncommon type of gastrointestinal lymphoma characterized by the presence of multiple polyps along the gastrointestinal tract. Most of this entity is in fact considered the counterpart of gastrointestinal tract involvement for mantle cell lymphoma (MCL). To our knowledge, there have been no reports on [fluorine-18]-fluorodeoxy-glucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) imaging for gastrointestinal MCL with MLP. We present the results of (18)F-FDG PET/CT imaging in a patient with gastrointestinal tract involvement of MCL showing continuous MLP from the stomach to the rectum and intestinal intussusception. FDG-PET/CT findings were false negative in typical MLP spreading widely over the gastrointestinal tract, but uptake was noted in large lesions with deep infiltration considered atypical as MLP. On FDG-PET/CT imaging, the Ki-67 proliferative index, which is a cell proliferation marker, showed neither correlation with the presence of uptake nor the maximum standardized uptake value.

Large solid-pseudopapillary neoplasm of the pancreas with aberrant protein expression and mutation of ß-catenin: a case report and literature review of the distribution of ß-catenin mutation.

Solid-pseudopapillary neoplasms (SPN) are rare pancreatic tumors. The etiology of SPN involves mutations in the gene that encodes ß-catenin (CTNNB1). We herein report the case of a 23-year-old woman with a large SPN with proliferating tumor cells that displayed both solid and pseudo-papillary patterns. The simultaneous nuclear accumulation and loss of membrane localization of ß-catenin and E-cadherin was specifically observed in the tumor cells. Further, the tumor cells were shown to harbor a missense mutation in exon 3 of CTNNB1. We also present a review of the literature describing the clustering of CTNNB1 mutations in patients with SPN.

Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food-borne transmission of hepatitis E virus and public health concerns.

AIM: In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. METHODS: Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. RESULTS: All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. CONCLUSION: Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health.

Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor.

Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4-positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.

Polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc) ameliorates dextran sulfate sodium-induced colitis in mice.

OBJECTIVE: Polaprezinc (N-(3-Aminopropionyl)-L-histidinato zinc), an anti-ulcer drug, has been reported to have an anti-inflammatory action in several inflammatory diseases. The aim of this study was to investigate the effect of polaprezinc on dextran sulfate (DSS)-induced colitis in mice. MATERIAL AND METHODS: Mice with colitis induced by DSS were intrarectally treated with polaprezinc (15 mg/kg) or zinc sulfate (7.5 mg/kg) every day after the administration of DSS for 7 days. Disease activity index (DAI) and histological tissue damage were assessed. Levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon were measured. Expression of heat shock protein (HSP) 25 and HSP70 in the colon was analyzed by Western blot analysis. RESULTS: DAI and histological scores were remarkably reduced in polaprezinc-treated mice with DSS-induced colitis. Polaprezinc suppressed the increase of MPO activity and the production of TNF-alpha and IFN-gamma in the colon tissues of mice with DSS-induced colitis. Expression of HSP25 and HSP70 was remarkably up-regulated in the colon tissues of polaprezinc-treated mice during DSS treatment. CONCLUSIONS: Polaprezinc suppresses DSS-induced colitis in mice, partly through inhibition of production of pro-inflammatory cytokine, suppression of neutrophils accumulation and cytoprotection by overexpression of HSPs. Polaprezinc could be useful in the treatment of inflammatory bowel diseases.

Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis.

OBJECTIVE: Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice. MATERIALS AND METHODS: BALB/c mice were given 3% DSS solution orally for 7 days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7 days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50-500 mg/kg) when treatment of DSS started. RESULTS: It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-alpha and IFN-gamma induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS. CONCLUSIONS: Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.