Second-line triple therapy in failures with vonoprazan-based triple therapy for eradication of Helicobacter pylori.

Gastric acid inhibition during treatment is important for the eradication of Helicobacter pylori (H. pylori) infection. A novel potassium-competitive acid blocker, vonoprazan (VPZ), has been demonstrated to achieve high eradication rates; however, the efficacy of second-line treatment in failures of VPZ-based triple therapy has not been well studied. The aim of the current study was to determine the efficacy of VPZ in a first-line regimen for H. pylori eradication, and the efficacy of a second-line regimen using metronidazole (MTZ) in failures with the first-line regimen. Of 580 subjects enrolled in the study, 524 patients completed first-line treatment (275 patients who received VPZ and 249 patients who received LPZ). First-line regimens consisted of a combination of clarithromycin (CAM) 200 or 400 mg twice a day, amoxicillin (AMPC) 750 mg twice a day, and either LPZ 30 mg or VPZ 20 mg twice a day, administered orally for 7 days. CAM and VPZ/LPZ were replaced with metronidazole (MTZ) 250 mg and rabeprazole 10 mg in the second-line regimens. The eradication of H. pylori was assessed by the H. pylori stool antigen test. The overall first-line eradication rate with VPZ was significantly higher than that with LPZ [91.0% (250/275) vs. 84.7% (211/249), respectively, P=0.030]. The dose of CAM (400 vs. 800 mg) did not affect the eradication rate in either the VPZ or LPZ regimens. The overall eradication rates of the second-line regimens with MTZ did not differ significantly between the VPZ-failure and LPZ-failure groups [87.0% (20/23) vs. 87.9% (29/33), respectively, P=0.700]. Therefore, VPZ was significantly more effective than LPZ for first-line treatment. In patients with failure of first-line eradication therapy, successful results of second-line eradication therapy did not differ between the VPZ- and LPZ-failure groups. In conclusion, VPZ-based triple therapy should be recommended for eradication of H. pylori.

[A case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus-positive patient].

We report a case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus (HIV)-positive patient. The patient was a 47-year-old Japanese woman who received salvage combination anti-retroviral therapy with darunavir plus ritonavir plus raltegravir plus tenofovir/emtricitabine in May 2009. She was diagnosed with lung adenocarcinoma (T3N3M1, stage IV) in November 2010 and was not found to possess any activating mutations in the epidermal growth factor receptor gene. Therefore, 6 courses of carboplatin plus pemetrexed and 3 courses of gemcitabine followed by erlotinib were administrated, and therapy was changed to home medical care. The only drug-related adverse event was grade 1 neutropenia, and drug interaction between the simultaneously administered anti-retroviral and chemotherapeutic agents was not confirmed. The patient battled lung adenocarcinoma for 1 year after the diagnosis and died of cancer progression in October 2011. Her performance status was stable and the CD4 (+) lymphocyte count and HIV load were well controlled throughout the course of treatment. In conclusion, the agents used for this patient show high tolerability and can be used as an effective treatment strategy for lung cancer occurring in HIV-positive patients.

A case report on a patient who presented with myelofibrosis, developed breast cancer with myeloid metaplasia, and finally showed immature NK-cell leukemia or AML without maturation with CD56 expression transformation in the pleura with extramedullary hematopoiesis: a 25-year course.

This study reports a female patient who suffered from primary myelofibrosis at 38 years of age, breast cancer with myeloid metaplasia at 49 years of age, and pleural effusion and multiple subcutaneous nodules at 62 years of age. She was finally diagnosed with immature NK-cell leukemia or AML without maturation with CD56 expression transformation of extramedullary hematopoiesis that developed in the pleura, and died 11 months later. Atypical cells in the pleural effusion had surface markers of CD13, CD33, CD34, and CD56 using a fluorescence-activated cell sorter analysis, and were positive for myeloperoxidase, CD34, CD43, and CD56 in a cell block material using an immunohistochemical method. Megakaryocytic and erythroblastic cells were also seen in the pleural effusion.

Bence-Jones protein-type myeloma with amyloid myopathy presenting as amyloidomas and extensive amyloid deposits in the muscularis propria: a rapidly fatal autopsy case.

This study reports a 59-year-old man who suffered from multiple skeletal muscle amyloidomas and showed a rapidly fatal course. He noticed left inguinal pain and gait disturbance due to muscle weakness of the left leg. Protein in urine (3.3 g/d) and Bence-Jones protein of the κ type (2.3 g/d) were detected. Bone marrow aspiration showed 11.6% monoclonal plasma cells in nucleated cells. A core needle-biopsied and resected left inguinal tumor showed the deposition of eosinophilic amorphous materials positive for Congo red stain and the κ-light chain. He was diagnosed with plasma cell myeloma with AL (amyloid light chain) amyloidosis. Multiple soft-part tumors developed, grew rapidly, and he died 3 months after admission. At autopsy, 3 large amyloidomas were observed in the skeletal muscles, and prominent amyloid deposits were also seen in the diaphragm, intercostal muscle, iliopsoas muscle, and cervical skeletal muscles examined. Massive amyloid materials deposited diffusely in the propria muscularis of the gastrointestinal tract: the tongue to the rectum.

Concurrent gastric MALT and Hodgkin lymphoma: a case report.

This report describes a 60-year-old man with concurrent gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and classical Hodgkin lymphoma (CHL). Atypical, medium-sized, lymphoid cells proliferated in the mucosa to muscular layer of the stomach showing a lymphoepithelial lesion; admixed with Hodgkin/Reed-Sternberg (HRS) cells and an inflammatory cell background. MALT lymphoma cells expressed CD20, CD79a, PAX5, and BOB.1, and HRS cells expressed CD30, CD15, Epstein-Barr virus-encoded RNA, and EBV-latent membrane protein 1. Only CHL invaded into the regional lymph nodes. Two possibilities of transformation of MALT lymphoma into CHL and de novo CHL within MALT lymphoma are discussed.

Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgkin lymphoma and developing as peripheral T-cell lymphoma 9 years later: a case report of composite lymphoma.

We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.

A case report of angioimmunoblastic T cell lymphoma (AITL) with localization of neoplastic clear cells in the outer zone of germinal centers.

Angioimmunoblastic T cell lymphoma (AITL) is characterized by the presence of atypical lymphocytes with clear cytoplasm and follicular dendritic cells, arborization of high endothelial blood vessels, and infiltration by inflammatory cells, such as epithelioid histiocytes, eosinophils, immunoblasts, and plasma cells. The neoplastic clear cells are localized around the high endothelial blood vessels or interfollicular areas. Recent reports have suggested that these neoplastic clear cells originate from helper T cells in germinal centers, based on their expression of CD10, PD-1, and CXCL13. We experienced a case of AITL which is histologically unique. A 61-year-old male presented to our hospital (Ogaki Municipal Hospital) with edema of his lower legs. Inguinal lymph node biopsy revealed that neoplastic clear T cells were mainly localized in the outer zone of germinal centers, specifically within the follicular dendritic cell (FDC) meshwork. Moreover, these cells were positive for CD3, CD4, CD10, CD43, CD45RO, PD-1, and weakly positive for CXCL-13. This is the first report showing that the neoplastic clear T cells were localized in the outer zone of germinal centers morphologically as well as immunohistochemically. In conclusion, this case report further supports the notion of germinal center helper T cell origin of neoplastic clear cells in AITL.

XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow.

A total of 29 cases of diffuse large B-cell lymphoma initially manifesting in the bone marrow (BM-DLBCL) were analyzed for V(H) gene sequence, and expression microarray of chemokines and chemokine receptors and immunohistochemical analysis were done. Seminested polymerase chain reaction (PCR) and sequencing analyses of 18 cases revealed that the V(H) gene usage in 6 cases was restricted to V(H)3-7, in 3 cases to V(H)4-34, and in 2 cases to V(H)4-39, which were all previously reported to be autoreactive. In total, 14 of 18 V(H) genes were those associated with autoimmune diseases, including V(H)3-21, V(H)3-23, and V(H)3-48. Furthermore, cDNA microarray analysis specific for chemokine and chemokine receptors revealed that chemokine receptor XCR1 expression was significantly elevated in the BM-DLBCL cases (P < .05), which was confirmed by quantitative reverse transcriptase-PCR and immunohistochemical analysis. Expression of the chemokine receptor XCR1 and frequent usage of autoreactive V(H) genes seem to be distinct characteristics of BM-DLBCL.

Coexistence of primary pulmonary Hodgkin lymphoma and gastric MALT lymphoma associated with Epstein-Barr virus infection: a case report.

We describe a 66-year-old woman with Epstein-Barr virus-associated lymphoproliferative disorder with lung and gastric tumors. We identified two lung tumors measuring 13 and 20 mm in diameter that consisted of CD30-, CD15-, and CD20-positive Hodgkin- and Reed-Sternberg-like cells and heterogeneous cellular infiltrates in a pronounced nodular pattern, with necrosis and vasculitis, diagnosed as nodular sclerosis classical Hodgkin lymphoma. A gastric tumor showed low-grade extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Neoplastic cells in all tumors expressed Epstein-Barr virus-encoded RNA based on in situ hybridization. The present case is a rare composite lymphoma arising from different extranodal organs, associated with EBV infection. Her medical history included gamma-knife therapy for clinical diagnosis with a suspicion of cerebral lymphoma.

A unique case of nasal NK/T cell lymphoma with frequent remission and relapse showing different histological features during 12 years of follow up.

Nasal natural killer (NK)/T cell lymphoma is an aggressive subtype of non-Hodgkin lymphomas, usually with a broad morphological spectrum, necrosis and angioinvasion, and is closely associated with Epstein-Barr virus (EBV) infection. We herein report a unique case of nasal NK/T cell lymphoma with frequent complete remission and relapse 12 years of follow up. A 9-year-old girl was diagnosed as having nasal NK/T cell lymphoma in 1995. The histological features were typical with diffuse lymphoid cell infiltration and angiocentric destruction. At the time of third relapse, however, biopsy showed infiltration of small sized lymphoid cells without necrosis and ulceration. These lymphoid cells were positive for both NK/T cell phenotype and EBV-encoded small RNAs. The tumor regressed spontaneously after biopsy and her clinical symptoms subsided. When she was admitted to the hospital in 2006 she had an extensive destructive lesion in the nasal cavity. These findings represent a rare case, in which histological findings changed in each time of relapse.

Primary cardiac B-cell lymphoma presented as heart tamponade and atrioventricular block: a case report.

BACKGROUND: Primay cardiac lymphoma is rare, and its diagnosis is not determined until autopsy. CASE: A 49-year-old man presented with heart tamponade and atrioventricular block. Bloody pericardiac effusion showed a monotonous proliferation of atypical large mononuclear cells, which demonstrated a lambda light-chain monoclonality by the fluorescence-activated cell-sorter method and clonal rearrangement bands by Southern blot analysis of the IgH gene. Transvenous biopsy excised from the right atrial tumor was diagnosed as diffuse large B-cell lymphoma. He underwent chemotherapy and permanent pacemaker implantation and is alive and well. CONCLUSION: Liquid cytology of cardiac effusion was very useful for rapid diagnosis, leading to a better prognosis.

Angioimmunoblastic T-cell lymphoma with autoimmune thrombocytopenia: a report of two cases.

We report two patients, a 68-year-old man (Case 1) and a 66-year-old man (Case 2), with polyclonal gammopathy, lymphadenopathy, thrombocytopenia, and high platelet-associated IgG (PAIgG) level. We initially diagnosed them as having angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). From confirmation of clear cells by careful observation and detection of rearrangement bands of T cell receptors by Southern blot hybridization analysis, we finally concluded that their diagnoses were compatible with angioimmunoblastic T-cell lymphoma (AILT). AILT with autoimmune thrombocytopenia (AIT) is very rare, and all the reported cases were Japanese ones.

Epstein-Barr virus-associated proliferative disorder presenting as Hodgkin's lymphoma and developing as aggressive natural killer-cell leukemia 19 years later: a case report of composite lymphoma.

We describe a patient who was diagnosed as having classic Hodgkin's lymphoma at 29 years of age, and aggressive natural killer-cell leukemia at 48 years. He died 42 days later. Hodgkin and Reed-Sternberg cells in the lymph node expressed CD30, CD15, T-cell intracellular antigen-1 (TIA-1), perforin, granzyme B, and Epstein-Barr virus-encoded RNA (EBER). Natural killer-cell leukemia cells in the bone marrow expressed cytoplasmic CD3epsilon, TIA-1, perforin, granzyme B, and EBER, and some neoplastic cells expressed CD56 (123C3). Fluorescence-activated cell sorter (FACS) analysis showed that neoplastic cells expressed CD56. Neither a rearrangement band of the T-cell receptor gene nor that of the immunoglobulin heavy chain gene was detected. Chromosomal abnormalities were noted.

Sustained remission after rituximab-containing chemotherapy for intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVL) is rare aggressive disseminated lymphoma associated with poor outcomes. Rituximab is a novel molecular agent that can reportedly improve outcomes for patients with diffuse large B-cell lymphoma. However, the safety and efficacy of rituximab in patients with IVL are unclear. A 76-year-old woman was hospitalized due to altered consciousness, fever and respiratory abnormalities. Definitive diagnosis of IVL was obtained following repeated biopsies of bone marrow. The patient received chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, and rituximab (R-CHOP), and achieved complete remission after 3 courses of treatment. She has remained in complete remission for over 3 years after diagnosis. This report suggests that rituximab-containing regimens could be safe and effective for elderly patients with IVL.

Sphingosine 1-phosphate potentiates human lung fibroblast chemotaxis through the S1P2 receptor.

Migration of fibroblasts plays an essential role in tissue repair after injury. Sphingosine 1-phosphate (S1P) is a multifunctional mediator released by many cells that can be released in inflammation and after injury. This study evaluated the effect of S1P on fibroblast chemotaxis toward fibronectin. S1P alone did not affect fibroblast migration, but S1P enhanced fibronectin-directed chemotaxis in a concentration-dependent manner. The effect of S1P was not mimicked by dihydro (dh) S1P or the S1P(1) receptor agonist SEW2871. S1P augmentation of fibroblast chemotaxis, however, was completely blocked by JTE-013, an S1P(2) antagonist, but not by suramin, an S1P(3) antagonist. Suppression of the S1P(2) receptor by small interfering (si)RNA also completely blocked S1P augmentation of fibroblast chemotaxis to fibronectin. S1P stimulated Rho activation and focal adhesion kinase (FAK) phosphorylation, and these were also significantly inhibited by the S1P(2) receptor antagonist (JTE-013) or by S1P(2) siRNA. Further, the potentiation of S1P signaling was blocked by the Rho-kinase inhibitor Y-27632 in a concentration-dependent manner. Inhibition of FAK with siRNA reduced basal chemotaxis toward fibronectin slightly but significantly, and almost completely blocked S1P augmented chemotaxis. These results suggest that S1P-augmented fibroblast chemotaxis toward fibronectin depends on the S1P(2) receptor and requires Rho and Rho-kinase, and FAK phosphorylation. By augmenting fibroblast recruitment, S1P has the potential to modulate tissue repair after injury. The pathways by which S1P mediates this effect, therefore, represent a potential therapeutic target to affect tissue repair and remodeling.

c-Maf expression in angioimmunoblastic T-cell lymphoma.

The oncogene c-Maf was recently found to be overexpressed in approximately 50% of multiple myeloma cases, and a role for c-Maf in promoting cyclin D2 expression has been postulated. We previously examined c-Maf expression in various T-cell lymphomas by reverse-transcription polymerase chain reaction and found extremely elevated c-Maf levels in angioimmunoblastic T-cell lymphoma (AILT). In this study, we examined T-cell lymphomas for c-Maf and cyclin expression immunohistochemically. Of 93 cases of T-cell lymphomas we investigated in the current study, c-Maf expression was seen in 23 out of 31 cases of AILT, 3 out of 11 of adult T-cell leukemia/lymphoma, 4 out of 19 of peripheral T-cell lymphoma, unspecified [PTCL(U)], and 0 out of 11 cases of mycosis fungoides, 0 out of 11 of anaplastic large cell lymphoma, and 1 out of 10 of extranodal NK/T-cell lymphoma, nasal type. Double immunostaining in AILT revealed that the majority of c-Maf-positive cells were also positive for CD43 (MT1), CD45RO (UCHL-1), and CD4 but were negative for CD20 (L26). Additionally, cyclins D1 and D2, which stimulate cell cycle progression, were overexpressed in a large number of the c-Maf-positive AILT samples. Quantitative reverse-transcription polymerase chain reaction analysis also showed that c-Maf was overexpressed in 8/31 cases of AILT, 0/19 cases of PTCL(U), 0/11 cases of anaplastic large cell lymphoma, 0/10 cases of extranodal NK/T-cell lymphoma, nasal type, and 2/8 cases of multiple myeloma, presenting significant difference between AILT and PTCL(U) (P=0.016, chi test). These findings strongly suggest that CD4-positive neoplastic T cells in AILT show c-Maf expression and provide new insight into the pathogenesis of AILT suggesting c-Maf to be a useful diagnostic marker for AILT.

Mucin biosynthesis: molecular cloning and expression of mouse mucus-type core 2 beta1,6 N-acetylglucosaminyltransferase.

Secreted mucins protect the underlying epithelium by serving as the major determinant of the rheological property of mucus secretion and the receptors for pathogens. These functions can be affected by the three branch structures, including core 2, core 4, and blood group I, which are synthesized by the mucus-type core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT-M). Decreased activity of this enzyme and expression of this gene have been found in colorectal cancer, which supports the important role of this enzyme in the protective functions of secreted mucins. We cloned full-length mouse (m) C2GnT-M cDNAs and showed that the deduced amino acid sequence was homologous to those of other C2GnT-Ms. The recombinant protein generated by mC2GnT-M cDNA exhibited core 2, core 4, and blood group I enzyme activities with a ratio of 1.00:0.46:1.05. We identified two different size transcripts by rapid amplification of cDNA ends and RT-PCR. Derived from the 6.6 kb mC2GnT-M gene composed of three exons and two introns, these two transcripts were intronless and differed by the length of the 3' untranslated region. In addition, exon 2 was found to be heterogeneous in size. This gene was highly expressed in the gastrointestinal tract, including colon, stomach, and small intestine. Antibodies generated against mC2GnT-M identified this enzyme in the goblet cells and other mucus cells/glands. This report provides the basis for further characterization of the regulation of mC2GnT-M gene expression and the biological functions of this gene.

Distribution of nestin and other stem cell-related molecules in developing and diseased human spinal cord.

In mammalian spinal cords, no neurogenesis has been observed after initial development. However developed mammalian spinal cords seemingly contain neural stem cells (NSC), which can give rise to neurons and glial cells when they are placed in appropriate environments. The purpose of the present paper was to investigate the developing, developed, and diseased human spinal cord to see which cell types have an immunophenotype similar to NSC. In 12 specimens from preterm neonates and term infants up to 14 months old, nestin was expressed in cells that extended fibrous processes and were located around the midline in the ependymal layer. In all the preterm neonates, Musashi-1 and glial fibrillary acidic protein (GFAP) were also expressed in this subpopulation, whereas Lewis X was detected in a less restricted subpopulation. Nestin expression by these cells was not detected in most adult spinal cords, but was observed in three spinal cords from 13 amyotrophic lateral sclerosis patients and eight of 14 spinal cords involved by the tumor. The present observations suggest that during gestation a subpopulation of cells in the ependymal layer remains undifferentiated as potential NSC/neural progenitor cells, and becomes unidentifiable in early infancy. These cells, however, appear in response to disease conditions, especially tumor involvement.