Okayama University Medical School Acta Medica Okayama 0386-300X 69 5 2015 Primary Duodenal Follicular Lymphoma Treated With Rituximab Monotherapy and Followed-up for 15 Years 301 306 EN Anna Seki Masaya Iwamuro Masao Yoshioka Nobuharu Fujii Hiroyuki Okada Soichiro Nose Katsuyoshi Takata Tadashi Yoshino Kazuhide Yamamoto Case Report 10.18926/AMO/53676 A 41-year-old woman was diagnosed with duodenal follicular lymphoma. She had no other lesions and was assigned to a "watch and wait" policy. Swelling of the inguinal lymph nodes appeared 45 months later, and rituximab monotherapy resulted in complete remission. However, follicular lymphoma recurred in the stomach, rectum and mesenteric and external iliac lymph nodes 81 months after the therapy. The patient received rituximab monotherapy again and has remained in complete remission in the fifteenth year after the initial diagnosis. This case suggests the usefulness of rituximab monotherapy in the long-term management of intestinal follicular lymphoma. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0046-8177 45 7 2014 Low-grade B-cell lymphoma presenting primarily in the bone marrow 1379 1387 EN Kayoko Iwatani Katsuyoshi Takata Yasuharu Sato Tomoko Miyata-Takata Noriko Iwaki Wei Cui Seiko Sawada-Kitamura Hiroshi Sonobe Maiko Tamura Katsuhiko Saito Katsuya Miyatani Rie Yamasaki Ichiro Yamadori Nobuharu Fujii Yasushi Terasaki Yoshinobu Maeda Mitsune Tanimoto Naoya Nakamura Tadashi Yoshino Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1083-8791 20 2 2014 Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease 183 191 EN Haruko Sugiyama Yoshinobu Maeda Hisakazu Nishimori Yoshiko Yamasuji Ken-ichi Matsuoka Nobuharu Fujii Eisei Kondo Katsuji Shinagawa Takehiro Tanaka Kengo Takeuchi Takanori Teshima Mitsune Tanimoto Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1618-1247 100 2 2012 Histological and immunohistochemical features of gingival enlargement in a patient with AML 254 257 EN Norihiro Sonoi Yoshihiko Soga Hiroshi Maeda Koichi Ichimura Tadashi Yoshino Kazutoshi Aoyama Nobuharu Fujii Yoshinobu Maeda Mitsune Tanimoto Richard Logan Judith Raber-Durlacher Shogo Takashiba Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0941-4355 18 3 2010 Total bacterial counts on oral mucosa after using a commercial saliva substitute in patients undergoing hematopoietic cell transplantation 395 398 EN Yuko Sugiura Yoshihiko Soga Kokoro Yamabe Soichiro Tsutani Ichiro Tanimoto Hiroshi Maeda Susumu Kokeguchi Nobuharu Fujii Fumihiko Ishimaru Mitsune Tanimoto Fusanori Nishimura Shogo Takashiba The commercial saliva substitute OralbalanceA (R) has been reported to alleviate symptoms of postradiotherapy xerostomia in head and neck cancer patients. OralbalanceA (R) may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are in a severely compromised condition, and saliva substitute must not promote infection. We reported previously that OralbalanceA (R) has antimicrobial effects against microbial species detected during HCT in vitro. This study was performed to determine the in vivo effects of OralbalanceA (R) on oral mucosal total bacterial counts in patients undergoing HCT. A total of 18 neutropenic patients undergoing HCT were enrolled in this study. Before and after 1 week of OralbalanceA (R) use, bacterial samples were obtained from patients by wiping an area of I center dot 1 cm on the buccal mucosa with sterilized cotton swabs. Total bacterial counts of the obtained samples were examined by quantitative polymerase chain reaction amplification of the bacterial 16S ribosomal RNA gene. As controls, bacterial samples were also obtained from ten healthy subjects, and total bacterial counts were examined. No significant increase in bacterial count was observed with use of OralbalanceA (R). None of the patients showed bacterial counts above the range found in healthy controls after using OralbalanceA (R). In neutropenic patients undergoing HCT, OralbalanceA (R) did not increase the total counts of oral mucosal bacteria beyond the range found in healthy controls. Oral care using OralbalanceA (R) may alleviate the symptoms induced by hyposalivation without promoting infection. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0941-4355 16 10 2008 Evaluation of xerostomia in hematopoietic cell transplantation by a simple capacitance method device 1197 1200 EN Yuko Sugiura Yoshihiko Soga Sachiko Nishide Kotoe Kono Kanayo Takahashi Nobuharu Fujii Fumihiko Ishimaru Mitsune Tanimoto Fusanori Nishimura Shogo Takashiba Goals Hematopoietic cell transplantation (HCT) may lead to the development of xerostomia. However, there have been few reports of xerostomia in HCT patients based on objective data. We investigated moisture in the oral mucosa in patients undergoing HCT by the capacitance method using a convenient device, Moisture Checker for Mucus (R) (MCM; Life Co., Ltd., Saitama, Japan). Subjects and methods Thirty-six patients undergoing HCT at Okayama University Hospital of Medicine and Dentistry (Male=22, Female=14; age=41.6 +/- 16.2 years old) were enrolled in this study. Moisture in the oral mucosa was measured by MCM in accordance with the manufacturer's instructions. The results were obtained as MCM values (%), which are the weight percentage of water content in the oral mucosal epithelium. As controls, moisture of the oral mucosa was also examined in healthy volunteers (Male=27, Female=35; age=43.0 +/- 14.6 years old). Main results Throughout the examination period, MCM values were significantly lower in patients who underwent HCT than in controls. The degree of mucosal moisture in HCT patients showed wide interindividual differences. Conclusion The degree of mucosal moisture in HCT patients was low and showed wide interindividual differences. Evaluation of xerostomia using such a device may contribute to appropriate oral care with saliva substitute. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0941-4355 16 4 2008 Antimicrobial effects of the saliva substitute, Oralbalance (R), against microorganisms from oral mucosa in the hematopoietic cell transplantation period 421 424 EN Yuko Sugiura Yoshihiko Soga Ichiro Tanimoto Susumu Kokeguchi Sachiko Nishide Kotoe Kono Kanayo Takahashi Nobuharu Fujii Fumihiko Ishimaru Mitsune Tanimoto Kokoro Yamabe Soichiro Tsutani Fusanori Nishimura Shogo Takashiba Goals The commercially available saliva substitute Oralbalance (R) has been reported to alleviate symptoms of post-radiotherapy xerostomia in head and neck cancer patients. Oralbalance (R) may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are severely compromised, and saliva substitute must therefore not promote infection. This study was performed to determine the effects of Oralbalance (R) on microbial species identified during HCT. Patients and methods Microbial identification of oral mucosa was performed in 28 patients undergoing HCT. The antimicrobial effects of Oralbalance (R) against bacteria and fungi detected in the HCT period were examined in vitro. Briefly, bacteria and fungi were spread on agar plates, and 0.1g of Oralbalance (R) gel was applied (about phi 1cm). After incubation at 37 degrees C for 24h, the presence of a transparent zone of inhibition around Oralbalance (R) was observed. Main results Not only bacterial species constituting normal flora of the oral mucosa but also those not usually constituting normal flora, e.g., coagulase-negative Staphylococcus, were detected. A transparent zone was observed around Oralbalance (R) in all bacterial species examined. No transparent zone was observed for Candida albicans, but growth was inhibited in the area where Oralbalance (R) was applied. Conclusions Oralbalance (R) does not facilitate increases in microorganisms in the HCT period. Oral care with Oralbalance (R) does not promote infection in patients undergoing HCT. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2002 Expression of minor histocompatibility antigen, HA-1, in solid tumor cells EN No potential conflict of interest relevant to this article was reported.