Dual-alkylator Conditioning Regimen with Busulfan and Melphalan for Bone Marrow Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelofibrosis : The Results of a Retrospective Study at a Single Institution in Japan

Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant morbidity and mortality, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative approach. While the optimal conditioning regimen before allo-HSCT for MF patients remains to be determined, recent studies have suggested that a thiotepa-busulfan-containing dual-alkylator regimen, FBT regimen, may be associated with favorable outcomes. In Japan, however, thiotepa is not indicated for MF. Here we describe the results of 6 cases of MF treated with melphalan-busulfan containing dual-alkylator regimen, FBM regimen, followed by their first allo-HSCT at a single institution. Neutrophil and platelet engraftment was achieved in all patients. And a full donor chimerism was confirmed in all patients at ＋30 days after allo-HSCT. The relatively small size and short observation period of our study make it difficult to draw a definitive conclusion ; however, our results suggest that a dualalkylator regimen of FBM may be a candidate for an conditioning for allo-HSCT for MF, which should be verified with a large cohort of patients.Article信州医学雑誌 71(6) : 393-402, (2023)journal articl

STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia

Large granular lymphocyte leukemia (LGLL) has been morphologically characterized as a group of lymphoproliferative diseases that include T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of natural killer cells (CLPD-NK). We investigated mutations in the Src homology 2 (SH2) domain of the signal transducer and activator of transcription 3 (STAT3) gene in Asian cohorts of T-LGLL and CLPD-NK (n=42 and 11, respectively). Two mutations, Y640F and D661Y, were identified using direct sequencing or allele-specific (AS) PCR. Y640F and D661Y mutations were found in seven and 18 patients, respectively. Two patients were positive for both mutations. Frequencies of STAT3 mutations in T-LGLL and CLPD-NK were 47.6% and 27.2%, respectively. Pure red cell aplasia (PRCA) was associated with the mutations (P=0.005). The mutations were persistently found at stable levels in some patients after more than 5years using AS-quantitative PCR. The results of the present study indicate that the SH2 domain of the STAT3 gene is frequently mutated in Asian T-LGLL and CLPD-NK, and that PRCA is closely correlated with the mutations. SH2 domain of the STAT3 gene is frequently mutated in Asian T cell large granular lymphocyte leukemia and chronic lymphoproliferative disorders of NK cells. Pure red cell aplasia is closely associated with the mutations.ArticleCANCER SCIENCE. 105(3):342-346 (2014)journal articl

Skin Tube Reconstruction for Esophageal Defects due to Postoperative Complications: Applying a skin flap in esophageal resection and reconstruction

Numerous improvements and advances in operational methods and techniques have occurred in the area of reconstruction for esophageal cancer. Patients with thoracic esophageal cancer who have previously had a gastrectomy usually undergo reconstruction using the colon and small intestine. The incidence of organ necrosis is not necessarily low after reconstruction with those organs. Generally, the main types of skin flaps and musculocutaneous flaps used for cervical and other esophageal reconstructions are deltopectoral (DP) flaps, pedicled musculocutaneous latissimus dorsi flaps and free anteriolateral thigh flaps. This kind of reconstruction is low invasive, relatively simple, and also causes very few fatal post-operative complications. Therefore, it is considered to be an effective reconstruction choice for the following types of patients: poor risk patients, patients whose gastrointestinal (GI) tract cannot be used for their reconstruction for some reason, and patients having a second reconstruction due to complications caused by organ necrosis after their first GI tract reconstruction

コウベジョガクインオヨビニシノミヤシナイニセイソクスルヤセイメダカ(Oryzias latipes)ノイデンシガタブンセキ

Medaka（Oryzias latipes)is a freshwater fish found naturally in Japan, Korea and China. In Japan, the wild populations of medaka consist of three genetically different clades(A,B and C). Clade A can be subdivided into three subclades and clade B into eleven, and destribution patterns of the mitotypes in each of subclades show strong geographical associations. Recently, the release of nonnative medaka has caused increased concern about potentially detrimental effects on the genetic structure of these wild populations.To quantify the genetic impactof nonnative medaka on wild populations, we examined genetic variations within the mitochondrial cytochrome b gene in wild populations of medaka at three sites in Kobe College and at five sites in Nishinomiya City using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)analyses. At Kobe College, almost all specimens had the B1a mitotype, a native mitotype belonging to subclade B-VⅡ(the Setouchi subgroup)and found at various locations within Hyogo Prefecture. This finding strongly suggests that the medaka population at Kobe College originates from one of the major native groups found in Nishinomiya City. At three out of the five sites examined in Nishinomiya City, two in the Kamino-cho area and a wastewater treatment plant in Koshienhama, specimens had either the B1a or B9 mitotype, which also belongs to subclade B-VⅡ and is found at the same locations as the B1a mitotype, suggesting that medaka populations at these setes originate from wild populations. By comparison, populations at two other sites in Nishinomiya City(Kamioichi and Naruohama)showed a high frequency of the B27 mitotype,which belongs to subclade Ⅱ（the Higashi-nihon Ⅱsubgroup)and is an original mitotype of himedaka, an orange-red type commercial strain of O.latipes that is widely distributed throughout Japan. The presence of the B27 mitotype in these populations implies thatgene introgression from himedaka populations to wild medaka populations has occurred

A Case of Cholesterol Crystal Embolization with Hemorrhagic Intestinal Ulcer

Cholesterol crystal embolization (CCE) is a rare systemic embolism caused　by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during　vascular manipulation such as vascular surgery or endovascular catheter manipulation, or　due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal　ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history　of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI)　for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed　tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and　bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small　intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small　intestine was performed. A histopathological examination indicated that small intestine　obstruction was caused by CCE. A histopathological examination indicated that small intestinal　obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular　manipulation, CCE should also be considered

Evaluation of intra-ductal cancer spread using contrast superb micro-vascular imaging (SMI) : a case report

Currently, breast conserving surgery has been adopted to treat more than half of all breast cancer patients in Japan. When performing breast-conserving surgery, an appropriate margin needs to be determined for radical cure. The resection volume influences the esthetic outcome, but a cancer-positive resection stump is also important risk factor of local recurrence. Additionally, the degree of cancer progression influences the surgical method, so understanding the appropriate resection margin is necessary for the surgeons. We report here on a 50- year old patient whose intra-ductal cancer progression was shown, as predicted, by contrast SMI (superb micro-vascular imaging). A one-cm size tumor mass was palpable with a clear boundary. B-mode ultrasound confirmed the presence of a breast duct towards the nipple from the tumor mass. Using contrast SMI, an accelerated blood flow was detected around the duct, which suggested intra-ductal progression. The pathological results also showed intra-ductal progression to the nipple from the tumor. Around the progression area, a meandering vessel was found and the vessel was able to be visualized by contrast SMI

Degos 病の関与が疑われた腸管気腫症の一例

症例は70歳代男性．既往に脳梗塞，パーキンソン病があり抗凝固薬を内服していた．デイサービス利用中に倦怠感および血圧低下を認め近医を受診し入院加療となった．入院２日目に40℃の熱発があり，腹部造影CT を施行したところfree air を認め外科的治療目的に当院へ救急搬送された．造影CT では肝彎曲部から脾彎曲部にかけての横行結腸に腸間膜気腫および腸管壁内ガスを認めた．明らかな腸間膜虚血および壊死を示唆する所見はなかった．消化管穿孔または腸管気腫症が考えられ緊急手術が検討されたが，腹部症状に乏しく液体成分など腸管内容の流出を示唆する所見がないことから一旦保存的加療を行った．また，体幹部を中心に小豆大までの皮膚潰瘍が多発していた．皮膚病理所見，既往および今回の病態からDegos 病と診断された．入院６日目に注腸造影および腹部CT を施行したところ，free air はほぼ消失しており，造影剤の腸管外漏出は認めず８日目に退院となった．Degos 病は皮膚の萎縮性丘疹を呈し，消化管の多発性潰瘍や穿孔，中枢神経系の出血や梗塞を特徴とし，病態としては末梢の血栓性血管炎が主体と考えられている．今回我々は，Degos病の関連が疑われた腸管気腫症の一例を経験したので文献的考察を加えて報告する．The patient was a 70 year-old-male. His past medical history was significant for cerebral infarction and Parkinson’s disease. He presented with malaise and hypotension and had been admitted to a local hospital three days ago. After admission，he had a fever of 40℃ and a computed tomography (CT) showed free air in the upper abdomen，he was referred to our hospital for an operation. A contrast-enhanced computed tomography also showed free air and pneumatosis intestinalis in transverse colon, with no evidence of mesenteric ischemia such as superior mesenteric artery occlusion (SMA) or non-occulusive mesenteric ischemia. Due to no abdominal pain and intraperitoneal fluid, we assessed that pneumatosis cystoides intestinalis was more probable than intestinal perforation. It was observed that the patient had many skin ulcers the size of red beans which were located around the chest and abdomen. A skin biopsy was performed，indicating Degos’ disease by a pathological exam. On day 6 of admission，we performed a barium enema exam and plain abdomen computed tomography (CT), it was seen that the free air almost disappeared and there was no leakage of the contrast medium. He was discharged on day 8. Patients with Degos’ disease present atrophic papula with perforation of intestinal or cerebral vascular accidents such as hemorrhage or infarction. This is considered a cause for bythrombotic angiitis of the peripheral vessels. We present a report with reference to the relevant literature

Eyelid Lengthening Combined with Penetrating Keratoplasty for Exposure Keratopathy in Graves' Ophthalmopathy-A case report

Upper eyelid retraction is a well-known component of Graves' disease. With greater degrees of retraction, corneal exposure is usually increased. We report here on a patient with corneal perforation following exposure keratopathy due to upper eyelid retraction. The patient was treated with penetrating keratoplasty and an upper eyelid lengthening procedure using Goretex^[○!R] dura substitute as an interpositional graft material. The exposure keratopathy resolved postoperatively and this condition has been maintained for 45 months since the operation, with a good cosmetic outcome and symmetry of the palpebral fissures