Kazuhiko Natori

Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients

Upshaw–Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but its clinical signs may be mild or absent during childhood. We have identified 37 patients with USS (24 females, 13 males) belonging to 32 families. The nine women from six families who were diagnosed during their first pregnancy are the focus of this report. Six of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the second–third trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after birth, and the remaining seven were all premature except one, who was born naturally following plasma infusions to the mother that had started at 8 weeks’ gestation. All nine USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated that eight women were compound heterozygotes of Y304C/G525D (2 siblings), R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has been previously reported. These observations emphasize the importance of measuring ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and pregnancy.

Pathophysiological implication of reversed CT halo sign in invasive pulmonary mucormycosis: a rare case report

BackgroundIt has been accepted that reversed halo sign (RHS) appeared on a computed tomography (CT) image in immunocompromised patients indicates an invasive fungal infection, but its pathophysiology remains obscure as to what this image implies. Therefore, the present report describes detailed radiological and histopathological findings of a case of invasive pulmonary mucormycosis (IPM) presenting RHS with comparison to those from a lesion of discrete nodule caused by invasive pulmonary aspergillosis (IPA), and discusses the pathophysiological implications of this characteristic image.Case presentationRHS had been clinically noted at the time of recovering of bone marrow function of a 64-year-old Japanese man who had chemotherapy for his acute lymphoblastic leukemia. Histological examination of the surgically removed lung revealed a lesion of IPM. This was composed of coagulation necrosis of septa at the center of lesion with preservation of air content which was encompassed outer rim comprising triplet structure; liquefaction, consolidation, and organization from the inner to the outer layer. In addition, Micro-CT examination confirmed reticular structure and monotonous high density at the central coagulation necrosis preserving air content and surrounding consolidation, and organization lesion of the IPM lesion.ConclusionOur investigations suggest that RHS might be understood as a kind of immune reconstitution syndrome and be the initial and prior status of air crescent sign.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480054198968132

Recombinant human thrombomodulin in the treatment of acute myeloid leukemia patients complicated by disseminated intravascular coagulation: retrospective analysis of outcomes between patients treated with heparin and recombinant human thrombomodulin therapy

BACKGROUND Recombinant thrombomodulin (rTM) is a promising anticoagulant. Improvements in disseminated intravascular coagulation (DIC) and the amelioration of bleeding complications in DIC patients were reported to be greater with rTM therapy than with unfractionated heparin therapy. However, it remains unknown whether rTM therapy affects the outcomes of patients with acute myeloblastic leukemia (AML). DESIGN AND METHOD We retrospectively analyzed 103 patients with AML and compared outcomes between patients treated with low molecular weight heparin therapy and rTM. The diagnostic criteria for DIC were previously proposed by the Japanese Ministry of Health and Welfare. Comparisons between qualitative variables were carried out using the χ(2) test. Survival probabilities were estimated by the Kaplan-Meier method, and differences in survival distributions were evaluated using the log-rank test. RESULTS Forty-seven patients developed DIC due to chemotherapy or their disease status. Fourteen patients were treated with rTM, while 33 patients were treated with low-molecular-weight heparin (LMWH). The log-rank test revealed that overall survival was significantly worse in the DIC group than in the non-DIC group (P=0.003), and was signfiacntly better in the rTM group than the LMWH group (P=0.016). CONCLUSION rTM was more efficient than LMWH because of the improvements it induced in overall survival.

Large plasmacytoma occupying the upper limb in a myeloma patient

Extramedullary disease (EMD) is an issue for patients with multiple myeloma (MM), since extramedullary spread of MM is associated with an aggressive course and a poor prognosis. Moreover, the mechanism of EMD development is uncertain. Here, we present extensive extramedullary plasmacytoma occupying the left upper limb of a 66-year-old female patient with MM with an extremely aggressive course and multiple visceral organ involvement without bone marrow infiltration or plasma cell leukemia. EMD of this large size is extremely rare and this case may provide a clue for better understanding of clinical features of EMD in MM.

Malignant lymphoma and Schistosoma japonica infection

Schistosoma japonica invades the human body through the skin with Oncomelania nosophora, an intermediate host, and adult schistosoma inhabit and lay eggs in the mesenteric and portal veins. Because of the extinction of Oncomelania nosophora in Japan, all new patients with acute schistosomiasis have become infected abroad. We report a case of malignant lymphoma with coexisting S. japonica infection. This 72-year-old man, who had experienced general malaise for one month, presented to our hospital with abdominal pain, distention and vomiting. He had cervical lymphadenopathy, conjunctival pallor, scleral icterus and abdominal distention caused by ileus. The liver and spleen were palpable 5 and 4 cm, respectively, below the costal margin. Single 1-cm inguinal lymph nodes were palpable bilaterally. Abnormal test results on admission were: haemoglobin concentration 104 g/l, platelet count 46 · 10/l, total protein 53 g/l, albumin 29 g/l, bilirubin 205 lmol/l, glutamic oxaloacetic transaminase 121 IU/l, lactate dehydrogenase 2460 IU/l. Biopsy of cervical lymph nodes showed nonHodgkin lymphoma (diffuse large B cell). Abdominal echography showed many hypoechoic areas in the spleen. Liver biopsy showed lymphoma and eggs of S. japonica (right and left, *1 Schistosoma japonicum egg, *2 infiltrating lymphoma cells). The clinicopathological stage was IVB. The patient did not undergo chemotherapy due to a worsening general condition and abdominal cavity bleeding of unknown origin; he died approximately one month after admission. Schistosomiasis occurs in Japan, China and the Philippines. Schistosoma eggs are most frequently found in the mucosal and submucosal layers of the colon, caecum and sigmoid colon, in that order. It is hypothesized that the relationship between S. japonica and cancer has much in common with that between Helicobacter pylori and mucosa-associated lymphoid tissue lymphoma, and that between Epstein–Barr virus and empyema-related lymphoma, in that the mechanisms of chronic inflammation act as cancer-promoting factors. In this case, lymphoma cells proliferated around egg-emboli in Glisson’s capsule and portal vein branches, suggesting a close relationship between the infection and the lymphoma.

Lobectomy for lung cancer in a myelodysplastic syndrome patient with decreasing platelet aggregation: report of a case

BackgroundMyelodysplastic syndromes (MDS) are clonal stem cell disorders of the bone marrow. Most patients with MDS have a high risk of bleeding. Thrombocytopenia and defective platelet aggregation contribute to bleeding. We report a surgical case of a patient with lung cancer concomitant with MDS.Case presentationA 72-year-old man presented to our hospital because of an abnormal shadow on chest x-ray suggesting a primary lung cancer. A peripheral blood smear examination found giant platelets without thrombocytopenia. He was diagnosed with MDS by bone marrow biopsy, and showed defective platelet aggregation despite a normal bleeding time. The patient underwent left lower lobectomy and transfusion of platelets because of chest wall bleeding.ConclusionsWe demonstrated that ordering platelet preparations might be desirable for an MDS patient with defective platelet aggregation who will undergo surgery, even for a normal platelet count and bleeding time.

P42. Multiple neoplasms consist of lung cancer and hematological malignancies.

Background The lung cancer is a cancer of the most in Japan and first place in cause of death. Lung cancer still has poor prognosis with cure only in early clinical stage. Recently, new anti-cancer agent and molecular target agents are increased but clinical outcomes are not satisfied. We report that we reviewed 39 cases of multiple neoplasms with lung cancer and the hematological malignancies.

Multiple neoplasms including hematological malignancies in elderly

Introduction.– Chronic myelogeneous leukemia (CML) is, so called, stem cell leukemia. There was a major change in CML treatment last two decades. Now CML therapy strategy gets special medicine, tyrosine kinase inhibitor. This special medicine brings good prognosis and good general condition. So we report a review of elderly CML cases. Methods.– From 2003 to 2012, we intended for 229 patients whom suffered from hematological malignancies. Sixty-five years old or older, 15 cases in thatdiagnosedCMLand15patientswere followed up until death or until December 2012. And we studied about age, gender, diagnosises, prognosis, and cause of death. Result.– From 2003 to 2012, CML patients are 39 cases in that 65years or over years patients are 15 cases. Gender is male 8 cases, female 7 cases, median age is 70 years. Clinical phase are chronic phase, and the chance to diagnosis were medical health check. 14 cases received imatinib therapyand1casewasbest supporting care because patient did not want to treat because he needed his own time. Imatinib therapy is 400mg/day po, and almost all patients are outer ward. Side effects aremainly edema, neutropenia and pain of lower limb, but all side effects was undercontrolable by medicine. Clinical outcome is that achieved complete remission is in 13 cases out of 15 cases. One case was remission failure, 1 case was best supporting care.Median overall survival time is 27months (ranged 10–122 months). Key conclusion.–Treatment inCML ishopeful in elderly, it is possible to treat the same as adult.

Prognostic factors in elderly multiple myeloma patients aged 65 years or older : Comparison with nonelderly patients with multiple myeloma

Background:  Although age is a prognostic factor in multiple myeloma (MM), the prognostic factors in elderly MM patients may be different to those in nonelderly MM patients due to the patients age. The difference in the significance of prognostic factors between elderly MM patients and the nonelderly MM patients was studied.