Long‐term outcome of patients with acquired chronic pure red cell aplasia (PRCA) following immunosuppressive therapy: a final report of the nationwide cohort study in 2004/2006 by the Japan PRCA collaborative study group

Immunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma‐associated, or large granular lymphocyte (LGL) leukaemia‐associated PRCA, which is thought to be immune‐mediated. To explore the overall long‐term outcome following immunosuppression and to identify the risk factors for death in these disorders, we conducted nationwide surveys in Japan 2004 and 2006, and identified a total of 185 patients with acquired chronic PRCA, including 72 idiopathic, 41 thymoma‐associated and 14 LGL leukaemia‐associated cases of PRCA for whom data was available. The present study evaluated 127 patients with these three subsets of PRCA. The median overall survival has not yet been reached in idiopathic PRCA. The estimated median overall survival times in patients with thymoma‐associated and LGL leukaemia‐associated PRCA were 142·1 and 147·8 months, respectively. Twenty‐two deaths were reported, and the response to induction therapy and relapse of anaemia were found to be associated with death. The major causes of death were infection in seven patients and organ failure in another seven patients. The results suggest that maintenance therapy and the management of infectious complications are crucial for improving the prognosis of chronic PRCA.     

Prognostic factors for recurrence of bile duct stones after endoscopic treatment by sphincter dilation

BACKGROUND: The long-term outcome for patients after endoscopic sphincter of Oddi dilation is poorly documented. This study investigates the recurrence rate for bile duct stones in patients followed for 1 year or more after endoscopic sphincter dilation and stone extraction, and assessed prognostic factors associated with recurrence of ductal calculi. METHODS: A total of 169 patients with bile duct stones were treated with endoscopic sphincter dilation between July 1998 and August 2001. Follow-up studies consisted of periodic biochemical tests and out-patient evaluations with endoscopic retrograde cholangiography or magnetic resonance cholangiography performed when follow-up exceeded 1 year. Putative risk factors for stone recurrence included gender, age, stone size and number, associated peripapillary diverticulum, gallbladder status, color of bile duct stones, and bile duct diameter. Statistical analysis consisted of both a Kaplan-Meier estimation and a multivariate Cox regression model. RESULTS: Complete stone clearance was achieved in 162 (95.8%) patients, of whom 151 were followed (13 patients died from unrelated disorders). Mean follow-up was 23 months. Stone recurrence was documented in 13 patients. Patients with dilated bile duct or peripapillary diverticulum were at high risk for recurrence. CONCLUSIONS: The interval between treatment of bile duct stones by endoscopic sphincter dilation and the recurrence of biliary calculi is relatively short. Bile duct size and peripapillary diverticula are risk factors for early recurrence.     

Thrombopoietin Induces Association of Crkl With STAT5 But Not STAT3 in Human Platelets

Crkl, a 39-kD SH2, SH3 domain-containing adapter protein, isconstitutively tyrosine phosphorylated in hematopoietic cells fromchronic myelogenous leukemia (CML) patients. We recently reported thatthrombopoietin induces tyrosine phosphorylation of Crkl in normalplatelets. In this study, we demonstrate that thrombopoietin inducesassociation of Crkl with a tyrosine phosphorylated 95- to 100-kDprotein in platelets and in UT7/TPO cells, a thrombopoietin-dependent megakaryocytic cell line. With specific antibodies against STAT5, wedemonstrate that the 95- to 100-kD protein in Crkl immunoprecipitates is STAT5. This coimmunoprecipitation was specific in that Crkl immunoprecipitates do not contain STAT3, although STAT3 becomes tyrosine phosphorylated in thrombopoietin-stimulated platelets. Thecoimmunoprecipitaion of Crkl with STAT5 was inhibited by the immunizingpeptide for Crkl antisera or phenyl phosphate (20 mmol/L). Afterdenaturing of Crkl immunoprecipitates, Crkl was stillimmunoprecipitated by Crkl antisera. However, coimmunoprecipitation ofSTAT5 was not observed. Coincident with STAT5 tyrosine phosphorylation, thrombopoietin induces activation of STAT5 DNA-binding activity asdemonstrated by electrophoretic mobility shift assays (EMSA). Using a-casein promoter STAT5 binding site as a probe, we have alsodemonstrated that Crkl antisera supershift the STAT5-DNA complex,suggesting that Crkl is a component of the complex in the nucleus.Furthermore, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin also induce Crkl-STAT5 complex formation in responding cells in astimulation-dependent manner. In vitro, glutathione S-transferase(GST)-Crkl bound to STAT5 inducibly through its SH2 domain. Theseresults indicate that thrombopoietin, IL-3, GM-CSF, and erythropoietincommonly induce association of STAT5 and Crkl and that the complextranslocates to the nucleus and binds to DNA. Interestingly, suchassociation between STAT5 and Crkl was not observed incytokine-stimulated murine cells, suggesting an intriguing possibilitythat components of the human STAT5-DNA complex may be different fromthose of the murine counterpart.     

Various Neurological Symptoms by Neurolymphomatosis as the Initial Presentation of Primary Testicular Lymphoma

Neurological symptoms induced by the infiltration of malignant lymphoma into the nervous systems are subsumed under the term neurolymphomatosis (NL). Here, we report the case of a 30-year-old Japanese man with primary testicular lymphoma complicated, as seen in various neurological findings, by secondary NL prior to testicular swelling. Painless right scrotal enlargement was noticed more than 1 month after the appearance of neurological complications such as right upper extremity numbness, dysarthria, facial palsy, and diplopia. Proactive investigation and biopsies of extranodal sites at high risk of central nervous system infiltration of malignant lymphoma, such as the testes, should be considered when secondary NL is suspected based on imaging findings.Key Words: Neurolymphomatosis, Primary testicular lymphoma, Diffuse large B-cell lymphoma, Central nervous system infiltration     

CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells

NANOG expression in prostate cancer is highly correlated with cancer stem cell characteristics and resistance to androgen deprivation. However, it is not clear whether NANOG or its pseudogenes contribute to the malignant potential of cancer. We established NANOG- and NANOGP8-knockout DU145 prostate cancer cell lines using the CRISPR/Cas9 system. Knockouts of NANOG and NANOGP8 significantly attenuated malignant potential, including sphere formation, anchorage-independent growth, migration capability, and drug resistance, compared to parental DU145 cells. NANOG and NANOGP8 knockout did not inhibit in vitro cell proliferation, but in vivo tumorigenic potential decreased significantly. These phenotypes were recovered in NANOG- and NANOGP8-rescued cell lines. These results indicate that NANOG and NANOGP8 proteins are expressed in prostate cancer cell lines, and NANOG and NANOGP8 equally contribute to the high malignant potential of prostate cancer.     

Surgical management of small bowel metastases from primary carcinoma of the lung

Purpose  

To investigate the treatment and outcomes in a series of seven cases of small bowel metastases from lung cancer.