Efficacy of postoperative adjuvant therapy for stage ilia breast cancer: Futraful vs futraful+tamoxifen for er-positive patients and futraful vs futraful + adriamycin for er-negative breast cancer

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located throughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage IIIa breast cancer. Patients with estrogen receptor-positive [ER( + )] breast cancer were treated with two types of regimens, ie, cyclophosphamide + adriamycin + fluorouracil (CAF; 2 cycles) + Futraful (FT) or CAF (2 cycles) + FT + tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER( + ) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation. The 5-year survival rate was 77.2% for the CAF + FT group and 74.6% for the CAF + FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF + FT + TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF + FT + TAM group was significantly higher than that for the corresponding patients in the CAF + FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF + FT+TAM group than in the CAF + FT group). Patients with estrogen receptor-negative [ER( -)] breast cancer were treated with two types of regimens, ie, CAF + FT or CAF + FT + adriamycin (ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478 (93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF + FT group and 63.0% for the CAF + FT + ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF + FT and CAF + FT + ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF + FT+ADR group than in the CAF + FT group.     

Loss of expression of DNA repair enzymes MGMT,hMLH1, and hMSH2 during tumor progression in gastric cancer

BACKGROUND: Disorders of the DNA repair system that protects against alkylating mutagens are known to play an important role in carcinogenesis. METHODS: We investigated the expression of the DNA repair enzyme that protects against alkylating mutagens, O(6)-methylguanine DNA methyltransferase (MGMT), and the mismatch repair (MMR) enzymes, hMLH1 and hMSH2, in 135 gastric cancer specimens by immunohistochemical means. RESULTS: The immunoreactivity of MGMT and MMR proteins correlated significantly with several clinicopathologic factors. The survival curve in 116 patients showed that a loss of MGMT or hMLH1, but not of hMSH2, correlated with a poor prognosis. Combined evaluation of MGMT and hMLH1 revealed that the survival of patients with negative status for both MGMT and hMLH1 was shortest. However, this significant association between patient survival and MGMT or hMLH1 expression disappeared when early and advanced cancers were separately analyzed, indicating that synchronous losses of MGMT and hMLH1 increase during tumor progression and stage. Further evaluation according to histologic type revealed that loss of MGMT, hMLH1, and hMSH2 expression significantly differed between early and advanced cancer in differentiated-type cancers. In contrast, in undifferentiated-type cancer, loss of MGMT and MMR expression was frequently found even in intramucosal (m) cancer, and no significant difference was found in loss of hMLH1 and hMSH2 between early and advanced cancer. CONCLUSION: These findings demonstrate that the reduced expression of MGMT, hMLH1, and hMSH2 in differentiated-type cancer may play an important role during tumor progression between the early and advanced stage. On the other hand, in undifferentiated-type cancer, loss of MGMT and the MMR proteins appears to be an important event at carcinogenesis or at an earlier step of tumor progression.     

Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica

Background  

Neuromyelitis optica (NMO) is a recurring inflammatory neurological disease characterized by severe optic neuritis and myelitis. The purpose of this study was to determine whether the retinal nerve fiber layer thickness (RNFLT) is correlated with the clinical presentations in patients with NMO and to determine the clinical factors that lead to poor visual outcomes.     

Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells

Protein kinase C delta (PKCδ) is a multifunctional PKC family member and has been implicated in many types of cancers, including liver cancer. Recently, we have reported that PKCδ is secreted from liver cancer cells, and involved in cell proliferation and tumor growth. However, it remains unclear whether the extracellular PKCδ directly regulates cell surface growth factor receptors. Here, we identify epidermal growth factor receptor (EGFR) as a novel interacting protein of the cell surface PKCδ in liver cancer cells. Imaging studies showed that secreted PKCδ interacted with EGFR‐expressing cells in both autocrine and paracrine manners. Biochemical analysis revealed that PKCδ bound to the extracellular domain of EGFR. We further found that a part of the amino acid sequence on the C‐terminal region of PKCδ was similar to the putative EGFR binding site of EGF. In this regard, the point mutant of PKCδ in the binding site lacked the ability to bind to the extracellular domain of EGFR. Upon an extracellular PKCδ‐EGFR association, ERK1/2 activation, downstream of EGFR signaling, was apparently induced in liver cancer cells. This study indicates that extracellular PKCδ behaves as a growth factor and provides a molecular basis for extracellular PKCδ‐targeting therapy for liver cancer.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

Spontaneous regression in recurrent epithelial ovarian cancer

Background Although spontaneous regression has been reported in several cancers, it is generally believed that this rare phenomenon does not occur in epithelial ovarian cancer. Case We presented a stage IV epithelial ovarian cancer patient with long-term disease-free survival after palliative local irradiation alone against recurrence. The recurrent supraclavicular lymph node was almost completely necrotic, and the swelling of the para-aortic lymph node spontaneously regressed. Conclusion The histologic features and unexpected clinical course in this patient strongly suggest that spontaneous regression occurred in recurrent epithelial ovarian cancer.     

张伯礼教授临床用对(队)药经验谈

张伯礼教授从事中医临床工作40余年,积累了丰富的临床经验,对于药物的配伍使用具有独到见解。主要介绍张伯礼教授临床用药心得,突出其在临床诊疗过程中对药（两味中药固定的组合配伍）与队药（两味以上中药固定的组合配伍）的使用,同时论述相关病理病机,如对采用队药与对药治疗湿邪为病、痰瘀互结等病证的见解。张教授将中医药传统理论与现代医学知识相结合,采用特定几味中药,或相须、或相使,优势互补,最终达到增强疗效的目的。     

Treatment of a patient with hemophilia A and hepatitis C virus-related cirrhosis by living-related liver transplantation from an obligate carrier donor

BACKGROUND: Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. METHODS: The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. RESULTS: The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. CONCLUSIONS: End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.