Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.     

Pediatric patients with eosinophilic esophagitis: an 8-year follow-up

BACKGROUND: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients. OBJECTIVE: We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history. METHODS: We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years. RESULTS: In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed. CONCLUSION: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus. CLINICAL IMPLICATIONS: Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.     

八项肝纤维化血清标志物比较研究

目的比较血清血小板衍生生长因子-BB(PDGF-BB)、转化生长因子-β1(TGF-B1)、基质金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-1(MMP-1)、透明质酸(HA)、Ⅲ型前胶原(PC Ⅲ)、Ⅳ型胶原(C Ⅳ)和层黏连蛋白(LN)及外周血单个核细胞(PBMC)内TIMP-1 mRNA、MMP-1 mRNA在肝纤维化中的诊断价值。方法常规肝穿活检、组织病理学诊断；RT-PCR检测PBMCs中MMP-1 mRNA、TIMP-1 mRNA水平；酶标法检测血清PDGF-BB、TGF-β1、TIMP-1和MMP-1含量；放射免疫法检测血清HA、PC Ⅲ、C-Ⅳ和LN含量。结果经ROC曲线分析，血清PDGF-BB、TIMP-1、HA、PC Ⅲ、C-Ⅳ、LN和TIMP-1 mRNA的AUC分别为0．985、0．726、0．318、0．728、0．727、0．583、0．463、0．876；血清PDGF-BB和PBMCs中TIMP-1 mRNA的灵敏度和特异度分别为90％、95％，73．7％、100％；两者联合检测的灵敏度为97．4％，特异度为95．0％。结论八项指标中，血清PDGF-BB的诊断价值最大。在筛选肝纤维化患者时，以血清PDGF-BB、PBMC中TIMP-1 mRNA联合检测最佳。     

Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia

In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.     

Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.     

Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.