Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into extra- and intrahepatic shunts. They occur during liver and systemic venous vascular embryogenesis and are associated with other congenital abnormalities. They carry a higher risk of benign and malignant liver tumors and, if left untreated, can result in significant medical complications including systemic encephalopathy and pulmonary hypertension.
Conclusion: This article reviews the various types of congenital portosystemic shunts and their anatomy, pathogenesis, symptomatology, and timing and options of treatment.
What is Known:
• The natural history and basic management of this rare congenital anomaly are presented.
What is New:
• This paper is a comprehensive review; highlights important topics in pathogenesis, clinical symptomatology, and treatment options; and proposes an algorithm in the management of congenital portosystemic shunt disease in order to provide a clear idea to a pediatrician. An effort has been made to emphasize the indications for treatment in the children population and link to the adult group by discussing the consequences of lack of treatment or delayed diagnosis.
Background: Merkel cell carcinoma is a rare but aggressive cutaneous primary small cell carcinoma. It is commonly seen in elderly affecting the head, neck, and extremities. Macroscopically may be difficult to distinguish MCC from other small cells neoplasms especially oat cell carcinoma of the lung.
In our recent phase I trial, we demonstrated that the AE37 vaccine is safe and induces HER-2/neu-specific immunity in a heterogeneous population of HER-2/neu (+) prostate cancer patients. Herein, we tested whether one AE37 boost can induce long-lasting immunological memory in these patients. Twenty-three patients from the phase I study received one AE37 boost 6-month post-primary vaccinations. Local/systemic toxicities were evaluated following the booster injection. Immunological responses were monitored 1-month (long-term booster; LTB) and 3-year (long-term immunity; LTI) post-booster by delayed-type hypersensitivity, IFN-γ ELISPOT and proliferation assays. Regulatory T cell (Treg) frequencies, plasma transforming growth factor-β (TGF-β) and indoleamine 2,3-deoxygenase (IDO) activity levels were also determined at the same time points. The AE37 booster was safe and well tolerated. Immunological monitoring revealed vaccine-specific long-term immunity in most of the evaluated patients during both LTB and LTI, although individual levels of immunity during LTI were decreased compared with those measured 3 years earlier during LTB. This was paralleled with increased Tregs, TGF-β levels and IDO activity. One AE37 booster generated long-term immunological memory in HER-2/neu (+) prostate cancer patients, which was detectable 3 years later, albeit with a tendency to decline. Boosted patients had favorable clinical outcome in terms of overall and/or metastasis-free survival compared with historical groups with similar clinical characteristics at diagnosis. We suggest that more boosters and/or concomitant disarming of suppressor circuits may be necessary to sustain immunological memory, and therefore, further studies to optimize the AE37 booster schedule are warranted.
Prothymosin alpha(Prot alpha), an immunologically active polypeptide derived initially from rat thymus, and now pig thymus, was tested for its effect on autoantigen-induced human T cell proliferation in vitro. Pig ProT alpha was found to enhance the autologous mixed lymphocyte response (auto-MLR). Optimum enhancement was achieved at doses which varied among different donors. Treatment of the stimulatory monocytes with ProT alpha resulted in considerably higher auto-MLR responses as compared to those with non treated monocytes. ProT alpha was without effect on T lymphocytes. In contrast, T lymphocytes exhibited enhanced proliferative activity when treated with ProT alpha in the environment of autologous monocytes. Moreover, supernatants from cultures of monocytes incubated with ProT alpha (ProT alpha-sup) were also shown to enhance the human auto-MLR either after addition in cultures or after preincubation with responder T lymphocytes. In addition, ProT alpha-sup did not demonstrate any detectable interleukin 1 (IL 1) or interleukin 2 (IL 2) - like activity. Furthermore, ProT alpha-sup induced an increase in IL 2 production in auto-MLR cultures. The enhancement of T-cell proliferation and IL 2 production by ProT alpha-sup was maximal when this material was added at the beginning of the auto-MLR, and no effect of ProT alpha-sup was seen if the latter was added 3 days after initiation of the culture. Finally, Prot alpha-sup was also shown to increase the expression of IL 2 receptors on T lymphocytes activated in the auto-MLR. These studies suggest that ProT alpha enhances the human auto-MLR through ProT alpha-sup which is released after interaction of monocytes with ProT alpha ProT alpha-sup then increases directly T lymphocyte proliferation by elevating IL 2 production and expression of IL 2 specific receptors on autoactivated T lymphocytes.
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