ObjectiveMorbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient's survival also were re-evaluated. Summary Background DataAlthough much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis. MethodsThe clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival. ResultsThere were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that co-existent hepatolithiasis and lower serum asparate aminotransferase levels (<90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin 210 mg/dL, 2) curative resection, 3) histologic type, 4) 384

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Papillary thyroid cancer (PTC) is the most common endocrine malignancy, accounting for 85-90% of all thyroid cancers. Genetic alternations involving the mitogen-activated protein kinase (MAPK) pathway are frequently demonstrated in PTC, such as RET/PTC, RAS, and B-type Raf kinase (BRAF) mutations. Over 90% of BRAF mutations are T1799A, resulting in a BRAF(V600E) mutation. BRAF(V600E) is present in approximately 50% of PTC and also found in aggressive histologic variants and PTC-derived anaplastic thyroid cancer, but is rare in follicular variants, and not found in follicular thyroid cancer. The tumorigenic role of BRAF(V600E) in the development of PTC was documented in thyroid-targeted BRAF(V600E) transgenic mice, and rat thyroid cells overexpressed with BRAF(V600E) suggested that BRAF(V600E) is an initiator of tumorigenesis and is required for tumor progression in PTC. Most clinical studies have demonstrated an association of BRAF(V600E) mutation with aggressive clinicopathologic characteristics and high tumor recurrence, although the results are controversial. The association is also observed in patients with papillary thyroid microcarcinomas and low-risk PTC. As a highly specific and unique mutation in PTC, testing for BRAF(V600E) in fine-needle aspiration specimens has been shown to refine the diagnostic accuracy of PTC in indeterminate cytology. Preoperative BRAF(V600E) analysis in low-risk patients may provide important value for prognostication, and these patients might benefit from receiving more intensive management and frequent follow-up. BRAF-targeted therapies have been developed to treat various human cancers including advanced thyroid cancers. Preclinical results are encouraging, but the anticancer effects of clinical trials are disappointing. Studies of multi-kinase inhibitors and/or combination with other regimens are underway in the treatment of advanced thyroid cancers. In this article, we review the pathogenesis of PTC, and the clinical implications of BRAF(V600E) mutation in the diagnosis, prognosis and potential targeted therapeutic strategies for thyroid cancers.

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The clinical manifestations of SARS showed high variability, and were related to the underlying health status of individual patients. Importantly, the development of ARDS was associated with significant mortality, despite aggressive therapy.