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Purpose: Predicting lymph node metastasis (LNM) in patients with bladder urothelial carcinoma (BUC) before radical cystectomy aids clinical decision making. Here, we aimed to develop and validate a nomogram to preoperatively predict LNM in BUC patients. Methods: Patients with histologically confirmed BUC, who underwent radical cystectomy and bilateral lymphadenectomy, were retrospectively recruited from two institutions. Patients from one institution were enrolled in the primary cohort, while those from the other were enrolled in the external validation cohort. Patient demographic, pathological (using transurethral resection of the bladder tumor specimens), imaging, and laboratory data were recorded. Univariate and multivariate logistic regression analyses were performed to explore the independent preoperative risk factors and develop the nomogram. Internal and external validation was conducted to assess nomogram performance. Results: 522 and 215 BUC patients were enrolled in the primary and external validation cohorts, respectively. We identified tumor grade, infiltration, extravesical invasion, LNM on imaging, tumor size, and serum creatinine levels as independent preoperative risk factors, which were subsequently used to develop the nomogram. The nomogram showed a good predictive accuracy, with area under the receiver operator characteristic curve values of 0.817 and 0.825 for the primary and external validation cohorts, respectively. The corrected C-indexes, calibration curves (after 1000 bootstrap resampling), decision curve analysis results, and clinical impact curves demonstrated that the nomogram performed well in both cohorts and was highly clinically applicable. Conclusion: We developed a nomogram to preoperatively predict LNM in BUC, which was highly accurate, reliable, and clinically applicable. [ABSTRACT FROM AUTHOR]

To clarify the clinicopathologic features of patients surviving ≥20 years after resection for hepatocellular carcinoma (HCC). Between 1961 and 1987, a total of 396 patients underwent hepatic resection for HCC; 53 (13.4%) patients survived ≥20 years, and 343 (86.6%) patients survived <20 years. A comparative study between the two groups was made. By March of 2007, 67.6% (36/53) patients are still alive, disease free; 5.7% (3/53) patients died of tumor recurrence or metastasis; 11.3% (6/53) patients died of liver failure; 5.7% (5/53) patients were lost during follow-up. The longest patient survived 43 years and 2 months. Five young patients got married after resection and have had babies. One patient with a tumor measuring 17 × 13 × 9 cm (largest tumor in this series) survived for 37 years after resection, still alive, free of disease. Reresection for recurrence was done in nine patients, mean survival being 26 years and 11 months. Reresection for solitary pulmonary metastasis was carried out in three patients, mean survival being 29 years and 2 months. In comparison with patients surviving <20 years, patients surviving ≥20 years were significantly younger ( P = 0.031), had a higher incidence of asymptomatic tumors (56.6 vs. 34.4%, P = 0.002); lower γ-glutamyl transpeptidase level (≤50 U/L, 64.2 vs. 25.9%, P < 0.000), lower proportion of liver cirrhosis (66.0 vs. 83.6%, P = 0.002); higher percentage of small tumors (≤5 cm, 62.3 vs. 29.9%, P < 0.000), single nodule tumors (90.6 vs. 62.9%, P < 0.000), and well-encapsulated tumors (86.8 vs. 43.6%, P < 0.000); lower proportion of tumor emboli in the portal vein (3.8 vs. 22.5%, P = 0.002), better differentiation of tumor cells (Edmondson grade I, 21.6 vs. 9.1%, P = 0.036), and higher curative resection rate (100 vs. 64.1%, P < 0.000). Early detection and curative resection are the principal factors improving long-term survival. Long-term follow-up after resection of HCC is very important, and should continue for the remainder of the patient’s life. Reresection for recurrence and metastasis is important approach to improve prognosis. [ABSTRACT FROM AUTHOR]

To clarify clinicopathologic differences between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), and identify potential factors influencing survival after hepatectomy for ICC. Comparison of clinicopathologic data was made between patients who underwent hepatectomy for ICC ( n = 272) and HCC ( n = 5,829) during the same period. Twenty-five clinicopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on prognosis of ICC. Compared with patients with HCC, ICC patients were more common in females and more elderly, had a lower proportion of asymptomatic tumors, lower serum alpha-fetoprotein, higher serum carcinoembryonic antigen, carbohydrate antigen 19–9 and alkaline phosphatase levels; lower incidence of hepatitis history, associated cirrhosis and serum hepatitis B surface antigen; lower proportion of small tumors, well-encapsulated tumors and tumor emboli in the portal vein; higher proportion of single tumor, perihila lymph node involvement and poor differentiation; and less frequency of limited resection (all, P < 0.0001). Distant metastasis was less frequent in patients with ICC ( P = 0.027). A total of 5-years overall and disease-free survival (in brackets) after resection was 26.4% (13.1%) and 44.5% (33.1%) ( P < 0.0001, P < 0.0001) for patients with ICC and HCC, respectively. Factors influencing survival after resection of ICC can be divided mainly into two categories: early detection of asymptomatic ICC ( P < 0.0001) and curative resection ( P = 0.002). ICC Patients have distinct clinicopathologic features as compared with HCC patients. Surgery remains the only effective treatment for ICC. Early detection of asymptomatic ICC and curative resection were the key to achieve optimal survival. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapy after liver transplantation for hepatocellular carcinoma (HCC) is one of the major contributory factors for HCC recurrence and metastasis. Sirolimus, a potent immunosuppressant, has been reported to be an effective inhibitor in a variety of tumors. The present study is designed to explore whether sirolimus could block the growth and metastatic progression of HCC. MHCC97H cells were used as targets to explore the effect of sirolimus on cell cycle progression, apoptosis, proliferation, and its antiangiogenic mechanism. LCI-D20, a highly metastatic model of human HCC in nude mice, was also used as the model tumor to explore the effect of sirolimus on tumor growth and metastatic progression. In vitro, sirolimus induced cell cycle arrest at the G1 checkpoint and blocked proliferation of MHCC97H cells but did not induce apoptosis. In vivo, sirolimus prevented tumor growth and metastatic progression in LCI-D20. Intratumoral microvessel density and circulating levels of VEGF in tumor-bearing mice were also significantly reduced in sirolimus treatment group. Quantitative RT-PCR showed that sirolimus down-regulated the mRNA expression of VEGF and HIF-1a, but not of bFGF, and TGF-b in MHCC97H cells. Furthermore, western blot analysis confirmed that sirolimus also decreased expression of HIF-1a at protein level, in parallel with the down-regulation of the levels of VEGF protein excretion in a time-dependent manner as compared to untreated control cells following anoxia. The immunosuppressive macrolide sirolimus prevents the growth and metastatic progression of HCC, and suppresses VEGF synthesis and secretion by downregulating HIF-1a expression. Sirolimus may be useful for clinical application in patients who received a liver transplant for HCC. [ABSTRACT FROM AUTHOR]