Independent Predictor Of Cause-specific Survival Research Articles

The impact of examined lymph node count on survival in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

IntroductionThe prognostic impact of the number of examined lymph nodes (ELNs) in different histological subtypes of cervical cancer remains unclear. We aimed to assess the impact of the number of ELNs in stage IA2–IIA cervical cancer with different histological subtypes.MethodsData of patients with stage IA2–IIA squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix between 1988 and 2013 were retrieved from the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were performed to analyze the effect of number of ELNs on cause-specific survival (CSS) and overall survival (OS).ResultsThe final data set identified 11,830 patients including 7,920 (66.9%) women with SCC and 3,910 (33.1%) with AC. The median number of ELNs was 19. The multivariate analysis indicated that the number of ELNs was an independent prognostic factor influencing CSS and OS, both as a continuous or a categorical variable. Patients with a higher number of ELNs had better survival outcomes. In SCC subtype, the number of ELNs was also the independent prognostic factor of CSS and OS in node-positive patients, but not in patients with node-negative disease. In AC patients, ELN count was not an independent predictor of CSS and OS regardless of lymph node status.ConclusionThe number of ELNs is an independent prognostic factor in patients with stage IA2–IIB cervical cancer. A higher number of ELNs is associated with better survival outcomes, especially in the node-positive SCC subtype.

Presence of Phosphorylated Hepatocyte Growth Factor Receptor/c-Met Is Associated with Tumor Progression and Survival in Patients with Conventional Renal Cell Carcinoma

Hepatocyte growth factor receptor (HGFR/c-Met) signaling is associated with tumor progression in various cancers. The clinical significance and pathologic roles of phosphorylated HGFR/c-Met in renal cell carcinoma (RCC) are not fully understood; therefore, this study sought to clarify the possible role of two tyrosine residues (pY1234/pY1235 and pY1349) in HGFR/c-Met. The kinetics of tyrosine phosphorylation at these two residues was examined in a human renal carcinoma cell line, ACHN cells. In addition, phosphorylated HGFR/c-Met expression (using phosphorylation site-specific antibodies for pY1234/pY1235 and pY1349) was examined in 114 tumor sections of conventional RCC patients by immunohistochemistry. The relationships between these expressions and clinicopathologic features and survival were also investigated. Although phosphorylation of Y1349 HGFR/c-Met was observed for 120 minutes after HGF treatment of ACHN cells, maximal phosphorylation of Y1234/Y1235 was observed at 30 minutes followed by a rapid inactivation. Median rates (range) of cancer cells immunopositive for pY1234/pY1235 HGFR/c-Met and pY1349 HGFR/c-Met in the tumor sections were 0% (0-5.2%) and 14.3% (0-64.3%), respectively. Positive expression of pY1349 HGFR/c-Met was significantly associated with high pT stage, presence of metastasis, and high-grade carcinoma. Multivariate Cox analysis revealed that the positive expression of pY1349 HGFR/c-Met was a significant and an independent predictor of cause-specific survival (odds ratio, 2.94; 95% confidence interval, 1.12-7.72; P = 0.028). Phosphorylated HGFR/c-Met may be important in the tumor progression of RCC. Expression of pY1349 HGFR/c-Met is a useful predictor for metastasis and survival of conventional RCC patients.

Clinical symptoms in localized renal cell carcinoma reflect its invasive potential: Comparative study between incidentally detected and symptomatic diseases

The objectives of this study were to analyze the association of clinical symptoms with several parameters in patients with organ-confined renal cell carcinoma (RCC), and investigate the difference in biologic characteristics between incidentally detected and symptomatic RCCs. This study included 132 patients who were pathologically diagnosed with organ-confined RCC after radical surgery, and their clinicopathologic features were compared to those in patients with incidentally detected and symptomatic diseases. In this series, 91 patients were incidentally diagnosed with RCC, while the remaining 41 had some clinical symptoms. The cause-specific survival in patients with incidental RCC was significantly higher than that in patients with symptomatic RCC, and the presence of clinical symptoms could be an independent predictor of cause-specific survival in these patients. Immunohistochemical staining of resected specimens from these patients were then performed with Ki-67, Bcl-2, matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor antibodies. Despite the lack of differences in Ki-67, Bcl-2, and vascular endothelial growth factor expression between these 2 groups, significantly increased expressions of MMP-2 and MMP-9 in symptomatic RCCs were observed compared with those in incidental RCCs. Moreover, the presence of clinical symptoms in organ-confined RCC was significantly correlated with immunoreactivities of MMP-2 and MMP-9. These findings suggest that clinical symptoms have a significant impact on the prognosis of patients with organ-confined RCC and that the appearance of clinical symptoms may reflect the increased invasive potentials characterized by overexpression of MMPs.

Clinical outcome of maximum androgen blockade using flutamide as second‐line hormonal therapy for hormone‐refractory prostate cancer

To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second-line hormonal therapy for advanced hormone-refractory prostate cancer (HRPC). The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second-line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first-line hormonal therapy, which failed. The effect of the second-line therapy was evaluated by serum prostate-specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second-line therapy. On initiating second-line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1-13) months. During the observation period there were no severe side-effects from the second-line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first-line therapy had a significantly higher incidence of PSA response to second-line therapy, despite no significant effect of other factors examined on the PSA response to second-line therapy. Furthermore, the cause-specific survival in responders to second-line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second-line therapy, could be used as independent predictors of cause-specific survival. MAB using flutamide as second-line hormonal therapy can give a comparatively favourable PSA response with no severe side-effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first-line therapy.

Expression of metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in transitional cell carcinoma of upper urinary tract: correlation with tumor stage and survival

Objectives To investigate the relationship between the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 and pT stage or survival in patients with transitional cell carcinoma of the upper urinary tract. MMP-2 and MMP-9 are associated with tumor invasion in several malignancies. TIMPs exert an anti-invasive effect by blocking MMP activity. Recent studies have shown, however, that TIMPs can also stimulate cell proliferation and angiogenesis. Methods Tumor sections surgically removed from 91 patients were examined for expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 by immunohistochemistry. We also determined the proliferation index and microvessel density in each tumor and investigated the independent roles of these factors in tumor stage and survival using multivariate analysis. Results Of 91 tissue samples, 50, 51, 45, and 39 were positive for MMP-2, MMP-9, TIMP-1, and TIMP-2 expression, respectively. Tumors positive for MMP-2, MMP-9, and TIMP-1 exhibited a greater proliferation index than tumors with negative expression ( P <0.001, P = 0.013, and P <0.001, respectively). The microvessel density of tumors positive for MMP-2 and TIMP-1 was greater than that of negative tumors ( P <0.001). The expression of MMP-2, MMP-9, and TIMP-1 was an independent predictor of high pT stage. Cox proportional hazard analysis identified TIMP-1 expression as an independent factor for cause-specific survival (odds ratio 5.2, P = 0.011), similar to microvessel density, pT4, and lymph node metastasis. Conclusions TIMP-1 expression correlated with pT stage and was an independent predictor of cause-specific survival. Our results suggest that TIMP-1 expression is a potentially useful tool for the selection of postoperative observation strategies in patients with transitional cell carcinoma of the upper urinary tract.

Parathyroid carcinoma: is there a role for adjuvant radiation therapy?

The authors proposed to determine risk factors associated with postoperative progression of parathyroid carcinoma within the neck (locoregional) and to assess the efficacy of postoperative adjuvant radiation therapy in preventing disease progression within the neck. A retrospective review of patients with pathologically confirmed parathyroid carcinoma who underwent surgical resection was performed. Risk factors identified on univariate analysis were applied in a proportional hazards analysis to identify significant independent predictors of locoregional disease progression and cause-specific survival after surgical resection. Fifty-seven patients were treated with surgery alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient follow-up and pathologically confirmed features to be included in the current analysis. Four patients were treated with surgery and adjuvant RT. Four patients received RT to the neck and mediastinum for unresectable locoregional disease progression. Patients were followed for a median of 75.6 months (range, 8.4-358 months). Twenty-five patients (44%) developed locoregional disease progression at a median of 27.1 months after surgery (range, 6.2-138.3 months). The univariate analysis revealed that surgical margin status and the institution at which the initial surgery was performed were predictive of locoregional progression-free survival. The institution at which the initial surgery was performed was found to be an independent predictor of cause-specific survival. Of the four patients treated with surgery and adjuvant RT, all were alive and without disease at the time of last follow-up. All four patients who received RT for locoregional disease progression after initial surgery achieved locoregional disease control. Patients with parathyroid carcinoma are reported to have a significant risk of locoregional disease progression after surgery alone. The results of the current study demonstrated that the risk of postoperative disease progression can be predicted by surgical margin status and the institution at which the initial surgery is performed. Patients treated with surgery and postoperative RT may have a lower risk of locoregional disease progression and improved cause-specific survival. RT can be used to provide locoregional control of recurrent disease.