scholarly journals Overexpression of Pyruvate Dehydrogenase Kinase-3 Predicts Poor Prognosis in Urothelial Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu-Hsuan Kuo ◽  
Ti-Chun Chan ◽  
Hong-Yue Lai ◽  
Tzu-Ju Chen ◽  
Li-Ching Wu ◽  
...  
Keyword(s):  
Dna Replication ◽  
Urothelial Carcinoma ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Dna Replication And Repair ◽  
Upregulated Genes ◽  
Disease Specific

BackgroundThe mitochondrial pyruvate dehydrogenase complex (PDC) link glycolysis to the tricarboxylic acid cycle by decarboxylating pyruvate to acetyl coenzyme A irreversibly. Cancer cells are characterized by a shift in cellular metabolism from mitochondrial respiration to glycolysis. PDC activity inhibition mediated by phosphorylation via pyruvate dehydrogenase kinase (PDK) has been linked to cancer. However, the clinical significance of PDKs in urothelial cancer prognosis is not clear. We investigated the role and prognostic value of PDK3 expression in patients with upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC).Patients and MethodsWe retrospectively analyzed clinical data and pathological features. Formalin-fixed urothelial carcinoma (UC) tissues were collected and embedded in paraffin. The correlation of PDK3 expression with clinical characteristics, pathological findings and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS) were analyzed by Pearson’s chi-square test, Kaplan–Meier analysis, and the multivariate Cox proportional hazards model.ResultsData from 295 patients with UBUC and 340 patients with UTUC were evaluated. High PDK3 expression significantly correlated with several pathologic variables such as high T stage, lymph node metastases, high tumor grade, vascular invasion, and high mitotic rate (all P < 0.001). High PDK3 expression was associated with poor disease-specific survival (DSS) (P < 0.0001) and metastatic free survival (MFS) (P < 0.0001) in a Kaplan–Meier analysis. Additionally, multivariate analysis demonstrated increased PDK3 expression is a significant predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.79, P = 0.009; in UTUC, 2.561, P = 0.03] and MFS (HR in UBUC, 1.907, P = 0.024; in UTUC, 1.793, P = 0.044). The gene co-expression analysis showed abundant PDK3 co-upregulated genes were involved in the processes of DNA replication and repair through the Gene Ontology classification system.ConclusionHigh PDK3 expression has been linked to negative pathologic characteristics and poor oncological outcomes, suggesting that it could be used as a predictive biomarker for UC. PDK3 mRNA levels and its co-upregulated genes were strongly associated with DNA replication and repair. These results suggest that PDK3 may play a key role in tumor proliferation and development.

scholarly journals A Cross Sectional Study on Loco-Regional Recurrences and Overall Survival Rate among Patients with Stage II (T2N0M0) Glottis Carcinoma Treated with Chemoradiation and Surgery

2021 ◽  
Vol 8 (04) ◽  
pp. 219-223
Author(s):  
Niharika Darasani
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Squamous Cell ◽  
Stage Ii ◽  
Overall Survival Rate ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Tertiary Teaching ◽  
Voice Preservation ◽  
Disease Specific

BACKGROUND Single modality treatment for stage I and stage II squamous cell carcinomas of glottis region gave excellent results. Since a long time these are treated either with definitive radiation therapy or surgical excision with endoscopes. There was not much difference with regard to voice preservation, local recurrence and disease-free survival period. Our aim was to study the clinical presentation and management protocol of glottis carcinoma in a tertiary hospital and observe the final outcome of stage II (T2N0M0) glottis carcinoma and specific factor for survival in patients treated with surgery, radiotherapy and concurrent chemoradiation. METHODS 43 patients of glottis carcinoma stage II (T2N0M0) attending a tertiary teaching hospital between May 2015 and April 2017 were included in the study. Demography and smoking status of subjects were recorded. Staging of the disease was according to American Joint Committee on Cancer (AJCC) Staging System 7th edition. Paraglottic space infiltration was taken as a criteria to upgrade the staging. The overall survival rate, recurrence free survival, disease specific survival rate and laryngeal function preservation rate were calculated. RESULTS Out of 43 patients, males were 90.69 % and 09.30 % were females. Male to female ratio was 10.57 : 1. Mean age was 58.62 ± 2.35 years. 67.44 % were current smokers, 27.90 % were former smokers and 02.32 % were non-smokers. The overall survival scores and disease specific survival was 100 % with 11.62 % locoregional recurrences. The voice preservation was 86.04 %. Radiotherapy was used in 72.09 %, chemoradiation in 18.60 % patients and 11.62 % patients underwent surgery. 11.62 % patients presented with locoregional recurrence during 24 months of follow up. 02.32 % patients had to undergo tracheostomy. CONCLUSIONS The overall survival scores and disease specific survival were 100 % with 11.62 % loco-regional recurrence. Voice preservation was 86.04 %. Proactive prevention rather than escalation of treatment protocol gives better prognosis. KEYWORDS Glottis, Larynx, Supra Glottis, Sub Glottis, Squamous Cell Carcinoma, Chemo Radiation and Trans Oral Laryngeal Surgeries

scholarly journals Transoral Surgery Alone for Human-Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

2013 ◽  
Vol 92 (2) ◽  
pp. 76-83 ◽  
Author(s):  
Steven M. Olsen ◽  
Eric J. Moore ◽  
Rebecca R. Laborde ◽  
Joaquin J. Garcia ◽  
Jeffrey R. Janus ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Robotic Surgery ◽  
Cell Carcinoma ◽  
Neck Dissection ◽  
Transoral Robotic Surgery ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Specific

The aim of this retrospective study was to describe the oncologic and functional results of treating oropharyngeal squamous cell carcinoma with transoral robotic surgery and neck dissection as monotherapy. A review was performed, including all patients who underwent transoral robotic surgery and neck dissection as the only means of therapy for oropharyngeal carcinoma from March 2007 to July 2009 at a single tertiary care academic medical center. We reviewed all cases with ≥ 24-month follow-up. Functional outcomes included tracheostomy dependence and oral feeding ability. Oncologic outcomes were stratified by human papillomavirus (HPV) status and tobacco use and included local, regional, and distant disease control, as well as disease-specific and recurrence-free survival. Eighteen patients met study criteria. Ten patients (55.6%) were able to eat orally in the immediate postoperative period, and 8 (44.4%) required a temporary nasogastric tube for a mean duration of 13.6 days (range 3 to 24 days) before returning to an oral diet. No patient required placement of a gastrostomy tube, and all patients are tracheostomy-tube–free. Among the HPV-positive nonsmokers (12/18, 66.7%), Kaplan-Meier estimated 3-year local, regional, and distant control rates were 90.9%, 100%, and 100%, respectively. Kaplan-Meier estimated disease-specific survival and recurrence-free survival were 100% and 90.9%, respectively. No complications occurred.

Impact of Smoking on Survival Outcomes in HPV-Related Oropharyngeal Carcinoma: A Meta-analysis

2020 ◽  
Vol 163 (6) ◽  
pp. 1114-1122
Author(s):  
Ryan Ference ◽  
David Liao ◽  
Qi Gao ◽  
Vikas Mehta
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Hazard Ratio ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Oropharyngeal Carcinoma ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Current Smoking ◽  
Disease Specific

Objective Characterize the survival impact of smoking on HPV-related (human papillomavirus) oropharyngeal squamous cell carcinoma. Data Sources Articles from 2000 to 2019 in the PubMed, Embase, and Cochrane Library databases were systematically reviewed for content and inclusion/exclusion criteria. Review Methods Two reviewers independently analyzed the databases for eligibility and quality of the articles. Demographic data, smoking history, and survival outcomes were recorded. Hazard ratios and 95% CIs were collectively analyzed through a random effects meta-analysis model. Results Fifteen articles were included in the meta-analysis for overall survival, disease-specific survival, disease-free survival, progression-free survival, and locoregional recurrence outcomes. The overall survival hazard ratio was 2.4 for ever having smoked (95% CI, 1.4-4.0; P = .0006, I2 = .384) and 3.2 for current smoking (95% CI, 2.2-4.6; P < .0001, I2 = 0). The hazard ratio for disease-specific survival in current smokers was 6.3 (95% CI, 1.3-29.3; P = .0194, I2 = 0). Ever smoking had a larger impact on overall survival and disease-specific survival than the 10–pack year smoking threshold. Conclusion Smoking negatively affects survival in patients with HPV-related oropharyngeal carcinoma across all outcomes. Current smoking during treatment is associated with the greatest reduction in survival, possibly secondary to diminished radiation therapy efficacy.

scholarly journals Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Jan J. Jobsen ◽  
Lambert Naudin ten Cate ◽  
Marnix L. M. Lybeert ◽  
Astrid Scholten ◽  
Elzbieta M. van der Steen-Banasik ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Distant Metastasis ◽  
Cancer Stage ◽  
Disease Specific Survival ◽  
Stage Iiia ◽  
Free Survival ◽  
Locoregional Failure ◽  
Distant Metastasis Free Survival ◽  
Disease Specific

Objective. The aim of this study is to look at possible differences in outcome between serosa and adnexal involvement stage IIIA endometrial carcinoma.Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed.Results. The 7-year locoregional failure rate was (LRFR) 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P=.0522). The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P=.3994). The 7-year disease-specific survival (DSS) was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa.Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa.

Role of adjuvant therapy after radical hysterectomy in intermediate-risk, early-stage cervical cancer

2020 ◽  
Vol 31 (1) ◽  
pp. 52-58
Author(s):  
Lijie Cao ◽  
Hao Wen ◽  
Zheng Feng ◽  
Xiaotian Han ◽  
Jun Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Treatment ◽  
Radical Hysterectomy ◽  
Concurrent Chemoradiotherapy ◽  
Intermediate Risk ◽  
Recurrence Free Survival ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Disease Specific ◽  
Lymphovascular Space Invasion

ObjectiveAdjuvant treatment remains a controversial issue for intermediate-risk cervical cancer. The aim of this study was to compare the prognosis of patients who underwent no adjuvant treatment, pelvic radiotherapy alone, or concurrent chemoradiotherapy after radical hysterectomy for intermediate-risk, early-stage cervical cancer.MethodsPatients with stage IB1–IIA2 (FIGO 2009) cervical squamous cell carcinoma treated with radical hysterectomy and pelvic lymph node dissection, with negative lymph nodes, surgical margins, or parametria, who had combined intermediate risk factors as defined in the Gynecologic Oncology Group trial (GOG-92; Sedlis criteria) were included in the study. Recurrence-free survival and disease-specific survival were compared.ResultsOf 861 patients included in the analysis, 85 patients received no adjuvant treatment, 283 patients were treated with radiotherapy, and 493 patients with concurrent chemoradiotherapy. After a median follow-up of 63 months (IQR 45 to 84), adjuvant radiotherapy or concurrent chemoradiotherapy was not associated with a survival benefit compared with no adjuvant treatment. The 5-year recurrence-free survival and corresponding disease-specific survival were 87.1%, 84.2%, 89.6% (p=0.27) and 92.3%, 87.7%, 91.4% (p=0.20) in the no adjuvant treatment, radiotherapy alone, and concurrent chemoradiotherapy groups, respectively. Lymphovascular space invasion was the only independent prognostic factor for both recurrence-free survival and disease-specific survival. Additionally, significant heterogeneity exists in Sedlis criteria: higher risk of relapse (HR=1.88; 95% CI 1.19 to 2.97; p=0.007) and death (HR=2.36; 95% CI 1.41 to 3.95; p=0.001) occurred in patients with lymphovascular space invasion and deep 1/3 stromal invasion compared with no lymphovascular space invasion, middle or deep 1/3 stromal invasion, and tumor diameter ≥4 cm.ConclusionsRadical hysterectomy alone without adjuvant treatment may achieve a favorable survival for patients with intermediate-risk cervical cancer as defined by Sedlis criteria. Criteria for adjuvant treatment in patients without high risk factors need to be further evaluated.

Comparison of survival rates in carcinoma in situ of the breast treated with total mastectomy to breast-conserving surgery and radiotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 519-519 ◽  
Author(s):  
M. N. Ibrahim ◽  
Z. Abdullah ◽  
L. Healy ◽  
C. Murphy ◽  
I. Y. Yousif ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Breast Conserving Surgery ◽  
Cox Proportional Hazards ◽  
Disease Specific Survival ◽  
Total Mastectomy ◽  
Kaplan Meier ◽  
Disease Specific

519 Background: Carcinoma in situ (CIS) of the breast is a precancerous lesion with the potential to progress to invasive cancer. In 2003, CIS accounted for 19% of all newly diagnosed invasive and non-invasive breast lesions combined in the United States. Current treatment options are mastectomy ± tamoxifen, and breast-conserving surgery with radiotherapy ± tamoxifen. As there are no randomized comparisons of these 2 treatments, data from the Surveillance Epidemiology and End Results (SEER) database was used to compare their survival rates. Methods: 88,285 patients were identified with CIS from 1988 - 2003. Of these, 27,728 patients were treated with a total mastectomy, and 25,240 patients received breast-conserving surgery with radiotherapy. Kaplan-Meier survival analyses and Cox proportional hazards regression were used to compare overall survival and disease specific survival at 5 and 10 years. Results: Kaplan-Meier analyses demonstrated 5 year overall survival rates for total mastectomy vs. breast conserving surgery with radiotherapy of 95.46% vs. 97.59% respectively (Log-rank P < 0.0001). The 5 year rates for disease specific survival were 99.16% vs. 99.72% respectively (Log-rank P < 0.0001). At 10 years the overall survival rates had fallen to 91.96% vs. 96.09% respectively (Log-rank P < 0.0001). The 10 year disease specific survival rates were 98.61% vs. 99.50% respectively (Log-rank P < 0.0001). Cox proportional hazards regression demonstrated a relative risk of 0.847 (95% confidence interval (CI) 0.790 - 0.907) and 1.110 (95% CI 0.931 - 1.324) for 5 year overall survival and disease specific survival respectively, when total mastectomy was compared with breast conserving surgery and radiotherapy. At 10 years, the relative risks were 0.865 (95% CI 0.820 - 0.913) and 1.035 (95% CI 0.900 - 1.190) for overall survival and disease specific survival respectively. Conclusions: Overall, when looking at disease-specific survival rates by multi-variate analysis, there does not appear to be a significant difference between total mastectomy and breast-conserving surgery with radiotherapy in the treatment of CIS. No significant financial relationships to disclose.

Impact of pathologic complete response to preoperative docetaxel-based chemotherapy on disease-free survival in esophagogastric adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 123-123
Author(s):  
Sylvie Lorenzen ◽  
Nils Homann ◽  
Salah-Eddin Al-Batran ◽  
Florian Lordick ◽  
Tibor Schuster ◽  
...  
Keyword(s):  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
Disease Specific Survival ◽  
Free Survival ◽  
The Impact ◽  
Disease Free ◽  
Disease Specific

123 Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after treatment with preoperative docetaxel/platin /fluoropyrimidine based chemotherapy. Methods: This analysis of a prospective database identified patients who received at least one cycle of preoperative docetaxel/platin/fluoropyrimidine-based chemotherapy for at least T3/4 and N+ disease. An association of pretreatment clinicopathologic factors and pCR was investigated. Overall survival, disease-free survival and disease-specific survival were analyzed according to the achievement of a pCR. Results: A total of 120 patients received preoperative docetaxel-based chemotherapy and underwent subsequent resection of the primary tumor. 15 pts (13%) had distant metastases (M1) at initial diagnosis. 18 patients achieved a pCR in the primary (15%). Median follow-up was 41.1months. The median DFS and OS for the whole population was 24.1 and 48.6 months, respectively. DFS was significantly prolonged in pCR compared to non-pCR patients (HR 2.65, 95% CI 1.1- to 6.2; 3-year DFS probability: 71.8%±10.7 and 37.7%±5.1, respectively, P-value log-rank test=0.018). For patients with a pCR the median DFS was not reached and for those without pCR the median DFS was 22.1 months. Patients with a pCR showed an almost 50% decreased risk of death compared to non-pCR patients (HR 0.53; 95%CI 0.23 to 1.23; P=0.131). Disease-specific survival (DSS) was significantly longer in pCR vs. non-pCR patients (HR 0.188, 95%CI 0.046-to 0.77; P= 0.021). Two clinicopathological parameters were identified as predictors of pCR: tumor localization in the EGJ (p=0.019) and intestinal tumor type according to Laurén’s classification (p=0.042). Conclusions: The analysis confirms that pCR to neoadjuvant chemotherapy is a predictor of favourable patient outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ and intestinal histology represent factors significantly associated with the achievement of pCR.

scholarly journals Prognostic Impact of Tumor Length in Esophageal Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Zhao Yang Wang ◽  
Yuanzhu Jiang ◽  
Wen Xiao ◽  
Xianbiao Xue ◽  
Xiangwei Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Disease Specific Survival ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Tumor Length ◽  
Disease Free ◽  
Disease Specific

Abstract Background: In clinical work, it has been increasingly found that the prognosis is still very different even for esophageal cancer (EC) patients with the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients.Methods: A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis.Results: Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR=1.30; 95% CI: 1.21-1.40, p<.001) and disease-free survival (DFS) (HR=1.38; 95% CI: 1.18-1.61, p<.001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS).Conclusion: The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.

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