Indicator Of Local Recurrence Research Articles

Expression of autophagy-related markers at the surgical margin of oral squamous cell carcinoma correlates with poor prognosis and tumor recurrence

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, and is associated with poor prognosis. Autophagy is a programmed cell survival mechanism involved in physiologic processes and various diseases including cancer. However, the relationship between autophagy and cancer is controversial. Several studies have claimed that the expression of autophagy-related proteins, namely microtubule-associated protein light chain3 (LC3) and p62/SQSTM1 (p62), is associated with poor prognosis in OSCC. In this study, we evaluated the expression of the autophagy-related markers LC3A/B and p62 by immunohistochemistry in 71 OSCC patient samples, especially focusing on surgical margins. Results were correlated with clinical characteristics. The expression of LC3A and LC3B was correlated with tumor recurrence and poor overall survival based on multivariate analysis, whereas the expression of p62 was correlated with only tumor recurrence and not prognosis. Thus, we suggest that the expression of autophagy-related markers at the surgical margins might be an indicator of local recurrence and poor prognosis in human OSCC. These results will aid in the development of new therapeutics and diagnostics for OSCC.

A predictive model to identify patients at risk of local recurrence following glansectomy for penile squamous cell cancer (SCC).

427 Background: Penile preserving surgery for penile cancer is associated with a higher risk of local recurrence (LR). This study developed a predictive model for LR following glansectomy and split skin graft reconstruction . Methods: Retrospective review performed of 177 patients undergoing glansectomy over a 10 year period. The clinicopathological features, LR patterns and cancer-specific survival (CSS) were recorded. Univariate and multivariate logistic regression was used to identify prognostic indicators for LR. The hazard ratio (HR) for LR was estimated using a KM analysis and based on these data we designed a postoperative model for the prediction of LR. Results: The median follow-up period following surgery was 41.4 (1.9-155) months. In total, 9.3 % of the patients developed a LR. Univariate, but not multivariate logistic regression identified perineural invasion (PNI), carcinoma in situ and high grade disease, but not basaloid variant, T stage, lymphovascular invasion and positive resection margins on the specimen to be predictors of LR. A risk model was designed using PNI, CIS and high grade disease in the resected specimen. KM analysis and log rank test revealed no significant differences in LR-free survival between patients with 0 vs 1 or 2 vs 3 risk factors whereas the chance of having local recurrence with 2 risk factors was significantly higher (HR = 5,75; 95% CI 1,43 to 23,15) than with 1 risk factor. A risk stratification model based on a cut-off score of > 1 out of 3 risk factors discriminated well between patients with a high vs low chance of recurrence in a Kaplan-Meier analysis (HR 9.18, 95% CI 3.29 to 25.65 P < 0.001). Indeed, ROC-curve analysis showed an optimal cut-off point of > 1 risk factors with an AUC of 0.77 (P < 0.001, specificity 63%, specificity of 85%) for prediction of LR. Conclusions: Although,LR after glansectomy does not affect the CSS, patients at risk of local recurrence can be identified when > 1 of the factors PNI, CIS and high grade are found on histopathological analysis of the glans. These findings can define the frequency of follow-up and -if validated on pre-op biopsy- potentially be helpful in planning the margins of surgical resection in patients with penile SCC.

Evaluation of swallowing disorders by use of transnasal esophagoscopy in patients treated for head and neck cancer.

The purposes of this study were to identify an index of symptoms and signs of swallowing disorders that indicate the occurrence of local recurrence or second primary malignancy and to evaluate the application of transnasal esophagoscopy in patients treated for head and neck squamous cell carcinoma (HNSCC). Patients treated for HNSCC with swallowing disorders who received transnasal esophagoscopy examinations between January 2010 and June 2014 were included in this study. Local recurrence and second primary malignancy were pathologically diagnosed. In total, 136 patients were examined and one-third of them had local recurrence or second primary malignancy. Thirty-two patients had local recurrence and 14 patients had second primary malignancy. Common swallowing disorders and objective transnasal esophagoscopy findings were similar between the patients with and without local recurrence or second primary malignancy. No definite index of symptoms and signs was an indicator of local recurrence or second primary malignancy in the patients treated for HNSCC. Routine transnasal esophagoscopy examination of patients treated for HNSCC with swallowing disorders is strongly recommended. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1137-E1143, 2016.

A Close Surgical Margin After Radical Prostatectomy is an Independent Predictor of Recurrence

The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy. We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined. Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p <0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors. In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy.

Abstract 669: Disparities in head and neck cancer: A case for chemoprevention with vitamin D

Abstract Worldwide head and neck cancer (HNC) is the sixth most frequently diagnosed cancer in men and is associated with significant morbidity, mortality and economic loss. African Americans (AA) experience significantly more HNC compared to Caucasian Americans (CA) and they have markedly reduced 5-year survival rates, 40% compared to 61% among CA. AA bear a disproportionate burden of HNC for reasons that are incompletely understood, but likely due to the complex interplay of environmental, genetic and health care access issues. An inverse association for vitamin (vit) D status and HNC cancer has been reported and hypovitaminosis D in AA is well documented; yet, vit D status has not been assessed in HNC patients stratified by race. Thus, objective of this prospective pilot study is to access vit D status in newly diagnosed AA and CA HNC patients by measuring the circulating metabolite of vit D, vit-D 25-OH and by assessing dietary levels utilizing the Block vit D/Calcium screener. Circulating calcium, parathyroid, and 1,25-Dihydroxy vit D are also being measured. In addition, to improve our understanding of mechanisms associated with the potential cancer protective effects of vit D in the context of HNC two HNC cell lines were treated with 2 µM cholecalciferol for 6 hours and protein harvested for proteome profiling. To date, 18 HNC patients have been evaluated, 8 AA and 10 CA. Mean circulating vit D 25-OH levels were 27.3 (+ 9.9) and 20.0 (+ 5.9) ng/mL in CA and AA, respectively supporting that vit D levels are suppressed to a greater extent in AA compared to CA HNC patients, even in sunny Florida. Dietary vit D estimates were non-significantly higher in AA HNC patients compared to CA who had higher total vit D levels, supporting differences in metabolism or potentially supplement use. None of the AA patients had vit D 25-OH levels &amp;gt; 30 ng/mL, a level suggested for optimum regulation of PTH, calcium absorption and bone density; 30% of CA patients expressed levels above 30 ng/mL. Proteome profiling of CAL27 and SSC25 HNC cell lines following vit D treatment revealed inverse modulation of proteins linked to HNC. Proteins down-regulated by vit D treatment included nucleophosmin (NPM), lactoylglutathione, heat shock protein beta-1 (HSPB1) Peroxiredoxin-1 (PRDX1) and Ras-related protein Rap-2b. Recent reports have linked NPM with the regulation of the oncogene FOXM1, also a potential biomarker for early detection. Disease-free survival rate is improved in HNC patients with low NPM expression. Similarly, HSPB1 has been shown to be over expressed in HNC and silencing of HSPB1 has been shown to decrease metastatic behavior in HSNCC. PRDX1 displays upregulation in oral premalignancy and is an indicator for local recurrence. Histone H2A type was up-regulated by Vitamin D. Study results support that newly diagnosed AA HNC patients have depressed vit D levels compared to CA cases and that vit D treatment inversely targets select proteins dysregulated in HNC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 669. doi:1538-7445.AM2012-669

Is Serum Placental Growth Factor a Prognostic Marker for Stage III Colorectal Cancer Patients?

To evaluate the clinical usefulness of serum placental growth factor (sPIGF) levels in stage III colorectal adenocarcinomas (CRC). Serum PIGF were measured in 70 healthy controls and in 80 stage III CRC patients. Also the association between preoperative sPGF levels, clinicopathological features and patients survival were evaluated in stage III CRC patients. sPIGF levels in stage III CRC patients were significantly higher than those in controls. There was no significant association between sPIGF levels and clinicopathological features and sPIGF is not a prognostic factor for survival. Multivariate regression analysis showed the sPIGF levels (hazard ratio=3.28; 95% CI=1.10-9.5, p=0.032) to be significant independent factors for local recurrence. Serum PIGF levels in stage III CRC patients are significantly higher compared with normal controls and may be an indicator of local recurrence in stage III CRC patients.

Circumferential Margin Involvement Is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

After preoperative (radio)chemotherapy, histologic determinants for prognostication have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival. A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival. Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively). Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.

P.3 Molecular markers as prognostic indicators for local recurrence in oral squamous cell carcinoma

P.3 Molecular markers as prognostic indicators for local recurrence in oral squamous cell carcinoma

41 Insulin growth factor-1 receptor (IGF-1R) expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study

41 Insulin growth factor-1 receptor (IGF-1R) expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study

140 Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study

140 Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study

Delayed bladder dysfunction after abdominoperineal resection: An indicator of local recurrence

It is generally not appreciated that the delayed onset of voiding dysfunction after abdominoperineal resection for rectal carcinoma may be the first sign of local pelvic recurrence. We herein present a series of 5 patients who were referred for urodynamic evaluation of voiding dysfunction beginning nine to twenty-four months after the original operative procedure. Urodynamic evaluation revealed low bladder wall compliance in 4 patients, and detrusor hyperref lexia in 1 patient. Computerized tomography scans confirmed the local tumor recurrence in all cases. The delayed onset of voiding complaints after abdominoperineal resection should prompt a high index of suspicion that a local tumor recurrence may be present.