Pathological Stage pT3 Research Articles

Successful Treatment of Clinically Diagnosed Cancer-Associated Retinopathy with Intravitreal Dexamethasone Implant Followed by 0.18 mg Fluocinolone Implant without Systemic Immunosuppression.

To report a case of clinically diagnosed cancer-associated retinopathy (CAR) successfully treated with intravitreal corticosteroid implants without systemic immunosuppression. Case report with multimodal imaging. An 80-year-old man without known systemic malignancy presented with debilitating shimmering, hemeralopia and rapidly progressive bilateral vision loss following uncomplicated cataract surgery. Mild vitritis, extensive photoreceptor loss, mottling of retinal pigmentary epithelium (RPE), and mild vascular attenuation were found in both eyes. Full field electroretinogram (ffERG) showed severe bilateral rod-cone dysfunction. Infectious etiologies and vitreoretinal lymphoma were ruled out. During cancer workup, intravitreal corticosteroid treatment was offered. Significant anatomical improvement with reconstitution of ellipsoid zone, improved RPE irregularities and functional improvement, were observed 3 weeks after bilateral intravitreal dexamethasone implants (Ozurdex). 2 months later, patient received bilateral intravitreal 0.18mg fluocinolone acetonide implants (YUTIQ). Later, a colonic adenocarcinoma was found (pathologic stage pT3 pN0). Patient recovered well from surgery and no chemotherapy was needed. 9 months since bilateral intravitreal fluocinolone acetonide implants (11 months since bilateral intravitreal dexamethasone implants), best corrected vision maintained at 20/25-2 OD, 20/20 OS without ongoing treatments. Bilateral reconstitution of ellipsoid zones and nearly resolution of RPE irregularities remained stable. Repeat ffERG demonstrated improved cone response OS and stable diminished rod response OU. Patient reports resolution of ocular symptoms. The sustained improvements with intravitreal corticosteroid monotherapy suggest potential advantages using local therapy over systemic treatment. Long term follow-up is warranted. Further research is needed to evaluate the efficacy of using 0.18mg fluocinolone implant (YUTIQ) to treat CAR.

Comparison of Testosterone Level of Seminal Vesicle Fluid in Patients With Prostate Cancer Versus Other Malignancies.

Testosterone is essential for prostate cancer development and growth. This study aimed to investigate the relationship between testosterone in seminal vesicles and prostate cancer incidence and its malignant phenotype. After obtaining institutional review board approval, seminal vesicle fluid samples were collected from patients who underwent prostatectomy or cystectomy. Pathological review demonstrated that 26 patients had benign prostate tissue and 149 had prostate cancer. First, testosterone levels in seminal vesicle fluid from benign prostate and prostate cancer samples were compared. Next, the relationship between pathological stage, International Society of Urological Pathology (ISUP) score, and testosterone concentrations in seminal vesicle fluid in the prostate cancer group were examined. Testosterone in seminal vesicles was significantly higher in the prostate cancer group [median (range), 1.94 (0.17-4.32) ng/ml] than in the benign prostate group (mainly bladder cancer) [1.45 (0.60-2.78) ng/ml] (p=0.001). Testosterone in seminal vesicles showed no difference in relation to pathological stage (pT2 vs. pT3) or ISUP score (12 vs. 345) (p=0.480 and p=0.964, respectively). Neoadjuvant chemotherapy for other cancers (e.g., bladder or rectal cancer) significantly reduced testosterone in seminal vesicles (p=0.013). Multivariate regression analysis revealed that testosterone in seminal vesicles was significantly correlated with prostate cancer, and not with neoadjuvant chemotherapy (p=0.023, p=0.457, respectively). Testosterone in seminal vesicles may contribute to prostate cancer incidence, but has no relationship with pathological grading.

'Stealth' Prostate Tumors.

The aim of this study was to determine the false negative rates of prebiopsy magnetic resonance imaging (MRI) and MRI-ultrasound (US) 12-core systematic prostate biopsy (PBx) by analyzing radical prostatectomy specimens. This retrospective study included 3600 prostate cancer (PCa) patients who underwent robot-assisted laparoscopic radical prostatectomy. Based on comparison of lobe-specific data on final pathology with preoperative biopsy and imaging data, the study population was subdivided into group I-contralateral (CL) benign PBx (n = 983), group II-CL and/or bilateral (BL) non-suspicious mpMRI (n = 2223) and group III-CL benign PBx + non-suspicious mpMRI (n = 688). This population was studied for the presence of PCa, clinically significant PCa (csPCa), extracapsular extension (ECE) (pathological stage pT3), positive frozen section and final positive surgical margin (PSM) in the CL lobe. Descriptive statistics were performed. In subgroups I, II and III, PCa was respectively detected in 21.5%, 37.7% and 19.5% of cases, and csPCa in 11.3%, 16.3% and 10.3% of cases. CL pT3 disease was seen in 4.5%, 4% and 5.5%, and CL surgical margins and/or frozen section analysis were positive in 6%, 7% and 5% of cases in subgroups I, II and III, respectively. There are still significant rates of false negatives in the standard care diagnostics of PCa. Further strategies are required to improve the accuracy of diagnosis and determination of tumor location.

PTEN Expression and Specific Clinicopathological Associations in Colorectal Carcinomas

Introduction: Colorectal carcinoma (CRC) refers to any cancerthat affects the colon and the rectum and it is a significantpublic health issue.1 It is the third most common cancer to bediagnosed globally and the fourth most frequent reason forcancer-related mortality. The diagnosis of CRCs occurs inplaces with affluent economies about 60% of the time. Thepresent study assessed phosphatase and tensin homolog(PTEN) expression in colorectal cancer and its associationwith tumor characteristics.Materials and Methods: The study was carried out over thecourse of 18 months, from 1 February 2021 to 31 July 2022, atthe SRMS IMS Bareilly Department of Pathology. The analysisincluded surgically removed specimens of colorectal cancerthat had been obtained at the SRMS, IMS Department ofPathology. The patient’s medical records provided the clinicalinformation.Results: Loss of PTEN expression was seen in 76.9% of CRCcases, while 23.1% of cases revealed positive expression.Maximum cases were of age>60 years and male predominancewas noted. In 62.5% of cases with tumor size ≥5 cm displayedloss of PTEN expression. In 52.5% loss of PTEN tumor caseswere histologically moderately differentiated, 37.5% were welldifferentiated, and 10% were poorly differentiated. 50% of caseswith pathologic tumor stage (pT3) and 65% left-sided tumorsshowed loss of PTEN expression.Conclusion: Loss of PTEN expression was observed in themajority of colorectal tumors along with its negative associationwith tumor size and pathologic tumor staging.

Predictive Value of Preoperative Prostate Health Index and Serum Testosterone Testing for Biochemical Recurrence after Radical Prostatectomy for Non-Metastatic Prostate Cancer.

To analyse the predictive value of prostate health index (PHI) combined with serum testosterone after radical prostatectomy (RP) for prostate cancer (PCa). A total of 132 PCa patients who received RP treatment from January 2016 to December 2019 were selected, retrospectively. And then these patients were divided into biochemical recurrence (BCR) group (n = 51) and non-biochemical recurrence (non-BCR) group (n = 81) based on whether BCR was present after RP. Basic data of PCa patients were collected, and preoperative prostate health index (PHI) and serum testosterone levels were measured in both groups. Logistic regression analysis was used to analyse the influencing factors of BCR after RP. The predictive value of PHI and serum testosterone on BCR after RP was analysed using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to plot survival curves, and log rank test was used to analyse the differences between survival curves. The BCR rate of patients in this study was 38.64% (51/132). Single-factor analysis showed that BCR after RP in PCa patients was associated with prostate-specific antigen (PSA), Gleason score, pathological stage, postoperative adjuvant therapy, testosterone and PHI (p < 0.05). Logistics regression analysis showed that PSA >20 ng/mL, Gleason score (8 scores), pathological stage pT3, increased PHI and increased testosterone were independent risk factors for BCR after RP. ROC curve analysis showed that the area under curve (AUC) of PHI and serum testosterone predicting BCR after RP alone and in combination were 0.769, 0.725 and 0.906, respectively. Kaplan-Meier survival analysis showed that preoperative high PHI and low testosterone are negatively correlated with recurrence-free survival rate. Preoperative PHI and testosterone can serve as simple prognostic indicators for postoperative BCR in PCa patients undergoing RP. PCa patients with higher PHI levels and lower testosterone levels may be more prone to developing BCR. The combination of PHI and testosterone has a higher value in predicting BCR after RP.

Morphologic Spectrum of Breast Carcinoma and Correlation of Hormone Receptors and Her2/Neu Status with Clinic-Pathologic Parameters at a Tertiary Care Hospital

Background: After cardiovascular problems, cancer is the 2nd biggest cause of mortality globally. Globally, breast cancer is recognized as the second most prevalent cancer in general, the most prevalent cancer in women, and the 5th major cause of cancer-related death. Objectives: To study the Morphologic Spectrum of Breast Carcinoma and correlation of hormone receptors and HER2/neu status with clinic-pathologic parameters Methods: A total of 97 consecutive cases of modified radical mastectomy were evaluated in the department of histopathology, Rehman Medical Institute Peshawar from February 2019 to December 2020. Expression of PR, ER and Her2/neu were scored similar to College of American Pathologist’s (CAP) guidelines. The analysis of data was done by using SPSS version. Results: Mean age of presentation was 49.6 years. The most prevalent histological subtype was invasive carcinoma of no particular type (72.2%). Grade II tumors were most frequent (43.3%). Lymphovascular and perineural invasion were present in 53.6% and 40.2% of cases respectively. Pathologic stage pT2 was most frequent (56.7%). Macrometastasis was noted in 61.8% of cases. ER and PR showed positivity in 59.8% and 51.5% of cases and Her2/neu was over expressed in 30.9% of cases. ER positivity inversely correlated with Her2/neu but directly with tumor size. Strong association was found between ER/PR positivity and HER2/neu with histologic grade. Conclusion: Our study showed a diverse spectrum of special type carcinomas, none of which showed HER2/neu over expression. Majority of our patients belong to a younger age group and presented with advanced disease. Triple negative breast cancer (TNBC) was commonest in our population after luminal A. HER2/neu overexpression was limited to grade 2 and 3 of invasive ductal carcinoma Keywords: Morphologic Spectrum; Breast Carcinoma; Hormone receptors

PD-L1 Tumor Cell Expression in Upper Tract Urothelial Carcinomas is Associated With Higher Pathologic Stage.

Upper tract urothelial carcinomas (UTUCs) are a rare and unique subset of urothelial carcinoma (UC). Patients with UTUC may qualify for treatment with immune checkpoint inhibitors if their tumor cells express programmed death ligand-1 (PD-L1). While several large studies have looked at PD-L1 expression in UC, most have not investigated UTUC as a separate group, and most have not used Food and Drug Administration approved PD-L1 stains and scoring systems. Moreover, comparison between studies of PD-L1 expression is challenging as a wide variety of different PD-L1 antibody clones, testing platforms, and cutoff values have been used in the literature. This is a retrospective study of 37 cases of resected UTUC. Representative tissue from each case was compiled into tissue microarrays and immunohistochemical stains for PD-L1 (Dako antibody clones 22C3 and 28-8) were performed. PD-L1 staining was evaluated using several established Food and Drug Administration approved scoring systems: tumor proportion score (TPS), combined positive score, and immune cell score. Associations between PD-L1 expression and clinicopathologic features were investigated. Overall expression of PD-L1 in UTUC was 29.7% when using a TPS cutoff of ≥1%. Total of, 55.6% of cases with higher pathologic stage (pT3 or pT4) were positive for PD-L1, compared with only 5.3% of cases with lower pathologic stage (pTis, pT1, or pT2; P=0.0011). When using a combined positive score cutoff of ≥10, there was no significant association between tumor stage and PD-L1 expression. There was no association between PD-L1 positivity and tumor grade, tumor location, sex, or age. There was 100% concordance between 22C3 and 28-8 in terms of positivity rate. Our study using approved testing methods shows that PD-L1 expression in UTUC is more often associated with high pathologic stage, which may reflect an immune response evasion mechanism that UC cells acquire later in disease progression. In addition we show that 29.7% of UTUCs are positive for PD-L1 TPS expression, comparable to the 20% to 30% reported in UC literature. Finally, PD-L1 22C3 and 28-8 clones show similar overall patterns of staining in this setting.

Can Tumour Volume Percentage in Radical Prostatectomy Predict Cancer Biochemical Recurrence? Determining a Cut-off Point and Composite Risk Factors Approach.

BackgroundIncidence of biochemical recurrence (BCR) after radical prostatectomy is relatively high and overall survival can be poor. Debate exists whether tumour volume predicts BCR and when treatments should be administered. In this study, we aimed to i) assess the impact of tumour volume percentage (TVP) as a predictor for BCR, ii) determine TVP cut-off point for BCR and iii) evaluate single and composite predictors of BCR.MethodsFrom March 2000 to December 2013, 1777 patients underwent laparoscopic radical prostatectomy for localized prostate cancer. None received neoadjuvant or adjuvant therapy. One hundred and forty-six patients experienced BCR (range 3 months-10 years). Using D’Amico classification, 146 matched controls without BCR were compared. Liu cut-point analysis was used to identify TVP with optimal sensitivity and specificity. Single and composite BCR risk predictors were analyzed using Cox hazards regression in cases and controls.ResultsMedian TVP was 10% (range 1–90%). Most of BCR peaked after 3 years of follow-up. TVP ≥8% was an independent predictor of BCR with HR 1.6 (p= 0.001, 95% CI= 1.11–2.48). TVP of 8% was associated with the highest accuracy: sensitivity 74% and specificity 53% (ROC curve= 0.7). At TVP ≥8%, pathological stage pT3 was associated with 1.7-fold higher risk of BCR compared to T2. Lymph node invasion was associated with 1.4-fold higher risk of BCR compared to no invasion. Combining TVP ≥8%, pT3 and lymph node invasion, HR jumped to 3.73 (p< 0.001, 95% CI= 2.27–6.14), whereas combining TVP ≥8%, positive surgical margin and lymph node invasion, HR was 2.68 (p= 001, 95% CI= 1.50–4.77).ConclusionTVP can be used as an independent predictor of BCR after radical prostatectomy for prostate cancer. TVP cut-point of ≥8% allows the best discrimination. TVP should be considered in combination with other clinico-pathological factors to improve prediction of long-term oncological outcomes and to stratify BCR risk.

Biochemical relapse in very high-risk prostate cancer after radical prostatectomy and DC-vaccine loaded with tumor RNA, hTERT, and survivin.

324 Background: Patients with very high-risk prostate cancer (VHR-PC) features experience worse outcome after radical prostatectomy. This study was designed to assess biochemical failure and toxicity of adjuvant dendritic cells vaccine (DCV) in prostate cancer patients who are at greatest risk for cancer progression. Methods: Twenty patients with pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx were enrolled into the approved study DC-005. The primary end point was clinical failure. Ten patients were tested for disseminated tumor cells (DTCs) to the bone marrow before inclusion to the study. Three patients out of 10 patients had positive DTCs detection in bone marrow. The mean age of the cohort was 63 years (SD 6.9 years), and three patients had postsurgical pN1 status. Eighteen patients had two or more high-risk factors (ISUP grade 5, T3- stage and or PSA &gt; 20 ng/mL). Autologous dendritic cells were transfected with mRNA for hTERT, survivin and tumor mRNA. The DCV product was applied intradermally after curative intended surgery once per week the first months, then once per months the first year, thereafter every 3 months for two years or until biochemical progression (PSA relapse cut-off ≥ 0.3). Results: After 5 years follow-up (FU) 62% (12/20 patients) had not biochemically progressed and with a median FU of 69 months all patients included in the study are alive. Five patients were treated with salvage and one patient with adjuvant radiation treatment, three patients received limited ADT, and three patients are on first line ADT, none of those eight patients have experienced castration resistant prostate cancer. The toxicity was mild with no serious adverse event related to DCV. Conclusions: Adjuvant DCV mitigates the time to biochemical progression. These results appear favorably compared to historical controls in VHR-PC. The clinical outcomes of this study warrants a future enlarged clinical trial. Clinical trial information: NCT01197625.

Clinicopathological and molecular features of sporadic colorectal cancers with DNA mismatch repair deficiency: A single center experience

DNA mismatch repair (MMR) proteins may play an important role in colorectal carcinogenesis. In our study, the clinicopathological features of defective MMR in sporadic colorectal adenocarcinomas (CRCs) cases were examined. This is a retrospective study, 457 consecutive cases of colorectal carcinoma with immunohistochemical (IHC) studies for DNA MMR were included.The immunohistochemically (IHC) MMR results of 457 cases were; nuclear expression was intact (proficient, pMMR) in 401 (87.7%) cases and loss of nuclear expression (deficient, dMMR) was found in 56 cases (12.3%). High probability of Lynch syndrome ratio was 2.4% (11/457) in all cases. The loss of PMS2 was predominantly detected in dMMRcases (78.6%). Seventy eight percent of dMMR tumors were located in the proximal colon. In dMMR tumors, prominent peritumoral lymphoid aggregates (LAs) (85.7%) and tumor-infiltrating lymphocytes (TILs) (78.6%) were observed. Among 56 colorectal cancers, we observed expanding /pushing growth pattern in 41 tumors (73.2%), and infiltrative growth pattern in 15 cancers (16.8%). Medullary, mucinous and signet ring cell carcinomas were observed in approximately half of the cases, but there was no statistically significant relationship. Eighty nine percent of dMMR cases had advanced pathologic tumor stage (pT3 or pT4), and this rate was 82.5% in pMMR cases. The average number of positive lymph nodes in cases with dMMR was higher than in pMMR. KRAS mutations were detected in 7.2% (4/13) patients and 14.3% (8/13) patients with MLH1 promoter methylation was observed. Seventy percent of patients with dMMR were alive (n=44) and the mean age of the patients who died was higher. A statistically significant relationship was found between the patients who died and the mean age of surviving patients (p = 0.036). We conclude that the dMMR patients constitutes have a number of distinctive clinicopathological features subtype of sporadic CRC. The overall frequency of defective MMR in colorectal carcinoma cases was found to be Turkish population similar to western studies. dMMR in CRCs were more likely to be of advanced pathologic tumor stage to have a mucinous tumor component and positive LN to show PMS2 loss and to harbour higher numbers of both peritumoral LAs and TILs. They were also more likely to be proximal colon and to occur in male.

Biopsy Grade Group as a reliable prognostic factor for BCR in Afro-Caribbean men with intermediate- and high-risk prostate cancer

The Grade Group (GG) classification is recommended by guidelines as a reliable prognostic factor of prostate cancer. However, most studies have been performed on the Caucasian population. Our objective was to validate GG classification as a safe way to classify intermediate- and high-risk patients with African ancestry. This was a retrospective study in an Afro-Caribbean population. A total of 1236 patients were included between 2000 and 2015. Patients were stratified according to (GG). Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analyses using the Cox model. There was no significant difference at 5 and 10-year BCR-free survival between the intermediate- and high-risk groups, based on the D'Amico classification. There was a highly significant difference in BCR-free survival at 5 (p < 0.0001) and 10 years (p < 0.0001) for patients of GG 1 and 2 vs 3, 4, and 5, respectively. There was no significant difference in 5-year BCR-free survival of patients of GG grades 1 and 2, whether lymph-node dissection was performed or not. There was a significant difference between GG 2 and 3 patients in 5 (p = 0.008) and 10-year BCR-free survival (p = 0.01). High PSA (p < 0.0001), pathological GG ≥ 3 (p < 0.0001), pathological stage pT3 (p < 0.0001) and positive margins (p < 0.0001) were factors for BCR in multivariate analysis. The GG 2015 classification appears to be a better prognostic factor than D'Amico classification for intermediate- and high-risk Afro-Caribbean patients.

Morphologic subtyping as a prognostic predictor for survival in papillary renal cell carcinoma: Type 1 vs. type 2

ObjectiveTo evaluate outcomes of surgically treated patients with clinically localized papillary renal cell carcinoma (RCC) and determine if papillary RCC subtype is associated with recurrence and survival. MethodsThis is a historical cohort study using the prospectively maintained Canadian Kidney Cancer Information System database between January 2011 and September 2018. All patients underwent partial or radical nephrectomy. Patient, tumor, treatment, and outcomes were compared between papillary RCC type 2 and type 1 cohorts. ResultsDuring the study period, 509 patients had clinically localized papillary RCC type 2 (n = 172) or type 1 (n = 337) histology. Sex, race, and comorbidities were similar between groups. Pathologic stage (pT3 or pT4), nuclear grade (3 or 4), and tumor diameter were higher in the type 2 papillary RCC cohort (P < 0.0001). A greater proportion of type 2 papillary RCC patients received radical nephrectomy (42.4% vs. 24.6%, P< 0.0001). More type 2 papillary RCC patients underwent lymph node dissection (19.6% vs. 5.5%, P< 0.0001) and had lymph node metastases removed during surgery (6.4% vs. 0.6%, P= 0.103). Overall, adjusting for age, grade, pathologic stage, positive nodes, and tumor size, type 2 papillary RCC had worse outcomes compared to type 1, as demonstrated by elevated all-cause mortality (hazard ratio = 7.7 [95% confidence interval: 2.0–28.9]), P=0.0027) and worse recurrence-free survival (hazard ratio = 8.2 [95% confidence interval: 3.6–19.0], P< 0.0001). ConclusionPatients with clinically localized type 2 papillary RCC present with higher risk disease and have worse prognosis compared to patients with clinically localized type 1 papillary RCC. To the best of our knowledge, this is the largest cohort study comparing papillary RCC subtypes.

Is the non-metastatic, locally advanced colon adenocarinoma a distinct biological tumor variant? A study based on pathological evaluation, immunohistochemical panel and survival.

to evaluate the clinical and pathological differences between locally advanced colonic adenocarcinomas (LACA) with adhesions between adjacent organs or structures, and colonic adenocarcinomas with other clinical presentations. we conducted a retrospective study from a convenience sample of patients with colonic adenocarcinoma, pathological stage pT3, distributed according to clinical and pathological characteristics in three groups: locally advanced tumors (LACA), pT3 tumors without adhesions or distant metastases (SF) and tumors with metastatic disease (M1). We evaluated clinical and pathological characteristics and the expression of seven immunohistochemical markers related to proliferation/apoptosis, cell invasion/migration and metastasis. we studied 101 patients: 30 LACA, 44 SF and 27 M1. Locally advanced tumors presented larger dimensions and were associated with increased lymphocyte infiltration rates, lower levels of bax expression, and CD 44v6 when compared with SF and M1 groups. We observed significant differences between LACA and M1 in relation to colonic location, histology, lymph node status and bax and CD44v6 expression. We found differences were observed between the three groups for tumor size and lymphocytic infiltrate. Survival was similar in the LACA and SF groups (p=0.66) and was lower in the M1 group (p<0.001). the data suggest that locally advanced colonic adenocarcinomas with adhesions between adjacent organs or structures represent a distinct entity.

The American Joint Committee on Cancer Eighth Edition: Changes in Thyroid Carcinoma Staging and an Update on Reporting

Abstract The AJCC Cancer Staging Manual, Eighth Edition (AJCC 8th edition) contains a number of significant changes, many of which affect the reporting of clinicopathologic parameters in thyroid cancers. The first key change is the separation of medullary thyroid carcinoma into its own chapter. Within differentiated and anaplastic thyroid carcinomas, anaplastic carcinomas are now assigned a T stage similar to differentiated thyroid carcinomas. However, this is largely cosmetic because these are still assigned stage group IV. Perhaps the most significant alteration from a reporting standpoint is revision of extrathyroidal extension (ETE) in terms of T staging. Pathologic stage pT3 is now subdivided into pT3a (by size) and pT3b (by ETE). Under AJCC 8th edition, pT3b is now defined by gross (clinical, radiologic, and/or macroscopic) ETE. Other key changes are the inclusion of level VII (anterior mediastinal) lymph nodes as N1a and changes in stage groupings, particularly with a new age cutoff of 55 years, and a downshift in several stage groups. In medullary thyroid carcinoma, the potential prognostic value of nonanatomic factors (ie, serum calcitonin, carcinoembryonic antigen, RET mutation status) is officially recognized, although not yet part of staging. The advent of the new terminology noninvasive follicular thyroid neoplasm with papillary-like nuclear features will remove a subset of tumors that qualify for this new designation from formal AJCC staging altogether.

Positive surgical margin following radical nephrectomy is an independent predictor of local recurrence and disease-specific survival

BackgroundPositive surgical margins (PSM) are recognized as an adverse prognostic sign and are often associated with higher rates of local and systemic disease recurrence. The data regarding the oncological outcome for PSM following radical nephrectomy (RN) is limited. We examined the predictive factors for PSM and its influence on survival and site of recurrence in patients treated with RN for renal cell carcinoma (RCC).MethodsClinical, pathologic and follow-up data on 714 patients undergoing RN for kidney cancer were analyzed. Secondary analysis included 44 patients with metastatic RCC upon diagnosis who underwent cytoreductive nephrectomy (CRN). Univariate and multivariable logistic regression models were fit to determine clinicopathologic features associated with PSM. A Cox proportional-hazards regression model was used to test the independent effects of clinical and pathologic variables on survival.ResultsPSM was documented in 17 cases (2.4%). PSM were associated with tumour size, advanced pathologic stage (pT3 vs. ≤ pT2) and presence of necrosis. On multivariate analysis, cancer-specific survival (CSS) was associated with tumour stage, size, presence of necrosis and PSM. PSM was also associated with local recurrence but not distant metastasis or overall survival (OS). CSS and OS were comparable between the PSM and metastatic RCC groups, but significantly lower than the negative margin group.ConclusionsThe prevalence of PSM following RN is rare. Pathological data, including advanced stage (> pT2), tumour necrosis and tumour size, are associated with the presence of PSM. PSM is associated with tumour recurrence and CSS. Patients with PSM are a potential group for adjuvant therapy or for more careful and thorough follow-up following surgery.

Upgrading and upstaging at radical prostatectomy in the post–prostate-specific antigen screening era: an effect of delayed diagnosis or a shift in patient selection?

Prostate cancer management changed in recent times given the recommendation against prostate-specific antigen screening, adherence to active surveillance, and "cytoreductive" surgery. We hypothesized that radical prostatectomy (RP) findings changed as well. All consecutive RPs (n=1348) and first time prostate needle biopsies (n=1719) in a period of 9 years were reviewed. The cohort was separated into 3 groups: (1) from May 2006 to April 2009, (2) from May 2009 to April 2012, and (3) from May 2012 to April 2015. The number of RPs decreased 15% from 551 in group 1 to 476 in group 2 and decreased a further 35% to 311 in group 3. Pure Gleason 6 (grade group 1) decreased from 46% in group 1 to 24% in group 2 (P<.001) to 12% in group 3 (P<.001). Gleason score 4+3=7 (grade group 3) increased from 9.8% in group 1 to 13.4% in group 2 (P=.07) to 20.6% in group 3 (P=.01). Gleason score 8, 9, or 10 (grade groups 4 and 5) increased from 0.9% in group 1 to 8.4% in group 2 (P<.001) to 13.2% in group 3 (P=.04). Pathologic stage pT3 or above increased from 15.5% in group 1 to 29.2% in group 2 (P<.01) to 38.3% in group 3 (P=.01). In needle biopsies, there was no difference in number of cancer diagnoses, number of positive cores, or distribution of grades among 3 groups. More patients with low-risk disease are opting for active surveillance, and patients with high-risk disease are offered cytoreductive surgery. Lack of similar changes in needle biopsies suggests that a decrease in screening is not playing a role in the changes seen at RPs.

Occult GI Bleed Secondary to Small Bowel GIST

A 63-year old female with a history of anemia thought secondary to GI-bleeding presented to the hospital with lethargy and fatigue. Past workup included endoscopic evaluations with EGDs, colonoscopies, capsule endoscopy, and enteroscopy without any evidence of an obvious potential source. Given her presentation and hemodynamic stability it was decided to perform a capsule endoscopy that revealed a proximal jejunal submucosal lesion that was confirmed on CT imaging. Subsequent laparascopic evaluation revealed a 5 x 3 cm tumor in the proximal jejunum with tumor necrosis. Pathology revealed a mitotic rate of 4/50 HPF and was consistent with a gastrointestinal stromal tumor (GIST) with a pathologic stage pT2, N0. She was discharged home and on GI clinic follow-up had a normal hemoglobin and no further episodes of acute GI-bleeding. Gastrointestinal stromal tumors (GISTs) represent approximately 1-3% of all GI malignancies with 30% occurring in the small bowel. Patients may present with symptoms of abdominal pain, nausea, vomiting, hematemesis, melena, or anemia. CT is 87% sensitive at revealing endoluminal and exophytic lesions in addition to evidence of metastases. Sodhi et al showed that use of CT-enterography can be useful in visualizing small bowel wall and luminal pathology causing obscure or occult GIB. Urgesi et al demonstrated that capsule endoscopy (CE) can be a useful and sensitive tool compared to traditional radiographic modalities in the identification of GISTs. In 2013, Zagorowicz et al argued rather convincingly that when available, balloon-assisted enterography (BAE) should be pursued when presenting symptoms indicate a source of bleeding in the small bowel. Still, CE is considered the preferred initial diagnostic test given that it is less invasive. In our case, prior CE did not reveal a culprit lesion and follow-up endoscopic procedures were also negative. The medical decision-making to pursue a repeat CE in our patient proved useful in source identification. Hence in patients with a history of occult GI-blood loss, it seems reasonable to consider CE an initial diagnostic tool, even in the setting of a prior negative study.Figure 1Figure 2

Abstract 2235: Clinical results of a Phase I/II trial of adjuvant therapeutic vaccination in high risk resected prostate cancer patients using autologous dendritic cells loaded with mRNA from primary prostate cancer tissue, hTERT and survivin

Abstract Prostate cancer patients diagnosed with high Gleason score (≥ 8) and large tumors (≥T2c) are considered high-risk patients and &amp;gt;50% will develop an early biochemical relapse. Presently, there is no curative therapy available for patients with biochemical relapse. Based on these findings we initiated in January 2011 a Phase I/II dendritic cell (DC) vaccine study. Patients included have pathological stage pT2 - pT3b, Gleason score 7b-10, pN0, pN+ or pNx and postoperative PSA &amp;lt; 0.2 μg/L. Following surgery autologous tumor cell lines were established from each patient using an in-house culturing method. mRNA from the tumor cell line was produced and used for DC vaccination in combination with mRNA hTERT and mRNA Survivin. DCs were differentiated from enriched monocytes, cultured for 2 days with IL4 and GM-CSF and matured with Jonuleit-maturation cocktail for 24 hours. The matured DCs were transfected separately with the 3 different mRNAs and then frozen and stored until use. The vaccination regimen includes one vaccine per week for four weeks, followed by monthly “vaccine boost” during the first year, then every 3 months the second and third year. Recently, a novel 3 days DC protocol using a TLR7/8-agonist maturation cocktail has been implemented at our department. Based on encouraging clinical results with this type of DCs in compassionate use patients with different types of tumors, we decided to change our DCs protocol to the new generation DCs. Of the 20 patients included in this trial 15 patients have been given the standard fast DCs and 5 have been vaccinated with the new type of DCs. 8 Patients given standard DC has completed 3 years of vaccination and 4 has completed 2 years of vaccination. 3 of 15 patient given standard DC has experienced PSA relapse during vaccination. None of the patients given the new type of DC has so far experienced raise in PSA levels. To our knowledge this is the first adjuvant DC vaccine study in high risk prostate cancer and we conclude that the study is feasible, safe and utmost promising. Extensive immune monitoring is ongoing taking advantage of the established autologous tumor cell lines from all patients. Citation Format: Anne Merete Aa. Tryggestad, Karol Axcrona, Iris Bigalke, Else M. Inderberg-Suso, Gjertrud Skorstad, Ulrika Axcrona, Steinar Aamdal, Gustav Gaudernack, Dolores Schendel, Wolfgang Lilleby, Svein Dueland, Gunnar Kvalheim. Clinical results of a Phase I/II trial of adjuvant therapeutic vaccination in high risk resected prostate cancer patients using autologous dendritic cells loaded with mRNA from primary prostate cancer tissue, hTERT and survivin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2235.

MP04-07 POVERTY IS ASSOCIATED WITH ADVERSE PROSTATE CANCER PATHOLOGY AMONG AFRICAN-AMERICAN MEN UNDERGOING RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: Prior studies have suggested that poverty is associated with advanced stage or aggressive prostate cancer at presentation. However, due to strong associations between poverty and race, the independent contribution of poverty, irrespective of race, remains unclear. To eliminate potential confounding, we sought to test for an association between poverty and adverse pathology in a population comprised exclusively of African-American (AA) men treated with radical prostatectomy (RP). METHODS: African American men who underwent radical prostatectomy between September 2010 and September 2015 at Temple University Hospital and the University of Pennsylvania were identified through our institutional databases. Median household income for each patient’s residential zip code was determined using United States Census Bureau data. The median income for the study population was calculated, and patients were stratified as either lowor high-income relative to the median. Pathological outcomes, CAPRA-S score, and rates of adverse pathology (defined as pathological stage pT3, pathological Gleason score 4+3, or lymph node involvement) were compared between income groups. Linear and logistic regression were used to test for associations of income with CAPRA-S score and adverse pathology, respectively. RESULTS: 385 African American men met inclusion criteria. Median household income was $40,031 (range $14,297-$162,617), The table compares disease-specific and pathological outcomes between low and high income men. Low income men had significantly higher PSA values (p<0.01), rates of seminal vesicle invasion (p<0.01), positive margin rates (p<0.01), CAPRA-S scores (p<0.01), and rates of adverse pathology (p1⁄40.02). Linear and logistic regression showed significant inverse associations of patient income with CAPRA-S score (p<0.01) and adverse pathology (p1⁄40.03). CONCLUSIONS: We observed a significant association of poverty with adverse pathology in a population of African-American men treated with RP. This suggests that poverty, irrespective of race, is associated with advanced stage or aggressive prostate cancers. Community outreach, education, and screening efforts should target low-income men to decrease prostate cancer morbidity. Source of Funding: None

Expression of bone sialoprotein in prostate cancer and its clinical significance

Objective To investigate the expression of bone sialoprotein (BSP) in prostate cancer and its clinical significance. Methods Prostate cancer tissues of different pathological grades (68 cases) and benign prostatic hyperplasia tissues (22 cases) were selected. SP method was used to detect the expression of BSP. Serum total prostate-specific antigen (tPSA) levels of prostate cancer were detected by electrochemiluminescence immunoassay before the operation. Results Compared with no or low expression in the adjacent normal glandular tissues, the detectable levels of BSP were examined in most of the prostate cancer tissues. The expression rate of BSP in prostate cancer tissues was higher than that in benign prostatic hyperplasia tissues [76.47 % (52/68) vs 13.64 % (3/22), χ2 = 27.614, P< 0.001]. The expression rates of BSP in well differentiated, moderately differentiated and poorly differentiated tissues according to cell differentiating degree (Gleason system) were 75.0 % (12/16), 77.5 % (31/40) and 75.0 % (9/12) respectively. There was no significant difference in various pathological grading (χ2 = 0.057, P= 0.972). The expression rates of BSP in pathological stage pT2, pT3 and pT4 tissues were 62.16 % (23/37), 95.24 % (20/21) and 90.0 % (9/10) respectively. A statistically significant association was found between BSP expression and pathological stage (χ2 = 9.338, P= 0.009). Serum tPSA level of prostate cancer group with BSP expression was higher than that with no BSP expression [(69.06±25.52) μg/L vs (38.00±21.64) μg/L, F= 19.355, P< 0.001]. Conclusion The high expression of BSP in prostate cancer has a relationship with pathological stage and serum tPSA level, it may play an important role in the biological behaviour of prostate cancer. Key words: Prostatic neoplasms; Bone sialoprotein; Prostate-specific antigen; Immunohistochemistry