Prognostic Grade Research Articles

Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma

Endometrial endometrioid carcinoma is usually divided into three histological subgroups: grade 1 (G1), grade 2 (G2), and grade 3 (G3). Most cases of endometrial endometrioid carcinoma G1/2 have a favorable prognosis, although some can have unfavorable outcomes, especially when they involve elderly patients, with similarities to endometrioid carcinoma G3 and serous carcinoma. This retrospective study evaluated whether TP53 abnormalities in endometrial endometrioid carcinoma could be used to supplement the current grading system and improve its ability to predict clinical outcomes. Immunohistochemical expression of TP53 was analyzed using tissue microarrays from the surgically resected specimens of 475 patients with endometrial endometrioid carcinoma. Weak or moderate expression was defined as TP53-normal expression, while absent or strongly positive expression was defined as TP53-aberrant expression. The endometrial endometrioid carcinomas had originally been diagnosed as G1 (69%), G2 (18%), and G3 (13%). Univariate analyses revealed that TP53-aberrant expression was associated with poor survival in G1 and G2 cases, but not G3 cases. In addition, age (<60 years vs. ≥60 years) was correlated with TP53-aberrant expression in G1 cases (3% vs. 16%, p = 0.001), but not in G2 or G3 cases. Based on immunohistochemical TP53 expression, the endometrial endometrioid carcinomas were reclassified using a prognostic grading system as high-grade (G1 or G2 with TP53- aberrant expression, and G3 with TP53-normal or -aberrant expression) or low-grade (G1 or G2 with TP53-normal expression). The multivariate analyses revealed that the prognostic grading system (using histological grade and TP53 expression) could independently predict poor progression-free survival (hazard ratio: 2.91, p < 0.001) and overall survival (hazard ratio: 3.62, p < 0.001). Therefore, combining immunohistochemical TP53 expression with the traditional histological grading system for endometrial endometrioid carcinoma may help improve its ability to accurately predict the patient's prognosis.

Various Clinicopathological Factors Impacting Recurrence in Stage I Endometrial Cancer: A Retrospective Study

Endometrial cancer usually has a good prognosis. The recurrence and survival in endometrial cancer are based on multiple prognostic factors like patient age, histological grade, myometrial invasion, and lymphovascular space invasion. We investigated various clinicopathological features determining tumor recurrence in stage I endometrial cancer with endometrioid histology. We retrospectively reviewed stage I endometrial cancer patients who underwent surgery at the Basavatarakam Indo American Cancer Hospital between 2010 and 2015. Patients who had tumor recurrence were documented. Various risk factors like size, grade, depth, lymphovascular involvement, etc., were studied, their relation with recurrence was noted, and statistical analysis was done. Twenty-three patients exhibited tumor recurrence in stage I EEC (13.3%). When considering the depth of myometrial invasion, the 5-year RFS of stage IA EEC is 90.4% in comparison with 66.6% when the depth of invasion is more than half of myometrial invasion. The 5-year RFS of the patients with stage I EEC is 100% in tumors with size less than 2 cms, 92.15% in tumor size 2–4 cms, and 70.45% when the tumor size is greater than 4 cms. The 5-year RFS of the patients is 94.7% in grade 1, 87.3% in grade 2, and 54.2% in grade 3. Depth of myometrial invasion, grade, and size of the primary tumor are shown to affect recurrence. LUS involvement, intracervical glandular involvement, and the lymphovascular space invasion did not affect recurrence in endometrioid endometrial cancer.

Risk Factors Predicting Recurrence of Bilateral Chronic Subdural Hematomas after Initial Bilateral Evacuation

Most patients with bilateral chronic subdural hematomas (bCSDH) undergo initial bilateral evacuation. Risk factors associated with the recurrence of bCSDH after initial bilateral evacuation have not been published to date. In this study, we aimed to identify risk factors related to recurrence of bCSDH after initial bilateral evacuation, and to develop a prognostic grading system for clinical reference. This study included 102 patients with bCSDH who underwent initial bilateral evacuation. Predictors of recurrence were identified via univariate analysis and multivariate logistic regression analysis. A prognostic grading system was created based on the independent predictors combined with a cutoff value. All cases were scored according to the prognostic grading system, and the recurrence rates of the different scores were reanalyzed. Anticoagulant use (odds ratio [OR], 84.266; 95% confidence interval [CI], 13.113-541.522; P < 0.001), severe brain atrophy (OR, 11.551; 95% CI, 2.558-52.163; P=0.001), and postoperative pneumocephalus volume (PostPV) (OR, 0.978; 95% CI, 0.957-1.000; P= 0.049) were independent risk factors for the recurrence of bCSDH after initial bilateral evacuation. The cutoff value of PostPV was >20.9484 cm3. A prognostic grading system was then developed, and the recurrence rates based on score were determined. Rates were 2.8% for a score of 0-1, 28.1% for a score of 2-3, and 100% for a score of 4-5, showing a significant increase in risk with increasing score (P<0.001). Anticoagulant use, severe brain atrophy, and PostPV were identified as independent risk factors for recurrence of bCSDH after initial bilateral evacuation. The prognostic grading system for recurrence of bCSDH after initial bilateral evacuation is reliable and applicable for clinical reference.

Applicability and limitations of a recently-proposed prognostic grading metric, initial brain metastasis velocity, for brain metastasis patients undergoing stereotactic radiosurgery.

This study, based on our brain metastasis (BM) patients undergoing stereotactic radiosurgery (SRS) procedures, aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV, scoring the cumulative number of BMs at the time of SRS divided by time [years] since the initial primary cancer diagnosis), is generally applicable. This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3498 patients who underwent SRS for BMs during the 19.5-year-period between July, 1998 and December, 2017. We excluded four lost to follow-up, 24 for whom the day of primary cancer diagnosis was not available, 665 with synchronous presentation and 651 with pre-SRS radiotherapy and/or surgery, ultimately studying 2150 patients. Patients were categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. In a multivariable model, iBMV was directly associated with a higher risk of death (p < 0.0001). The median survival time of patients with iBMV scores < 2.00, 10.0 (95% CI; 9.2-10.9) months, was longer than that of patients with iBMV scores ≥ 2.00, 6.3 (5.6-6.7) months, showing a significant difference between the two groups (HR 1.599, 95% CI 1.458-1.753, p < 0.0001). The same results were obtained in patients with non-small cell lung, breast, kidney or other cancers. Among 608 patients who underwent repeat SRS for newly-developed BMs, iBMV score categories correlated well with brain metastasis velocity risk groups (p < 0.0001). Our present results support the validity of iBMV for predicting survival after SRS.

Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?

In order to better time salvage radiotherapy (SRT) for post-radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system. Using the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir+ 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG. A total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA≥ 1.0 ng/mL had higher recurrence risks (hazard ratio= 2.78, P< .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio= 2.15, P= .021; and hazard ratio= 2.49, P= .010, respectively) versus PSA 0.2-0.49 ng/mL. In men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA< 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.

CT-based radiomic features predict tumor grading and have prognostic value in patients with soft tissue sarcomas treated with neoadjuvant radiation therapy

PurposeIn soft tissue sarcoma (STS) patients systemic progression and survival remain comparably low despite low local recurrence rates. In this work, we investigated whether quantitative imaging features (“radiomics”) of radiotherapy planning CT-scans carry a prognostic value for pre-therapeutic risk assessment. MethodsCT-scans, tumor grade, and clinical information were collected from three independent retrospective cohorts of 83 (TUM), 87 (UW) and 51 (McGill) STS patients, respectively. After manual segmentation and preprocessing, 1358 radiomic features were extracted. Feature reduction and machine learning modeling for the prediction of grading, overall survival (OS), distant (DPFS) and local (LPFS) progression free survival were performed followed by external validation. ResultsRadiomic models were able to differentiate grade 3 from non-grade 3 STS (area under the receiver operator characteristic curve (AUC): 0.64). The Radiomic models were able to predict OS (C-index: 0.73), DPFS (C-index: 0.68) and LPFS (C-index: 0.77) in the validation cohort. A combined clinical-radiomics model showed the best prediction for OS (C-index: 0.76). The radiomic scores were significantly associated in univariate and multivariate cox regression and allowed for significant risk stratification for all three endpoints. ConclusionThis is the first report demonstrating a prognostic potential and tumor grading differentiation by CT-based radiomics.

Topographic Phenotypes of Alopecia Areata and Development of a Prognostic Prediction Model and Grading System

Diverse assessment tools and classification have been used for alopecia areata; however, their prognostic values are limited. To identify the topographic phenotypes of alopecia areata using cluster analysis and to establish a prediction model and grading system for stratifying prognoses. A retrospective cohort study of 321 patients with alopecia areata who visited a single tertiary referral center between October 2012 and February 2017 and underwent 4-view photographic assessment. Clinical photographs were reviewed to evaluate hair loss using the Severity of Alopecia Tool 2. Topographic phenotypes of alopecia areata were identified using hierarchical clustering with Ward's method. Differences in clinical characteristics and prognosis were compared across the clusters. The model was evaluated for its performance, accuracy, and interobserver reliability by comparison to conventional methods. Topographic phenotypes of alopecia areata and their major (60%-89%) and complete regrowth probabilities (90%-100%) within 12 months. A total of 321 patients were clustered into 5 subgroups. Grade 1 (n = 200; major regrowth, 93.4%; complete regrowth, 65.2%) indicated limited hair loss, whereas grades 2A (n = 66; major regrowth, 87.8%; complete regrowth, 64.2%) and 2B (n = 20; major regrowth, 73.3%; complete regrowth, 45.5%) exhibited greater hair loss than grade 1. The temporal area was predominantly involved in grade 2B, but not in grade 2A, despite being comparable in total extent of hair loss. Grade 3 (n = 20; major regrowth, 45.5%; complete regrowth, 25.5%) included diffuse or extensive alopecia areata, and grade 4 (n = 15; major regrowth, 28.2%; complete regrowth, 16.7%) corresponded to alopecia (sub)totalis. No significant differences in prognosis (hazard ratio [HR] for major regrowth, 0.79; 95% CI, 0.56-1.12) were found between grades 2A and 1, whereas grades 2B (HR, 0.41; 95% CI, 0.21-0.81), 3 (HR, 0.24; 95% CI, 0.12-0.50), and 4 (HR, 0.16; 95% CI, 0.06-0.39) had significantly poorer response. Among multiple models, the cluster solution had the greatest prognostic performance and accuracy. The tree model of the cluster solution was converted into the Topography-based Alopecia Areata Severity Tool (TOAST), which revealed an excellent interobserver reliability among 4 dermatologists (median quadratic-weighted κ, 0.89). Temporal area involvement should be independently measured for better prognostic stratification. The TOAST is an effective tool for describing the topographical characteristics and prognosis of hair loss and may enable clinicians to establish better treatment plans.

3089 Clinicopathologic and Prognostic Significance of LGR5, a Cancer Stem cell Marker in Peritoneal Metastasis of a Colorectal Origin

OBJECTIVES/SPECIFIC AIMS: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is expressed on Wnt/β-catenin-dependent adult stem cell populations of the colon. Cancer stem cells are hypothesized to be the driving force behind tumor progression and metastasis, making them attractive therapeutic targets. Our aim was to analyze the clinicopathologic and prognostic significance of LGR5 expression in a cohort of colorectal cancer patients with peritoneal metastasis. METHODS/STUDY POPULATION: A total of 49 Formalin-fixed paraffin-embedded (FFPE) tissue blocks of primary or metastatic tumors and their respective normal tissues were collected from the tissue bank for time period 2009-2015. LGR5 expression was assessed at the protein level through immunohistochemical (IHC) staining of tissue microarray (TMA) constructs consisting of pairs of tumor and normal colon tissue. The correlation between LGR5 expression and clinicopathologic parameters and prognosis was assessed by statistical analysis. RESULTS/ANTICIPATED RESULTS: Of the 49 patient sample, 30(61.22%) were female vs. 19 (38.78%) males. Age range at initial diagnosis ranged from 31.7 years to 84.4 years, with a median age of 61.29 years. Duration of follow-up ranged from 1 – 9 years with a median of 5 years.LGR5 expression was higher in colorectal cancer than in normal mucosa. In univariate survival analysis overexpression of LGR5 was significantly associated with improved survival (p=0.002).Of significance, LGR5 positivity was an independent prognostic marker for better prognosis in a multivariate survival analysis adjusting for prognostic variables age, stage, gender, tumor histology and grade (HR 2.67. 95% CI 1.01-7.00, P = 0.046). DISCUSSION/SIGNIFICANCE OF IMPACT: LGR5 was significantly over expressed in colorectal cancer compared to normal tissues. LGR5 was noted to be an independent prognostic variable for an improved survival outcome in colorectal cancer patients with peritoneal metastasis, making LGR5 a potential therapeutic target in colorectal cancer patients with peritoneal metastasis.

Prostatic Adenocarcinoma: A Grading from Gleason to the New Grade-Group System: A Historical and Critical Review

The introduction of the Gleason grading system revolutionised prognostic parameters and determination of patient treatment regiments for prostatic adenocarcinomas, and has become synonymous with prostate cancer, almost universally applied in clinical settings to predict radical prostatectomy specimen findings, potential biochemical failure, local recurrences, lymph nodes or distant metastases in patients not receiving any treatment as well as those receiving treatment including radiation therapy, surgical treatment such as radical prostatectomy and other therapies etc,. However, characterisation and classification of prostate cancer is very different compared to 40-50 years ago when Gleason scores were first introduced. Despite this radical shift in classification, the Gleason system has remained one of the most important prognostic factors in prostate cancer, only possible as a result of timely and appropriate modifications to this characterisation system made in 2005 and 2014. However, even after these modifications, certain limitations of the Gleason system remain, due to which a new prostate cancer prognostic grade group system was introduced in 2014, which was widely accepted in the 2014 ISUP consensus conference, and incorporated into the WHO classification of thetumor of the Urinary System and Male Genital Tract in 2016. Herein, this article will discuss how this new prognostic grade group system, which is regarded as simpler and more accurate than the Gleason system risk stratification groups, will be used in conjunction with the Gleason system to improve patient prognosis and treatment.

Assessment of prostate cancer prognostic Gleason grade group using zonal-specific features extracted from biparametric MRI using a KNN classifier.

PurposeTo automatically assess the aggressiveness of prostate cancer (PCa) lesions using zonal‐specific image features extracted from diffusion weighted imaging (DWI) and T2W MRI.MethodsRegion of interest was extracted from DWI (peripheral zone) and T2W MRI (transitional zone and anterior fibromuscular stroma) around the center of 112 PCa lesions from 99 patients. Image histogram and texture features, 38 in total, were used together with a k‐nearest neighbor classifier to classify lesions into their respective prognostic Grade Group (GG) (proposed by the International Society of Urological Pathology 2014 consensus conference). A semi‐exhaustive feature search was performed (1–6 features in each feature set) and validated using threefold stratified cross validation in a one‐versus‐rest classification setup.ResultsClassifying PCa lesions into GGs resulted in AUC of 0.87, 0.88, 0.96, 0.98, and 0.91 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5 for the peripheral zone, respectively. The results for transitional zone and anterior fibromuscular stroma were AUC of 0.85, 0.89, 0.83, 0.94, and 0.86 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5, respectively.CONCLUSIONThis study showed promising results with reasonable AUC values for classification of all GG indicating that zonal‐specific imaging features from DWI and T2W MRI can be used to differentiate between PCa lesions of various aggressiveness.

Titanyum Protezlerle Yapılan Timpanoplastide Prognostik Faktörlerin Değerlendirilmesi

Aim: This study aimed to assess the effects of preoperatively measured middle ear risk index (MERI) and intraoperative ossicular chain findings on postoperative hearing in patients who underwent ossiculoplasty performed by using universal titanium prostheses.Materials and Methods: Patients who underwent ear surgery using universal titanium prostheses due to malfunctioning in the incus were included. Preoperative ear examination results, surgical findings, and MERI scores were assessed. Preoperative and postoperative air-conduction and bone-conduction hearing thresholds and air-bone gap were assessed at 0.5, 1, 2, and 4 kHz frequencies.Results: We found that presence of the malleus and stapes suprastructure and prognostic MERI grading affected the reconstruction success rate. The air-bone gap results were found to be 100%, 87.5% and 12.5% in the mild, moderate, and severe MERI groups, respectively.Discussion and Conclusion: In line with the literature, we observed that preoperative MERI scoring might help surgeons develop a patient-specific operation strategy by providing guidance during ossiculoplasty

Agreement in Histological Assessment of Mitotic Activity Between Microscopy and Digital Whole Slide Images Informs Conversion for Clinical Diagnosis

Validating digital pathology as substitute for conventional microscopy in diagnosis remains a priority to assure effectiveness. Intermodality concordance studies typically focus on achieving the same diagnosis by digital display of whole slide images and conventional microscopy. Assessment of discrete histological features in whole slide images, such as mitotic figures, has not been thoroughly evaluated in diagnostic practice. To further gauge the interchangeability of conventional microscopy with digital display for primary diagnosis, 12 pathologists examined 113 canine naturally occurring mucosal melanomas exhibiting a wide range of mitotic activity. Design reflected diverse diagnostic settings and investigated independent location, interpretation, and enumeration of mitotic figures. Intermodality agreement was assessed employing conventional microscopy (CM40×), and whole slide image specimens scanned at 20× (WSI20×) and at 40× (WSI40×) objective magnifications. An aggregate 1647 mitotic figure count observations were available from conventional microscopy and whole slide images for comparison. The intraobserver concordance rate of paired observations was 0.785 to 0.801; interobserver rate was 0.784 to 0.794. Correlation coefficients between the 2 digital modes, and as compared to conventional microscopy, were similar and suggest noninferiority among modalities, including whole slide image acquired at lower 20× resolution. As mitotic figure counts serve for prognostic grading of several tumor types, including melanoma, 6 of 8 pathologists retrospectively predicted survival prognosis using whole slide images, compared to 9 of 10 by conventional microscopy, a first evaluation of whole slide image for mitotic figure prognostic grading. This study demonstrated agreement of replicate reads obtained across conventional microscopy and whole slide images. Hence, quantifying mitotic figures served as surrogate histological feature with which to further credential the interchangeability of whole slide images for primary diagnosis.

Statistical Analysis of Survival Models Using Feature Quantification on Prostate Cancer Histopathological Images

Background: Grading of prostatic adenocarcinoma is based on the Gleason scoring system and the more recently established prognostic grade groups. Typically, prostate cancer grading is performed by pathologists based on the morphology of the tumor on hematoxylin and eosin (H and E) slides. In this study, we investigated the histopathological image features with various survival models and attempted to study their correlations. Methods: Three texture methods (speeded-up robust features, histogram of oriented gradient, and local binary pattern) and two convolutional neural network (CNN)-based methods were applied to quantify histopathological image features. Five survival models were assessed on those image features in the context with other prostate clinical prognostic factors, including primary and secondary Gleason patterns, prostate-specific antigen levels, age, and clinical tumor stages. Results: Based on statistical comparisons among different image features with survival models, image features from CNN-based method with a recurrent neural network called CNN-long-short-term memory provided the highest hazard ratio of prostate cancer recurrence under Cox regression with an elastic net penalty. Conclusions: This approach outperformed the other image quantification methods listed above. Using this approach, patient outcomes were highly correlated with the histopathological image features of the tissue samples. In future studies, we plan to investigate the potential use of this approach for predicting recurrence in a wider range of cancer types.

Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

AimsSquamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading...

Prognostic grading system specifically for elderly patients with brain metastases after stereotactic radiosurgery: a 2-institution study.

OBJECTIVEWith the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)-BSBM.METHODSFor this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998-2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM.RESULTSTwo factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299-1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078-1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4-5, the score is either 4 or 5; for ES-BSBM 2-3, the score is either 2 or 3; and for ES-BSBM 0-1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4-19.3) in ES-BSBM 4-5, 6.9 (95% CI 6.4-7.4) in ES-BSBM 2-3, and 2.8 (95% CI 2.5-3.6) in ES-BSBM 0-1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2-23.4), 7.9 (95% CI 7.4-8.5), and 3.2 (95% CI 2.8-3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older.CONCLUSIONSThe authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

Validity of a Recently Proposed Prognostic Grading Index, Brain Metastasis Velocity, for Patients With Brain Metastasis Undergoing Multiple Radiosurgical Procedures

This study of our patients with brain metastasis who underwent multiple stereotactic radiosurgery (SRS) procedures aimed to validate whether the recently proposed prognostic grading system, brain metastasis velocity (BMV), is generally applicable. The BMV scores the cumulative number of new brain metastases thatdeveloped after the first SRS divided by time (years) since the initial SRS. Patients were categorized into 3 classes by their BMV scores (ie, ≤3, 4-13, and ≥14). This retrospective cohort study was approved by the Tokyo Women's Medical University Institutional Review Board (number 1981). We used our prospectively accumulated database, which included 833 patients who underwent a second SRS procedure for newly detected lesions, using a gamma knife, for brain metastases. Patients who had whole-brain radiation therapy were excluded. The procedures took place during the 19-year period between July 1998 and June 2017. Furthermore, among the 833 patients, 250 underwent a third SRS procedure, and 88 had a fourth SRS procedure. The median survival times (MSTs) after the second SRS were 12.9months (95% confidence interval [CI], 10.2-17.1) for the BMV group with a score of ≤3; 7.5months (CI, 6.5-9.0) for the group scoring 4 to 13, and 5.1months (CI, 4.0-5.6) for the group scoring ≥14 (P=.0001). The corresponding MSTs after the third SRS were 13.2months (95% CI, 9.1-21.6), 8.0months (CI, 6.2-11.2), and 5.7months (CI, 4.8-7.8; P=.0001). Respective MSTs after the fourth SRS were 13.2months (95% CI, 9.1-21.6), 8.0months (CI, 6.2-11.2), and 5.7months (CI, 4.8-7.8; P<.0001). The mean BMV score of patients with small cell lung cancer, 24.8, was significantly higher than that of patients with non-small cell lung cancer, 17.7 (P=.032). Our present results support the validity of BMV for predicting survival not only after the second SRS but also after the third and fourth SRS.

Cigarette smoking is not associated with prostate cancer diagnosis and aggressiveness: a cross sectional Italian study.

The aim of our study is to explore the association between cigarette smoking and the risk of prostate cancer (PCa) diagnosis as well as high grade disease in men undergoing prostate biopsies. From 2008 to 2016, we prospectively enrolled a consecutive series of men with no history of PCa undergoing prostate biopsies. Variables assessed the day of the biopsy included: Family history of PCa, age, body mass index (BMI), comorbidities, digital rectal examination (DRE), prostate volume, PSA, free PSA, smoking status, number of cigarette/day, smoking time, smoking starting age and smoking cessation. Smoking variables were evaluated as predictors of PCa and high grade PCa (Prognostic Grade Group ≥3) using adjusted logistic regression analyses. Overall 1080 patients were enrolled, out of them 499/1080/753 (46%) had never smoked; 168/1080/753 (16%) were smokers and 413/1080 (38%) were former smokers. Out of the 451/1080 (41%) patients with PCa 175/451 (39%) presented high grade disease. As expected family history, age, dyslipidemia, PSA, digital rectal examination and prostate volume were independent predictors of PCa. As well age, DRE, and PSA were independent predictors of high-grade disease. Smoking status (OR=0.983; CI: 0.689-1.402) and the associated variables were not independent predictors of PCa or high grade PCa (OR: 1.250; CI: 0.593-1.327). In our cross-sectional study, smoking is not predictive of PCa or high-grade disease. Further studies should evaluate if smoking could influence PCa diagnosis and aggressiveness.

Surveillance after prostate focal therapy

Long-term outcomes from large cohorts are not yet available upon which to base recommended follow-up protocols after prostate focal therapy. This is an updated summary of a 2015 SIU-ICUD review of the best available current evidence and expert consensus on guidelines for surveillance after prostate focal therapy. We performed a systematic search of the PubMed, Cochrane and Embase databases to identify studies where primary prostate focal therapy was performed to treat prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) should be performed at 3-6months, 12-24months and at 5years after focal therapy. Targeted biopsy of the treated zone should be performed at 3-6months and fusion biopsy of any suspicious lesion seen on mpMRI. Additionally, a systematic biopsy should be performed at 12-24months and again at 5years. In histological diagnosis, characteristic changes of each treatment modality should be noted and in indeterminate situations various immunohistochemical molecular markers can be helpful. Small volume 3 + 3 (Prognostic grade group [PGG] 1) or very small volume (< 0.2cc or < 7mm diameter) 3 + 4 (PGG 2) are acceptable in the treated zone at longitudinal follow-up. Significant volumes of 3 + 4 (PGG 2) or more within the treated zone should be treated. Any clinically significant cancer subsequently arising within the non-treated zone should be treated and handled in the same way as any de novo prostate cancer. Patients should be counseled regarding whole-gland and focal approaches to treating these new foci where appropriate. One or two well-delineated foci of significant cancer can be ablated to keep the patient in the 'active surveillance pool'. More extensive disease should be treated with traditional whole-gland techniques. Focal therapy remains a nascent field largely comprising single center cohorts with little long-term data. Our current post-focal therapy surveillance consensus recommendations represent the synthesis of the best available evidence as well as expert opinion. Further work is necessary to define the most oncologically safe and cost-effective way of following patients after focal therapy.

Study of Clinicopathological Spectrum and Pattern of Expression of Cyclooxygenase‑2 in Urothelial Carcinomas of Bladder

Abstract Introduction: Overexpression of cyclooxygenase-2 (COX2) in urothelial carcinoma of bladder (UCB) had been studied in the past by different workers and the results were contradictory. The objective of the present study was to evaluate the prognostic implication of COX2 expression in primary urothelial carcinomas of the urinary bladder and its correlation with clinical parameters, tumor stage, grade, and recurrence. Materials and methods: A total of 68 cases who underwent surgery for urothelial carcinoma in our medical college from January 2013 to December 2015 were evaluated in our study. Hematoxylin and eosin-stained slides were examined by two faculties applying standard reporting protocol. Tumor staging and grading was performed as per the WHO guidelines. Immunohistochemistry for expression of COX2 was performed to study any correlation of tumor grade with COX2 expression. The distribution of COX2 positivity was studied in tumors stratified according to established bladder cancer prognostic factor, for example, tumor size, grade, invasion, and spread. Results: Out of 68 cases, 42 cases showed COX2 positivity (61%). In low-grade cases of bladder carcinoma, COX2 positivity was 16 out of 24 cases (60%), and in high-grade cases, COX2 positivity was 10 out of 18 cases (64.28%).Conclusion: In the present study, the association of COX2 overexpression with advanced tumor invasion and tumor grade has been substantiated. Hence, COX2 expression can be taken as a prognostic factor along with other usual prognostic factors in patients of UCB.

Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue

Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002–2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence. Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby identifying patients more at-risk for recurrence. Such findings, achievable by biopsy or prostatectomy tissue measurement, could inform treatment strategies. Metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically-benign tissues in cancer environments.