Rectal Examination Research Articles

Immunohistochemical Glutamine Synthetase As a Surrogate Marker for Beta Catenin (Exon 3 Deletion) in a Rare Case of Hepatic Adenomatosis with Early Malignant Transformation to Well Differentiated Hepatocellular Carcinoma

Abstract Introduction/Objective Hepatic adenomatosis (HA) is a rare entity defined by ≥ 10 hepatocellular adenomas (HCAs). About half of HA cases are asymptomatic and incidentally found. Compared to individual HCAs, HA carries a higher risk of complications including: tumor rupture, bleeding, and an approximate 4.2% overall frequency of malignant transformation. Methods/Case Report A 29-year-old woman presented to the emergency department (ED) requesting a CT scan. She was seen by a gastroenterologist days prior to her ED visit for ongoing sharp rectal pain for 2-3 months. After a recent rectal exam, she was recommended to have a CT abdomen/pelvis to rule out a potential abscess. CT did not show a perianal or perirectal abscess but instead identified a 9.1 cm right hepatic lobe mass. A liver MRI showed a 6.4 x 8.5 cm mass with arterial enhancement. The patient had a prior history of OCP use. She underwent robotic wedge resection of liver segment 6 with cholecystectomy. Gross examination showed a 6 cm tumor with many smaller nodules ranging in size from 0.5-2.2 cm. Our case was submitted entirely for histologic examination. Microscopy demonstrated well differentiated hepatocellular carcinoma (WDHCC) confirmed with positive immunohistochemical (IHC) staining for HepPar1 and Arginase. Tumor cells showed mild patchy cytological atypia, occasional pseudoglands, and architectural atypia with “nodule in nodule growth.” There was reticulin loss in multiple areas and CD34 showed strong diffuse sinusoidal staining. Glypican 3, CRP, and HAA were negative. Low Ki-67, LFABP retention, and absent nuclear staining of beta catenin (BC) were noted. Glutamine synthetase (GS) was diffuse and homogeneous. The gallbladder was unremarkable. Results (if a Case Study enter NA) NA Conclusion This case emphasizes that, despite negative nuclear BC staining, diffuse homogenous staining of GS is a quality surrogate marker for BC mutations (ex. exon 3 deletions). Thorough gross, microscopic, and molecular examination in HA cases is essential for identifying transformation to WDHCC.

Assessment of age specific serum Prostate Specific Antigen (PSA) levels for Indian population: A retrospective analysis at a tertiary healthcare facility.

Prostate-specific antigen (PSA) is a key marker for prostate cancer screening, but its utility is debated, prompting exploration of PSA derivatives for improved accuracy. While racial variations in serum PSA levels are documented, limited data exists for the Indian population. Given increasing life expectancy and heightened awareness of prostate cancer, this study aims to establish age-specific PSA ranges in an Indian cohort, contributing vital insights for population-specific screening and diagnosis. A cross-sectional study was conducted on 4860 men with lower urinary tract symptoms (LUTS). Data, collected from April 2016 to March 2023, included age, PSA levels, digital rectal examination (DRE), and biopsy results. Statistical analysis involved Spearman's correlation, descriptive statistics, and confidence intervals. Of the studied participants, 809 underwent prostatic biopsy, revealing malignancy in 500 cases. Age-specific PSA values were studied in 4170 subjects and showed positive correlation with increasing age and prostate size. Most cancers were metastatic (66%), emphasizing the need for early detection. Age-specific PSA ranges were lower in the Indian population compared to the West. This study's Indian cohort exhibited higher PSA values than some previous Indian studies but lower than Western populations, aligning with global trends. The rising incidence of prostate cancer in India underscores the importance of understanding the disease burden. PSA levels exhibit race-specific variations, cautioning against direct extrapolation of Western data to the Indian population. This study contributes age-specific PSA ranges for an Indian cohort, facilitating nuanced prostate cancer screening strategies.

The Diagnosis and Management of Chronic Constipation in Italy: Results from a Survey Conducted among Italian Gastroenterologists.

Background: Chronic constipation (CC) is one of the most common disorders of gut-brain interaction (DGBI). The management of CC requires specific skills due to its complex and multifactorial pathophysiology and its multistep treatment. The aims of this study were to evaluate the availability and the use of diagnostic tools for CC in Italy and the therapeutic management of CC by Italian gastroenterologists (GEs). Methods: A survey was conducted during the 28th meeting of the Italian Federation of Digestive Disease Societies (FISMAD; Rome, Italy, 11-14 May 2022). The survey explored the presence of a clinic dedicated to DGBIs, the availability and the use of specific diagnostic tools, the routine use of digital rectal examination (DRE), and the therapeutic approach to CC by Italian GEs. Results: The survey was taken by 236 GEs. The most significant results were that 42% of respondents had a clinic dedicated to DGBI in their institute; DRE was regularly performed by 56.8% of GEs when evaluating a CC patient; young GEs (≤40 years) performed DRE less frequently than older ones (p < 0.001); anorectal manometry was available to 44.3% of GEs; balloon expulsion test (BET) was available to 19.1% of GEs; GEs with a clinic dedicated to DGBI had more frequent access to anorectal physiology testing (p < 0.001); diet and lifestyle advice were the most frequently prescribed treatments; and fiber and macrogol were the second and third most prescribed treatments, respectively. Conclusions: The survey provides an interesting picture of CC management by Italian GEs. The results are in line with previous data collected about 10 years ago among Italian GEs ("CHRO.CO.DI.T.E study"); DRE is still rarely performed by Italian GEs (particularly by young GEs). The availability of anorectal physiology testing is still limited, and BET, which could be easily performed in everyday clinical settings, is rarely performed. Lifestyle suggestions, macrogol and fiber are the preferred treatment, as recommended by all guidelines. These results will be useful to identify as yet unmet educational needs and critical issues to improve CC management.

Perinatal outcomes based on number of digital exams in patients with PPROM.

ACOG recommends speculum exams, rather than digital exams, for evaluation of the cervix after preterm prelabor rupture of membranes (PPROM). However, in clinical practice, digital exams may be necessary. We examined whether increasing numbers of digital exams were associated with adverse outcomes in PPROM. This was a single center retrospective cohort study of patients admitted between 2019 and 2021 with PPROM at 24-34 weeks gestation. The primary outcome was intraamniotic infection and inflammation (triple I), compared between patients who had <1 or >2 digital exams during expectant management of PPROM. Secondary outcomes included latency, antepartum events, and other maternal and neonatal morbidities. Groups were compared using univariate analysis and Cox proportional hazards model to account for time between admission and delivery and potential confounders. Of 125 patients included in the analysis, 46 (36.8%) had < 1 and 79 (63.2%) had  2 digital exams. There was no significant difference in triple I between groups (adjusted hazard ratio [aHR] 1.03, 95% confidence interval (CI) 0.47, 2.26). There were no significant differences in composite maternal or neonatal morbidities or latency from admission to delivery between groups (8 days (interquartile range (IQR) 3, 14) vs. 6 days (IQR 3, 12)). There was a higher rate of spontaneous labor as the indication for delivery in the group with 2 exams (aHR 2.07, 95% CI 1.04, 4.11). In this retrospective cohort study, ≥2 digital exams during expectant management of PPROM was not associated with change in infectious morbidity or pregnancy latency. There was an increase in spontaneous labor in the group with more exams; this may be due to confounding by indication, as patients who are in prodromal labor are more likely to receive digital exams. These results suggest equipoise in exam type in the management of PPROM.

Bilateral transobturator hysterosuspension using titanium tape-shaped mesh implants in women with apical prolapse of the internal genitalia

BACKGROUND: Pelvic organ prolapse is a common pathology with several relapses of the disease after surgical treatment using exclusively self-tissues, which necessitates the development of new surgical techniques using durable and biological inert materials. AIM: To evaluate the effectiveness and safety of an original surgical technique for apical prolapse correction in patients of reproductive and pre- and postmenopausal age. MATERIAL AND METHODS: Twenty-nine patients were examined and operated on using a developed original technique with the use of narrow tape-shaped titanium mesh implants. RESULTS: Follow-up was conducted at 1, 6, 12, and 24 months postoperatively. Comparison of patient survey indicators in the pre- and postoperative periods showed an improvement in the patients’ quality of life and an increase in their social and sexual activity. During the first month, 15 (51.7%) patients reported intermittent pulling pains in the perineal and/or inguinal–femoral folds, and 4 (13.8%) reported frequent urination. Clinical examination revealed complete preservation of the surgical correction of prolapse in all patients. Gynecological and rectal examinations and transperineal and transvaginal echography did not show displacement of pelvic organs or titanium implants. Mesh-associated complications were not noted during the observation period. CONCLUSION: The developed original technique for surgical correction of second-degree apical prolapse with the use of narrow ribbon-shaped titanium mesh implants is effective and safe. This is evidenced by the normalization of the uterus position in the pelvis, absence of displacement of pelvic organs in the near and distant postoperative periods, and absence of mesh-associated complications during the observation time.

B-349 Diagnostic Performance of the Atellica IM High-Sensitivity PSA Assay in Men Undergoing Prostate Cancer Screening

Abstract Background This study evaluated the diagnostic performance of the Atellica® IM High-Sensitivity PSA (hsPSA)* assay in men &amp;gt;50 years undergoing prostate cancer (PC) screening in conjunction with digital rectal exam (DRE). Methods Serum samples were collected prospectively from 2671 subjects &amp;gt;50 years referred to a urologist for evaluation of PC from 26 sites across the United States. To establish PC versus benign disease, all subjects underwent a transrectal prostate biopsy ≤60 days after blood draw. At the cutoff of 4.0 ng/mL for the hsPSA assay, the percentage of PCs detected (sensitivity) and corresponding percentage of biopsies avoided in men without PC (specificity) were determined. Results Cancer prevalence (malignant biopsy) was 58.5% (1562/2671) among the diagnostic population. Preliminary results demonstrated that for DRE alone, sensitivity and specificity were 30.9% (482/1562) and 83.0% (920/1109) compared to biopsy. For hsPSA alone at the cutoff of 4.0 ng/mL, sensitivity was 88.7% (1386/1562). The table provides incidence of cancer and positive biopsies by subgroups defined by DRE and hsPSA. hsPSA detected 61.1% (955/1562) of PCs that DRE did not. Of those DRE+, 71.8% (482/671) had positive biopsy. Of those DRE+ and hsPSA ≥4.0 ng/mL, 78.6% (431/548) had positive biopsy, which significantly increased PC detection by 7.0% (95% CI:1.4%-12.5%). Similarly, in the DRE- population, while 54.0% of subjects had positive biopsy, subjects both DRE- and hsPSA &amp;lt;4.0 ng/mL had only 38.5% positive biopsies, a significant difference of 16.5% (95% CI: 6.3%-27.8%). Conclusions Using DRE alone detected only 3 out of 10 patients with PC. It was observed that when used in conjunction with DRE, the hsPSA assay improved both sensitivity and specificity of PC detection over DRE alone. CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

B-347 Analytical Performance Evaluation of the High Sensitivity PSA Assay and the Free PSAII Assay on the Atellica IM Analyzer

Abstract Background Measurement of serum prostate specific antigen (PSA) levels may be used in prostate cancer (PC) screening, but elevated PSA levels also are observed in patients with other etiologies such as benign prostatic hypertrophy. Studies suggest that measuring PSA with or before digital rectal examination (DRE) provides a better method of detecting PC than DRE alone. The free prostate specific antigen (fPSA) assay is an aid for distinguishing PC from benign prostate conditions in men 50 years or older with PSA values 4.0-10.0 ng/mL (µg/L) and DRE findings nonsuspicious for PC. The goal of this study was to evaluate the analytical performance of the high sensitivity PSA (hsPSA)* and free PSA (fPSAII)* assays on the Atellica® IM Analyzer. Methods Detection capability studies were performed per CLSI EP17-A2. Precision testing was performed per CLSI EP05-A3 with native human serum and QC samples, 3 reagent lots, 1 analyzer, 2 runs/day, 2 replicates/run for 20 days. For Atellica® hsPSA and fPSAII assays a multi-site reproducibility study was conducted per CLSI EP-05 A3 using native and contrived serum samples, 3 reagent lots, and 3 different sites and analyzers; samples were assayed in triplicate for five days, two runs/day ∼2 hours apart. Linearity testing was performed per CLSI EP06-A on a dilution series made from a high PSA sample (native human male serum pool) and a low sample (native human female serum), 4 replicates, 3 reagent lots, and 1 analyzer. Specimen equivalency was determined by Weighted Deming regression model per CLSI EP09c-ed3. Results Results are presented in the table. Conclusions The Atellica IM hsPSA assay and fPSAII assays detection capability, precision, linearity, and specimen equivalency were acceptable. *CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

B-346 Diagnostic Performance of the Atellica IM Free PSA Assay in Men Undergoing Prostate Cancer Screening

Abstract Background Measurement of free prostate specific antigen (fPSA) in serum is used to aid in distinguishing prostate cancer (PC) from benign prostate conditions in men 50 years or older with hsPSA of 4.0-10.0 ng/mL (µg/L) and digital rectal exam (DRE) nonsuspicious for PC. Studies were performed to evaluate clinical performance for the Atellica® IM fPSAII assay* [fPSAII/hsPSAx100 ratio]. Methods Serum samples were prospectively collected from 1250 patients referred to an urologist for PC evaluation at 26 sites throughout the United States. At diagnostic cutoffs for %fPSAII spanning the spectrum of %fPSAII values, the percentage of PCs detected (sensitivity) and the corresponding percentage of biopsies avoided in men without PC (specificity) were tabulated. At a pre-specified sensitivity near 90%, %fPSAII specificity (relative to biopsy result) was compared to hsPSA specificity. The mean PC probabilities on biopsy and nonparametric 95% CI (2.5th and 97.5th percentiles) were calculated. The difference between these proportions was evaluated to estimate the improvement in specificity of %fPSAII relative to hsPSA alone. Difference in specificity was significant if the zero value was not bounded by 2.5th and 97.5th percentile values of the improvement estimate with a minimum of 5% improvement in specificity. Results Sensitivity and specificity results are presented in the table. The cutoffs provided a range of sensitivity estimates from 86%-100%. At 22% cutoff, sensitivity (90.3%) plus specificity (21.4%) is greater than 110.0%. Significant improvement in %fPSAII specificity over hsPSA alone was 8.9% with 95% CI of 6.8%-11.5%. Conclusions The clinical performance of the Atellica IM Analyzer fPSAII assay was acceptable and demonstrated an improvement in detection of PC than using hsPSA alone in this study. *CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

B-345 The PSA and free PSA Concentrations in Serum of Apparently Healthy Subjects Using the Atellica IM hsPSA and fPSAII Assays

Abstract Background PSA assays are recommended in the screening for prostate cancer (PC) among males 50 years and older. Those with PSA results in the gray zone (between 4 ng/mL and 10 ng/mL) and a nonsuspicious digital rectal examination (DRE) may be further tested with the free PSA (fPSA) assays to improve detection of PC. PSA and fPSA are also detected in apparently healthy subjects. The goal of this study was to evaluate the distribution of high sensitivity PSA (hsPSA), fPSAII, and %fPSAII (fPSAII/hsPSA x 100) values generated on the Atellica® IM Analyzer among apparently healthy subjects by age decade. Methods Serum samples were prospectively collected from apparently healthy subjects at multiple sites across the United States: 673 males 50-70+ years presenting at primary care facilities for routine PSA testing (&amp;gt;120 samples in each age decade (50-59, 60-69, 70+ years) and 113 samples in each of two younger decades (30-39, 40-49 years). Distribution statistics include the mean, median, interquartile range, 2.5th, 95th, and 97.5th percentiles. Results In this study, using samples from healthy men 30-70+ years (N=786), it was observed that median hsPSA results increased with every decade from 0.682 ng/mL at 30-39 years to 2.183 ng/mL at age 70+ years. The 97.5th percentiles were below 4.0 ng/mL in men &amp;lt;50 years, and above 4.0 ng/mL in men &amp;gt;50 years. All men (100%) 30-49 years had an hsPSA result below 4.0, and 95.5% of men 50-59 years had an hsPSA result below 4.0. The percent of subjects with hsPSA values above the cut-off of 4.0 was 6.6% among men 60-69 years and 12.4% among men &amp;gt;70 years. Median hsPSA values for each age group were comparable to median PSA values reported for healthy men older than 50 years old without cancer undergoing routine health check-ups in the United States and other countries (median hsPSA value was 0.90 among men 50-59 years). For both hsPSA and fPSAII, it was observed that average values increased with each successive decade for subjects 30-70+ years. The range across decades was 0.904-2.183 ng/mL for hsPSA and 0.23-0.46 ng/mL for fPSAII. However, the average %fPSAII (fPSA/hsPSAx100) values did not consistently rise over time because hsPSA variances also increase, a pattern previously documented. Conclusions The distribution of Atellica® IM hsPSA and fPSAII assay values from apparently healthy males was determined. CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

307 - Correlation of Early Postpartum Anal/Faecal Incontinence with Endoanal Ultrasound, Digital Rectal Examination, Machine Learning-supported Electric Impedance Spectroscopy, and High-Resolution Anorectal Manometry Results: Exploratory Results from a Prospective, Comparative, Multicentre Clinical Study

307 - Correlation of Early Postpartum Anal/Faecal Incontinence with Endoanal Ultrasound, Digital Rectal Examination, Machine Learning-supported Electric Impedance Spectroscopy, and High-Resolution Anorectal Manometry Results: Exploratory Results from a Prospective, Comparative, Multicentre Clinical Study

Clinicopathological Study of Prostate Diseases and Its Correlation with PSA Level, Size of Prostate and Gleason’s Scoring System in Case of Prostatic Carcinoma

Background: Prostate gland diseases significantly impact adult males globally, with an increasing prevalence due to aging populations. The primary conditions affecting the prostate are inflammation, benign prostatic hyperplasia (BPH), and tumors, with BPH being the most common. Prostatic carcinoma is also prevalent, with a high lifetime risk. Prostate cancer incidence increases with age, and early detection relies on digital rectal examination, transrectal ultrasonography, and PSA testing. Aim of the study: The study aims to find out correlation between PSA, Gleasons scoring system and HER-2/NEU gene in prostatic cancer. Methods: This study, conducted from July 2017 to June 2019 at BIRDEM General Hospital, enrolled 110 male patients aged 50-100 with clinical signs of prostatic diseases. Patients provided written informed consent and met specific inclusion criteria. Specimens were obtained via TURP, simple or radical prostatectomy, preserved in 10% neutral buffered formalin and examined for pathological lesions. PSA levels were measured using an immunoassay, and Gleason scoring was used for carcinoma categorization. Data were collected via questionnaires and analyzed using SPSS software. Result: The study analyzed 110 prostatic disease cases, with patients averaging 67.7 years. The most common diagnosis was BPH with inflammation (50.9%), followed by BPH without inflammation (35.5%) and adenocarcinoma (13.6%). Urgency (80%), increased micturition frequency (78.2%), poor stream (78.2%), and urinary retention (77.3%) were the most common symptoms. There was a significant correlation between serum PSA levels and prostate size (p &lt; 0.001), with higher PSA levels indicating larger prostates and a higher likelihood of adenocarcinoma. The most frequent Gleason score was 4+4=8 (40%). HER2/neu overexpression showed a marginal correlation with PSA levels (p=0.053). Conclusion: The study found that the most common age group for prostatic diseases was 61-70 years. Benign prostatic hyperplasia (BPH) was the most frequent lesion. Grade II (31-50g) prostate size was common on ultrasound. Most patients had a PSA level of 0-5 ng/ml, aiding early diagnosis and reducing morbidity

Is Era of the Digital Rectal Examination (DRE) for Prostate Cancer Detection and Management Over?

Is Era of the Digital Rectal Examination (DRE) for Prostate Cancer Detection and Management Over?

The correlation of neurosurgery motor examinations with ISNCSCI motor examinations in patients with spinal cord injury: a multicenter TRACK-SCI study.

The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment is the gold standard for evaluation of neurological function after spinal cord injury (SCI). Although it is an invaluable tool for diagnostic and research purposes, it is time consuming and can be impractical in acute injury settings. Clinical neurosurgery motor examinations (NMEs) could serve as an expeditious surrogate for SCI research when ISNCSCI motor examinations are not feasible. The aim of this study was to evaluate the agreement between motor examinations performed by the neurosurgery clinical team and ISNCSCI examiners. The multicenter prospective Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI) registry was queried to identify patients with recorded neurosurgery and research motor examinations within 24 hours of each other. Pearson correlations and modified Bland-Altman analyses were performed using data from matching upper-extremity, lower-extremity, and combined examinations. Kappa analysis was used to test interrater reliability with respect to determination of American Spinal Injury Association Impairment Scale (AIS) grade. There were 72 pairs of matching clinical and research examinations in 63 patients. NME scores were strongly correlated with ISNCSCI motor scores (R = 0.962, p < 0.001). Both upper- and lower-extremity NME scores were strongly correlated with upper- and lower-extremity ISNCSCI motor scores, respectively (R = 0.939, p < 0.001; and R = 0.959, p < 0.001, respectively). In modified Bland-Altman analyses, total, upper-extremity, and lower-extremity NME scores and ISNCSCI motor scores showed low systematic bias and high agreeability (total: bias = 0.3, limit of agreement [LoA] = 36.6; upper extremity: bias = -0.5, LoA = 17.6; lower extremity: bias = 0.8, LoA = 24.0). There were 66 pairs of examinations that had thorough sensory and rectal examinations for AIS grade calculation. Using kappa analysis to test the interrater reliability of AIS grade calculation using NME versus ISNCSCI motor scores, the authors found a weighted kappa of 0.883 (SE 0.061, 95% CI 0.736-0.976), indicating strong agreement. Overall, this study suggests that ISNCSCI motor scores and NME scores are strongly correlated and highly agreeable. When conducting SCI research, a thorough clinical motor examination may be a useful surrogate when ISNCSCI examinations are missing.

Prostate Cancer: A Review of Genetics, Current Biomarkers and Personalised Treatments.

Prostate cancer is the second leading cause of cancer deaths in men, second only to lung cancer. Despite this, diagnosis and prognosis methods remain limited, with effective treatments being few and far between. Traditionally, prostate cancer is initially tested for through a prostate serum antigen (PSA) test and a digital rectum examination (DRE), followed by confirmation through an invasive prostate biopsy. The DRE and biopsy are uncomfortable for the patient, so less invasive, accurate diagnostic tools are needed. Current diagnostic tools, along with genes that hold possible biomarker uses in diagnosis, prognosis and indications for personalised treatment plans, were reviewed in this article. Several genes from multiple families have been identified as possible biomarkers for disease, including those from the MYC and ETS families, as well as several tumour suppressor genes, Androgen Receptor signalling genes and DNA repair genes. There have also been advances in diagnostic tools, including MRI-targeted and liquid biopsies. Several personalised treatments have been developed over the years, including those that target metabolism-driven prostate cancer or those that target inflammation-driven cancer. Several advances have been made in prostate cancer diagnosis and treatment, but the disease still grows year by year, leading to more and more deaths annually. This calls for even more research into this disease, allowing for better diagnosis and treatment methods and a better chance of patient survival.

Anogenital distance and the risk of Late-onset hypogonadism

Objective: to investigate the association between anogenital distance (AGD) and the risk of Late-onset Hypogonadism (LOH). Methods: We prospectively recruited 145 consecutive patients referred for transrectal prostate biopsy due to prostate-specific antigen (PSA) elevation or abnormal digital rectal examination, between September 2019 and December 2021. Two variants of AGD, anus to scrotum base (AGDas) and anus to dorsal insertion of penis (AGDap) were measured. Serum total testosterone levels in fasting conditions between 07.00 and 11.00 h were determined. Patients filled out the Aging Males’ Symptoms (AMS) scale questionnaire. Results: LOH was diagnosed in 29% of the participants and presented both AGDs shorter than men without LOH, with an AGDap of 116.09 mm (9.02 mm) versus 128.71 (10.76), and an AGDas 29.70 (8.01) versus 39.93 (11.64); both p &lt; 0.05. ANCOVA test showed a significant association between the presence of LOH and both AGD measurements. Besides, AGD measurements presented adequate accuracy for the diagnosis of LOH. Conclusions: This work adds to the scientific evidence that AGD—a biomarker of fetal exposure—could provide a non-invasive measure to address LOH, providing a potential useful clinical tool.

Modelling the Non-linear Associations between Age and Health: Implications for Care

Abstract Background Ageing is a complex biological process that weakens the body's defences against various health problems and diseases. This decline is not uniform or linear; rather, it varies significantly among individuals. Understanding the non-linear progression of ageing is crucial for identifying critical periods where intervention might be most beneficial. This study aimed to explore nonlinearities in the association between age and health outcomes. Methods Using generalised additive models, we analysed data from the 2020 wave of the United States Health and Retirement Study. This modelling approach allows for the detailed examination of nonlinearities in health outcomes across different ages. Our sample consisted of adults aged over 50 (n = 1338; mean = 68; range = 50 – 95). We assessed seven health outcomes (heart conditions, diabetes, cholesterol, blood pressure, fatigue, back pain, and headaches) and seven protective behaviours (prostate exams, mammograms, cholesterol screenings, pap smears, flu vaccinations, dental check-ups, and smoking patterns) reflecting various aspects of health status and behaviour. Results The analysis indicated a significant and pronounced non-linear relationship between age and certain health outcomes, namely headaches, blood pressure, diabetes, and heart conditions. Additionally, ageing was non-linearly associated with specific health behaviours, including the uptake of prostate exams, mammograms, flu vaccinations, and smoking prevalence. Notably, distinct patterns emerged concerning health behaviours in relation to age-specific screening policies. Conclusion The findings of this study reveal that the probability of developing health problems or engaging in health protective behaviours do not increase/decrease linearly in direct proportion to age. Rather, the probability curve exhibits fluctuations, presenting periods of heightened odds interspersed with phases of relative stability. Such non-linearity may be partially attributed to policy decisions but could also reflect a complex interplay of factors such as weakened immune systems, access to healthcare, personal health beliefs, and the evolving perception of risk as one grows older.

Application value of magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer.

Magnetic resonance spectroscopy (MRSI) can distinguish between benign and malignant prostate diseases. This study investigated the potential of MRSI for diagnosing prostate cancer and guiding prostate biopsy. We retrospectively reviewed 234 patients with suspected prostate cancer who underwent MRSI with targeted prostate biopsy. Patients were divided into two groups according to their puncture pathology: prostate cancer (n = 103, 44.02%) and benign prostatic disease (n = 131, 55.98%). The t-test, Mann-Whitney U test, or chi-square test was used to compare the groups. The diagnostic abilities of MRSI, prostate-specific antigen level, digital rectal examination, and magnetic resonance imaging without contrast for prostate cancer were compared using the area under the receiver operating characteristic curve (AUC-ROC); the ARC-ROC values were 0.831, 0.768, 0.692, and 0.656, respectively. The AUC-ROC value for diagnosing prostate cancer using the CC/c ratio was 0.853. CC/c ratio > 0.97 was identified as the optimal threshold for diagnosing prostate cancer (sensitivity, 86.5%; specificity, 78.6%; Youden index, 0.651). Spearman correlation analysis revealed a correlation between the CC/c ratio and Gleason score (r = 0.737, p < 0.001). Using the CC/c ratio of MRSI as an adjunct to targeted prostate biopsy can improve the detection rate of positive biopsies and evaluate prostate cancer invasiveness.

Precision molecular insights for prostate cancer prognosis: tumor immune microenvironment and cell death analysis of senescence-related genes by machine learning and single-cell analysis

BackgroundProstate cancer (PCa) is a prevalent malignancy among men, primarily originating from the prostate epithelium. It ranks first in global cancer incidence and second in mortality rates, with a rising trend in China. PCa's subtle initial symptoms, such as urinary issues, necessitate diagnostic measures like digital rectal examination, prostate-specific antigen (PSA) testing, and tissue biopsy. Advanced PCa management typically involves a multifaceted approach encompassing surgery, radiation, chemotherapy, and hormonal therapy. The involvement of aging genes in PCa development and progression, particularly through the mTOR pathway, has garnered increasing attention.MethodsThis study aimed to explore the association between aging genes and biochemical PCa recurrence and construct predictive models. Utilizing public gene expression datasets (GSE70768, GSE116918, and TCGA), we conducted extensive analyses, including Cox regression, functional enrichment, immune cell infiltration estimation, and drug sensitivity assessments. The constructed risk score model, based on aging-related genes (ARGs), demonstrated superior predictive capability for PCa prognosis compared to conventional clinical features. High-risk genes positively correlated with risk, while low-risk genes displayed a negative correlation.ResultsAn ARGs-based risk score model was developed and validated for predicting prognosis in prostate adenocarcinoma (PRAD) patients. LASSO regression analysis and cross-validation plots were employed to select ARGs with prognostic significance. The risk score outperformed traditional clinicopathological features in predicting PRAD prognosis, as evidenced by its high AUC (0.787). The model demonstrated good sensitivity and specificity, with AUC values of 0.67, 0.675, 0.696, and 0.696 at 1, 3, 5, and 8 years, respectively, in the GEO cohort. Similar AUC values were observed in the TCGA cohort at 1, 3, and 5 years (0.67, 0.659, 0.667, and 0.743). The model included 12 genes, with high-risk genes positively correlated with risk and low-risk genes negatively correlated.ConclusionsThis study presents a robust ARGs-based risk score model for predicting biochemical recurrence in PCa patients, highlighting the potential significance of aging genes in PCa prognosis and offering enhanced predictive accuracy compared to traditional clinical parameters. These findings open new avenues for research on PCa recurrence prediction and therapeutic strategies.

Abstract A031: Methylomic Biomarkers Associated with Prostate Cancer in Black Men

Abstract Introduction: The prostate cancer (PCa) disparity remains the highest cancer disparity in the US, with Black men facing an estimated 78% higher incidence and 230% higher mortality than White men. However, current understanding of risk factors for PCa such as socioeconomic status (SES), diet, and genetics cannot fully explain these disparities. Our objective is to examine DNA methylation (DNAm) markers in a cohort of Black men and assess their associations with PCa status. Methods: We randomly selected 100 Black men for DNAm profiling (50 cases diagnosed with clinically significant (Gleason Grade 3+) prostate cancer and 50 age-matched controls) from two larger cohorts. The cohorts recruited 400 Black men who were newly diagnosed with sporadic PCa as well as 400 controls matched on age and race. All men were 40-79 at recruitment and were enrolled from urology clinics at five Chicago-area medical institutions. All PCa cases underwent a transrectal prostate biopsy for abnormal prostate-specific antigen (PSA) or digital rectal exam and had a histologically confirmed prostate cancer and were not previously diagnosed with PCa. All men in the control group had been recruited from community prostate cancer screening events or were referred to participating urology clinics and had a negative prostate biopsy for a PSA &amp;lt;10ng/ml and were not diagnosed with PCa for 2 years of follow-up. Men with prior PCa diagnosis or conditions known to affect PSA levels were excluded. After enrollment and informed consent, all men provided demographic and lifestyle data via three questionnaires, followed by venipuncture for DNA collection. These specimens were obtained using buffy coat extraction after red blood cell lysis, centrifugation, and pipetting off the overlying plasma and buffy coat for freezing followed by Illumina EPIC arrays for DNAm assays. We examined DNAm markers in gene promoter regions associated with PCa using logistic regression and adjusted for multiple testing using Bonferroni correction. All models controlled for age, BMI, smoking status, first degree family history of PCa, blood cell types, and technical control variables. Results: We found 2,180 CpG sites in gene promoter regions associated with any PCa in this population. The top ten strongest associations identified in our models include loci on genes that have already been associated with prostate cancer progression (MAFG, FAM65B, OSM, PRKAG2), risk (SLC11A1, LAT), and metastasis (S1PR4) as well as immune system functioning (RAP1GAP2). Conclusions: Our initial findings suggest that DNAm markers may be useful predictors of clinically significant PCa status among Black men. Additional research is currently ongoing to expand the sample size of the DNAm profiling and to explore links between these loci and social determinants of health, as well as associations with more advanced (i.e., higher Gleason Grade) PCa. Citation Format: Brian T. Joyce, Yishu Qu, Jun Wang, Kai Zhang, Zequn Sun, Lifang Hou, Adam B. Murphy. Methylomic Biomarkers Associated with Prostate Cancer in Black Men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A031.

Bacillus Calmette-Guérin Instillations May Mimic Prostate Cancer on Multiparametric Magnetic Resonance Imaging.

Granulomatous prostatitis (GP) is a rare and benign inflammatory condition of the prostate, often mimicking prostate cancer (PCa) in clinical and radiological evaluations. This study examines the characteristics and diagnostic challenges of GP in a cohort of 12 patients who received Bacillus Calmette-Guérin (BCG) therapy following treatment for non-muscle-invasive bladder urothelial carcinoma. In this case series, we analyze their clinical presentations, MRI findings, and histopathological results. Patients presented with elevated PSA levels and firm or nodular prostates on digital rectal examination, complicating the differentiation from PCa. Multiparametric MRI showed lesions with hypointensity on T2-weighted images, hypersignal on diffusion-weighted imaging and hyposignal on the apparent diffusion coefficient map, further mimicking malignancy. Histopathological examination remains the gold standard for diagnosing GP, distinguishing it from PCa through the identification of granulomas and associated inflammatory cells. This study underscores the importance of awareness and accurate diagnosis of GP to avoid unnecessary biopsies and treatments, highlighting the need for a multidisciplinary approach combining clinical, imaging, and pathological data.