Negative Biopsy Research Articles

Incidental Dysplasia During Total Proctocolectomy With Ileoanal Pouch: Is It Associated With Worse Outcomes?

Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer. In cases of invisible or nonendoscopically resectable dysplasia found at colonoscopy, total proctocolectomy with ileal pouch anal anastomosis can be offered with good long-term outcomes; however, little is known regarding cancer-related outcomes when dysplasia is found incidentally after surgery on final pathology. Using our prospectively collected pouch registry, we identified patients who had preoperative colonic dysplasia or dysplasia found only after colectomy. Patients with cancer preoperatively or after colectomy were excluded. Included patients were divided into 3 groups: PRE (+preoperative biopsy, negative final pathology), BOTH (+preoperative biopsy and final pathology), and POST (negative preoperative biopsy, +final pathology). Long-term outcomes in the 3 groups were assessed. In total, 517 patients were included: PRE = 125, BOTH = 254, POST = 137. After a median follow-up of 12 years (IQR 3-21), there were no differences in overall, disease-free, or pouch survival between groups. Cancer/dysplasia developed in 11 patients: 3 (2%) in the PRE, 5 (2%) in the BOTH, and 3 (2%) in the POST group. Only 1 cancer-related death occurred in the entire cohort (PRE group). Disease-free survival at 10 years was 98% for all groups (P = .97). Pouch survival at 10 years was 96% for PRE, 99% for BOTH, and 97% for POST (P = .24). The incidental finding of dysplasia on final pathology after proctocolectomy was not associated with worsened outcomes compared with preoperatively diagnosed dysplasia.

Abstract 17577: Cardiomyopathy With Positive ATTR Mutation but Negative Tc-PYP Scan: A Conundrum

Background: Cardiac amyloidosis (CA) is a Hypertrophic Cardiomyopathy (HCM) mimic. Technetium labeled pyrophosphate (Tc-PYP) scan provides a rapid & non-invasive means for identifying ATTR-type CA with 99% sensitivity and specificity. We present 2 patients who were referred to HCM clinic but were found to have genetic testing positive for hTTR. In both cases, Tc-PYP scan was negative. Case Presentation: Outlined in Figure 1. Discussion: Both cases present a diagnostic and management dilemma. Neither of these two patients can be strictly considered asymptomatic carriers of the ATTR gene as both had phenotypic expression in the form of cardiomyopathy & massive LVH on imaging. Yet, in both Tc-PYP scan was negative. Neither had the ATTR mutations (Phe64Leu and Val30Met) that have reported association with negative Tc-PYP scan. Another possibility is early CA, which maybe rarely associated with negative Tc-PYP scan. Patient 1 refused endomyocardial biopsy, so early CA remains on the differential for her. Patient 2 had a negative endomyocardial biopsy. Her case is unique due to history of liver transplant 20 years prior to presentation making phenotypic CA less likely, but not impossible as there have been prior reports of cardiac disease progressing even after liver transplantation in familial ATTR. She also had tacrolimus exposure, which is known to cause LVH in rare cases. Both patients had hypertension, which could have also contributed to LVH. This case series serves to highlight the importance of maintaining a broad differential diagnosis in patients undergoing evaluation for HFpEF and severe LVH, particularly in cases of positive genetic testing but negative PYP scan for CA. From a management standpoint, it is unclear if early initiation of tafamidis might have a role in preventing cardiomyopathy progression in such patients with diagnostic uncertainty & ongoing concern for early CA.

De Novo Granuloma of the Membranous Vocal Fold: A Marker of Occult Malignancy.

De novo occurrence of granuloma (granulation tissue) on the membranous vocal fold is not readily explained by usual causes of granuloma at the vocal process. We describe a series of patients. Case series. Single academic institution. Cases were identified over a 16-year period. All patients exhibited granulation tissue on pathology. Demographic details, presentation, treatment, histology, and clinical outcomes were recorded. Five patients (mean age: 74.0 ± 6.1 years, 40.0% male, 40.0% former smokers) underwent a biopsy. Persistent or recurrent granulation led to a second biopsy in 4 patients an average of 1423.5 days later, revealing a new diagnosis of squamous cell carcinoma (SCC) in situ in one and mild dysplasia in another. Further persistence or recurrence led to a third biopsy or excision an average of 302.3 days later in 3 patients, demonstrating SCC in situ in 1. An average of 2.5 biopsies were required with a mean time to SCC in situ diagnosis of 919.5 days from presentation. Two patients continued to demonstrate persistent granulation tissue on histology. The membranous vocal fold is an atypical location for granuloma and portends a risk of occult malignancy. The occurrence of de novo granuloma at this site should prompt close long-term clinical surveillance with a low threshold for biopsy. Consideration should be given to tissue collection in the operating room to adequately sample the lesion's base. Concern should persist even after a negative biopsy, and serial observation with repeat biopsy as needed should be pursued.

The evaluation, diagnosis, and treatment of malignant mixed Müllerian tumor of the cervix: A case report

Introduction: Cervical cancer is the most common gynecologic malignancy in India, the most common histology being squamous cell carcinoma. Malignant mixed Müllerian tumor of the cervix, also referred to as carcinosarcoma of the cervix is an unusual entity. Hence, there is a dearth of literature on evaluation and management of such tumors, which is also reflected in the fact that there are no specific consensus guidelines on the same. We present the case of a 35-year-old woman who was diagnosed to have malignant mixed Müllerian tumor of the cervix. Case Report: Carcinosarcoma cervix is a rare entity, with postmenopausal women being more commonly affected. This makes our case a very unique one, as our patient is a premenopausal, 35-year-old young woman who presented with abnormal uterine bleeding and was subsequently diagnosed to have carcinosarcoma of the cervix. The clinical presentation and management of the case have been discussed. Conclusion: Malignant mixed Müllerian tumor is an aggressive and rare tumor which can affect the uterus, ovaries, or the cervix. A negative biopsy may not help to rule out the diagnosis of the same. Multimodality treatment including surgical intervention, chemotherapy with paclitaxel and carboplatin, and radiotherapy could benefit this subset of patients.

Effects of Antibiotic Eradication Therapy on H. Pylori-Negative Stage IE Gastric MALT Lymphoma ─ Real World Experience

Background: Helicobacter pylori (H. pylori) infection plays a critical role in the pathogenesis of gastric MALT lymphoma and its eradication can lead to tumor regression with a complete response (CR) rate of 78% in early-stage disease and a 5-year survival rate > 95%. However, 10% of patients have gastric MALT lymphoma with no detectable H. pylori infection (Zullo et al., J Clin Gastroenterol 2010). There is controversy regarding whether H. pylori-negative gastric MALT patients should receive a trial of antibiotic therapy. The NCCN guideline recommends skipping antibiotics and proceeding directly to radiation therapy. On the other hand, the ESMO guideline recommends H. pylori eradication (HPE) as the first-line therapy for every patient with gastric MALT lymphoma irrespective of H. pylori status. This report aimed to evaluate the effectiveness of H. pylori eradication therapy in patients with limited-stage gastric MALT lymphoma. Methods: A retrospective analysis was performed to identify patients diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. H. pylori infection was determined by immunostaining of gastric mucosa, serology, stool antigen, or urea breath test. H. pylori status was considered positive when at least one of those tests showed positive results and negative when all of the performed test results in that patient were negative. The primary outcome was the CR rate defined as no macroscopic findings of lymphoma and negative biopsy resultsfrom the follow-up endoscopy 3-6 months following completion of treatment. Results: A total of 52 patients were identified; the median age was 68 years (range 52-87), and 29 (55.8%) were male. H. pylori infection was detected in 36.5% (19/52) patients by at least one of the methods - 14 cases by immunostaining, 3 cases by serology, and 1 each by stool antigen and urea breath test. The PCR or FISH for t(11;18) was performed in 10 cases (19.2%) and 2 cases of t(11;18) were detected (both were H. pylori-negative). All 19 H. pylori-positive patients were treated for H. pylori eradication (HPE) and 63% (12/19) achieved a CR. Of the 33 H. pylori-negative patients, 8 (24.2%) received HPE as the initial treatment and 1 (12.5%) responded with a CR. The treatment outcomes after HPE therapy showed the CR rate was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (63.2% vs 12.5%, p=0.033) (Table 1). Only 2 of the 12 H. pylori-positive patients achieving CR have relapsed after a median follow-up of 89.7 months (range 2.9-227.8); the one H. pylori-negative patient that received HPE also remains in CR at 9+ months. The other first-line treatments applied for the 25 H. pylori-negative patients were radiation therapy in 18 (54.5%), single-agent rituximab in 3 (9.0%), surgical resections in 2 (6%), oral chlorambucil in 1 (3%), and observation in 1 (3%) The outcomes are shown in Figure 1. Conclusion: In our United States patient population, the incidence of H. pylori-negative gastric MALT lymphoma was 63%, much higher than previously reported (Zullo et al., J Clin Gastroenterol 2010) and similar to that found by other US investigators (Strati et al. 10.1002/ajh.25447). For limited-stage H. pylori-positive gastric MALT lymphoma, HPE is an effective first-line treatment and should be used. For patients who have no detectable H. pylori infection with multiple methods, the CR rate with HPE is very low in our experience. Although there is likely little harm to trying HPE (as ESMO guidelines suggest), this delays definitive radiation therapy. These data will be useful in patient counseling and treatment decision-making.

Opportunistic prostate-specific antigen testing in Norwegian men: a public health challenge.

To describe age-specific prostate-specific antigen (PSA) distributions and resulting prostate cancer diagnoses that arise from population-wide opportunistic PSA testing. Over 8 million PSA tests were performed on >1.4 million Norwegian men from 2000 to 2020. During this period 43 486 men were diagnosed with localised prostate cancer. Most of the PSA testing reflected opportunistic testing. Age-specific PSA value distributions were constructed for men aged 45-75 years with and without prostate cancer. The distributions of PSA values in men with and without prostate cancer widened with age and overlapped extensively from 3 to 7 ng/mL. Localised prostate cancer diagnoses increased 10-fold from the age of 45 to 75 years. PSA testing identified intermediate- or high-grade cancers in 21% (95% confidence interval [CI] 19-23%) of men aged 50-54 years and 42% (95% CI 41-43%) of men aged 70-74 years. Grade group (GG)1, GG2, GG3 and ≥GG4 constituted 49%, 31%, 10% and 10% of cancers identified at age 50-54 years and 26%, 26%, 18%, and 30% of cancers identified at age 70-74 years. Opportunistic PSA testing increases with ageing and often generates values that cannot discriminate benign prostate enlargement from prostate cancer. A clinical cascade using additional imaging or serum tests is necessary to avoid negative biopsies and the overdiagnosis of indolent disease. The declining specificity of PSA testing with ageing poses a significant public health challenge especially among older men aged ≥70 years.

P037 - Risk of detecting prostate cancer based on the PSAD and PIRADS lesions in MRI in patients with a negative previous biopsy.

P037 - Risk of detecting prostate cancer based on the PSAD and PIRADS lesions in MRI in patients with a negative previous biopsy.

Cancer Detection Rate of MRI Ultrasound Fusion Prostate Biopsy in 1,039 Patients and Number Needed to Biopsy in Targeted Lesion

Objective: To determine the cancer detection rate (CDR) of magnetic resonance imaging ultrasound fusion prostate biopsy (MRI/US fusion prostate biopsy) in Thailand. The secondary aim was to estimate the number needed to biopsy (NNB) for each prostate lesion in a targeted biopsy, classified by Prostate Imaging-Reporting and Data System (PI-RADS). Materials and Methods: The data of 1,039 consecutive patients who underwent a MRI/US fusion prostate biopsy at Siriraj Hospital between September 2017 and February 2021 was included and retrospectively reviewed. Those included had previous negative biopsies and were biopsy naïve. The data was analyzed to find the detection rate and NNB. Results: The overall detection rate of MRI/US fusion prostate biopsy was 58.71%, whereas that of systematic biopsy was 45.72%. Clinically significant prostate cancer (csPCa) (Gleason score ≥ 3+4) detection rate of MRI/US fusion prostate biopsy was 51.01%. When categorized by PI-RADS category 3, 4, and 5 were 12.16%, 44.98%, 85.71% respectively. NNB in targeted biopsy of PI-RADS 3, 4, and 5 were 8, 7, and 3 times sequentially. Positive predictive factors for prostate cancer (PCa) detection were age, prostate-specific antigen density (PSAD) and PI-RADS, whereas prostate volume was a negative predictive factor. Conclusion: This study supports the role of MRI/US fusion prostate biopsy in PCa detection and should not avoid systematic biopsies. The higher the PI-RADS was, the greater the csPCa detection rate. NNB is helpful in guiding the least amount of biopsied cores for each lesion.

Incidental prostate cancer after holmium laser enucleation of the prostate: Critical analysis of independent risk factors and impact on surgical outcomes.

The objectives of this study are to evaluate the impact of incidental prostate cancer (iPCa) and its different grade group (GG) on the surgical outcomes of holmium laser enucleation of the prostate (HoLEP) and, furthermore, to assess the independent risk factors associated with the detection of iPCa. A retrospective chart review was conducted at a single institution for HoLEP cases that were performed between 2017 and 2022. Patients with a preoperative diagnosis of prostate cancer and those without baseline prostate-specific antigen (PSA) levels within 1 year were excluded. Four hundred seventeen patients were divided into three groups: benign prostatic hyperplasia-377; clinically insignificant (GG 1)-29; and clinically significant prostate cancer (GG 2-5)-11. The preoperative parameters analysed included age, body mass index, race/ethnicity, use of 5-alpha-reductase inhibitors, PSA, prostate size, PSA density, and history of negative prostate biopsy. To evaluate the association between clinical and demographic variables, a multivariable-adjusted logistic regression analysis was performed. We also assessed intraoperative and post-operative outcomes among these three groups. A total of 417 patients were analysed; 40 (9.6%) patients had iPCa, of which 29 (72.5%) and 11 (27.5%) were clinically nonsignificant and significant prostate cancer, respectively. Of all the demographic and preoperative variables analysed, hypertension was significantly associated with overall prostate cancer diagnosis (p< 0.05), and no other variable including patient age, preoperative PSA, PSA density, prostate size, or prior prostate biopsy were associated with increased risk of overall prostate cancer or clinically significant prostate cancer diagnosis. Most cases of iPCa were GG1, and 34 (85%) were managed with active surveillance. The rate of iPCa after HoLEP was 9.6%, with most cases being GG 1 (72.5%) and managed through active surveillance. Age, prostate size, baseline PSA, and prior negative prostate biopsies were not associated with increased risk of iPCa.

Defining the Longitudinal Risk of CIN 3+ for

To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and <CIN2 histology, stratified by biopsy result. The authors linked administrative databases including cytology, pathology, cancer registries, and physician billing history to identify participants referred to colposcopy between January 2012 and December 2013 with high-grade cytology (atypical squamous cells [ASC]-H, high-grade squamous intraepithelial lesion [HSIL], invasive squamous cell carcinoma, adenocarcinoma, atypical glandular cells [AGC], adenocarcinoma in situ) and had <CIN2 (with and without biopsy confirmation) at colposcopy. Three- and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis. Among 4,168 women referred to colposcopy for ASC-H, HSIL, squamous cell carcinoma, or adenocarcinoma, the 3- and 5-year CIN3 incidence rates were 17.7%/20.0% no biopsy, 13.0%/15.1% negative biopsy, and 18.9%/20.0% low-grade squamous intraepithelial lesion (LSIL) biopsies. The 3- and 5-year incidences of invasive cancer were: 1.25%/1.68% no biopsy, 0.78%/1.04% negative biopsy, and 0%/0% LSIL biopsy. When the initial cytology was AGC/adenocarcinoma in situ (n = 944), the 3- and 5-year rates of CIN3 were 7.42%/8.39% no biopsy, 7.41%/9.26% negative biopsy, and 7.69%/7.69% LSIL biopsy. The invasive cancer rates were 1.12%/1.54% no biopsy, 0.46%/0.46% negative biopsy, and 0.0%/0.0% LSIL biopsy. By screening cytology, participants referred for HSIL had the highest 3- and 5-year rates of CIN3 (18.9% and 21%) compared with AGC (7.22%/8.28%) and ASC-H (15.5%/18%). The 3- and 5-year invasive cancer rates were 1.38%/1.75% HSIL, 0.85%/1.17% AGC, and 0.91%/1.36% ASC-H. In participants referred for high-grade cytology where colposcopy shows <CIN2, the subsequent risk of invasive cancer at 5 years is sufficiently elevated to warrant close surveillance in colposcopy.

Concordance between Axillary Ultrasound and Sentinel Biopsy in Clinically Node-Negative Early Breast Cancer

Objective: To determine the sensitivity of axillary ultrasound in detecting axillary nodal metastasis in clinically and radiologically uninvolved axillary nodes in early carcinoma breast by comparing with sentinel node biopsy histopathology on frozen section. Study Design: Comparative cross-sectional study Place and Duration of Study: Breast Clinic, CMH, Rawalpindi Pakistan, from Aug 2020 to May 2021. Methodology: Patients included in the study presented with breast cancer lesions with clinically impalpable axillary lymph nodes aged 18-75. Patients with clinically impalpable nodes underwent an ultrasound of the axilla; if suspicious nodes were found, the patient had subsequent axillary node dissection. Sentinel node biopsy (SLNB) was performed on axillary ultrasound in all patients with no suspicious or benign-looking nodes. Histopathological reporting was taken as standard. Lymph nodal status on axillary ultrasound, SLN biopsy and axillary lymph node clearance were documented and analyzed. Results: Twenty-nine patients were included who had benign-looking lymph nodes on axillary ultrasound and underwent sentinel lymph node biopsy. The mean age of the patients was 54.03 ± 7.94. Out of 29 patients, 24(82.8%) patients had negative Sentinel lymph node biopsy, and 5(17.2%) had positive Sentinel lymph node biopsy, who then underwent axillary lymph node dissection. Conclusion: Sentinel lymph node biopsy is the gold standard to determine axillary lymph nodes involved in early carcinoma breast, which seem benign on pre-operative axillary ultrasound.

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy.

Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy. In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer. With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7-19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort. Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

Effect of Breast Screening Regimen on Breast Cancer Outcomes: A Modeling Study.

Guidelines vary for the age at which to begin breast cancer screening and the interval between examinations. A validated computer model was used to compare estimated outcomes between various screening regimens. The OncoSim-Breast microsimulation model (Canadian Partnership Against Cancer) was used to simulate a cohort of 1.53 million Canadian women born in 1975. The effect of screening regimen on absolute breast cancer mortality rates, stage at diagnosis, number needed to be screened to avert a breast cancer death or save a life year, abnormal recall rates and negative biopsy rates was examined for unscreened women or those entering screening at age 40 or 50 and screened annually or biennially to age 74. Compared to no screening, absolute mortality reduction was 4.6 (biennial 50-74), 5.9 (biennial 40-74) and 7.9 (annual 40-74) fewer deaths per 1000 women. The absolute rate of diagnosis of advanced cancers (Stage 2, 3 and 4) falls in favor of earlier stages as the number of lifetime screens increases. Annual screening beginning at age 40 until age 74 would provide an additional reduction of 2 and 3.3 breast cancer deaths per 1000 women compared to biennial screening beginning at ages 40 and 50, respectively. There is a corresponding drop in the absolute number of Stage 2, 3 and 4 cancers diagnosed.

Serum Testosterone and Dihydrotestosterone and Incidence and Progression of Lower Urinary Tract Symptoms: Results From the REDUCE Study.

Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.

Is therapeutic lymph node dissection of value for lymph node recurrence in melanoma?

BackgroundTherapeutic lymphadenectomy (TLND) is still performed in most melanoma patients to treat nodal recurrences after initial negative lymph node biopsy (-SLNB), despite the lack of evidence for survival benefit. We sought to compare melanoma-specific survival (MSS) and distant metastasis-free survival (DMFS) of patients who underwent TLND versus no TLND using our institutional and MSTL-1 databases. MethodsWe identified 146 patients with nodal recurrence following -SLNB: 132 underwent TLND and 14 did not. DMFS and MSS were evaluated for the cohorts followed by a matched-pair analysis between the cohorts. ResultsNo difference was observed in five-year DMFS (p ​= ​0.454) and five-year MSS (p ​= ​0.945) between the two groups. The matched-pair analysis showed similar results (p ​= ​0.329 and p ​= ​0.363 for DMSF and MSS, respectively). ConclusionsFrom this limited retrospective study, TLND for nodal recurrence after a -SLNB does not appear to improve DMFS or MSS in melanoma patients compared to no TLND.

Significant prostate cancer risk after MRI-guided biopsy showing benign findings: Results from a cohort of 381 men

BackgroundMRI-guided biopsy (MGB) contributes to the diagnosis of clinically significant Prostate Cancer (csPCa). However, there are no clear recommendations for the management of men after a negative MGB. The aim of this study was to assess the risk of csPCa after a first negative MGB. MethodsBetween 2014 and 2020, we selected men with a PI-RADS score ≥ 3 on MRI and a negative MGB (showing benign findings) performed for suspected prostate cancer. MGB (targeted and systematic biopsies) was performed using fully integrated mobile fusion imaging (KOELIS). The primary endpoint was the rate of csPCa (defined as an ISUP grade ≥ 2) diagnosed after a first negative MGB. ResultsA total of 381 men with a negative MGB and a median age of 65 (IQR: 59–69, range: 46–85) years were included. During the median follow-up of 31 months, 124 men (32.5%) had a new MRI, and 76 (19.9%) were referred for a new MGB, which revealed csPCa in 16 (4.2%) of them. We found no statistical difference in the characteristics of men diagnosed with csPCa compared with men with no csPCa after the second MGB. ConclusionWe observed a risk of significant prostate cancer in 4% of men two years after a negative MRI-guided biopsy. Performing a repeat MRI could improve the selection of men who will benefit from a repeat MRI-guided biopsy, but a clear protocol is needed to follow these patients. Level of evidence4

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

PurposeCurrently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.MethodsUrine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).ResultsIn Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.ConclusionThis urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Cancer Detection Rate and Abnormal Interpretation Rate of Prostate MRI Performed for Clinical Suspicion of Prostate Cancer

PurposeTo report cancer detection rate (CDR) and abnormal interpretation rate (AIR) in prostate MRI performed for clinical suspicion of prostate cancer (PCa). Materials and methodsThis retrospective single-institution, three-center study included patients who underwent MRI for clinical suspicion of PCa between 2017 and 2021. Patients with known PCa were excluded. Patient-level Prostate Imaging-Reporting and Data System (PI-RADS) score was extracted from the radiology report. AIR was defined as number of abnormal MRI (PI-RADS score 3-5) / total number of MRIs. CDR was defined as number of clinically significant PCa (csPCa: Gleason score ≥7) detected at abnormal MRI / total number of MRI. AIR, CDR, and CDR adjusted for pathology confirmation rate were calculated for each of three centers and pre-MRI biopsy status (biopsy-naive and previous negative biopsy). ResultsA total of 9,686 examinations (8,643 unique patients) were included. AIR, CDR, and CDR adjusted for pathology confirmation rate were 45.4%, 23.8%, and 27.6% for center I; 47.2%, 20.0%, and 22.8% for center II; and 42.3%, 27.2%, and 30.1% for center III, respectively. Pathology confirmation rate ranged from 81.6% to 88.0% across three centers. AIR and CDR for biopsy-naive patients were 45.5% to 52.6% and 24.2% to 33.5% across three centers, respectively, and those for previous negative biopsy were 27.2% to 39.8% and 11.7% to 14.2% across three centers, respectively. ConclusionWe reported CDR and AIR in prostate MRI for clinical suspicion of PCa. CDR needs to be adjusted for pathology confirmation rate and pre-MRI biopsy status for interfacility comparison.

Comparison of patients with biopsy positive and negative primary angiitis of the central nervous system.

There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. From the multicentre retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. Two hundred patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (odds ratio [OR] 2.90; 95% CI: 1.25, 7.10; P = 0.01) and more often presented with seizures (OR 8.31; 95% CI: 2.77, 33.04; P < 0.001) or cognitive impairment (OR 2.58; 95% CI: 1.11, 6.10; P = 0.03). On imaging, biopsy positive patients more often had non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80; 95% CI: 15.72, 233.06; P < 0.001) or ≥1 cerebral microbleed (OR 8.08; 95% CI: 3.03, 25.13; P < 0.001), and less often had ≥1 acute brain infarct (OR 0.02; 95% CI: 0.004, 0.08; P < 0.001). In the multivariable model, non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (adjusted OR 8.27; 95% CI: 1.78, 38.46; P < 0.01) and absence of ≥1 acute brain infarct (adjusted OR 0.13; 95% CI: 0.03, 0.65; P = 0.01) were significantly associated with a positive biopsy. Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS.

The Diagnostic Utility of Lip Biopsy in Paediatric Crohn's Disease: A 10-year Single-centre Retrospective Study

BackgroundOral manifestations of paediatric Crohn's disease (CD) are reported in up to 60% of cases. Lip biopsy can be used to histologically diagnose oral CD. We evaluated the utility of lip biopsy in children under initial investigation for potential CD. MethodsA 10-year retrospective review of electronic patient records at a single tertiary paediatric surgery centre was performed. All patients aged ≤16 years who underwent lip biopsy were included. Clinical features, histology, and diagnostic details were extracted. ResultsForty-two children underwent lip biopsy. Median age at biopsy was 13.3 years (11.0–14.9). Final diagnosis was CD in 21/42 (50%) children, indeterminant colitis in 3/42 (7%), orofacial granulomatosis (OFG) in 3/42 (7%), coeliac disease in 1/42 (2%), and eosinophilic oesophagitis in 1/42 (2%). Thirteen children (31%) received no formal diagnosis. The most common symptoms reported were oral ulceration (33/42, 79%), lip swelling (21/42, 50%), and abdominal pain (19/42, 45%). Lip biopsy histology was normal in 11/42 (26%). In 24/42 (57%), non-granulomatous inflammation was seen. In 7/42 (17%) lip biopsy identified granulomatous inflammation: three (7%) had endoscopic biopsies concordant for CD, three (7%) had negative endoscopic biopsies but were diagnosed with CD, and one was diagnosed with OFG (2%). Sensitivity was 29% and specificity was 95%. ConclusionLip biopsy has low sensitivity but high specificity for diagnosing CD. Lip biopsy diagnosed CD in 7% when endoscopic biopsies were negative, enabling treatment. LB is a useful diagnostic test for CD in children presenting with oral symptoms. Level of EvidenceIII.