Additional Biopsies Research Articles

Sextant Biopsy-Based Criteria for Clinically Insignificant Prostate Cancer Are Also Valid for the 12-Core Prostate Biopsy Scheme: A Multicenter Study of Urooncology Association, Turkey

Background: Epstein criteria based on sextant biopsy are assumed to be valid for 12-core biopsies. However, very scarce information is present in the current literature to support this view. Objectives: To investigate the validity of Epstein criteria for clinically insignificant prostate cancer (PCa) in a cohort of the currently utilized 12-core prostate biopsy (TRUS-Bx) scheme in patients with low-risk and intermediate-risk PCa. Method: Pathological findings were separately evaluated in the areas matching the sextant biopsy (6-core paramedian) scheme and in all 12-core schemes. Patients were divided into 2 groups according to the final pathology report of RP as true clinically significant PCa (sPCa) and insignificant PCa (insPCa) groups. Predictive factors (including Epstein criteria) and cutoff values for the presence of insPCa were separately evaluated for 6- and 12-core TRUS-Bx schemes. Then, different predictive models based on Epstein criteria with or without additional biopsy findings were created. Results: A total of 442 patients were evaluated. PSA density, biopsy GS, percentage of tumor and number of positive cores, PNI, and HG-PIN were independent predictive factors for insPCa in both TRUS-Bx schemes. For the 12-core scheme, the best cutoff values of tumor percentage and number of positive cores were found to be ≤50% (OR: 3.662) and 1.5 cores (OR: 2.194), respectively. The best predictive model was found to be that which added 3 additional factors (PNI and HG-PIN absence and number of positive cores) to Epstein criteria (OR: 6.041). Conclusions: Using a cutoff value of “1” for the number of positive biopsy cores and absence of biopsy PNI and HG-PIN findings can be more useful for improving the prediction model of the Epstein criteria in the 12-core biopsy scheme.

912 Comparison of Magnetic Resonance Imaging Cognitive Prostate Biopsy Versus Magnetic Resonance Imaging-Ultrasound Fusion Prostate Biopsy in The Detection of Prostate Cancer

Abstract Introduction Prostate biopsy is performed to obtain tissue specimens to diagnose prostate cancer (CaP). Superimposing magnetic resonance imaging (MRI) on the prostate biopsy machine can improve the targeting of abnormal prostate lesions found on MRI scans. We compare the results of MRI cognitive prostate biopsy to MRI-US fusion biopsy in the detection of prostate cancer. Method Data was collected retrospectively for all patient that had an MRI and prostate biopsy from 01/01/2019 to 31/12/2019. Electronic patient records and radiology imaging software were used to collate data. Results 319 patients with at least PIRADS 3 on MRI prostate were identified. CaP was detected in 70% (26/37) of the cognitive biopsy cohort and 66% (186/282) of the fusion biopsy cohort. None of the patients required additional biopsies. Only the fusion biopsy cohort had complications which were Urosepsis - 7, Haematuria - 3, Urinary retention - 1 and Rectal bleeding- 1. Conclusions Our study suggests the CaP detection rates were similar in both cohorts. However, similar patient numbers are required to avoid selection bias. 66.5% of all PIRADS 3 lesions were found to be ≥ Gleason 7. We recommend using magnetic resonance imaging-ultrasound fusion prostate biopsy to enhance prostate cancer detection rates.

What is the Optimal Method Assessing for Persistent Villous Atrophy in Adult Coeliac Disease?

Methods of assessing gluten-free diet (GFD) adherence in adults with coeliac disease (CD) include serological testing, dietitian evaluation, questionnaires and repeat duodenal biopsies. Persisting villous atrophy (VA) is associated with CD complications, however gastroscopy with biopsies is expensive and invasive. This study aimed to assess the abilities of a duodenal bulb (D1) biopsy and the Celiac Dietary Adherence Test (CDAT) to detect persisting VA in adults with CD. A prospective observational study of adult CD patients referred for follow-up duodenal biopsies was performed. Quadrantic biopsies were taken from the second part of the duodenum (D2), in addition to a D1 biopsy. Patients underwent follow-up serological testing, and completed the CDAT and Biagi Score. These non-invasive adherence markers were compared against duodenal histology. 368 patients (mean age 51.0 years, 70.1% female) had D1 and D2 biopsies taken at follow-up gastroscopy. Compared to D2 biopsies alone, additional D1 biopsies increased detection of VA by 10.4% (p<0.0001). 201 patients (mean age 50.3 years, 67.7% female) completed adherence questionnaires and serology. When detecting VA, sensitivities and specificities of these markers were 39.7% and 94.2% for IgA- tTG, 38.1% and 96.4% for IgA-EMA, 55.6% and 52.2% for CDAT and 20.6% and 96.4% for the Biagi score. Bulbar biopsies increase detection of persisting VA by 10.4%. Serology, CDAT and Biagi performed poorly when predicting VA. The gold standard for predicting persisting VA remains repeat biopsy.

Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid

An accurate diagnosis of mucous membrane pemphigoid (MMP) is essential to reduce diagnostic and therapeutic delay. To assess the diagnostic accuracy of direct immunofluorescence microscopy on mucosal biopsy specimens and immunoserology in a large cohort of patients with suspected MMP. This retrospective cohort study was carried out in a single tertiary care center for blistering diseases between January 2002 and March 2019. Eligible participants were patients with suspected MMP and paired data on at least a mucosal biopsy specimen for direct immunofluorescence microscopy (DIF) and indirect immunofluorescence microscopy (IIF) on a human salt-split skin substrate (SSS). In addition, an optional DIF test on a skin biopsy specimen and one or more performed routine immunoserologic tests were analyzed. Data analysis was conducted from April 2019, to June 2020. Diagnostic accuracy of DIF, IIF SSS, and immunoblot for BP180 and BP230. Of the 787 participants, 121 (15.4%) received the diagnosis of MMP (50 men [41.3%], 71 women [58.7%]; mean [SD] age at diagnosis, 60.1 [17.7] years). Sixty-seven of the patients with MMP (55.4%) had monosite involvement, of which oral site was the most frequently affected (51 [42.1%]). No significant difference was found between the sensitivity of DIF on a perilesional buccal biopsy and a normal buccal biopsy (89.3% vs 76.7%). Three patients with solitary ocular involvement showed a positive DIF of only the oral mucosa. In 6 patients with a negative mucosal DIF, a skin biopsy confirmed diagnosis of MMP. Overall, IIF SSS was less sensitive (44.6%), but highly specific (98.9%). The sensitivity of immunoblot (66.1%) was higher compared to SSS, but with lower specificity (91.3%). This comparative diagnostic accuracy study of a cohort of 787 patients found a high sensitivity of a mucosal DIF biopsy for diagnosis of MMP, and lower sensitivity of serologic analysis. A biopsy can be taken from either perilesional or normal buccal mucosa. An additional DIF biopsy of another mucosal site or of affected or unaffected skin may increase the diagnostic yield and is recommended in patients with negative DIF results and high clinical suspicion.

Utility of gastric and duodenal biopsy sampling in adult eosinophilic esophagitis patients to rule out other gastrointestinal disorders

Rationale According to consensus guidelines, if eosinophilic esophagitis (EoE) is suspected, not only esophageal but also gastric and duodenal biopsy specimens should be sampled in order to exclude other generalized or eosinophilic gastrointestinal (GI) disorders, such as eosinophilic gastroenteritis or celiac disease. However, the diagnostic yield for this remains unclear. Aim To assess the diagnostic yield of biopsy sampling from the stomach and duodenum in adult EoE patients to rule out generalized or eosinophilic GI disorders. Methods A retrospective chart-review was conducted in untreated adult EoE patients that underwent upper endoscopy with biopsies sampled from the esophagus, stomach and duodenum. Standardized (electronic) case-report forms were used to extract clinical, endoscopic and histologic data. Results In total, 93 adults (71% males, age 36.4 (interquartile range 28.4 − 49.1) years) with untreated EoE (≥15 eosinophils/high-power-field) were included. Symptoms of dysphagia and food impaction were reported in 93% and 58%, respectively of the patients. Typical endoscopic EoE-features were present in 77 (85%) patients. The yield of routinely sampled gastric and duodenal biopsy specimens in our cohort was 3.6% (95% confidence interval: 2.6–4.8%) (n/N = 1/93) for a relevant other generalized or eosinophilic GI diagnosis and 30% for other histological diagnosis such as non-specific or H. Pylori gastritis. In total, 62 (67%) patients presented with other GI symptoms and/or endoscopic abnormalities of the stomach and/or duodenum – which both may be suggestive for other relevant GI conditions. The diagnostic yield for a relevant generalized or eosinophilic GI disorder in this subgroup was, 4.8% (95%CI 3.4 − 6.7%) (n/N = 1/62). Conclusion Gastric and duodenal biopsy specimens seem to have limited diagnostic value for the exclusion of generalized or eosinophilic GI disorders in adults with EoE. KEY POINTS Evidence is lacking on the diagnostic value of additional biopsies sampled form the stomach and duodenum to rule out other relevant generalized or eosinophilic gastrointestinal (GI) disorders. The yield of gastric and duodenal biopsies routinely sampled in our cohort was 3.6% for a relevant other generalized or eosinophilic GI diagnosis and 30% for other histological diagnosis such as non-specific or H. Pylori gastritis. The diagnostic yield for a relevant generalized or eosinophilic GI disorder in the subgroup of patients (67%) presenting with other GI symptoms and/or endoscopic abnormalities of the stomach and/or duodenum - which both may be suggestive for other relevant GI conditions was, 4.8%. Gastric and duodenal biopsy specimens seem to have limited diagnostic value for the exclusion of generalized or eosinophilic GI disorders in adults with EoE.

Acute Variceal Bleed in Cirrhosis is Associated With Reversible Changes in Tight Junction Protein Expression in the Intestine: A Proof-of-Concept Study

Tight junction proteins (TJPs) play an important role in gut-barrier dysfunction in cirrhosisand its complications such as acute variceal bleed (AVB). However, the dynamics of TJPs expression after AVB, its relation to bacterial translocation, and impact on clinical outcome is largely unknown. The aim of this study was to study the expression of TJPs in cirrhosis and assess its dynamic changes in AVB. In addition, the relation of TJPexpression to endotoxemia and clinical outcomes was assessed. In this prospective pilot study, 17 patients of cirrhosis with AVB, 59 patients of cirrhosis without AVB (non-AVB cirrhosis), and 20 controls were assessed for claudin-2 and claudin-4 expression in the duodenal biopsy. In the AVB-cirrhosis group, additional biopsies were obtained after 3 weeks. Endotoxemia was assessed by measuring IgG anti-endotoxin antibody levels. Claudin expression was correlated with a 6-month survival. Claudin-2 expression was downregulated in patients with AVB and non-AVB cirrhosis in villi (P<0.001 and 0.013) and crypts (P<0.001 and 0.012), respectively, compared with the controls. Claudin-4 expression was similar in villi (P=0.079), but lower in crypts (P= 0.007) in patients with cirrhosis. Claudin-2 expression was upregulated on serial biopsies in both villi and crypts (P= 0.003 and 0.001, respectively) in AVB-cirrhosis with postbleed expression comparable with those with non-AVB cirrhosis. IgG anti-endotoxin antibody levels were elevated in cirrhosis with no correlation with claudin-2/4 expression. Claudin-2 expression independently predicted survival at 6 months. Both claudin-2 and claudin-4 expression are downregulated in cirrhosis. AVB is associated with dynamic changes in TJPs expression. Gut-barrier dysfunction might predict outcomes independent of bacterial endotoxemia in cirrhosis.

Changing biological behaviour of NETs during the evolution of the disease: progress on progression.

Following improvements in the management and outcome of neuroendocrine neoplasms (NENs) in recent years, we see a subset, particularly of pancreatic NENs, which become more aggressive during the course of the disease. This is reflected by an increase in the Ki-67 labelling index, as a marker of proliferation, which may lead to an occasion of increase in grading, but generally does not appear to be correlated with histologically confirmed dedifferentiation. A systematic review of the literature was performed in PubMed, Cochrane Library, and Embase until May 2020 to identify cases that have behaved in such a manner. We screened 244 articles: only seven studies included cases in their cohort, or in a subset of the cohort studied, with a proven increase in the Ki-67 during follow-up through additional biopsy. In addition to these studies, we have also tried to identify possible pathophysiological mechanisms implicated in advanced NENs, although currently no studies appear to have addressed the mechanisms implicated in the switch to a more aggressive biological phenotype over the course of the disease. Such progression of the disease course may demand a change in the management. Summarising the overall evidence, we suggest that future studies should concentrate on changes in the molecular pathways during disease progression with sequential biopsies in order to shed light on the mechanisms that render a neoplasm more aggressive than its initial phenotype or genotype.

When Benign Behaves Badly: Atypical Hemangiomas on Contrast-Enhanced Ultrasonography.

Hemangioma is the most common benign liver tumor and is frequently encountered as an incidental finding on imaging. The classic enhancement pattern of hemangioma is diagnostic on contrast-enhanced ultrasound (CEUS), and it follows the same pattern of enhancement on computed tomography and magnetic resonance imaging. However, there is a subset of hemangiomas that demonstrate atypical enhancement patterns on CEUS. The ability to recognize the different enhancement patterns and discern when additional imaging or biopsy may be necessary is essential to accurately interpret an atypical hemangioma on CEUS. This article reviews various enhancement patterns of hemangioma on CEUS to avoid pitfalls in characterization of focal liver lesions on CEUS.

Is Additional Systematic Biopsy Necessary in All Initial Prostate Biopsy Patients With Abnormal MRI?

PurposeTo determine whether additional systematic biopsy is necessary in all biopsy naïve patients with MRI visible lesions by taking PI-RADS score and prostate volume into consideration.Materials and MethodsPatients who underwent combined systematic biopsy (SB) and cognitive MRI-targeted biopsy (TB) in our hospital between May 2018 and June 2020 were retrospectively reviewed. The detection rate of clinical significant prostate cancer (csPCa), biopsy grade group (GG) concordance, and disease upgrading rate on radical prostatectomy were compared between SB and TB and further stratified by PI-RADS v2.0 category and prostate volume.ResultsA total of 234 patients were analyzed in this study. TB alone detected more csPCa and less clinically insignificant prostate cancer (cisPCa) than SB alone in the whole cohort (57.3 vs 53%, P = 0.041; 3.8 vs 7.7%, P = 0.049 respectively). The additional SB indicated only a marginal increase of csPCa detection but a remarkable increase of cisPCa detection compared with targeted biopsy (59.4 vs 57.3%, P = 0.064; 3.8 vs 7.7%, P = 0.012). As stratified by PI-RADS category, the difference of csPCa detection rate between TB and SB was not significant either in PI-RADS 5 subgroup (83.8 vs 76.3%, P = 0.07) or in PI-RADS 3–4 subgroup (43.5 vs 40.9%, P = 1.0). Additional SB decreased the rate of disease upgrading on radical prostatectomy (RP) than TB alone in PI-RADS 3–4 subgroup (14.5 vs 25.5%, P = 0.031) other than PI-RADS 5 subgroup (6 vs 6%, P = 1.0). When stratified by prostate volume (PV), TB alone detected more csPCa than SB in small prostate (PV < 30 ml) group (81.0 vs 71.0%, P = 0.021) but not in large prostate (PV ≥ 30 ml) group (44.0 vs 42.7%, P = 0.754). The additional SB did not significantly decrease the rate of disease upgrading on RP than TB alone in either small or large prostate (6.4 vs 8.5%, P = 1.0; 13.8 vs 22.4%, P = 0.063).ConclusionThe combination biopsy method was no superior than targeted biopsy alone in PI-RADS 5 or in small volume prostate subgroup.

Association Between Specimen Length and Number of Sections and Diagnostic Yield of Temporal Artery Biopsy for Giant Cell Arteritis.

To investigate the association between specimen length and number of sections evaluated and the diagnostic yield of temporal artery biopsy (TAB) for giant cell arteritis (GCA). A pathologist reviewed all TABs performed for suspected GCA between January 1991 and December 2012. The blocks of all the inadequate and negative biopsy specimens were recut, and further slides at deeper levels were stained with hematoxylin and eosin in order to avoid missing inflammatory changes. In total, findings from 662 TABs were included in the study (71% female; mean age 73.2 years). A total of 427 TAB specimens (65%) were classified as negative, and 235 (35%) were classified as positive for GCA. Compared to those with negative TAB results, patients with positive TAB results were older and more frequently female. There was no difference in postfixation TAB specimen length between TAB specimens negative and positive for GCA (mean 6.5 mm versus 6.9 mm; P = 0.068). Cuts of additional biopsy sections revealed inflammation at deeper levels in 26 of 408 TAB specimens (6.4%) originally reported as uninflamed. The inflamed section was the second in 14 TAB specimens, the third in 9 specimens, and the fourth in 3 specimens. Piecewise logistic regression identified 5 mm as the TAB specimen length change point for diagnostic sensitivity. Compared to a TAB specimen length of <5 mm, the age- and sex-adjusted odds ratio for positive TAB results in samples ≥5 mm long was 1.5 (95% confidence interval 1.0-2.0), P = 0.032. A postfixation TAB specimen length of at least 5 mm should be sufficient to make a histologic diagnosis of GCA. In order not to miss inflammatory changes, at least 3 further sections at deeper levels should be evaluated in all negative TAB specimens.

Conditional progression-free survival in men on active surveillance for prostate cancer stratified by NCCN risk.

222 Background: Active surveillance (AS) is an accepted management strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However, how patients’ risk of disease progression evolves over time during AS has not been well defined. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. Methods: We reviewed our institutional database of 1254 men enrolled in AS for localized PCa from 1996-2016. Our AS protocol includes prostate specific antigen (PSA) and digital rectal exam (DRE) every 4-6 months for 3 years, then annually. Mandatory confirmatory 12 core biopsy is done at 12-18 months. Multiparametric magnetic resonance imagining (mpMRI) or additional systematic or MRI-fusion biopsies are done at the discretion of physician and patient. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. Results: Of 1254 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. Conclusions: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS.

PSA velocity to predict clinical progression in African American and non-Hispanic White patients with low-risk prostate cancer undergoing active surveillance.

196 Background: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. Methods: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. Results: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p&lt;0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). Conclusions: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols.

Does diagnostic mammography need to be a routine component of the initial evaluation of a breast symptom in women 30‐39 years of age?

Diagnostic mammography is routinely ordered, along with targeted breast ultrasound, to evaluate breast symptoms in women 30-39years of age. However, in this age group, mammography is often limited by breast density and the probability of detecting an occult malignancy is low. We sought to evaluate whether diagnostic mammography detected any new incidental malignancies in women aged 30-39years presenting with focal breast symptoms. This retrospective study included women 30-39years of age who had a diagnostic mammogram performed for focal breast symptoms at a single institution from 2002 to 2017. Descriptive analyses were performed to determine the rate of incidental mammographic findings outside of the region of the presenting symptom that 1) led to additional imaging and/or biopsies and 2) were found to be malignant. During the 16-year study period, 1770 evaluations were performed, of which 249 (14.1%) were found to have an additional incidental mammographic abnormality. Further diagnostic imaging was required in 211 (11.3%), core biopsy in 67 (3.8%), and excisional biopsy in 8 (0.5%). None of the mammographically detected incidental findings resulted in a new diagnosis of breast cancer. In the evaluation of focal benign breast symptoms in women 30-39years of age, diagnostic mammography did not detect any new incidental malignancies outside of the area of interest, but instead led to additional unavailing imaging and biopsy procedures. The mammography component of the diagnostic evaluation of younger average-risk women may potentially be omitted if the presenting symptom is determined to be benign with ultrasound alone.

Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography

Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive. The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.

Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy

ObjectivesThis study evaluates cases with clinically significant prostate cancer (csPCa) missed by targeted biopsy (TB) and analyzes the diagnostic impact of an additional systematic biopsy (SB) in a large patient collective. MethodsConsecutive patients with a 3 T multiparametric prostate MRI (mpMRI) and a subsequent MRI/US fusion-guided TB plus 12-core US-guided SB from 01/2014 to 04/2019 were included in this study. Primary study endpoint was the analysis of cases with a csPCa missed by TB and detected by SB. Secondary study objectives were the PCa detection and the correlation with clinical and MRI parameters. ResultsIn total 785 patients met the inclusion criteria. 342 patients had a csPCa (median PSAD 0.29 ng/mL/cm3). In 42 patients (13 %), a csPCa was detected only by SB. In 36 of these cases, the localization of the positive SB cores matched with the cancer suspicious region described on mpMRI (mCSR). Cases with a csPCA missed by TB showed either an insufficient MRI segmentation (prostate boundary correlation) (31 %) and/or insufficient lesion registration (lesion transfer, tracking, and/or matching) (48 %), a missed small lesion (14 %), or a failed center of a large lesion (10 %). Median PSAD of patients with non-significant PCa detected by SB was 0.15 ng/mL/cm3. ConclusionsMain reasons for missing a csPCa by TB were insufficient prostate segmentation or imprecise lesion registration within MRI/US fusion-guided biopsy. Consequently, verification of MRI quality, exact mCSR assessment, and advanced biopsy experience may improve accuracy. Altogether, an additional SB adds limited clinical benefit in men with PSAD ≤ 0.15 ng/mL/cm3.

Nonpalpable breast lesions: impact of a second-opinion review at a breast unit on BI-RADS classification.

To compare BI-RADS classification, management, and outcome of nonpalpable breast lesions assessed both by community practices and by a multidisciplinary tumor board (MTB) at a breast unit. All nonpalpable lesions that were first assigned a BI-RADS score by community practices and then reassessed by an MTB at a single breast unit from 2009 to 2017 were retrospectively reviewed. Inter-review agreement was assessed with Cohen's kappa statistic. Changes in biopsy recommendation were calculated. The percentage of additional tumor lesions detected by the MTB was obtained. The sensitivity, AUC, and cancer rates for BI-RADS category 3, 4, and 5 lesions were computed for both reviews. A total of 1909 nonpalpable lesions in 1732 patients were included. For BI-RADS scores in the whole cohort, a fair agreement was found (κ = 0.40 [0.36-0.45]) between the two reviews. Agreement was higher when considering only mammography combined with ultrasound (κ = 0.53 [0.44-0.62]), masses (κ = 0.50 [0.44-0.56]), and architectural distortion (κ = 0.44 [0.11-0.78]). Changes in biopsy recommendation occurred in 589 cases (31%). Ninety of 345 additional biopsies revealed high-risk or malignant lesions. Overall, the MTB identified 27% additional high-risk and malignant lesions compared to community practices. The BI-RADS classification AUCs for detecting malignant lesions were 0.66 (0.63-0.69) for community practices and 0.76 (0.75-0.78) for the MTB (p< 0.001). Agreement between community practices and MTB reviews for BI-RADS classification in nonpalpable lesions is only fair. MTB review improves diagnostic performances of breast imaging and patient management. • The inter-review agreement for BI-RADS classification between community practices and the multidisciplinary board was only fair (κ = 0.40). • Disagreements resulted in changes of biopsy recommendation in 31% of the lesions. • The multidisciplinary board identified 27% additional high-risk and malignant lesions compared to community practices.

Can the dynamic spectral imaging (DSI) color map improve colposcopy examination for precancerous cervical lesions? A prospective evaluation of the DSI color map in a multi-biopsy clinical setting

BackgroundColposcopy serves as a subjective examination of the cervix with low sensitivity to detect cervical intraepithelial dysplasia (CIN) grade 2 or worse (CIN2 +). Dynamic spectral imaging (DSI) colposcopy has been developed to provide an objective element to cervix examinations and has been proven to increase sensitivity of detecting CIN2 + . We aimed to assess the performance of the DSI color map and compared it to histological diagnoses of cervical biopsies in determining the CIN grade present.MethodsWomen were included in a consecutive, prospective manner at Randers Regional Hospital, Denmark. Women were eligible to participate if they were referred for colposcopy due to abnormal cervical smear (threshold: ≥ ASCUS) or follow-up after previously diagnosed CIN. All women had four biopsies taken, one directed by colposcopists alone prior to viewing the DSI color map, one directed by the worst color on the respective DSI color map, and two additional biopsies. All biopsies were analyzed separately. We calculated sensitivity, specificity, positive predictive values, and negative predictive values (NPVs) with 95% confidence intervals (CIs).ResultsA total of 800 women were recruited. Of these, 529 (66.1%) were eligible for inclusion. The sensitivity of the DSI color map was found to be 48.1% (95% CI 41.1–55.1) in finding CIN grade 2 or worse (CIN2 +) when compared to the histological diagnosis of the DSI directed biopsy. This was 42.5% (95% CI 36.7–48.5) when compared to the final histological diagnosis of all four cervical biopsies and with an NPV of 53.5% (95% CI 50.5–56.5).ConclusionThe worst color indicated by the DSI map might not consistently reflect the true grade of cervical dysplasia present. Thus, even though the DSI color map indicates low-grade changes, colposcopists should still consider taking biopsies from the area as high-grade changes might be present.Trial registration: NCT04249856, January 31 2020 (retrospectively registered).

Diagnostic utility of multiple site duodenal biopsies in celiac disease.

Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.

Endoscopic Detection of Helicobacter pylori by the Rapid Urease Test.

Helicobacter pylori infection can be detected on endoscopic biopsy of the gastric mucosa, by means of several techniques. The biopsy specimens are usually taken from the prepyloric region, but additional biopsy specimens obtained proximally increase the sensitivity of invasive tests and are recommended, especially if the patient has recently been treated with a proton-pump inhibitor. The effects of an increased risk of sampling error and the lower prevalence of H. pylori infection on the diagnostic accuracy of standard invasive tests needs to be considered. Despite evidence of enhanced yield with additional biopsies, combined Rapid Urease Tests (RUTs) have not been widely adopted. The other endoscopic tests, histology , and culture are also prone to sampling error and adoption of appropriate biopsy protocols should be widely adopted to enhance diagnostic yield.

The Value of Additional Conventional Transbronchial Biopsy in the Negative Results of Rapid On-site Evaluation During Endobronchial Ultrasound With Guide Sheath to Diagnose Small Peripheral Lung Cancer.

Objective: The accuracy of rapid on-site evaluation (ROSE) during endobronchial ultrasonography with guide sheath (EBUS-GS) was reported to be approximately 90% for diagnosing small peripheral pulmonary lesions (PPLs). When ROSE during EBUS-GS for diagnosing small peripheral lung cancer is carried out and does not include malignant cells in a position whereby the probe was located within or adjacent to the lesion, the best technique for overcoming the lower diagnostic yield remains unknown. This study aimed to evaluate factors affecting positive results of ROSE during EBUS-GS in such a probe position. Moreover, when the results of ROSE were consistently negative, we evaluated the effectiveness of conventional transbronchial biopsy (TBB) in addition to EBUS-GS alone. Methods: We performed a retrospective analysis of consecutive patients who underwent EBUS-GS combined with ROSE for diagnosing small peripheral lung cancer (≤30 mm). We classified the results of ROSE into two groups based on the presence of malignant cells: the ROSE positive group (included malignant cells) and the ROSE negative group (did not include malignant cells). The significant predictors of positive ROSE results during EBUS-GS were analyzed using multivariate logistic regression analyses. Results: We identified 67 lesions (43 lesions in the ROSE positive group and 24 lesions in the ROSE negative group, respectively). Multivariate logistic analysis revealed that the significant factor affecting positive ROSE results was lesion size (>15 mm) (OR = 9.901). The diagnostic yield of additional conventional TBB to EBUS-GS was significantly higher than that of EBUS-GS alone (75.0% vs 33.3%, P = .041). Conclusion: The positive results of ROSE during EBUS-GS were significantly influenced by lesion size (>15 mm). When the results of ROSE during EBUS-GS were consistently negative in a position whereby the probe was located within or adjacent to the lesion, additional conventional TBB was effective to improve the diagnostic yield compared with EBUS-GS alone.