Additional Biopsies Research Articles

Abstract OT3-02-01: Development of cell-free nucleic acid-based tests for early detection of breast cancer: The STRIVE study

Abstract Background: Mammography (digital 2D or digital 3D/tomosynthesis) is the cornerstone of current screening strategies for breast cancer, but new approaches are needed to further reduce the proportion of cancers diagnosed at advanced stages and more effectively identify those women in need of additional testing and biopsies. Circulating cell-free nucleic acids (cfNAs) shed from tumors, isolated from peripheral blood, and analyzed with ultra-deep and broad sequencing of cancer-associated genes, have great potential for early cancer detection. The ultimate goal is to develop blood cfNA cancer screening tests for use in conjunction with established risk factors and/or radiographic features for improved cancer detection. Development of these tests requires large, well-annotated cohorts of asymptomatic participants with adequate volumes of prediagnostic blood. The STRIVE Study cohort was recently established to train and validate cfNA-based tests for early detection of breast cancer. Eligibility criteria and trial design: The STRIVE Study is a new prospective, multi-ethnic mammography cohort that will recruit 120,000 subjects from 15+ US breast cancer screening centers (including Mayo Clinic and Sutter Health sites). Eligibility criteria require only that a participant has a scheduled routine screening mammogram at a participating center and has not received a biopsy prior to the research blood draw. Participants are recruited within 28 days of screening mammography (digital or tomosynthesis), consent electronically, provide blood samples, and complete an on-line risk factor questionnaire. Participants will be followed for all cancer diagnoses, cancer recurrences, and death for at least 5 years. Pertinent medical record information, imaging findings (including breast density), and follow-up data will be transferred electronically to a central database throughout the study period. Additional blood samples will be collected from participants with abnormal mammogram results, or who are diagnosed with cancer, to document and better understand the evolution of cfNA signals. Recruitment began in February 2017. Primary Aims: To train and validate a cfNA blood-based test to identify breast cancer overall in a cohort of women undergoing screening mammography. Statistical Methods: The study will be divided into a training phase (1/3 of participants) and an independent clinical validation phase (remaining 2/3 of participants). In the training phase, statistical machine learning techniques will be used to develop algorithms incorporating cfNA signals, clinical characteristics, or radiological features. In the validation phase, the prespecified locked algorithm developed from the training phase will be clinically validated in an independent group of women. Contact information for people with a specific interest in the trial: Additional details regarding the STRIVE Study are available on the ClinicalTrials.gov website (NCT03085888). For site-specific questions, please call 844-366-9738 for the Mayo Clinic and 1-855-578-7483 for Sutter Health. Citation Format: Liu MC, Cummings S, Vachon CM, Kerlikowske K, Couch FJ, Morris EA, Olson JE, Polley EC, Conners AL, Ellis RL, Patel B, Maimone IV S, Zhang N, Hamilton S, Clarke CA, Allen BA, Maddala T, Hartman A-R. Development of cell-free nucleic acid-based tests for early detection of breast cancer: The STRIVE study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-02-01.

Abstract P6-03-05: Risk of needle-track seeding with serial ultrasound guided biopsies in triple negative breast cancer

Abstract Background: Image-guided percutaneous needle biopsy of the breast is a common procedure. In breast cancer patients (pts) undergoing core biopsies and surgical resection on the same day, the rate of tumor cell displacement along the needle track has been reported to be up to 50%. However, the clinical significance of this finding in triple negative breast cancer (TNBC) patients (pts) undergoing serial biopsies while receiving neoadjuvant chemotherapy (NACT) is unknown. Here we report the incidence of needle-track seeding (NTS) in a cohort of TNBC pts enrolled on a molecular triaging protocol involving serial biopsies of the index breast lesion. Methods: We reviewed the clinical records of 144 consecutive TNBC pts enrolled on a molecular triaging protocol at MD Anderson Cancer Center. Per protocol, all pts underwent a pre-treatment research biopsy and were initiated on anthracycline based NACT (AC). Pts with inadequate response to front-line NACT were encouraged to undergo additional biopsies of the index breast lesion prior to switching therapies. Serial breast ultrasound (US) was performed to monitor therapeutic response and incidental evidence of needle-track seeding noted on US was documented. Results: Clinicopathological characteristics of the pts are summarized in Table 1. 89% (128/144) of pts had a diagnostic breast biopsy done at another center prior to presenting at MDACC. To date, we have performed 209 US guided biopsies of index breast lesions in 144 pts. 92% (193/209) of these biopsies were done mainly for research purposes. 1.4% (2/144) of pts were found to have evidence of NTS on follow up US. The first pt had a T1N0 (1.9cm), grade 3, invasive ductal carcinoma (IDC) at diagnosis. She underwent a diagnostic biopsy followed by a research biopsy before initiating AC. She was found to have NTS as well as progression of disease (PD) on follow up US after 2 cycles of AC. The second pt had a T2N0 (3cm), grade 3 IDC at diagnosis. She underwent a diagnostic biopsy at another center, followed by a research biopsy before initiating AC. Like the first pt, she was found to have NTS and PD on follow up US after 2 cycles of AC. Both pts are currently on neoadjuvant clinical trials of novel agents. Conclusion: The rate of NTS detected on US in TNBC pts undergoing serial biopsies of index breast lesions while receiving NACT is low and further studies are needed to determine the impact of serial biopsies on long term outcomes in TNBC. Table 1: Patient CharacteristicsCharacteristicN=144Age - Median (years, interquartile range)55 (46-62)Tumor Size Mean (cm, standard deviation)3.4 (2.2)T1 – n(%)35 (24)T2 – n(%)89 (62)T3 – n(%)19 (13)T4 – n(%)1 (1)Clinical Nodal Status Negative – n(%)74 (51)Positive – n(%)70 (49)Grade 1 – n(%)1 (1)2 – n(%)17 (12)3 – n(%)124 (86)Unknown – n(%)2 (1)Histologic Subtype Invasive ductal carcinoma – n(%)121 (84)Invasive lobular carcinoma – n(%)2 (1)Mixed ductal and lobular carcinoma – n(%)3 (2)Metaplastic carcinoma – n(%)13 (9)Not specified – n(%)5 (3)Laterality Right – n(%)72 (50)Left – n(%)72 (50) Citation Format: Yam C, Santiago L, Candelaria RP, Adrada BE, Rauch GM, Hess KR, Litton JK, Piwnica-Worms H, Mittendorf EA, Ueno NT, Lim B, Murthy RK, Damodaran S, Helgason T, Huo L, Thompson AM, Gilcrease MZ, Symmans WF, Moulder SL, Yang W. Risk of needle-track seeding with serial ultrasound guided biopsies in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-05.

Anterior cruciate ligament tear induces a sustained loss of muscle fiber force production.

Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers. We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing. Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends. While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve, 2018.

Feasibility and clinical utility of EUS guided biopsy of pancreatic cancer for next-generation genomic sequencing.

296 Background: Next-generation sequencing technology has made genomic profiling guided therapy a reality for many cancer types. The aim of this study is to investigate the feasibility of genomic profiling using standard clinical endoscopic ultrasound (EUS) core biopsy samples of Pancreatic Cancer (PC) to allow personalised cancer care. Methods: 78 patients underwent additional research biopsy at the time of diagnostic EUS biopsy. En-face frozen section was performed to enable targeted macro-dissection prior to DNA extraction, quantification and targeted gene sequencing (Agilent Comprehensive Cancer Gene Panel). Matching formalin-fixed (FFPE) diagnostic EUS biopsies and fresh frozen surgical resection specimens also underwent genomic profiling for comparison. Whole genome (WGS) and RNA sequencing was performed in selected patients. Results: Targeted panel sequencing ( n = 61) revealed known PC genes ( KRAS, GNAS, TP53, CDKN2A, SMAD4) in 36 patients with histological evidence of PC. Potentially actionable somatic mutations (BRCA1, BRCA2, ATM, BRAF, JAK3) were found in 6 (17%) patients. WGS ( n = 5) of EUS samples confirmed mutations identified on panel sequencing and revealed relevant mutational signatures and structural variation patterns that can act as putative biomarkers of therapeutic responsiveness. RNA sequencing ( n = 54) segregated patients into key clinically relevant molecular PC subtypes based on transcriptome and reveals novel molecular insights into advanced, unresectable PC ( n = 38). Conclusions: We demonstrate here novel multi-omic analysis of pancreatic cancer using standard clinical EUS guided fine needle biopsies. Multi-omic analysis of EUS biopsies offers potential clinical utility to guide personalized therapy of PC in both the neoadjuvant and advanced settings.

Reduction of MRI-targeted biopsies in men with low-risk prostate cancer on active surveillance by stratifying to PI-RADS and PSA-density, with different thresholds for significant disease.

BackgroundThe fear of undergrading prostate cancer (PCa) in men on active surveillance (AS) have led to strict criteria for monitoring, which have resulted in good long-term cancer-specific survival, proving the safety of this approach. Reducing undergrading, MRI-targeted biopsies are increasingly used in men with low-risk disease despite their undefined role yet. The objective of this study is to investigate the rate of upgrading using MRI-targeted biopsies in men with low-risk disease on AS, stratified on the basis of PI-RADS and PSA-density, with the aim to reduce potential unnecessary repeat biopsy procedures.MethodsA total of 331 men were prospectively enrolled following the MRI-PRIAS protocol. MR imaging was according to Prostate Imaging Reporting and Data System (PI-RADSv2) guidelines. Suspicious MRI lesions (PI-RADS 3–5) were additionally targeted by MRI-TRUS fusion biopsies. Outcome measure was upgrading to Gleason score (GS) ≥3+4 with MRI-targeted biopsies, stratified for PI-RADS and PSA-density.ResultsIn total, 25% (82/331) of men on AS showed upgrading from GS 3+3. Only 3% (11/331) was upgraded to GS ≥8. In 60% (198/331) a suspicious MRI lesion was identified, but in only 41% (82/198) of men upgrading was confirmed. PI-RADS 3, 4 and 5 categorized index lesions, showed upgrading in 30%, 34% and 66% of men, respectively. Stratification to PI-RADS 4–5, instead of PI-RADS 3–5, would have missed a small number of high volume Gleason 4 PCa in PI-RADS 3 category. However, further stratification into PI-RADS 3 lesions and PSA-density <0.15 ng/mL2 could result in a safe targeted biopsy reduction of 36% in this category, without missing any upgrades.ConclusionsStratification with the combination of PI-RADS and PSA-density may reduce unnecessary additional MRI biopsy testing. Overall, the high rate of detected upgrading in men on AS may result in an unintended tightening of continuing in AS. Since patients, included under current AS criteria showed extremely favorable outcome, there might be no need to further restrict continuing on AS with MRI and targeted biopsies.

Diagnostic significance of lymph node core needle biopsy for lymphoproliferative disease: a clinicopathologic study of 1 013 cases

Objective: To study the clinicopathologic features of lymphoproliferative disease by lymph node core needle biopsy(CNB)and to evaluate the diagnostic significance of CNB for lymphoproliferative disease. Methods: The annual distribution, entity constitute, clinical finding, gross feature, morphologic change, affiliate study and repeat biopsy diagnosis of 1 013 cases of lymph node CNB diagnosed at West China Hospital of Sichuan University from January 2009 to December 2015 were investigated. Results: (1) Proportion of lymph node CNB in total amount of biopsy specimens increased from 0.2% in 2009 to 0.8% in 2015.(2) The study cohort included 471 lymphomas, 12 atypical lymphoid hyperplasia (ALH), 136 suspected lymphomas, 372 benign lesions, and 22 cases of descriptive diagnoses. The most common types were diffuse large B cell lymphoma and T-lymphoblastic lymphoma. (3) Majority of patients were adolescents and children younger than 20 years or the elderly older than 60 years. 53.1% CNB tumor specimen consisted of ≥4 tissue cores and 40.5% were >2 cm in length. (4) 104 CNB cases with previous history of excision biopsy was included 45 carcinomas(no metastatic carcinoma was found), 32 lymphomas for treatment observation.1/14 suspicious lymphomas, 1/1 ALH and 3/22 cases benign lesions were diagnosed as lymphoma by repeat biopsy respectively. (5) 217 CNB cases were diagnosed as lymphoma by subsequent CNB (70), or subsequent excision biopsy (147) including 78.5%(73/93) suspected lymphomas, 5/7 ALH and 32.3%(20/62)benign lesions. Conclusions: Lymph node CNB has certain clinical indications, although limited for the diagnosis of lymphoproliferative disorders. Suspected lymphomas and ALH diagnosed by CNB should be followed by repeat tissue biopsy. For the benign lesions by CNB it does not rule out additional biopsy to further investigate the lesion.

Impact of breast MRI in women eligible for breast conservation surgery and intra-operative radiation therapy

PurposeThe current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3–6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up. Materials and methodsWe retrospectively identified patients treated by a single surgeon who were eligible for IORT based on institutional eligibility criteria which included: women age ≥55, grades 1–2, size <3 cm, estrogen receptor (ER) positive, Her-2 neu non-amplified and low/intermediate Ki-67, unifocal invasive ductal/mixed histology carcinomas. All patients must have undergone a physical exam and bilateral diagnostic mammography with ultrasound. From this population, we identified all patients who had undergone bilateral breast MRI as part of pre-operative evaluation. ResultsA total of 215 women were identified who met all eligibility criteria. MRI detected additional abnormalities in the breast in 89 patients (41%). Sixty-eight women underwent additional biopsies, with a total of 117 separate lesions biopsied. Of these, pathology was benign in 61 (52.1%), atypical ductal hyperplasia (ADH) in 21 (18%), ductal carcinoma in-situ (DCIS) in 17 (14.5%) and invasive disease in 18 (15.4%). Six patients had MRI-detected abnormalities in the contralateral breast only, with biopsies identifying invasive disease (3), DCIS (1) and benign (2) findings. MRI showed abnormalities in both breasts in 6 patients and 18 additional lesions were biopsied which reveled invasive carcinoma (6), DCIS (7), ADH (3) and benign findings (2). Fifteen patients had either multifocal/multicentric disease or index lesion >3 cm on MRI and were deemed ineligible for IORT. Based on either MRI size or biopsy results, management was ultimately changed for 27 patients (12.5%). Extramammary findings were observed in 17 patients and 11 of these patients underwent further imaging studies all of which returned negative results. ConclusionPreoperative bilateral breast MRI is a valuable tool in the proper selection of patients best suited for IORT. Even in highly selected, favorable risk patients, MRI detected additional lesions that changed surgical and radiation therapy recommendations in 12.5% of patients. However, the cost/benefit ratio needs to be taken into consideration given the high frequency of benign biopsies and additional radiological work-up.

Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies

The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

Screening by Chromo Endoscopy for Colorectal Cancer and Dysplasia in Ulcerative Colitis: An Algerian Prospective Cohort

Patients with longstanding extensive ulcerative colitis have an increased risk of colorectal cancer. Aims : To determine the incidence of dysplasia and colorectal cancer, in patients with longstanding ulcerative colitis. To evaluate prospectively, the proportion of dysplastic lesions detected by chromoendoscopy from targeted biopsies of macroscopically visible abnormalities, as opposed to random biopsies of colonic mucosa. Patients and methods : In this prospective study, consecutive patients with clinically inactive, longstanding UC (more than 8 years) were recruited from 4 centers; colonoscopy with chromoendoscopy using 0.1% methylene blue was performed for each patient. Four mucosal biopsy specimens were taken every 10 cm between the cecum and the rectum, with additional biopsies or removal of any mucosal abnormality. All the endoscopies were performed by a single specialist in gastroenterology. All the biopsies have been reviewed by a pathologist experienced in gastroenterology. Results: Two hundred and twenty four chromoendoscopies were performed in 106 patients. We diagnosed 49 neoplastic lesions in 31 patients; there were six adenocarcinomas, eight high grade dysplasia, 24 low grade dysplasia, and 11 lesions indefinite for dysplasia. We took 8035 random biopsies and found seven dysplastic lesions in six patients: one high grade dysplasia, two low grade dysplasia and four lesions indefinite for dysplasia. Random biopsies alone diagnosed dysplasia in two patients (1.8%), and had clinical impact only in one patient (0.9%). Conclusion : In our cohort, we experienced a high diagnostic yield of chromoendoscopy in the detection of neoplasia in high risk IBD patients. Random biopsies don’t have clinical impact and should be abandoned.

Initial experience of magnetic resonance imaging/ultrasonography fusion transperineal biopsy: Biopsy techniques and results for 75 patients.

PurposeThe aim of this study is to describe the technique and to report early results of transperineal magnetic resonance imaging and ultrasonography (MRI-US) fusion biopsy.Materials and MethodsA total of 75 patients underwent MRI-US fusion transperineal biopsy. Targeted biopsy via MRI-US fusion imaging was carried out for cancer-suspicious lesions with additional systematic biopsy. Detection rates for overall and clinically significant prostate cancer (csPCa) were evaluated and compared between systematic and targeted biopsy. In addition, further investigation into the detection rate according to prostate imaging reporting and data system (PI-RADS) score was done. Results of repeat biopsies were also evaluated.ResultsOverall cancer detection rate was 61.3% (46 patients) and the detection rate for csPCa was 42.7% (32 patients). Overall detection rates for systematic and targeted biopsy were 41.3% and 57.3% (p<0.05), respectively. Detection rates for csPCa were 26.7% and 41.3%, respectively (p<0.05). The cancer detection rates via MRI fusion target biopsy were 30.8% in PI-RADS 3, 62.1% in PI-RADS 4 and 89.4% in PI-RADS 5. Rates of csPCa missed by targeted biopsy and systematic biopsy were 0.0% and 25.0%, respectively. The cancer detection rate in repeat biopsies was 61.1% (11 among 18 patients) in which 55.5% of cancer suspected lesions were located in the anterior portion.ConclusionsTransperineal MRI-US fusion biopsy is useful for improving overall cancer detection rate and especially detection of csPCa. Transperineal MRI-US targeted biopsy show potential benefits to improve cancer detection rate in patients with high PI-RADS score, tumor located at the anterior portion and in repeat biopsies.

Additional Cervical Lymph Node Biopsy is Not a Significant Prognostic Factor for Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era: A Propensity Score-matched Analysis from an Epidemic Area.

Introduction: This study aimed to evaluate the prognostic value of cervical lymph node biopsy and whether different biopsy methods would lead different outcomes in NPC in the intensity-modulated radiotherapy (IMRT) era.Material and Methods: 1492 patients with biopsy-proven, non-metastatic NPC, and treated by IMRT with or without chemotherapy were retrospectively reviewed. Cervical lymph node biopsy was performed in 183 (12.3%) patients: 61(4.1%) by needle puncture and 118(7.9%) by excision biopsy. Propensity-score matching was used to match patients in both arms at an equal ratio. Overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and nodal relapse-free survival (NRFS) were assessed using the Kaplan-Meier method and compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model.Results: In the original cohort of 1492 patients, patients receiving cervical lymph node biopsy had comparable survival (OS: P = 0.736, DMFS: P = 0.749, LRFS: P = 0.538, NRFS: P = 0.093,) with patients receiving isolated napharynx biopsy. The results for the propensity-match cohort of 316 patients were similar. Interestingly, compared with the control group and needle puncture biopsy group, a slightly lower nodal recurrence rate was observed in the excision biopsy group (P = 0.082 and P = 0.072, respectively). Adjusting for the known prognostic factors in multivariate analysis, cervical biopsy did not cause a higher risk of death, distant metastasis, or nodal relapse.Conclusions: Pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, suggesting the resist of the biopsy and more aggressive treatment after the biopsy may be unnecessary.

Subungual nail bed melanoma masquerading as tinea ungium

Subungual amelanotic melanoma can masquerade as onychomycosis. Recently a man whose amelanotic nail bed melanoma presented as persistent onychodystrophy was reported in the Dermatology Online Journal. The patient had a persistent nail dystrophy; culture and biopsy of the nail demonstrated Candida and dermatophyte infection, respectively. However, he subsequently presented with a nodule that was biopsied and demonstrated melanoma. Similar to that patient, we recently described a 67-year-old woman with a four-year history of persistent nail dystrophy of the left fourth fingernail who had a periodic acid-Schiff staining of the nail plate demonstrating fungal hyphae. Her nail plate subsequently detached, demonstrating a friable nodule; a biopsy of the nodule demonstrated melanoma. In conclusion, in individuals with new morphologic changes to a dystrophic nail or with persistent nail dystrophy despite appropriate therapy, it is important for clinicians to consider performing additional evaluation and possible biopsy to exclude malignancy.

Theory of Additional Corpus Biopsy for Epidemiology and Diagnosis of Helicobacter Pylori

Background: There is still debate on the best sites for biopsy- based tests of Helicobacter pylori infection in patients with gastritis. This study was designed to determine if it is important to add corpus biopsies to the routine antral ones for identification of H. pylori, especially in case of gastric atrophy and/or intestinal metaplasia. Methods: A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in peptic ulcer disease. Preliminary studies have reported that the prevalence of H pylori infection increases with age, but detailed information on the prevalence of the bacteria in any defined population and on the factors that may influence the pattern of distribution remains scanty. Results: Up to 85% of people infected with H. pylori never experience symptoms or complications. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of nonulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool. Conclusion: H. pylori has been associated with colorectal polyps and colorectal cancer. It may also be associated with eye disease.

Benign Breast Disease

Benign breast disease constitutes any abnormality that upon further workup is found to be noncancerous and does not establish premalignant potential. Benign breast diseases can present in various ways, such as breast pain, a palpable breast lump, nipple discharge, or an imaging abnormality. Appropriate workup is essential to ensure that the new change is benign. This may entail additional imaging, biopsy, or surgery if necessary. Surgeons need to be able to recognize the presentation, appropriate workup, and treatment recommendations for the various benign breast diseases. This review addresses the broad range of benign breast lesions and their management recommendations. This review contains 7 figures, 5 tables and 54 references Key words: benign breast disease, breast cyst, breast mass, breast pain, idiopathic granulomatous mastitis, nipple discharge, papilloma, periductal mastitis, sclerosing adenosis

Benign Breast Disease

Benign breast disease constitutes any abnormality that upon further workup is found to be noncancerous and does not establish premalignant potential. Benign breast diseases can present in various ways, such as breast pain, a palpable breast lump, nipple discharge, or an imaging abnormality. Appropriate workup is essential to ensure that the new change is benign. This may entail additional imaging, biopsy, or surgery if necessary. Surgeons need to be able to recognize the presentation, appropriate workup, and treatment recommendations for the various benign breast diseases. This review addresses the broad range of benign breast lesions and their management recommendations. This review contains 7 figures, 5 tables and 54 references Key words: benign breast disease, breast cyst, breast mass, breast pain, idiopathic granulomatous mastitis, nipple discharge, papilloma, periductal mastitis, sclerosing adenosis

Percutaneous transcatheter biopsy for intracardiac mass diagnosis.

The differential diagnosis of intracardiac masses (ICM) is wide. While imaging modalities can suggest a diagnosis, clinical decision making usually requires histopathologic diagnosis. The aim of this study was to describe the procedural technique, safety outcomes, diagnostic accuracy and clinical utility of percutaneous transcatheter biopsy (TCB) for histopathologic diagnosis of ICM. The records of all patients undergoing TCB of ICM at the Mayo Clinic catheterisation laboratories in Rochester, Minnesota, between 2002 and 2017 were retrieved and reviewed. TCB of ICM to establish histopathologic diagnosis was performed in 29 patients. Masses were located in the right-sided chambers in 93% of cases. Echocardiographic guidance was used. Ventricular arrhythmias requiring immediate cardioversion occurred in 7% of patients. No other complications were noted. The average number of samples retrieved per procedure was 7±3.6. A histopathologic diagnosis was made by TCB in 72% and altered clinical decision making in 52% of patients overall. Eleven patients (38%) who would otherwise have required excisional biopsy were able to avoid cardiovascular surgery. Each additional biopsy sample was associated with an increase in the likelihood of making a histopathologic diagnosis (OR 1.74, 95% CI: 1.05-2.87, p=0.032). Echo-guided percutaneous TCB of ICM provides an accurate diagnosis and alters clinical management in the majority of cases. The procedural complication rate is low. An increase in the number of samples retrieved markedly improves the ability to render a diagnosis. TCB may therefore be considered as a first-line approach for the histopathologic diagnosis of ICM.

Prospective Outcome Analysis of the Safety and Efficacy of Partial and Complete Cryoablation in Organ-confined Prostate Cancer

To determine the rate of complications and change in International Prostate Symptom Score and Sexual Health Inventory for Men scores following cryotherapy treatment of low- and intermediate-risk prostate cancer. The secondary end points were the change in prostate-specific antigen post cryotherapy and biopsy-proven recurrence. Enrollment occurred from 2007 to 2015 to assess long-term complications of cryotherapy. A prostate biopsy was performed at 1 year or in the event of biochemical failure. Subjects were staged and graded by standard 12- to 14-core transrectal ultrasound (TRUS) biopsy. A subset of subjects underwent additional 3-dimensional mapping biopsy if the cancer was suspected to be downgraded. Analyses of functional outcomes were stratified into focal and nonfocal treatments. The study consisted of 393 men with low- and intermediate-risk prostate cancer, aged 44-89 years. Patient IPSS scores improved significantly in the nonfocal treatment strata at all time points and after 1 year in the focal strata with a median drop at 1 year of 4 points (P <.001). No significant difference was detected for a change in preprocedural SHIM score in either treatment strata after 2 years (P >.7). Eighty-two patients (20.9%) had a rise in prostate-specific antigen resulting in biochemical failure. Seventy patients had detected recurrence for an overall recurrence rate of 20.4% in 343 patients. A total of 109 patients (27.7%) reported urinary retention and urgency post cryotherapy, with 15.3% requiring catheterization for up to 3 weeks. Thirty-seven patients (9.4%) experienced urethral meatal stricture, and 36 patients (9.2%) reported unresolved new-onset erectile dysfunction. Complication rates, most significantly erectile dysfunction, are decreased in this study compared with those previously reported in the literature for cryotherapy for prostate cancer.

Attitudes of patients with metastatic cancer towards research biopsies.

To evaluate the attitudes of patients with different cancers towards research biopsies outside a clinical trial. Patients with metastatic cancer completed a questionnaire that assessed patients' willingness to consider research biopsies. Research biopsies were divided into two groups: biopsies performed as stand-alone procedures (research purposes only biopsy, RPOB) or performed during a clinically indicated biopsy (additional pass biopsy, APB). Factors analyzed included biopsy timing, biopsy site, sociodemographic information and information about prior trial participation. Univariate and multivariable analyses were conducted using random-effects logistic regression. One hundred and sixty-five patients with cancer (40 melanoma, 37 colorectal, 32 breast, 30 lung, 26 prostate) completed the questionnaire. Patients with melanoma demonstrated the greatest willingness to consider a research biopsy compared to patients with other cancer types (P<0.05). Patients' ethnicity, time since previous biopsies, time since metastatic diagnosis, and previous trial enrolment were all statistically significant for willingness to consider a research biopsy on univariate analysis. When adjusting for statistically significant variables on univariate analysis, the odds of patients considering APBs were 14.6 times greater than RPOBs (P<0.0001). Patients were also more willing to consider having blood or skin taken for research purposes (P<0.0001) compared to liver and bone biopsies. Patients with cancer show a greater willingness to consider APBs compared to RPOBs, and biopsies performed at less invasive body sites. There are differences in the attitudes of patients with different cancers towards research biopsies. Further research addressing motivations and barriers to research biopsies should be considered to increase the availability of this important resource.

Endometrial receptivity enhancement through induced injury and repair during ovarian stimulation: the Receptivity Enhancement by Follicular-phase Renewal after Endometrial ScratcHing (REFRESH) trial protocol.

STUDY QUESTIONDoes intentional endometrial injury (i.e. endometrial scratching) during ART enhance pregnancy rates?SUMMARY ANSWERWe propose a randomized controlled clinical trial in women performing ART in which the intervention group will undergo an additional endometrial biopsy during exogenous ovarian stimulation.WHAT IS KNOWN ALREADYAlthough endometrial receptivity has been extensively studied, the mechanisms behind the implantation of an embryo remain largely a mystery. Intentional endometrial injury has been put forward by many researchers as an inexpensive clinical tool capable of enhancing endometrial receptivity. However, despite its widespread use, the benefit of endometrial scratching is still a contentious and unresolved issue.STUDY DESIGN, SIZE, DURATIONPragmatic two-arm randomized, single-centre, controlled open-label trial in women undergoing exogenous gonadotropin ovarian stimulation for ART followed by a fresh embryo transfer in a gonadotropin-releasing hormone antagonist suppressed cycle. The trial will include 360 women in total with a 1:1 allocation ratio and an expected total duration of up to 45 months.PARTICIPANTS/MATERIALS, SETTING, METHODSSubjects in the intervention group will undergo an endometrial biopsy during the follicular phase, on the sixth to eighth day of exogenous stimulation. Furthermore, nested within this clinical trial, we will also evaluate whether the transcriptomic signatures of the material collected during the biopsy may accurately distinguish women who become pregnant from those who do not. These endometrial transcriptomic signatures will be assessed both immediately after the biopsy and following in-vitro decidualization.MAIN RESULTS AND THE ROLE OF CHANCEOur primary objective is to assess the effect of endometrial injury during exogenous gonadotropin ovarian stimulation on clinical pregnancy rates after ART. Secondary efficacy and safety outcomes include: live-birth delivery after 24 weeks, the endometrial transcriptomic profile among women in the intervention group, short-term safety (e.g. procedure intolerance due to pain, post-procedure bleeding) and long-term safety (e.g. cancelled transfers, miscarriage) outcomes.LIMITATIONS, REASONS FOR CAUTIONOwing to its pragmatic design, this study may have limited power to determine one or more of our secondary outcomes and whether there are specific subgroups of women who may benefit significantly from performing endometrial scratching and endometrial transcriptomic profiling.WIDER IMPLICATIONS OF THE FINDINGSDespite the weak biological plausibility, heterogeneity in the existing randomized controlled trials and lack of evaluation of any potential risks associated with endometrial scratching, this procedure is still widely applied in current clinical practice. This clinical trial aims to pragmatically assess the potential benefits and harms of the generalized use of this strategy.STUDY FUNDING/COMPETING INTEREST(S)this study has received a grant from the Research Foundation—Flanders (FWO, 1524417N). This organization has no further role in the study, namely with regards to protocol development, study conduction and evaluation of results.TRIAL REGISTRATION NUMBERNCT02061228.TRIAL REGISTRATION DATE10 February 2014.DATE OF FIRST PATIENT’S ENROLMENT3 April 2014.PROTOCOL VERSION2.0.

Impact of multiple blastocyst biopsy and vitrification-warming procedures on pregnancy outcomes

To assess the impact of multiple blastocyst biopsy and vitrification-warming procedures on clinical outcomes. Retrospective study. Private fertility clinic. Preimplantation genetic diagnosis (PGD) patients undergoing comprehensive chromosome screening, including monogenic disorder and chromosome rearrangement cases. Warming and transfer of euploid blastocysts biopsied and vitrified-warmed once (group 1 [G1, control]; n = 2,130), biopsied once but vitrified-warmed twice (group 2 [G2]; n = 34), or biopsied and vitrified-warmed twice (group 3 [G3]; n = 29). Thaw (for transfer) survival rate and clinical pregnancy rate (CPR). The thaw survival rates were 98.4% for G1, 97.3% for G2, and 93.3% for G3, with once biopsied and vitrified-warmed embryos being significantly higher than twice biopsied and vitrified-warmed embryos (G1 vs. G3; P=.032). There was a slight reduction in CPR with an additional vitrification-warming (G1 54.3% vs. G2 47.1%) and larger reduction with an additional embryo biopsy (G2 47.1% vs. G3 31.0%), but neither difference was statistically significant. However, the combined effect of both additional biopsy and vitrification-warming resulted in a significantly reduced CPR (G1 54.3% vs. G3 31.0%; P=.013). This study indicates that blastocysts biopsied and vitrified-warmed twice have reduced clinical outcomes compared with blastocysts biopsied and vitrified-warmed once. PGD patients should be advised that performing a second biopsy and vitrification-warming in cases of failure to obtain a result from initial biopsy will reduce the chance of pregnancy. Patients with inherited disorders may elect to proceed with the second biopsy and vitrification to avoid transfer of embryos with the genetic condition.