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39 result(s) for "Ramalingam, Preetha"
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Ovarian teratomas: clinical features, imaging findings and management
Ovarian teratomas are the most common type of germ cell tumors. There are three major subtypes of ovarian teratomas including mature, immature, and monodermal teratomas. Ultrasound, computed tomography and magnetic resonance imaging can demonstrate specific imaging findings for mature teratoma. Imaging features of immature and monodermal teratomas are less specific, but a combination of clinical features and imaging findings can help in the diagnosis. Imaging is also very helpful in guiding management. In this article, we review the epidemiology, histopathology, clinical presentation, imaging features and management of ovarian teratomas.
ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer
ObjectiveThe objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer.MethodsFrom April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2–IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an ‘inadvertent’ simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only.Results100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23–67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients—that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0–68.3). Three patients developed recurrent disease within 2 years of surgery—that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%).DiscussionOur prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.
Transition From a Standard to a Hybrid On-Site and Remote Anatomic Pathology Training Model During the Coronavirus Disease 2019 (COVID-19) Pandemic
As teaching hospitals institute social distancing and defer nonemergent procedures to cope with the coronavirus disease 2019 pandemic, the need for daily on-site presence, unless necessary, has been reduced for all medical staff, including trainees. Pathology training programs must adapt to these changes to ensure overall safety without significantly compromising training and the educational mission of the institution. To describe the hybrid on-site and remote anatomic pathology training model in response to the coronavirus disease 2019 pandemic that was implemented in our pathology department and report the clinical fellows' responses to the survey about their experiences. The hybrid model was implemented March 25, 2020. Fellows alternate weekly between working on site and working remotely. On site, fellows wear personal protective equipment and maintain social distancing. Remotely, fellows use digital pathology to review cases and supplement with online educational activities. Virtual \"coffee breaks,\" meditation, and exercise are part of the curriculum. Online platforms, including WebEx, Google Classroom, and Canvas, are used to continue educational activities. The survey was open May 19 through June 8, 2020. Twenty-eight of the 29 clinical fellows (96%) responded. Many of the respondents indicated substantial increase in their skill with using digital pathology and online platforms during the pandemic. The top most helpful resources were the United States and Canadian Academy of Pathology interactive microscopy courses (found very or somewhat helpful by 22 of 23 clinical fellows; 96%), ExpertPath (19 of 23; 82%), the College of American Pathologists virtual learning series (18 of 23; 78%), the World Health Organization Blue Books (16 of 23; 70%), the American Society of Cytopathology webinars (14 of 23; 61%), and our institutional digital slide collection (12 of 23; 52%). Hybrid on-site and remote training can maximize anatomic pathology learning opportunities while maintaining the safety of trainees, hospital personnel, and the community.
Comparative genomics of high grade neuroendocrine carcinoma of the cervix
In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.
A paper-based HPV E7 oncoprotein assay for cervical precancer detection at the point of care
Cervical cancer, while preventable through screening and treatment of cervical precancer, remains a global challenge with a disproportionately high burden of disease in resource-limited settings, especially in low- and middle-income countries (LMICs). Lack of affordable, easy-to-use screening and diagnostic tests contributes to this disparity. Most commercially available tests are not appropriate for use in LMICs due to resource constraints. Specifically, HPV mRNA and oncoprotein tests that have high specificity for cervical precancer and cancer require complex sample preparation protocols and expensive instrumentation. To address these limitations, an HPV E7 oncoprotein assay for HPV16, 18, and 45 was developed that is appropriate for use at the point of care. The assay is paper-based, involves only five simple steps, and does not require instrumentation. A clinically relevant limit of detection was demonstrated with cellular samples. Additionally, clinical performance was demonstrated with a small pilot study ( n  = 19), in which the HPV E7 paper-based assay was found to have 95% accuracy when compared to histopathologic diagnosis of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+). With further clinical validation, this assay could enable highly specific point-of-care testing for cervical precancer and cancer that is instrumentation-free, affordable, and ideal for use in resource-limited settings.
Long-term outcomes after cervical cancer screening in El Salvador: primary human papillomavirus screen-and-treat compared with cytology
IntroductionFrom 2012 to 2017, the Cervical Cancer Prevention in El Salvador (CAPE) piloted and scaled up a human papillomavirus (HPV) screen-and-treat intervention. Findings resulted in El Salvador’s adoption of the strategy as part of the national programme, but long-term clinical outcomes are unknown. Here, we compare the detection of high-grade cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and HPV infection after recommended screening intervals between two groups: women who participated in CAPE and a comparable group screened via cytology.MethodsCAPE participants who had undergone screening at least 5 years previously (screen-and-treat group) and women in the same age range with conventional cytology screening 2 to 3 years previously (cytology group) were recruited for repeat screening with primary HPV testing. Women with positive HPV results were referred for colposcopy and cervical biopsy to determine further management. Women with negative HPV results received recommendations for routine future screening according to national guidelines.ResultsA total of 6631 women were enrolled (screen-and-treat = 4087; cytology=2544). Significantly less CIN2+ was detected in the screen-and-treat group at 0.7% (29/4087) than in the cytology group at 2.1% (54/2544) (p<0.001) with a risk ratio of 0.41 (95% CI 0.26 to 0.61). HPV positivity was also lower in the screen-and-treat group at 9.5% (388/4077) compared with the cytology group at 11.5% (293/2445) (p=0.008).ConclusionAt the first round of repeat screening after the implementation of CAPE, women who underwent HPV testing in a screen-and-treat strategy had significantly less CIN2+ and HPV positivity compared with those who underwent cytology. These outcomes occurred despite a longer screening interval for HPV testing than cytology. Findings provide reassurance for women and health systems that primary HPV screen-and-treat programmes with extended screening intervals, like the one in El Salvador, are achievable and effective in low- and middle-income settings.
Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms
Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression not only in SCLC but also in different NEN types. This comprehensive characterization of DLL3 can help guide future clinical trial design targeting DLL3 in NEN including LCNEC and EP-NEN that are lacking standard of care treatment options.
Advanced stage (FIGO IVB) neuroendocrine cervical carcinoma
A 41-year-old gravidity 5/parity 3 (G5P3) woman presented with a 6 month history of intermittent vaginal spotting. Two months before consultation, she began having lower abdominal and pelvic pain and two episodes of postcoital bleeding. Although she had an abnormal pap smear 5 years previously, her most recent pap smear obtained 2 years prior to symptom onset was normal. After the second episode of postcoital bleeding, the patient consulted her gynecologist who performed a pap smear that was negative for intraepithelial lesion or malignancy but positive for human papillomavirus (HPV) 18. Pelvic examination revealed normal vaginal mucosa and an enlarged cervix with a 5 cm exophytic and necrotic nodular lesion along the cervical os. There was no vaginal or parametrial extension. Cervical biopsies and endocervical curettage were obtained.