Publications by authors named "Jenna Marcus"

26 Publications

  • Page 1 of 1

Infliximab De-escalation in Patients With Crohn's Disease in Clinical Remission Is Safe and Well-tolerated.

Inflamm Bowel Dis 2021 Jun 18. Epub 2021 Jun 18.

Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1093/ibd/izab131DOI Listing
June 2021

The ASCCP Cervical Cancer Screening Task Force Endorsement and Opinion on the American Cancer Society Updated Cervical Cancer Screening Guidelines.

J Low Genit Tract Dis 2021 Jul;25(3):187-191

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.

Abstract: The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.
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http://dx.doi.org/10.1097/LGT.0000000000000614DOI Listing
July 2021

Pitfalls in Frozen Section: A Case of Incidental Papillary Mesothelioma.

Int J Surg Pathol 2021 May 12:10668969211018259. Epub 2021 May 12.

12286Rutgers-New Jersey Medical School, Newark, NJ, USA.

Well-differentiated papillary mesothelioma is an uncommon benign, although potentially recurrent mesothelial lesion that occurs in the peritoneum of women over a wide age range. We recently encountered an incidental case sent for frozen section at the time of hysterectomy for endometrial carcinoma. Familiarity with this lesion will help prevent overinterpretation as a serous carcinoma.
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http://dx.doi.org/10.1177/10668969211018259DOI Listing
May 2021

Predictors and Outcomes of Ustekinumab Dose Intensification in Ulcerative Colitis: A Multicenter Cohort Study.

Clin Gastroenterol Hepatol 2021 Mar 26. Epub 2021 Mar 26.

Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Ustekinumab has been shown to be effective for the treatment of ulcerative colitis (UC); however, >40% of patients have suboptimal clinical response after induction and maintenance dosing every 8 weeks. The best management approach for these patients is unclear. Many undergo empiric dose intensification to every 4 weeks or every 6 weeks, a nonstandardized decision because of limited data supporting therapeutic drug monitoring of ustekinumab. In Crohn's disease, approximately 50% of patients undergo ustekinumab dose intensification, which seems to be effective based on prior work from our group and others. However, similar data in UC are lacking. In this real-world multicenter cohort study, we sought to identify predictors and outcomes of ustekinumab dose intensification in UC.
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http://dx.doi.org/10.1016/j.cgh.2021.03.028DOI Listing
March 2021

COVID-19 Vaccination Intent and Perceptions Among Patients With Inflammatory Bowel Diseases.

Clin Gastroenterol Hepatol 2021 08 4;19(8):1730-1732.e2. Epub 2021 Feb 4.

Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Patients with inflammatory bowel disease (IBD) develop coronavirus disease 2019 (COVID-19) at similar rates as the general population, and there was initial concern regarding potential for severe illness. Vaccinations were authorized for emergency use in the United States in December 2020 and aim to halt the spread of COVID-19. However, there are concerns that people will be hesitant to receive the vaccine for a variety of reasons including insufficient data in certain populations including those with IBD. We surveyed patients with IBD to identify potential concerns regarding COVID-19 vaccination.
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http://dx.doi.org/10.1016/j.cgh.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859624PMC
August 2021

A Pilot Study of Human Papillomavirus Detection in Urine Using a Novel Nucleic Acid Amplification Test.

J Appl Lab Med 2021 Mar;6(2):474-479

Albert Einstein College of Medicine, Bronx, NY, USA.

Introduction: Human papillomavirus (HPV) testing is the standard-of-care for cervical cancer screening globally. Urine is a promising alternative to collecting a cervical specimen during a pelvic exam for HPV testing. There are no studies to date of HPV testing of urine using the Xpert HPV test.

Methods: We conducted a pilot study of 40 women; 30 women undergoing colposcopy because of a previous abnormality and 10 undergoing routine screening, to evaluate HPV detection in urine by the Xpert HPV test on the GeneXpert platform. Xpert HPV testing of urine was done according to the manufacturer's instructions for testing cervical specimens. These results were compared to a reference of combined results of 2 research HPV genotyping tests conducted on cervical specimens and to repeat Xpert HPV testing of urine.

Results: Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as HPV positive if at least 1 test was positive, were 64.3% (95% confidence interval [95%CI]  = 42.1-76.1%) and 100% (97.5%CI = 71.5-100%), respectively. Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as positive if both tests were positive, were 66.7% (95%CI = 44.7-84.4%) and 86.7% (95%CI = 59.5-98.3%), respectively. Kappa values for first vs. second and first vs. third testing of urine by Xpert were 0.89 (95%CI = 0.79-1.00) and 0.90 (95%CI = 0.81-1.00), respectively.

Discussion: Given the call for global elimination of cervical cancer and widespread availability of GeneXpert, optimizing Xpert HPV testing of urine may be warranted.
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http://dx.doi.org/10.1093/jalm/jfaa238DOI Listing
March 2021

Direct oral anticoagulant use in gynecologic oncology: A Society of Gynecologic Oncology Clinical Practice Statement.

Gynecol Oncol 2021 01 28;160(1):312-321. Epub 2020 Nov 28.

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United States of America.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.
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http://dx.doi.org/10.1016/j.ygyno.2020.11.020DOI Listing
January 2021

Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.

Inflamm Bowel Dis 2020 Nov 6. Epub 2020 Nov 6.

Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.

Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.

Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).

Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
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http://dx.doi.org/10.1093/ibd/izaa283DOI Listing
November 2020

Predictors of Ustekinumab Failure in Crohn's Disease After Dose Intensification.

Inflamm Bowel Dis 2021 Jul;27(8):1294-1301

Division of Gastroenterology, Hepatology and Endoscopy, Boston, MA.

Background: Many patients with Crohn's disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD.

Methods: This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors of these outcomes.

Results: We included 123 patients who underwent ustekinumab dose intensification to q4w (n = 64), q5w (n = 1), q6w (n = 55), or q7w (n = 3). Multivariable logistic regression demonstrated that perianal disease, Harvey-Bradshaw Index, and opioid use at time of intensification were associated with failure to achieve remission. Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic.

Conclusion: Perianal disease, Harvey-Bradshaw Index, current opioid use, and current corticosteroid use are associated with ustekinumab failure after dose intensification in CD. Larger, prospective studies are needed to corroborate these findings and guide therapeutic strategies for patients who lose response to standard ustekinumab dosing.
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http://dx.doi.org/10.1093/ibd/izaa282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314105PMC
July 2021

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.

Clin Gastroenterol Hepatol 2021 Aug 6;19(8):1627-1634. Epub 2020 Jul 6.

Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Background & Aims: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis.

Methods: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT.

Results: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death.

Conclusions: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.
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http://dx.doi.org/10.1016/j.cgh.2020.06.051DOI Listing
August 2021

A demonstration of automated visual evaluation of cervical images taken with a smartphone camera.

Int J Cancer 2020 11 19;147(9):2416-2423. Epub 2020 May 19.

Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

We examined whether automated visual evaluation (AVE), a deep learning computer application for cervical cancer screening, can be used on cervix images taken by a contemporary smartphone camera. A large number of cervix images acquired by the commercial MobileODT EVA system were filtered for acceptable visual quality and then 7587 filtered images from 3221 women were annotated by a group of gynecologic oncologists (so the gold standard is an expert impression, not histopathology). We tested and analyzed on multiple random splits of the images using two deep learning, object detection networks. For all the receiver operating characteristics curves, the area under the curve values for the discrimination of the most likely precancer cases from least likely cases (most likely controls) were above 0.90. These results showed that AVE can classify cervix images with confidence scores that are strongly associated with expert evaluations of severity for the same images. The results on a small subset of images that have histopathologic diagnoses further supported the capability of AVE for predicting cervical precancer. We examined the associations of AVE severity score with gynecologic oncologist impression at all regions where we had a sufficient number of cases and controls, and the influence of a woman's age. The method was found generally resilient to regional variation in the appearance of the cervix. This work suggests that using AVE on smartphones could be a useful adjunct to health-worker visual assessment with acetic acid, a cervical cancer screening method commonly used in low- and middle-resource settings.
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http://dx.doi.org/10.1002/ijc.33029DOI Listing
November 2020

Severe hypertriglyceridemia during treatment with intraperitoneal cisplatin and paclitaxel for advanced stage fallopian tube carcinoma.

Gynecol Oncol Rep 2020 May 20;32:100552. Epub 2020 Feb 20.

Rutgers New Jersey Medical School, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Women's Health, Newark, NJ, United States.

This case report describes a patient who developed severe hypertriglyceridemia (1871 mg/dL) and hyperlipidemia (LDL 132 mg/dL) during intraperitoneal (IP) administration of cisplatin and paclitaxel as adjuvant treatment for stage IIIC fallopian tube carcinoma. After an evaluation with her primary care physician, she was treated with gemfibrozil and rosuvastatin for the duration of her treatment. There was complete resolution of hypertriglyceridemia after completion of chemotherapy. This adverse event is rare and has not been reported in the literature with this chemotherapeutic regimen. A pre-chemotherapy evaluation for dyslipidemia may be beneficial in the detection and monitoring of this condition.
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http://dx.doi.org/10.1016/j.gore.2020.100552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049626PMC
May 2020

Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridioides difficile Infection.

J Clin Gastroenterol 2020 09;54(8):701-706

Department of Medicine.

Goals: We investigated the long-term efficacy and safety of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI).

Background: FMT has emerged as a promising therapy for patients with rCDI unresponsive to standard medical therapy, though long-term efficacy and safety data are scarce.

Materials And Methods: A multicenter retrospective study was performed on patients treated with FMT for rCDI with ≥6 months of clinical follow-up post-FMT. Patients were contacted to document sustained efficacy, potential adverse events, and antibiotic exposure. The electronic medical record was reviewed to confirm patient-reported outcomes and obtain additional data. The primary outcome was sustained cure, as defined by the absence of Clostridioides difficile infection (CDI) at any timepoint after FMT.

Results: Of 528 patients treated, 207 were successfully contacted. The mean follow-up post-FMT was 34 (range: 6 to 84) months. One hundred fifty-seven patients (75.8%) reported sustained cure at the time of follow-up. One hundred patients (48%) reported the use of antibiotics for non-CDI indications post-FMT, of whom 11 (11%) had experienced CDI post-FMT. Fifty-two of the original 528 patients (9.8%) treated with FMT had died at the time of follow-up contact; none were felt attributable to the procedure. New medical conditions or diagnoses post-FMT were reported in 105 patients (50.5%). Fifteen reported improvement post-FMT in previously diagnosed medical conditions.

Conclusions: In this largest and longest study to date on efficacy and safety after FMT for treatment of rCDI, we found that the majority of patients experienced long-term cure. Although a number of new conditions developed post-FMT, there was no clustering of diseases associated with dysbiosis.
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http://dx.doi.org/10.1097/MCG.0000000000001281DOI Listing
September 2020

A Deceptive Spread: Myoinvasion of Endometrial Carcinoma Imitating Adenoma Malignum.

Int J Surg Pathol 2020 May 5;28(3):284-286. Epub 2019 Nov 5.

Rutgers-New Jersey Medical School, Newark, NJ, USA.

Endometrioid type of endometrial carcinoma is the most common form of uterine malignancy. The majority of patients in the developed world present with the low-grade, low-stage type of this malignancy. The current treatment of early-stage endometrioid carcinoma provides most patients with a favorable outcome. One of the important factors that determine the outcome of early-stage endometrial carcinoma is the involvement of cervical stroma. One of the very rare forms of cervical stromal involvement by endometrioid carcinoma is termed "adenoma malignum type" invasion due to its similarity to the infamously deceptive type of cervical adenocarcinoma called adenoma malignum. Since adenoma malignum is often discovered incidentally, finding adenoma malignum type of myoinvasion may deceive a pathologist to diagnose the simultaneous presence of endometrial carcinoma and adenoma malignum in the same patient as 2 separate entities. Also, this type of myoinvasion may be missed altogether for its subtle nature. In this article, we report a case of low-grade, low-stage endometrioid carcinoma with adenoma malignum type of myoinvasion. We have pointed out the subtle nature of this lesion and the important features to remember to successfully identify it.
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http://dx.doi.org/10.1177/1066896919886113DOI Listing
May 2020

Clinical Predictors of Recurrence After Primary Clostridioides difficile Infection: A Prospective Cohort Study.

Dig Dis Sci 2020 06 30;65(6):1761-1766. Epub 2019 Oct 30.

Massachusetts Host-Microbiome Center, Brigham and Women's Hospital, Boston, MA, USA.

Background: Recurrent Clostridioides difficile infection (CDI) is a major public health threat. While clinical prediction tools exist, they do not incorporate the newest Infectious Diseases Society of America guidelines.

Methods: This was a prospective longitudinal study of patients experiencing their first episode of uncomplicated CDI. Patients were followed from diagnosis through 8 weeks post-completion of their anti-CDI therapy to assess recurrence. Stool was collected at diagnosis and weekly for 8 weeks following treatment. Recurrence was defined as diarrhea as well as a positive stool test by toxin EIA (EIA) for C. difficile. Fisher's exact test for binary variables and Student's t test for continuous variables were performed. Cox regression was performed to assess for predictors of CDI recurrence.

Results: Seventy-five patients were enrolled between August 1, 2015, and September 1, 2018. Mean age 58.1 years ± 15.5, 69.3% female, 74.7% were white, 11.3% had baseline irritable bowel syndrome, and 54.7% were actively using PPIs. Over the 8-week follow-up period, 22 patients developed a confirmed CDI recurrence. Univariate predictors of recurrence included treatment with metronidazole (40.9% vs 15.1%, p = 0.03), initially diagnosis by EIA (77.3% vs 43.4%, p = 0.007) and platelet count (206 ± 72.1 vs 270.9 ± 114.8, p = 0.03). A Cox regression model revealed primary diagnosis by EIA (HR 3.39, 95% CI 1.23, 9.31, p = 0.018) and treatment with metronidazole (HR 3.27 95% CI 1.31-8.19, p = 0.01) remain predictors for CDI recurrence.

Conclusion: In a large prospective longitudinal cohort of uncomplicated CDI patients, treatment with metronidazole and diagnosis via EIA were the most robust predictors of CDI recurrence.
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http://dx.doi.org/10.1007/s10620-019-05900-3DOI Listing
June 2020

Correction: Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions.

Oncogene 2020 Feb;39(8):1830

Genetics, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.

The original version of this Article contained an error in the author affiliations. Vladislav V. Verkhusha was incorrectly associated with the School of Mathematics, Statistics & Applied Mathematics, National University of Ireland Galway, Galway, Ireland. The correct affiliation is Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.
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http://dx.doi.org/10.1038/s41388-019-1039-4DOI Listing
February 2020

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

Gynecol Oncol 2019 10 16;155(1):39-50. Epub 2019 Aug 16.

Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan.

Objective: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer.

Methods: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy.

Results: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged.

Conclusion: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.
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http://dx.doi.org/10.1016/j.ygyno.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537353PMC
October 2019

Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions.

Oncogene 2019 07 8;38(30):5839-5859. Epub 2019 Jul 8.

Genetics, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.

The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells.
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http://dx.doi.org/10.1038/s41388-019-0844-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859949PMC
July 2019

Pitfalls of Frozen Section in Gynecological Pathology: A Case of Ovarian Serous Surface Papillary Adenofibroma Imitating Malignancy.

Int J Surg Pathol 2019 May 18;27(3):268-270. Epub 2018 Dec 18.

1 Rutgers-New Jersey Medical School, Newark, NJ, USA.

Serous cystadenofibromas are uncommon benign ovarian lesions, consisting of both fibrous and epithelial components, that are usually cystic but may contain solid or papillary architecture that can be confused with a malignancy on imaging. Papillary architecture seen on frozen section may also falsely steer the pathologist in the direction of a diagnosis of a borderline serous tumor. Overcalling the lesion may lead to more aggressive surgery than necessary, so extensive tissue sampling and consideration of this entity is important in possibly avoiding this mistake.
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http://dx.doi.org/10.1177/1066896918818894DOI Listing
May 2019

Pitfalls of Frozen Section in Gynecological Pathology: A Rare Case of Ovarian Lymphoma in an HIV-Positive Woman Resembling Dysgerminoma on Frozen Section.

Int J Surg Pathol 2019 Jun 25;27(4):387-389. Epub 2018 Nov 25.

1 Rutgers-New Jersey Medical School, Newark, NJ, USA.

Primary lymphoma of the ovary, particularly in an HIV-positive woman, is exceptionally rare, and ovarian lymphoma may not be considered at the time of intraoperative consultation. In this article, we present a case in an HIV-positive woman thought to be a dysgerminoma at the time of frozen section, but which was found to be a diffuse large B-cell lymphoma of the ovary.
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http://dx.doi.org/10.1177/1066896918813658DOI Listing
June 2019

Multicystic Mesothelioma of the Omentum Presenting as an Incidental Finding.

Int J Surg Pathol 2019 Apr 2;27(2):174-175. Epub 2018 Sep 2.

1 Rutgers New Jersey Medical School, Newark, NJ, USA.

Multicystic mesotheliomas of peritoneal origin (also termed benign multicystic mesotheliomas) are uncommon and are exceptionally rare in the omentum. Lack of familiarity of this entity could lead to overinterpretation as a malignancy or present a challenge at frozen section. We describe a case of multicystic mesothelioma arising in the omentum found incidentally at laparotomy for endometriosis. Frozen section evaluation presented a challenge. Grossly, the mass in the omentum was multicystic and mucoid, raising the concern for a mucinous neoplasm. The cysts, however, were lined by flattened cells without atypia. At permanent section evaluation, calretinin positivity confirmed the mesothelial origin. Awareness of this entity is important, as it may be interpreted as a malignancy, particularly intraoperatively.
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http://dx.doi.org/10.1177/1066896918796290DOI Listing
April 2019

Female Sex Hormone Receptor Profiling in Uterine Adenosarcomas.

Int J Gynecol Cancer 2018 03;28(3):500-504

Objective: This study aimed to identify the hormonal receptor status in uterine adenosarcoma (AS) and uterine AS with sarcomatous overgrowth (AS + SO), including those with high-grade histologic features (nuclear pleomorphism, atypical mitoses, necrosis), with or without heterologous elements. Estrogen receptor (ER) status, including estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein-coupled estrogen receptor (GPER), and progesterone receptor (PgR) status were examined.

Methods: From August 2001 to November 2013, 11 patients with histologic diagnosis of uterine AS were identified. Tumor tissue sections were stained for ERα, ERβ, GPER, and PgR and examined both for percentage of overall cells stained and for intensity of staining. Descriptive statistics were calculated using clinicopathologic data abstracted from the medical record.

Results: Eight cases of AS and 3 cases of AS with high-grade features were identified. Seven of 8 tumor samples of AS showed strong or moderate intensity immunostaining for ERα; all AS + SO tumor samples showed minimal to no immunoreactivity for ERα. There was a significant decrease in ERα H scores in high-grade tumors when compared with AS (P = 0.01). Lower PgR H scores were observed in high-grade tumors compared with those in AS (P = 0.04). Estrogen receptor β immunostaining was variable, and GPER immunostaining was absent in the majority of tumor samples.

Conclusions: Higher expression of ERα and PgR was observed in AS when compared with those with AS + SO and high-grade features. Both tumor subtypes showed similar levels of ERβ and GPER expression, although significant differences in ERβ and GPER expression were not detected. In contrast to our previous findings in uterine carcinosarcoma, ERs ERβ and GPER do not seem to play a significant role in AS in this study.
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http://dx.doi.org/10.1097/IGC.0000000000001183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125779PMC
March 2018

Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer.

Gynecol Oncol 2017 12 4;147(3):558-564. Epub 2017 Oct 4.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Objective: Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer.

Methods: This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching.

Results: Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78).

Conclusion: Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2017.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523384PMC
December 2017

Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma.

J Surg Oncol 2018 Feb 8;117(2):236-244. Epub 2017 Aug 8.

Ovarian Cancer Action Research Center, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.

Background And Objectives: To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI.

Methods: This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome.

Results: LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047).

Conclusion: LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.
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http://dx.doi.org/10.1002/jso.24801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526036PMC
February 2018

Virilization and Enlarged Ovaries in a Postmenopausal Woman.

Int J Surg Pathol 2017 Sep 6;25(6):507-508. Epub 2017 Jun 6.

1 Rutgers-New Jersey Medical School, Newark NJ, USA.

A patient with postmenopausal bleeding and virilization was found to have bilaterally enlarged ovaries with a yellow cut surface. Histology revealed cortical stromal hyperplasia with stromal hyperthecosis. This hyperplastic condition should not be mistaken for an ovarian neoplasm.
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http://dx.doi.org/10.1177/1066896917713134DOI Listing
September 2017
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