Search

Squamous cell carcinoma of the ovary (SCC) is a rare and aggressive disease and optimal treatment is unknown. Here we report the case of a 29- year-old woman who presented with abdominal pain and was ultimately found to have a multi-septate, gas containing pelvic mass with mixed fat, soft tissue, and calcified components concerning for a ruptured teratoma with fistulization to the distal ileum and cecum on imaging. Operative findings included a 20 cm pelvic mass arising from the right ovary with frank invasion into the ileum and cecum and dense adhesion to the anterior abdominal wall on surgical exploration. Pathologic specimens were remarkable for stage IIIC SCC of the ovary arising in a mature teratoma, with a tumor proportion score of 40%. She progressed on first line treatment with cisplatin, paclitaxel and pembrolizumab as well as second line treatment with gemcitabine and vinorelbine. She died nine months after her initial diagnosis.

e18765 Background: An estimated 94,000 women have newly diagnosed gynecologic cancer (ovarian, uterine, cervical, and vulvovaginal) annually–with rates increasing over the last 20 years. Surgical site infections (SSIs) complicate up to 4% of all hysterectomies in the United States. Other surgical sequelae, such as operative length, estimated blood loss, wound dehiscence, and 30-day readmission, further complicate the post-surgical course of this vulnerable population. Methods: A quality improvement initiative was conducted in a large academic health system between January to June 2022 to investigate whether implementing an SSI bundle, defined as a set of 11 evidence-based practices performed collaboratively, can reduce intraoperative and postoperative complications. The study population included women who received gynecologic oncologic surgery. To evaluate trends following the implementation of an SSI prevention bundle, we studied two time periods: 1/1/22-3/31/22 and 4/1/22-6/30/22. Trends were analyzed using chi-squared and a two-sample t-test. Results: Over our six-month study period, 233 patients underwent primary gynecologic oncologic surgery. Robotic-assisted hysterectomies were the most common (27.89%, n = 65), followed by total abdominal hysterectomies (21%, n = 49), laparoscopic hysterectomies (7.72%, n = 18), and supracervical hysterectomies (3%, n = 7). An invasive, abdominal approach was needed for less than half of the surgeries for whom intraoperative and postoperative outcomes were measured (46.35%, n = 108). Following the implementation of our SSI bundle, there was a rise in estimated blood loss (134.49 to 252.67 mL), operative length (199.24 to 227.23 min), and length of stay (1.58 to 2.20 days). Yet, there was a decline in the SSI rate from 4.62% to 3.7% (p = 0.97) and 30-day all-cause readmission from 12.96% to 7.4% (p < 0.05). The overall incidence of 30-day wound dehiscence also declined over six months from 3.7% to 1.85% (p = 0.74). Upon intersectional analysis, patients with SSI were older (55.93 vs. 62, p = 0.39) and were more likely to be obese (BMI 27.04 vs. 31.06, p < 0.05). Individuals with functional status limitations, ECOG score > 2, had longer lengths of stays (4.7 vs. 1.76 days, p < 0.05), estimated blood loss (230 vs. 185.9 mL, p = 0.12), and operative length (374 vs. 205.2 min, p < 0.001). Those with a supracervical hysterectomy also had a longer length of stays (4 days, p < 0.05), blood loss (921.43 mL, p < 0.001), and operative lengths (315.14 min, p < 0.001). Conclusions: Following the implementation of an evidence-based SSI quality improvement project, cancer patients had fewer SSI, hospital readmissions, and wound dehiscence. High ECOG scores, supracervical hysterectomies, and obesity were all associated with worse postoperative outcomes. Prospective studies on postoperative surgical quality are needed to improve care for our most vulnerable patients.

PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Progesterone therapy is a viable treatment for complex atypical hyperplasia (CAH) and endometrial adenocarcinoma, though reliable molecular determinants of response are not available. To explore if analysis of pre-therapy endometrial biopsies could yield biomarkers of response to progesterone, patients with CAH or adenocarcinoma undergoing treatment with progestins were included in this cross-sectional study. Immunohistochemistry for progesterone receptor (PR) was performed. Manual PR expression scores (PRES) were first calculated for biopsies by counting PR-positive nuclei in 12 sensitive vs 9 resistant samples. Significant differences in manual PRES were detected in the stroma (p

OBJECTIVES:To assess whether comprehensive genomic profiling (CGP) in the setting of routine clinical care allows molecular classification of recurrent endometrial cancer (EC) into the four Cancer Genome Atlas (TCGA) categories: POLE ultramutated, microsatellite instable, copy-number low, and copy-number high and whether this approach can identify genomic alterations (GAs) which inform treatment decisions. METHODS:Archival tissues from 74 patients diagnosed with recurrent EC were prospectively analyzed using hybrid-capture-based genomic profiling. Tumor mutational burden and microsatellite instability were measured. Clinically relevant GAs (CRGAs) were defined as GAs associated with targeted therapies available on-label or in mechanism-driven clinical trials. RESULTS:Using POLE mutational analysis, mismatch repair status, and p53 mutational analysis as surrogate for 'copy-number' status CGP segregated all cases into four TCGA molecular subgroups. While recurrent serous ECs were predominantly copy-number high, we found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors. Every tumor sample had at least one GA and 91% (67/74) had at least one CRGA. In this series 32% (24/74) of patients received a matched therapy based on the results of CGP. Objective responses to the matched therapy were seen in 25% (6/24) of patients with an additional 37.5% (9/24) achieving stable disease leading to a clinical benefit rate of 62.5% with a median treatment duration of 14.6 months (range 4.3-69 months). CONCLUSIONS:CGP allows molecular classification of EC into four TCGA categories and allows identification of potential biomarkers for matched therapy in the setting of routine clinical care.

PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell–cell contact. PTPRK regulates cell–cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling. [ABSTRACT FROM AUTHOR]

ObjectivesParents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk.MethodsUsing questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high-risk infants and for comparison in 114 low-risk infants (infants from families without ASD history).ResultsIn low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high-risk infants with GI symptoms were weaned earlier than those without symptoms (P

All girls presenting with virilization (which signifies severe hyperandrogenism) warrant thorough investigation. Ovarian hyperthecosis (OHT) is a rare cause of virilization in premenopausal women. Here, we report the case of a previously healthy 12-year-old Chinese girl with signs of virilization at puberty. Her serum total testosterone was elevated at 5.1 nmol/L (146.97 ng/dL) (normal: <1.4 nmol/L, <40.35 ng/dL). Workup for Cushing syndrome, sex development disorders, congenital adrenal hyperplasia, and adrenal and ovarian androgen-secreting tumors was unrevealing. Ovarian and adrenal venous sampling demonstrated ovarian hyperandrogenism without lateralization. Ovarian biopsy revealed nests of theca cells in the stroma of the right ovary, substantiating the diagnosis of OHT. A single dose of a GnRH analog resulted in the complete suppression of serum testosterone, supporting the diagnosis of OHT. Medical treatment with hormonal replacement therapy normalized serum testosterone levels. Our case report illustrates the diagnostic approach to virilization among girls at puberty and the diagnosis of OHT as the underlying pathology. [ABSTRACT FROM AUTHOR]

Purpose: To identify patient and hospital characteristics associated with extended surgical cytoreduction in the treatment of ovarian cancer. Methods: A retrospective analysis using the National Inpatient Sample (NIS) database identified women hospitalized for surgery to remove an ovarian malignancy between 2013 and 2017. Extended cytoreduction (ECR) was defined as surgery involving the bowel, liver, diaphragm, bladder, stomach, or spleen. Chi-square and logistic regression were used to analyze patient and hospital demographics related to ECR, and trends were assessed using the Cochran-Armitage test. Results: Of the estimated 79,400 patients undergoing ovarian cancer surgery, 22% received ECR. Decreased adjusted odds of ECR were found in patients with lower Elixhauser Comorbidity Index (ECI) scores (OR 0.61, p<0.001 for ECI 2, versus ECI≥3) or residence outside the top income quartile (OR 0.71, p<0.001 for Q1, versus Q4), and increased odds were seen at hospitals with high ovarian cancer surgical volume (OR 1.25, p<0.001, versus low volume). From 2013 to 2017, there was a decrease in the proportion of cases with extended procedures (19% to 15%, p<0.001). There were significant decreases in the proportion of cases with small bowel, colon, and rectosigmoid resections (p<0.001). Patients who underwent ECR were more likely treated at a high surgical volume hospital (37% vs 31%, p<0.001) over the study period. For their hospital admission, patients who underwent ECR had increased mortality (1.6% vs. 0.5%, p<0.001), length of stay (9.6 days vs. 5.2 days, p<0.001), and mean cost ($32,132 vs. $17,363, p<0.001). Conclusions: Likelihood of ECR was associated with increased medical comorbidity complexity, higher income, and undergoing the procedure at high surgical volume hospitals. The proportion of ovarian cancer cases with ECR has decreased from 2013–17, with more cases performed at high surgical volume hospitals. [ABSTRACT FROM AUTHOR]

Congenital cataracts are one of the major causes of childhood‐onset blindness around the world. Genetic diagnosis provides benefits through avoidance of unnecessary tests, surveillance of extraocular features, and genetic family information. In this study, we demonstrate the value of genome sequencing in improving diagnostic yield in congenital cataract patients and families. We applied genome sequencing to investigate 20 probands with congenital cataracts. We examined the added value of genome sequencing across a total cohort of 52 probands, including 14 unable to be diagnosed using previous microarray and exome or panel‐based approaches. Although exome or genome sequencing would have detected the variants in 35/52 (67%) of the cases, specific advantages of genome sequencing led to additional diagnoses in 10% (5/52) of the overall cohort, and we achieved an overall diagnostic rate of 77% (40/52). Specific benefits of genome sequencing were due to detection of small copy number variants (2), indels in repetitive regions (2) or single‐nucleotide variants (SNVs) in GC‐rich regions (1), not detectable on the previous microarray, exome sequencing, or panel‐based approaches. In other cases, SNVs were identified in cataract disease genes, including those newly identified since our previous study. This study highlights the additional yield of genome sequencing in congenital cataracts. [ABSTRACT FROM AUTHOR]

Background: High-grade endometrial stromal sarcomas (HGESS) are very rare uterine tumors, and HGESS during pregnancy is exceedingly rare. This is the first-ever published case of a uterine sarcoma with a concurrent pregnancy that was treated successfully with surgery and adjuvant chemotherapy. Case: A 24-year-old, gravida 1, female at 12 weeks of gestational age presented with vaginal bleeding and was found to have a cervical polyp with spindle-cell malignancy on biopsy. The patient underwent a hysterectomy, bilateral salpingectomy, and lymph node dissection with ovarian preservation. Results: Pathology was diagnostic of HGESS. The patient received adjuvant chemotherapy and remained in remission 15 months postoperatively. Conclusions: Surgery and adjuvant chemotherapy should be strongly considered for the treatment of HGESS during pregnancy. Ovarian preservation should be considered for patients desiring future fertility. (J GYNECOL SURG 34:105) [ABSTRACT FROM AUTHOR]

Objective: To determine whether annual screening reduces ovarian cancer mortality in women with a family history of breast or ovarian cancer. Methods: Data was obtained from the Prostate, Lung, Colorectal, and Ovarian cancer trial, a randomized multi-center trial conducted to determine if screening could reduce mortality in these cancers. The trial enrolled 78,216 women, randomized into either a screening arm with annual serum cancer antigen 125 and pelvic ultrasounds, or usual care arm. This study identified a subgroup that reported a first degree relative with breast or ovarian cancer. Analysis was performed to compare overall mortality and disease specific mortality in the screening versus usual care arm. In patients diagnosed with ovarian cancer, stage distribution, and survival were analyzed as a secondary endpoint. Results: There was no significant difference in overall mortality or disease specific mortality between the two arms. Ovarian cancer was diagnosed in 48 patients in the screening arm and 44 patients in the usual care arm. Screened patients were more likely to be diagnosed at an earlier stage than usual care patients. Patients in the screening arm diagnosed with ovarian cancer experienced a significantly improved survival compared to patients in the usual care arm; relative risk 0.66 (95% CI, 0.47 to 0.93). Conclusion: Screening did not appear to decrease ovarian cancer mortality in participants with a family history of breast or ovarian cancer. Secondary endpoints, however, showed notable differences. Significantly fewer patients were diagnosed with advanced stage disease in the screening arm; and survival was significantly improved. Further investigation is warranted to assess screening efficacy in women at increased risk. [ABSTRACT FROM AUTHOR]

Auxiliary-directed biocatalysis is a powerful and relatively benign tool for chemical synthesis. We recently reported the use of theobromine as a chemical auxiliary for directing CYP3A4-catalyzed oxidations with predictable regio-, chemo- and stereo-selectivity (J. Am. Chem. Soc., 2011, 133, 7853). This highly successful strategy enabled the direct, regio- and stereo-selective hydroxylation of unactivated C–H bonds. However, recovering the products and starting materials from the resulting biocatalytic mixtures has proven challenging. To address this issue, we capitalized on the chemical auxiliary present on the starting material and enzymatic reaction products. The chemical auxiliary was used as a template to generate molecularly imprinted polymers (MIPs). When used in solid-phase extractions, the MIPs reported here allow for the recovery (＞90%) of theobromine-containing products and starting materials from complex mixtures such as cellular membrane extracts. This strategy, which avoids the use of large amounts of organic solvents, represents an effective, easily-tailored, and reusable way to improve the recovered yield of biocatalytic transformations while extending the usefulness of a chemical auxiliary. [ABSTRACT FROM AUTHOR]

Background: Anomalies of the female reproductive tract have been associated with poor pregnancy outcomes. In the case of an ectopic pregnancy, these risks are especially high. Case: A 29-year-old, gravida 1 female with a pregnancy at 9 weeks' gestational age, who presented for care, was found to have a uterine-horn ectopic pregnancy. Imaging confirmed the presence of a unicornuate uterus with the pregnancy located in a noncommunicating uterine horn. Excision of the ectopic pregnancy was recommended, and the patient underwent a robotic assisted resection of the noncommunicating rudimentary uterine horn and the pregnancy. Results: There were no postoperative complications. The patient's pathology was consistent with a tubal/cornual ectopic pregnancy. She stated that she would like to conceive in the future. Any future pregnancies in this patient will need to be monitored closely because of her risk of a higher complication rate. Conclusions: This is the first reported case describing a robotic approach as a feasible treatment option to minimize risk and complications. In the past, the patient in this case would likely have undergone an open procedure at risk for high blood loss and a prolonged recovery time. With the use of this approach, the patient underwent an uncomplicated, minimally invasive procedure with minimal blood loss. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical management of ovarian cancer remains a major clinical challenge as many patients develop resistance to standard platinum-based chemotherapy drugs over time. Testing novel targeted strategies and combination therapies may open the door to new possibilities for the treatment of this disease. One such approach includes targeting p53 with a peptide called ReACp53. While mutations in p53 are common in many cancers, ovarian cancers, in particular, are characterized by the dysfunction of this protein. The aim of this study is to evaluate the potential of combining ReACp53 with standard platinum-based chemotherapy to target ovarian cancer tumor cells. Using in vitro and in vivo preclinical models, we demonstrate enhanced efficacy when combining ReACp53 and carboplatin to target a subset of ovarian cancer cell lines and primary patient tumor samples. Collectively, our results indicate that this combinatorial approach may be applicable for targeting human ovarian tumors. Ovarian malignancies are a leading cause of cancer-related death for US women. High-grade serous ovarian carcinomas (HGSOCs), the most common ovarian cancer subtype, are aggressive tumors with poor outcomes. Mutations in TP53 are common in HGSOCs, with a subset resulting in p53 aggregation and misregulation. ReACp53 is a peptide designed to inhibit mutant p53 aggregation and has been shown efficacious in targeting cancer cells in vitro and in vivo. As p53 regulates apoptosis, combining ReACp53 with carboplatin represents a logical therapeutic strategy. The efficacy of this combinatorial approach was tested in eight ovarian cancer cell lines and 10 patient HGSOC samples using an in vitro organoid drug assay, with the SynergyFinder tool utilized for calculating drug interactions. Results demonstrate that the addition of ReACp53 to carboplatin enhanced tumor cell targeting in the majority of samples tested, with synergistic effects measured in 2 samples, additivity measured in 14 samples, and antagonism measured in 1 sample. This combination was found to be synergistic in OVCAR3 ovarian cancer cells in vitro through enhanced apoptosis, and survival of mice bearing OVCAR3 intraperitoneal xenografts was extended when treated with the addition of ReACp53 to carboplatin versus carboplatin alone. Results suggest that carboplatin and ReACp53 may be a potential strategy in targeting a subset of HGSOCs. [ABSTRACT FROM AUTHOR]

Objective: Palliative care (PC) utilization in cancer care has been shown to alleviate symptoms, increase goals of care discussions, and reduce invasive end of life measures. This study examined the association of inpatient PC consultation with readmission and hospitalization costs among patients with ovarian cancer., Methods: All records for women (≥18 years) hospitalized with a diagnosis of ovarian cancer were tabulated from the 2010-2020 Nationwide Readmissions Database. Multivariable logistic, Poisson, and linear regressions were used to evaluate the association of PC consultation during index hospitalization with length of stay, rates of 30-day non-elective readmission, time to readmission, as well as overall number of readmissions and hospitalization costs., Results: Of an estimated 285,487 patients included, 25,957 (9.0%) received a PC consultation, with an increase from 5.1 to 11.7% ( P < 0.001) across the period. Factors associated with use of PC included: increasing age (AOR 1.03/yr, 95% CI 1.03-1.03, P < 0.001) and Elixhauser comorbidity index (AOR 1.19/point, 95% CI 1.17-1.21). PC was associated with lower risk adjusted rates of 30 day (11.63%, 95% CI 11.0-12.3 vs 20.25%, 95% CI 20.0-20.6) non-elective readmission ( P < 0.001). The adjusted incident rate ratio of readmission after PC consultation was 0.41 [0.38-0.43], P < 0.001. Patients receiving PC additionally had less cost associated with their index hospital stay; -$2,407 [-$2,669.86- -$2,144.43], P < 0.001)., Conclusions: Inpatient PC consults appear to be associated with reduced medical readmissions for patients with ovarian cancer, as well as decreased hospital resource use, however disparities exist. Continued increase in access and early PC referral should be considered., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The inherent advantages of red-shifted fluorescent proteins and fluorescent protein-based biosensors for the study of signaling processes in neurons and other tissues have motivated the development of a plethora of new tools. Relative to green fluorescent proteins (GFPs) and other blue-shifted alternatives, red fluorescent proteins (RFPs) provide the inherent advantages of lower phototoxicity, lower autofluorescence, and deeper tissue penetration associated with longer wavelength excitation light. All other factors being the same, the multiple benefits of using RFPs make these tools seemingly ideal candidates for use in neurons and, ultimately, the brain. However, for many applications, the practical utility of RFPs still falls short of the preferred GFPs. We present an overview of RFPs and RFP-based biosensors, with an emphasis on their reported applications in neuroscience.