British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for genetic testing in epithelial ovarian cancer in the United Kingdom.

Standard of care genetic testing has undergone significant changes in recent years. The British Gynecological Cancer Society and the British Association of Gynecological Pathologists (BGCS/BAGP) has re-assembled a multidisciplinary expert consensus group to update the previous guidance with the latest standard of care for germline and tumor testing in patients with ovarian cancer. For the first time, the BGCS/BAGP guideline group has incorporated a patient advisor at the initial consensus group meeting. We have used patient focused groups to inform discussions related to reflex tumor testing - a key change in this updated guidance. This report summarizes recommendations from our consensus group deliberations and audit standards to support continual quality improvement in routine clinical settings.

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC). METHODS: Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node). RESULTS: Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions. CONCLUSIONS: Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01505829.

Diffusion-weighted MRI in Advanced Epithelial Ovarian Cancer: Apparent Diffusion Coefficient as a Response Marker.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10-5mm2s-1) was repeatable (upper and lower 95% limits of agreement of 12 × 10-5mm2s-1 [95% confidence interval {CI}: 6 × 10-5mm2s-1 to 18 × 10-5mm2s-1] and -15 × 10-5mm2s-1 [95% CI: -21 × 10-5mm2s-1 to -9 × 10-5mm2s-1]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS. OBJECTIVE: To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. METHOD: Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes. RESULTS: We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. CONCLUSIONS: This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

Modelling DW-MRI data from primary and metastatic ovarian tumours.

OBJECTIVES: To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer. METHODS: Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*). RESULTS: Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1%, DDC 4.3%, α 7.0%, D 13.2%, f 44.0%, D* 165.1%. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64% of lesions. CONCLUSIONS: The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability. KEY POINTS: • DW-MRI data in ovarian cancer show deviation from mono-exponential behaviour • Parameters derived from the stretched exponential model showed good repeatability (CV 7%) • The bi-exponential model was unsuitable because of poor parameter repeatability • The stretched exponential model showed comparable repeatability to the mono-exponential model • The extra parameter (α) provides scope for investigation of heterogeneity or response.

The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know.

Many treatment options are available to patients with endometrial, cervical, or ovarian cancer. Magnetic resonance (MR) imaging plays an important role in the patient journey from the initial evaluation of the extent of the disease to appropriate treatment selection and follow-up. The purpose of this review is to highlight the added role of MR imaging in the treatment stratification and overall care of patients with endometrial, cervical, or ovarian cancer. Several MR imaging techniques used in evaluation of patients with gynecologic malignancies are described, including both anatomic MR imaging sequences (T1- and T2-weighted sequences) and pulse sequences that characterize tissue on the basis of physiologic features (diffusion-weighted MR imaging), dynamic contrast agent-enhanced MR imaging, and MR spectroscopy. MR imaging findings corresponding to the 2009 revised International Federation of Gynecology and Obstetrics staging of gynecologic malignancies are also described in detail, highlighting possible pearls and pitfalls of staging. With the growing role of the radiologist as a core member of the multidisciplinary treatment planning team, it is crucial for imagers to recognize that MR imaging has become central in tailoring treatment options and therapy in patients with gynecologic malignancies.

Urethral Mesh Assessment in Cancer Patients.

Urethral mesh placement has become a common surgical intervention for the management of stress urinary incontinence. While this procedure offers significant benefits, it is not without potential complications. This review article aims to provide a comprehensive overview of urethral mesh assessment in oncologic patients. The article explores normal magnetic resonance imaging (MRI) and computed tomography (CT) mesh appearances and highlights the pathological aspects associated with urethral mesh complications including both short-term and long-term post-operative complications. By understanding the spectrum of normal findings of urethral mesh and the possible complications, clinicians can improve patient outcomes and make informed decisions regarding urethral mesh management in this patient population.

The revised FIGO staging system for uterine malignancies: implications for MR imaging.

Cancers of the uterine corpus and cervix are the most common gynecologic malignancies worldwide. The International Federation of Gynecology and Obstetrics (FIGO) staging system was first established in 1958, when it was recognized that the recurrence rate and patient outcomes were directly related to the degree of tumor spread at the patient's initial presentation. Changes in understanding of tumor biology led to a recent update in the FIGO staging system that reflects the variation in treatment strategies between endometrial and cervical cancer. Patients with endometrial cancer are primarily treated with hysterectomy; thus, staging is done at surgery and histologic analysis. Magnetic resonance (MR) imaging may accurately depict the extent of endometrial cancer at diagnosis and, in conjunction with the tumor grade and histologic subtype, help stratify risk, which determines the therapeutic course. Cervical carcinoma is staged at clinical examination because many tumors are inoperable at the time of patient presentation. Preoperative MR imaging criteria are not formally included in the revised FIGO staging system because cervical carcinoma is most prevalent in developing countries, where imaging resources are limited. However, MR imaging is highly sensitive and specific for depicting important prognostic factors and, when available, is recommended as an adjunct to clinical examination. The MR imaging findings of uterine carcinoma should be discussed in a multidisciplinary setting in conjunction with clinical and histologic findings, an approach that provides accurate staging and risk stratification and allows for individualized treatment.

Evaluation of the Efficacy of a Hypoglycemia Protocol to Treat Severe Hypoglycemia.

PURPOSE: The purpose of this quality improvement project was to evaluate the efficacy of the facility's Hypoglycemia Protocol when treating severe hypoglycemia (defined as blood glucose < 50 mg/dL). DESCRIPTION: The diabetes clinical nurse specialists conducted a retrospective chart review of diabetic inpatients with severe hypoglycemia who were treated per the Hypoglycemia Protocol from October 1, 2017, through April 30, 2019. The primary outcome was achievement of euglycemia (defined as blood glucose ≥ 80 mg/dL) 15 to 30 minutes post treatment with either oral carbohydrates or intravenous dextrose. OUTCOME: Two hundred twenty-two patients received treatment with oral carbohydrates versus 120 patients who received intravenous dextrose. Fifty patients receiving oral carbohydrates versus 106 patients receiving intravenous dextrose achieved euglycemia after 1 treatment. Compared with treatment with intravenous dextrose, the odds ratio of the rise in blood glucose to 80 mg/dL or greater within 15 to 30 minutes post treatment for a patient given oral carbohydrate was decreased by 97.2%. CONCLUSION: Intravenous dextrose was more efficacious than oral carbohydrate treatment in patients with diabetes experiencing severe hypoglycemia. In response, the Hypoglycemia Protocol was revised to increase oral carbohydrate treatment for severe hypoglycemia and to expedite escalation from oral to intravenous treatment.

Placental MRI: Identification of radiological features to predict placental attachment disease regardless of reader expertise.

PURPOSE: To compare the accuracy of placental MRI in reporting placental adhesive disease in readers with different expertise and to identify the most reliable MRI features that predict placental pathology regardless of reader expertise. METHODS: Retrospective analysis of 27 placental MRI studies by six radiologists with different expertise levels; specificity, sensitivity, and accuracy were used to quantify the predictive performance of eight radiological features previously described in the literature. Histopathological evaluation was used as a diagnostic gold standard when available and the presence of the radiological features was decided by consensus. Features with higher sensitivity and specificity were identified and the optimal cut-off was calculated to obtain the resulting accuracy. RESULTS: The accuracy for seniors with expertise was non-statistically higher (0.83) compared to senior with no expertise (SWE) (0.65) and juniors (0.74) with SWE having tendency to over-estimate the severity of abnormality (26% vs 17%), whilst junior underestimated the degree of placental infiltration when compared to seniors with expertise (18.5% vs 0%, p = 0.006). Dark bands was the criteria with the highest sensitivity (95%) and high specificity (74%), followed by myometrial thinning (89%-76%) and uterine bulging (86%-81%). These three features demonstrated substantial (K) agreement. Using these features with optimal diagnostic cut-off, the accuracy increased to 0.91 for both the seniors and SWE and to 0.93 for the juniors. CONCLUSION: Placental MRI is most accurately interpreted by experienced radiologists; however, less experienced readers can obtain an accurate diagnosis relying on set criteria that are easier to be identified.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Differentiating uterine sarcoma from leiomyoma: BET1T2ER Check!

Although rare, uterine sarcoma is a diagnosis that no one wants to miss. Often benign leiomyomas (fibroids) and uterine sarcomas can be differentiated due to the typical low T2 signal intensity contents and well-defined appearances of benign leiomyomas compared to the suspicious appearances of sarcomas presenting as large uterine masses with irregular outlines and intermediate T2 signal intensity together with possible features of secondary spread. The problem is when these benign lesions are atypical causing suspicious imaging features. This article provides a review of the current literature on imaging features of atypical fibroids and uterine sarcomas with an aide-memoire BET1T2ER Check! to help identify key features more suggestive of a uterine sarcoma.

MRI findings in-between leiomyoma and leiomyosarcoma: a Rad-Path correlation of degenerated leiomyomas and variants.

Leiomyomas are the most common benign tumors of the uterus. On the opposite side, leiomyosarcomas are rare malignant uterine tumors that account for a significant proportion of uterine cancer deaths. Especially when large and degenerated, leiomyomas and leiomyoma variants can have overlapping imaging characteristics with those of leiomyosarcomas. Although not always possible, it is paramount to be able to differentiate between leiomyomas and leiomyosarcomas on imaging, as the therapeutic management can differ. This pictorial review aims to familiarize radiologists with imaging features of leiomyomas and various types of leiomyoma degeneration and variants, together with their pathology correlates.

MRI of the endometrium - from normal appearances to rare pathology.

MRI was recently included as a standard pre-operative diagnostic tool for patients with endometrial cancer. MR findings allow a better risk assessment and ultimately guides the surgical planning. Therefore, it is vital that the radiological interpretation is as accurate as possible. This requires essential knowledge regarding the appropriate MRI protocol, as well as different appearances of the endometrium, ranging from normal peri- and post-menopausal changes, benign findings (e.g. endometrial hyperplasia, polyp, changes due to exogenous hormones) to common and rare endometrium-related malignancies. Furthermore, this review will emphasize the role of MRI in staging endometrial cancer patients and highlight pitfalls that could result in the underestimation or overestimation of the disease extent.

What is the significance of solitary bony abnormalities on bone scintigrams of children with malignancy?

This investigation was undertaken to evaluate the significance of solitary bony abnormalities on bone scintigrams of children with known or suspected malignancy. A total of 215 bone scans were performed in 183 children in order to look for possible metastasis over a 10-year period. Forty-nine scans (22.8%) were found to have single lesions, of which 18 were due to uptake at the primary site and were excluded from further consideration. Of the remaining 31 lesions, 13 (41.9%) were confirmed as metastases, 17 lesions were proved to be benign, and 1 indeterminate. Solitary hot spots in children with known or suspected malignancy are common and therefore have to be taken seriously due to their higher malignant potential.

Primary Care Practice Redesign: Challenges in Improving Behavioral Health Care for a Vulnerable Patient Population.

This study examined a program focused on integrating mental health in a family medicine practice in an economically challenged urban setting. The program included using a behavioral health technology platform, a behavioral health collaborative composed of community mental health agencies, and a community health worker (CHW). Of the 202 patients screened, 196 were used for analysis; 56% were positive for anxiety, 38% had scores consistent with moderate to severe depression, and 34% were positive for post-traumatic stress disorder. There was a statistically significant difference in the diagnosis of depression when comparing the screened group to a control group. Only 27% of patients followed through with behavioral health referrals despite navigational assistance provided by a CHW and assured access to care through a community agency engaged with the Behavioral Health Alliance. Further qualitative analysis revealed that there were complex patient factors that affected patient decision making regarding follow-up with behavioral health care.

Volatility and Persistence of Value-Based Purchasing Adjustments: A Challenge to Integrating Population Health and Community Benefit Into Business Operations.

With the passage of the Deficit Reduction Act of 2005 and the Patient Protection and Affordable Care Act in 2010, Medicare's Inpatient Prospective Payment System (IPPS) began a transition to value-based purchasing (VBP) that rewards or penalizes hospitals based on patient satisfaction, clinical processes of care, outcomes, and efficiency metrics. However, hospital-level volatility vs. persistence in value-based payments year-over-year could result in unpredictable cash flows that negatively influence investment behavior, drive underinvestment in community benefit/population health management initiatives, and make management of the factors that drive the VBP adjustment more challenging. To evaluate the volatility and persistence of hospital VBP adjustments, the sample includes VBP adjustments and the associated domain scores for the 2,547 hospitals that participated in the program from 2013 to 2016. The sample includes urban (74%), teaching (29.1%), system affiliated (46.5%), and not-for-profit (63.6%) facilities. Volatility was measured using basic descriptive statistics, relative risk ratios, and a fixed effect, autoregressive, dynamic panel model that robust-clustered the standard errors. There is substantial change in a given facility's total VBP score with an average standard deviation of 10.74 (on a 100-point scale) that is driven by significant volatility in all metrics but particularly by efficiency and outcomes metrics. Relative risk ratios have dropped substantially over the life of the program, and there is low persistence of VBP scores from one period to the next. Findings indicate that if hospitals receive a positive adjustment in 1 year, they are almost as likely to receive a negative adjustment as a positive adjustment the following year. Furthermore, using a fixed-effect dynamic panel model that controls for autocorrelation, we find that only 13.5% of a facility's prior year IPPS adjustment (positive or negative) carries forward to the next year. The low persistence makes investment in population health management and community benefit more challenging.

Image-guided biopsy in patients with suspected ovarian carcinoma: a safe and effective technique?

In patients with suspected advanced ovarian carcinoma, a precise histological diagnosis is required before commencing neo-adjuvant chemotherapy. This study aims to determine the diagnostic accuracy and complication rate of percutaneous biopsies performed under ultrasound or computed tomography guidance. Between 2002 to 2007, 60 consecutive image-guided percutaneous biopsies were performed in patients with suspected ovarian cancer. The following variables were recorded: tissue biopsied, imaging technique, experience of operator, biopsy needle gauge, number of passes, complications, and final histology. Forty-seven patients had omental biopsies, 12 pelvic mass biopsies, and 1 para-aortic lymph node biopsy. Thirty-five biopsies were performed under ultrasound, 25 under computed tomography guidance. Biopsy needle gauges ranged from 14-20 swg with two to five passes for each patient. There were no complications. Histology was obtained in 52 (87%) patients. Percutaneous image-guided biopsy of peritoneal disease or pelvic mass is safe with high diagnostic accuracy. The large-gauge biopsy needle is as safe as the small gauge needle, but has the added value of obtaining tissue samples for immunohistochemistry and genomic studies.

Complexities of Addressing Food Insecurity in an Urban Population.

There is an association between food insecurity, poor health outcomes, and increased health care spending. The Temple Food Insecurity Program was initiated to screen patients for food insecurity as part of the post Temple University Hospital discharge process. The community is economically challenged and food insecurity is a significant problem. Food insecure patients were identified and referred to community-based resources, with a 30-day follow-up call. Screening was successful in 3655 patients, 27% (n = 987) of whom reported food insecurity. Of these patients, 66% (n = 647) were already receiving benefits through the Supplemental Nutrition Assistance Program (SNAP), but were still food insecure. All patients with food insecurity were referred to one of 2 resources for help. Despite significant need, less than a quarter of patients connected with these resources. Qualitative data revealed that some patients did not remember the information provided to them, were overwhelmed with poor health or other social determinants of health, had competing priorities, did not perceive the need for food assistance; and experienced system barriers. Health literacy also was an issue. Health care systems addressing food insecurity should consider the high prevalence of food insecurity in impoverished regions, the reality that SNAP benefits may not alleviate food insecurity for many patients, and the need for individualized, custom care plans that address barriers and reflect patient priorities and capabilities. Engaging patients differently may be aided by additional communication from community food resources directly to patients who provide permission for this added service.