Post-operative opioid analgesic prescribing patterns in gynecologic oncology patients following the implementation of a statewide -prescription monitoring and reporting system.

OBJECTIVE: To analyze the effect of the Connecticut Prescription Monitoring and Reporting System (CPMRS) on the number of opioid tablets prescribed to gynecologic oncology patients post-operatively. DESIGN/PARTICIPANTS: This was a retrospective chart review of patients who received surgery for suspicious masses, premalignant, or malignant conditions of uterus, tubes, ovaries, or cervix. Charts were divided into two groups before and after the implementation of an updated prescription monitoring system in July 2016. Quantitative data were collected on the number of opioids prescribed from hospital discharge summaries. Qualitative data included prescription and/or -recommendation of nonopioid analgesics and type of procedure (open versus minimally invasive). Demographic information included age, ethnicity, and insurance coverage. OUTCOMES: We identified a statistically significant, 50 percent decrease in opioid tablets in the After July 2016 group (n = 226) compared with the Before July 2016 group (n = 136) (p < 0.001). As anticipated, fewer opioid tablets were prescribed following minimally invasive procedures compared to open cases (p = 0.007). On examining nonopioid analgesic data, we found more patients received a prescription for nonopioid analgesics in the After July 2016 group compared with the Before July 2016 group (p < 0.001). CONCLUSION: This study confirms a decrease in opioid tablets prescribed to post-operative gynecologic oncology patients since July 2016. This difference cannot be attributed to the implementation of the CPMRS alone, but chronologically relates to updated requirements. Additionally, our results re-emphasize that minimally invasive surgery has a reduced number of prescribed opioids. A multi-institutional study is required with more patients to detail the factors involved in further decreasing opioid prescribing.

ACR Appropriateness Criteria® Pretreatment Evaluation and Follow-Up of Endometrial Cancer.

To date, there is little consensus on the role of pelvic imaging in assessing local disease extent during initial staging in patients with endometrial carcinoma, with practices differing widely across centers. However, when pretreatment assessment of local tumor extent is indicated, MRI is the preferred imaging modality. Preoperative imaging of endometrial carcinoma can define the extent of disease and indicate the need for subspecialist referral in the presence of deep myometrial invasion, cervical extension, or suspected lymphadenopathy. If distant metastatic disease is clinically suspected, preoperative assessment with cross-sectional imaging or PET/CT may be performed. However, most patients with low-grade disease are at low risk of lymph node and distant metastases. Thus, this group may not require a routine pretreatment evaluation for distant metastases. Recurrence rates in patients with endometrial carcinoma are infrequent. Therefore, radiologic evaluation is typically used only to investigate suspicion of recurrent disease due to symptoms or physical examination and not for routine surveillance after treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Placenta Accreta Spectrum Disorder.

Placenta accreta spectrum disorder (PASD) is the current terminology recommended by the International Federation of Obstetrics and Gynecology (FIGO) and should replace terms such as abnormally adherent/invasive placenta or morbidly adherent placenta. PASD refers to a variety of potential clinical complications, which may result from abnormal placental implantation. More specifically, placenta accreta refers to a defect in the decidua basalis where the chorionic villi adhere directly to the myometrium with trophoblastic invasion. Accurate antenatal diagnosis is needed to plan for an appropriate delivery strategy at an experienced center in order to reduce maternal and potential fetal morbidity and mortality. Obtaining radiologic and clinical data when PASD is first suspected can play a significant role in formulating an appropriate delivery strategy. Depending on the clinical risk factors and initial imaging findings, transabdominal ultrasound of the pregnant uterus with duplex Doppler and transvaginal ultrasound as needed are the most appropriate imaging procedures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Profiling microdissected epithelium and stroma to model genomic signatures for cervical carcinogenesis accommodating for covariates.

This study is the first comprehensive, integrated approach to examine grade-specific changes in gene expression along the entire neoplastic spectrum of cervical intraepithelial neoplasia (CIN) in the process of cervical carcinogenesis. This was accomplished by identifying gene expression signatures of disease progression using cDNA microarrays to analyze RNA from laser-captured microdissected epithelium and underlying stroma from normal cervix, graded CINs, cancer, and patient-matched normal cervical tissues. A separate set of samples were subsequently validated using a linear mixed model that is ideal to control for interpatient gene expression profile variation, such as age and race. These validated genes were ultimately used to propose a genomically based model of the early events in cervical neoplastic transformation. In this model, the CIN 1 transition coincides with a proproliferative/immunosuppression gene signature in the epithelium that probably represents the epithelial response to human papillomavirus infection. The CIN 2 transition coincides with a proangiogenic signature, suggesting a cooperative signaling interaction between stroma and tumor cells. Finally, the CIN 3 and squamous cell carcinoma antigen transition coincide with a proinvasive gene signature that may be a response to epithelial tumor cell overcrowding. This work strongly suggests that premalignant cells experience a series of microenvironmental stresses at the epithelium/stroma cell interface that must be overcome to progress into a transformed phenotype and identifies the order of these events in vivo and their association with specific CIN transitions.

ACR Appropriateness Criteria® Gestational Trophoblastic Disease.

Gestational trophoblastic disease (GTD), a rare complication of pregnancy, includes both benign and malignant forms, the latter collectively referred to as gestational trophoblastic neoplasia (GTN). When metastatic, the lungs are the most common site of initial spread. Beta-human chorionic gonadotropin, elaborated to some extent by all forms of GTD, is useful in facilitating disease detection, diagnosis, monitoring treatment response, and follow-up. Imaging evaluation depends on whether GTD manifests in one of its benign forms or whether it has progressed to GTN. Transabdominal and transvaginal ultrasound with duplex Doppler evaluation of the pelvis are usually appropriate diagnostic procedures in either of these circumstances, and in posttreatment surveillance. The appropriateness of more extensive imaging remains dependent on a diagnosis of GTN and on other factors. The use of imaging to assess complications, typically hemorrhagic, should be guided by the location of clinical signs and symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Clinically Suspected Adnexal Mass, No Acute Symptoms.

There are approximately 9.1 pelvic surgeries performed for every histologically confirmed adnexal malignancy in the United States, compared to 2.3 surgeries per malignancy (in oncology centers) and 5.9 surgeries per malignancy (in other centers) in Europe. An important prognostic factor in the long-term survival in patients with ovarian malignancy is the initial management by a gynecological oncologist. With high accuracy of imaging for adnexal mass characterization and consequent appropriate triage to subspecialty referral, the better use of gynecologic oncology can improve treatment outcomes. Ultrasound, including transabdominal, transvaginal, and duplex ultrasound, combined with MRI with contrast can diagnose adnexal masses as benign with specific features (ie, functional masses, dermoid, endometrioma, fibroma, pedunculated fibroid, hydrosalpinx, peritoneal inclusion cyst, Tarlov cyst), malignant, or indeterminate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Gynecologic malignancies.

The pioneers in the field of gynecologic oncology set out to establish an evidence-based approach to the care of women with gynecologic cancer, combining the modalities of surgery, chemotherapy, and radiation. Quality of life has become the cornerstone of care for these patients, in addition to advancing survival through surgical technology, collaborative research trials, and molecular approaches to early diagnosis and management. This article addresses the epidemiology, screening, preventive strategies, diagnosis, staging, surgical care, adjuvant therapy, prognosis, and recurrence management of three common gynecologic malignancies encountered in the operating arena: endometrial, cervical, and vulvar cancer.

ACR Appropriateness Criteria® Staging and Follow-Up of Ovarian Cancer.

In the management of epithelial ovarian cancers, imaging is used for cancer detection and staging, both before and after initial treatment. The decision of whether to pursue initial cytoreductive surgery for ovarian cancer depends in part on accurate staging. Contrast-enhanced CT of the abdomen and pelvis (and chest where indicated) is the current imaging modality of choice for the initial staging evaluation of ovarian cancer. Fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT and MRI may be appropriate for problem-solving purposes, particularly when lesions are present on CT but considered indeterminate. In patients who achieve remission, clinical suspicion for relapse after treatment prompts imaging evaluation for recurrence. Contrast-enhanced CT is the modality of choice to assess the extent of recurrent disease, and fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT is also usually appropriate, as small metastatic foci may be identified. If imaging or clinical examination confirms a recurrence, the extent of disease and timing of disease recurrence then determines the choice of treatments, including surgery, chemotherapy, and radiation therapy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Frequent HOXA11 and THBS2 promoter methylation, and a methylator phenotype in endometrial adenocarcinoma.

PURPOSE: This study was designed to determine whether there is a methylator phenotype in stage I and II endometrioid endometrial adenocarcinoma, and if so, whether methylation correlates with recurrence. EXPERIMENTAL DESIGN: Bisulfite-converted DNAs from 24 stage I and II primary cancers (12 recurrent and 12 nonrecurrent), and 5 endometrial cancer cell lines were analyzed for methylation in the promoter regions of seven genes. A methylation index (MeI) was calculated for each tumor. Frequent HOXA11 and THBS2 methylation prompted analysis of case-matched bloods and 25 additional nonrecurrent primary cancers. Statistical analysis included Fisher's exact and Student t tests. RESULTS: Rates of methylation in the initial tumor series were as follows: HOXA11, 70.8%; THBS2, 62.5%; MLH1, 33.3%; CTNNB1, 16.7%; VDR, 4.2%; CDKN2A, 4.2%; and THBS1, 0%. There was no difference in the MeI of recurrent and nonrecurrent cases. However, cell lines had higher mean MeI. High rates of HOXA11 and THBS2 methylation were confirmed in the additional nonrecurrent tumors. None of the 24 case-matched bloods had HOXA11 methylation, whereas three blood DNAs showed THBS2 methylation. There was a statistically significant difference in the rate of HOXA11 methylation in recurrent and nonrecurrent tumors (P = 0.0167). CONCLUSIONS: Endometrial adenocarcinomas have a methylator phenotype. No correlation between MeI and clinicopathologic variables in early stage tumors was observed. High rates of methylation were found in the HOXA11 and THBS2 promoter regions. HOXA11 promoter methylation was significantly more frequent in recurrent than nonrecurrent cases. HOXA11 methylation in early stage endometrial cancer is associated with poor outcome.

Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary (CCCO) with trametinib and metformin in a patient with chemotherapy-refractory disease.

PURPOSE: Compared to other subtypes of epithelial ovarian cancer, clear cell carcinoma of the ovary bears an ominous reputation for chemotherapy resistance, increased relapse rate, and diminished survival. Among patients with distinct histopathologic subtypes, molecular analyses have identified a variety of known drivers of the malignant behavior, and depict a striking heterogeneity. METHODS: A patient with rapidly metastatic CCCO that was refractory to taxane, platinum, pemetrexed, and bevacizumab-based strategies underwent molecular profiling which disclosed dual MAPK and PI3K/AKT/mTOR pathway mutations. RESULTS: Combined targeted therapy with trametinib and metformin resulted in a dramatic disease regression without toxicity. CONCLUSION: The case highlights the utility of precision medicine combining individual molecular diagnosis with rational therapeutic intervention with targeted agents.

Three cases of hemolytic uremic syndrome in ovarian cancer patients treated with combination gemcitabine and pegylated liposomal doxorubicin.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare coagulation disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute uremia. Reports have described this fatal syndrome in association with cytotoxic agents. To our knowledge, no case reports of HUS in ovarian cancer patients receiving treatment with combination gemcitabine and pegylated liposomal doxorubicin (PLD) have been reported. CASE REPORTS: Three patients with recurrent ovarian carcinoma each developed profound hypertension and peripheral edema while receiving combination gemcitabine and PLD. The first patient had rapid hemolysis, thrombocytopenia, renal failure and respiratory distress. The other patients experienced slowly progressive renal failure and mild hematologic abnormalities. Two of the three patients had favorable outcomes. CONCLUSION: The reported incidence of gemcitabine-induced HUS is rare. Clinicians should suspect HUS if blood pressure elevation or peripheral edema develop.