Water only fasting and its effect on chemotherapy administration in gynecologic malignancies.

OBJECTIVE: As a protective response, during starvation organisms withdraw energy from growth and reproduction to focus on cellular maintenance. Cancer cells cannot undergo this differential response which has been theorized as an adjunct to improve both the effect of chemotherapy treatment and reduce treatment side effects. We sought to investigate the feasibility and effect of short-term fasting in patients receiving chemotherapy for gynecologic malignancy. METHODS: A randomized control trial was conducted of women with gynecologic malignancies receiving at least 6 planned chemotherapy cycles. Fasting patients maintaining a water-only fast for 24 h before and 24 h following each chemotherapy cycle were compared to nonfasting patients. Treatment related side effects and quality of life (QOL) was assessed using NCCN-FACT FOSI-18 questionnaire. RESULTS: Analysis included data from 120 cycles of chemotherapy. The majority of patients had stage 3 and 4 malignancy requiring multi-agent chemotherapy. Eleven patients had ovarian, 8 had uterine, and 1 had cervical cancer. Ninety percent received taxane and platinum-based doublet therapy. Weight loss and unanticipated hospitalizations were similar between treatment groups. Fewer dose reductions or delays were seen in the fasting group. There was no significant difference in mean QOL scores, but fasting group QOL scores improved over the course of treatment to a level that reached the minimal clinically important difference. CONCLUSION: A 48-h fast is well tolerated without increasing weight loss, hospital admissions, or chemotherapy dose reduction/delays. Fasting resulted in fewer treatment modifications and improved quality of life scores over the course of treatment.

Combination therapy with paclitaxel, carboplatin and megestrol acetate for the management of advanced stage or recurrent carcinoma of the endometrium: a phase II study.

OBJECTIVE: To determine overall survival (OS), progression-free interval (PFI), and toxicity in patients with advanced stage or recurrent endometrial cancer (EMCA) treated with combination paclitaxel, carboplatin and megestrol acetate. STUDY DESIGN: Patients with stage III/IV or recurrent EMCA were enrolled between October 2004 and April 2008 and received paclitaxel (175 mg/m2) and carboplatin (AUC 6) every 21 days for 6 cycles and megestrol acetate 40 mg orally 4 times daily for up to 5 years. Dose reductions were based on grade 3/4 hematologic toxicity. Survival was calculated from time of study enrollment. RESULTS: A total of 28 patients were evaluable: 21 (75%) patients with stage III/IV disease and 7 (25%) with recurrent disease. Three patients with recurrence received prior radiation. Mean PFI was 40.2 months (29.7-50.6). Mean OS was 50.1 months (41.5-58.7). After a median 40.4 months (range, 5.6-68.4) of follow-up, 13 patients (46%) had no evidence of disease, 4 were alive with disease, and 10 were dead of disease. One patient died without evidence of disease. Twenty-three patients (82%) completed 6 cycles of chemotherapy. Ten patients experienced a dose reduction. Myelosuppression was common, with 22 patients (78%) experiencing grade 3/4 neutropenia and 6 patients (21%) experiencing grade 3/4 anemia. Three patients had a deep vein thrombosis. One patient experienced a pulmonary thromboembolus. CONCLUSION: Combination therapy with paclitaxel, carboplatin and megestrol acetate demonstrates activity. Myelosuppression is common but can be managed with colony-stimulating factors. The addition of hormonal therapy to cytotoxic chemotherapy may improve survival.

Reporting Subclonal Immunohistochemical Staining of Mismatch Repair Proteins in Endometrial Carcinoma in the Times of Ever-Changing Guidelines.

CONTEXT.­: The current College of American Pathologists reporting guideline for mismatch repair protein (MMRP) immunohistochemistry for Lynch syndrome (LS) screening considers the presence of any positive nuclear staining as intact MMRP expression. This would include tumors with combined areas of subclonal retention and loss of MMRP staining. OBJECTIVE.­: To evaluate the clinical significance of reporting subclonal staining patterns of MMRP immunohistochemistry in endometrial carcinoma. DESIGN.­: We retrospectively reviewed 455 consecutive MMRP immunohistochemistry results of endometrial carcinoma in hysterectomy specimens from 2012 through 2017 and identified cases with subclonal MMRP staining. These results were correlated with the patient's personal and family history of LS-associated carcinoma, MLH1 promoter methylation status, and LS genetic testing. RESULTS.­: Subclonal staining of MMRP was seen in 48 of 455 cases (10.5%) on review. Thirty cases demonstrated isolated subclonal staining and were reported by pathologists as follows: subclonal (n = 5), complete MMRP loss (n = 4), and intact MMRP (n = 21). Eighteen cases had subclonal staining in combination with complete loss of other MMRP. Cases reported as subclonal or complete MMRP loss had appropriate clinical follow-up. Two of 2 cases with isolated subclonal MSH6 loss tested positive for LS. One of 3 cases with isolated subclonal MLH1/PMS2 loss was negative for MLH1 promoter methylation; LS genetic testing was not performed because of cost. CONCLUSIONS.­: Our study reveals that LS germline mutation can be detected in endometrial carcinoma patients whose tumors display sole subclonal MMRP staining. Our results stress the importance of reporting subclonal staining patterns to ensure appropriate clinical follow-up.

Availability of the HPV Vaccine in Regional Pharmacies and Provider Perceptions Regarding HPV Vaccination in the Pharmacy Setting.

There is increasing support for HPV vaccination in the pharmacy setting, but the availability of the HPV vaccine is not well known. Additionally, little is known about perceptions of medical providers regarding referring patients to community pharmacies for HPV vaccination. The purpose of this study was to determine HPV vaccine availability in community pharmacies and to understand, among family medicine and obstetrics-gynecology providers, the willingness of and perceived barriers to referring patients for HPV vaccination in a pharmacy setting. HPV vaccine availability data were collected from pharmacies in a southern region of the United States. Family medicine and obstetrics-gynecology providers were surveyed regarding vaccine referral practices and perceived barriers to HPV vaccination in a community pharmacy. Results indicated the HPV vaccine was available in most pharmacies. Providers were willing to refer patients to a community pharmacy for HPV vaccination, despite this not being a common practice, likely due to numerous barriers reported. Pharmacist-administered HPV vaccination continues to be a commonly reported strategy for increasing HPV vaccination coverage. However, coordinated efforts to increase collaboration among vaccinators in different settings and to overcome systematic and legislative barriers to increasing HPV vaccination rates are still needed.

Prognostic significance of the relative dose intensity of chemotherapy in primary treatment of epithelial ovarian cancer.

OBJECTIVE: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. In this study, we sought to determine the prognostic significance of RDI in patients with epithelial ovarian cancer (EOC). METHODS: A retrospective analysis of chemotherapy naïve patients treated between 2001 and 2008 with intravenous taxane and platinum was performed. RDI was calculated as the delivered dose intensity (total dose delivered/total time of therapy) divided by standard dose intensity calculated for each regimen and compared to progression-free survival (PFS). Multivariate recursive partitioning survival analysis was utilized. RESULTS: 138 EOC patients completed initial taxane/platinum-based chemotherapy following surgical cytoreduction. The most common reasons for dose delays and reductions were thrombocytopenia (38%) and neutropenia (31%). 24% of treatment delays were due to social reasons such as transportation constraints or scheduling conflicts. The average RDI was 90% (range, 24-126%). The mean PFS was 31 months (range, 3-117). Patients that achieved an RDI between 70% and 110% had a mean PFS of 32 months compared to 20 months in patients with an RDI of <70% or >110% (p=0.046). 14 patients (10%) had a RDI of <70%. CONCLUSIONS: RDI is a significant predictor of survival in patients with EOC. Effort should be made to achieve an RDI of at least 70%. Dose reductions and treatment delays could be minimized by utilizing prophylactic colony stimulating factors and educating patients about the importance of adhering to their treatment schedule.

A cohort study evaluating robotic versus laparotomy surgical outcomes of obese women with endometrial carcinoma.

OBJECTIVE: Minimally invasive surgery offers advantages for management of obese patients, but technical difficulty often deters its utilization. Compared to laparotomy, robotic surgery should allow comparable staging and improved surgical outcomes. Therefore, we evaluated outcomes in robotic and laparotomy cohorts of obese women with endometrial cancer at our institution. METHODS: Retrospective robotic and laparotomy cohorts of obese women (BMI ≥ 30 kg/m(2)) undergoing surgical management of primary endometrial cancer from March 2006 to March 2009 were formulated utilizing a computerized database. Patient demographics, operative statistics, peri-operative complications, and pathologic details were collected in an intent to treat analysis. Chi-square or Fisher's exact test and t-test were used for statistical analysis. RESULTS: 73 women underwent robotic surgical management, 11% converted to laparotomy. Mean BMI (39.8 vs. 41.9, p=0.152), number of co-morbidities (2.49 vs. 2.62, p=0.690), number of previous surgeries (0.97 vs. 0.94, p=0.841), and lymphadenectomies performed (65.8% vs. 56.7%, p=0.227) were similar between cohorts. Total lymph nodes obtained were not statistically different between cohorts (8.01 vs. 7.24, p=0.505). Total operative time and room time was significantly longer for robotic surgery; however, estimated blood loss, the percentage of patients receiving transfusion, hospital length of stay, wound complications (4.1% vs. 20.2%, p=0.002) and other complications (9.6% vs. 29.8%, p=0.001) were improved for the robotic cohort. CONCLUSIONS: Robotic management of obese women with endometrial cancer yields acceptable staging results and improved surgical outcomes. Although operating time is longer, hospital time is shorter. Robotic surgery may be an ideal approach for these patients.

Assessment of risk factors for 30-day hospital readmission after surgical cytoreduction in epithelial ovarian carcinoma.

OBJECTIVE: To evaluate factors that place epithelial ovarian cancer (EOC) patients at increased risk for hospital readmission. METHODS: A retrospective review of patients diagnosed with EOC undergoing surgical cytoreduction at the University of Alabama at Birmingham from 2001 to 2008 was performed. Patients who required readmission were identified. Demographic data, comorbidities, surgical data including bowel resections, and hospital length of stay were evaluated. RESULTS: A total of 207 patients were identified. The mean age at diagnosis was 64 years (range, 32-89 years), 58% had optimal debulking (n=120), and the mean number of comorbidities was 1.3 (range, 0-6). Readmission within 30 days of discharge occurred in 33 (16%) of 207 patients. The readmission group had a statistically higher number of comorbidities (1.75 vs 1.01, P=0.025). The most common reasons for readmission were small bowel obstruction/ileus, wound complications, and thromboembolic events. CONCLUSIONS: The most common reason for readmission after cytoreductive surgery for EOC is small bowel obstruction/ileus. Studies assessing postoperative disease management programs including nursing telephone follow-up, administration of outpatient intravenous fluids, and continuation of antithrombotic agents may offer opportunities to reduce readmissions.

Pharmacists' Perceived Barriers to Human Papillomavirus (HPV) Vaccination: A Systematic Literature Review.

About 45:000 cancers are linked to HPV each year in the United States alone. The HPV vaccine prevents cancer and is highly effective, yet vaccination coverage remains low. Pharmacies can play a meaningful role in increasing HPV vaccination access due to their availability and convenience. However, little is known about pharmacists' perceived barriers to HPV vaccination. The objective of this systematic review was to summarize existing literature on perceived barriers to administering HPV vaccination reported by pharmacists. Barriers identified from selected studies were synthesized and further grouped into patient, parental, (pharmacist's) personal, and system/organization barrier groups. Six studies were included in this review. The cost of the HPV vaccine, insurance coverage and reimbursement were commonly reported perceived barriers. Adolescent HPV vaccination barriers related to parental concerns, beliefs, and inadequate knowledge about the HPV vaccine. Perceived (pharmacist's) personal barriers were related to lack of information and knowledge about HPV vaccine and recommendations. At the system/organization level, barriers reported included lack of time/staff/space; difficulty in series completion; tracking and recall of patient; perceived competition with providers; and other responsibilities/vaccines taking precedence. Future strategies involving pharmacy settings in HPV-related cancer prevention efforts should consider research on multilevel pharmacy-driven interventions addressing barriers.

The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in patients receiving myelosuppressive chemotherapy for gynecologic malignancies.

OBJECTIVE: Pegfilgrastim is indicated to decrease the incidence of febrile neutropenia in patients with gynecologic malignancies who are receiving myelosuppressive chemotherapy. We sought to compare the safety and efficacy of day 1 pegfilgrastim administration to day 2 administration in patients with gynecologic malignancies. METHODS: We retrospectively evaluated patients receiving both chemotherapy and pegfilgrastim from June 1, 2006 to August 31, 2007 for a gynecologic malignancy. Abstracted data included patient demographics, pathology, blood counts, toxicity, and chemotherapy. After administration of chemotherapy, all patients either received 6 mg of pegfilgrastim subcutaneously on day 1 or day 2. RESULTS: 1226 administrations of pegfilgrastim in 230 patients were identified. 490 administrations of pegfilgrastim were given on day 1 compared to 736 on day 2. 70% of patients had ovarian cancer with a median age of 64 years (range 15-88). 79% of patients had stage III, IV, or recurrent disease and 67% were undergoing primary chemotherapy. The most common chemotherapy was docetaxel/carboplatin (53%) followed by paclitaxel/carboplatin (19%). The mean absolute neutrophil count (ANC) nadir was 4810/mm(3) in the day 1 cohort compared to 4212/mm(3) in the day 2 cohort (p=.004). The incidence of Grade 3/4 neutropenia was similar in both groups (4.9% in day 1 vs. 5.7% in day 2; p=.63). Grade 3/4 febrile neutropenia was uncommon in both cohorts (0 episodes vs. 3 episodes; p=.41). Treatment delays were similar in both cohorts (5.9% vs. 7.5%; p=.35). Dose modifications were also similar in both cohorts (2.8% vs. 5.3%; p=.06). CONCLUSION: Day 1 administration of pegfilgrastim is as effective as day 2 administration in the prevention of neutropenia in patients with gynecologic malignancies. Treatment delays and dose modifications were not increased after day 1 administration of pegfilgrastim. Administering pegfilgrastim on day 1 appears to be safe, effective, and convenient in selected patients receiving myelopsuppressive chemotherapy for gynecologic malignancies.

Fixed-dose rate gemcitabine plus carboplatin in relapsed, platinum-sensitive ovarian cancer patients: results of a three-arm Phase I study.

OBJECTIVES: Standard infusion of gemcitabine plus carboplatin showed improved efficacy compared to carboplatin alone in patients with platinum-sensitive (Pt-S) ovarian cancer (OC). Fixed-dose rate (FDR) administration of gemcitabine produces more efficient intracellular phosphorylation of gemcitabine to its active form. This study was designed to identify the maximum tolerated dose (MTD), toxicity profile, and response rate of FDR gemcitabine plus carboplatin in Pt-S OC. METHODS: Patients with measurable OC relapsing > or =6 months after exposure to platinum (N=60) were assigned to one of three treatment cohorts, each with a different delivery schedule and escalating doses of both FDR gemcitabine (10 mg/m(2)/min) and standard infusion carboplatin (60 min). MTDs were determined using dose-limiting toxicities (DLTs). Measurable disease was assessed using modified RECIST criteria. CA-125 levels were evaluated using Rustin criteria. Toxicities were assessed using NCI Common Toxicity Criteria, version 2.0. RESULTS: The MTD of Arm 1 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 1, every 21 days. The MTD of Arm 2 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 2.5+AUC 2.5 on days 1 and 8, every 21 days. Patient accrual on Arm 3 consisting of bi-weekly FDR gemcitabine plus carboplatin was terminated because dose level 1 exceeded the MTD. Overall response rates were 38.1% (Arm 1), 58.8% (Arm 2), and 44.4% (Arm 3). CONCLUSIONS: FDR gemcitabine+carboplatin on a 21-day schedule was active and produced no unusual safety signals in patients with Pt-S OC.

Large cell neuroendocrine carcinoma of the endometrium: a report and review of the literature.

Large-cell neuroendocrine tumor of the endometrium is a rare tumor type which is difficult to diagnose. Our routine tissue sampling is often non-productive and these tumors can be mistaken for other poorly differentiated carcinomas. Sites of metastatic disease sometimes confuse the identification of the primary organ, and histological diagnosis requires a choice of neuroendocrine biomarkers. In addition, there are no published diagnostic criteria for LCNEC of the endometrium and diagnostic criteria must be translated from the WHO classification of tumors of the lung. Once a diagnosis is reached, there are no large series to direct treatment. Consensus opinion appears to favor surgery for early stage disease followed by chemotherapy with etoposide and platinum-based agents. While there are many hurdles to overcome, the proper diagnosis of LCNEC of the endometrium is of utmost importance in a disease characterized by rapid progression and poor prognosis. We examine a case of large cell neuroendocrine tumor of the endometrium with rapid progression over a period of two months which precluded her planned chemotherapy.

Effecting the sixth core competency: a project-based curriculum.

OBJECTIVE: In agreement with the Accreditation Council for Graduate Medical Education guidelines, a systems-based practice (SBP) curriculum was implemented to provide a hands-on, team-based experience, while providing an opportunity to contribute to quality improvement, and to develop a method to assess residents' understanding of SBP. STUDY DESIGN: During departmental conferences, issues affecting our health care operations were identified. Seven teams were formed and the actionable items were investigated. The salient issues and potential solutions were presented to the department. RESULTS: This project resulted in the development of tools designed to assess competency in SBP, communication skills, and professionalism. Completion of a pre- and posttest and annual oral examination questions revealed a significant improvement in the comprehension of SBP. CONCLUSION: This project served as an effective educational forum for the competencies of SBP, communication skills, and professionalism. This initiative also offered improvement of patient care and/or educating peer providers, thereby fulfilling the goal of SBP in the process of education.

Traumatic diaphragmatic rupture: a rare cause of postoperative shortness of breath.

BACKGROUND: Shortness of breath is a common symptom reported by patients after gynecologic procedures. Delayed traumatic diaphragmatic rupture is a rare cause of shortness of breath. CASE: This report describes the diagnosis and management of a patient with a delayed presentation of a ruptured right hemidiaphragm after a laparotomy for a pelvic mass. CONCLUSION: Although rare, delayed presentation of traumatic diaphragmatic rupture should be considered in patients with a history of blunt chest or abdominal trauma as a possible cause of shortness of breath in the postoperative setting.

Surgical staging in endometrial cancer.

Early presentation of endometrial cancer permits effective management with excellent clinical outcome. The addition of hysteroscopy to dilatation and curettage (D&C) in the evaluation of postmenopausal bleeding adds little to the detection of malignancy. Imaging studies such as computed tomography, magnetic resonance imaging, and positron-emission tomography may be of use in determining the presence of extrauterine disease in patients medically unfit for surgical staging. However, these studies are not sufficiently sensitive to replace surgical staging and have little role in routine preoperative evaluation. Clinical staging alone is clearly inadequate, as 23% of preoperative clinical stage I/II patients are upstaged with comprehensive surgical staging. Preoperative tumor grade from D&C or office biopsy may be inaccurate and lead to an underestimate of tumor progression if used to determine which patients should be surgically staged. Clinical estimation of depth of invasion, with or without frozen section, is inaccurate and may lead to underestimation of disease status when surgical staging is not performed. The practice of resecting only clinically suspicious nodes should be discouraged as it is no substitute for comprehensive surgical staging. Comprehensive surgical staging provides proper guidance for postoperative adjuvant therapy, avoiding needless radiation in 85% of clinical stage I/II patients. Finally, resection of occult metastasis with surgical staging may improve survival.

A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).

Early abdominal incision recurrence in a patient with stage I adenocarcinoma of the endometrium.

BACKGROUND: Although most patients with a surgical stage I endometrial cancer have an excellent prognosis, some patients will experience a recurrence. Endometrial cancer typically recurs at the vaginal cuff or in the pelvis; however, it can recur distantly in the abdomen or lung. Although recurrences have been reported at laparoscopic trochar sites, it is unusual to have a recurrence in the abdominal incision after laparotomy. CASE: A 51-year-old woman was diagnosed with stage Ib grade 2 adenocarcinoma of the endometrium and stage IV endometriosis. Six months after surgery, she presented with a mass in the lateral aspect of her Maylard incision. Computed tomography scans of the chest, abdomen, and pelvis showed no evidence of recurrent disease. The mass was resected and confirmed to be an adenocarcinoma similar to the endometrial primary. CONCLUSION: This case is interesting because of the rapid recurrence of the endometrial primary at an unusual site-the abdominal incision. It illustrates the need to carefully evaluate all suspicious masses, even as early as 6 months after diagnosis and surgical staging.

High grade primitive neuroectodermal tumor of the uterus: A case report.

•Primitive neuroectodermal tumor of the uterus is extremely rare.•Diagnosis requires timely evaluation with molecular analysis.•Different combinations of adjuvant chemotherapy have been reported.

Extensive cutaneous metastases of ovarian cancer after prolonged response to liposomal doxorubicin.

•Cutaneous metastases are rare and clinically challenging to manage. When present, they often represent end-stage disease.•Treatments for cutaneous metastases are limited, and primarily palliative in nature.

Morbidity and mortality conference in obstetrics and gynecology: a tool for addressing the 6 core competencies.

BACKGROUND: Residency program directors are challenged to effectively teach and assess the Accreditation Council for Graduate Medical Education's (ACGME) 6 competencies. The purpose of this study was to characterize the morbidity and mortality (M&M) conference as a cost-effective and efficient approach for addressing the ACGME competencies through evaluation of resident participation and case diversity. METHODS: In our modified M&M conference, senior residents submit a weekly list of cases to the conference proctors. The resident presents the case, including a critique of management, using the medical literature. The resident submits a case summary evaluating patient care practices, integrating scientific evidence, and evaluating systemic barriers to care. Completed case summaries are distributed and archived for reference. RESULTS: During a 3-year period, 30 residents presented 196 cases. Of these, 37 (19%) directly related to systems-based practice, 20 (10%) involved problems with inadequate communication, and 11 (6%) included issues of professionalism or ethics. All cases involved practice-based learning and medical knowledge. CONCLUSIONS: The M&M conference addresses the core competencies through resident participation as well as directed analysis of diverse cases.