Combined trastuzumab and radiation therapy for HER2-positive uterine serous carcinoma: A case report.

Overexpression of HER2 in endometrial cancer is associated with poor prognosis, aggressive disease, and resistance to standard therapies. Recent studies have shown that HER2-targeted therapies, such as trastuzumab, can be effective in treating HER2-positive endometrial cancer in combination with chemotherapy. Currently, the management of advanced-stage HER2-positive uterine serous carcinoma (USC) consists of adjuvant platinum-based chemotherapy with concurrent trastuzumab followed by trastuzumab maintenance therapy until disease recurrence or prohibitive toxicity. In the setting of persistent pelvic disease following systemic therapy, consolidation with tumor-directed radiation therapy also offers an opportunity to eradicate residual disease. With the emergence of molecular tumor classifications and systemic therapies (chemotherapy, immunotherapy, and target therapies), the landscape of adjuvant multi-modality therapy is ever changing and increasingly individualized. Currently, there is no prospective evidence to guide pelvic radiotherapy with concurrent trastuzumab in endometrial cancer, and as a result, no reported toxicity in endometrial cancer patients. In this case report, we present two patients with HER2-positive USC who received multi-agent chemotherapy with trastuzumab followed by pelvic radiation therapy and concurrent trastuzumab. Both patients tolerated this multimodal treatment without significant or persistent moderate or severe adverse events. These two cases provide insight into the safety and feasibility of administering radiation therapy with trastuzumab in endometrial cancer in the maintenance phase. Our report suggests that trastuzumab-based therapy may be a promising treatment option for HER2-positive endometrial cancer patients who receive concurrent or adjuvant chemotherapy and radiation therapy.

Trends and factors associated with radical cytoreductive surgery in the United States: A case for centralized care.

OBJECTIVES: To describe the US national trends and factors associated with cytoreductive surgical radicality in women with advanced ovarian cancer (OC). METHODS: An analysis of the National Inpatient Sample database was performed. All admissions from 1993 to 2011 for advanced OC cytoreductive surgery (CRS) were identified and categorized as simple pelvic (SP), extensive pelvic (EP), and extensive upper abdominal (EUA) surgery. Annual trends in CRS were analyzed. Associations between patient- and hospital-specific factors, with CRS radicality as well as perioperative complications were explored between 2007 and 2011. RESULTS: In total, 28,677 un-weighted admissions were analyzed. The rate of EP and EUA resections increased over time (8% to 18.1% and 1.3% to 5.4%, P<0.01, respectively). On multivariate analysis, patients were more likely to undergo EUA resections in the Northeast (OR 1.44) or West Coast (OR 1.47) at urban (OR 2.3), or large hospitals (OR 1.4), or if they had private insurance (OR 1.45). EUA surgeries were performed more frequently at high-volume ovarian cancer centers (OR 2.65); additionally, fewer complications were observed after EUA at high compared with low and medium volume hospitals (10.2%, 21.2%, and 21.7%, respectively; P=0.01). Specifically, patients treated at high volume hospitals experienced lower rates of hemorrhage, vascular/nerve injury, prolonged hospitalization, and non-routine discharge than at lower (P<0.05). CONCLUSIONS: The US rate of radical cytoreductive surgery for advanced ovarian cancer is increasing. At high-volume hospitals, patients receive more radical surgery with fewer complications, supporting further study of a centralized ovarian cancer care model.

Perioperative fluid status and surgical outcomes in patients undergoing cytoreductive surgery for advanced epithelial ovarian cancer.

OBJECTIVE: The objective of this study is to investigate the impact of fluid status on perioperative outcomes of patients undergoing cytoreductive surgery (CRS) for advanced epithelial ovarian cancer (EOC). METHODS: Patients undergoing CRS for stage III or IV EOC at a comprehensive cancer center from 12/2010 to 05/2015 were identified. Those who underwent upper abdominal procedures or colon resections were included. Demographic, perioperative, and 30-day complication data were collected. Perioperative weight change was utilized as a surrogate for fluid status. The time to diuresis (tD) was defined as the postoperative day the patient's weight began to downtrend. RESULTS: One hundred ten patients were included. Median age was 62years and median BMI 25.8kg/m2. The majority (74.5%) were stage IIIC. At least 1 bowel resection was performed in 60 cases (54.5%). A median of 5381mL of crystalloid (range 1000-17,550mL) and 500mL of colloids (range 0-2783mL) was given intraoperatively. The median perioperative weight change was +7.3kg (range-0.9kg to +35.7kg). The median tD was 3days (range 1-17days). On univariate analysis, net positive fluid status was associated with unscheduled reoperation, anastomotic leak, surgical site infections (SSI), and length of stay >5days. On multivariate analysis, fluid status was independently associated with SSI (p=0.01). CONCLUSIONS: Perioperative fluid excess is common in patients undergoing CRS for EOC and is independently associated with SSI.

Selective cardiac surveillance in patients with gynecologic cancer undergoing treatment with pegylated liposomal doxorubicin (PLD).

OBJECTIVE: The study objective was to examine the safety and cost savings of selective cardiac surveillance (CS) during treatment with pegylated liposomal doxorubicin (PLD). METHODS: A retrospective, dual institution study of women receiving PLD for the treatment of a gynecologic malignancy was performed. The study period was 2002-2014. At both institutions, a selective strategy for CS was implemented in which only high-risk women with a cardiac history or with symptoms suggestive of cardiac toxicity during PLD treatment underwent a cardiac evaluation. Patient demographics, clinical and treatment history were evaluated. Cost analyses were performed utilizing professional/technical fee rates for echocardiogram and multi-gated acquisition scan for each state. RESULTS: PLD was administered in 184 women. The mean patient age was 62.7years, and 79% were treated for recurrent ovarian or peritoneal carcinoma. The median cumulative administered dose of PLD was 300mg/m(2); 24 received >550mg/m(2). The median follow-up time was 20months. Of the 184 patients, the majority (n=157, 85.3%) did not undergo either an initial cardiac evaluation or surveillance during or post-PLD treatment. Fifty-three patients considered high risk for anthracycline-induced cardiotoxicity underwent CS. Only three patients (1.6%) in the entire cohort developed CHF that was possibly related to PLD treatment; all had significant pre-existing cardiac risk factors. Selective instead of routine use of CS in the study population resulted in a cost savings of $182,552.28. CONCLUSION: Utilizing cardiac surveillance in select women undergoing PLD treatment for gynecologic malignancies resulted in significant health care cost savings without adversely impacting clinical outcomes.

Management of the abnormal Papanicolaou smear and colposcopy in pregnancy: an evidenced-based review.

Women diagnosed with abnormal Papanicolau smears or cervical abnormalities during pregnancy present a challenge to health care providers, as conventional management guidelines appropriate for the non-pregnant population may be contraindicated. The physiologic effects of pregnancy that may result in greater difficulty with the colposcopic examination include increased cervical mucus production that may obscure visualization, cervical hyperemia, gland prominence, and eversion of the columnar epithelium. The squamo-columnar junction may also be difficult to visualize in early pregnancy, but will often evert as the pregnancy continues. Because of these changes, cervical dysplasia may have a more prominent appearance in the gravid patient. Therefore, colposcopy should be performed by a skilled examiner with expertise in the cervical changes of pregnancy. The primary goal of colposcopy during pregnancy is to exclude the presence of invasive cancer, and thus, many cervical lesions may be followed with serial cytology and colposcopy during pregnancy or by deferring further colposcopic examination until the postpartum period. Cervical biopsy should be avoided unless a malignancy is suspected and endocervical sampling is contraindicated. Herein, we present a contemporary, evidence-based review of the colposcopic examination and guidelines for triaging and evaluating abnormal cervical cytology and lesions that are diagnosed during pregnancy.

Malignant melanoma of the vulva: an extension of cutaneous melanoma?

OBJECTIVE: To determine the prognostic significance of the 2002 revisions of the American Joint Committee on Cancer (AJCC) Staging System for cutaneous melanoma in melanoma of the vulva and review the current surgical utilized for treatment of this neoplasm. METHODS: Demographic, surgical and outcomes data were obtained from the records of vulvar melanoma patients treated from 1990 to 2006 at five academic medical centers. The 2002 modifications of the AJCC staging system for cutaneous melanoma, Breslow thickness and Clark level, were applied to all subjects. Kaplan-Meier Modeling and Linear Regression analysis were utilized for data analysis. Statistics were performed with SAS v 9.1. RESULTS: Seventy-seven patients were identified with a median age of 62 years. 73% had Stage I/II disease. Surgical radicality did not impact recurrence rates or survival. Breslow thickness was associated with recurrence (p=0.002) but not survival. Only the 2002 modified AJCC staging criteria were predictive of overall survival (p=0.006) in patients with malignant melanoma of the vulva. CONCLUSIONS: In the largest multi-site series of vulvar melanoma, the AJCC-2002 staging system for cutaneous malignant melanoma appears to be applicable to primary vulvar melanoma. Moreover, surgical radicality was associated with significant morbidity but not with improvement in survival. Utilization of standard operative staging and resection principles in cutaneous melanoma should be used for all vulvar melanoma patients. Moreover, these patients should also be considered for enrollment in cutaneous melanoma clinical trials.

Total laparoscopic hysterectomy versus laparoscopic-assisted vaginal hysterectomy in endometrial cancer: surgical and survival outcomes.

STUDY OBJECTIVE: To compare surgical and survival outcomes of patients with early-stage endometrial cancer (EC) who underwent total laparoscopic hysterectomy (TLH) or laparoscopic-assisted vaginal hysterectomy (LAVH) +/- lymphadenectomy. DESIGN: Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: Two tertiary care academic medical centers. PATIENTS: Patients with EC treated by TLH or LAVH from 1998 through 2006. INTERVENTIONS: TLH and LAVH were performed in 80 and 24 patients, respectively. Patient demographics and clinical variables were collected, and surgical and survival outcomes were determined. MEASUREMENTS AND MAIN RESULTS: Median operating time was significantly higher for patients undergoing LAVH than for those undergoing TLH (212.5 and 183.5 minutes, respectively; p = .039). EBL was also greater in patients undergoing LAVH (median 220 mL) compared with those undergoing TLH (median100 mL; p = .001). After a median follow-up time of 51.5 months, there was no difference in recurrence or survival rates between the groups. CONCLUSION: Early-stage EC can be treated effectively with either TLH or LAVH. TLH patients may experience shorter operating times and less blood loss. When performed by experienced laparoscopists, TLH may be more feasible than LAVH in this cohort of patients.

Sentinel lymph node biopsy in early-stage cervical cancer: utility of intraoperative versus postoperative assessment.

OBJECTIVE: To determine the diagnostic accuracy of sentinel lymph node (SLN) detection using lymphoscintigraphy, intraoperative blue dye, and radiocolloid in patients with early-stage cervical cancer. METHODS: Intra-cervical injection of technetium-99 sulfur colloid and lymphoscintigraphy were performed preoperatively. Isosulfan blue was injected intra-cervically immediately prior to surgery. SLNs were excised and examined intraoperatively (imprint cytology and frozen section) and postoperatively (H and E histology and immunohistochemistry (IHC) for cytokeratin). RESULTS: Thirty eight patients were evaluable. Laparoscopy and laparotomy were performed in 28.9% and 71.1%, respectively. Subjects had squamous cell carcinoma (n=26), adenocarcinoma (n=10) or adenosquamous (n=2) histologies. 55.3% had cervical tumors <2 cm. The overall SLN detection rate was 92.1%. The external iliac region just distal to the common iliac bifurcation was the most common SLN location. A mean of 2.1 SLNs were detected per patient with bilateral SLNs observed in 47.4%. On final pathology, metastatic nodal disease was identified in 15.7% of patients. Of these, 83.3% were detected in the SLNs. Sensitivity of SLN detection of metastasis was 100% for patients with cervical tumors <2 cm. However intraoperative evaluation by imprint cytology and frozen section correctly identified lymph node metastasis in only 33.3%. CONCLUSIONS: SLN detection is feasible and accurately reflects pelvic nodal basin status when performed in early-stage cervical cancer patients. However, while current intraoperative pathology techniques for assessing nodal metastases reliably detect metastases larger than 2 mm, they lack sufficient sensitivity to detect micrometastasis and isolated tumor cells.

Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze.

This study investigated the effect of estrogen treatment on working memory and reference memory of female rats. In addition, the impact of estrogen on the sensitivity of these two types of memory to the cholinergic antagonist scopolamine was investigated. At 35 days of ages, rats were ovariectomized and implanted chronically with Silastic capsules containing either 25% crystalline estradiol or 100% cholesterol. Thirty days after surgery, animals were trained on an eight-arm radial maze with four arms baited to assess both working and reference memory performance. Following training, females were given scopolamine hydrobromide (0.2 mg/kg i.p.) prior to retesting on the task. Results indicated that estrogen treatment improved working memory performance during maze acquisition but did not affect reference memory performance. Scopolamine treatment impaired performance on the working memory component, but not the reference memory component, while estrogen prevented the impairment of working memory by scopolamine. Results support previous evidence that estrogen selectively enhances performance on tasks that depend on working memory.

Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally.

In a previous study, administration of high doses of estradiol benzoate (100 microgram/kg for 3 days im) to ovariectomized Long-Evans rats counteracted impairments of reinforced T-maze alternation induced by systemic administration of scopolamine, a muscarinic receptor blocker. In the current study, daily administration of lower doses of estradiol benzoate (5 microgram/kg for 3 weeks sc) increased the number of correct reinforced alternations during T-maze acquisition in ovariectomized rats compared to oil-treated controls and prevented impairments of reinforced alternation induced by injection of scopolamine hydrobromide (0.2 mg/kg ip). Furthermore, scopolamine (20 microgram) delivered bilaterally to the dorsal hippocampus reduced reinforced T-maze alternation in ovariectomized rats previously trained to complete this task while daily treatment with estradiol benzoate (5 microgram/kg sc) for 1 week prior to scopolamine infusion counteracted this impairment. In summary, physiological levels of estrogen improved performance during acquisition of reinforced T-maze alternation and prevented impairments induced by scopolamine administered systemically or intrahippocampally.

Sexual behavior of Flinders Line female rats bred for differential cholinergic sensitivities.

Flinders Lines are two strains of rats selectively bred for their divergent physiological responses to cholinergic drug challenges. Flinders Sensitive Line (FSL) rats are highly sensitive to cholinergic stimulation of various autonomic and behavioral responses compared to Flinders Resistant Line (FRL) rats. Because cholinergic innervation contributes to the regulation of female sexual behaviors in rats, a study was conducted to compare the sexual responses of FSL females to those of FRL females, as well as to those of Long-Evans (LE) females, a conventional rat strain. Ovariectomized FSL rats exhibited significantly higher incidences of lordosis and proceptive behaviors than ovariectomized FRL and LE rats over a range of estrogen doses (2, 3, 4, 5, or 20 microgram(s)/kg estradiol benzoate at 48 h before testing) administered in combination with progesterone (1 or 2 mg/kg at 4-6 h before testing). In addition, the muscarinic antagonist scopolamine inhibited lordosis behavior strongly in FRL females over a range of doses (0.25, 0.5, 1, 2, or 4 mg/kg), but failed to inhibit lordosis in FSL females. Results indicate that FSL females are highly sensitive to the behavioral effects of gonadal steroids and highly insensitive to the effects of a muscarinic antagonist. The enhanced sexual behavioral responses of FSL females could be a consequence of their well-established cholinergic hypersensitivity or a consequence of other undocumented characteristics of FSL females such as hypersensitivity to ovarian hormones. FSL females could provide a valuable model for the study of estrogen action at behavioral, cellular, and molecular levels.

Safety, efficacy, and cost of pancreaticoduodenal resection in a specialized center based at a community hospital.

OBJECTIVE: To determine whether pancreaticoduodenal resection (PDR) for benign and malignant disease can be performed safely, efficiently, and economically at a 50-bed community hospital. DESIGN: Retrospective review of 39 consecutive PDRs performed in an 18-month period. Indications for surgery, length of hospital stay, complications, and patient charges were analyzed. SETTING: A suburban 50-bed community hospital. PATIENTS: Thirty-nine patients (15 male and 24 female) referred for PDR for benign and malignant disease. MAIN OUTCOME MEASURES: Mortality and morbidity rates, length of hospital stay, care, and cost. RESULTS: Of 39 patients who underwent PDRs, 1 patient (2.6%) died of myocardial infarct. Intraoperative blood transfusions were required by 3 patients (8%). The mean postoperative hospital stay was 11 days. Twenty-four patients (62%) were discharged by day 11. Fifteen patients (38%) were hospitalized 11 to 24 days. Complications in 10 patients (28%) included pancreatic or biliary fistula (n = 6), upper gastrointestinal tract bleeding (n = 1), partial wound dehiscence (n = 1), bacteremia (n = 1), and pneumonia (n = 1). No patient required reoperation. Three patients were rehospitalized within 1 month. Mean patient charges were $21,864, and mean reimbursements were $19,669. CONCLUSIONS: Pancreaticoduodenal resection can be accomplished with low morbidity and mortality rates and a short stay at a community hospital. Thorough preoperative investigations to exclude unresectable lesions must precede every PDR for malignant disease. Mortality and morbidity rates in this series were similar to those for patients with similar diagnoses who were operated on in academic centers. Cost for and length of hospital stay of these 39 patients were significantly lower than those in other reported series.

Estrogen enhances performance of female rats during acquisition of a radial arm maze.

Estrogen can influence the expression of behaviors not associated directly with reproduction, including learning and memory. However, the effects of estrogen on learning and memory in mammals are complex, dependent on a variety of factors. The radial arm maze is a traditional experimental task that takes advantage of the natural foraging strategy of rats and provides an appropriate measure for studying the effects of estrogen on working memory in this species. In the experiments reported here, ovariectomized rats were implanted subcutaneously with 5-mm Silastic capsules containing 25% estradiol diluted with cholesterol. Control females received 5-mm Silastic capsules containing 100% cholesterol. Results of three separate experiments demonstrated that estradiol administered by Silastic implants for 30 days prior to eight-arm radial maze training, during the 24 days of maze training, or both significantly improved working memory performance compared to females treated with cholesterol alone, as indicated by improved arm choice accuracy over trials. The positive effect of estradiol exposure prior to training suggests that estrogen may induce neuronal changes that persist beyond the period of exposure with functional consequences for behavior.

Estrogen and estrogen-progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats.

The purpose of the experiments was to determine if steroid hormone treatments would attenuate the effect of the muscarinic receptor blocker scopolamine on a memory task. Ovariectomized rats were trained first to alternate for food reward between the arms of a T maze. Following training, females treated with scopolamine hydrobromide (0.2 mg/kg ip) did not alternate correctly between the arms of the T maze and responded at chance levels. However, when estradiol benzoate (25 micrograms) was administered 72, 48, and 24 hr before testing alone or in combination with progesterone (500 micrograms) administered 4-6 hr before testing, females alternated successfully between the arms of the T maze following scopolamine administration. Results indicate that gonadal steroids can completely counteract the impairment of T maze performance induced by scopolamine in female rats.

Effects of a muscarinic antagonist on various components of female sexual behavior in the rat.

The effects of the muscarinic antagonist scopolamine on lordosis, solicitation, pacing, approach, attractivity, and activity were evaluated in ovariectomized rats brought into sexual receptivity with estrogen and progesterone. Systemic (1 mg/rat) or intraventricular (10 micrograms bilaterally) administration of scopolamine significantly reduced the incidence of lordosis and solicitation behaviors and disrupted typical pacing of sexual contacts with a stimulus male. In addition, females avoided contact with a stimulus male, but not a stimulus female, following intraventricular infusion of scopolamine. The levels of general activity and frequencies of sexual contacts were similar in females treated intraventricularly with scopolamine and vehicle solutions. Consequently, scopolamine disrupted various components of sexual behavior, including lordosis, solicitation, pacing, and approach, without altering female attractivity or general activity.

When 'something is wrong': a case for investigating vague health complaints.

When a chronically ill elderly woman complained that she felt something was wrong, close attention and follow-up by physician and nursing home staff paid off.

Implementing a "Do-Not-Resuscitate" (DNR) policy in a nursing home.

During implementation of a new Do-Not-Resuscitate (DNR) policy in New York State, decisions by 233 nursing home patients of their surrogates were evaluated. Eighteen patients with capacity (mean age +/- SD = 76.4 +/- 12.1 years) chose DNR; 30 patients with capacity (mean age +/- SD = 76.2 +/- 10.7 years) chose to be resuscitated (CODE); 54 patients without capacity, (mean age +/- SD = 86.1 +/- 9.1 years) had surrogates who chose DNR; and 131 patients without capacity and with surrogates (mean age +/- SD = 81.9 +/- 9.8 years) remained CODE. Most patients with capacity who chose DNR had multiple sclerosis, while most choosing CODE had strokes. Most patients who lacked capacity had dementia. Forty-five percent of surrogates did not respond regarding CODE status during the three-month study interval, and 10% wanted additional time to decide. Patient age appeared to be a factor in surrogate choice for DNR but not in patients with capacity making their own decision. Reasons for patients with capacity choosing DNR are discussed; perceived quality of life and premorbid feelings by patients help in the decision-making process.