Patient, treatment and discharge factors associated with hospital readmission within 30days after surgery for vulvar cancer.

OBJECTIVES: The majority of hospital readmissions are unexpected and considered adverse events. The goal of this study was to examine the factors associated with unplanned readmission after surgery for vulvar cancer. METHODS: Patient demographic, treatment, and discharge factors were collected on 363 patients with squamous cell carcinoma in situ or invasive cancer who underwent vulvectomy at our institution between January 2001 and June 2014. Clinical variables were correlated using χ2 test and Student's t-test as appropriate for univariate analysis. Multivariate analysis was then performed. RESULTS: Of 363 eligible patients, 35.6% had in situ disease and 64.5% had invasive disease. Radical vulvectomy was performed in 39.1% and 23.4% underwent lymph node assessment. Seventeen patients (4.7%) were readmitted within 30days, with length of stay ranging 2 to 37days and 35% of these patients required a re-operation. On univariate analyses comorbidities, radical vulvectomy, nodal assessment, initial length of stay, and discharge to a post acute care facility (PACF) were associated with hospital readmission. On multivariate analysis, only discharge to a PACF was significantly associated with readmission (OR 6.30, CI 1.12-35.53, P=0.04). Of those who were readmitted within 30days, 29.4% had been at a PACF whereas only 6.6% of the no readmission group had been discharged to PACF (P=0.003). CONCLUSIONS: Readmission affected 4.7% of our population, and was associated with lengthy hospitalization and reoperation. After controlling for patient comorbidities and surgical radicality, multivariate analysis suggested that discharge to a PACF was significantly associated with risk of readmission.

A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer.

BACKGROUND: Genetic abnormalities underlie the development and progression of cancer, and represent potential opportunities for personalized cancer therapy in Gyn malignancies. METHODS: We identified Gyn oncology patients at the MGH Cancer Center with tumors genotyped for a panel of mutations by SNaPshot, a CLIA approved assay, validated in lung cancer, that uses SNP genotyping in degraded DNA from FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53). RESULTS: Between 5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis. Median age 60 (29-84) yrs. Tumors were ovarian 123 (49%), uterine 74(30%), cervical 14(6%), fallopian 9(4%), primary peritoneal 13(5%), or rare 16(6%) with the incidence of testing high grade serous ovarian cancer (HGSOC) halving over time. SNaPshot was positive in 75 (30%), with 18 of these (24%) having 2 or 3 (n=5) mutations identified. TP53 mutations are most common in high-grade serous cancers yet a low detection rate (17%) was likely related to the assay. However, 4 of the 7 purely endometrioid ovarian tumors (57%) harbored a p53 mutation. Of the 38 endometrioid uterine tumors, 18 mutations (47%) in the PI3Kinase pathway were identified. Only 9 of 122 purely serous (7%) tumors across all tumor types harbored a 'drugable' mutation, compared with 20 of 45 (44%) of endometrioid tumors (p<0.0001). 17 pts subsequently enrolled on a clinical trial; all but 4 of whom had PIK3CA pathway mutations. Eight of 14 (47%) cervical tumors harbored a 'drugable' mutation. CONCLUSION: Although SNaPshot can identify potentially important therapeutic targets, the incidence of 'drugable' targets in ovarian cancer is low. In this cohort, only 7% of subjects eventually were treated on a relevant clinical trial. Geneotyping should be used judiciously and reflect histologic subtype and available platform.

Management and outcomes for elderly women with vulvar cancer over time.

OBJECTIVE: To examine changes over time in survival and treatment for women diagnosed with vulvar squamous cell carcinoma included in the Surveillance, Epidemiology, and End Results (SEER) Program. DESIGN: Retrospective analysis. SETTING: USA, data obtained from the SEER Program for 1988-2009. POPULATION: Women with vulvar squamous cell carcinoma. METHODS: Women were stratified by age: <50, 50-64, 65-79, and ≥80 years. Differences in survival and treatment patterns were analysed between age groups. Multivariate logistic regression models were constructed to examine treatment patterns. Kaplan-Meier and Cox proportional hazards survival methods were used to assess survival. MAIN OUTCOME MEASURES: Vital status from the date of diagnosis until death, censoring or last follow-up. RESULTS: The final study group consisted of 8553 women, 1806 (21.12%) <50 years, 2141 (25.03%) 50-64 years, 2585 (30.22%) 65-79 years, and 2021 (23.63%) >80 years old. After adjusting for patient and tumour characteristics, older women were less likely to have surgery and more likely to receive radiotherapy. Compared with women under 50 years, women 50-64 had a two-fold higher risk of death (HR 1.91, 95% CI 1.55-2.34); those 65-79 years had a four-fold higher risk of death (HR 4.01, 95% CI 3.32-4.82), and those ≥80 years had a seven-fold higher risk of death (HR 6.98, 95% CI 5.77-8.46). These trends stayed relatively constant over the time periods studied. CONCLUSIONS: Women over 50 years are at a higher risk of vulvar cancer-specific mortality, which increases with age. These trends stayed relatively constant over the time periods studied.

Effect of tracheal mucus and tracheal cytology on racing performance in Thoroughbred racehorses.

REASON FOR PERFORMING STUDY: Accumulations of mucus within the trachea are often found during endoscopic examinations of the airways of poorly performing racehorses, but the clinical importance of this finding is unknown. OBJECTIVES: To determine the effect of tracheal mucus, pharyngeal lymphoid hyperplasia (PLH) and cytological indices of tracheal aspirate on racing performance in Thoroughbred horses assessed by race place and whether the horse was raced. METHODS: Endoscopic examination of the nasopharynx, larynx and trachea was performed, and a tracheal aspirate obtained monthly at Thistledown racetrack from April to December, 2002 and 2003. Horses received a score of 0-4 for the degree of PLH and 0-4 for the amount of mucus visible in the trachea. The tracheal aspirate was assessed for turbidity, and total and differential cell counts. Generalised estimating equations models were used as repeated measures models for each risk factor and the level of association assessed through the risk factor's P value in the model. RESULTS: Moderate to severe tracheal mucus (2-4) was a risk factor for poor racing performance. There was no association between degree of PLH, cell counts or turbidity of tracheal wash fluid and racing performance. However, horses that raced had higher total neutrophil counts in tracheal wash aspirates than horses that did not race. CONCLUSIONS: Grades 2-4 tracheal mucus should be considered a potential cause of poor racing performance in Thoroughbred horses. CLINICAL RELEVANCE: Because moderate to severe tracheal mucus accumulation, and not increased tracheal neutrophils, was a risk factor for poor racing performance, functionally significant airway inflammation may best be confirmed by the presence of mucus rather than increased number of neutrophils in the trachea.

Electromyographic activity of the stylopharyngeus muscle in exercising horses.

REASONS FOR PERFORMING STUDY: There is a need to understand the process which leads to failure of recruitment of the stylopharyngeus muscle in clinical cases of nasopharygeal collapse. We therefore studied the timing and intensity of stylopharyngeus muscle activity during exercise in horses. OBJECTIVE: To measure the electromyographic (EMG) activity of the stylopharyngeus muscle in exercising horses and correlate it with the breathing pattern. METHODS: Five horses were equipped with a bipolar fine wire electrode placed on the stylopharyngeus muscle and a pharyngeal catheter. The horses exercised on a treadmill at speeds corresponding to 50 (HRmax50), 75 and 100% of maximum heart rate, and EMG activity of the stylopharyngeus muscle and upper airway pressures were recorded. The EMG activity of the stylopharyngeus muscle was then correlated to the breathing pattern and the activity quantified and reported as a percentage of the baseline activity measured at HRmax50. RESULTS: There was ongoing activity of the stylopharyngeus muscle throughout the breathing cycle; however, activity increased towards the end of expiration and peaked early during inspiration. Tonic activity was present during expiration. Peak, mean electrical and tonic EMG activity increased significantly (P<0.05) with exercise intensity. CONCLUSION: The stylopharyngeus muscle has inspiratory-related activity and tonic activity that increases with speed. POTENTIAL RELEVANCE: The stylopharyngeus muscle is one of a group of upper airway muscles that function to support and maintain the patency of the nasopharynx during inspiration. Failure of recruitment of the stylopharyngeus muscle during exercise is a potential explanation for clinical cases of dorsal pharyngeal collapse, but further work investigating the activity of the stylopharyngeus muscle in horses affected by this disease is needed.

The effect of bilateral glossopharyngeal nerve anaesthesia on swallowing in horses.

REASONS FOR PERFORMING STUDY: Dysfunction of the glossopharyngeal nerve has been implicated as a cause of dysphagia in horses. However, recent studies have indicated that this is not the case. OBJECTIVES: To determine whether bilateral glossopharyngeal nerve anaesthesia would cause dysphagia in horses or result in measurable alterations in the timing, function, or sequence of swallowing. METHODS: Swallowing was evaluated in 6 normal horses with and without bilateral glossopharyngeal nerve anaesthesia. Swallowing dynamics were assessed subjectively and objectively based on time from prehension of food until swallowing, number of tongue movements until initiation of swallowing, depth of bolus at the base of the tongue prior to initiation of swallow and evidence of tracheal aspiration using fluoroscopy and endoscopy. RESULTS: There was no evidence of aspiration or dysphagia in horses before or after bilateral glossopharyngeal nerve block. No observed or measured differences in swallowing sequence or function could be detected in blocked compared to unblocked horses. However, there was a trend in blocked horses for the number of tongue pushes and the time to swallowing to be increased. CONCLUSIONS: Glossopharyngeal nerve function may not be essential for normal swallowing function in otherwise healthy horses. POTENTIAL RELEVANCE: Clinically, normal swallowing is not an appropriate test of glossopharyngeal nerve function and dysphagic horses should not be assumed to have glossopharyngeal nerve dysfunction.

Effects of stylopharyngeus muscle dysfunction on the nasopharynx in exercising horses.

REASONS FOR PERFORMING STUDY: Nasopharyngeal collapse has been observed in horses as a potential cause of exercise intolerance and upper respiratory noise. No treatment is currently available and affected horses are often retired from performance. OBJECTIVE: To determine the effect of bilateral glossopharyngeal nerve block and stylopharyngeus muscle dysfunction on nasopharyngeal function and airway pressures in exercising horses. METHODS: Endoscopic examinations were performed on horses at rest and while running on a treadmill at speeds corresponding to HRmax50, HRmax75 and HRmax, with upper airway pressures measured with and without bilateral glossopharyngeal nerve block. RESULTS: Bilateral glossopharyngeal nerve block caused stylopharyngeus muscle dysfunction and dorsal nasopharyngeal collapse in all horses. Peak inspiratory upper airway pressure was significantly (P = 0.0069) more negative at all speeds and respiratory frequency was lower (P = 0.017) in horses with bilateral glossopharyngeal nerve block and stylopharyngeus muscle dysfunction compared to control values. CONCLUSIONS: Bilateral glossopharyngeal nerve anaesthesia produced stylopharyngeus muscle dysfunction, dorsal pharyngeal collapse and airway obstruction in all horses. POTENTIAL RELEVANCE: The stylopharyngeus muscle is probably an important nasopharyngeal dilating muscle in horses and dysfunction of this muscle may be implicated in clinical cases of dorsal nasopharyngeal collapse. Before this information can be clinically useful, further research on the possible aetiology of stylopharyngeus dysfunction and dysfunction of other muscles that dilate the dorsal and lateral walls of the nasopharynx in horses is needed.

Efficacy of oral and intravenous dexamethasone in horses with recurrent airway obstruction.

REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. OBJECTIVES: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.

Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats.

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.

Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy. METHODS: Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB--IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998. Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan--Meier method and log-rank test were used for survival analysis. RESULTS: The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20--75 years). Median cervical tumor diameter was 3.2 cm (range 0.5--11.0 cm). Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001). PE and VAC chemotherapy was associated with increased survival (P < 0.01). CONCLUSION: NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival.