External vacuum devices in the treatment of erectile dysfunction: a one-year study of sexual and psychosocial impact

This prospective study assessed the sexual and psychosocial effects of 12 months' use of an external vacuum device in the treatment of erectile dysfunction. Results showed that the external vacuum device produced erections sufficient for intercourse in 87% of the men in our sample. The dropout rate was only 20% over the 12-month period. Use of the external vacuum device was associated with improvements in men's and their partners' sexual functioning. These improvements included erections of better quality, increased partner arousal, and increased frequency of orgasm and sexual satisfaction for men and women. The external vacuum device was also associated with decreases in general psychiatric symptomatology for men. Similar improvements in psychological functioning were not found for partners. Side effects and factors in patient and partner acceptance of the external vacuum device are discussed.     

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Ovarian cancer is the eighth most common cancer and cancer death in women worldwide (1). High-grade serous tubo-ovarian cancer (HGSC) constitutes ∼70% of all ovarian malignancies and has the worst prognosis (2). Current treatment of most patients with HGSC consists of cytoreductive surgery and combination chemotherapy with platinum-containing DNA–cross-linking drugs and taxane-based microtubule-stabilizing agents (2). Although treatment significantly improves survival, most women relapse with chemotherapy-refractory disease and eventually succumb (3). Multiple mechanisms of chemoresistance have been documented (4, 5), including reduced intracellular drug accumulation (6), detoxification by increased levels of glutathione (7), altered DNA damage repair (8, 9), dysfunctional apoptotic pathways (10, 11), and hyperactivation of various cell signaling pathways (12–14). These mechanistic studies are consistent with recent genomic analyses that reveal marked clonal evolution of HGSC during therapy (15). Other evidence, however, supports a hierarchical organization of HGSC, featuring intrinsically chemoresistant “cancer stem cells” (CSCs) that can escape initial treatment and seed recurrence (16–18).Although there is uniform agreement that HGSC patients should receive surgery and chemotherapy, the optimal order and timing of these modalities remain controversial. Two main options exist: primary debulking surgery with adjuvant chemotherapy (PDS), or neoadjuvant chemotherapy, followed by interval debulking surgery (NACT) (19–24). In either case, the surgical standard of care is to seek maximal cytoreduction, with the objective being to leave no visible residual disease. However, the precise definition of such “optimal debulking” can vary among different centers, surgeons, and reports (19, 21, 24, 25).Several studies have found similar outcomes after PDS or NACT, including two highly influential randomized trials (EORTC and CHORUS) carried out across multiple countries (22, 23, 26–28). In both trials, however, the question of potential bias in patient recruitment has been raised, favoring potentially those with more extensive disease, who are less likely benefit from “upfront” surgery (23, 28). Consistent with this interpretation, overall survival in these trials was significantly shorter than that seen in other HGSC cohorts (19, 24, 29, 30). Closer examination of these reports reveals additional factors that might have influenced their conclusions. The EORTC study had inconsistencies in optimal debulking rates between participating centers, with the PDS-associated complete debulking data highly influenced by the results from a single institution (23). The CHORUS study involved 76 clinical sites, and there were substantial differences in surgery execution and chemotherapy drug selection/dosage between them (28).At Princess Margaret Cancer Center, retrospective data showed that PDS patients with no visible disease postresection survived substantially longer (7-y survival, >60%) than those receiving NACT (7-y survival, ∼10%). Furthermore, although residual tumor postresection is a critical determinant of survival, its influence on the PDS group was far more dramatic than on NACT group (24). Of course, this report suffers from deficiencies common to all retrospective analyses, including lack of randomization to account for tumor burden at diagnosis and other factors; indeed, the NACT group in this study did have more extensive disease.Another controversy in HGSC management focuses on the potential benefit of earlier diagnosis. Earlier diagnosis of primary HGSC is generally assumed to enhance patient survival and quality of life (3). Intuitively, one might predict that the same reasoning would apply to recurrent disease; however, survival is similar in relapsed patients treated earlier, based on increasing serum CA125 levels, than in those treated only when physical symptoms of recurrence appear (31). Conceivably, the lead time between CA125 rise and clinical recurrence is too short for earlier chemotherapy to be beneficial; if so, then patient survival might be extended by more sensitive methods, such as testing for circulating tumor DNA (ctDNA) (32, 33).To address these issues, we developed a mathematical framework that models the dynamics of HGSC progression, response to surgery and chemotherapy, and recurrence. Our results, generated over a wide range of parameters and accounting for hierarchical and stochastic models of tumor initiation, argue that PDS is superior to NACT when complete debulking is feasible and suggest that, with currently available therapies, the benefits of earlier detection are intrinsically restricted to primary HGSC.     

An empirical study of the use of living versus deceased study subjects: associations with liver cancer in the selected cancers study.

PURPOSE: In case-control studies, the issue of whether living or deceased controls should be used for deceased cases has been controversial. METHODS: Using data from a study of cancer among men that selected both live (n = 1910) and deceased controls (n = 596) for cases of liver cancer (109 deceased, 59 living), we examined the effects of using information from proxy respondents (cases and controls) and from live cases and controls on associations between liver cancer and known risk factors. Cases diagnosed between 1984 and 1988 were selected from eight population-based cancer registries. Live controls were recruited by random digit dialing, deceased controls from death certificate files. Controls were matched to cases on geographic area, year-of-birth, and race. RESULTS: Adjusted odds ratios (OR) calculated for deceased cases and controls, when compared to odds ratios for live cases and controls, were attenuated towards the null value for history of hepatitis (4.7 vs. 14.9), blood transfusions (1.1 vs. 7.8), and cirrhosis (9.3 vs. 51.1). When all cases and living controls were used, odds ratios did not differ substantially from those for living cases and controls except for cirrhosis (OR = 154.2). For smoking, the odds ratios were similar in all analyses. Adjustment for type of interview (self, proxy) did not eliminate differences between results for living and deceased subjects; significant interactions were found between type of interview and hepatitis, cirrhosis, and blood transfusions. CONCLUSIONS: Selection of live controls for deceased cases is recommended to decrease misclassification in measures of exposure.     

Inadvertent ligation of the left pulmonary artery

In five patients, aged 4 days to 20 months, the left pulmonary artery was inadvertently ligated at the time of attempted closure of the patent ductus arteriosus. The complication was recognized in these patients between 1 day and 5 years later from findings of chest radiography, two-dimensional echocardiography with spectral analysis of Doppler shifted echoes, and angiography. In three patients, the presence of asymmetric pulmonary blood flow on chest radiographs obtained after surgery initially suggested the diagnosis. In the other two patients with bronchopulmonary dysplasia, the diagnosis was made by means of two-dimensional echocardiography and Doppler spectra in one and angiography in the other. On angiograms, the left pulmonary artery distal to the ligation was visualized by delayed opacification from aortic collaterals in three patients and by means of pulmonary venous wedge injection in one. Radiographic and echocardiographic examination with Doppler spectra may permit prompt diagnosis and early correction of this complication.     

A research tool for measurement of recovery from sedation: the Vancouver Sedative Recovery Scale.

The need for a research tool to measure recovery from sedation was identified during the design phase of a study investigating sedative protocols following open heart surgery in children. A thorough review of the literature failed to show any scales that measure degree of sedation in children at various times after initial awakening. The Vancouver Sedative Recovery Scale (VSRS) was developed through an iterative process during which we identified numerous indicators of levels of alertness among sedated children, and then determined the applicability and face validity of these indicators. The VSRS evaluated in this study consists of 12 distinct items that encompass three categories of indicators (response; eye appearance and function; and body movement). Total possible VSRS scoring ranges from 0 to 22 (higher score indicating more alert) because some of the 12 items have more than two rating levels. The VSRS was administered to 82 pediatric intensive care unit and postanesthesia recovery patients, with each patient assessed simultaneously by at least two observers. Internal consistency as measured by Cronbach's alpha was excellent: 0.85. Interobserver agreement or reliability as measured by intraclass correlation was also very high: 0.90; and for individual items Cohen's kappa ranged from 0.65 to 0.89. We consider the VSRS to be a good beginning in our effort to quantify level of alertness after sedation in the pediatric patient population.     

Head and neck lesions: MR-guided aspiration biopsy

Aspiration biopsy guided with computed tomography (CT) has long been a valuable tool in the evaluation of head and neck disease. The ability to obtain diagnoses without the need for surgery has had a significant effect on patient treatment. Magnetic resonance (MR) imaging is now rapidly replacing CT as the primary imaging study for many head and neck diseases. The standard stainless steel needles used for CT-guided biopsy are unsuitable for MR-guided biopsy because significant ferromagnetic artifacts obscure the underlying anatomy. A new needle has recently been designed specifically for use with MR imaging. This needle has far less magnetic susceptibility and therefore does not cause significant image distortion. The authors describe the use of this needle in MR-guided aspiration biopsy of a variety of lesions in the head and neck.