BACKGROUND: The optimal management of non-invasive (mucosal and/or ductal) urothelial carcinoma of the prostate remains elusive and there is a paucity of data to guide treatment. OBJECTIVE: Our objective was to systematically review and synthesize treatment responses to conservative management of non-invasive prostatic urothelial carcinoma using intravesical therapy. METHODS: A systematic literature search using MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science databases from inception to November 2019 was performed. Risk of bias assessment was performed using the Newcastle-Ottawa scale for non-randomised studies. Pooled estimates of complete response in the bladder and prostate and prostate only were performed using a random effects model. Pre-specified subgroup analyses were generated to assess differences in complete responses for: BCG therapy vs other agents, ductal vs mucosal involvement, CIS vs papillary tumors and TURP vs no TURP. RESULTS: Nine studies including 175 patients were identified for inclusion in the systematic review and meta-analysis. All were retrospective case series and most evaluated response to BCG therapy. The pooled global complete response rate for intravesical therapy was 60%(95%CI: 0.48, 0.72), and for prostate 88%(95%CI: 0.81, 0.96). Pre-specified analyses did not demonstrate statistically significant differences between subgroups of interest. CONCLUSIONS: Management of non-invasive prostatic urothelial carcinoma using intravesical therapy yields satisfactory results. Caution should be taken in treating patients with papillary tumors and ductal involvement, as data for these populations is limited. TURP may not improve efficacy, but is required for staging. Current recommendations are based on low quality evidence, and further research is warranted.
Mutations in BRCA1 and BRCA2 increase a woman's lifetime risk of developing breast cancer by 43% to 84%. It was originally postulated that BRCA1/2-associated breast cancers develop more rapidly than sporadic cancers and may lack preinvasive lesions. More recent studies have found preinvasive lesions in prophylactic mastectomy specimens from mutation carriers; however, there is little information on the presence of preinvasive lesions in tissue adjacent to breast cancers. Our aim is to investigate the role of preinvasive lesions in BRCA-associated breast carcinogenesis. We retrospectively compared BRCA1/2-associated breast cancers and sporadic breast cancers for the prevalence of preinvasive lesions [ductal carcinoma in situ (DCIS), lobular carcinoma in situ, and atypical lobular hyperplasia] in tissue adjacent to invasive breast cancers. Pathology was reviewed for 73 BRCA1/2-associated tumors from patients with breast cancer. We selected 146 patients with mutation-negative breast cancer as age-matched controls. Among the BRCA1/2-associated breast cancers, 59% had at least one associated preinvasive lesion compared with 75% of controls. Preinvasive lesions were more prevalent in BRCA2 mutation carriers than in BRCA1 mutation carriers (70% versus 52%, respectively). The most common preinvasive lesion in both groups was DCIS; 56% of BRCA1/2-associated breast cancers and 71% of the sporadic breast cancers had adjacent intraductal disease, respectively. Preinvasive lesions, most notably DCIS, are common in BRCA1/2-associated breast cancers. These findings suggest that BRCA1/2-associated breast cancers progress through the same intermediate steps as sporadic breast cancers, and that DCIS should be considered as a part of the BRCA1/2 tumor spectrum.
e20568 Background: Many cancer survivors with non-active disease suffer with pain and other symptoms. This study investigated differences in symptoms and opioid use among cancer pain patients with active versus non-active disease. Methods: Data were obtained from 518 consecutive new patients seen at the Pain Management Center of MD Anderson Cancer Center from 01/01/09 to 06/30/09. Measures: Usual pain was rated on the Brief Pain Inventory. The Edmonton Symptom Assessment Scale (ESAS) was used for ratings of fatigue, shortness of breath, poor appetite, depression, anxiety, drowsiness, difficulty thinking clearly and insomnia. Opioid use was calculated in morphine equivalency daily dose (MEDD) milligrams based on the sum of long- and short-acting opioids used per day. Analyses of Data: Independent samples t-tests were used to make comparisons between patients with active versus non-active disease on continuous variables. Chi-square tests were used to make comparisons across disease status on categorical variables. Results: 349 patients had active disease; 169 patients had non-active disease. Patients with active disease received significantly higher MEDD (125.6 ± 158.8 mg) versus patients with non-active disease (74.4 ± 87.0 mg). Patients with active disease reported significantly higher mean scores on fatigue, poor appetite, and drowsiness. Average weekly pain scores were comparable and moderately high for both groups of patients. Other symptoms and clinical characteristics were not significantly different across disease status. Conclusions: Plausible explanations for the higher opioid use and symptom burden among patients with active disease are cancer treatments and disease progression. A higher level of pain medication is often needed to achieve pain management during active treatment or following recent surgery. The finding of higher fatigue, poor appetite, and drowsiness among those with active disease is also consistent with the symptom burden expected from treatment. Although patients with active disease have a greater symptom burden and need for pain medication, there is a need for pain and symptom management among patients in the non-active disease phase of survivorship.
Background: Previous work examining ethanol's autonomic effects has found contrasting patterns of age‐related differences in ethanol‐induced hypothermia between adolescent and adult rats. Most studies have found adolescents to be less sensitive than adults to this effect, although other work has indicated that adolescents may be more sensitive than adults under certain testing conditions. To test the hypothesis that adolescents show more ethanol hypothermia than adults when the amount of disruption induced by the test procedures is low, but less hypothermia when the experimental perturbation is greater, the present study examined the consequences of manipulating the amount of perturbation at the time of testing on ethanol‐induced hypothermia in adolescent and adult rats. Methods: The amount of test disruption was manipulated by administering ethanol through a chronically indwelling gastric cannula (low perturbation) versus via intragastric intubation (higher perturbation) in Experiment 1 or by either familiarizing animals to the handling and injection procedure for several days pretest or leaving them unmanipulated before testing in Experiment 2 . Results: The results showed that the handling manipulation, but not the use of gastric cannulae, altered the expression of ethanol‐induced hypothermia differentially across age. When using a familiarization protocol sufficient to reduce the corticosterone response to the handling and injection procedure associated with testing, adolescents showed greater hypothermia than adults. In contrast, the opposite pattern of age differences in hypothermia was evident in animals that were not manipulated before the test day. Surprisingly, however, this difference across testing circumstances was driven by a marked reduction in hypothermia among adults who had been handled before testing, with handling having relatively little impact on ethanol hypothermia among adolescents. Conclusions: Observed differences between adolescents and adults in the autonomic consequences of ethanol were dramatically influenced by whether animals were familiarized with the handling/injection process before testing. Under these circumstances, adolescents were less susceptible than adults to the impact of experimental perturbation on ethanol‐induced hypothermia. These findings suggest that seemingly innocuous aspects of experimental design can influence conclusions reached on ontogenetic differences in sensitivity to ethanol, at least when indexed by ethanol‐induced hypothermia.
