Long‐term follow‐up of 3‐month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To report our long‐term follow‐up of an institutional randomized prospective trial of radical prostatectomy (RP) with or without a 3‐month course of neoadjuvant hormone therapy (NHT), which results in pathological downstaging, but generally no reduction in biochemical recurrence (BCR) on early follow‐up (at 3 years).

PATIENTS AND METHODS

From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to RP only or 3 months of goserelin acetate and flutamide before RP. BCR was defined as a detectable serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after surgery, with a confirmatory increase.

RESULTS

The median follow‐up for BCR‐free patients was 8 years. There was no significant difference in BCR‐free probabilities between groups (P = 0.7). The BCR‐free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% confidence interval, CI, 12–16%). A Cox regression showed no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56–2.39, P = 0.7). Overall, two patients had local recurrence and six developed metastases, and were evenly distributed among the RP only and NHT groups.

CONCLUSION

Although our study was not originally powered to detect differences in BCR, there was no overall benefit in BCR‐free probability, local recurrence or metastasis with 3 months of NHT at 8 years of follow‐up. Pending evidence of improvement in patient outcomes, NHT before RP appears to be unjustified outside of clinical trials.     

Adherence to surveillance among patients with superficial bladder cancer

BACKGROUND: Patients diagnosed with superficial bladder cancer who have not undergone total cystectomy are at high risk for recurrence, and bladder surveillance with cystoscopy is recommended for such patients every 3-6 months. We examined the degree to which bladder cancer patients undergo the recommended surveillance procedures and identified patient and primary care provider characteristics associated with nonadherence to these recommendations. METHODS: We used information obtained from the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare-linked database to identify 6717 patients aged 65 years or older who were diagnosed with superficial bladder cancer from 1992 through 1996 and who survived for at least 3 years after diagnosis but did not have a total cystectomy. We used information obtained from Medicare claims forms to examine the frequency with which these patients had a surveillance examination of the bladder during each of five contiguous 6-month intervals from month 7 to month 36 following diagnosis. We examined characteristics of patients and their physicians that were associated with low-intensity surveillance (defined as having an examination during fewer than two of the five possible follow-up intervals). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Only 40% of the entire cohort had an examination during all five intervals; 1216 patients (18.1%) had low-intensity surveillance. Patient characteristics that were independently associated with low-intensity surveillance were being age 75 years or older (adjusted OR = 1.54, 95% CI = 1.35 to 1.74), nonwhite (adjusted OR = 1.94, 95% CI = 1.57 to 2.40), and having favorable tumor histology (adjusted OR = 0.59, 95% CI = 0.48 to 0.72 for poorly differentiated versus referent well-differentiated tumor grade) and high comorbidity (adjusted OR = 1.72, 95% CI = 1.30 to 2.27). Residence in an urban area or in a census tract with low median income was also associated with low-intensity surveillance. CONCLUSIONS: The actual practice of surveillance for patients with superficial bladder cancer differs substantially from the standards recommended in clinical guidelines.     

An evaluation of ventilation system flow rates and levels of carbon dioxide,ambient temperature,and relative humidity in restaurants

Studies of the indoor air quality of restaurants have rarely focused on ventilation system performance in relation to air pollutants and climatic factors. This study was conducted in eight restaurants to examine this issue by determining the ventilation flow rates and the levels of carbon dioxide (CO2), ambient temperature, and relative humidity during at least one complete shift of serving a meal. The mean values of number of dining patrons, ventilation flow rates, and the levels of CO2, ambient temperature, and relative humidity were not significantly different in the nonsmoking dining rooms and the smoking dining rooms. The mean ventilation flow rates in individual restaurants ranged from 42-113 cubic feet per minute per person (cfm/person), overall exceeding the recommended lower limit of 30 cfm/person. The mean levels of CO2 in two restaurants (646 and 819 ppm) were below, and in the other six restaurants (ranging 1,012-1,820 ppm) were above the recommended upper limit of 1000 ppm. The levels of CO2 in each restaurant significantly correlated with the number of dining patrons and in four restaurants accumulated gradually over time. In the nonsmoking dining rooms, the levels of CO2 increased significantly as the ventilation How rates decreased. The mean ambient temperature in restaurants (ranging from 22 degrees C - 24 degrees C) were within the recommended range of 20 degrees C - 26 degrees C. The mean relative humidity in six restaurants (ranging from 46%-59%) were within the recommended upper limit of 60 percent, and in two restaurants (62% and 71%) were slightly higher than this recommended limit. It was concluded that although the mean ventilation flow rates in all restaurants exceeded the recommended value, the design of the ventilation system or the distribution of air flow rate in some sections of restaurants were not appropriate to keep the levels of CO2 and relative humidity at some measurement locations below the recommended limits.     

Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis.

OBJECTIVE: The objective of this study was to report on three members of a family with familial expansile osteolysis; the important point about these patients was that none of them had middle-ear ossicles. STUDY DESIGN AND SUBJECTS: A retrospective case review including three cases with familial expansile osteolysis. SETTING: Department of Otolaryngology in a tertiary referral center. INTERVENTIONS: Each patient underwent computerized tomography of the temporal bone in the coronal view, audiometric and tympanometric evaluations, biochemical investigation, whole body isotope scans by Tc-99 mMDP and X-ray. Also the patients' pedigree was studied. Two of the patients had exploratory middle-ear surgery as well. RESULTS: The temporal-bone computed-tomography scan in the coronal view of all three patients and also exploratory middle-ear surgery, which was done on two of the patients, showed no ossicles in the middle ear of either ear in all three cases. This feature hadn't been reported in previous studies. Hearing loss was revealed in the medical histories since childhood. Audiometry indicated mild to moderate conductive and mixed hearing loss and also an AD-type tympanogram pattern along with an absence of acoustic reflexes in both ears of the cases. Both serum alkaline phosphatase and hydroxyproline levels were elevated. There was an increase in uptake and activity at multiple foci of the whole skeleton. No improvement in hearing thresholds was obtained after reconstruction of the middle ear. CONCLUSION: The total absence of middle-ear ossicles can probably be regarded as a new symptom in some patients with familial expansile osteolysis. Common ossiculoplasty for improving the hearing thresholds in this condition may be unsuccessful; therefore, both surgeons and patients must be completely aware of the contingent undesirable results.     

Effects of garlic supplementation on liver enzymes: A systematic review and meta‐analysis of randomized controlled trials

Current evidence on the beneficial effects of garlic on liver enzymes is contradictory. Therefore, the aim of this systematic review and meta‐analysis is to evaluate the effect of garlic supplementation on human liver enzymes, such as Alanine Transaminase (ALT/SGPT) and Aspartate Transaminase (AST/SGOT). To collect the required data, PubMed, Scopus, ISI Web of Science, and Google scholar databases were systematically searched from inception to June 2019. A meta‐analysis was conducted using the random‐effects model to evaluate the effects of garlic supplementation on ALT and AST levels. The Cochran's Q‐test and inconsistency index were also used to evaluate heterogeneity among the studies. Among a total of 15,514 identified articles, six studies (containing 301 participants) met the inclusion criteria. Results of the meta‐analysis showed that garlic supplementation significantly decreased AST level (Hedges' g = ?0.36, 95% confidence interval [CI]: ?0.72, ?0.004, p = .047); whereas, it had no significant effect on ALT level (Hedges' g = ?0.22, 95% CI: ?0.64, 0.20, p = .310). Results showed that garlic supplementation reduced AST levels significantly; however, had no significant effect on ALT levels. Further studies are still needed to confirm the results.     

Deletions of the INK4A Gene in Superficial Bladder Tumors : Association with Recurrence

The INK4A and the INK4B genes map to chromosome 9p21, an area frequently deleted in bladder neoplasms. In addition to the p16 protein, the INK4A encodes for a second product, termed p19(ARF). We analyzed tissues from 121 patients with initial Ta and T1 tumors. Deletions of the INK4A gene were observed in 17 of 121 (14.1%) cases. Point mutations were identified in 2 of 64 (3.1%) tumors. The INK4A-exon 1beta and the INK4B gene were codeleted with INK4A in all of the homozygously deleted cases analyzed. The p16 promoter underwent de novo methylation in 7 of 47 (14.9%) evaluable cases. The p16-positive phenotype was observed in 18 of 56 (32%) evaluable cases. p16 negative phenotype correlated with deletion and methylation status. A statistically significant association between INK4A homozygous deletions and tumor size was observed (P = 0.003). Patients bearing tumors with INK4A homozygous deletions had a lower recurrence-free survival (P = 0.040) than those with wild type INK4A. In conclusion, deletions and methylation of the INK4A gene occur frequently in superficial bladder tumors. However, only those deletions that affect both the p16 and the p19(ARF), deregulating both the pRb and p53 pathways, correlated with clinicopathological parameters of worse prognosis.     

Formaldehyde exposure,acute pulmonary response,and exposure control options in a gross anatomy laboratory

Formaldehyde exposure, acute pulmonary response, and exposure control options were evaluated in a group of 34 workers in a gross anatomy laboratory. Time-weighted average (TWA) exposure to formaldehyde ranged from 0.07–2.94 parts per million (ppm) during dissecting operations. More than 94% were exposed to formaldehyde in excess of the ceiling value of 0.3 ppm recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). The eight-hour TWA exposure of 31.7% of the subjects exceeded the action level of 0.5 ppm set by the Occupational Safety and Health Administration (OSHA). Reported symptoms included irritation of eye (88%), nose (74%), throat (29%), and airways (21%). Forced vital capacity (FVC) and forced expiratory volume in 3 seconds (FEV₃) decreased, and FEV₁/FVC increased during the exposure. The changes of FEV₃ were statistically different from those of the controls. The results strongly support the necessity for designing and testing special local exhaust-ventilated worktables with necessary flexibility for dissecting operations.     

Organochlorine pesticides and male genital anomalies in the child health and development studies

Increasing rates of cryptorchidism and hypospadias in human populations may be caused by exogenous environmental agents. We conducted a case-control study of serum levels of p,p'-dichlorodiphenyltrichloroethane (DDT) and its major metabolite, p,p'-dichlorodiphenyldichloroethylene (DDE), and cryptorchidism and hypospadias in the Child Health and Development Study, a longitudinal cohort of pregnancies that occurred between 1959 and 1967, a period when DDT was produced and used in the United States. Serum was available from the mothers of 75 male children born with cryptorchidism, 66 with hypospadias, and 4 with both conditions. We randomly selected 283 controls from the cohort of women whose male babies were born without either of these conditions. Overall, we observed no statistically significant relationships or trends between outcomes and serum measures. After adjusting for maternal race, triglyceride level, and cholesterol level, compared with boys whose mothers had serum DDE levels < 27.0 ng/mL, boys whose mothers had serum DDE levels > or = 61.0 ng/mL had odds ratios of 1.34 [95% confidence interval (CI), 0.51-3.48] for cryptorchidism and 1.18 (95% CI, 0.46-3.02) for hypospadias. For DDT, compared with boys whose mothers had serum DDT levels < 10.0 ng/mL, boys whose mothers had serum DDT levels > or = 20.0 ng/mL had adjusted odds ratios of 1.01 (95% CI, 0.44-2.28) for cryptorchidism and 0.79 (95% CI, 0.33-1.89) for hypospadias. This study does not support an association of DDT or DDE and hypospadias or cryptorchidism.     

Using respirators and goggles to control exposure to air pollutants in an anatomy laboratory

BACKGROUND: Engineering or administrative methods are often insufficient or impractical to control exposure to chemicals in anatomy laboratories. This study explored the feasibility of wearing one or a combination of respirators and goggles used as personal protective equipment (PPE) to control exposure in one such laboratory. METHODS: A group of 28 subjects were briefly trained in wearing PPE, fit-tested, and asked to complete a questionnaire regarding their subjective reaction after wearing the assigned PPE ensemble while working in the laboratory. The subjects' exposure to formaldehyde was also measured and generally exceeded the recommended limits. RESULTS: When a full-face respirator or the combination of a half-mask respirator and goggles was worn, a majority of subjects reported no odor problem and no irritation to eyes or upper respiratory system. Subjects accepted the PPE to certain degrees, but those using respirators encountered difficulties communicating with others. CONCLUSIONS: The combination of a half-mask respirator and goggles was the most feasible ensemble to control exposure to air pollutants in an anatomy laboratory.