Disparities in survival after trimodality therapy for esophageal adenocarcinoma.

Trimodality therapy with neoadjuvant chemoradiation followed by surgery has emerged as the standard of care for the treatment of locally advanced esophageal cancer. Yet, there is considerable variation in survival within this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. We identified 4,679 patients from the National Cancer Database (NCDB) of the American College of Surgeons who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006 to 2013. We excluded patients with stage IV disease and unknown pathological nodal status. We performed regression analyses using a Cox proportional hazards model to identify independent predictors of overall survival. On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that pathologically node-positive patients who received additional adjuvant chemotherapy were associated with improved survival. Compared to private insurance, Medicaid (HR 1.45, CI 1.22-1.73, P < 0.0001), Medicare (HR 1.17, CI 1.04-1.31, P = 0.0082), or having no insurance (HR 1.50, CI 1.17-1.92, P = 0.0012) were all negative predictors of overall survival. In patients with esophageal adenocarcinoma who have undergone trimodality therapy, a number of different factors are associated with overall survival. In particular, socioeconomic factors relating to access to care are independent predictors of survival. Despite receiving the standard of care, treatment disparities persist in this population of patients.

Prognostic significance of lymph node yield in ypN0 rectal cancer.

BACKGROUND: Neoadjuvant radiation therapy for locally advanced rectal adenocarcinoma decreases lymph node yield. This study investigated the association between survival and number of lymph nodes evaluated in patients with pathologically negative nodes after neoadjuvant therapy. METHODS: Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and had pathologically negative lymph nodes were included from the Surveillance, Epidemiology, and End Results (SEER) database over a 7-year interval (January 2004 to December 2010). Systematic dichotomization for optimal cut-off point identification was performed using statistical modelling. RESULTS: A total of 3995 patients met the inclusion criteria. The majority had T3 (66·7 per cent) and moderately differentiated (71·5 per cent) tumours. The median number of lymph nodes retrieved was 12 (i.q.r. 7-16). An optimal cut-off of nine lymph nodes was identified. Increasing age (P < 0·001), increasing T category (T4 versus T1, P < 0·001; T3 versus T1, P = 0·010), response to neoadjuvant therapy (P < 0·001) and number of nodes evaluated (P < 0·001) were significant factors for overall survival in univariable analysis. After adjustment in the multivariable model, the group with nine or more nodes examined had significantly better overall survival (hazard ratio (HR) 0·76, 95 per cent c.i. 0·65 to 0·88, P < 0·001; 5-year survival 83·2 versus 78·0 per cent) and cancer-specific survival (HR 0·76, 0·64 to 0·92, P = 0·004; 5-year survival 87·9 versus 85·1 per cent) than the group with one to eight nodes examined. CONCLUSION: Overall and cancer-specific survival were worse where fewer than nine lymph nodes were identified after neoadjuvant therapy for locally advanced rectal cancer.

Robotic-assisted laparoscopic radical cystoprostatectomy and extracorporeal continent urinary diversion: highlight of surgical techniques and outcomes.

BACKGROUND: We report our technique for robotic-assisted laparoscopic radical cystoprostatectomy (RARCP) and extracorporeal urinary diversion and present their clinical outcomes. METHODS: Between October 2003 and December 2008 we performed 58 RARCPs with extracorporeal continent urinary diversion. Preoperative, operative and postoperative data was evaluated. RESULTS: Mean patient age was 68 (range 46-89) years, with an average American Society of Anesthesiologists classification of 2.9. Mean operative time was 8 (range 5-11) h. Median blood loss was 450 ml. Thirteen patients received intra-operative blood transfusions and 22 patients received peri-operative blood transfusions. Continent urinary diversions were performed by means of the Studer technique (n = 42) or Indiana pouch (n = 16). Mean number of lymph nodes examined on lymphadenectomy was 27 (range 0-52). CONCLUSIONS: Our RARCP and continent diversion technique is a safe and feasible option for primary urothelial carcinoma of the bladder. Oncological and surgical outcomes are comparable to open cystectomy series.

Surgical palliation at a cancer center: incidence and outcomes.

HYPOTHESIS: Surgical intervention in palliative care is common; however, the indications, risks, and outcomes are not well described. DESIGN: Retrospective review of surgical cases during a 1-year period with a minimum 1-year survival update. SETTING: A National Cancer Institute-designated comprehensive cancer center. PATIENTS: Patients with a cancer diagnosis undergoing operative procedures. MAIN OUTCOME MEASURES: Number of palliative surgeries and analysis of length of stay, morbidity, and mortality. RESULTS: Palliative surgeries comprised 240 (12.5%) of 1915 surgical procedures. There were 170 major and 70 minor procedures. Neurosurgical (46.0%), orthopedic (31.3%), and thoracic (21.5%) surgical procedures were frequently palliative. The most common primary diagnoses were lung, colorectal, breast, and prostate cancers. Length of hospital stay was 12.4 days (range, 0-99 days), with 21.3% of procedures performed on an outpatient basis. The 30-day mortality was 12.2%, with 5 patients dying within 5 days of their procedure. The overall mortality was 23.3% (56/240). Mortality for surgical procedures classified as major was 21.9% (44/170) and 10.0% (7/70) for those classified as minor (Fisher exact test, P<.01). CONCLUSIONS: Significant numbers of palliative procedures are performed at our cancer center. Overall morbidity and mortality were high; however, a significant number of patients had short hospital stays and low morbidity. Palliative surgery should remain an important part of end-of-life care. Patients and their families must be aware of the high risks and understand the clear objectives of these procedures.

Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716.

BACKGROUND: SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Delta-9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists in vitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans. METHODS: Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration. RESULTS: Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time x concentration curve. SR141716 was well tolerated by all subjects. CONCLUSIONS: SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.

Reproductive factors and risk of intermediate- or high-grade B-Cell non-Hodgkin's lymphoma in women.

PURPOSE: The incidence rates of non-Hodgkin's lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.

Prognostic factors for hearing preservation in vestibular schwannoma surgery.

OBJECTIVE: To determine whether prognostic indicators for hearing preservation could be identified in patients with vestibular schwannoma undergoing middle fossa craniotomy resection. STUDY DESIGN: Prospective case review. SETTING: Private practice tertiary referral center. PATIENTS: 333 patients with serviceable hearing and vestibular schwannoma resected by middle fossa craniotomy from 1992 to 1998. MAIN OUTCOME MEASURES: Potential prognostic indicators, including tumor size and nerve of origin, preoperative pure-tone average, speech discrimination, distortion product otoacoustic emission testing, age, auditory brainstem response (ABR), and electronystagmography. RESULTS: Postoperative hearing near preoperative levels was attained in 167 patients (50%), with an American Academy of Otolaryngology-Head and Neck Surgery Class A hearing result in 33% and a Class B result in 26%. Comparison of potential prognostic indicators between groups with hearing preserved and the group with no measurable hearing revealed significant differences in preoperative hearing, ABR, and tumor origin data. Better preoperative hearing, shorter intraaural wave V latency, shorter absolute wave V latency, and superior vestibular nerve origin were associated with higher rates of hearing preservation. CONCLUSIONS: Preoperative hearing status, ABR, and intraoperative tumor origin data were shown to be of value as prognostic indicators.

The HRAS1 minisatellite locus and risk of ovarian cancer.

Approximately 10% of ovarian cancers are due to mutations in highly penetrant inherited cancer susceptibility genes. The highly polymorphic HRAS1 minisatellite locus, located just downstream from the proto-oncogene H-ras-1 on chromosome 11p, consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. Mutant alleles of this locus represent a major risk factor for cancers of the breast, colorectum, and bladder, and it was found that BRCAI mutation carriers with at least one rare HRAS1 allele have a greater risk of ovarian cancer than BRCA1 carriers with only common HRAS1 alleles. There are no conclusive studies of HRAS1 alleles in sporadic epithelial ovarian cancer. A case-control study of HRAS1 alleles was performed on DNA from 136 Caucasian patients with ovarian cancer and 108 cancer-free controls using conventional (Southern blot) and PCR-based methods to determine the frequency of rare HRAS1 alleles. Odds ratios (ORs) were estimated using unconditional logistic regression methods. A single degree of freedom test was used to assess the significance of linear trend across categories of increasing exposure. A statistically significant association between rare HRAS1 alleles and risk of ovarian cancer was observed [OR, 1.70; 95% confidence interval (CI), 1.03-2.80; P = 0.04]. Having only one rare allele was associated with a relative risk of 1.66 (95% CI, 0.91-3.01), whereas having two rare alleles increased the relative risk to 2.86 (95% CI, 0.75-10.94; trend P = 0.03). Analysis of HRAS1 allele types by the age of the case at diagnosis revealed that younger cases (<45 years) had a borderline statistically significant increased association with rare HRAS1 alleles compared to older cases (> or = 0 years; OR, 1.89; 95% CI, 0.90-3.98; P = 0.09). Rare HRAS1 alleles contribute to ovarian cancer predisposition in the general population. Thus, the HRAS1-variable number of tandem repeats locus may function as a modifier of ovarian cancer risk in both sporadic and hereditary ovarian cancer.

Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group.

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)

Sex steroid and prolactin profiles in male American black bears (Ursus americanus) during denning.

Serum sex steroid and prolactin profiles were examined in the male American black bear, Ursus americanus during denning. Sera collected in December and the following March from 8 denning male black bears in Minnesota, U.S.A. were assayed for testosterone, estradiol-17 beta and prolactin. Eight bears were confirmed to be the denning mode based on a serum urea to creatinine ratio less than 10. Serum testosterone concentrations tended to increase from December to the subsequent March whereas serum estradiol-17 beta concentrations tended to decrease during this period. There were few changes in serum prolactin concentrations between December and March. These findings suggest that spermatogenesis and testicular steroidogenesis initiated during denning may be influenced by changes in serum sex steroid concentrations in the American black bear.

Pharmacodynamic effects of new de-nicotinized cigarettes.

The effects of cigarette smoking result from the delivery of nicotine, other components of smoke, and sensory stimulation. In the present study, pharmacological effects of new tobacco-derived de-nicotinized cigarettes (controls) were compared with standard cigarettes. The de-nicotinized cigarettes had the appearance, draw and taste of standard cigarettes but contained and delivered virtually no nicotine (< 0.06 mg), but delivered tar and carbon monoxide (CO). They were compared with cigarettes that delivered nicotine, CO and tar. Subjects (n = 20: 10 men, 10 women) participated in four experimental sessions in which they smoked either a standard cigarette or a de-nicotinized cigarette after either 3 or 12 h of tobacco deprivation. Heart rate, blood pressure, and EEG were recorded before, and for 1 h after, ad lib smoking. Plasma nicotine concentrations verified that de-nicotinized cigarettes did not deliver nicotine. The de-nicotinized cigarettes did not increase heart rate or activate the EEG. The subjects preferred the cigarettes that delivered nicotine compared to the de-nicotinized cigarettes. However, both types of cigarettes reduced subjective measures of tobacco craving and withdrawal. These data extend previous research that suggested the process of smoking and components of tobacco smoke other than nicotine mediate some effects of cigarette smoking. The de-nicotinized cigarettes may prove useful in evaluating effects of smoking independent of the delivery of nicotine.

Pharmacokinetics and pharmacodynamics of moist snuff in humans.

INTERVENTION: Four brands of moist snuff and a non-tobacco mint snuff were tested. Subjects reported to the laboratory for five experimental sessions. After baseline measurement of dependent variables, each subject placed 2 g of one of the brands of snuff (or one Skoal Bandits pouch) between the cheek and gum for 30 minutes. The subjects remained in the experimental laboratory for an additional 60 minutes. SUBJECTS: Ten volunteers who were daily users of smokeless tobacco. MAIN OUTCOME MEASURES: Plasma nicotine concentration, cardiovascular effects, and subjective effects. RESULTS: Large amounts of nicotine were delivered rapidly to the bloodstream. The amount of nicotine absorbed and the rate of absorption were related to the pH of the snuff product in aqueous suspension. Cardiovascular and subjective effects were related to the amount of nicotine absorbed. CONCLUSIONS: Snuff products are capable of rapidly delivering high doses of nicotine, which can lead to dependence. Long-term use of snuff can lead to a number of adverse health effects including oral cancers, cardiovascular diseases, and gingival diseases. For these reasons, it is important that the public health community considers oral snuff use as a burden on public health in the same way that cigarette smoking is recognised.

Effects of cigarette smoking through a partially occluded filter.

The effects of a commercially available corn syrup solution that is applied to the filter end of a cigarette causing an occlusive barrier to cigarette smoke were evaluated. The manufacturer claims that the solution reduces exposure to nicotine, carbon monoxide (CO), and other constituents of tobacco smoke and may aid in smoking cessation by providing a means of gradual nicotine dose reduction. Nineteen volunteers (10 men) smoked commercial cigarettes treated with 0, 1, 2, or 3 drops of the corn syrup solution in a double-blind, crossover experiment. Increases in plasma nicotine after smoking averaged 13.3, 10.5, 9.7, and 6.0 ng/ml in the 0, 1, 2, and 3 drop conditions, respectively. In the 3 drop condition, there was a significant reduction in exhaled CO levels. Subjects reported increased difficulty in cigarette draw and a trend toward decreased strength as a function of the number of drops applied. Cardiovascular and EEG measures of smoking were not significantly affected by the application of the drops. Cigarettes treated with 0, 1, 2, or 3 drops of the solution were machine smoked using methods of the Federal Trade Commission (FTC); nicotine yields were 1.0, 1.0, 0.78, and 0.73 mg of nicotine. These results indicate that Take Out drops reduce exposure to nicotine and other constituents of tobacco smoke from a single cigarette.

The acute pain service: effective or expensive care?

The effect of introducing an Acute Pain Service into a District General Hospital was evaluated by conducting an audit of pain, emesis, sleep and satisfaction before and after inception. A total of 1518 questionnaires were collected; in which surgical patients had been asked to assess their experience pre- and postoperatively. The introduction of an Acute Pain Service significantly (p < 0.0001) improved in-patient perception of pain relief upon return of consciousness after anaesthesia and for 2 days postoperatively, when compared with the experience before its inception. The incidence of emetic sequelae did not increase and both patient satisfaction (p < 0.001) and sleep pattern (p < 0.05) in hospital were significantly improved. An estimate of the economic benefit suggests that the development of Acute Pain Services may be cost effective as well as providing an improved quality of service for patients undergoing surgery.

Dexpanthenol enemas in ulcerative colitis: a pilot study.

OBJECTIVE: To test the hypothesis that topical administration of pantothenic acid, a precursor of coenzyme A, might result in increased tissue levels of coenzyme A, improvement of fatty acid oxidation, and amelioration of ulcerative colitis. MATERIAL AND METHODS: In an open-label pilot study, three patients with active left-sided ulcerative colitis received nightly enemas that contained 1,000 mg of dexpanthenol for 4 weeks. Before and after the study, patients submitted stool specimens for short-chain fatty acid analysis and urine collections for measurement of pantothenic acid and dicarboxylic acids; they also underwent flexible sigmoidoscopy for procurement of biopsy specimens for histologic examination and measurement of colonic coenzyme A activity. A clinical disease activity index and histologic disease activity index were used to assess response. RESULTS: Despite increases in urinary pantothenic acid, no significant changes were found in colonic tissue coenzyme A concentrations, fecal short-chain fatty acid concentrations, or urinary dicarboxylic acid concentrations. Moreover, no significant changes in clinical or histologic disease activity were noted. Although stool frequency and rectal bleeding remained unchanged, all patients noted increased abdominal cramping, and one patient had an increased extent of disease. CONCLUSION: Topically administered dexpanthenol seems to be absorbed, but at the dose used in this study, it did not influence concentrations of colonic coenzyme A activity, fecal short-chain fatty acids, or clinical response in patients with active left-sided ulcerative colitis.

Comparison of dose regimens for the administration of recombinant pro-urokinase in a canine thrombosis model.

Pro-urokinase represents an important addition to the array of thrombolytic drugs currently available for clinical use because of its high clot specificity but distinctly different mechanism compared with that of t-PA. Recombinant pro-urokinase (r-proUK) is a single-chain precursor of high molecular weight urokinase which has been expressed in a mouse myeloma cell line. The present study was conducted to determine the dosing regimen which would produce optimal clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radio-labelled clot which was formed in the heat-damaged femoral arteries of 39 male beagle dogs. The animals were divided into six heparinized treatment groups, each receiving one of five dosing regimens or the vehicle for r-proUK. The total dose (80,000 U/kg) was divided into an initial loading bolus, followed by either a second bolus or by infusions for various time periods, as shown below: Group Treatment Regimen % Lysis 1 r-proUK Bolus/bolus, 50%/50% at 0 and 15 min 52 +/- 7 2 r-proUK Bolus/bolus, 50%/50% at 0 and 30 min 62 +/- 7 3 r-proUK Bolus/infusion, 20%/80% infused to 30 min 41 +/- 8 4 r-proUK Bolus/infusion, 20%/80% infused to 60 min 66 +/- 5 5 r-proUK Bolus/infusion, 50%/50% infused to 30 min 73 +/- 4 6 Vehicle Bolus/infusion, 50%/50% infused to 30 min 12 +/- 6 It was concluded that optimal clot lysis and restoration of femoral flow was accomplished using a regimen in which 50% of the dose was given as a bolus, followed immediately by the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose used in this study, r-proUK did not produce degradation of fibrinolytic or hemostatic plasma proteins.

Alcohol, tobacco and recreational drug use and the risk of non-Hodgkin's lymphoma.

A population based case-control study was conducted to determine whether risk of non-Hodgkin's lymphoma (NHL) in the absence of HIV infection is related to the previous use of tobacco, alcohol or recreational drugs. A total of 378 residents of Los Angeles County who were diagnosed with high- or intermediate-grade NHL were compared with individually age-, race- and sex-matched neighbourhood control subjects with regard to history of use of tobacco products, alcohol and ten specific recreational drugs. Risk of NHL among women decreased with increased consumption of alcoholic beverages (trend P = 0.03), with risk 50% lower among those consuming five or more drinks per week than among non-drinkers. Cocaine, amphetamines, Quaaludes and lysergic acid diethylamide (LSD) were each associated with a significantly increased risk of NHL in men with risk greater among those with more frequent use of these drugs. Confounding factors could not be excluded in these findings. The use of multiple types of drugs was also associated with a significantly increased risk of NHL in men (trend P = 0.005) with risk greatest among those using five or more types of drugs (odds ratio = 5.8, 95% confidence limits = 1.2-28.4); among these drugs, cocaine use appeared to account for the elevated risk of NHL among men based on multivariable analyses.

Seasonal changes in spermatogenesis and testicular steroidogenesis in the male black bear Ursus americanus.

American black bears, Ursus americanus, are seasonal breeders with a mating season in late spring to early summer. The objectives of this study were to determine whether there are seasonal changes in spermatogenesis and immunolocalization of testicular steroidogenic enzymes, and to correlate these changes with peripheral steroid concentrations. Three captive mature bears were maintained in open cages during the summer season and provided with chambers for denning during the winter. Testicular biopsies and blood samples were obtained from anaesthetized bears on 12 March, 15 June, 12 October and 15 January. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised against bovine adrenal cholesterol side-chain cleavage cytochrome P450 (P450scc), human placental 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), porcine testicular 17 alpha-hydroxylase cytochrome P450 (P450c17) and human placental aromatase cytochrome P450 (P450arom). Spermatogenesis changed seasonally: spermatogonia and degenerating spermatocytes were observed in October; spermatogonia and primary spermatocytes were present in January; spermatogonia, spermatocytes and round spermatids were present in March; and spermatogonia through spermatozoa were present in June. P450scc and P450c17 were immunolocalized in spermatids and Leydig cells in June, whereas in October these enzymes were present only in Leydig cells. 3 beta HSD was localized in Leydig cells in June and October with more intense staining in June. Localization of P450arom changed seasonally: no immunostaining in October; positive immunostaining in Sertoli cells in January; more extensive immunostaining in Sertoli cells, peritubular-myoid cells and round spermatids in March; and strong immunostaining in Sertoli cells and round and elongating spermatids in June. Serum testosterone and oestradiol concentrations changed seasonally: testosterone and oestrogen were low in October and January, slightly higher in March, and high in June. The present study demonstrates that in the black bear seasonal changes in spermatogenesis are accompanied by changes in the immunolocalization of testicular steroidogenic enzymes that are correlated with changes in serum testosterone and oestradiol concentrations. The presence of P450arom in Sertoli cells at the beginning of testicular recrudescence suggests that aromatase and oestrogen may play a role in re-initiating spermatogenesis.