Combining Algorithms to Find Signatures That Predict Risk in Early-Stage Stomach Cancer.

This study applied two mathematical algorithms, lattice up-stream targeting (LUST) and D -basis, to the identification of prognostic signatures from cancer gene expression data. The LUST algorithm looks for metagenes, which are sets of genes that are either overexpressed or underexpressed in the same patients. Whereas LUST runs unsupervised by clinical data, the D -basis algorithm uses implications and association rules to relate gene expression to clinical outcomes. The D -basis selects a small subset of the metagene (a signature) to predict survival. The two algorithms, LUST and D-basis, were combined and applied to mRNA expression and clinical data from The Cancer Genome Atlas (TCGA) for 203 stage 1 and 2 stomach cancer patients. Two small (four-gene) signatures effectively predict survival in early-stage stomach cancer patients. These signatures could be used as a guide for treatment. The first signature (DU4) consists of genes that are underexpressed on the long-survival/low-risk group: FLRT2, KCNB1, MYOC, and TNXB. The second signature consists of genes that are overexpressed on the short-survival/high-risk group: ASB5, SFRP1, SMYD1, and TACR2. Another nine-gene signature (REC9) predicts recurrence: BNC2, CCDC8, DPYSL3, MOXD1, MXRA8, PRELP, SCARF2, TAGLN, and ZNF423. Each patient is assigned a score that is a linear combination of the expression levels for the genes in the signature. Scores below a selected threshold predict low-risk/long survival, whereas high scores indicate a high risk of short survival. The metagenes associate with TCGA cluster C1. Both our signatures and cluster C1 identify tumors that are genomically silent, and have a low mutation load or mutation count. Furthermore, our signatures identify tumors that are predominantly in the WHO classification of poorly cohesive and the Lauren class of diffuse samples, which have a poor prognosis.

Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide implementation and audit leads to improved value and patient outcomes.

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.

Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies.

BACKGROUND: Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO(2)) may be an effective option for some patients. METHODS: In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded. RESULTS: Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO(2) were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO(2) is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies. CONCLUSIONS: Based on the evidence and expert consensus opinion, HBO(2) is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO(2) therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO(2) may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft-tissue necrosis, and osteonecrosis); andHBO(2) may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis.

Dose-dependent attenuation of heroin self-administration with lobeline.

Behavioural studies have yielded results that show lobeline has the ability to attenuate d-methamphetamine self-administration. Further in vivo and in vitro studies have demonstrated a blockade of mu-opioid receptors with lobeline. The present investigation examined the ability of lobeline to attenuate heroin intravenous (i.v.) self-administration when administered prior to testing. Male Sprague-Dawley rats were surgically implanted with jugular catheters and trained to lever press for i.v. heroin infusions (18 microg/kg) under a fixed ratio-2 schedule wherein two active lever presses resulted in heroin delivery. Rats then were tested for heroin self-administration after pretreatment with subcutaneous lobeline injections (0.3, 1.0, or 3.0 mg/kg, 15 min prior to testing sessions). At doses of 1.0 and 3.0 mg/kg, lobeline attenuated self-administration of heroin. The results suggest a potential for lobeline to be used in pharmacotherapy for opioid abuse.

Cytology and outcome of LSIL: cannot exclude HSIL compared to ASC-H.

OBJECTIVE: The cytological features associated with clinical outcome of 'LSIL cannot exclude HSIL (LSIL-H)' in comparison with 'atypical squamous cells cannot exclude HSIL (ASC-H)' are incompletely described. METHODS: LSIL-H and ASC-H Pap tests reported in a regional laboratory during a 13-month period were reviewed by two pathologists. Cytological features suspicious for HSIL were evaluated against a check list of 52 atypical features. All histology over 2 years of follow up for tests reclassified as LSIL-H and ASC-H was retrieved to determine clinical outcome. Atypical cytological features were correlated with outcome. RESULTS: The review yielded 89 LSIL-H and 86 ASC-H. The highest ranked atypical cytological feature in each group was increased nuclear cytoplasmic ratio. Clinical outcome was positive (CIN II/III or AIS) in 44 (49%) LSIL-H and 33 (38%) ASC-H. Round (P = 0.02) and naked nuclei (P = 0.009) were significant correlates of outcome amongst LSIL-H tests, but no feature correlated with outcome in the ASC-H group. CONCLUSIONS: LSIL-H is different to ASC-H because of the 11% higher frequency of a positive outcome and the cytological features associated with outcome.

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort.

OBJECTIVE: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome. METHODS: All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved. RESULTS: The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test. CONCLUSION: In this population, ThinPrep was superior to the conventional Pap test.

Postoperative chemotherapy in advanced ovarian granulosa cell tumors.

The objective of this research is to assess the use of first-line postoperative chemotherapy in patients with advanced ovarian granulosa cell tumor (GCT). A retrospective population-based case series identified 60 women with stage IC or greater ovarian GCT over a 25-year period. Five patients were excluded because of incomplete information. None of the patients had received chemotherapy or radiotherapy prior to the diagnosis of advanced GCT. All patients had, at a minimum, a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology was centrally reviewed and the diagnosis confirmed. Of the 55 eligible patients, the 21 women with stage III and IV disease were the main focus of the study. Clinical outcomes and survival were compared between 13 women who received combination chemotherapy and eight who did not. Univariate analysis was conducted to assess the impact of age at diagnosis, size of residual disease, and adjuvant use of radiation therapy on prognosis. For the 55 patients, median age at diagnosis was 54 years (range 22-79). Median length of follow-up was 4.4 years (range 0.3-23.3). Median time to progression was 2.3 years (range 0.3-5.3). Sixty percent of those with no macroscopic disease after primary surgery recurred within 4.5 years of diagnosis. All patients with gross residual disease (>2 cm) were dead within 4 years of diagnosis. Overall 5 years survival rate was 61.6% (95% CI (49.3-76.9)). Among stage III and IV patients, there were no differences with respect to age at diagnosis and use of radiation therapy between those who did and did not receive chemotherapy. The only statistically significant difference was the presence of macroscopic residual disease (82% vs. 22%). Although there was no statistical significant difference in overall survival, there was a trend toward a poorer outcome in the group that received chemotherapy. Survival of patients with macroscopic residual disease was not influenced by use of chemotherapy (P = 0.976). We conclude that the presence of macroscopic residual disease after primary surgery was the most important prognostic factor. Although these patients were more likely to receive postoperative chemotherapy, there was no evidence to document a beneficial effect of systemic therapy in this group of women.

Identification and action of juvenile hormone III from sexually mature alate females of the red imported fire ant, Solenopsis invicta.

Analysis of extracts of hemolymph obtained from sexually mature alate females of Solenopsis invicta from monogyne colonies resulted in identification of juvenile hormone III (JH III). The average amount of JH III was 0.32+/-0.04 pmol/&mgr;molof hemolymph. Topical application of 0.038 pmol of JH III was sufficient to stimulate alates to shed their wings in the presence of the queen. The time in which alates were induced to dealate decreased linearly with increasing concentrations of JH III from 0.038 to 3.8 pmol. However, higher JH III concentrations deviated from linearity and did not reach dealation times comparable with those that occur after mating flights. Thus, it appears that the mechanism of dealation that occurs when female alates are out of the influence of their queen is different from the one associated with mating flights. Application of 0.42 &mgr;mol of precocene II inhibited dealation of alates in queenless colonies. However, this inhibition was reversed after applying 38 pmol JH III to precocene-treated alates. The sizes of corpora allata (CA) from sexuals treated with JH III did not differ from those of controls. However, the sizes of CA were reduced in alates treated with precocene II. The results indicated that JH was important to dealation.

The effects of perinatal exposure to lead on the discriminative stimulus properties of cocaine and related drugs in rats.

RATIONALE: Developmental lead exposure may alter responsiveness to cocaine well into adulthood, and ultimately influence drug-use patterns. OBJECTIVES: The present study examined the effect of perinatal lead exposure on the discriminative stimulus properties of cocaine. METHODS: Female rats were treated with 0, 8, or 16 mg lead daily for 30 days before breeding with untreated males. This exposure regimen continued through gestation and until postnatal day (PND) 21, i.e., weaning. At PND 60 male pups were trained to discriminate between saline and cocaine (5 mg/kg) injections. After acquisition, a series of generalization/substitution tests were performed using a cumulative dosing procedure. RESULTS: Developmental lead exposure produced subsensitivity to SKF-82958 (D1-like dopamine receptor agonist), quinpirole (D2-like dopamine receptor agonist), and apomorphine (mixed D1-like/D2-like dopamine receptor agonist); but no differences were evident among lead-treatment groups on generalization/substitution tests with cocaine, d-amphetamine, or GBR-12909. Furthermore, when the kappa-opioid receptor agonist U69,593 was administered prior to cocaine (5 mg/kg), generalization to the cocaine stimulus decreased in control rats, but generalization in lead-exposed rats was not altered. Group differences were not evident in tolerance or recovery of tolerance to cocaine following repeated cocaine administration (60 mg/kg per day for 14 days). Furthermore, no differences were found across groups in concentrations of lead in brain, although pups exposed to 16 mg lead had slightly elevated blood lead concentrations (<7 microg/dl). CONCLUSIONS: These results further a growing research literature that suggests developmental lead exposure can produce long-lasting changes in drug responsiveness, even after exposure to the toxicant has been discontinued.

Quality of life in ovarian cancer patients receiving chemotherapy.

OBJECTIVE: A descriptive study was performed to evaluate the variables which influence the quality of life of women with ovarian cancer undergoing chemotherapy treatment. METHODS: The study involved a chart review of 60 women with ovarian cancer and analysis of their compiled EORTC QLQ-C30 Quality of Life (QoL) questionnaires. Analyses were performed using SPSS software to test the relationship of a number of biomedical variables with QoL outcomes. RESULTS: In comparing QoL scores between newly diagnosed women receiving first-line (cisplatin) chemotherapy and women receiving palliative (carboplatin) therapy for recurrent disease, those receiving first-line therapy had more appetite disturbance, diarrhea, and nausea than women in the latter group. Over time, global QoL declined for newly diagnosed patients, while it improved for those with recurrent disease. A third finding was that younger women reported more fatigue over the course of their treatment than older women. Finally, lower QoL was found to be able to predict death within 12 months after starting treatment. CONCLUSIONS: The EORTC QLQ-C30 can be used to test clinical assumptions and to influence treatment programs of women with ovarian cancer undergoing chemotherapy. The results confirmed the assumption that carboplatin has less of an impact on QoL than cisplatin. Also, the finding of improvements in QoL over time, for the women with recurrent disease, supports the use of carboplatin as palliative treatment. The differences observed in QoL between survivors and nonsurvivors 12 months after starting treatment may help identify high-risk patients for closer monitoring. Brief, structured QoL assessments before clinic appointments may be useful for improving the overall care of ovarian cancer patients.

Low-level lead exposure and intelligence in children.

Numerous prospective and cross-sectional studies of the relation between low-level lead exposure and cognitive functioning in children have suggested that intellectual and academic performance declines as lead burdens increase. Kaufman [Arch. Clin. Neuropsychol. (2001)] raises questions regarding interpretive issues along these lines, and therein challenges the wisdom of using the available lead/IQ data complex as an essential element of the decision-making process that leads to policy statements. In this article, we address some of the concerns expressed by Kaufman, and conclude that each of his five points are logically or statistically flawed, as is his overall strategy of critiquing individual studies after methodologically sound meta-analyses have been performed. Kaufman is perhaps correct that the findings from correlational research on low lead levels and IQ loss should be interpreted with caution, but the caution extends equally if not more greatly in the direction of previous research having underestimated the relationship between the two variables in question.

Perinatal exposure to lead attenuates the conditioned reinforcing properties of cocaine in male rats.

The purpose of this study was to examine the effects of developmental lead exposure on drug responsiveness later in the life cycle. Adult female rats were gavaged daily with 0, 8, or 16 mg lead for 30 days before breeding with non-exposed males. The respective exposure regimens were maintained throughout gestation and lactation (perinatal exposure). In Experiment 1, at postnatal day (PND) 30 or 90, pups were trained with 0, 1.25, 2.5, or 5 mg/kg cocaine HCl (IP) in a biased conditioned place preference (CPP) procedure. At both PND 30 and 90, an attenuation in CPP was present in animals exposed to 8 or 16 mg lead relative to control rats. Using an identical lead-exposure regimen, a conditioned place aversion (CPA) procedure with 0, 10, 20, or 40 mg/kg lithium chloride (IP) was employed for Experiment 2. No significant differences were present among pups from each lead-exposure group conditioned and tested at PND 30 or 90, thus suggesting that an impairment of associative mechanisms was not solely responsible for the pattern of attenuation present in Experiment 1. Subsequent analyses of blood-lead in all experiments demonstrated concentrations below 5 microg/dl for all animals at PND 30 and below detectable limits (<1 microg/dl) at PND 90. The findings suggested attenuation in cocaine reinforcement with perinatal lead exposure even though the metal apparently had gained clearance from soft tissue.

Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats.

The effects of adult and perinatal lead treatment on the development of locomotor sensitization produced with repeated morphine administration was investigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg/kg morphine sulfate or water vehicle (ip) and locomotor activity was monitored for 14 consecutive days. While both control and lead-exposed animals demonstrated a locomotor sensitization to morphine, the magnitude of the increased locomotor response was reduced in lead-treated animals. Subsequent analysis of blood-lead in the adult lead-exposed animals indicated residue levels ranging between 20 and 30 microg/dl. In Experiment 2, adult female rats were treated daily with 0, 8, or 16 mg lead via gavage for 30 days before breeding with non-exposed males. Lead exposure in dams continued through gestation and until pups were weaned at postnatal day (PND) 21. At PND 60, male offspring received morphine or vehicle challenges identical to those described in Experiment 1. Animals perinatally exposed to dams receiving 16 mg lead daily demonstrated an enhanced behavioral response to morphine relative to control animals. Analysis of offspring blood indicated lead levels below detectable limits (<1 microg/dl) for all animals. The results suggest exposure to lead at environmentally relevant levels produces long-lasting changes in drug-induced behavior, and the developmental period in which lead exposure occurs is a significant contributor to the manifestation of these effects.

Dietary cadmium exposure alters characteristics of training, substitution, and tolerance when morphine is used as a discriminative stimulus.

This study examined the possibility that cadmium, a toxicant in high concentration in all tobacco products, may alter the stimulus properties of morphine. Adult male rats were exposed to regular laboratory chow (Group Control) or chow containing 100 ppm added cadmium chloride (Group Cadmium). Following an initial 30 day exposure period, control and cadmium-exposed animals were trained to discriminate between i.p. injections of 3.00 mg/kg morphine sulfate and vehicle (distilled water) in a two-choice drug discrimination task. Subsequently, the morphine dose-effect generalization function (0.75-6.00 mg/kg) was determined for control and cadmium-exposed animals. Additional substitution tests were conducted with increasing doses of the high efficacy mu agonist fentanyl (0.0016-0.04 mg/kg), the intermediate efficacy mu agonist (-)-metazocine (0.60-5.00 mg/kg), and the kappa agonist (+/-)-bremazocine (0.03-0.12 mg/kg). Also, increasing doses of the selective mu antagonist naloxone (0.0008-0.50 mg/kg) were presented against the training dose of morphine (3.00 mg/kg) and 0.02 mg/kg fentanyl. Finally, training was discontinued, and control and cadmium-exposed animals were injected with 8.00 mg/kg morphine in the home cage every 12 hr for 2 weeks, prior to redetermining the morphine dose effect function. Following a 1 week recovery period where morphine injections were discontinued, a final determination of the morphine dose-effect function was made. The results of the investigation indicated that cadmium exposure, without affecting the rate-changing properties of the drugs, slowed initial acquisition of the morphine discrimination, decreased the potency of selective doses of naloxone with respect to antagonizing the stimulus effects of morphine and fentanyl, and blocked the development of tolerance to morphine. Morphine, fentanyl, and (-)-metazocine generalized (substituted) equally across both groups, while (+/-)-bremazocine failed to substitute for the morphine stimulus in either group. These findings add to the growing literature on the interaction between metal poisoning and drug selection/abuse.

Developmental lead exposure alters the stimulatory properties of cocaine at PND 30 and PND 90 in the rat.

The aim of this study was to examine the effects of perinatal lead exposure on locomotor responding following acute and repeated cocaine challenges (sensitization). Adult female rats were gavaged daily with 0, 8, or 16 mg lead acetate for 30 days prior to breeding. This exposure regimen was maintained throughout gestation and lactation (perinatal exposure). On Day 21, male pups were weaned and lead exposure was discontinued for the remainder of the study. Beginning on postnatal day (PND) 30 or PND 90, and continuing for 14 successive days, separate groups of perinatally-exposed animals were presented with challenges of 10 mg/kg cocaine HCl (i.p.), and tested for locomotor responding. Following this testing period, dose-effect profiles were determined, with animals receiving daily injections of 0, 10, 20, and 40 mg/kg cocaine. The results indicated that both at PND 30 and PND 90 lead-exposed animals were less responsive to the initial administration of cocaine, but exhibited a supersensitivity to the stimulatory effects associated with repeated administration of cocaine, i.e., behavioral sensitization to cocaine was augmented by perinatal lead exposure. Analyses of blood lead levels following the completion of testing revealed that lead levels were below detectable limits for all animals (< 1 microg/dl). Collectively, these findings show that developmental lead contamination produces changes in cocaine sensitivity long after exposure has been discontinued and the toxicant has gained clearance from blood.

Use of fecal extract trails to enhance trap catch in German cockroach (Dictyoptera: Blattellidae) monitoring stations.

An aqueous extract of German cockroach, Blattella germanica (L.), fecal material was evaluated for inducing trail-following behavior in German cockroaches. In arena tests the fecal extract was found to stimulate trail following in 74% of adult male cockroaches. Significantly fewer cockroaches (22%) followed water-treated (control) trails. Residual activity of the fecal extract trails was evaluated by bioassay after the trails had been stored in the refrigerator or in the open air. Although trails stored in the refrigerator showed no decline in activity after 14 d, those stored in the open air declined significantly after 3 d, inducing only 40% of adult male cockroaches to follow the trail. After 7 d the activity of trails stored in the open air was further reduced to 23%. The ability of fecal-extract trails to influence trap catch in monitoring stations was determined by bioassay. Paper trails treated with fecal extract or water were positioned between cockroach harborages and monitoring stations inside 122-cm2 arenas. The presence of the fecal extract-treated trails significantly enhanced trap catch. Mean catch in the traps with fecal extract trails was 28 cockroaches compared with a mean of 11 cockroaches in the control traps. The trap catch ratios of adults to nymphs in the treated and control treatments were not significantly different.

Vitellin and vitellogenin in the soldier bug, Podisus maculiventris: identification with monoclonal antibodies and reproductive response to diet.

A 171,000 M(r )polypeptide of Podisus maculiventris (Say) (Heteroptera: Pentatomidae) that constituted 16% of the protein in eggs also constituted up to 25% of the protein in hemolymph of fed females. It was identified as the major or sole apoprotein of vitellogenin. Eggs contained major polypeptides of 171, 106, and 51 kDa. The hemolymph polypeptide was identified with a polypeptide (vitellin) in egg extracts by comparing molecular weights, specificity of occurrence in fed females, and immunological reactivities. Females, starved for 5 days after eclosion to assure complete previtellogenic development, produced vitellogenin within a day after feeding on larval Galleria mellonella, and within 4 days after feeding on an artificial diet. Appearance of vitellogenin preceded ovarian growth by 2-3 days. Two monoclonal antibodies raised against egg proteins of P. maculiventris were selected for their strong reaction against egg extract and female hemolymph and null reaction against male hemolymph. Only one 170-kDa band in egg and hemolymph reacted with the antibodies on denaturing Western blots. These monoclonal antibodies are being used to develop an enzyme-linked immunosorbent assay (ELISA) to quantitate reproductive response of females to diets of differing quality.

Management of aggressive histologic variants of endometrial carcinoma at the Tom Baker Cancer Centre between 1984 and 1994.

OBJECTIVE: The aim of this study was to determine the patient characteristics and outcome of patients with aggressive histologic variants (AV) of endometrial carcinoma, including uterine papillary serous carcinoma (UPSC), uterine clear cell carcinoma (UCCC), and mixed type. METHODS AND MATERIALS: All cases with AV histological type of endometrial carcinoma from January 1984 to December 1994 at the Tom Baker Cancer Centre were identified using the Alberta Cancer Registry. Relevant data from the charts of these patients were entered into a study database (Microsoft Excel) and analyzed for presentation, demography, treatment parameters, and outcome of treatment. All pathology was reviewed at the time of diagnosis. Statistical analysis was performed using the S-plus statistics computer program. Univariate and multivariate analyses were used to assess independent prognostic factors using the Cox proportional hazards model. RESULTS: A total of 103 patients with AV histological type were identified and analyzed; there were 61, 31, and 11 cases of UPSC, CCC, and mixed tumors, respectively. Sixty-three patients had Stage I, 11 had Stage II, 15 had Stage III, and 14 had Stage IV disease. The median age of patients was 67 years with a range of 36 to 86 years. Median follow-up was 60 months with a range of 36 to 156 months. The Cox proportional hazards model showed that lymphvascular space invasion and stage are the two independent prognostic factors affecting recurrence and survival. Forty six percent of all cases underwent surgery alone, 39% underwent treatment which included pelvic RT, and 17% underwent treatment which included chemotherapy. Pelvic recurrence was reduced significantly by radiotherapy in Stages I, II, and III (19% recurrence with no RT vs 7% recurrence with RT, P < 0.005). Chemotherapy improved overall survival, but made little difference in distant relapse rates. CONCLUSIONS: Stage Ia cases treated by surgery alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. Patients with Ib, Ic, II, and III have significantly lower pelvic failure rates if treated with pelvic radiation, but still have a high distant failure rate. Systemic therapy did not significantly improve distant relapse-free survival, but did extend overall survival. Stage IV patients usually died within 6 months with a few responding to systemic chemotherapy. These results suggest that there is a need for randomized trials for these patients.

Urolithiasis following formation of a continent urostomy: case report and review of the literature.

BACKGROUND: Formation of urinary stones in a continent urostomy (Indiana pouch) has been described as a late complication. Management of a patient with symptomatic multiple large stones and review of the literature are outlined. CASE REPORT: A 32-year-old woman presented with recurrent urinary tract infections and pyelonephritis 6 years after a total pelvic exenteration and creation of a continent urostomy for central recurrent carcinoma of the cervix after radical pelvic radiation. Multiple large stones were found to be the underlying etiology. Laparotomy, enterocystotomy, and removal of stones were performed without apparent complication. CONCLUSION: It is recommended that for single calculi or multiple small stones, electroshock wave lithotripsy or the percutaneous endoscopic approach be considered. For larger stones the use of laparotomy and enterocystostomy may be appropriate.

Chronic cadmium exposure attenuates conditioned place preference produced by cocaine and other drugs.

Adult male rats were exposed ad lib for 40 days to 100 ppm dietary cadmium chloride (group cadmium) or an identical diet with no added cadmium (group control). Conditioned place preference (CPP) was conducted in a two-chamber apparatus in which all drugs were paired with the least-preferred side as determined by a pretest. In Experiment 1, animals received 0, 2.5, or 5 mg/kg cocaine HCl (IP) for 4 days and vehicle only for 4 days. Control animals showed a place preference for the drug side at 2.5 and 5 mg/kg, while the cadmium-exposed animals showed a preference at 5 mg/kg only. In Experiment 2, animals received 0, 5, or 10 mg/kg of the D1/D2 dopamine receptor agonist apomorphine HCl (SC) for 4 days and vehicle only for 4 days. Control animals showed a place preference at 5 and 10 mg/kg, while metal-exposed animals showed a preference at 10 mg/kg only. To determine the possible effects of alterations of learning mechanisms by cadmium, a conditioned place aversion (CPA) procedure was employed for Experiment 3. Animals received 0, 10, or 40 mg/kg lithium chloride (IP) for 4 days or vehicle only for 4 days. Control animals showed a significant place aversion at 40 mg/kg, while cadmium-exposed animals did not. These findings are discussed within a framework of possible metal-induced disturbance of neurochemical function and/or associative processing.