Neural network analysis of combined conventional and experimental prognostic markers in prostate cancer: a pilot study.

Prostate cancer is the second most common malignancy in men in the UK. The disease is unpredictable in its behaviour and, at present, no single investigative method allows clinicians to differentiate between tumours that will progress and those that will remain quiescent. There is an increasing need for novel means to predict prognosis and outcome of the disease. The aim of this study was to assess the value of artificial neural networks in predicting outcome in prostate cancer in comparison with statistical methods, using a combination of conventional and experimental biological markers. Forty-one patients with different stages and grades of prostate cancer undergoing a variety of treatments were analysed. Artificial neural networks were used as follows: eight input neurons consisting of six conventional factors (age, stage, bone scan findings, grade, serum PSA, treatment) and two experimental markers (immunostaining for bcl-2 and p53, which are both apoptosis-regulating genes). Twenty-one patients were used for training and 20 for testing. A total of 80% of the patients were correctly classified regarding outcome using the combination of factors. When both bcl-2 and p53 immunoreactivity were excluded from the analysis, correct prediction of the outcome was achieved in only 60% of the patients (P = 0.0032). This study was able to demonstrate the value of artificial neural networks in the analysis of prognostic markers in prostate cancer. In addition, the potential for using this technology to evaluate novel markers is highlighted. Further large-scale analyses are required to incorporate this methodology into routine clinical practice.     

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.     

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. PATIENTS AND METHODS: Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. RESULTS: No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. CONCLUSION: The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.     

Platelet-binding immunoglobulins in pregnancy-induced hypertension I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and R = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and R = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.     

Impact of body mass index on IVF and ICSI outcome: a retrospective study

A group of 140 women with a body mass index (BMI) < or = 24 kg/m(2) undergoing 291 cycles was compared with a group of 138 women with a BMI >24 kg/m(2) in 291 cycles, with respect to duration of ovarian stimulation and dose of gonadotrophin, number of oocytes collected, cleavage and implantation rate, clinical pregnancy, miscarriage and delivery rates. Patients with a BMI > 24 kg/m(2) demonstrated a significant decrease in the number of follicles after stimulation (P = 0.01), a comparative increase in the number ampoules of gonadotrophin used (P = 0.03) and a lower number of eggs collected (P = 0.05). The mean number of embryos on days 1, 2 and 3 was significantly lower in the group with BMI > 24 kg/m(2) (P < 0.001). No significant difference was found in clinical pregnancy and miscarriage rates between the two groups. In spite of the lower response in women with BMI > 24 kg/m(2), the delivery rate per retrieval was not different (24.6 versus 24.8%). These results indicate a lower stimulation response in women with elevated BMI, but no adverse effect on IVF outcome. In relation to wellbeing, however, it is recommended that patients with a high BMI reduce their weight before IVF treatment.     

Risk-adjusted cesarean rates: what risk factors for cesarean delivery are important to practicing obstetricians?

OBJECTIVE: To determine which primary cesarean delivery risk factors are important to practicing physicians. STUDY DESIGN: A sample of current members of the American College of Obstetrician Gynecologists were surveyed about the risk factors for primary cesarean delivery that they thought were most important. Data on demographic and practice characteristics were also collected. Sample size was determined by theoretical saturation. RESULTS: Theoretical saturation was reach at 60 responses. A total of 290 surveys were returned. The 10 most common factors listed by physicians as preexisting patient risk factors for primary cesarean delivery were, in descending order of importance, medical problems, maternal obesity, macrosomic infant, malpresentation, multiple gestation, maternal age, Bishop score, patient's fear, preterm labor, and postdate pregnancy. Six of the 10 factors listed by respondents are in previously published risk-adjustment models. CONCLUSION: Our study suggested that the addition of obesity and birth weight to previously published risk-adjustment models should improve representation of practicing obstetricians' views.     

Prevention of acute exacerbation of chronic obstructive pulmonary disease after bronchoscopic lung volume reduction with endobronchial valves

IntroductionBronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBVs) has emerged as an important treatment method for patients with severe chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD (AECOPD) are a frequent complication following BLVR with EBV. However, there is no consensus on the prevention of AECOPD.ObjectivesOur study aims to compare the outcomes of different prophylactic measures on the occurrence of AECOPD after BLVR with EBV.MethodsWe conducted a multicenter, retrospective study of patients who underwent BLVR with EBV at six different institutions. Emphasis was directed towards the specific practices aimed at preventing AECOPD: antibiotics, steroids, antibiotics plus steroids, or no prophylaxis. Subgroups were compared, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated.ResultsA total of 170 patients were reviewed. The rate of AECOPD was 21.2% for the full cohort. Patients who received prophylaxis had a significantly lower rate of AECOPD compared with those who did not (16.7% vs. 46.2%; p = 0.001). The rate was lowest in patients who received antibiotics alone (9.2%). There was no significant difference in the rate of AECOPD between patients who received steroids alone or antibiotics plus steroids, compared with the other subgroups. The OR for AECOPD was 4.3 (95% CI: 1.8–10.4; p = 0.001) for patients not receiving prophylaxis and 3.9 (95% CI: 1.5–10.1; p = 0.004) for prophylaxis other than antibiotics alone.ConclusionsAdministration of antibiotics after BLVR with EBV was associated with a lower rate of AECOPD. This was not observed with the use of steroids or in combination with antibiotics.