Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.     

Differential induction of apoptosis in undifferentiated and differentiated HL-60 cells by DNA topoisomerase I and II inhibitors

The effects of monocytic/macrophage and granulocytic differentiation induced by phorbol myristate acetate (TPA) and all-trans retinoic acid, respectively, were tested on the induction of apoptosis in human promyelocytic leukemia HL-60 cells treated with topoisomerase I and II inhibitors. Using a filter-binding assay, we observed a strong inhibition of DNA fragmentation induced by 3- and 24-hour continuous exposure to camptothecin, VP-16, VM-26, and m-AMSA in TPA- differentiated cells. The inhibition of the typical internucleosomal DNA fragmentation was confirmed by agarose gel electrophoresis. By contrast, drug-induced DNA fragmentation was not inhibited in retinoic acid-differentiated cells, and apoptosis occurred in these cells after 4 to 5 days in the absence of drug treatment. The TPA inhibitory effect was maximal after 24 hours of treatment and was correlated with differentiation, because phorbol dibutyrate ester was active, whereas 4- alpha-TPA, a nontumor promoter that does not induce differentiation, was not active. Using alkaline elution, we observed that TPA and retinoic acid differentiation were associated with changes in topoisomerase-mediated DNA breaks that were not correlated with their differential effects on drug-induced DNA fragmentation. Moreover, TPA also inhibited DNA fragmentation induced by vinblastine, cycloheximide, calphostin C, and x-rays. Using a cell-free system, we observed that DNA fragmentation was not inhibited in nuclei from TPA-differentiated cells. Rather, inhibition of apoptosis seemed to take place in the cytoplasm. We conclude that phenotypic changes associated with TPA- induced differentiation include inactivation of a cytoplasmic activity that can induce DNA fragmentation associated with apoptosis.     

Venous Thromboembolic Events Following Major Pelvic and Abdominal Surgeries for Cancer: A Prospective Cohort Study

Objective

The aim of this study was to evaluate the incidence and risk factors for post-hospital discharge venous thromboembolism (VTE) following abdominal cancer surgery without post-discharge prophylaxis.

Methods

This was a single-center, prospective cohort study. Patients were evaluated at 1, 3, and 6 months from surgery for the presence of proximal deep vein thrombosis (DVT; screening ultrasound at 1 month and questionnaire at each visit). Cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan–Meier methods, and multivariable analysis was performed using a Cox proportional hazards model.

Results

Of 284 patients enrolled, 79 (28%) underwent colorectal laparotomy, 97 (34%) underwent hepatobiliary laparotomy, 100 (35%) underwent gynecological laparotomy, and 8 (3%) underwent exploratory laparotomy without resection. All patients received pre- and postoperative inpatient prophylaxis. The cumulative incidence of VTE at 1 month was 0.35% (95% CI 0.05–2.48), 2.5% at 3 months (95% CI 1.19–5.15), and 7.2% at 6 months (95% CI 4.72–10.97). Screening ultrasound performed 4 weeks after surgery in 50% of patients was negative for thrombosis in all cases. Event distribution was similar according to the type of surgery (open/laparoscopic) and type of cancer. Seventeen (6.6%) patients died (95% CI 3.5–9.4) (two had a VTE-related death). Postoperative chemotherapy and Caprini score were significantly associated with VTE [hazard ratios 3.77 (95% CI 1.56–9.12) and 1.17 (95% CI 1.02–1.34), respectively].

Conclusion

The incidence of post-hospital discharge proximal DVT and/or symptomatic VTE following abdominal and pelvic cancer surgery appears to be low. The cumulative number of events increased at 6 months, but this was likely due to additional risk factors that were not related to surgery. Postoperative chemotherapy increases the risk of VTE.

     

Improving access to geriatric mental health services: a randomized trial comparing treatment engagement with integrated versus enhanced referral care for depression, anxiety, and at-risk alcohol use

OBJECTIVE: The authors sought to determine whether integrated mental health services or enhanced referral to specialty mental health clinics results in greater engagement in mental health/substance abuse services by older primary care patients. METHOD: This multisite randomized trial included 10 sites consisting of primary care and specialty mental health/substance abuse clinics. Primary care patients 65 years old or older (N=24,930) were screened. The final study group consisted of 2,022 patients (mean age=73.5 years; 26% female; 48% ethnic minority) with depression (N=1,390), anxiety (N=70), at-risk alcohol use (N=414), or dual diagnosis (N=148) who were randomly assigned to integrated care (mental health and substance abuse providers co-located in primary care; N=999) or enhanced referral to specialty mental health/substance abuse clinics (i.e., facilitated scheduling, transportation, payment; N=1,023). RESULTS: Seventy-one percent of patients engaged in treatment in the integrated model compared with 49% in the enhanced referral model. Integrated care was associated with more mental health and substance abuse visits per patient (mean=3.04) relative to enhanced referral (mean=1.91). Overall, greater engagement was predicted by integrated care and higher mental distress. For depression, greater engagement was predicted by integrated care and more severe depression. For at-risk alcohol users, greater engagement was predicted by integrated care and more severe problem drinking. For all conditions, greater engagement was associated with closer proximity of mental health/substance abuse services to primary care. CONCLUSIONS: Older primary care patients are more likely to accept collaborative mental health treatment within primary care than in mental health/substance abuse clinics. These results suggest that integrated service arrangements improve access to mental health and substance abuse services for older adults who underuse these services.     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Global health goals: lessons from the worldwide effort to eradicate poliomyelitis

The Global Polio Eradication Initiative was launched in 1988. Assessment of the politics, production, financing, and economics of this international effort has suggested six lessons that might be pertinent to the pursuit of other global health goals. First, such goals should be based on technically sound strategies with proven operational feasibility in a large geographical area. Second, before launching an initiative, an informed collective decision must be negotiated and agreed in an appropriate international forum to keep to a minimum long-term risks in financing and implementation. Third, if substantial community engagement is envisaged, efficient deployment of sufficient resources at that level necessitates a defined, time-limited input by the community within a properly managed partnership. Fourth, although the so-called fair-share concept is arguably the best way to finance such goals, its limitations must be recognised early and alternative strategies developed for settings where it does not work. Fifth, international health goals must be designed and pursued within existing health systems if they are to secure and sustain broad support. Finally, countries, regions, or populations most likely to delay the achievement of a global health goal should be identified at the outset to ensure provision of sufficient resources and attention. The greatest threats to poliomyelitis eradication are a financing gap of US 210 million dollars and difficulties in strategy implementation in at most five countries.     

Use of topical misoprostol to reduce radiation‐induced mucositis: Results of a randomized,double‐blind,placebo‐controlled trial

Radiation‐induced mucositis is an acute reaction of the mucosa of patients undergoing head and neck radiotherapy. It can have debilitating and dose‐limiting consequences. There is no consensus on an accepted intervention that significantly reduces its severity. Misoprostol is a synthetic prostaglandin E₁ analogue, with properties of a mucosal cytoprotectant. We designed a randomized, double‐blind, placebo‐controlled trial of misoprostol in patients with head and neck cancer. The aim of this study was to determine if topical misoprostol was effective in reducing the severity of radiation‐induced mucositis in patients receiving radical dose radiotherapy. The effect of this intervention on a patient’s general well‐being was also investigated. The primary end‐point of the study was the incidence of Radiation Therapy Oncology Group grade 3 mucositis. Between 1999 and 2002, 83 patients were recruited into the study at Westmead and Nepean Hospitals, Sydney. Forty‐two patients were randomized to receive misoprostol and 41 to receive a placebo. Most patients received radiotherapy in the adjuvant setting (52 of the 83) and had either an oral cavity (42 of the 83) or an oropharyngeal (16 of the 83) cancer. We could not identify any significant difference in the incidence of severe mucositis based on whether patients were allocated to receive misoprostol or placebo. There was no significant difference in the mean area under the mucositis curve (13.2 vs 16.6; P = 0.1). Patients allocated to misoprostol did report slightly increased soreness (7.6 vs 6.9; P = 0.04) and a greater use of analgesics. However, this difference did not translate into a worse feeling of general well‐being as measured by a simple visual analogue scale (5.8 vs 5.2; P = 0.3). In conclusion, we were unable to identify a reduction in radiation‐induced mucositis in patients receiving misoprostol. There is a paucity of high‐level evidence on potentially useful interventions and a continued need for new and innovative research, incorporating quality‐of‐life measurements, in patients experiencing radiation‐induced mucositis.