Gastric cancer and survival

The survival of patients with cancer of the stomach in a Melbourne series showed no improvement over a 20-year period. Of 246 patients, 8.1% survived for a period of five years, and 4.8% survived for 10 years after presentation. A further plea is made to establish a "100%" register of cancer.     

Navigating on the medical management freeway

Ready or not, the role of the medical group manager is rapidly expanding and only those who are well prepared and in control will survive. The views of a medical management consultant are presented in this entertaining article on a critical subject, along with guidelines for developing formal organizational goals.     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Breast cancer in young women: Imaging and clinical course

The purpose of this study was to characterize presenting imaging findings in women younger than 40 diagnosed with invasive breast cancer in the context of pathology and clinical course. Retrospective chart and imaging reviews were performed in patients under 40 diagnosed with breast cancer between July 1, 2004, and December 31, 2013. Patient demographic, imaging, pathology, and clinical data were collected. Overall and recurrence-free survival were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were performed to identify factors associated with recurrence-free survival. Our study cohort consisted of 110 patients with invasive mammary carcinoma. One hundred one (91.8%) presented with a palpable mass. The mean size of all lesions on imaging was 3.5 cm ± 2.9 cm. Malignant calcifications were present in 54 (49.1%) cases. Imaging demonstrated multifocal or multicentric disease in 45 (40.9%) cases. Seventy four (67.3%) cancers were high grade. Luminal genomic subtypes were the most common (n = 61, 55.5%). At presentation, 4 (3.6%) patients had bilateral malignancy and 8 (7.3%) patients had distant metastatic disease. Ninety seven (88.2%) underwent neoadjuvant chemotherapy and 67 (60.9%) underwent radiation therapy. Seventy five (68.2%) of the patients underwent mastectomy. The restricted mean time to recurrence was 9.01 years (standard error 3.162 months). ER positivity was associated with compromised recurrence-free survival. The overall survival rate was 0.962 at 10 years. Young patients diagnosed with breast cancer typically present with advanced breast imaging findings and undergo aggressive treatment. Recurrence often occurs >5 years from diagnosis, and ER positive subtypes are at increased risk for recurrence.     

Quality of Life Assessment,of Ileogastrostomy

Twenty of 26 (77%) consecutive patients undergoing ileogastrostomy, performed by the same surgeon (IGMC) between February 1989 and May 1992, responded to a mailed quality of life survey. Average present weight was reported as 50.9 kg less than a mean preoperative weight of 139.7 kg. Mean time of follow-up was 24.75 months. When comparing perceptions before and after surgery, several quality of life improvements were noted in the areas of vocation, relationships, emotional well-being and physical well-being. Post-surgery, jobs were rated more satisfying, eating habits improved, self-image and self-confidence increased and body disparagement declined. Satisfaction with sexual relations increased, as did frequency. In general, relations with partners, co-workers and friends seemed to improve. Exercise also increased significantly. In contrast, foul flatus, bloating, and bowel movements regularly hampered activities or caused embarassment when in public. Despite these physical side-effects, we observed that a large majority of persons undergoing ileogastrostomy noted significant improvements in quality of life.     

Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

A comparison of perinatal mortality between ethnic Chinese and ethnic whites: Why the Chinese rate was lower

Objectives. To confirm the observation that has been occasionally reported in the literature that perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and to assess the reasons for this lower perinatal mortality rate.

Methods. Secondary‐analysis based on published data.

Results. This exercise demonstrates that the perinatal mortality rate was lower in ethnic Chinese than in ethnic whites. The birth weight distribution in ethnic Chinese was more favourable with reduced births at two extremes of the distribution, and the exposure to risk factors for perinatal death by their mothers was also lower.

Conclusion: Perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and the lower perinatal mortality rate in ethnic Chinese is probably caused by their favourable birth weight distribution and lower exposure to risk factors of perinatal death by their mothers.     

Helicobacter pylori-induced diarrhea post-ileogastrostomy

A retrospective study of all ileogastrostomy procedures (n=26) performed in 1993 by one surgeon (IGMC) was carried out to investigate the hypothesis that Helicobacter pylori may be implicated in certain severe cases of postoperation nausea and diarrhea. Ten of 26 persons (38.5%) displayed nausea and notable diarrhea (greater than or equal to ten bowel movements per day), seven of which warranted upper GI investigation. One hundred per cent (seven of seven) of these persons were found to possess H. pylori upon C-14 breath test. In four of six cases eradication therapy (1 g amoxicillin b.i.d./20 mg omeprazole b.i.d. for 2 weeks) corresponded with a resolution of severe nausea and diarrhea (one additional case involved omeprazole use only), suggesting that H. pylori should be considered as a possible cause of these symptoms post-ileogastrostomy. Additionally, in four of seven cases persons were re-tested (C-14 breath analysis) at least 1 month post-therapy and in this group three persons were found to be free of the organism. All three cases of notable diarrhea and nausea resolved with treatment, providing the strongest evidence for a possible association between infection and these symptoms.     

Public involvement in health care priority setting: an economic perspective

Background  Public involvement in health care decision making and priority setting in the UK is being promoted by recent policy initiatives. In 1993, the British Medical Association called for public consultation where rationing of services was to be undertaken. The approach to priority setting advocated by many health economists is the maximization of quality adjusted life years (QALYs). Typically, for a particular health care programme, the QALY calculation takes account of four features: (1) the number of patients receiving the programme, (2) the survival gain, (3) the gain in quality of life and, (4) the probability of treatment success. Only one feature, that relating to quality of life, is based upon public preferences. If the QALY is to be used as a tool for health care resource allocation at a societal level then it should incorporate broader societal preferences.
Methods  This study used an interview-based survey of 91 members of the general public to explore whether the traditional QALY maximization model is a good predictor of public responses to health care priority setting choices.
Results and conclusions  Many respondents did not choose consistently in line with a QALY maximization objective and were most influenced by quality of life concerns. There was little support for health care programmes that provided a prognostic improvement but left patients in relatively poor states of health. The level of respondent engagement in the survey exercise was not sensitive to the provision of supporting clinical information.     

Neuropsychologic status in multiple sclerosis after treatment with glatiramer

BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.