Ethical Issues of Participant Recruitment in Surgical Clinical Trials

Although the historical background of ethical principles of human subjects research are the same for surgery and nonsurgical fields, surgical clinical trials raise several specific ethical issues. Placebo arms in surgical trials are problematic because the closer the sham surgery is to a real operation, the greater the risks for subjects. In order to ethically enter subjects into a clinical trial, a researcher must have equipoise—that is, uncertainty about which treatment arm is more effective. Surgeons must diligently maintain skepticism about whether new treatments are actually better until objective data are available. The dynamic of informed consent between surgeons and patients may be negatively impacted if patients are convinced that new treatments are better even when there are no objective data. Although clinical trials in surgery often are challenging to develop and complete, there is an ethical and social responsibility for surgeons to participate in clinical trials so that data can be gathered to determine what treatments are safe and effective.     

Outcome and Prognostic Factors After Adrenalectomy for Patients with Distant Adrenal Metastasis

Background

The purpose of this study was to describe a single-institution experience with adrenal metastasectomy and to elucidate factors that may bear prognostic significance.

Methods

This is a single-center, retrospective review of patients with adrenal metastasis who underwent adrenalectomy performed with curative intent between 2000 and 2012. The Kaplan–Meier method was used to evaluate overall survival from time of adrenalectomy to death or last follow-up. Primary endpoint was death from any cause. Clinical variables were examined for association with survival.

Results

The study included 62 patients with mean age of 60 (±12) years; 55 % (34 of 62) were male, 85 % (53 of 62) presented with isolated adrenal metastasis, and 82 % (51 of 62) had metachronous disease with median disease-free interval (DFI) of 22 months (range, 6–217 months). Non-small cell lung cancer (NSCLC) was the most common primary comprising 50 % of cases. Median survival for the study population was 30 months (range, 1–145 months) and 5-year survival was 31 %. Patients with NSCLC had significantly shortened survival compared with non-NSCLC with median and 5-year survival of 17 versus 47 months and 27 % versus 38 %, respectively (p = .033). Synchronous metastasis (p = .028) and DFI < 12 months (p = .038) were also associated with worse survival outcome, though male gender (p = .69) and oligometastatic disease (p = .62) were not.

Conclusions

Adrenal metastasectomy resulted in median survival of 30 months and 5-year survival of 31 %. Shorter survival was associated with lung primary, short disease-free interval, and synchronous metastasis, but not with the presence of oligometastatic disease provided that the primary cancer and additional metastatic lesions were adequately controlled and amenable to resection.     

Blurry Boundaries: Do Epithelial Borderline Lesions of the Breast and Ductal Carcinoma In Situ Have Similar Rates of Subsequent Invasive Cancer?

Background

The histology of epithelial “borderline lesions” of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS.

Methods

Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma.

Results

A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.

Conclusions

When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite “borderline” histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.     

Rectal Cancer and Teaching Hospitals: Hospital Teaching Status Affects Use of Neoadjuvant Radiation and Survival for Rectal Cancer Patients

Background

For rectal cancer, it is unknown how use of radiation, treatment cost, and survival differ based on hospital teaching designation.

Methods

Private insurance claims data linked with the Pennsylvania Cancer Registry were used to identify rectal cancer patients undergoing surgery from 2004 to 2006. Patients with missing data of interest were excluded. Hospitals were characterized as follows: large (≥200 beds) versus small size (<200 beds), teaching versus nonteaching, and urban versus rural. Logistic regression was used to model the use of neoadjuvant radiotherapy, and Cox proportional hazards models were used to compare cancer-specific survival between hospital types.

Results

A total of 432 patients were analyzed. There was no difference in the distribution of cancer stages among the various hospital types (all p > 0.20). Teaching hospitals were associated with significantly higher utilization of neoadjuvant radiotherapy for stage II and III cancers compared with nonteaching facilities (57 vs. 28 %; p < 0.0001). On multivariate analysis, teaching status was the only hospital designation associated with use of neoadjuvant radiation (p < 0.001); hospital size and rural/urban designation were not significant. Nonteaching hospitals were more likely to use adjuvant radiotherapy for stage II and III disease (13 vs. 30 %; p < 0.01). Teaching hospitals had lower odds of death from rectal cancer when evaluating all stages [hazard ratio (HR) = 0.35; p < 0.0001] with similar costs of inpatient treatment (teaching: US $30,769 versus nonteaching: US $26,892; p = 0.22).

Conclusions

Teaching designation was associated with higher incidence of neoadjuvant radiotherapy for stage II and III disease, with improved cancer-specific survival compared with nonteaching hospitals, and with similar treatment costs.