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.     

Predicting Postoperative Morbidity Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CS+HIPEC) with Preoperative FACT-C (Functional Assessment of Cancer Therapy) and Patient-Rated Performance Status

Background

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) is associated with significant perioperative morbidity. One goal of our ongoing patient-reported health-related quality of life (HRQoL) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC.

Methods

A retrospective analysis of a prospectively collected clinical database for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done. Patients completed the Functional Assessment of Cancer Therapy questionnaire plus the colon symptom subscale, in addition to the Eastern Cooperative Oncology Group (ECOG) performance status rating prior to CS+HIPEC. The trial outcome index (TOI), a specific measure of function, symptoms, and physical well being of the patient, was analyzed. The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C.

Results

Of 855 patients, 387 (45.2 %) participated in the HRQoL trials. Mean age was 53.3 years, and 213 (55 %) were female versus 174 (45 %) males. There were 240 patients (62 %) who had a complication versus 147 (38 %) who had no complication. A 30-day mortality rate of 7.7 % (30) was documented. Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7; P < 0.001. Independent predictors of 30-day mortality on multivariate analysis included TOI (0.05), age (0.001), and smoking (0.001). Patients with a higher TOI score were less likely to suffer a mortality (95 % CI 0.9–1.0, P = 0.05). Patients with a higher emotional well being (EWB) score were less likely to suffer a complication 0.9 (95 % CI 0.87–1.0, P = 0.04). Other independent predictors of postoperative morbidity included diabetic status (P = 0.05), ECOG performance status (0.001), and gender (0.02).

Conclusions

Preoperative HRQoL, as measured by FACT-C and ECOG performance status and added to traditional factors, helps predict postoperative morbidity and mortality following CS+HIPEC.     

New Sentinel Node Mapping Technologies for Early Gastric Cancer

The sentinel node (SN) concept has revolutionized the surgical staging of both melanoma and breast cancer over the past two decades. The application of this concept can yield benefits for patients by preventing various complications related to unnecessary prophylactic regional lymph node dissection in patients with cancer-negative SNs. Clinical application of SN mapping in patients with early gastric cancer has been a controversial issue for years. However, a recent meta-analysis and a prospective multicenter trial of SN mapping for early gastric cancer have shown acceptable SN detection rates and accuracy of determination of lymph node status. For early stage gastric cancer such as cT1N0M0, for which a better prognosis can be achieved through conventional surgical approaches, the establishment of individualized, minimally invasive treatments that may retain the patients’ quality of life should be the next surgical challenge. Although there are many unresolved technical issues, laparoscopic SN biopsy with laparoscopic minimized gastrectomy or endoscopic mucosal resection/endoscopic submucosal dissection has the potential to achieve this goal.     

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.