Lymph node evaluation and survival after curative-intent resection of duodenal adenocarcinoma: A matched cohort study.

BACKGROUND: Lymph node (LN) metastasis in patients with duodenal adenocarcinoma is associated with poor prognosis; however, the optimal extent of LN assessment and the interaction between LN assessment and adjuvant systemic therapy is poorly understood. METHODS: Resected non-metastatic duodenal adenocarcinoma patients (n = 1743) were identified in the National Cancer Database (1998-2011). Logistic regression analysis identified covariates associated with LN metastasis. The influence of increasing LN cut-off points on overall survival (OS) was analysed using the log-rank test and Cox proportional hazards modelling. Adjuvant chemotherapy (AC) and surgery alone cohorts were matched (1:1) by propensity scores based on the likelihood of nodal metastasis or survival hazard on Cox modelling. OS in the matched cohort was compared by Kaplan-Meier estimates. RESULTS: LN metastases were present in 865 (49.6%) patients. Increasing LN assessment was associated with an increased likelihood of nodal involvement (P = 0.008). In node-negative patients, increasing LN assessment was associated with a decreased risk of death, with the largest actuarial survival differences observed for ≥15 LN (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.82, P = 0.001). In the propensity score-matched cohort of node-negative patients, AC was associated with non-significant improvements in 5-year actuarial (66.1% versus 58.7%, HR 0.79, 95% CI 0.53-1.18, P = 0.249), and did not vary by adequacy of LN counts (<15 LNs: HR 0.79, 95% CI 0.51-1.24, P = 0.305; ≥15 LNs: HR 0.90, 95% CI 0.35-2.30, P = 0.900). CONCLUSIONS: The extent of LN identification has prognostic significance in resected node-negative duodenal adenocarcinoma, but cannot be implicated in the selection of node-negative patients for AC.

Preoperative radiotherapy in the management of retroperitoneal liposarcoma.

BACKGROUND: Histological subtype influences both prognosis and patterns of treatment failure in retroperitoneal sarcoma. Previous studies on the efficacy of neoadjuvant radiotherapy (NRT) have incorporated multiple histological types with heterogeneous tumour biology. The survival impact of NRT specifically for patients with retroperitoneal liposarcoma is poorly defined. METHODS: Patients who underwent resection with curative intent for retroperitoneal liposarcoma and who received NRT or surgery alone were identified in the US National Cancer Data Base (2004-2013). Cox regression was used to identify co-variables associated with overall survival. NRT and surgery-alone cohorts were matched 1 : 1 by propensity scores based on the survival hazard on Cox modelling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: A total of 2082 patients with retroperitoneal liposarcoma were identified; 1908 underwent surgery alone and 174 received NRT before surgical resection. Median tumour size was 22·0 cm and 34·9 per cent of tumours were high grade. In the unmatched cohort, NRT was not associated with improved overall survival (χ2 = 3·49, P = 0·062). In the propensity score-matched cohort, NRT was associated with an improvement in survival (median overall survival 129·2 versus 84·3 months; P = 0·046; hazard ratio (HR) 1·54, 95 per cent c.i. 1·01 to 2·36). This effect appeared most pronounced for tumours with adjacent organ invasion (median overall survival not reached versus 63·8 months; P = 0·044; HR 1·79, 1·01 to 3·19). CONCLUSION: NRT improved survival in patients undergoing surgery for retroperitoneal liposarcoma, particularly those with high-risk pathological features.

The state of general surgery training: a different perspective.

BACKGROUND: Much has been written about the influences of Accreditation Council for Graduate Medical Education (ACGME) work restrictions, the litigious climate in American medicine, and the proliferation of subspecialty fellowships on general surgery training. Few previous studies have addressed general surgical residents' perceptions of surgical training on a national level. METHODS: A 38-question Institutional Review Board-approved survey was sent via e-mail to the program directors at all ACGME-approved general surgical training programs for distribution to categorical general surgery residents. Voluntary responses to statements focusing on job satisfaction, quality of life, and the influences of operative experience, work hours, fellows, physician extenders, as well as faculty and administration on resident training were solicited. RESULTS: Overall, 997 responses were received from residents of all clinical levels from 40 states. Most respondents were from university-based programs (79%) with a broad representation of program sizes (mean of 6 graduates per year; range 2 to 11). Residents believe that they will be prepared to enter clinical practice at the conclusion of their training (86%), that the duration of surgical training is adequate (85%), and that they are exposed to sufficient case volume and complexity (85% and 84%, respectively). Only 360 respondents (36%) believe that they are financially compensated appropriately. Although most respondents support the ACGME work-hour restrictions (70%), far fewer feel that they improve their training or patient care (46.6% and 46.8%, respectively). Most respondents are proud to be surgical residents (88%), view surgery as a rewarding profession (87%), and would choose surgery as a profession again (77%). CONCLUSIONS: Surgical residents are positive regarding the quality of their training and life, although they feel poorly compensated for their work. Most residents intend to pursue fellowship training. Survey responses were consistent irrespective of gender, ethnicity, and program type.

Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer.

The identification of pathogen-associated molecular patterns, conserved microbial structures that act on Toll-like receptors, has led to a novel avenue of investigation aimed at developing a new generation of cancer immunotherapies. Ligation of Toll-like receptors results in the induction of robust immune responses that may be directed against tumor-associated antigens. Recent data suggest that such strategies may result in enhanced antitumor immunity. Nonetheless, as clinically effective immunotherapy for cancer remains a somewhat distant goal, attention has shifted toward multimodality approaches to cancer therapy, sometimes combining novel immune interventions and conventional treatments. The traditional view of radiation therapy as immunosuppressive has now been challenged, prompting a re-evaluation of its potential as an adjunct to immunotherapy. Radiation therapy can enhance the expression of tumor-associated antigens, induce immune-mediated targeting of tumor stroma, and diminish regulatory T cell activity. Recent evidence suggests that radiation therapy may also activate effectors of innate immunity through TLR-dependent mechanisms, thereby augmenting the adaptive immune response to cancer. In this paper, we will review evidence for enhanced tumor-directed immunity resulting from radiation exposure and early promising data suggesting synergistic effects of radiation and TLR-targeted immunotherapies.