Lack of Independent Significance of a Close (<1 mm) Circumferential Resection Margin Involvement in Esophageal and Junctional Cancer

Background

For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors.

Methods

CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan–Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis.

Results

A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004).

Conclusions

A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.     

A peptide inhibitor of c-Jun promotes wound healing in a mouse full-thickness burn model

Significant damage to tissue surrounding burn injuries occurs after the removal of the thermal source. This damage is caused by a combination of both necrotic and apoptotic cell death in the zone of stasis. Preserving the zone of stasis can reduce the wound size and thereby improve wound healing. We tested whether a peptide previously identified to inhibit necrotic and apoptotic cell death in neurons through c-Jun inhibition could enhance wound healing. We first tested the effects of this peptide on a keratinocyte and fibroblast cell line in culture. The peptide promoted proliferation of keratinocytes but had no effect on fibroblast proliferation, while the peptide also inhibited ultraviolet-induced apoptosis of keratinocytes. We finally tested the peptide in vivo, using a mouse model of burn injury. Wounds that were treated with the peptide reepithelialized faster than controls, while cell death surrounding the wound site was markedly reduced 24 hours postinjury, suggesting that the prevention of apoptosis as well as the proliferative effects of this peptide contribute to the wound healing process. Our data implicate c-Jun in multiple processes during wound repair and demonstrate that treatment of burn injuries using inhibitors of c-Jun dimerization at the time of injury can promote wound healing.     

Biological fate and clinical implications of arginine metabolism in tissue healing

Since its discovery in 1987, many biological roles (including wound healing) have been identified for nitric oxide (NO). The gas is produced by NO synthase using the dibasic amino acid l ‐arginine as a substrate. It has been established that a lack of dietary l ‐arginine delays experimental wound healing. Arginine can also be metabolized to urea and ornithine by arginase‐1, a pathway that generates l‐ proline, a substrate for collagen synthesis, and polyamines, which stimulate cellular proliferation. Herein, we review subjects of interest in arginine metabolism, with emphasis on the biochemistry of wound NO production, relative NO synthase isoform activity in healing wounds, cellular contributions to NO production, and NO effects and mechanisms of action in wound healing.     

Traumatic rupture of the thoracic aorta: Cohort study and systematic review

PURPOSE: Through a systematic review of the literature, we identified the optimal management of traumatic ruptures of the thoracic aorta (TRTA) and reported the results of a cohort of patients treated with the clamp-and-sew technique (CAS) at a tertiary trauma center. METHODS: Studies were identified through Medline and the Cochrane library and from reference lists and papers from the authors' files. Studies with a single consistent protocol (CAS, Gott shunt [GS], left heart bypass [LHB], or partial cardiopulmonary bypass [PCPB]) that reported mortality and neurologic outcomes were included. Relevance, validity, and data extraction were performed in duplicate. A retrospective review of charts from June 1992 to August 2000 provided the database for our experience. RESULTS: Twenty studies reporting on 618 patients were found to be relevant. Interobserver agreement for relevance and validity decisions was high. Mortality rates for repair with CAS, GS, LHB, and PCPB were 15%, 8%, 17%, and 10%, respectively, and for paraplegia they were 7%, 4%, 0%, and 2%, respectively. The difference in mortality rates was not statistically significant. CAS had a higher incidence of neurologic deficits than GS (odds ratio [OR], 1.8; 95% CI, 0.4-8), LHB (OR, 6.4; 95% CI, 0.8-50), and PCPB (OR, 3.4; 95% CI, 1-10). In our cohort of 25 patients, 21 underwent surgery with CAS. The median abbreviated injury severity score was 20 (range, 4-50). The mean aortic clamp time was 30 +/- 12 minutes. Aortic repair was achieved with graft interposition in 43% of patients, and simple suture was achieved in 57% of patients. Mortality (10%) and neurologic complication (paraplegia, 11%; paraparesis, 5%) rates were not statistically different from those reported in the literature. CONCLUSION: CAS is associated with a similar mortality rate but a higher incidence of neurologic deficits than methods with distal aortic perfusion.     

True identity by immunohistochemistry and molecular morphology of undifferentiated malignancies of the head and neck

Although conventional squamous carcinomas can often be recognized with little difficulty by experienced pathologists, it remains a fact that a substantial number of head and neck malignancies are capable of posing real challenges to the diagnostic pathologist. Those head and neck tumors showing the least kinship with normal host tissues—that is, the undifferentiated malignancies—are a particular problem and an approach to dealing with them is traced out below. As a matter of basic light microscopy, these tumors can usually be relegated to 1 of 4 categories: small round cell tumors, spindle cell tumors, large polygonal cell (epithelioid) tumors, and pleomorphic tumors. Once they have been so subclassified, these lesions can then be studied by immunohistochemistry and, when necessary, by molecular methods as well. Immunohistochemistry often permits these tumors to be assigned to a particular tissue type, specifically, epithelial, mesenchymal, lymphoid, or melanocytic. Application of additional immunohistochemical antibodies, in turn, can permit further refinement of this impression (eg, allowing distinction of a neuroendocrine tumor from a carcinoma). In selected instances, molecular techniques (such as in situ hybridization) may be employed both for diagnostic as well as for prognostic purposes. It should be borne in mind, however, that the pathologist's diagnosis will sometimes only be as good as the clinical information provided, which is why the diagnosis of undifferentiated malignancies of the head and neck truly is a multifaceted process, demanding the close cooperation of pathologists, clinicians, and radiologists. © 2009 Wiley Periodicals, Inc. Head Neck, 2009