Review of high‐risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology

Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These “high‐risk” cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high‐risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high‐grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high‐risk anatomic locations. Both the National Comprehensive Cancer Network^® (NCCN^®) and the American Joint Committee on Cancer (AJCC) identify several of these high‐risk features of cutaneous SCC. The purpose of this article was to review the high‐risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high‐risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578–594, 2017     

PRELIMINARY RESULTS OF HEPATIC RESECTION FOR CENTRALLY LOCATED LARGE HEPATOCELLULAR CARCINOMA

Resection of large hepatocellular carcinoma (HCC) located in the central portion of the liver remains a surgical challenge. Over a 2 year period, from July 1989, 19 HCC patients whose main tumour (mean diameter 11.3 cm, range 6–19cm) was located in the central part of the liver (defined as Couinaud's segments IV, V, VIII) had liver resections. Liver cirrhosis was found in 14 patients (73.7%). Extended major hepatectomy could be performed in only three patients. The operative morbidity and mortality were 26.3% and 0%, respectively. The resection margin in 14 patients was less than 1 cm. At the time this paper was written 11 patients were alive and disease free, five patients survived longer than 30 months. The 1 year disease free rate and survival rate were 73.7% and 84.2%, respectively. The preliminary results reveal that with careful preservation of non-tumourous liver, resection of centrally located large HCC is still advocated even in a cirrhotic liver, and that the resection margin width should not be a major concern.     

Optical coherence tomography for presurgical margin assessment of non‐melanoma skin cancer – a practical approach

In the clinical setting, optical coherence tomography (OCT) is applicable for the non‐invasive diagnosis of skin cancer and may in particular be used for margin definition prior to excision. In this regard, OCT may improve the success rate of removing tumor lesions more effectively, preventing repetitive excision, which may subsequently result in smaller excisions. In this study, we have aimed to evaluate the applicability of OCT for in vivo presurgical margin assessment of non‐melanocytic skin tumors (NMSC) and to describe the feasibility of different scanning techniques. A total number of 18 patients planned for excision of lesions suspicious of NMSC were included in this study. Based on OCT, we defined the specific tumor margins on 19 lesions preoperatively using different scanning modalities. Sixty‐one margin points and five complete tumor margins were analysed on 18 patients with a total of 19 lesions including 63% basal cell carcinoma (BCC) (n = 12), 16% (n = 3) squamous cell carcinoma (SCC) and 21% of other types of skin tumors (n = 4) were classified. In 84% of the cases (n = 16), the OCT‐defined lateral margins correctly indicated complete removal of the tumor. The surgical margins chosen by the surgeon never fell below the OCT‐defined margin. Regarding the techniques of marginal definition, punctual tumor border scan in the perpendicular direction, with an extension of free‐run scans for unsure cases can hardly be recommended. This study shows that suspected NMSC can effectively be confirmed, and furthermore, resection margin can be minimized under OCT control without reducing the rate of complete removal.     

Fluorescence imaging of invasive head and neck carcinoma cells with integrin αvβ6-targeting RGD-peptides: an approach to a fluorescence-assisted intraoperative cytological assessment of bony resection margins

We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin αvβ6 as a potential approach for a fluorescence-assisted intraoperative cytological assessment of bony resection margins (F-AICAB) in patients who had bone-infiltrating squamous cell carcinoma (SCC) of the head and neck. This was assessed to demarcate invasive carcinoma cells that stained for αvβ6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin αvβ6-targeting fluorescence-labelled RGD peptides were added to the cytological samples and the accuracy of the resulting signal assessed by comparing it with the cytological findings. The value of F-AICAB was evaluated to find out if it could help to improve future diagnoses, tests, and treatments. Integrin αvβ6 was strongly expressed in invasive SCC cells and qualified as a marker for bone-infiltrating carcinoma cells. It showed a high affinity to bind to invasive SCC cells and enabled swift and specific demarcation of αvβ6-stained carcinoma cells. It was also diagnostic, with a sensitivity of 100% (95% CI 81.3% to 99.3%), specificity of 98.3% (95% CI 94.4% to 99.0%), positive predictive value of 92% (95% CI 70.2% to 94.3%), and negative predictive value of 100% (95% CI 96.9% to 99.9%), compared with the cytological findings. The targeting of specific integrin subtypes with selective, synthetic ligands, adapted for multimodal imaging, is a promising new approach to diagnosis. Further studies are necessary to provide more evidence for successful clinical translation and to establish the impact on clinical procedures.     

Expression of vascular endothelial growth factor receptor‐3 mRNA in the rat developing forebrain and retina

Vascular endothelial growth factor receptor (VEGFR)‐3, a receptor for VEGF‐C and VEGF‐D, is expressed in neural progenitor cells, but there has been no comprehensive study of its distribution in the developing brain. Here, the temporal and cell‐specific expression of VEGFR‐3 mRNA was studied in the developing rat forebrain and eye. Expression appeared along the ventricular and subventricular zones of the lateral and third ventricles showing ongoing neurogenesis as early as embryonic day 13 but was progressively down‐regulated during development and remained in the subventricular zone and rostral migratory stream of the adult forebrain. VEGFR‐3 expression was also detectable in some differentiating and postmitotic neurons in the developing cerebral cortex, including Cajal‐Retzius cells, cortical plate neurons, and subplate neurons. Expression in the subplate increased significantly during the early postnatal period but was absent by postnatal day 14. It was also highly expressed in nonneural tissues of the eye during development, including the retinal pigment epithelium, the retinal ciliary margin, and the lens, but persisted in a subset of cells in the pigmented ciliary epithelium of the adult eye. In contrast, there was weak or undetectable expression in the early neural retina, but a subset of retinal neurons in the postnatal and mature retina showed intense signals. These unique spatiotemporal mRNA expression patterns suggest that VEGFR‐3 might mediate the regulation of both neurogenesis and adult neuronal function in the rat forebrain and eye. J. Comp. Neurol. 518:1064–1081, 2010. © 2009 Wiley‐Liss, Inc.     

Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin

Aims:  The current Royal College of Pathologists guidelines for pancreatoduodenectomy specimen reporting recommend that microscopic evidence of tumour within 1 mm of a resection margin (RM) should be classified as R1. No clinical evidence exists to justify this classification. The aim of this study was to identify the proportion of pancreatoduodenectomy specimens in which 'equivocal' RMs are present (tumour involvement within 1 mm of, but not directly reaching, one or more resection margins) and whether the survival of these patients was similar to that of patients with 'unequivocal' RM involvement.
Methods and results:  Patients with histologically confirmed pancreatic ductal adenocarcinoma undergoing pancreatoduodenectomy between 1997 and 2007 ( n  = 163) were identified from a prospective database. One hundred and twenty-eight cases (79%) were classified as R1. Of these, 57 (45% of all R1 cases) were based on 'equivocal' margin involvement. There was no significant difference in overall survival between equivocal and unequivocal R1 resections (log rank, P  = 0.102). All R1 resections had a poorer survival on univariate (log rank, P  = 0.013), but not multivariate, analysis (Cox, P  = 0.132).
Conclusions:  Our results indicate that cases with microscopic tumour involvement within 1 mm of a resection margin should be considered synonymous with incomplete excision for resected pancreatic cancer.     

Lid margin split in the surgical correction of epiblepharon

Purpose: To describe the technique of splitting the lid margin combined with the excision of redundant skin and muscle during the surgical correction of epiblepharon and to report its clinical outcome. Methods: A combined procedure that included splitting the lid margin to repair lower eyelid epiblepharon was performed on 31 eyes of 19 consecutive patients. Lid margin splitting was performed along the grey line on the medial third or half of the lower eyelid by making a 1 mm‐deep incision. Having made a transverse subciliary skin incision and a dissection between the tarsus and the orbicularis oculi muscle, the subcutaneous tissue of the superior edge of the incision was secured to the tarsus with interrupted sutures to evert the cilia. An excision of the redundant skin and orbicularis tissue was made and the skin was closed. The patients were followed for direct inspection of the wound, the split lid margin, the direction of the lashes and the status of the cornea. Results: The mean postoperative follow‐up period was 29.4 weeks. Symptoms disappeared in all patients. In 30 eyelids of 19 patients the cilia did not touch the cornea, even in the down‐gaze. In one eyelid the cilium touched the medial conjunctiva, but not the cornea. The cosmetic outcome of the lower lid was satisfactory in all cases and the wounds of the split lid margin healed without scarring. To date, there have been no complications such as wound dehiscence, ectropion or eyelid retraction. Conclusions: The lamellar splitting of the lid margin is a beneficial addition to the repair of prominent lower lid epiblepharon, especially on the medial aspect of the eyelid. This simple technique ensures easier eversion of the cilia in epiblepharon repair, without disturbing the posterior lamella or causing unfavourable results.     

螺旋CT在术前预测直肠癌环周切缘受累的价值

目的 观察螺旋CT检查在术前预测进展期直肠癌环周切缘受累的准确性.方法 39例病理证实直肠癌病人,以空气作为肠腔内对比剂进行螺旋CT扫描,按全直肠系膜切除术原则进行手术,将CT扫描与病理组织学检查结果 进行比较.结果 螺旋CT准确判断出肿瘤在直肠系膜间隙内侵犯的深度.8例环周切缘阳性的病人均可见直肠系膜内明显的肿瘤浸润,7例病人通过螺旋CT准确判断出环周切缘受累.预测环周切缘受累灵敏度为87.5%(7/8),特异度为93.3%(29/31),准确度为92.3%(36/39),阳性预测值为77.8%(7/9),阴性预测值为96.7%(29/30).结论 术前螺旋CT检查可准确预测肿瘤环周切缘状态.     

Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy

BACKGROUND: Patients receiving breast conservation therapy have a lifelong risk of local recurrence. To minimize this risk, surgeons have explored various approaches to examining the surgical margins of the resection specimen. If tumor cells are found at the margin, there is a high probability that residual tumor remains in the surgical cavity. This review examines published reports about standard and innovative approaches to assessing surgical margins, the clinical significance of margin size, and risk factors for positive margins. METHODS: Published literature abstracted in Medline was reviewed using the Gateway site from the National Library of Medicine. CONCLUSIONS: It is still not clear whether obtaining a radical margin will decrease the rate of local recurrence after breast conserving surgery. What is clear is that it is absolutely unacceptable to have tumor cells directly at the cut edge of the excised specimen, regardless of the type of post-surgical adjuvant therapy.