Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Urokinase plasminogen activator is immunocytochemically detectable in squamous cell but not basal cell carcinomas.

The presence of plasminogen activators (PA) in a variety of solid tumors appears to correlate, in a number of instances, with enhanced invasive or metastatic capabilities. In the present study, we have immunocytochemically examined basal cell (BCC) and squamous cell carcinomas (SCC) comprising a spectrum of histologic subtypes for the presence of urokinase-type (uPA) and tissue-type (tPA) PA. Neither uPA nor tPA was noted in any BCC, whether of the nodular, infiltrative, morpheaform, or basosquamous variety. uPA but not tPA was seen in 12 of 16 SCC examined; the tumors lacking uPA were all histologically well differentiated. No relationship between uPA expression and depth of invasion was noted, and uPA was not preferentially expressed at tumor borders. We conclude that uPA presence in SCC may relate to the degree of differentiation.

Blood pressure as a parameter in dermatologic surgery.

Elevated blood pressure is a major cause of perioperative bleeding and postoperative hematoma. Seventy-five patients scheduled for dermatologic surgical procedures were prospectively asked if they were aware of any personal history of hypertension. If patient response alone is relied on as a preoperative screen for hypertension, over half of the individuals affected with this disease will be missed. Epinephrine-containing local anesthetics were found not to increase blood pressure in doses commonly employed by dermatologists; in fact, they lowered blood pressure in hypertensive individuals.

Aging of the skin: implications for cutaneous surgery.

There are precious few benefits, save perhaps experience and wisdom, that those of advanced age may claim over those who continue to dwell in their youth. One somewhat paradoxical advantage, however, is the ability of older patients to apparently heal better than younger patients after cutaneous surgery. In older patients, the incision lines are less red, the scarring is less hypertrophic, and "normalization" of appearance occurs more rapidly. And yet, the "wrapping" does not necessarily reflect the contents of the "box." Unfavorable age-dependent alterations in the physical properties of the skin and the wound-healing cascade may affect the viability and structural integrity of the postoperative result. Surgery on the aged population must therefore couple the optimism for a pleasing aesthetic result with the caution reflecting a cutaneous substrate altered by the perturbations of time. This somewhat shaky balance, although not altogether understood, is worthy of study by the physician approaching the patient of advanced age.

Risk factors for local recurrence of primary cutaneous squamous cell carcinomas. Treatment by microscopically controlled excision.

Four hundred fourteen primary cutaneous squamous cell carcinomas were treated by microscopically controlled excision. A five-year mortality-table adjusted cure rate of 93.3% was achieved. The following six parameters were analyzed for correlation with the local recurrence rate: sex, age, lesion diameter, history of previous therapy, anatomic site, and number of stages of Mohs' surgery required for treatment. Only the number of stages correlated significantly with the recurrence rate. However, subpopulations at high risk for recurrent disease could be identified. These consisted of male patients younger than 60 years of age, male patients requiring five or more stages of Mohs' surgery, and patients of either sex with carcinoma of the lower extremity. Modifications of microscopically controlled excision may be warranted in selected patients.

Delayed reconstruction following Mohs' chemosurgery for skin cancers of the head and neck.

The case records of 52 patients with 55 cutaneous neoplasms treated by Mohs' chemosurgery and subsequently reconstructed by plastic surgeons were reviewed to determine if delay between resection and reconstruction adversely affected the outcome of reconstruction. Reconstruction was performed from 5 to 61 days after Mohs' chemosurgery for 45 basal cell carcinomas and 10 other cutaneous neoplasms. There were no complications during the interval between resection and reconstruction. Following reconstruction, minor wound complications occurred in 6% of patients; there were no major complications. Microscopic examination of the re-excised wound revealed residual disease in 2 of 45 cases of basal cell carcinoma and 0 of 10 other cutaneous malignancies. Both patients with residual basal cell carcinomas (i.e., false-negative margins after Mohs' surgery) had presented to the Mohs' surgeon with recurrent tumors. During a follow-up period of 3 months to 3 years after complete resection, recurrent tumor developed in 2 of 45 cases of basal cell carcinoma and 3 of 8 cases of squamous cell carcinoma. Delayed reconstruction, usually 5 to 20 days after Mohs' chemosurgery, can be performed without significant morbidity. Re-excision of the Mohs' chemosurgical wound for pathologic examination can detect residual disease and may be especially indicated for large recurrent wounds.

Chemosurgical report: recurrence (persistence) of tumor following excision by Mohs surgery.

The persistence (clinical recurrence) of tumor following excision by Mohs surgery may not solely be due to biologic properties of the neoplasm such as multifocality. Various technical difficulties intrinsic to the technique that may contribute to recurrence are discussed and illustrated.

The dynamics of flap movement: effect of pivotal restraint on flap rotation and transposition.

Flaps that rotate or transpose around a cutaneous pedicle are restrained by the tethering effect of that base of tissue. Flap design that fails to adjust for this force may eventuate in unwanted degrees of tension and/or surrounding tissue displacement. This concept is discussed and illustrated for the rotation, rhombic, and bilobed flap.

Mohs surgery report: spindle cell fibrohistiocytic tumors: classification and pathophysiology.

Four patients with spindle cell cutaneous fibrohistiocytic neoplasms are presented. A classification scheme for this group of tumors is discussed along with the histologic and immunohistochemical criteria needed to establish the diagnosis. Cutaneous malignant fibrous histiocytoma (atypical fibroxanthoma) may behave biologically as a neoplastic rather than reactive mesenchymal tumor with definite invasive and metastatic potential.

Mohs surgery report: design of an appropriate rhombic flap for a circular defect created by Mohs microscopically controlled surgery.

The rhombic flap is a transposition flap based on exact geometric design. The rhombic transposition principle, however, can be applied to circular as well as to geometric wounds. A method is suggested by which the best rhombic flaps for any specific anatomic site can be generated without conversion of the wound to a rhombic design.

Chemosurgical report: a nongeometric approach to wound closure following Mohs surgery.

Scars are best camouflaged by placing incisions precisely within preexistent creases and cosmetic junctions rather than only following the regional favorable scar direction. Since natural rhytids, contours, and junctions are not straight or composed of geometric shapes, this requires an understanding of techniques of creating scars of irregular curvature. Such a method is presented and illustrated with clinical examples.

Subcutaneous island pedicle flaps.

Aesthetic reconstruction of cutaneous defects is dependent on the availability of matching regional tissue. The ability to transfer comparable local skin can be enhanced by the use of the subcutaneous island pedicle flap. The design, implementation, and anatomy of this flap are discussed and illustrated.

Metastatic basal cell carcinoma originating in the supra-parotid region.

This case illustrates that massive tumor size, ulceration, or history of multiple recurrences are not absolute prerequisites for metastatic BCC. It supports the hypothesis that tumor proximity to major lymphatic systems or large-caliber blood vessels may be of significance. BCCs originating in skin overlying the parotid gland have the potential to penetrate to a rich vascular and lymphatic plexus as well as compromise the integrity of the facial nerve. Early treatment of these neoplasms utilizing accurate methods of microscopic control appears warranted to prevent the serious consequences of recurrences and deep tissue involvement.

The fasciae of the face: an anatomic and histologic analysis.

The face has two distinct fascial components--a superficial layer and a deep layer. The anatomy of the fasciae in relation to surgically significant vessels, nerves, and muscles is examined with anatomic and histologic specimens.