Rajiv Grover

Bcl-2 expression in malignant melanoma and its prognostic significance

Programmed cell death (apoptosis) is now recognized as an important factor in tumour growth. Bcl-2 is an oncogene which promotes tumour progression by specifically inhibiting programmed cell death. Bcl-2 oncoprotein was measured using flow cytometry in 42 surgically excised regional lymph node metastases from patients with a median follow-up of 45 months. Fifteen patients in the study were found to have bcl-2 expression which was associated with significantly shorter survival (log-rank test, P<0.002). In addition, multivariate analysis confirmed the predictive value of bcl-2 independent of other established prognostic markers (chi(2)=7.02, P<0.01). Oncogenic control of programmed cell death is therefore important in melanoma progression and bcl-2 measurement provides a useful marker of prognosis for regional lymph node metastases.

Avoiding hematoma in cervicofacial rhytidectomy: a personal 8-year quest. Reviewing 910 patients.

Hematoma remains the most common complication of rhytidectomy and can lead to prolonged facial edema and skin necrosis. A number of ancillary procedures have been suggested to reduce hematoma, including dressings, drains, fibrin glue, tumescence, and adrenaline. The aim of this study was to investigate the statistical effect of these parameters on hematoma incidence in a large series of face lifts. Over an initial 6-year period, 678 consecutive face lifts were performed and included in the first part of the study. The effect of dressings, drains, fibrin glue, and tumescence on hematoma rate was investigated retrospectively. In the second part of the study, the specific effect of adrenaline was analyzed while all other parameters were kept constant. The 229 patients with adrenaline-containing infiltrations were compared with the 232 patients whose infiltration had no adrenaline. Retrospective analysis of both groups was performed using Fisher’s exact test. In the first part of the study investigating 678 consecutive face lifts, no difference in hematoma rate (4.4 percent overall) was observed with the use of dressings (p > 0.5), drains (p > 0.4), fibrin glue (p > 0.6), or tumescence (p > 0.5). In the second part of the study, the specific effect of withdrawing adrenaline in a comparative group of 461 face lifts significantly reduced the incidence of hematoma requiring surgical evacuation (p < 0.0001). There was also a significant reduction in the incidence of minor hematoma requiring only aspiration (p = 0.02). There was no change in the incidence of any other face lift complications observed during this part of the study. This study found a significant reduction in the incidence of hematoma following face lifting. Although many of the suggested ancillary methods used to reduce hematoma did not produce any statistical reduction in the incidence of this complication, the exclusion of adrenaline had a profound effect. The technique and implications with respect to safety and outcome are described.

Endoscopic brow lift: a personal review of 538 patients and comparison of fixation techniques.

Since the introduction of endoscopic brow lifting in the mid-1990s, it has become widely accepted as a method for rejuvenation of the upper third of the face. Despite the multitude of brow fixation techniques, there are few long-term studies providing accurate analysis of outcome. The aims of this investigation were to evaluate the long-term objective results of endoscopic brow lifting and to establish whether the technique of fixation altered the longevity of aesthetic outcome. The outcome of endoscopic brow lifts carried out on 538 consecutive patients over a 6-year period was assessed. For each patient, midpupil-to-brow distance was measured preoperatively and at intervals postoperatively. Two different fixation methods were compared: fibrin glue (n = 189, group 1; 104 records available) and polydioxanone sutures tied through bone tunnels (n = 349, group 2; 220 records available). In 214 patients, an upper lid blepharoplasty was performed simultaneously (85 in group 1 and 129 in group 2). At 1 month postoperatively, each fixation technique had produced a significant change in mean pupil to brow height (5.93 mm in group 1 and 6.21 mm in group 2, with no significant difference between the two methods; p = 0.17). However, when measurements were compared more than 3 months postoperatively (mean, 9.4 months), there was a significant difference, with some relapse in the patients treated with fibrin glue (p < 0.01). However, in group 2 (tunnel fixation), measurements remained stable, with 6.21 mm at 1 month compared with 6.16 mm long term (no significant difference, p = 0.34). In contrast, in group 1 (fibrin glue), measurements showed significant reduction, with a 1-month result of 5.93 mm and a long-term outcome of 3.79 mm (p < 0.01). Upper lid blepharoplasty had no effect on the long-term outcome of either group (p > 0.3 in group 1, p > 0.4 in group 2). Complications were few in both groups. In group 1, there was one infection, two instances of significant alopecia (both temporary), and one reoperation for relapse. In group 2, four patients required minor surgical revision of a lateral port scar and three minor areas of temporal alopecia, which recovered in less than 3 months. One patient had a paresis of the frontal branch that had recovered after 4 months. The endoscopic brow lift is therefore a safe and effective technique for increasing mean pupil to brow height. Fixation with polydioxanone sutures tied through bone tunnels produces a significantly more stable result than fibrin glue, without greater risk. This lends weight to experimental evidence that periosteal fixation must be maintained for at least 6 weeks to be secure.

Reducing complications in cervicofacial rhytidectomy by tumescent infiltration: A comparative trial evaluating 678 consecutive face lifts

Tumescent infiltration has been widely used in body-contouring surgery to facilitate dissection and reduce blood loss. Although its use in facial surgery has been suggested, there are presently no comparative studies of its efficacy. The aim of this study was to investigate the long-term outcome in a large series of consecutive face lifts performed with and without tumescence. During a 6-year period, 678 consecutive face lifts were performed: 449 without tumescence and 229 with tumescent infiltration using 200 ml on each side of the face. The spectrum of techniques included the extended superficial musculoaponeurotic system (SMAS) procedure, the lateral SMASectomy, the extended supraplatysmal plane lift, and the cutaneous face lift. Complications, such as hematoma, skin necrosis, alopecia, and scar quality, were compared between groups using Fisher’s exact test. The use of tumescent infiltration facilitated dissection, particularly in the neck. Postoperative swelling and bruising were reduced in the tumescent group. In comparisons of major complications between groups, no difference was seen in hematoma rate (p > 0.5), although the incidence of other complications was significantly reduced by tumescent infiltration. Significant reduction was observed in the rate of skin necrosis (p = 0.03), alopecia (p = 0.006), hypertrophic scarring (p = 0.001), stretched scarring (p = 0.003), and scar revision (p < 0.001). This is the first comparative study of tumescent infiltration in facial rejuvenation surgery. Tumescence made dissection easier and significantly reduced the incidence of troublesome complications. The surgical technique and aesthetic implications for rejuvenation surgery are discussed.

The efficacy of surgical drainage in cervicofacial rhytidectomy: a prospective, randomized, controlled trial.

Background: Postoperative drainage is often used instinctively in face lifting on the assumption that it may reduce the likelihood of complications. This potential benefit should be balanced against cost, discomfort, and the possibility of provoking bleeding and hematoma on removal. Evidence-based decisions on drainage are problematic, since no prospective studies have examined its role. This study was designed to address this issue directly. Methods: Fifty consecutive patients undergoing face lift over a 3-month period were randomized to drainage of one side of the face only, with the contralateral side serving as a paired control. Bruising, swelling, and hematoma or seroma were assessed objectively, independently of the operating surgeon and subjectively by the patients. Results: Postoperative hematoma and edema were not influenced by the use of drains (p > 0.5). Patients reported no difference between the two sides with respect to swelling (p = 0.6) or discomfort (p = 0.5). However, drains produced a statistically significant reduction in postoperative bruising both on clinical assessment (p = 0.005) and patient assessment (p = 0.002). Conclusions: This article represents the first prospective, randomized, controlled trial assessing the use of postoperative drainage in facial rejuvenation surgery. Surgical drains do not influence postoperative complications, but they do significantly reduce bruising and so may facilitate the patients return to normal activity.

An analysis of p16 protein expression in sporadic malignant melanoma.

Inactivation of the p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactivation in melanocytic progression by measuring the level of p16 protein in a range of sporadic, benign and malignant melanocytic lesions. Using dual parameter flow cytometry, p16 protein expression was measured in 30 benign melanocytic naevi, 38 primary and 51 metastatic melanomas. A high level of p16 expression was demonstrated in benign melanocytic naevi (96% median nuclear positivity), with a significant reduction in primary melanomas (69%, P< 0.001). The median nuclear positivity of primary melanomas was significantly higher (P<0.03) than the level of expression in metastatic lesions (median positivity 37%). A progressive loss of p16 expression was demonstrated from benign melanocytic naevi through to primary and metastatic lesions. These data suggest that loss of p16 protein expression is not only associated with the early transformation of benign lesions, but also with the later stages of malignant progression.

Measurement of invasive potential provides an accurate prognostic marker for giant cell tumour of tendon sheath

Giant cell tumours of tendon sheath vary from solitary nodules to a multinodular variety that exhibits local infiltration. Recent advances in molecular oncology have defined a gene, nm23, expressed in normal cells which is responsible for inhibiting infiltration. The aim of this study was to investigate the expression of nm23 in a series of 52 giant cell tumours using immunohistochemistry and to assess its prognostic potential, nm23 expression was absent in 21% of tumours and this was associated with a highly significant risk of local recurrence (P<0.0001). Multivariate analysis of outcome showed nm23 expression to be more reliable than other clinicopathological parameters for predicting outcome. This immunohistochemieal test for nm23 is easily performed on standard paraffin sections and is recommended as an accurate prognostic marker for giant cell tumours of tendon sheath.

Measurement of c-myc oncoprotein provides an independent prognostic marker for regional metastatic melanoma.

Patients with melanoma who develop nodal metastatic disease represent a group with heterogeneous clinical outcome. Nodal positivity remains the most accurate prognostic marker for regional melanoma although it fails to predict outcome in a significant number of patients. Recent studies have illustrated the prognostic potential of c-myc oncogene expression in melanoma. The aim of this study was to measure c-myc oncoprotein in a series of regional metastatic specimens from 48 patients, and evaluate its use as a marker of clinical outcome. Oncoprotein expression was detected in 46 (96%) of the tumours with a median positivity of 68% (range 0-98%). Survival analysis revealed a significant association between oncoprotein positivity and survival (Long-Rank test, chi 2 = 15.2, P < 0.001). Multivariate analysis of outcome showed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including nodal positivity (chi 2 = 8.34, P = 0.003). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for regional metastatic melanoma.

Validation of tissue microarray for the immunohistochemical profiling of melanoma.

Tissue microarray technology allows high throughput profiling of cancer specimens by immunohistochemical staining. Protein expression varies throughout tumour specimens resulting in heterogeneous staining patterns, which has led to doubts as to the accuracy of tissue microarray. In an effort to validate the use of tissue microarray for melanoma immunohistochemical investigation, a study was conducted comparing the concordance of MCAM staining between whole tumour specimens and tissue microarray core biopsies. Data on full tissue sections were compared with the results of one to four 0.6 mm core biopsies per tumour on a tissue array. It was revealed that concordance of tissue array core biopsies in quadruplicate compared with full-section analysis for the expression and intensity of expression of MCAM.

Reducing Postoperative Morbidity After the Insertion of Gold Weights to Treat Lagophthalmos

&NA; Paralysis of the orbicularis oculi muscle leads to an unopposed action of the levator of the upper eyelid (lagophthalmos) in facial nerve palsy. The resultant exposure of the cornea may lead to keratitis, corneal ulceration, and eventual blindness. Although many surgical options exist in the treatment of lagophthalmos, upper lid loading with a gold weight implant has become one of the preferred methods to reduce the complications that may follow. The problems encountered after gold lid loading and methods to reduce postoperative morbidity are not well documented. The objective of this study was to determine the range of morbidity seen after gold weight insertion and to evaluate the effect of supratarsal fixation on subsequent morbidity. After retrospective reviews by questionnaire and case note analysis, supratarsal fixation was found to noticeably reduce the rate of implant ulceration and extrusion. This study demonstrates upper lid loading to be an effective method for the treatment of lagophthalmos, and it supports fixation of gold weights in reducing surgical morbidity. Misra A, Grover R, Withey S, et al. Reducing postoperative morbidity after the insertion of gold weights to treat lagophthalmos. Ann Plast Surg 2000; 45:623‐628