Intra-lesional interleukin-2 for the treatment of in-transit melanoma.

PURPOSE: To investigate the role of intra-lesional interleukin-2 (IL-2) injection for treatment of in-transit melanoma metastases. METHODS: Consecutive patients with in-transit metastases were treated with intra-lesional IL-2 injections. Two independent observers evaluated response to treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. A blinded pathologist confirmed clinical response with post-treatment biopsies. RESULTS: Thirty-nine patients were included. Patients received biweekly IL-2 injections. At each treatment session, a mean of 2.08 ml (5 µ/ml) of IL-2 were distributed amongst a mean of 12 (range 1-57) in-transit lesions. Patients were followed for an average of 30.4 months (range 2.2-66.6 months). The overall patient response rate was 82%. A complete response was obtained in 20 patients (51%), a partial response in 12 (31%), and no response in seven (18%). Of the 629 in-transit metastases, 479 (76%) completely resolved. Complete responders had a significant in transit-free (P = 0.0005) and an overall (P = 0.012) survival advantage compared with partial responders. CONCLUSIONS: The treatment of in-transit metastatic melanoma with intra-lesional IL-2 resulted in a 76% percent clearance of lesions. Complete response is associated with superior in transit-free and overall survival when compared with partial response.

Development of a breast reconstruction satisfaction questionnaire (BRECON): dimensionality and clinical importance of breast symptoms, donor site issues, patient expectations, and relationships.

OBJECTIVES: To develop a valid, reliable and responsive, self-administered questionnaire to assess women's satisfaction with breast reconstruction. METHODS: Item generation: Three sources for item inventory were utilized: focus groups, expert panel, and literature review.Item reduction: Item impact scores were derived from patients and experts each ranking the importance and frequency of each item. Correlation between patient and expert scores was calculated. The highest impact questions were maintained. RESULTS: Four focus groups comprising 20 women generated 515 items, 10 experts developed 171 items, and literature review produced 227 items. These 913 potential items were reduced to 183 by combining redundancy. The 183 items underwent formal reduction by assessing importance and frequency of each item. Thirty-two of 40 reconstructed women and 19 of 19 experts responded to the mail-out. Seventy-seven items of the women's top 100 also made the experts' top 100 list. Intraclass correlation between patients and experts was 0.71 [0.62 0.77], indicating "good" but not "excellent" agreement, reinforcing the importance of patient involvement in questionnaire development. Women rated abdominal donor site issues higher than experts, and experts rated breast softness and symmetry higher than women. CONCLUSIONS: A 100-item pilot questionnaire for breast reconstruction satisfaction was developed for psychometric testing.

Long-term limb allograft survival using a short course of anti-CD45RB monoclonal antibody, LF 15-0195, and rapamycin in a mouse model.

BACKGROUND: The purpose of this study was to determine if a short course of monoclonal antibody (mAb) against CD45RB, LF 15-0195, and rapamycin would achieve long-term survival by inducing tolerance in a mouse limb transplant model. METHODS: Group 1 (n=9) consisted of nine isogenic (C57BL/6) transplants. Group 2 (n=3) included C57BL/6-to-BALB/c transplants receiving no drug therapy. Group 3 mice (n=4) were treated with mAb (3 mg/kg) and LF (2 mg/kg), and Group 4 (n=13) was treated with mAb, LF, and rapamycin (2 mg/kg). Both treatment groups received drug treatment for only 14 days posttransplantation. Animals were sacrificed if they displayed evidence of rejection or when deemed to be tolerant (defined as >day 100). RESULTS: All isografts had normal histology and graft function on day 100. Untreated C57BL/6-to-BALB/c allografts developed acute rejection within 10 days. The combination of mAb and LF prolonged allograft survival to a mean of 39+/-7 days. In Group 4, two animals had to be sacrificed at days 28 and 76 due to acute urinary retention. Transplant tolerance was achieved in 8 of the remaining 11 animals with a mean survival time of 100+/-12 days. Donor specific tolerance was demonstrated through permanent acceptance of skin grafts from the donor strain and rejection of skin grafts from C3H mice. Three Group 4 animals showed clinical and histological signs of mild, chronic rejection. Dendritic cells isolated from tolerant recipients exerted a suppressive effect in mixed lymphocyte reaction. CONCLUSION: A short course of anti-CD45RB mAb and LF 15-0195 prolonged limb allograft survival. The addition of rapamycin induced limb allograft tolerance which is associated with the generation of tolerogenic dendritic cells that suppressed T-cell proliferation.

Minimizing morbidity in the treatment of penile melanoma: Mohs micrographic surgery and sentinel lymph node biopsy.

The combination of Mohs micrographic surgery and sentinel lymph node biopsy in the treatment of penile melanoma is novel. Mohs surgery allows the removal of penile malignancies with microscopically controlled tumor-free borders, while maintaining cosmetic and functional demands through the maximal preservation of normal tissue. Sentinel lymph node biopsy minimizes the morbidity associated with inguinal node dissection. At 30 months follow-up, these two modalities together have achieved local control and regional nodal staging while minimizing functional morbidity.

Scalp and forehead reconstruction.

The reconstruction of defects that involve the scalp and forehead presents unique aesthetic and functional challenges. This article reviews the surgical anatomy of these regions and presents an algorithm for decision making in reconstructive surgery. Nonmicrosurgical techniques are briefly reviewed. The microsurgical reconstruction of scalp and forehead defects differs from the more common oropharyngeal reconstructions in several ways, including flap choices, choices for recipient vessels, and the opportunity to use conventional and microsurgical techniques simultaneously to improve outcomes. Each of these considerations is reviewed and the authors' preferred techniques presented.

Sentinel node biopsy as an adjunct to limb salvage surgery for epithelioid sarcoma of the hand.

BACKGROUND: Epithelioid sarcomas of the hand are rare, high-grade tumors with a propensity for regional lymphatic spread approaching 40%. CASE PRESENTATION: A 54-year-old male with an epithelioid sarcoma of the palm was treated with neoadjuvant radiation, wide excision, and two-stage reconstruction. Sentinel lymph node biopsy was used to stage the patient's axilla. Sentinel node biopsy results were negative. The patient has remained free of local, regional and distant disease for the follow-up time of 16 months. CONCLUSION: The rarity of this tumor makes definitive conclusions difficult but SLN biopsy appears to be a useful adjunct in the treatment of these sarcomas.

A new, validated instrument to evaluate competency in microsurgery: the University of Western Ontario Microsurgical Skills Acquisition/Assessment instrument [outcomes article].

BACKGROUND: The authors present a model for microsurgery learning as well as a validated instrument to evaluate microsurgical competency. METHODS: Novice microsurgeons participated in three 3-hour sessions wherein they completed a number of increasingly complex, standardized microsurgical tasks. Performance was recorded and graded using a newly developed University of Western Ontario Microsurgery Skills Acquisition/Assessment (UWOMSA) instrument. The knot-tying and anastomosis modules contained three categories with five-point Likert scales. Each learner's performance was assessed by two blinded surgeons. Reznick's validated global rating scale for operative performance was utilized to establish criterion validity. Within-scale scores were compared via intraclass correlation and between-scale scores with Pearson correlation coefficient. Linear regression was used to evaluate the effect of various predictors on UWOMSA scores. RESULTS: Thirty-seven videos (9.6 hours) were reviewed, including 20 knot-tying sessions and 17 anastomoses. Interrater reliability of UWOMSA was high, with an intraclass correlation coefficient of 0.75 (0.57, 0.87). The intraclass correlation of the global rating scale was 0.79 (0.62, 0.89). Intrarater reliability of the UWOMSA was also high, with an intraclass correlation of 0.69 (0.48, 0.83). The intraclass correlation of the global rating scale was 0.69 (0.47, 0.84). Measures of criterion validity demonstrated strong agreement between UWOMSA and the global rating scale (Pearson correlation coefficient, 0.96; p < 0.001). Measures of construct validity demonstrated that higher scores on the UWOMSA were associated with faster knot tying (p < 0.0001) and higher postgraduate year level (p = 0.05). CONCLUSIONS: The UWOMSA instrument performed well in terms of reliability and validity. Further study is planned to assess the instrument's ability to predict microsurgical skills translation to the clinical setting.

Acquisition of evidence-based surgery skills in plastic surgery residency training.

INTRODUCTION: The teaching and learning of critical appraisal skills and evidence-based practices by surgical residents has been identified as an unmet need in many surgical training programs. METHODS: Monthly journal clubs over a calendar year were the setting for a critical appraisal curriculum. Preassigned homework assignments and carefully selected articles with specific methodologies were posted electronically and formed the course material. Pretests and posttests on medical statistics and methodology were administered. Presurveys and postsurveys on attitudes toward evidence-based surgery (EBS) were administered. RESULTS: Precourse surveys revealed a lack of confidence in residents' knowledge of epidemiology and biostatistics, with an increase in confidence postcourse (2.6 vs 2.9; p = 0.4). Precourse and postcourse, there was strong support for more critical appraisal training in residency (5.1 vs. 4.8; p = 0.1) and an agreement that understanding evidence-based practices is important for the clinical practice (4.6 vs. 4.6; p = 0.4) as well as the research endeavors of a plastic surgeon (5.4 vs. 5.5; p = 0.8). Pretest scores, when compared with PGY level, showed an increase in knowledge with increasing PGY level (p = 0.6). Average pretest scores were 6.5 of a total of 15 points, or 43%. Posttest scores were improved, at 7.8 of 15, or 52% (p = 0.6). Sixty-four percent of learners felt that journal club was a good venue for teaching critical appraisal skills precurriculum. Fifty percent of learners were still of that impression at course completion (p = 0.3). The modest improvement in test scores indicates an impact on critical appraisal skills, but reliance on journal clubs to teach these skills is insufficient. CONCLUSIONS: Through monthly journal clubs and self-directed assignments, critical appraisal skills were improved across PGY levels in an academic surgical training program; however, other settings and methods of teaching are required to augment a curriculum in evidence-based surgery.

Sensibility following innervated free TRAM flap for breast reconstruction: Part II. Innervation improves patient-rated quality of life.

BACKGROUND: Restoring sensory innervation may be a useful adjunct in free flap head and neck reconstruction but, as yet, has not been shown to improve outcomes of breast reconstruction. The authors' previous study demonstrated objectively improved sensation in a group of innervated transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction patients relative to noninnervated flaps. This study compared patient-rated outcomes of free TRAM breast reconstruction in innervated versus noninnervated flaps. METHODS: Twenty-seven women were randomized prospectively to undergo either innervated or noninnervated free TRAM flap breast reconstruction. For innervated flaps, the T10 intercostal nerve was harvested with the TRAM flap and neurotized to the T4 sensory nerve at the recipient site. Three validated outcome tools were administered after surgery: the Medical Outcomes Study 36-Item Short Form Health Survey, the Body Image after Breast Cancer Questionnaire, and the Functional Assessment of Cancer Therapy-Breast. Results were correlated with previously reported objective sensibility outcomes. RESULTS: Eighteen of 27 women returned their questionnaires a mean 48 months after free TRAM flap reconstruction. Demographic analysis revealed no significant differences in patient age, height, smoking, radiation therapy, and nipple-areola complex reconstruction between randomized patient groups. There was a statistically significant improvement in all three measures in patients who were randomized to receive innervated free TRAM flaps compared with those receiving noninnervated flaps. CONCLUSION: This study demonstrates that innervation of free TRAM flaps used for breast reconstruction not only improves sensibility but also has a positive effect on patient-rated quality of life.

Mohs micrographic surgery in the treatment of lentigo maligna and melanoma.

BACKGROUND AND OBJECTIVES: The treatment of lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging due to lesion location, size, patient age, and potential for recurrence and spread. The largest studies to date confirm that for melanocytic tumours, MMS provides high local control rates while minimizing tissue loss. Herein we report our local control rate for melanoma treated by MMS over a decade. METHODS: Charts were reviewed on all patients with melanocytic tumors treated by a single physician (JPA) using MMS over the time period of 1993-2002. Demographic, surgical and pathological details were recorded. Patients were followed for local, regional and distant recurrences. RESULTS: The patient population was comprised of 199 patients with 202 melanomas. There were 69 invasive lesions, with a mean Breslow depth of 0.92 mm (0.2-3.6 mm). The mean number of levels required to clear the lesions was 2.7 (1-7), resulting in a mean defect size of 11.8 cm2 (0.9-70.7 cm2). Patients with LMM were significantly older (73.2 vs. 66.5 yrs, p = 0.012) and had larger defects after MMS (16.74 cm2 vs. 10.27 cm2) than patients with LM. At a mean follow-up of 29.8 months, there were no local recurrences, four regional recurrences, and two distant recurrences. CONCLUSION: MMS is an effective modality for the clearance of melanocytic tumors.

Sensibility following innervated free TRAM flap for breast reconstruction.

BACKGROUND: The free transverse rectus abdominis musculocutaneous (TRAM) flap has proven to be a reliable means of recreating the aesthetic breast form after mastectomy. The purpose of this study was to determine whether neurotization of the free TRAM flap improved sensation of the reconstructed breast. METHODS: Twenty-seven patients undergoing 37 free TRAM flap reconstructions were randomized to receive either an innervated (12 patients, 18 breasts) or a noninnervated flap (15 patients, 19 breasts). A nerve repair between the T10 intercostal of the TRAM flap and the anterior sensory branch of the fourth intercostal nerve was performed for innervation. Sensory testing (Semmes-Weinstein monofilaments, hot-cold discrimination, two-point discrimination) was performed by one blinded examiner in a standardized pattern. RESULTS: Mean follow-up was 16 months. Demographic analysis revealed no significant differences in patient age, height, smoking, radiation therapy, and nipple-areola reconstruction between patient groups (p > 0.3). Patients in the noninnervated group, however, were heavier (p = 0.03). Preoperative sensation was not significantly different in the noninnervated and innervated groups. Postoperative pressure threshold and temperature discrimination were significantly improved in the innervated flaps (p < 0.05). Noninnervated flaps displayed a pattern of increasing sensibility from the center toward the periphery while innervated flaps regained sensation throughout. CONCLUSIONS: Innervation of the free TRAM flap provides improved sensation to the reconstructed breast and is a simple adjunct to breast reconstruction.

The perimeter technique for lentigo maligna: an alternative to Mohs micrographic surgery.

BACKGROUND: Lentigo maligna (LM) presents a challenge for complete surgical excision because of its extensive subclinical spread and predilection for the face. OBJECTIVE: To report our experience using the staged perimeter technique as an alternative to Mohs micrographic surgery for treatment of LM. METHODS: The perimeter procedure was performed on 11 patients with LM between March 2003 and June 2004. Data on patient and lesion characteristics, number of stages required to obtain clear margins, and follow-up was obtained by chart review. RESULTS: A mean of 1.9 stages were required to achieve clear margins. A mean of 7 tissue specimens were sent to pathology per patient for evaluation. After a mean follow-up of 4.7 months, all patients were free of recurrence. CONCLUSIONS: The perimeter technique is a simple method of margin-controlled excision of LM. The main advantage is that all margins are examined with permanent sections. The main drawback is that multiple operative sessions are required to complete the procedure. This technique does not require specific Mohs training and is therefore applicable to non-Mohs surgeons.

Choice of recipient vessels in delayed TRAM flap breast reconstruction after radiotherapy.

This study compared the use of the internal mammary and thoracodorsal recipient vessels in a uniform group of patients who underwent delayed TRAM flap reconstruction after radiotherapy, focusing on usability rates and outcomes. The authors identified 123 delayed TRAM flap patients who had undergone postmastectomy radiotherapy from a prospective database (1990 to 2001). Recipient vessel unusability rates were calculated on the basis of reports of inspection of a vessel, either by direct intraoperative dissection or by findings from color Doppler examination (internal mammary vessels only). Charts were reviewed for outcomes including flap loss, vascular complications, fat necrosis, and lymphedema; t-test and chi-square analyses were performed to compare outcomes and unusability rates, and multiple regression analysis was performed to determine factors influencing outcome. Of the 123 planned free TRAM flaps, 106 were completed as free flaps and 17 were performed as pedicled flaps because of unusable recipient vessels. Of the free flaps, 45 were anastomosed to the internal mammary vessels, 55 to the thoracodorsal vessels, and six to other vessels. The internal mammary and thoracodorsal groups did not differ significantly in body mass index, abdominal scars, smoking history, time delay between irradiation and TRAM flap reconstruction, or flap ischemia time. Radiation doses to the axilla (thoracodorsal), internal mammary chain, and supraclavicular fossa were similar between the groups. The internal mammary vessels were rejected in 11 (20 percent) of 56 cases, and the thoracodorsal vessels were rejected in 19 (26 percent) of 74 cases (p = 0.42). In cases with unusable internal mammary vessels, 46 percent (n = 5) had inadequate veins, 27 percent (n = 3) had inadequate arteries, and in 27 percent (n = 3) both vessels were inadequate. In the 19 cases with unusable thoracodorsal vessels, 84 percent (n = 16) were excessively scarred, 11 percent (n = 2) had inadequate vessels, and 5 percent (n = 1) were absent. Outcomes were similar regardless of recipient vessels used (internal mammary versus thoracodorsal): total flap loss, 0 percent versus 4 percent (p = 0.20); vascular complications, 6.7 percent versus 11 percent (p = 0.46); arm lymphedema, 4.4 percent versus 9 percent (p = 0.37); partial flap loss, 9 percent versus 6 percent (p = 0.54); and fat necrosis, 18 percent versus 15 percent (p = 0.69). Multivariate analysis revealed a trend for higher complication rates in smokers and with the use of the thoracodorsal vessels as the recipients. Overall, no discernible unusability or outcome differences were detected between the internal mammary and thoracodorsal groups.

Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma.

BACKGROUND: Local recurrence rates of 15% to 30% after treatment of soft tissue sarcoma (STS) are still common but unacceptable. Our hypothesis was that a refined neoadjuvant chemotherapy and radiation protocol (modified Eilber protocol) improves local control rates while minimizing major morbidity. METHODS: Consecutive patients with STS deep to the fascia of the extremity or trunk during 1984 to 1996 were treated with 3 days of doxorubicin (30 mg/day) and sequential radiation (300 cGy/day for 10 days). Wide excision with limb preservation was performed 4 to 8 weeks after radiation completion. Treatment complications, margins, local recurrence, and survival were prospectively documented. RESULTS: Of 75 patients, 66% had tumors >5 cm, and 71% were grade 2/3. In eight patients, negative margins were not achieved, and four of these had amputation (95% limb salvage). Three of the remaining four had local recurrence with a 5- and 7-year actuarial local control rate of 50% and 25%, respectively. In contrast, of the 67 patients with negative margins, a local control rate of 97% at 5 years and 94% at 7 years and an overall survival of 63% were achieved. Although margin (P = .001) and stage (P = .035) were correlated, these were not significant on multivariate Cox regression analysis. Risk factors for death included tumor stage (hazard ratio, 1.54; P = .001) and tumor grade (hazard ratio, 1.4; P = .02). Three patients (4%) required reoperation for tissue loss, and eight patients (10.6%) developed minor wound complications. CONCLUSIONS: This modified Eilber protocol seems to maximize local control and minimize major wound complications for extremity/truncal STS.

Management of lentigo maligna and lentigo maligna melanoma: seminars in surgical oncology.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) represent a character, histogenetic subclass of melanocytic malignancies. They often present with a prolonged phase of slow growth but once invasion has occurred, the prognostic features are identical to all other melanomas. These lesions occur primarily on the head and neck where they evolve from areas of pigmented staining to the more typical features identifiable with malignant melanomas on other skin surfaces. The treatment options and recent advances in management are reviewed.