Rogerio I. Neves

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

BACKGROUND Sentinel‐lymph‐node biopsy is associated with increased melanoma‐specific survival (i.e., survival until death from melanoma) among patients with node‐positive intermediate‐thickness melanomas (1.2 to 3.5 mm). The value of completion lymph‐node dissection for patients with sentinel‐node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel‐node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph‐node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma‐specific survival. Secondary end points included disease‐free survival and the cumulative rate of nonsentinel‐node metastasis. RESULTS Immediate completion lymph‐node dissection was not associated with increased melanoma‐specific survival among 1934 patients with data that could be evaluated in an intention‐to‐treat analysis or among 1755 patients in the per‐protocol analysis. In the per‐protocol analysis, the mean (±SE) 3‐year rate of melanoma‐specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log‐rank test) at a median follow‐up of 43 months. The rate of disease‐free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log‐rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log‐rank test); these results must be interpreted with caution. Nonsentinel‐node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases. (Funded by the National Cancer Institute and others; MSLT‐II ClinicalTrials.gov number, NCT00297895.)

Complications in tissue expander breast reconstruction: a comparison of AlloDerm, DermaMatrix, and FlexHD acellular inferior pole dermal slings.

AbstractAcellular dermal matrix (ADM) is frequently used in tissue expander breast reconstruction (TEBR) for coverage of the inferior pole. Several published studies have suggested increased rates of complications with the use of ADM. It is unknown, however, if the type of ADM used for TEBR impacts complication rates. The aim of this study is to compare 3 different types of ADM for TEBR in regard to clinically significant complications, specifically infection. We performed a retrospective analysis of primary breast cancer-related TEBR with or without ADM. Exclusion criteria consisted of prior major breast surgery, inadequate data, or loss to follow-up. Reconstructions were grouped by dermal sling type, AlloDerm, DermaMatrix (DM), FlexHD (FHD), or no ADM. Complications included cellulitis, abscess, seroma, expander leak or puncture, skin necrosis, wound dehiscence, or hematoma. Those requiring admission to hospital or reoperation were considered significant. Of 284 breasts reconstructed, 49 used AlloDerm, 110 used DM, 62 used FHD, and 64 used no ADM. The total complication rate with AlloDerm was 22% [95% confidence interval (CI), 11–34], with DM was 15% (95% CI, 8–21), and with FHD was 18% (95% CI, 8–28) (P = 0.47). Infectious complication rates for AlloDerm, DM, and FHD were equal at 10% (P = 0.97). The total complication rate of all ADM reconstructions as a grouped cohort was 17% compared to 11% without ADM (P = 0.48). The overall incidence of infectious complications with ADM was 10% compared to 2% without ADM (P = 0.09). There is no difference in the clinically significant overall complication rate or incidence of infection between AlloDerm, DM, and FHD. Isolating infectious complications, there is a trend toward increased incidence with ADM compared to reconstructions without.

The Role of Free Tissue Transfer Following Oncologic Resection in the Lower Extremity

The current treatment of extremity sarcomas is multimodal, consisting of limb-sparing surgery, adjuvant radiotherapy, and/or chemotherapy. This approach has decreased the need for amputations and increased the demand for coverage of large composite defects. To date, the role of microsurgery in lower extremity reconstruction after oncologic resection has not been well defined. This study reviews a single centers experience with free tissue transfer for reconstruction of the lower extremity after oncologic resection. Fifty-nine free flaps were performed in 57 patients over a 5-year period. Forty-six patients (78%) underwent primary reconstruction and 35 patients (61%) received adjuvant therapy. Overall flap success rate was 96.6%. Most flaps were soft-tissue types including musculocutaneous (78%), skin only (11%), and muscle plus skin graft (4%). Osteocutaneous flaps were uncommon. There were major complications in 12% and minor complications in 7%. This study demonstrates that free tissue transfer for lower extremity reconstruction following oncologic resection has a high success rate that is similar to other free flap applications. It has become an integral part of lower extremity sarcoma management. Free flaps permit uninterrupted adjuvant therapy and enhance the efficacy of limb salvage surgery.Cordeiro PG, Neves RI, Hidalgo DA. The role of free tissue transfer following oncologic resection in the lower extremity. Ann Plast Surg 1994;33:9–16

Abdominoplasty combined with other intraabdominal procedures.

One hundred three patients underwent abdominoplasty combined with other intraabdominal procedures including 67 tubal ligations, 34 total abdominal hysterectomies and 2 cholecystectomies, from January 1983 to July 1991. The patients were divided into two groups, those undergoing the standard or total abdominoplasty and those undergoing limited abdominoplasty with or without liposuction in delimited areas. In this series of 103 patients, we found only two minor complications and only three patients were transfused with autologous units of blood. When performed by well-schooled surgical teams, abdominoplasty may be combined with intraabdominal procedures with gratifying results.Gemperli R, Neves Rl, Tuma P Jr, Bonamichi GT, Ferreira MC, Manders EK: Abdominoplasty combined with other intraabdominal procedures. Ann Plast Surg 1992;29:18–22

Circulating Tumor Cells in Melanoma Patients

Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression.

A comparison of donor and recipient site sensation in free tissue reconstruction of the oral cavity.

In patients who undergo oral cavity reconstruction, loss of sensation plays a vital role in producing disturbances in postoperative oral function. Microsurgical techniques have provided a method of addressing this deficit through the use of sensate cutaneous free flaps in which microneural anastomoses are performed between a sensory nerve supplying the flap, and a recipient nerve in the head and neck. The purpose of this study was to compare the cutaneous sensation of the radial forearm flap and lateral arm flap donor sites, the two most commonly used intraoral sensate flaps. For comparison, sensation was also determined in five intraoral sites: the tip of tongue, lateral tongue, cheek, gingiva, and hard palate. Sensation was evaluated at the two potential donor sites in 66 random subjects using static and moving two-point discrimination, thermal sensation differences, and Semmes-Weinstein monofilament pressures. In the same subjects Semmes-Weinstein monofilament pressures were used to evaluate intraoral sensation. Information was recorded on age, sex, smoking and denture status. All four sensory evaluations demonstrated that the lateral arm flap donor site was more sensitive than the radial forearm donor site. Thermal sensitivity differentials (0.52 vs. 0.40°C, p < 0.001), static two-point discrimination (15.4 vs. 15.0 mm, p < 0.2), moving two-point discrimination (5.8 vs. 4.8 mm, p < 0.03), and Semmes-Weinstein monofilament pressures (5.10 vs. 4.08 g per square millimeter, p < 0.001) all indicated a more sensitive lateral arm flap donor site. Older subjects had significantly decreased sensation at both donor sites based on static two-point discrimination and Semmes-Weinstein monofilament testing. No sex differences were noted. Based on Semmes-Weinstein monofilament testing in the mouth, the tip of the tongue is the most sensitive area (2.26 g per square millimeter), followed by the hard palate (3.60 g per square millimeter), the lateral tongue (4.08 g per square millimeter), the cheek (4.77 g per square millimeter), and the gingiva (8.06 g per square millimeter). Smokers had significantly decreased sensation at the tip of tongue and hard palate. Denture wearers had significantly diminished sensation in all intraoral locations except the lateral tongue. Older patients had significantly diminished sensation at all intraoral sites. No sex differences were noted. The lateral arm flap donor site is a more sensitive region than the radial forearm flap donor site. However, the lateral arm flap donor site is less sensitive than the tip of tongue and hard palate, while the radial forearm flap donor site is less sensitive than the tip of tongue, hard palate, lateral tongue, and cheek. This suggests that for certain locations, intraoral sensate flaps may require measures such as sensory reeducation protocols to approach normal recipient site sensation.

Sentinel lymph node biopsy in cutaneous melanoma: Analysis of 240 consecutive cases

BACKGROUND The objective of this study was to evaluate practical rules for sentinel lymph node biopsy for melanoma and discuss the indications and outcomes of 240 patients. METHODS A prospective, nonrandomized analysis was performed on 240 patients in a referral cancer center. The median patient age was 51 years, and the median Breslow thickness was 1.60 mm. Ulceration was found in 30.4 percent of the cases. The median follow-up was 27.81 months. The sentinel lymph node biopsy was performed in 240 patients with cutaneous melanoma thicker or equal to 1 mm. The operation was performed with preoperative lymphoscintigraphy and postoperative immunohistochemistry. A statistical analysis was performed comparing the need for a gamma probe in each location, the value of the experience, the need for immunohistochemistry, positivity compared with Breslow thickness, reasons for the success of the lymph node localization, and evolution. RESULTS A total of 263 lymph node basins were identified (160 in the axilla, 86 in the inguinal region, and 17 in less common locations, including the popliteal, epitrochlear, and cervical regions). In every lymph node basin, the success of localization was directly related to use of the probe. The success rate for finding the sentinel lymph node increased year by year. Lymph node analysis disclosed positivity of 12.5 percent with hematoxylin and eosin staining and 17.5 percent with immunohistochemistry (excluding the sentinel lymph node not found disclosed 13.2 percent with hematoxylin and eosin and 18.5 percent with HMB45). Immunohistochemistry increased positivity by 40 percent. Positivity was directly related to Breslow thickness (p < 0.001). CONCLUSIONS This study shows the importance of the gamma probe in all lymph node basins but mainly in the axilla and unusual basins, as well as the importance of experience and immunohistochemistry. As a new procedure, it was possible to recognize the pattern of recurrence in the follow-up.

Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

Vismodegib and sonidegib are Hedgehog pathway inhibitors (HPIs) approved for treatment of patients with advanced basal cell carcinoma. The adverse events (AEs) associated with these therapies can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described in this article.

Cutaneous melanoma in childhood and adolescence: retrospective study of 32 patients.

This study was performed to analyse the behaviour, risk factors, prognosis and evolution of cutaneous melanoma in childhood and adolescence treated in a single institution. A retrospective study was performed between 1980 and 2000 of patients aged 18 years or younger followed at the Hospital do Câncer de São Paulo, Brazil. Data included demographic status, risk factors, clinical and histopathological characteristics of the primary and metastatic lesions, stage and follow-up. Seventeen female (53.1%) and 15 male (46.9%) patients were studied. Twelve patients (37.5%) were aged 12 years or younger. The trunk was the most common location (14 patients; 43.8%). Five patients (15.6%) had giant congenital melanocytic naevus, three (9.4%) had xeroderma pigmentosum and one (3%) had dysplastic melanocytic naevus. Nodular melanoma was the most frequent histological type and 43.8% had a thickness of more than 4 mm. Five of the 32 patients (15.6%) were lost to follow-up and 15 (46.9%) were alive at the last years follow-up, 11 (34.4%) without disease and four (12.5%) with active disease. The 5-year overall survival was 64.34%. An overall survival of 11.71% was found in patients with visceral metastasis with or without cutaneous and/or lymph node involvement, whereas the corresponding value was 90.48% (P value=0.0002) in patients with only cutaneous and/or lymph node metastasis. Cutaneous melanomas are uncommon in the young and are seldom diagnosed in the early stages, perhaps due to a reluctance to accept this diagnosis in this age group. Prevention and early stage diagnosis depend upon the recognition that this disease is present in the young.

Distally based fasciocutaneous flap of the calf for cutaneous coverage of the lower leg and dorsum of the foot.

&NA; Cutaneous injuries of the inferior third of the leg and dorsum of the foot represent a great challenge for plastic surgeons. The poor vascularization and subsequent poor healing encountered in these regions demand detailed knowledge of the local anatomy to select the best surgical alternative for each patient. In patients in whom local or free muscular flaps are not suitable, the fasciocutaneous flaps seem to be a good alternative. The distal pedicled fasciocutaneous flap of the calf was used to cover skin defects of the leg and foot in 22 patients. In 4 patients the authors designed an island flap to prevent a large defect in the donor area and to decrease the time of hospitalization and recovery of the patient. In a severe defect, the flap was used as a cross‐leg flap. The results were satisfactory because the flap provided stable coverage for different defects with few complications. The island flap is a good option for achieving a better aesthetic result and can be used in select patients. de Almeida OM, Monteiro Jr AA, Neves RI, de Lemos RG, Braz JC, Brechtbuhl ER, Gemperli R, Ferreira MC. The distally based fasciocutaneous flap of the calf for cutaneous coverage of the lower leg and dorsum of the foot. Ann Plast Surg 2000;44:367‐374