Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Impact of conversion on short and long-term outcome in laparoscopic resection of curable colorectal cancer.

INTRODUCTION: Long-term outcome of patients following conversion during laparoscopic surgery for colorectal cancer is not often reported. Recent data suggest a negative impact of conversion on long-term survival. This study aimed to evaluate the impact of conversion on the perioperative outcome and on long-term survival in patients who underwent laparoscopic resection for curable colorectal cancer. METHODS: Evaluation of our prospective in-hospital collected data of patients who underwent laparoscopic surgery for curable colorectal cancer over a 5-year period. Long-term data were collected from our outpatient's clinic data and personal contact when necessary. RESULTS: During the study period, 175 patients were operated on laparoscopically for curable colon cancer (stage I-III). Mean follow-up was 33±18 months with a minimum follow-up of 12 months. For various reasons, 25 patients (14.4%) had to be converted to open surgery. Short-term outcome revealed a trend towards longer operations, a higher rate of surgical complications, and a longer hospital stay in the converted group. Five-year, Kaplan-Meier, disease-free analysis was worse for converted patients. Overall survival did not differ between the 2 groups. Cox proportional hazards regression analysis revealed that conversion and AJCC stage were independent risk factors for recurrence. CONCLUSIONS: Conversion in laparoscopic surgery for curable colorectal cancer is associated with a worse perioperative outcome and worse disease-free survival.

Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.

BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device. METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups. RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC. CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.

A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery.

BACKGROUND: This randomized, double-arm trial was designed to study the benefit of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in intraoperative margin assessment for breast-conserving surgery (BCS) and the associated reduction in reoperations. METHODS: In the device group, the probe was applied to the lumpectomy specimen and additional tissue was excised according to device readings. Study arms were compared by reoperation rates and by correct surgical reaction confirmed by histology. RESULTS: Three hundred patients were enrolled. Device use was associated with improved correct surgical reaction, defined as additional re-excision in all histologically detected positive margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control arm. There were no differences in excised tissue volume or cosmetic outcome. CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection is safe and effective in BCS and decreases the rate of repeat operations.

Sentinel node-guided evaluation of drainage patterns for melanoma of the helix of the ear.

The head and neck region, and especially the ear and its helix, is notorious for its ambiguous pattern of lymphatic drainage. Therefore, the primary nodal drainage basins in melanoma of the helix of the ear are often unpredictable. The aim of the study was to examine the value of sentinel lymph node biopsy in melanoma of the helix of the ear and to describe the natural history of the disease. Fifteen consecutive patients (14 men) with primary melanoma of the helix of the ear (median thickness, 1.2 mm; range, 0.7-10.0) underwent preoperative lymphoscintigraphy, followed by intraoperative lymphatic mapping, using blue dye in combination with a hand-held gamma probe and sentinel lymphadenectomy. The melanomas were characterized by low mitotic rate, low lymphocytic infiltrate, low spontaneous-regression rate, and mostly epitheloid cell type. In one patient, preoperative lymphoscintigraphy failed to demonstrate the draining nodes. The sentinel lymph nodes were identified and retrieved in all patients during surgery. In 13 patients (87%), they were found in the upper jugular lymphatic basin (level IIA); none were found in the retroauricular region. All sentinel lymph nodes were tumor-negative. At a median follow-up of 39 months (range, 12-73), all 15 patients were disease-free. In conclusion, sentinel lymph node biopsy for helix melanoma is an excellent alternative to elective lymph node neck dissection and superficial parotidectomy, with a high success rate and low morbidity. Melanoma of the helix of the ear has an indolent natural history.

Immunohistochemical expression of platelet growth factor and vascular endothelial growth factor in patients with melanoma with and without redness (Brenner sign).

OBJECTIVE: To assess whether an erythematous eruption in the vicinity of or distant from a melanoma lesion might be related to the vascular endothelial growth factor, the platelet-derived endothelial cell growth factor, or both. METHODS: Biopsy specimens from 13 patients with primary melanoma, 6 of whom had erythematous eruptions and 7 who did not, were studied by immunohistochemistry for the expression of vascular endothelial growth factor and platelet-derived endothelial cell growth factor. RESULTS: Vascular endothelial growth factor was positive in 3 of 6 patients (50%) with melanoma and redness (Brenner sign) and in 4 of 7 patients (57%) with melanoma without redness. Platelet-derived endothelial cell growth factor was positive in all 6 patients (100%) with melanoma and redness and in 4 of 7 patients (57%) with melanoma without redness. CONCLUSION: Platelet-derived endothelial cell growth factor may have a part in the pathogenesis of the redness observed in patients with melanoma, called Brenner sign, by affecting vasculature function.

Improved sentinel node identification by SPECT/CT in overweight patients with breast cancer.

UNLABELLED: Overweight has been reported as a cause for the nonvisualization of sentinel nodes (SNs) on preoperative planar lymphoscintigraphy in patients with breast cancer. The purpose of this study was to assess whether SPECT/CT may improve SN identification in overweight patients. METHODS: Lymphoscintigraphy was performed in 220 consecutive patients with breast cancer. Body mass index (BMI) was calculated for each. A total of 122 patients were overweight or obese (BMI, > or = 25). Planar images and SPECT/CT images were interpreted separately, and SN identification on each of the modalities was related to BMI and to findings at surgery. RESULTS: Planar imaging identified SNs in 171 patients (78%) with a BMI (mean +/- SD) of 25.2 +/- 4 kg/m2 and failed to do so in 49 patients (22%) with a BMI of 28 +/- 8 kg/m2. In 29 of the latter patients (59%), SNs were identified on SPECT/CT. SPECT/CT detected "hot" nodes in 200 patients (91%) and failed to do so in 20 patients with a BMI of 29.2 +/- 6.6 kg/m2. For the 122 overweight or obese patients, planar assessment failed to identify SNs in 34 patients (28%) and SPECT/CT failed to do so in 13 patients (11%) (P < 0.001). For 116 patients, surgery took place in our hospital (Tel-Aviv Sourasky Medical Center). An intraoperative blue dye technique failed to detect SNs in 48 patients (41%) with a BMI of 28.2 +/- 7 kg/m2. SPECT/CT localized hot nodes in 36 (75%) of the latter patients, and planar imaging did so in 22 (46%) of those patients. Of 19 patients for whom scintigraphy failed, 6 (32%) had nodal metastatic involvement. CONCLUSION: The addition of SPECT/CT to lymphoscintigraphy improved SN identification in overweight patients with breast cancer. Moreover, SPECT/CT accurately identified SNs in 75% of patients for whom the identification of SNs by the intraoperative blue dye technique failed.

Lymphoscintigraphy for sentinel node mapping using a hybrid single photon emission CT (SPECT)/CT system in oral cavity squamous cell carcinoma.

BACKGROUND: We assessed the added clinical value of fused single photon emission computed tomography (SPECT) and low-dose CT images compared with planar images for sentinel node (SN) mapping in patients with oral cavity squamous cell carcinoma (SCC). METHODS: Twenty consecutive patients with newly diagnosed biopsy-proven SCC of the oral cavity were enrolled. Scintigraphy was performed using a hybrid gamma-camera/low-dose CT system. Planar images and fused SPECT/CT images were interpreted separately. All patients underwent a sentinel node biopsy (SNB) followed by a neck dissection. All SNs underwent meticulous pathologic examination and immunohistochemistry staining (cytokeratin complex) in addition to routine pathologic examinations of the neck dissection specimen. RESULTS: The sensitivity for the detection of nodal metastases was 87.5%. SPECT/CT improved SN identification and/or localization compared with planar images in 6 patients (30%). CONCLUSIONS: SPECT/CT SN mapping provides additional preoperative data of clinical relevance to SNB in patients with oral cavity SCC.

A biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, temozolomide (Temodal), interferon-alfa and interleukin-2 for metastatic melanoma: a phase II study.

Our objective was to evaluate the toxicity and antitumor efficacy of concurrent biochemotherapy in metastatic melanoma patients and the effectiveness of adding temozolomide to protect the brain from metastases. Twenty-three patients with advanced inoperable melanoma were hospitalized for 5-6 days for the following treatment: cisplatin 20 mg/m daily for 4 days, vinblastine 1.6 mg/m daily for 4 days and oral temozolomide 250 mg/m daily for 5 days, with 18 x 10 IU/m intravenous interleukin-2 by continuous infusion for 4 days (the dose was cut daily by 50%) and 5 x 10 U/m interferon-alfa subcutaneously daily for 5 days, repeated at 28-day intervals for a maximum of nine courses. According to the standard World Health Organization response criterion, the objective response rate was 43.4% and the median survival was 18.6 months. All but one patient survived for more than 12 months, and no responding patient progressed first in the brain. Substituting dacarbazine by temozolomide in the MD Anderson melanoma section protocol appears to offer protection against dissemination of brain metastases, equal activity in the periphery and a possible lower incidence of toxicity due to the oral route.

Detection of hepatocyte growth factor/scatter factor receptor (c-Met) and MUC1 from the axillary fluid drainage in patients after breast cancer surgery.

BACKGROUND: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer. OBJECTIVE: To evaluate the presence and prognostic value of MUC1 and Met-hepatocyte growth factor/scatter factor in the axillary drainage of these patients. METHODS: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-HGF/SF and beta-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status. RESULTS: RT-PCR assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.0 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05). CONCLUSION: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system.

UNLABELLED: Lymphoscintigraphy is performed before sentinel node (SN) biopsy for SN mapping. It is of clinical importance mainly if the tumor is located in body parts with ambiguous lymph node drainage. The purpose of this study was to assess the clinical benefit of fused SPECT/CT images to planar images for SN mapping. METHODS: Thirty-four consecutive patients with cutaneous malignant melanoma (n = 28) and squamous cell carcinoma (n = 6) and scheduled for SN biopsy were enrolled. Primary tumors were located in the trunk (n = 12), in the extremities (n = 12), in the head and neck (n = 9), and in the penis (n = 1). Scintigraphy was performed using a hybrid gamma-camera/low-dose CT system. Planar images and fused SPECT/CT images were interpreted separately. RESULTS: SPECT/CT identified multiple draining basins in 6 of 12 patients (50%) with trunk melanoma and in 3 of 9 patients (33%) with head and neck melanoma or mucosal tumor. In 9 of 21 patients (43%) with a primary tumor located in the head and neck or trunk region, SPECT/CT-fused images identified SNs that were missed on planar images, 2 of which were involved with tumor. Three of the 9 nodes were located close to the injection site and were hidden by its scattered radiation, and 2 were in-transit nodes. Another 4 nodes, identified on fused images only, were located in an additional basin to those identified on planar images. Fused images were of no added value either in patients with limb melanoma or in a patient with a penile melanoma. CONCLUSION: SPECT/CT SN mapping provides additional data that are of clinical relevance to SN biopsy in patients with trunk or head and neck melanoma and in patients with mucosal head and neck tumor.

Revision parathyroidectomy guided by intraoperative radionuclide imaging.

BACKGROUND: Technetium-99m sestamibi scintigraphy has become one of the most popular techniques for localization of the parathyroid gland after failure of primary neck exploration. OBJECTIVE: To examine the efficacy of sestamibi with the hand-held gamma ray detecting probe for the identification of parathyroid adenomas during revision parathyroidectomy. METHODS: We reviewed six cases of probe-assisted neck exploration for parathyroid lesions following unsuccessful primary exploration. RESULTS: In all cases the pathologic glands were successfully detected and removed. CONCLUSIONS: With careful planning, a gamma ray detecting probe can be used optimally 2-3 hours after technetium-99m sestamibi injection. The probe is efficient, easy and convenient to use.