Radioimmunodetection of melanoma: preliminary results of a prospective study

A prospective study to evaluate the clinical usefulness of radioimmunodetection of melanoma in clinical practice is ongoing at the National Cancer Institute of Milan, Italy. Technical conditions for the application of the method were previously reported. In this trial, 99mTc-labelled F(ab')2 fragments of the 225.28S monoclonal antibody were used against a high molecular weight melanoma associated antigen (HMW-MAA). Retrospective studies on radioimmunodetection of melanoma have already been made by our group and by other Centers in about 300 patients. This study concerns the evaluation of the regional extension of primary melanoma. 23 patients with 32 suspected lymphatic involvements of melanoma on the trunk and arms underwent immunoscintigraphy. No false positive results were observed; 3 false negatives, one corresponding to a micrometastasis, were noticed. Specificity corresponds to 100% and sensitivity to 78.6%.     

Sampling of sentinel lymph nodes: a simulation study

OBJECTIVE: To analyze the effects of various slicing schemes on the detection of metastases in lymph nodes. STUDY DESIGN: Use of an advanced computer simulation tool. RESULTS: Bisectioning along the longitudinal axis is an inadequate approach. Slicing ellipsoid lymph nodes along their longitudinal axis also results in a lower rate of detecting metastases since metastatic deposits have a predilection to localize subcapsularly. CONCLUSION: Ellipsoid lymph nodes must be sliced perpendicular to the longest axis to increase the rate of detecting metastases.     

Assessing good operating conditions for intraoperative imaging of melanoma sentinel nodes by a portable gamma camera

ObjectiveTo provide guidance for reliable identification of low-activity sentinel nodes in the setting of melanoma surgery using a commercial hand-held gamma camera.MethodsThe average uptake of ^99mTc nanocolloid by sentinel nodes was evaluated in 95 excised nodes using a Sentinella 102^® (Oncovision, Valencia, Spain) portable gamma camera. The device sensitivity was assessed for different source depths and collimator distances, imaging an 8-mm sphere filled with a known-activity solution of ^99mTc. Five nuclear medicine physicians were asked to identify the source at different activity levels and positions within the field of view. For each image the number of signal counts inside a circular region of interest (ROI) was measured, while the variability of ROI counts among operators was assessed. The number of counts providing a minimal, near-constant inter-operator variability was determined as a criterion for a consistent identification of the source. Either the minimum activity or the acquisition time needed to collect the appropriate statistics were then calculated.ResultsThe median SN uptake (0.5%) turned out to be compatible with values reported in the literature. The sensitivity of the compact gamma camera ranged from ∼25 cpm/kBq to ∼1 cpm/kBq. A total of 50 counts in the ROI circumscribing the lymph node-simulating sphere appeared to be a robust criterion for identification of the source.ConclusionsTen megabecquerels of injected activity at the time of surgery and one minute of acquisition allows reliable identification of sentinel nodes for collimator-to-source distances up to 10 cm.     

Identification of identical TCRs in primary melanoma lesions and tumor free corresponding sentinel lymph nodes

It is generally believed that priming of efficient T-cell responses takes place in peripheral lymphoid tissues. Although this notion has been rigidly proven for infectious diseases, direct evidence for lymph node priming of in vivo T-cell responses against tumors is still lacking. In the present study, we conducted a full and nonbiased comparison of T-cell clonotypes in melanoma lesions and corresponding sentinel lymph nodes. Whereas most tumor lesions comprised a high number of T-cell clonotypes, only a small number of clonally expanded T cells were detected in the draining lymph nodes. Comparative clonotype mapping demonstrated the presence of identical T-cell clonotypes in the tumors and the respective sentinel lymph nodes, only when tumor cells were present in the latter. However, taking advantage of clonotype specific PCR amplification, TCR sequences representing clonally expanded T cells at the tumor site could be detected in the lymph nodes draining the tumors even in the absence of tumor cells. Evidence for the tumor-specific characteristics of these cells was obtained by in situ staining with peptide/HLA class I complexes demonstrating the presence of MART-1/HLA-A2- and MAGE-3/HLA-A2-reactive T cells at the tumor site, as well as in the draining lymph node. Our data indicate that T-cell responses to melanoma are primed in the sentinel lymph node by cross presentation of tumor antigens by dendritic cells.     

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/μCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 × 12.5 cm FOV) with a LEHR collimator (135 cpm/μCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.     

Survival benefit of sentinel lymph node biopsy in Asian melanoma patients

Sentinel lymph node biopsy (SLNB) provides important prognostic information for early-stage melanomas. However, statistics regarding the survival comparison between SLNB and nodal observation in Asia, where acral lentiginous melanoma (ALM) predominates, are limited. This study aimed to identify if SLNB offered survival benefits over nodal observation in early-stage melanomas in Taiwan. The retrospective study included 227 patients who met the SLNB criteria according to the National Comprehensive Cancer Network guidelines and were treated at National Taiwan University Hospital from June 1997 to June 2021. Survival analysis was performed using Kaplan–Meier curves and Cox proportional hazards regression models. Of the study population, ALM accounted for 73.1%; 161 patients (70.9%) underwent SLNB and 66 patients (29.1%) were under nodal observation. Multivariate analysis showed significantly improved melanoma-specific survival (hazard ratio [HR], 0.6; p = .02) in the SLNB group. Among those who underwent completion lymph node dissection (CLND), the non-sentinel node positivity rate was 44.4%. Immediate CLND resulted in significantly longer melanoma-specific survival and distant-metastasis-free survival (DMFS) compared to nodal observation. (HR, 0.2; p = .01 for melanoma-specific survival. HR, 0.3; p = .046 for DMFS). In conclusion, SLNB may provide survival benefits of cutaneous melanoma over nodal observation in the Taiwanese population.     

CCN1 is a novel target to reduce the metastasis of melanoma

Melanoma is becoming increasingly common in recent years and has a very high mortality rate, owing largely to its highly metastatic nature. It tends to metastasize early in the course of the disease, and after metastasis is resistant to most current therapies. Preclinical data has indicated that heparin administered to patients as an antithrombotic treatment also has anti-metastatic properties. Heparin has been shown to interfere with the binding of the integrin Very Late Antigen 4 (VLA-4) to its ligand Vascular Cell Adhesion Molecule 1 (VCAM-1) and in a recent paper the laboratory of Bendas (Thrombosis and Haemostasis, Prepublished online) demonstrated that CCN1 binds to VLA-4 and interference in this binding by heparin results in reduced strength of the VLA-4/VCAM-1 binding. This indicates that CCN1 might represent a good target for reducing the metastasis, and thus mortality, of melanoma.     

The color of drugs: a preliminary survey

An inquiry has been conducted on the colours considered more suitable for four kinds of drugs. In general, while light colours are indicated for antianxiety and sleep-inducing drugs, bright colours are indicated for antidepressant and tonics.     

Oligochaeta of Lake Taimyr: a preliminary survey

Lake Taimyr in Siberia is northernmost among the world's large lakes: 73°40–75°20N, 99–106°E. The lake area is up to 4650 km² in summer, with a maximum depth of 26 m and a mean depth of only 2.8 m. The ice-free period lasts about three months. The water level sinks 5.5–6 m during winter, so that 85% of the bottom surface is frozen into ice for some time and subjected to negative temperatures, probably down to –20 °C. In artificially melted sediment samples, 75–92% of animals survived. The average summer biomass of zoobenthos is about 1 g m^–2 wet weight, a half of this being formed by Oligochaeta. Altogether 76 samples with 3742 oligochaete specimens collected by V. N. Grëze in 1943–1944 were studied. At least 14 taxa of Tubificidae, Lumbriculidae, and Enchytraeidae were found in the lake, and some more enchytraeids in an adjacent river. Many immature animals could not be identified to species. Naididae were completely lacking probably due to the absence of macrovegetation. The shallow freezing zone is inhabited mostly by Alexandrovia ringulata. The profundal fauna is dominated by Lamprodrilus isoporus, Stylodrilus sp., and Isochaetides sp.     

Sessile foraminifera of the Hawaiian archipelago: a preliminary survey

As part of the Hawaiian Biological Survey, this study reports on the distribution of nine species of sessile foraminifera collected by dredge, grab, and around the Hawaiian Archipelago. The distributional survey includes data from the frontslopes of coral reefs to depths of 600 m and extends from the island of Hawaii and north to Pearl and Hermes Atoll in the North West Hawaiian Island chain. Species reported for the first time from Hawaii include Calcituba polymorpha, Discanomalina semipunctata, Halyphysema tumanowiczii, agenina divaricans, and Sageninafrondescens. Other sessile forams collected were-Ammolagena clavata, Biarritzina proteiformis, Carpenteria monticularis, and Miniacina miniacea.     

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.     

Pollination systems in the Asclepiadaceae: a survey and preliminary analysis

Using published and unpublished records of pollination in the dicot family Asclepiadaceae (the 'milkweeds') we offer a preliminary analysis of present-day pollination systems in the family. Variation in principal pollinators is apparent at and below the tribal level. The tribes Marsdenieae and Stapelieae and Asclepiadeae subtribe Gonolobineae are primarily Diptera-pollinated, a tentative conclusion also for the tribe Periploceae, and we emphasize the ubiquity and importance of fly pollination in the family. The rest of the tribe Asclepiadeae is pollinated in the main by Hymenoptera and Lepidoptera. Lack of data makes it impossible to draw even initial conclusions for the remaining tribes, Secamoneae and Fockeeae. Within the Asclepiadeae, there has been a trend towards more diverse pollination systems (incorporating butterflies and wasps) in the New World compared to the Old World. In terms of the taxonomic breadth of pollinators of individual species, Stapelieae is the most specialized tribe. We emphasize that this is only a preliminary account of pollination in the Asclepiadaceae, and detail areas where further work is urgently required.