Validation study of the s classification for melanoma patients with positive sentinel nodes: the Montreal experience.

BACKGROUND: Standard of care is to perform a complete lymph node dissection (CLND) in melanoma patients with positive sentinel lymph nodes (SLNs). However, less than 20% will have metastases in non-SLNs. The S classification was described to predict the non-SLN status, hoping to identify a subset of patients who can be spared the CLND. We tried to validate the feasibility and usefulness of this classification. MATERIALS AND METHODS: We performed a retrospective chart review. All melanoma cases between 1996 and 2006 were included, and 359 patients with SLN biopsies were identified. All pathology slides were reviewed with an emphasis on the S classification. RESULTS: There were 365 SLN biopsies performed. A total of 82 patients (22.8%) had positive SLNs, while 277 patients (77.2%) had negative SLNs. There were 22 patients classified as SI, 18 as SII, 37 as SIII, and 5 were unclassified. On CLND, only 10 patients (12.2%) had positive non-SLNs. None of these were classified as SI while 2 patients (11%) were classified as SII and 8 (22%) as SIII. The S category was found to be a predictor of non-SLN status, and this reached statistical significance (P = 0.044). On univariate analysis, only an increasing Breslow depth and ulceration were predictive of a non-SI status. CONCLUSION: Our results suggest that the S classification is easily feasible and predicts the status of non-SLNs. No patient with SI status was found to have additional non-SLN positive nodes. A larger-scale, prospective trial should be done to confirm these results and possibly spare patients the morbidity of CLND with a positive SLN.

Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG.

UNLABELLED: Early detection of breast cancer is crucial for efficient and effective treatment. We have developed an instrument for positron emission mammography (PEM) called PEM-I that performs high-resolution metabolic imaging of breast cancer. Images of glucose metabolism are obtained after injection of 75 MBq FDG. The PEM detectors are integrated into a conventional mammography system, allowing acquisition of the emission images immediately after the mammogram, without subject repositioning, and accurate coregistration of images from the 2 modalities. In this article, we present the results of the first clinical pilot study with the instrument. METHODS: Sixteen subjects (age range, 34-76 y) were studied. All subjects were nondiabetic, nonpregnant, and without a history of cancer. They had recently been found to have suggestive mammography findings or a palpable breast mass and underwent lumpectomy or mastectomy within 2 wk of the study. Results from the PEM study were compared with those from mammography and pathology. A PEM test was classified positive (indicating the presence of cancer) if significant focal uptake was seen in the image or if the counting rate in the breast with suggestive findings was significantly higher than in the contralateral breast. RESULTS: Of the 16 subjects studied, 14 were evaluable. Ten cancerous tumors and 4 benign tumors were confirmed by pathologic examination after complete removal of the tumor. PEM correctly detected the presence of disease in 8 of 10 subjects. Findings were false-negative in 2 instances and false-positive in none, giving the instrument 80% sensitivity, 100% specificity, and 86% accuracy. CONCLUSION: Our preliminary results suggest that PEM can offer a noninvasive method for the diagnosis of breast cancer. Metabolic images from PEM contain unique information not available from conventional morphologic imaging techniques and aid in expeditiously establishing the diagnosis of cancer. In all subjects, the PEM images were of diagnostic quality, with an imaging time of 2-5 min.

Positron emission mammographic instrument: initial results.

Performance characteristics of a positron emission mammographic (PEM) instrument were studied. This dedicated metabolic breast imaging system has spatial resolution of 2.8-mm full width at half maximum (FWHM), coincidence resolving time of 12-nsec FWHM, and absolute efficiency of 3%. Hot spots with diameter of 16 mm in a phantom with signal-to-background activity ratio of 6:1 were distinguishable with a scanning time of 5 minutes.

Small-bowel resection for metastatic melanoma.

OBJECTIVE: To determine whether complete resection of small-bowel metastases from melanoma improves patient survival. DESIGN: A computer-aided chart review. SETTING: Hospitals associated with McGill University. PATIENTS: Twenty patients (17 men, 3 women), identified from 1524 patients with melanoma, who underwent surgery to the small bowel for metastases. Patient age and clinical presentation, tumour site and stage were recorded. INTERVENTION: Exploratory laparotomy with complete or partial resection of involved small bowel. MAIN OUTCOME MEASURES: Operative morbidity, mortality and length of survival related to the extent of small-bowel resection. RESULTS: Eleven patients had complete resection, 8 patients had partial resection and 1 patient had a palliative bypass only. Long-term survival (ranging from 2 to 10 years) was 36% in those who had complete resection and 0% in those who had partial resection; operative morbidity and mortality were 20% and 15% respectively. CONCLUSION: Complete resection of small-bowel metastases in patients with metastatic melanoma can result in long-term survival.

Training general practitioners in surgical and obstetrical emergencies in Ethiopia.

A 6-month course for training general practitioners (GPs) in surgical emergencies was developed and piloted in Ethiopia. The course was designed after an assessment of the surgical manpower needs in Ethiopia. Seven GPs were selected by the Ministry of Health (MOH) from rural hospitals that had no surgical specialists but had operating facilities. The course consisted of 1 week of lectures followed by 11 weeks each in obstetrics/gynaecology and general surgery. The GPs trained in district hospitals under the supervision of surgical specialists. Emphasis was placed on practical experience in managing a limited number of previously identified surgical emergencies. Follow up 9 months after completion of the course showed that five of the seven GPs had completed significant numbers of life saving procedures. Complications occurred largely in advanced disease. Difficulties remain with the recognition of the GPs' training and their supervision. We conclude that GPs can be trained to provide life saving surgery in a short training programme at a modest cost, but mechanisms for ensuring ongoing support need to be established.

The spectrum of surgery in Ethiopia.

Ethiopia's need for surgical services is assessed from on-site reviews of operating-room records in various hospitals and compared with data from other countries. Information on surgical manpower and total operations for the country were obtained from the Ministry of Health of Ethiopia. In Ethiopia the ratio of surgeons to population is very low (0.32 surgeons per 100,000 population) and inadequate numbers of essential operations (e.g., cesarean section and inguinal-hernia repair) are performed. The average age of the surgical patient is young (37 years), and men are operated on twice as frequently as women. Of the 9422 operations performed during 6 months in the central, regional and rural hospitals surveyed, 7037 (75%) could be performed by a general practitioner or a paramedic specially trained for the procedure and would not require a fully trained general surgeon. The implications for surgical manpower training are discussed.

The distribution of cancer specimens from two pathology centres in Ethiopia.

A relative frequency study of cancers in Ethiopia was conducted using pathology data from two major Ethiopian pathology centres. The cancer distribution is similar to that described in other East African countries. Carcinomas of the cervix and breast are the most common biopsied cancers in women. Lymphatic cancer and soft tissue sarcomas are the commonest biopsied cancers in men.

Productivity of needle localization to facilitate excision of nonpalpable, mammographically suspicious lesions.

The use of needle localization to aid excisional biopsy of nonpalpable breast lesions is now common, and the literature suggests that 13% to 33% of such lesions are malignant. During the 4 years from 1984 to 1988, all women who underwent fine-needle localization in preparation for biopsy were studied to identify factors that might facilitate the selection of those more likely to harbour a cancer, thus sparing patients with benign disease operative intervention. In all, 124 biopsies were performed on nonpalpable lesions that were suspicious on mammography; 51 lesions were malignant and 73 benign. The average age of the patients was 56 years (55 years for those with benign lesions and 61 for those with malignant lesions). The family history, history of breast disease, symptoms and calcification seen on mammography were not significantly different between the two groups. Only 25% of the malignant lesions were noninvasive. In 10% of the patients who had invasive lesions there was lymph-node involvement. The rate of malignancy in this patient population (41%) was slightly better than that reported in the literature, and a larger proportion of patients had noninvasive disease. The authors conclude that none of the above-mentioned risk factors could be used in the preoperative selection of patients for open biopsy.

Clinical evaluation of liposomal tumor antigen vaccines in patients with stage-III melanoma.

In this study, we report the results of an active-specific immunotherapy phase I study using autologous tumor-associated antigens (TAA) incorporated within liposomal carriers in patients with metastatic malignant melanoma. A group of 13 patients were entered into the study and given subcutaneous (s.c.) injections of liposome-TAA preparations at 2- to 4-week intervals. Clinical and laboratory monitoring did not reveal any short- or long-term systemic or local toxicity. Three patients had a complete response, and two patients had a partial response (50% or greater size reduction in one or more tumor sites). The remaining eight patients showed no response with disease progression. Two of these eight patients are still undergoing treatment. The TAA preparations stimulated peripheral blood lymphocyte proliferation (PBL) in vitro in those patients exhibiting a clinical response: no such responses were observed in the nonresponder patients. NK cell activity did not correlate with PBL proliferation or clinical response status, whereas PBL cytostatic activity against heterologous melanoma tumor cells correlated with clinical responsiveness. This form of immunotherapy appears to be a safe and feasible candidate for a much larger phase I/II study.

Double blind randomized prospective trial of levamisole/placebo in stage I cutaneous malignant melanoma.

One hundred and fifty-six Stage I, Clark's Level III, IV, and V cutaneous malignant melanoma patients were randomized, 83 to Levamisole and 73 to placebo. One hundred and thirty-seven patients were evaluable. Their median follow-up time was 5 years. The 2 groups were comparable in terms of patient characteristics, except for a slightly higher percentage of Clark's level III in the placebo group (57.8 vs 52%). Severe toxicity leading to discontinuation of the medication occurred in 32 patients in the Levamisole arm, versus 10 in the placebo arm. Thirty per cent of patients receiving Levamisole have recurred in comparison with 26% of those on placebo treatment, and despite a trend in the delay of appearance of distant metastasis in the patients receiving Levamisole (30 months versus 9 months in the placebo patients), this drug does not appear to be effective in altering the disease-free survival or the survival of Stage I patients in the dosage schedule utilized in this study.

Implantable device for venous access.

This paper reports the experience at the Royal Victoria Hospital in Montreal with the first 50 Port-A-Cath devices implanted for venous access in patients requiring long-term chemotherapy. There were 25 women and 22 men, ranging in age from 18 to 85 years. Twenty-two devices were implanted for hematologic malignant disease, 26 for solid tumours and 2 for benign disease. The mean operative time was 46.3 minutes, using a percutaneous subclavian stick technique in 94% of insertions. Blood sampling and infusions were easy in 88% and 92% respectively. Seventy-eight percent of the patients accepted the device well. Nine devices were removed, four at the end of therapy (median functioning time of 208.5 days) and five because of sepsis (median time 18 days). The median time of the still-functioning devices in live patients is 141.5 days. Septic complications were seen in 12%, blockage in 6% and skin necrosis in 2%. One death occurred from sepsis in a poor-performance patient with stage IV breast cancer and hypercalcemia. We breast cancer and hypercalcemia. We believe that the Port-A-Cath is efficient, safe and easily accessible for patients on long-term chemotherapy.

The effect of hyperthermia on the cytotoxicity of melphalan in Chinese hamster ovary cells.

The heat stability of melphalan during incubation at temperatures from 37 degrees C to 45 degrees C was determined by spectrophotometric and HPLC analyses and by direct measurement of melphalan cytotoxicity using a colonogenic assay Although OD 250 changed little during exposure to temperatures up to 45 degrees C for periods of up to 1 h, the melphalan HPLC peak decreased as function of incubation time and temperature. Loss of cytotoxicity following heating paralleled the decay of the melphalan HPLC peak. Despite the inactivation of melphalan by heat, the cytotoxic effects of melphalan were enhanced at elevated temperatures from 38 degrees C to 42 degrees C and synergism was observed at lethal temperatures above 42 degrees C.

Polyploidy and habitat differentiation in Dactylis glomerata L. from Galicia (Spain).

The microdistribution of diploid and tetraploid plants of Dactylis glomerata L. was examined and related to their immediate environment in several sites in central Galicia, where morphologically indistinguishable individuals of both ploidies grow in sympatry. The two related cytotypes differed in habitat preference. Diploids were mainly confined to the low-density forest-floor habitat in woodlands of mostly ancient origin, whereas tetraploids were widespread in varied habitats but clearly predominant in open areas, particularly in disturbed anthropic sites. The in situ comparison of plant performance showed that where plants of each ploidy were more common they produced more tillers, panicles and seeds. This habitat preference closely reflected differences in life-history characteristics. The tetraploids had an early and short flowering time almost always completed before the aestival drought, whereas the diploids began to flower several weeks later and flowered throughout the drought. Comparisons along artificial gradients of soil water availability and light transmittance indicated that the cytotypes had distinct physiological requirements which probably originated in metabolic and more general genetic differentiation and could be directly attributable to ploidy. Habitat differentiation increases the species' colonizing ability. It also amplifies divergence in reproductive strategy between diploids and tetraploids, which reduces ineffective crossing between cytotypes and thereby permits them to coexist in sympatry. The effect of hybridization at the polyploid level on the differentiation between cytotypes was assessed from the recent introduction of a foreign tetraploid entity into the study area. Hybridization between the two distinct tetraploids was found to increase habitat differentiation between the diploids and the tetraploids, but the major part of this differentiation is probably attributable to ploidy itself.

Effects of thermal adaptation at 40 degrees C on membrane viscosity and the sodium-potassium pump in Chinese hamster ovary cells.

We have demonstrated increased heat resistance in Chinese hamster ovary cells grown to confluence at 37 degrees C and thermally adapted at the nonlethal temperature of 40 degrees C for 24 h. Membrane viscosity, estimated by fluorescence anisotropy, was inversely related to temperature, from 5 degrees C to 45 degrees C. For a given temperature viscosity was consistently higher in thermally adapted cells than in native cells. Having demonstrated a change in membrane structure associated with thermal adaptation, we carried out a study of the Na+-K+ pump in native and thermally adapted cells as an example of a vital active transport process known to be sensitive to membrane viscosity. 86Rb uptake measured from 31 degrees C to 50 degrees C increased steadily to 46 degrees C and then decreased rapidly in both native and thermally adapted cells. Detailed measurement of ouabain-sensitive 86Rb influx demonstrated an increase in both Km and Vmax between 37 degrees C and 45 degrees C, but there was no difference between native and thermally adapted cells. We have thus demonstrated an adaptive structural change in the cell membrane of mammalian cells which may be related to the induction of thermal resistance at 40 degrees C but which is not associated with any change in this active transport system.

Effect of pregnancy upon malignant melanoma.

Results of this study suggest melanomas diagnosed, initiated or stimulated during pregnancy have worse prognoses than do those of patients not having this history. For those female patients who have had melanomas without a history of the preceding factors, it appears they can become pregnant following the diagnosis and treatment of melanoma without increased hazard. Further biochemical studies on hormone receptors and correlation with the clinical course are needed to clarify the influences of endocrines on malignant melanomas.