Technical issues and pathologic implications of sentinel lymph node biopsy in early-stage breast cancer patients

BACKGROUND AND OBJECTIVES: Recent studies have demonstrated that the sentinel lymph node (sN) can be considered a reliable predictor of axillary lymph node status in breast cancer patients. However, some important issues, such as optimization of the technique for the intraoperative identification of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla still require further elucidation. The objectives of this study was to assess (1) the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, and (2) the correlation between the size of sN metastasis (micrometastasis < or = 2 mm; macrometastasis > 2), primary tumour size, and the status of nonsentinel nodes (nsN) in the axilla. METHODS: Between October of 1997 and December of 1999, 212 patients with breast cancer (average age: 61 years; range, 40-79 years) underwent sN biopsy before performing standard axillary dissection. In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed. RESULTS: Overall, the sN was identified in 206 of 212 patients (97.1%); at histologic examination of all dissected nodes, 77 of 206 patients had positive nodes (37.3%). The false-negative rate was 6.5% (5/77), the negative predictive value was 96.3% (129/134), and accuracy was 97.6% (201/206). Among 72 patients with positive sN, micrometastases were detected in 21 cases and macrometastases in 51. When micrometastases only were observed, the sN was the exclusive site of nodal metastasis in 17 of 21 cases (80.9%); in the remaining 4 cases (19.1%), nsN metastases were detected in 3 of 14 pT1c patients (21.5%), and 1 of 5 pT2 patients (20%). Macrometastases were detected in patients with tumors classified as pT1b or larger: the sN was the exclusive site of metastasis in 3 of 4 pT1b patients (75%), in 14 of 29 pT1c patients (48.2%), and in 3 of 18 pT2 patients (16.6%). The specific contribution of the two different techniques used in the identification of the sN was evaluated; the detection rate was 73.8% (113 of 153) with Patent Blue-V alone, 94.1% (144 of 153) with RGS alone, and 98.7% (151 of 153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) with each of the three procedures (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). CONCLUSIONS: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, due to the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar with each one of the methods assessed. That patients with small tumours (<1 cm) and sN micrometastasis are very unlikely to harbour metastasis in nsN should be considered when planning randomised clinical trials aimed at defining the effectiveness of sN guided-axillary dissection.     

Antibiotic prophylaxis with teicoplanin in patients undergoing breast reconstruction with the transverse rectus abdominis myocutaneous flap

Summary The authors report the results of a randomized clinical trial of antibiotic prophylaxis for post-operative infection following breast reconstruction with the transverse rectus abdominis myocutaneous (TRAM) flap. The aim was to evaluate the efficacy and tolerability of short-term parenteral prophylaxis with teicoplanin; the endpoint of the study was the reduction of wound contamination assessed by microbiologic culture of drain fluid. From October 1990 to March 1992, 38 patients were recruited: 20 patients were included in the antibiotic prophylaxis arm (teicoplanin i.v. 400 mg one hour before operation and in the following 12 h plus 200 mg i.v. at 24 h after operation) and 18 patients in the control group. Analysis of drain fluid showed a higher contamination (15/18=83%) in the control group (Staphylococcus epidermides, Streptococcus alfa-emoliticus, Enterobacter aerogenes, Peptostreptococcus magnus) as compared to the prophylaxis arm with teicoplanin (2/20=10%) (Staphylococcus coagulase-negative) (p< 0.0001). Moreover, 11 patients in the control group suffered from fever > 37.5° C as compared to one patient in the antibiotic prophylaxis group (p<0.0001); the post-operation stay was 13.3±4.3 and 9.0±1.6 in the control and antibiotic arm, respectively (p=0.0002). There were no antibiotic related side effect in this study. These results seem to confirm the value of parenteral short-term antibiotic prophylaxis of post-operative infection in this type of clean operative procedure.     

Radiotherapy in low-grade glioma adult patients: a retrospective survival and neurocognitive toxicity analysis

Purpose

The treatment of low-grade glioma is still debated. Surgery is the first-line approach, and the correct timing of radiation therapy has not yet been defined since “early” radiation therapy improves relapse-free survival but not overall survival. Since a longer progression-free survival is desirable, the main issue related to radiotherapy is the incidence of late neurocognitive toxicity.

Materials and methods

Ninety-five patients with low-grade glioma were consecutively treated with early (within 3 months) or late (at disease progression) post-surgical radiation therapy. Clinical and therapeutic factors were entered into the analysis overall (OS) and progression-free (PFS) survival, and the distribution in two accrual periods identified based on the evolution of imaging procedures and radiotherapy techniques were compared. For 6/18 long survivors (LS) without evidence of disease, neurocognitive evaluation was obtained and the dose to the hippocampus region was retrospectively calculated.

Results

Univariate analysis of OS showed a statistically significant advantage for grade 1 and oligodendroglioma histology, better performance status [Karnofsky index (KI)], age <40 years, radical surgery, no steroid treatment; PFS was significantly related with younger age, better KI and “early” radiotherapy. Multivariate analysis of OS confirmed the significance of all variables except surgery; for PFS, only “early” radiotherapy and better KI retained significance. Memory impairment was evident in 4/6 of the LS tested; quality of life was good and executive functions were normal.

Conclusion

Radiotherapy remains an essential component in the treatment of low-grade glioma. Prospective studies are needed to evaluate the relative contributions of the disease itself and of surgery, radiation and chemotherapy to long-term neurocognitive damage.     

Investigating the association between Notch3 polymorphism and migraine

OBJECTIVE: The aim of the present study was to evaluate whether the functional Notch3 polymorphism T6746C, which is not causative for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), might be a risk factor for migraine. BACKGROUND: It has been recently demonstrated that migraine is characterized by subclinical brain infarctions and white matter lesions. Several genetic risk factors have been associated with migraine, but no study has unraveled a possible relationship between migraine and Notch3, which is involved in vascular damage. Mutations in Notch3 gene have been demonstrated to be pathogenetic for CADASIL, a small vessel disease of the brain characterized by migraine. METHODS: A total of 156 migraine patients and 128 nonheadache healthy volunteers entered the study. Demographic and clinical characteristics were carefully recorded, and a neurological work-up was performed. Moreover, each subject underwent a blood sampling for Notch3 genotype determination. RESULTS: Notch3 genotypes as well as allele frequencies did not differ in migraine patients compared to controls, even adjusting for the presence of possible confounds. No difference has been found either in migraine patients with aura or in those without aura. CONCLUSIONS: These findings support the view that functional polymorphism T6746C in Notch3 gene is not involved in increasing the risk of migraine or migraine subtypes.