Sentinel lymph node biopsy for staging breast cancer

Cadherin-11 is a calcium-dependent cell adhesion molecule that is expressed in cells of the mesenchymal lineage during embryonic development. In this study we show, for the first time, that cadherin-11 gene is expressed in the bone marrow and bone cells obtained from rabbits of various age groups. Furthermore, a quantitative measurement of gene expression revealed that cadherin-11 was expressed in young rabbits (6 week-old: open epiphysis) at a level of 6.7 x 10(5) +/- 0.7 x 10(5) molecules; in mature rabbits (8-10 month-old: closed epiphysis) at 11 x 10(5) +/- 0.9 x 10(5) molecules; and in aged rabbits (4-5 year-old) at a level of 1.2 x 10(5) +/- 0.2 x 10(5) molecules/microg total RNA. The relative level of cadherin-11 gene expression in mature rabbit marrow was found to be approximately 50% greater than in young rabbits. However, aged animals showed a reduction in cadherin-11 specific gene expression of greater than 900% as compared with mature animals. Age-related changes in bone remodeling/turnover lead to reduced bone density and high fracture risk, and since cadherins play a crucial role in tissue morphogenesis, this marked decrease may represent an index of the aging process in bone.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Lymphatic mapping and sentinel node biopsy in breast cancer

BACKGROUND: Sentinel lymph node biopsy is a recently developed, minimally invasive technique for staging the axilla in patients with breast cancer. It has been suggested that this technique will avoid the morbidity associated with more extensive axillary dissection. A wide range of different methods and materials has been employed for lymphatic mapping, but there has been little consensus on the most reliable and reproducible technique. METHODS: This is a comprehensive review of all published literature on sentinel node biopsy in breast cancer, using the Medline and Embase databases and cross-referencing of major articles on the subject. RESULTS AND CONCLUSION: Sentinel node biopsy is a valid technique in breast cancer management, providing valuable axillary staging information. The optimal technique of lymphatic mapping utilizes a combination of vital blue dye and radiolabelled colloid. However, there remain controversial issues which require to be resolved before sentinel node biopsy becomes a widely accepted part of breast cancer care.     

Axillary lymph node microcalcifications disclosing breast cancer]

It is well known that vertebral schisis is frequent in enuretic children but the true incidence in the normal population is not clear, because all series published are referred to children with associated urinary anomalies, who were submitted to voiding cystography and or intravenous pyelography. This determine a statistical bias. The aim of our study was to compare the prevalence of vertebral schisis in enuretic children and in the general pediatric population. Therefore, we chose 142 enuretic children without associated urological or neurological anomalies and a control group of 152 children, assumed as general population, who were submitted to spinal X-rays during screening for scoliosis or congenital dysplasia of the hip. Vertebral schisis was found in 65% (93/142) of enuretics and in 18% (28/152) of control group children. Maximum association between enuresis and vertebral schisis was found in primary monosymptomatic nocturnal enuresis (82%), while minimum association was found in children with secondary enuresis (57%). The difference in percentage of association enuresis-schisis was statistically significant between enuretics and control group and between primary monosymptomatic and secondary enuresis (p < 0.001). The results of this paper are simply add knowledges on the prevalence of the sacral schisis in enuretic children. But, to speculate the different prevalence in different types of enuresis, the results should confirm that the phenomenon of enuresis is multifactorial and the primary monosymptomatic and secondary enuresis have different etiological factor.     

Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer

Lymphoscintigraphy associated with radioguided biopsy of the sentinel node (SN) is well established in clinical practice for melanoma. In breast cancer, the SN concept is similarly valid, and lymphoscintigraphy is a useful method for localizing the axillary SN. The aim of this study was to optimize the lymphoscintigraphy technique in association with a gamma ray detecting probe (GDP) for identifying and removing the SN in breast cancer patients. METHODS: Two-hundred fifty patients with operable breast tumor underwent lymphoscintigraphy before surgery. Three different size ranges of 99mTc-labeled colloid particles (<50, <80 and 200-1000 nm) were used, with either subdermal (above tumor) or peritumoral injection. Early and late scintigraphic images were obtained in anterior and oblique projections, and the skin projection of the detected SN was marked. Sentinel nodes were identified and removed with the aid of the GDP during breast surgery; they were tagged separately. Complete axillary dissection followed. In 40 patients, a blue dye was also administered in addition to subdermal radiolabeled colloid to compare blue dye mapping with lymphoscintigraphy localization. RESULTS: Lymphoscintigraphy successfully revealed lymphatic drainage in 245 of 250 patients (98%). The axillary SN was identified in 240 patients (96%). SN biopsy correctly predicted axillary node status in 234 of 240 patients (97.5%). Lymphoscintigraphy and GDP detected the SN most easily and consistently when 200-1000 nm colloid was administered subdermally in an injection volume of 0.4 ml. Blue dye mapping was successful in 30 of 40 patients (75%). In 26 of these patients, the dye and lymphoscintigraphy identified the same node; in 4 cases different nodes were identified. None of these four patients had axillary disease. CONCLUSION: Lymphoscintigraphy is a simple procedure that is well tolerated by patients. Sentinel node identification is more reliable when large-size radiolabeled colloids are injected in a relatively small injection volume (0.4 ml). Use of a GDP greatly facilitates precise pinpointing and rapid removal of the SN.     

Demonstration of the sentinel lymph node in axillary dissection for breast cancer

OBJECTIVES: The sentinel node is defined as the first-line axillary lymphatic drainage node in breast cancer. If the sentinel node can be identified, during axillary dissection for breast cancer, resection could be limited reducing subsequent morbidity. However, before modifying the standard dissection procedure, it is important to prove that the sentinel node is representative of the metastatic status of other axillary nodes. PATIENTS AND METHODS: Between March and December 1996, 86 patients (mean age 58 years, range 32-82) underwent amputation (n = 20), tumorectomy with dissection (n = 56) or tumorectomy followed by secondary dissection (n = 10) for breast cancer. Ten ml of diluted patent blue was injected either into the peripheral portion of the tumor or the tumorectomy cavity. Node dissection was performed 10 to 20 minutes after injection. The blue sentinel node was identified prior to standard dissection. RESULTS: A mean 12 nodes were removed (range 4-21). Seventy-nine sentinel nodes were identified (91%) and in 7 cases (8%) a sentinel node could not be identified. In 7 other cases the sentinel node was a false negative, i.e. non malignant despite metastases in other dissected nodes. In all the other cases, the status of the sentinel node predicted the status of the other nodes, i.e. a non-metastatic sentinel node associated with other metastatic nodes. Finally, in 7 cases, the sentinel node was the only invaded node among the nodes dissected. During the last 3 months of the study, the sentinel node was identified in 100% of the cases and was representative of the overall dissection. CONCLUSION: Identifying the sentinel node is an alternative to standard axillary node dissection procedures. The method requires a training period and identification can be improved with radioimmunologic guidance. Patient selection within the framework of a rigorous multidisciplinary protocol is indispensable. A nationwide study is currently being conducted to validate these preliminary results.     

Sentinel lymph node biopsy for melanoma

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.     

Predicting regional lymph node metastasis in carcinoma of the penis: a comparison between fine-needle aspiration cytology, sentinel lymph node biopsy and medial inguinal lymph node biopsy

OBJECTIVE: To evaluate the accuracy of clinical examination and fine-needle aspiration cytology (FNAC) in detecting groin metastases in patients with carcinoma of the penis, and to assess the positive and negative predictive value (PPV, NPV) of a preliminary sentinel lymph-node biopsy (SNB) and biopsy of the most medial of the horizontal group of inguinal lymph nodes (MIN) in selecting patients for an ilio-inguinal block dissection. PATIENTS AND METHODS: The study comprised 28 patients (56 groins) with Stage I (one), Stage II (11) and Stage III (16) carcinoma of the penis. All patients underwent a detailed clinical examination followed by FNAC of the palpable inguinal nodes, and were subsequently submitted for block dissection. The MIN, the SN and the rest of the inguinal and iliac nodes were histologically examined separately for metastases. RESULTS: The clinical evaluation had a sensitivity of 74%, a specificity of 61%, a PPV of 57% and a NPV of 77%. The corresponding values for FNAC were all 100%, and the specificity and PPV for both MIN and SN were 100%. The sensitivity and NPV of MIN were higher than for SN, although not significantly so. CONCLUSION: Clinical examination alone is inaccurate in selecting patients with carcinoma of the penis for block dissection. FNAC is accurate and specific when nodes are palpable; in those with impalpable nodes a preliminary MIN biopsy followed by SNB if the MIN biopsy is negative will accurately select all patients with metastases in the groin nodes. This can be performed by examining frozen sections of the lymph nodes; if positive, block dissection can be carried out at the same time.     

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

Metabolic control analysis (MCA) has provided the language and framework for quantitative study of control over flux, or over metabolites, by individual enzymes of a pathway. By contrast, top-down control analysis (TDCA) yields an immediate overview of the control structure of the whole system of interest, giving information about the control exercised by large sections of complex pathways. Unlike MCA, TDCA does not rely on the use of specific inhibitors or genetic manipulation to determine control coefficients. The method and an application of TDCA to ketogenesis are described.     

Positive developments for patients with breast cancer as a result of the sentinel node biopsy procedure

As an increasing number of large prospective studies show a high accuracy of the sentinel node for the staging of the axilla in women with invasive breast cancer, there is no need to test the value of this new technique in a randomised trial. Much more emphasis should be given to a reliable implementation of the technique in general practice, requiring a closely co-operating multidisciplinary team meticulously performing the different steps of the technique. The guidelines designed by the Dutch Working Group on the Sentinel Node in Breast Cancer include a learning phase of--arbitrarily--50 procedures in patients also undergoing a complete axillary dissection. What remains is the need for a treatment trial aimed at reducing the morbidity of the treatment of axillary metastases while retaining equal regional tumour control and patient survival. As the indication for adjuvant systemic treatment has shifted from the N-stage to T-stage parameters (size, grade, mitotic activity), the axillary nodal status has become less important as a staging tool. Thus, comparison of surgery or radiotherapy of sentinel node positive patients in a randomised trial appears to be a logical next step.     

Sentinel node localization in breast cancer

The immutans (im) mutant of Arabidopsis shows a variegated phenotype comprising albino and green somatic sectors. We have cloned the IM gene by transposon tagging and show that even stable null alleles give rise to a variegated phenotype. The gene product has amino acid similarity to the mitochondrial alternative oxidase. We show that the IM protein is synthesized as a precursor polypeptide that is imported into chloroplasts and inserted into the thylakoid membrane. The albino sectors of im plants contain reduced levels of carotenoids and increased levels of the carotenoid precursor phytoene. The data presented here are consistent with a role for the IM protein as a cofactor for carotenoid desaturation. The suggested terminal oxidase function of IM appears to be essential to prevent photooxidative damage during early steps of chloroplast formation. We propose a model in which IM function is linked to phytoene desaturation and, possibly, to the respiratory activity of the chloroplast.     

Changes in lymph node dissection for pancreatic cancer

Two step pancreatoduodenectomy for periampullary carcinoma was first reported in 1912 by Kausch. Pancreatoduodenectomy performed for carcinoma of the head of the pancreas was first reported in 1937 by Brunschwig. Before this report, all previous pancreatoduodenectomy had been performed for other periampullary tumors. By the 1960's, pancreatoduodenectomy was performed for pancreatic cancer without lymph node dissection. However, Fortner advocated regional pancreatectomy for pancreatic cancer in 1973. In our institute, also, extended radical pancreatectomy by translateral retroperitoneal approach has been performed during the past 2 decades. Many Japanese surgeons also adopted extend pancreatectomy. In the 1980's, extended radical pancreatectomy consisted of paraaortic lymph node dissection, total pancreatectomy, and complete resection of extrapancreatic nerve plexus. However, based on the many clinicopathologic studies, pancreatoduodenectomy was better operative procedure than total pancreatectomy. Although extended radical pancreatectomy has the advantage of long-time survival, disadvantage of nutritional status and quality of life was produced by this operative procedure. Tarverso and Longmire reported new operative procedure of pylorus preserving pancreatoduodenectomy (PPPD) in 1978. Recently, this operative procedure was indicated for pancreatic cancer. However, there is a question whether PPPD is the best operative procedure for pancreatic cancer or not.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.