Amyand's hernia with acute phlegmonous appendicitis: case report.

Any inguinal hernia containing the vermiform appendix is called Amyand's hernia. Amyand hernias are very rare and even rarer is the association of Amyand hernia with acute appendicitis. Due to the rarity of this entity, it constitutes a challenging case in terms of diagnosis and treatment. The surgical management is not yet standardized and there are no clear guidelines. There are some controversies regarding whether to perform an appendectomy if appendix appears normal or whether mesh can be used for the hernia repair if appendectomy is performed. We describe a case of Amyand hernia in a 90-year old man with acute appendicitis and we review current literature regarding surgical strategy.

Dual inhibition of REV-ERBß and autophagy as a novel pharmacological approach to induce cytotoxicity in cancer cells.

REV-ERBα and REV-ERBß nuclear receptors regulate several physiological processes, including circadian rhythm and metabolism. A previous study reported the REV-ERBα gene to be co-overexpressed with ERBB2 in breast cancer cell lines. Surprisingly, we found that several tumor types, including a number of breast cancer cell lines, predominantly express the REV-ERBß variant. This pattern was independent of ERBB2 and ER status, and opposite to that of non-cancer mammary epithelial HMEC cells, in which REV-ERBα was the major variant. Consistent with this molecular profile, REV-ERB target genes in both circadian and metabolic pathways were derepressed upon silencing of REV-ERBß, but not REV-ERBα. Strikingly, we found that REV-ERBß is a determinant of sensitivity to chloroquine, a clinically relevant lysosomotropic agent that suppresses autophagy. The cytoprotective function of REV-ERBß appears to operate downstream of autophagy blockade. Through compound screening, we identified ARN5187, a novel lysosomotropic REV-ERBß ligand with a dual inhibitory activity toward REV-ERB-mediated transcriptional regulation and autophagy. Remarkably, although ARN5187 and chloroquine share similar lysosomotropic potency and have a similar effect on autophagy inhibition, ARN5187 is significantly more cytotoxic. Collectively, our results reveal that dual inhibition of REV-ERBß and autophagy is an effective strategy for eliciting cytotoxicity in cancer cells. Furthermore, our discovery of a novel inhibitor compound of both REV-ERB and autophagy may provide a scaffold for the discovery of new multifunctional anticancer agents.

A risk score model predictive of the presence of additional disease in the axilla in early-breast cancer patients with one or two metastatic sentinel lymph nodes.

BACKGROUND: Axillary lymph node dissection (ALND) in early-breast cancer patients with positive sentinel node (SLN+) may not always be necessary. AIMS: To predict the finding of ≥1 metastatic axillary node in addition to SLN+(s); to discriminate between patients who would or not benefit from ALND. METHODS: Records of 397 consecutive patients with 1-2 SLN+s receiving ALND were reviewed. Clinico-pathological features were used in univariate and multivariate analyses to develop a logistic regression model predictive of the risk of ≥1 additional axillary node involved. The discrimination power of the model was quantified by the area under the receiver operating characteristic curve (AUC) and validated using an independent set of 83 patients. RESULTS: In univariate analyses, the risk of ≥1 additional node involved was correlated with tumor size, grade, HER-2 and Ki-67 over-expression, number of SLN+s. All factors, but Ki-67, retained in multivariate regressions were used to generate a predictive model with good discriminating power on both the training and the validation sets (AUC 0.73 and 0.75, respectively). Three patient groups were defined based on their risk to present additional axillary burden. CONCLUSIONS: The model identifies SLN+-patients at low risk (≤15%) who could reasonably be spared ALND and those at high risk (>75%) who should receive ALND. For patients at intermediate risk, ALND appropriateness could be individually evaluated based on other clinico-pathological parameters.

EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms.

Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification and rearrangement are early events in tumorigenesis, this implies that they should be preserved throughout the tumor. However, in primary GBM, EGFRvIII expression is focal and sporadic. Unexpectedly, we found EGFR amplification and rearrangement throughout the tumor, including regions with no EGFRvIII expression, suggesting that mechanisms exist to modulate EGFRvIII expression even in the presence of high gene amplification. To study this phenomenon, we characterized three GBM cell lines with endogenous EGFRvIII. EGFRvIII expression was heterogeneous, with both positive and negative populations maintaining the genetic alterations, akin to primary tumors. Furthermore, EGFRvIII defined a hierarchy where EGFRvIII-positive cells gave rise to additional positive and negative cells. Only cells that had recently lost EGFRvIII expression could re-express EGFRvIII, providing an important buffer for maintaining EGFRvIII-positive cell numbers. Epigenetic mechanisms had a role in maintaining heterogeneous EGFRvIII expression. Demethylation induced a 20-60% increase in the percentage of EGFRvIII-positive cells, indicating that some cells could re-express EGFRvIII. Surprisingly, inhibition of histone deacetylation resulted in a 50-80% reduction in EGFRvIII expression. Collectively, this data demonstrates that EGFR amplification and rearrangement are early events in tumorigenesis and EGFRvIII follows a model of hierarchical expression. Furthermore, EGFRvIII expression is restricted by epigenetic mechanisms, suggesting that drugs that modulate the epigenome might be used successfully in glioblastoma tumors.

Role of emergency thoracic ultrasonography in spontaneous pneumomediastinum. Two case report.

Early identification of spontaneous pneumomediastinum in an Emergency Department is possible with thoracic ultrasound. We report two cases of spontaneous pneumomediastinum, diagnosed in a 26-year old man with chronic asthma and a 19-year old athlete, and discuss the role of thoracic US alongside conventional X-ray and thoracic CT in emergency medicine. The patients were transferred to an Emergency Department, where conservative treatment produced a good outcome. The greater sensitivity and specificity of thoracic US over conventional supine X-ray in the detection of occult pneumothorax is ever more appreciated. However, training in the diagnosis of pneumomediastinum is required.

[Relation of non-alcoholic hepatic steatosis to early carotid atherosclerosis in diet-controlled impaired glucose tolerance subjects]. / Relazione della steatoepatite non alcolica all'aterosclerosi carotidea precoce in pazienti con Intolleranza ai carboidrati.

AIMS: To compare carotid artery intima-media thickness values, as a reliable marker of early atherosclerosis, in individuals with and without nonalcoholic hepatic steatosis, and to evaluate whether such differences are mediate by metabolic syndrome variables. MATERIALS AND METHODS: Carotid intima-media thickness (by ultrasonography), hepatic steatosis (by ultrasonography), insulin resistance (by Homeostasis Model Assessment-HOMA), steatohepatitis (by histologic specimen) were measured in 54 non-alcoholic steatohepatitis, and 54 IGT, compared with 54 healthy subjects. RESULTS: Subjects with nonalcoholic steatohepatitis had markedly greater carotid intima-media thickness measurements (1.38±0.12 vs 1.12±0.10 mm; p<0.001) than controls. The marked differences in carotid intima-media thickness that were observed between the groups were little affected by adjustment for age, sex, body mass index, waist/hip ratio, diabetes duration, blood pressure, lipids. CONCLUSIONS: These results suggest that in IGT non smoking subjects, the significant increase of carotid intima-media thickness in presence of nonalcoholic steatohepatitis cannot be mediated by HOMA-estimated insulin resistance; thus the NAFDL and NASH can be independent features of metabolic syndrome and other unknown factors can be responsible to progression of steatosis to NAFLD and NASH.

Immunohistochemical discrimination of wild-type EGFR from EGFRvIII in fixed tumour specimens using anti-EGFR mAbs ICR9 and ICR10.

BACKGROUND: The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours determined by the FDA-approved EGFR PharmDx kit (Dako) or other standard anti-EGFR antibodies and the response to the EGFR inhibitors. METHOD: In this study, we investigated the potential of our anti-EGFR monoclonal antibodies (mAbs; ICR9, ICR10, ICR16) for immunohistochemical diagnosis of wild-type EGFR and/or the type-III deletion mutant form of EGFR (EGFRvIII) in formalin-fixed, paraffin-embedded human tumour specimens. RESULTS: We found that the anti-EGFR mAb in the EGFR PharmDx kit stained both wild-type and EGFRvIII-expressing cells in formalin-fixed, paraffin-embedded sections. This pattern of EGFR immunostaining was also found with our anti-EGFR mAb ICR16. In contrast, mAbs ICR10 and ICR9 were specific for the wild-type EGFR. CONCLUSION: We conclude that mAbs ICR9 and ICR10 are ideal tools for investigating the expression patterns of wild-type EGFR protein in tumour specimens using immunohistochemistry, and to determine their prognostic significance, as well as predictive value for response to therapy with EGFR antibodies.

Accuracy of sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with locally advanced breast cancer and clinically positive axillary nodes.

BACKGROUND: Feasibility and accuracy of sentinel node biopsy (SLNB) after the delivery of neo-adjuvant chemotherapy (NAC) is controversial. We here report our experience in NAC-treated patients with locally advanced breast cancer and clinically positive axillary nodes, and compare it with the results from our previous randomized trial assessing SLNB in early-stage breast cancer patients. PATIENTS AND METHODS: Sixty-four consecutive patients with large infiltrating tumor and clinically positive axillary nodes received NAC and subsequent lymphatic mapping, SLNB and complete axillary lymph node dissection (ALND). The status of the sentinel lymph node (SLN) was compared to that of the axilla. RESULTS: At least one SLN was identified in 60 of the 64 patients (93.8%). Among those 60 patients, 37 (61.7%) had one or more positive SLN(s) and 23 (38.3%) did not. Two of the patients with negative SLN(s) presented metastases in other non-sentinel nodes. SLNB thus had a false-negative rate, a negative predictive value and an overall accuracy of 5.1%, 91.3% and 96.7%, respectively. All these values were similar to those we reported for SLNB in the settings of early-stage breast cancer. CONCLUSION: SLNB after NAC is safe and feasible in patients with locally advanced breast cancer and clinically positive nodes, and accurately predicts the status of the axilla.

The role of the c-Jun N-terminal kinase 2-α-isoform in non-small cell lung carcinoma tumorigenesis.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family and have been implicated in tumorigenesis. One isoform in particular, JNK2α, has been shown to be frequently activated in primary brain tumors, to enhance several tumorigenic phenotypes and to increase tumor formation in mice. As JNK is frequently activated in non-small cell lung carcinoma (NSCLC), we investigated the role of the JNK2α isoform in NSCLC formation by examining its expression in primary tumors and by modulating its expression in cultured cell lines. We discovered that 60% of the tested primary NSCLC tumors had three-fold higher JNK2 protein and two- to three-fold higher JNK2α mRNA expression than normal lung control tissue. To determine the importance of JNK2α in NSCLC progression, we reduced JNK2α expression in multiple NSCLC cell lines using short hairpin RNA. Cell lines deficient in JNK2α had decreased cellular growth and anchorage-independent growth, and the tumors were four-fold smaller in mass. To elucidate the mechanism by which JNK2α induces NSCLC growth, we analyzed the JNK substrate, signal transducer and activator of transcription 3 (STAT3). Our data demonstrates for the first time that JNK2α can regulate the transcriptional activity of STAT3 by phosphorylating the Ser727 residue, thereby regulating the expression of oncogenic genes, such as c-Myc. Furthermore, reintroduction of JNK2α2 or STAT3 restored the tumorigenicity of the NSCLC cells, demonstrating that JNK2α is important for NSCLC progression. Our studies reveal a novel mechanism in which phosphorylation of STAT3 is mediated by a constitutively active JNK2 isoform, JNK2α.

Intra-operative evaluation of the sentinel lymph node for T1-N0 breast-cancer patients: always or never? A risk/benefit and cost/benefit analysis.

AIM: To investigate whether omitting intra-operative staging of the sentinel lymph node (SLN) in T1-N0 breast-cancer patients is feasible and convenient because it could allow a more efficient management of human and logistic resources without leading to an unacceptable increase in the rate of delayed axillary lymph node dissection (ALND). METHODS: According to the experimental procedure, T1a-T1b-patients were to not receive any intra-operative SLN evaluation on frozen sections (FS). In all T1c-patients, the SLN was macroscopically examined; if the node appeared clearly free of disease, no further intra-operative assessment was performed; if the node was clearly metastatic or presented a dubious aspect, the pathologist proceeded with analysis on FS. T2-patients, enrolled in the study as reference group, were treated according to the institutional standard procedure; they all received SLN staging on FS. RESULTS: The study included 395 T1-N0-patients. Among the 118 T1a-T1b-patients whose SLN was not analyzed at surgery, 12 (10.2%) were recalled for ALND. In the group of 258 T1c-patients, 112 received SLN analysis on FS and 146 did not. An SLN falsely negative either at macroscopic or FS examination was found in 33 (12.8%) cases. Overall, the rate of recall for ALND was 11.6% as compared to 8.4% in T2-patients. Using the experimental protocol, the institution reached a 9.6% cost saving, as compared to the standard procedure. CONCLUSIONS: Omission of SLN intra-operative staging in T1-N0-patients is rather safe. It provides the institution with both management and economical advantages.

[Ultrasound in diagnosis of superior mesenteric artery syndrome]. / Imaging con ultrasuoni nella diagnosi della sindrome dell'arteria mesenterica superiore.

OBJECTIVE: To reveal a possible reduction of the aorto-mesenteric angle and to diagnose suspected cases of superior mesenteric artery (SMA) syndrome. It was controlled, prospective study in which, in order to reveal a possible reduction of aorto-mesenteric angle, the following techniques. MATERIALS AND METHODS: In a cohort of patients referred to our department by their general practitioners for unexplained dyspepsia and/or abdominal pain an abdominal ultrasonography with power colour Doppler was performed; patients with reduced SMA angle were screened by gastroduodenoscopy, hypotonic duodenography, contrast-enhanced spiral computerized tomography. RESULTS: In a cohort of 1468 patients, 460 subjects were taken into consideration, specifi cally the patients where US and power colour Doppler had been adequately performed. US detected a signifi cant reduction of the SMA angle in 20 of those patients; in these 20 subjects, gastroscopy showed duodenal compressive pulsation in 5 of the 20 patients under examination, and X-ray revealed a compression of the third segment of the duodenum in 18 of them. The following CT examination confi rmed the presence of a reduced angle and various degrees of duodenal compression in all patients. US and CT examinations gave overlapping results (p>0.05) in diagnosing pathological aorta-mesenteric angle. CONCLUSIONS: The analysis of data led the authors to believe that the incidence of reduced aorto-mesenteric angle and SMA syndrome might be underrated. US power colour Doppler imaging that is a rapid, repeatable, and non invasive, low cost and easy to perform diagnostic procedure, is useful in epidemiological screening of reduced aorto-mesenteric angle to diagnose suspected cases of SMA syndrome in patients with inexplicable abdominal pain.

Effects of antioxidants on postprandial oxidative stress and endothelial dysfunction in subjects with impaired glucose tolerance and type 2 diabetes.

AIM: To compare changes in the oxidation-reduction balance and endothelial function before and after meal in patients with type 2 diabetes or impaired glucose tolerance and determine the effects of standard antioxidant supplementation. METHODS: Forty diabetics and 40 subjects with impaired glucose tolerance were compared with a control group. We assessed before and after a test meal (homogenized milkshake containing 80 g of saturated fat, amounting to 1,480 kcal), some reactive oxygen species, inflammation markers and flow-mediated vascular dilatation. These parameters were then reassessed after standard antioxidant treatment. RESULTS: After the meal, diabetics, subjects with impaired glucose tolerance and controls had higher levels of oxidant compounds compared to fasting levels. In subjects with diabetes and impaired glucose tolerance (IGT), Vascular Adhesion Molecule-1 and CRP were higher after the meal--diabetic subjects exhibited lower fasting flow-mediated dilatation, which deteriorated significantly after the meal. Antioxidant administration significantly improved the parameters investigated in all subjects. CONCLUSIONS: In diabetic subjects, altered glycaemia and lipaemia are closely correlated with markers of systemic oxidative stress. Our results show that the abnormal changes in oxidative-reductive balance parameters are paralleled by similar changes in markers of endothelial dysfunction and inflammation at 4 h after ingestion of a fatty meal. Supplementation with a pool of antioxidants can reduce oxidative stress and inflammation in healthy subjects and, more importantly, in IGT patients. This previous aspect suggests that the timing of antioxidant supplementation has an important role in endothelium protection in healthy and pre-diabetic subjects, and along with prompt antioxidant treatment before irreversible endothelial damage has occurred, may have an important protective role in subjects with IGT-patients who require administration of adequate dietary antioxidants.

Sentinel node biopsy compared with complete axillary dissection for staging early breast cancer with clinically negative lymph nodes: results of randomized trial.

BACKGROUND: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary dissection in breast cancer patients with negative SLNs. Evidence of a similar efficacy, in terms of survival and regional control, of this strategy as compared with axillary resection is based on few clinical trials. In 1998, we started a randomized study comparing the two strategies, and we present here its results. MATERIALS AND METHODS: Patients were randomly assigned to sentinel lymph node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm). Main end points were overall survival (OS) and axillary recurrence. RESULTS: One hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no axillary recurrence was observed in the SLNB arm. OS and event-free survival were not statistically different between the two arms. CONCLUSIONS: The SLNB procedure does not appear inferior to conventional ALND for the subset of patients here considered.

Analysis of human immunodeficiency virus type 1 vector cis- and trans-acting elements production by means of Semliki Forest virus.

Recombinant Semliki Forest virus (SFV) is an attractive viral vector system owing to its ability to allow high efficiency of viral protein expression. To produce recombinant pseudotyped human immunodeficiency virus type 1 (HIV-1) virions, we designed a chimeric SFV/HIV vector system that contains both the HIV-1 cis- and trans-acting elements under the transcriptional control of the SFV replicase and investigated the ability of the hybrid SFV/HIV system to produce lentiviral particles capable of transducing target cells. Co-transfection of target cells with the two helper SFV packaging system RNAs along with each SFV/Gag-Pol, SFV/VSV(G) as well as SFV/HIV-1 vector unit replicon led to the generation of efficient transducing competent recombinant SFV/HIV particles. In contrast, co-transduction of target cells with the SFV/HIV chimeric virions produced recombinant particles with low transducing ability. Our data suggest that both the genomic and the subgenomic RNAs containing the HIV-1 vector unit were negatively selected for incorporation into recombinant particles, despite the fact that the SFV-driven HIV-1 vector replicon was the only one containing a lentiviral packaging sequence. The results of this study provide insights relevant to the design of chimeric lentiviral vectors.

The role of axillary lymph node dissection in breast cancer patients with sentinel lymph node micrometastases.

AIM: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND). MATERIALS AND METHODS: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN. RESULTS: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring

T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120.

Immune-based approaches of cell therapy against viral pathogens such as the human immunodeficiency virus type 1 (HIV-1) could be of primary importance for the control of this viral infection. Here, we designed a chimeric cell surface receptor (105TCR) to provide primary human T-lymphocytes with antibody-type specificity for the HIV-1 envelope glycoprotein. This receptor includes the single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody F105, CD8alpha hinge and the transmembrane and the cytoplasmic domains of TCRzeta. Our results show that 105TCR is expressed at the cellular surface and is capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient effector T-cell responses, including extracellular signal-regulated kinase phosphorylation and cytokine secretion. Moreover, human primary CD8+ T-lymphocytes transduced by oncoretroviral and lentiviral vectors containing the 105TCR gene are able to mediate in vitro-specific cytolysis of envelope-expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest that 105TCR is particularly suited for in vivo efficacy studies.

[The use of evidence-based medicine data]. / Qualche riflessione sull'uso dei dati della "evidence-based medicine.".

Although the basic concepts behind evidence-based medicine (EBM) have been largely accepted, some aspects regarding its theoretical background and its methodological characteristics and practical applications (mainly concerning the therapeutic choices) in daily clinical practice are still subject of debate. This is a real problem, and we have not yet found a fully satisfactory solution. With regard to the theoretical point of view, the most radical antagonists of EBM contest that it is an "abstract building" which has lost contact with the day-to-day clinical reality. In spite of these criticisms, at present the medical community largely considers EBM as a real improvement in the methodology of clinical research and as a helpful support for medical practice. However, in applying the principles of EBM, a dangerous mistake has to be avoided: the meaning and benefit of EBM consist of the fact that it suggests but does not impose rational medical options. The practice of EBM must respect the liberty of the doctors and try to increase their professional and ethical responsibilities. These principles require wisdom and caution in drafting the guidelines generated by EBM and compel us to take into account some psychological side-effects of its diffusion among the physicians and common people.

Usefulness and limits of distal echo-Doppler velocimetric indices for assessing renal hemodynamics in stenotic and non-stenotic kidneys.

BACKGROUND: Distal echo-Doppler velocimetric indices are widely used for revealing the presence of a renal artery stenosis but there is scarce information as to whether they reflect the renal hemodynamics in stenotic and nonstenotic kidneys. OBJECTIVES AND METHODS: We evaluated the pulsatility and resistive indices (PI and RI), acceleration (A) and acceleration time (At) and correlated their values with those of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal vascular resistance (RVR) and filtration fraction (FF) estimated by single kidney scintigraphy in 24 kidneys with 70-95% renal artery stenosis (atherosclerotic n = 17, fibromuscular n = 7) and in 27 non-stenotic kidneys (11 contralateral to renal artery stenosis and 16 of patients with essential hypertension). In patients with stenotic kidneys, these measurements were repeated within 7 days after a successful percutaneous transluminal renal angioplasty (PTRA) (in 11 arteries performed in combination with stent implantation). RESULTS: Prior to dilation we found that the stenotic kidneys had significantly lower values of ERPF, GFR and higher RVR than the non-stenotic kidneys and that these hemodynamic alterations were associated with those, also statistically significant, of the four velocimetric indices. In non-stenotic kidneys, there were highly significant relationships between PI and ERPF, and RVR (r = -0.68 and 0.81 respectively P < 0.01); similar relationships were found for RI (r = -0.67 and 0.78 P < 0.01) whereas no such correlations were found between these two velocimetric indices and GFR and FF; also no correlations were found between A and Atand ERPF, GFR, RVR and FF. In stenotic kidneys no significant correlations were found between any of the velocimetric and the hemodynamic indices. Renal artery dilation induced clear cut increments in ERPF, GFR and reduction in RVR in post-stenotic kidneys, which were associated with normalization of all four velocimetric indices. No relationships were observed between the renal hemodynamic and the velocimetric changes induced by dilation; however in post-stenotic kidneys the relationships between PI and RI, ERPF and RVR were restored as in nonstenotic kidneys. CONCLUSIONS: These data indicate that PI and RI can be used to assess ERPF and RVR both in non-stenotic and post-stenotic kidneys; however, none of the velocimetric indices examined in this study can provide valid informations on the renal hemodynamics of stenotic kidneys and on their changes induced by PTRA.

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.