Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21.4% for NACT versus 15.9% for adjuvant chemotherapy (5.5% increase [95% CI 2.4-8.6]; rate ratio 1.37 [95% CI 1.17-1.61]; p = 0.0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38.2% for NACT vs 38.0% for adjuvant chemotherapy; rate ratio 1.02 [95% CI 0.92-1.14]; p = 0.66), breast cancer mortality (34.4% vs 33.7%; 1.06 [0.95-1.18]; p = 0.31), or death from any cause (40.9% vs 41.2%; 1.04 [0.94-1.15]; p = 0.45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Copyright (c) The Author(s). Published by Elsevier Ltd.

To evaluate the effectiveness of sentinel lymph node biopsy (SLNB) as an optimal staging method in oral and oropharyngeal squamous cell carcinoma (OOSCC) and the impact of the extent of SLN involvement on the decision for neck dissection (ND).A prospective cohort study was performed in 96 consecutive patients with stage T1 to T4N0M0 OOSCC (mean follow-up, 62.9 months). SLN localization was determined using cervical lymphoscintigraphy and single-photon emission computed tomography. Patients underwent SLNB examination and ND. The ND specimen was investigated by hematoxylin and eosin (H&E) staining and the SLNs were investigated using H&E staining and step-serial sectioning and cytokeratin antibodies AE1 and AE3. The statistical study calculated the sensitivity and negative predictive value (NPV). The sample size of 96 patients was calculated for a 95% confidence interval with an accuracy of ±2% and an estimated a priori sensitivity of 99% compared with the benchmark. The impact of extent of SLN involvement on the decision for ND was analyzed by χ2 test. A logistic regression model was used to assess the association of predictor variables with SLN involvement and neck disease.The diagnostic accuracy, sensitivity, NPV, and negative likelihood ratio were 95%, 88%, 94%, and 0.06. The statistical comparison between the extent of metastatic involvement of the SLN and neck disease was important for SLN macrometastasis (odds ratio = 11.9), but not for SLN micrometastasis (odds ratio = 0.93).SLNB examination is an excellent staging method in OOSCC. The present data indicate a very small risk of additional lymph node metastasis with SLN micrometastasis.

Objective: To evaluate the results for sentinel node biopsy (SNB) in patients with multifocal breast cancer (MBC) in comparison to in those with unifocal breast cancer (UBC).Patients and methods: A total of 1535 prospective SNB (174 on patients with MBC) were performed at 9 hospitals. In most patients, Tc-99 m albumin colloids were injected intraparenchymally into each tumoral focus for SNB.Results: The overall identification rate was 93.8%; no differences between groups were observed (94.8% in MBC vs 93.4% in UBC). The mean number of sentinel nodes detected was 1.46, being higher in the MBC group than in the UBC group (1.58 vs 1.45; p = 0.036). Extraaxillary sentinel nodes were found in 19.6%; extra-axillary sentinel nodes were more common in the MBC group (23.4% vs 18.9%, ns) and in the internal mammary chain and in level III axillary lymph nodes. The incidence of sentinel node metastasis was 27.3% (29.1% MBC vs 26.7% UBC, ns), and the mean number of positive sentinel nodes was 0.42 in the MBC group vs 0.32 in the UBC group (p = ns). Axillary dissection identified the same rate of positive additional nodes (29.7%) in both groups.Conclusions: The diagnostic yield of SNB seems similar in MBC and UBC. In MBC, there appears to be a specific pattern of lymphatic drainage, with a higher number of sentinel nodes detected and probably a higher number of extra-axillary sentinel nodes. (C)2007 SERAM. Published by Elsevier Espana, S.L. All rights reserved.

BACKGROUND:The indication for sentinel node biopsy (SNB) has not been fully established yet for patients with ductal carcinoma in situ (DCIS).AIM:To relate the conversion rate to invasive carcinoma with sentinel node positivity in high risk DCIS, and to refine the clinical presentation analysis in order to better select patients for SNB. For this purpose, a risk score was devised.METHODS:From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were included in a prospective sentinel node database. The conversion rate to invasive carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS, in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma.RESULTS:Both clinical presentation and corresponding risk score were closely related to conversion to invasive carcinoma. The association of risk score and sentinel node positivity approached but did not reach statistical significance (P=0.06); therefore a subset of further selected higher risk patients could not be defined.CONCLUSION:The relevance of SNB positivity cannot be overlooked in high-risk DCIS patients, however, because SNB is not free from morbidity and cost, more studies are needed to refine its final indication.

The use of deep (intratumoral, peritumoral) and superficial (subdermal, subareolar) administration is recognized as valid in sentinel lymph node biopsy for breast cancer. Herein, we are presenting a clinical case in which a personalized methodology was a determining factor in axillary staging.Initially, the radiotracer was injected intratumorally guided by ultrasound. The ultrasound scan identified a previously unknown axillary lymphadenopathy, with focal cortical thickening, this being a non-specific ultrasound finding, but with possibility of biopsy.The lymphoscintigraphy did not show uptake in the mentioned node, hence, a second subareolar dose was administered. On this occasion, the lymphoscintigraphy detected drainage to the sentinel node, which was the only one positive for micrometastasesLa utilización de las vías de administración profunda (intratumoral, peritumoral) y superficial (subdérmica, subareolar) está reconocida como válida en la biopsia del ganglio centinela en el cáncer de mama. Presentamos un caso clínico en donde la individualización de la metodología fue determinante en la estadificación axilar.Inicialmente se administra el radiotrazador por vía intratumoral guiada por ecografía. En dicha exploración se identifica una adenopatía axilar no conocida previamente, con engrosamiento cortical focal, hallazgo ecográfico inespecífico, pero subsidiario de biopsia.La linfogammagrafía no mostró captación en dicho ganglio, por lo que se decide reinyección de una 2.a dosis por vía subareolar. En esta ocasión la linfogammagrafía detecta drenaje a dicho ganglio centinela, siendo el único de los analizados que resultó positivo para micrometástasis

Epidemiologic studies on exocrine pancreatic cancer show a large heterogeneity in diagnostic criteria applied to define "caseness." Reanalyses conducted after review of diagnostic information have yielded substantially different results than those based on more crude classifications of disease. During a multicenter prospective study on mutations in the K-ras gene in pancreatic and biliary diseases, hospital diagnoses from 602 patients were reviewed by a panel of experts. There were two main motivations to do so: a generic interest for the quality of the diagnostic data, and the anticipation that a firm diagnosis could be needed to assess whether patients whose tumors did not harbor the mutation were true negatives or false negatives. In addition, the review of diagnoses was helpful to minimize tissue misclassification, and it had a high educational value for clinicians and epidemiologists. This article illustrates why and how this was so through a brief presentation of the 10 most significant cases. With respect to selection and classification of subjects, the main issues that studies on pancreatic cancer need to address are the differential diagnosis of exocrine pancreatic cancer and pancreatitis, the differential diagnosis of exocrine pancreatic cancer and other abdominal tumors, and the use of survival as a hallmark of pancreatic cancer. In epidemiologic studies of pancreatic cancer, it is warranted that a panel of experts centrally reviews all the existing diagnostic evidence (cytohistological and other) of all patients, regardless of whether they have cytohistological confirmation and of their hospital discharge diagnosis.

BACKGROUND:Biliary obstruction in the rabbit causes increased release of atrial natriuretic peptide (ANP). Circulating bile, raised biliary pressure or absence of bile in the duodenum may be implicated in this hepatocardiac syndrome.METHODS:An experimental model was developed to elucidate the mechanism linking obstructive jaundice and increased plasma ANP. Hepatic and renal function, biliary tree pressure and ANP plasma concentrations were investigated in conscious rabbits 4 and 24 h after common bile duct ligation, biliovenous shunting or external drainage via a biliary fistula.RESULTS:Bilirubin concentration increased after bile duct ligation and creation of a biliovenous shunt. Plasma creatinine increased abruptly in rabbits with a biliovenous shunt. At 4 h, the ANP increase in animals with a biliovenous shunt was ninefold that observed after bile duct obstruction while no change was noted after external biliary diversion (mean 350 versus 45 versus 9 fmol/l; P < 0.01). Relief of biliary tree obstruction was associated with a return of ANP levels towards basal normal values.CONCLUSION:Raised plasma ANP in obstructive jaundice is not the result of an increased biliary pressure per se or absence of bile in the proximal duodenum but of the passage of bile components to the circulation.

Clinical quality assessment is reviewed in 3231 patients operated on in the major ambulatory surgery (MAS) program of a 300-bed community hospital over 18 months. The substitution index was 29.96%. Unplanned admission rate was 2.9%, mainly related to anaesthetic complications. Post-operative morbidity occurred in 60 patients (1.9%); all but one being minor. Patient satisfaction was evaluated through a mail questionnaire. None of the respondents was dissatisfied with the process and 95% of them would choose MAS again. The MAS program provides safe and high quality surgical management and is widely accepted by patients.

BACKGROUND Emergency operation in the elderly carries a high risk of death. We investigated the incidence of euthyroid sick syndrome (ESS) and associated nutritional and endocrine abnormalities and their relationship to postoperative outcome in this population. METHODS Sixty-six patients older than 70 years of age requiring emergency operations were assessed before any therapeutic intervention. Values for thyroid hormones, catecholamines, cortisol, interleukin-6, interleukin-1, C-reactive protein, and the Acute Physiology and Chronic Health Evaluation II score were determined. Nutritional assessment was carried out. Mortality rates and duration of hospital stay were related to ESS and albumin concentrations. RESULTS ESS was diagnosed in 34 patients (51.50%) and was associated with worse Acute Physiology and Chronic Health Evaluation II scores (10.9 vs 8.6; p = 0.004), hypoalbuminemia (34.7 vs 40.8 gm/L; p = 0.0001), lower triceps skinfold (11.8 vs 14.6 mm; p = 0.03), and higher cortisol and norepinephrine levels (937 vs 741 nmol/L [p = 0.04] and 358 vs 250 pg/ml [p = 0.02], respectively), interleukin-6 plasma concentrations (347 vs 113 pg/ml; p = 0.01), death rate (20% vs 0%; p = 0.02), and length of hospital stay (17.2 vs 11.8 days; p = 0.03). A serum albumin level less than 35 gm/L was virtually always associated with ESS. CONCLUSIONS ESS is highly prevalent in the elderly with acute surgical problems and is associated with poor nutrition, higher sympathetic response, and worse postoperative outcome. The serum albumin level at admission is a specific marker of ESS.

AIM: the study of the frequency and evolution of upper digestive tract dyspepsia in a group of patientsoperated for early gastric cancer (EGC) and to perform a strategy of diagnosis for the patients with long term upper digestive tract dyspepsia.METHODS: clinical data of 35 patients operated for EGC were retrospectively evaluated. The frequency, characteristics and evolution time of upper digestive tract dyspepsia, main when it began more than 6 months before surgery, were analyzed. Radiologic and endoscopic exams carried out for diagnosis were also evaluated. Histological diagnosis of surgical specimens were considered, looking for the presence of chronic atrophic gastritis, intestinal metaplasia, and peptic gastric ulcer.RESULTS: long-term upper digestive tract dyspepsia was present in 27 patients (mean evolution time of 43.4 months). Clinical changes of previous symptoms that suggested gastric carcinoma were not found in 15 patients. Concurrent peptic gastric carcinoma were not found in 15 patients. Concurrent peptic gastric ulcer along with EGC was diagnosed by histology in 11 patients, and chronic atrophic gastritis and intestinal metaplasia were both present in the non-tumoral gastric mucosa in all cases.CONCLUSIONS: 1) Unespecific upper digestive tract dyspepsia is frequently found in patients with EGG. 2) Endoscopy should be the first exam performed in patients with upper digestive tract dyspepsia. 3) The patients with gastric ulcer, chronic atrophic gastritis or intestinal metaplasia must be submitted to sequential endoscopic follow-up.

BACKGROUND: The request for medical attention derived from Olympic Games is variable, with few previously published experiences and thus, the estimations made by the organizers are difficult.METHODS: The health care program established during the 1992 Olympic Games held in Barcelona is described and the clinical cases attended are reported.RESULTS: The number of persons accredited by the Barcelona Olympic Committee was 132,286, Health care attendance was provided in the sports installations, the olympic villages of the journalists and athletes, olympic family hotels, press centers and the International Youth Camp, A Polyclinic was in operation in the Olympic Village with a 24 hour Emergency Department, A total of 15,552 visits were made, 524 of which were sent to the Emergency Department of the Olympic Hospital (Hospital del Mar in Barcelona). Three hundred twenty visits were programed in the Out Patient Departments of the Hospital and a total of 81 patients were admitted to the hospital with a mean stay of 3.9 days. The most common medical problems encountered were those related with the locomotor system.CONCLUSIONS: The health care program designed for the Barcelona 1992 Olympic Games was adequate to attend the health care demand required.

OBJECTIVE:This study investigated the pathogenesis of water and sodium metabolism derangements in obstructive jaundice. SUMMARY BACKGROUND DATA:Obstructive jaundice is associated with hypodipsia, depletion of extracellular water, alterations of the water and sodium regulating hormones, and an increased incidence of renal failure. Plasma atrial natriuretic factor (ANF) increases after common bile duct ligation in the rabbit. The present study was designed to investigate ANF-secreting cardiac atrial cells in this animal model. METHODS:Plasma ANF and the percentage of atrial cells staining for ANF were determined in jaundiced and sham-operated rabbits at 24 (group OJ-24, n = 11; group SO-24, n = 5) and 72 hours (group OJ-72, n = 11; group SO-72, n = 5) after surgery. The atrial ANF content was also determined. RESULTS:Plasma ANF was higher in jaundiced animals than in controls both at 24 (63 +/- 44 fmol/mL vs. 17 +/- 10 fmol/mL, p < 0.02) and at 72 hours (73 +/- 49 fmol/mL vs. 12 +/- 11 fmol/mL). In the two OJ groups, the percentage of positive ANF cells per 200-power field in the right atrial appendage was higher than in the SO groups both at 24 (62 +/- 11% vs. 31 +/- 12%, p < 0.003) and at 72 hours (56 +/- 18% vs. 31 +/- 12%, p < 0.01). Similar results were obtained in the right auricular wall. The percentage of positive ANF cells was significantly higher in the left atrium in which significant differences between the OJ and SO groups were also noted. The right atrial ANF content was higher in the OJ than in SO groups (437 +/- 323 pmol/mg of protein vs. 83 +/- 44 pmol/mg of protein). CONCLUSIONS:Cardiac endocrine activity is increased in experimental obstructive jaundice. ANF may be involved in the pathogenesis of the renal and water and sodium metabolic disturbances present in this disease.

To elucidate the pathogenesis of renal dysfunction associated with obstructive jaundice, body water compartments were measured using a multi-isotope dilution technique in ten patients with biliary tract obstruction and in ten control subjects matched for age, sex, weight, height and body surface area. Expressed as a fraction of body-weight, total body water was reduced in jaundiced patients (41.8 versus 46.2 per cent, P less than 0.02). Extracellular water volume was also reduced in patients with jaundice (20.3 versus 24.3 per cent, P less than 0.003) owing to a reduction of the interstitial space (16.1 versus 19.5 per cent, P less than 0.004) and, to a lesser degree, of the plasma volume (4.2 versus 4.8 per cent, P = 0.1). There was a close correlation in jaundiced patients between plasma volume and the creatinine clearance rate (r2 = 0.56, P less than 0.02) and between plasma volume and extracellular volume (r2 = 0.77, P less than 0.0001). Extracellular volume in such patients also correlated with the percentage weight loss (r2 = 0.42, P = 0.04). Obstructive jaundice is associated with a contracted extracellular water compartment, although extracellular water, as a percentage of body-weight, increased in proportion to the body-weight lost. Reduction of the interstitial volume and a marginally reduced plasma volume may be determinant factors in the pathogenesis of the renal and haemodynamic disturbances observed in patients with biliary tract obstruction.

Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 +/- 30 versus 226 +/- 40 mL/4 days; p = 0.004 and 12 +/- 9 versus 171 +/- 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 +/- 7 versus 6.7 +/- 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 +/- 56 versus 101 +/- 71 mL/4 days; p = 0.0001). At 24 hours, plasma ANP (41 +/- 7 versus 10.7 +/- 1 fmol/mL, p = 0.0001), ADH (21.8 +/- 7 versus 12.3 +/- 6 pg/mL, p = 0.008) and Ald (14.5 +/- 5 versus 3.7 +/- 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 +/- 5 versus 3 +/- 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group SO2, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones.