Primary total hip arthroplasty with a fully porous-coated uncemented stem: up to twenty-eight years. Retrospective cohort study.

PURPOSE: The use of cementless prosthesis has increased in the last 30 years with the aim of improving the long-term results of total hip arthroplasties in young and active patients. Encouraging results have recently been reported for cementless titanium and cobalt chromium stems. However, there are few studies with long-term follow-up, and the majority have analysed several models of uncemented stems due to their modifications over the years. Therefore, the aim was to assess the long-term survival rate of the Mittelmeier Mark III or Autophor 900-S stem. METHODS: A retrospective cohort study of both gender patients under 70 years old with at least one implanted Mittelmeier Mark III uncemented stem was performed. Survival rate was defined as the proportion of stems that did not need a surgical revision from any cause. Clinical status was evaluated using the Merle d'Aubigne scale modified by Matta (excellent/good/fair/poor). RESULTS: Between 1990 and 1999, 73 stems were implanted. The mean (SD) age at surgical time was 49.3 (9.9) years, and the median (range) of follow-up was 22 (1-28) years. The overall survival rate was 93% (68/73, 95%CI: 85-97%). The stem revisions were due to stem breakage (n = 2), to aseptic loosening (n = 2) and to septic loosening (n = 1). Clinical results were: excellent 84%, good 15% and fair 1.5%. CONCLUSIONS: The Mittelmeier Mark III stem had an excellent survival rate with a stable long-term fixation and excellent clinical outcomes.

Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors.

BACKGROUND: The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). PATIENTS AND METHODS: We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. RESULTS: In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors. CONCLUSIONS: We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Aberrant gene methylation and bronchial dysplasia in high risk lung cancer patients.

INTRODUCTION: The risk for lung cancer is incremented in high degree dysplasia (HGD) and in subjects with hypermethylation of multiple genes. We sought to establish the association between them, as well as to analyze the DNA aberrant methylation in sputum and in bronchial washings (BW). METHODS: Cross sectional study of high risk patients for lung cancer in whom induced sputum and autofluorescence bronchoscopy were performed. The molecular analysis was determined on DAPK1, RASSF1A and p16 genes using Methylation-specific PCR. RESULTS: A total of 128 patients were enrolled in the study. Dysplasia lesions were found in 79 patients (61.7%) and high grade dysplasia in 20 (15.6%). Ninety eight patients out of 128 underwent molecular analysis. Methylation was observed in bronchial secretions (sputum or BW) in 60 patients (61.2%), 51 of them (52%) for DAPK1, in 20 (20.4%) for p16 and in three (3.1%) for RASSF1A. Methylated genes only found in sputum accounted for 38.3% and only in BW in 41.7%, and in both 20.0%. In the 11.2% of the patients studied, HGD and a hypermethylated gene were present, while for the 55.1% of the sample only one of both was detected and for the rest of the subjects (33.6%), none of the risk factors were observed. CONCLUSIONS: Our data determines DNA aberrant methylation panel in bronchial secretions is present in a 61.2% and HGD is found in 15.6%. Although both parameters have previously been identified as risk factors for lung cancer, the current study does not find a significative association between them. The study also highlights the importance of BW as a complementary sample to induced sputum when analyzing gene aberrant methylation.

[Runners with back pain: to run or not to run?]. / Coureurs souffrant de maux de dos: courir ou ne pas courir?

We evaluated the perceived impact of physical activity on back pain in runners. Information from 777 runners participating in a half marathon was obtained with a questionnaire about basic data, features of the weekly training and the relationship between running activity and back pain. Half the runners (54.1%) reported a history of back pain. Among them, almost twice as many reported an improvement (49%) than a worsening (27%) of pain with running. No significant associations were found between perceived impact of running on back pain and other factors. In our study favorable effects were much more frequent than unfavorable ones. Further studies are needed to better understand these effects.

Metaplastic carcinoma of the breast with chondroid differentiation (matrix-producing carcinoma): study of the diagnostic cost-effectiveness of fine-needle aspiration biopsy and needle core biopsy.

UNLABELLED: Metaplastic carcinoma with chondroid differentiation (MMPC) is a subtype of breast metaplastic carcinoma with mesenchymal differentiation. Although fine-needle aspiration (FNAB) and core-needle biopsy (CNB) are commonly used for the diagnosis of breast cancer, not enough studies proving the diagnostic cost-effectiveness of these techniques for the identification of MMPC have been published so far. The aim of this study was to investigate the concordance between the presurgical diagnosis using FNAB/CNB and the definitive diagnosis in the surgical specimen in pure MMPC. A case of MMPC is also reported. STUDY DESIGN: All cases of MMPC diagnosed in our institution from 1995 to 2011 were reviewed. The presence of chondroid differentiation in cytological studies or biopsies and the proportion of chondroid matrix in the surgical specimen were evaluated. RESULTS: A total of 13 cases of pure MMPC were collected. The diagnosis was suspected in 25% of FNABs and was rendered in 40% of CNBs. CONCLUSIONS: The chondroid component in MMPC is hard to identify by FNAB and CNB. The random distribution and proportion of the chondroid differentiation in the tumour and the expertise in performing the technique and in identifying the chondroid component may play an important role in the diagnosis of MMPC using these techniques.

Recién nacidos de madre con enfermedad autoinmunitaria. Experiencia en un hospital comarcal / Newborns whose mother has autoimmune disease. A community hospitals’ experience

Las madres con enfermedad autoinmunitaria (EAI) pueden presentar exacerbaciones de su enfermedad durante la gestación y el puerperio, con implicaciones fetales y neonatales. El objetivo del presente estudio fue describir las incidencias de estas madres y la afección neonatal asociada. Se realizó un análisis retrospectivo entre los años 2004 a 2010, controlándose 29 madres con EAI. Se registraron 52 embarazos, 39 RN vivos y 13 abortos. Durante la gestación se produjeron 10 complicaciones: una vasculitis digital, una pancreatitis, una glomerulonefritis, una diabetes gestacional, 2 amenazas de parto prematuro, 3 preeclampsias y 1 eclampsia. En el posparto, una exacerbación lúpica. Entre los RN 20,5% presentaron bajo peso y 4 transferencia de anticuerpos maternos con un lupus neonatal (LNN). Posteriormente, 8 niños (20,5%) desarrollaron asma, uno oligoartritis ANA negativa y otro púrpura trombocitopénica autoinmunitaria. En nuestro hospital la tasa de abortos y prematuridad es similar a la descrita en la literatura. Destaca la presencia de un caso de LNN con paso transplacentario de anti-Sm(AU)

Mothers with autoimmune diseases (AID) may have exacerbations of their disease during pregnancy and postpartum period, with fetal implications and neonatal complications. The aim of this study was to describe miscarriages during pregnancy and postpartum problems among mothers with AID and associated neonatal pathology. Retrospective data was recorded from 2004 to 2010. 29 mothers with AID were analyzed, 65% of whom had lupus erythematosus (SLE). There were 52 pregnancies, which resulted in 39 newborns. There were 10 instances of maternal complications (25.6%) during the pregnancies, including 1 with digital vasculitis, 1 with pancreatitis, 1 outbreak of glomerulonephritis, 1 case of gestational diabetes, 2 patients at risk for preterm birth, 3 with preeclampsia and 1 with eclampsia. During the postpartum period, there was one case of SLE exacerbation. Among the newborns 20.5% had low birth weight and 4 exhibited the transplacental passage of maternal antibodies with one case of neonatal lupus. Among complications beyond the neonatal period, 8 (20.5%) children developed asthma, one presented negative ANA oligoarthritis and another presented immune thrombocytopenic purpura. In our hospital, the rates of miscarriage, prematurity and LBW among the newborns of mothers with AID are similar to those reported in the literature. The observation of a case of NL with the transplacental passage of anti-Sm is remarkable(AU)

Newborns whose mother has autoimmune disease. A community hospitals' experience.

Mothers with autoimmune diseases (AID) may have exacerbations of their disease during pregnancy and postpartum period, with fetal implications and neonatal complications. The aim of this study was to describe miscarriages during pregnancy and postpartum problems among mothers with AID and associated neonatal pathology. Retrospective data was recorded from 2004 to 2010. 29 mothers with AID were analyzed, 65% of whom had lupus erythematosus (SLE). There were 52 pregnancies, which resulted in 39 newborns. There were 10 instances of maternal complications (25.6%) during the pregnancies, including 1 with digital vasculitis, 1 with pancreatitis, 1 outbreak of glomerulonephritis, 1 case of gestational diabetes, 2 patients at risk for preterm birth, 3 with preeclampsia and 1 with eclampsia. During the postpartum period, there was one case of SLE exacerbation. Among the newborns 20.5% had low birth weight and 4 exhibited the transplacental passage of maternal antibodies with one case of neonatal lupus. Among complications beyond the neonatal period, 8 (20.5%) children developed asthma, one presented negative ANA oligoarthritis and another presented immune thrombocytopenic purpura. In our hospital, the rates of miscarriage, prematurity and LBW among the newborns of mothers with AID are similar to those reported in the literature. The observation of a case of NL with the transplacental passage of anti-Sm is remarkable.

Definitive diagnosis of neuroendocrine tumors using fine-needle aspiration-puncture guided by endoscopic ultrasonography.

BACKGROUND: The detection and diagnosis of neuroendocrine tumors (NETs) is challenging. Endoscopic ultrasonography (EUS) has a significant role in the detection of NETs suspected from clinical manifestations or imaging techniques, as well as in their precise localization and cytological confirmation using EUS-Fine-needle aspiration-puncture (FNA). OBJECTIVE: To assess the usefulness and precision of EUS-FNAP in the differential diagnosis and confirmation of NETs, in a retrospective review of our experience. PATIENTS AND METHODS: in a total of 55 patients with suspected NETs who underwent radial or sectorial EUS, 42 tumors were detected in 40 cases. EUS-FNA using a 22G needle was performed for 16 cases with suspected functional (hormonal disorders: 6 cases) and non-functional NETs (10 cases). Ki 67 or immunocytochemistry (ICC) testing was performed for all.There was confirmation in 9 cases (5 female and 4 male) with a mean age of 51 years (range: 41-81 years).All tumors were located in the pancreas except for one in the mediastinum and one in the rectum, with a mean size of 19 mm (range: 10-40 mm). RESULTS: There were no complications attributable to FNA. Sensitivity was 100% and both precision and PPV were 89%, as a false positive result suggested a diagnosis with NET during cytology that surgery finally revealed to be a pancreatic pseudopapillary solid tumor. CONCLUSIONS: EUS-FNA with a 22G needle for NETs has high sensitivity and PPV at cytological confirmation with few complications.

Breast Cancer OncoGuia: surgical pathology report guidelines

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What are the preoperative factors that can determine the presence of metastases in other axillary nodes in breast cancer when the sentinel node is positive?

AIM: To determine whether preoperative factors, such as size of metastases in the sentinel lymph node (SLN), number of positive SLNs (1, >1), tumoral grade, lymphovascular invasion (LVI) and tumoral size can predict the presence of metastases in non-SLNs, when the SLN is positive. METHODS: The study population was 1 146 breast cancer patients. Lymphadenectomy was performed in 150. Three groups of patients were established depending on the size of the metastases in SLNs: group A: <2 mm; group B: 2 < or =GC < or =5 mm; group C: > 5 mm. Either the chi(2) test or Fisher's test was performed to compare categorical variables, and a multivariate conditional logistic regression model for data sets was performed to identify the deterministic factors of metastases presence. RESULTS: Ten percent of group A, 28% of group B and 52% of group C presented non-SLN metastases. Patients with >1 positive-SLN presented significantly more non-SLN metastases than those with only one positive-SLN; 56% of patients with LVI presented non-SLN metastases versus 26% of those without LVI. The tumoral grade and size did not seem to have any influence on the number of patients with non-SLN metastases. The number of positive-SLNs and size of metastases were statistically associated with the presence of metastases. CONCLUSIONS: In this study population, the probability of finding non-SLN metastases was statistically related to the size of the SLN metastases and the number of positive-SLNs.

[Lymphoscintigraphy and sentinel node biopsy in non-palpable breast cancer]. / Linfogammagrafía y biopsia del ganglio centinela en el carcinoma no palpable de mama.

OBJECTIVE: The aim of the study was to evaluate the efficacy of lymphatic mapping and sentinel node biopsy in non-palpable breast cancer (NPBC) patients in comparison with palpable breast cancer (PBC) patients. MATERIAL AND METHODS: 199 breast cancer patients were studied. Patients were classified into two groups: NPBC and PBC. Following sentinel node biopsy all patients underwent axillary lymphadenectomy. Surgery was performed at 4-24 h after peritumoral injection of 111MBq 99mTc-nanocolloid. Histological sentinel node analysis was performed by cytological imprinting and delayed study. The following parameters were analyzed in both groups: scintigraphic and surgical detection rates, true positives (TP), true negatives (TN), sensitivity (S), predictive negative value (PNV), false negative rate (FNR) and global precision (GP) of the technique. RESULTS: No significant differences were observed (p > 0.05) in either the lymphoscintigraphy or surgical sentinel node detection, or drainage to internal mammary chain (p = 0.211) in both groups. Metastatic axillary prevalence was lower in NPBC group (p = 0.019). Similar S, NPV and GP values (>90 %) and FNR (< or = 6 %) were found in both groups. CONCLUSIONS: The reliability of the technique is similar in both groups. Drainage is predominantly axilar. Drainage to internal mammary chain was more frequently seen in medial tumours and in NPBC. Metastatic axillary prevalence was lower in the NPBC group.

Linfogammagrafía y biopsia del ganglio centinela en el carcinoma no palpable de mama / Lymphoscintigraphy and sentinel node biopsy in non-palpable breast cancer

Objetivo. Analizar las detecciones radioisotópica y quirúrgica del ganglio centinela (GC) en el carcinoma no palpable de mama (CNPM) y comparar los resultados en este grupo con los del grupo de tumores palpables de mama (CPM). Material y métodos. Se estudian 199 pacientes. Se les realizó biopsia del GC y linfadenectomía axilar (LDNA). Se establecen dos grupos: CNPM y CPM. La cirugía tuvo lugar entre las 4-24 horas de la administración peritumoral de 111MBq de 99mTc-nanocoloide. La histopatología del GC fue mediante impronta peroperatoria y estudio diferido. Se analiza el porcentaje de detección gammagráfica y quirúrgica y la vía de drenaje del GC según la palpación del tumor y su localización en la mama; los verdaderos positivos (VP), verdaderos negativos (VN), falsos negativos (FN), la sensibilidad (S), el valor predictivo negativo (VPN), la tasa de falsos negativos (TFN) y la precisión global (PG) de la técnica. Resultados. No se observaron diferencias estadísticamente significativas (p > 0,05) ni en la detección gammagráfica y quirúrgica del GC, ni en la existencia de drenaje a mamaria interna (p = 0,211) entre ambos grupos. La prevalencia de metástasis axilar fue menor en el grupo CNPM (p = 0,019). La S, el VPN y la PG de la técnica fue similar en los dos grupos (> 90 %), así como la TFN (<= 6 %). Conclusiones. La fiabilidad de la técnica es similar en los dos grupos. El drenaje predominante es axilar. El drenaje a mamaria interna predominó en los tumores mediales y en CNPM. La prevalencia metastásica axilar es menor en el CNPM

Objective. The aim of the study was to evaluate the efficacy of lymphatic mapping and sentinel node biopsy in non-palpable breast cancer (NPBC) patients in comparison with palpable breast cancer (PBC) patients. Material and methods. 199 breast cancer patients were studied. Patients were classified into two groups: NPBC and PBC. Following sentinel node biopsy all patients underwent axillary lymphadenectomy. Surgery was performed at 4-24h after peritumoral injection of 111MBq 99mTc-nanocolloid. Histological sentinel node analysis was performed by cytological imprinting and delayed study. The following parameters were analyzed in both groups: scintigraphic and surgical detection rates, true positives (TP), true negatives (TN), sensitivity (S), predictive negative value (PNV), false negative rate (FNR) and global precision (GP) of the technique. Results. No significant differences were observed (p > 0.05) in either the lymphoscintigraphy or surgical sentinel node detection, or drainage to internal mammary chain (p = 0.211) in both groups. Metastatic axillary prevalence was lower in NPBC group (p = 0.019). Similar S, NPV and GP values (> 90 %) and FNR (<= 6 %) were found in both groups. Conclusions. The reliability of the technique is similar in both groups. Drainage is predominantly axilar. Drainage to internal mammary chain was more frequently seen in medial tumours and in NPBC. Metastatic axillary prevalence was lower in the NPBC group

Principales características del pilomatricoma múltiple y su asociación con una mutación de la betacatenina. Réplica / Principal features of multiple pilomatricoma and its association with beta-catenin mutation. Reply

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Mútiples pilomatrixomas asociados a enfermedad celíaca / Multiple pilomatrixomas associated with celiac disease

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Diet, length of gestation, and fecal short chain fatty acids in healthy premature neonates.

BACKGROUND: Excretion of fecal short-chain fatty acids (SCFAs) may indicate changes in colonic or colonocyte metabolism. The aim of this study was to detect the influence of gestational age and feeding practices on SCFA concentrations and profiles in healthy preterm infants. METHODS: A total of 198 fecal samples (28 infants) were collected from 8 to 21 days of age from 3 groups of preterm infants born at 33 to 37 weeks of gestation and fed either breast milk (group I) or Nutramigen, a lactose-free formula (group II), and extremely preterm infants born before 33 weeks of gestation and fed breast milk (group III). Total SCFA concentrations and SCFA profiles were analyzed using a gas chromographic (GC) procedure. RESULTS: Total fecal SCFA excretion did not differ significantly between group I (mean, 24.0 micromol/g; range, 1.3 to 118.8 micromol/g) and group II (mean, 23.0 micromol/g; range, 3.0 to 73.3 micromol/g). Conversely, differences occurred between SCFA profiles and became significant after day 17. The main differences were a significant increase in the butyric acid concentration (12% versus 30%) with group II. Compared with group I, fecal SCFA concentrations were 3.2-fold lower (7.4 micromol/g; range, 0.3 to 37.4 micromol/g) in group III with no significant changes in the profiles. CONCLUSIONS: Fecal SCFA excretion may vary in absence of any digestive disease. During this study, in terms of gestational age, total SCFA concentrations were significantly lower in extremely premature infants compared with infants born less premature, despite their known higher deficiency in intestinal lactase activity. In terms of diet, the absence of lactose did not lead to a decrease in colonic fermentation and induced changes in SCFA patterns. These new baseline data may offer clues to further development of milk formulas.

Cholesterol crystallization in gall-bladder bile of pigs given cholesterol-beta-cyclodextrin-enriched diets with either casein or soyabean concentrate as protein sources.

Cholesterol precipitation from supersaturated bile is the earliest and determinant step in the formation of cholesterol gallstones, which is thought to be diet-dependent. Bile composition, appearance and growth of cholesterol crystals were studied in fresh gall-bladder biles from pigs adapted to four different protein-containing diets over 3 weeks: 160 g dietary protein/kg as casein (C16; n 6), or as soyabean-protein concentrate (S16; n 6), or a mixture of both protein sources (casein-soyabean protein, 70:30, w/w) (CS16; n 6), or 320 g of the mixed protein/kg (CS32; n 6). Moreover, all four diets contained 3 g cholesterol/kg and 50 g beta-cyclodextrin/kg as modifiers of bile composition towards cholesterol pro-crystallization. Cholesterol precipitation was most active after the high-protein diet, CS32, and the casein diet, C16, and lowest after the soyabean-protein diet, S16. It was intermediate after the mixed diet, CS16, but still much lower than in the former two groups. These diet-induced variations were suggested to be mediated through modifications in the biliary profile of bile acids, whereas all other biliary constituents studied were essentially unchanged. The fasting level of plasma cholesterol was lowest in both 160 g protein/kg diets containing soyabean protein (S16 and CS16), highest for the high-protein diet CS32, and intermediate for the C16 diet. These results should encourage clinical studies on the effect of soyabean protein, or other vegetable proteins, for primary or recurrence prevention of cholelithiasis at its earliest stage.

Effects of soy protein diet on digestive lumenal polyamines and colonic cell proliferation in pigs.

This study was performed to determine whether erythrocyte and digestive lumenal polyamine concentrations are affected by a soy protein diet when compared to a casein diet. We also determined the effects of these diets on colonic cell proliferation. Sixteen pigs received either a 16% soy protein or casein diet for 25 days. The erythrocyte putrescine was higher in pigs fed the soy protein diet. Significant levels of polyamines were observed in the digestive lumen on both diets. Lumenal putrescine and cadaverine were higher in the proximal colon in the casein group. Lumenal spermidine was higher in the caecum and colon in the soy protein group. No significant differences in the ornithine decarboxylase activity nor in the proliferative cell nuclear antigen labelling index were observed in the colonic mucosa regardless of the regimen. These results indicate that the dietary source of protein induces significant changes in lumenal polyamines in the colon. The physiological effects of these changes need to be further investigated.