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.

[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.

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.

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.

[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.

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.

Influence of bile salt molecular species on cholesterol crystallization from supersaturated model biles.

Time-sequential enzymatic determination of cholesterol (CH) crystals harvested by ultrafiltration, and concomitant polarizing light microscopy observations corroborated the striking importance of the bile salts (BS) species in determining CH crystals formation rate from supersaturated model biles incubated in vitro. The more hydrophilic tauroursodeoxycholate, taurohyocholate, glycohyocholate, taurohyodeoxycholate, glycohyodeoxycholate and glyco-3 alpha, hydroxy-6 oxo-5 beta-cholanate inhibited CH precipitation through the formation of a stabilized liquid-crystalline phase. In contrast, in all hydrophobic systems (taurine (T) and glycine (G) conjugates of cholate (C), deoxycholate (DC) and chenodeoxycholate (CDC)), CH crystals precipitated with time. When crystallized CH concentrations were plotted vs. time, the figures showed a sigmoidal pattern, consistent with the transition from metastable systems to stable equilibrium states. Over the equilibration period, the nucleation kinetics (as inferred from enzymatic measurements) and all crystallization events (as microscopically observed) were both shifted in time, depending on the BS species: they were earliest in CDC systems, then in DC systems, and finally in C systems. In the latter, the delay was clearly due to the formation of a transient labile liquid-crystalline phase. G-conjugation also induced a significant delay in CH precipitation, compared to T-conjugation. At last, maximum crystallized CH concentrations at equilibrium were in the decreasing order: C > CDC > DC and T-conjugates > G-homologues. All data are discussed in connection with BS hydrophobicities, with predictions from the phase equilibria of aqueous biliary lipid systems and with new insights into CH crystal habits.

Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their resulting cholesterol nucleating activity in pigs.

We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs.

Marrow aplasia during high dose mebendazole treatment.

A patient with chronic liver disease was treated with large doses of mebendazole for a hepatic hydatid cyst. Eighteen days after beginning treatment he developed marrow aplasia which reverted to normal after the drug was stopped. This is the marrow aplasia which reverted to normal after the drug was stopped. This is the sixth patient described as developing marrow aplasia when treated with large doses of mebendazole. We suggest that the aplasia is related to the dose of the drug, and that the patient's chronic liver disease was an important factor in its genesis. Patients treated with large doses of mebendazole should have their blood counts monitored during treatment.

Oligofructose contributes to the protective role of bifidobacteria in experimental necrotising enterocolitis in quails.

Bifidobacteria are dominant in the gut of full-term infants, although colonisation by them is often delayed in preterm neonates. Bifidobacteria are recognised to have beneficial effects on digestive disorders and they might prevent neonatal necrotising enterocolitis (NEC), a gastrointestinal disease that predominantly affects premature infants. They have been shown to protect gnotobiotic quails against NEC-like lesions when the birds were inoculated with faecal flora from preterm infants, decreasing the clostridial population. The present study was designed to investigate whether oligofructose, which stimulates the activity of bifidobacteria, may enhance their protective role. Experiments were done in eight groups of germ-free quails for 28 days. The groups differed as to their bacterial status, diet and environment. Quails were inoculated with one of two flora from premature twins. The first flora included Bifidobacterium pseudo-catenulatum, Escherichia coli and no clostridia. The second flora included clostridial species and was associated with B. infantis-longum. Caecal bacterial population and metabolism changes were investigated with a lactose (6%) diet versus a lactose-oligofructose (3%-3%) diet, either in a gnotobiotic environment or in an ordinary environment permitting post-colonisation by exogenous bacteria. In both environments and with both flora, oligofructose significantly increased the level of bifidobacteria and this was associated with a decrease of E. coli or C. perfringens and C. ramosum. The bacterial changes in the ordinary environment depended on the initial composition of the microflora and the colonisation resistance against exogenous bacteria was more efficient with the flora that included B. pseudo-catenulatum. The changes in caecal pH and short-chain fatty acids were minimal. It was demonstrated that, irrespective of the environmental conditions, the use of oligofructose helped to prevent the overgrowth of bacteria implicated in necrotising enterocolitis in preterm neonates.

Whole-body protein turnover in humans fed a soy protein-rich vegetable diet.

OBJECTIVES: This study was designed to compare the whole-body protein turnover in humans after the ingestion of a soy protein-rich vegetable diet with that of a control group fed a western animal protein-rich diet. SUBJECTS: Twelve male volunteers were divided into two groups of six subjects who were given for two weeks either a 85% vegetable protein diet (diet VP) or a control western animal protein-rich diet (diet AP). INTERVENTIONS: Whole-body protein turnover was estimated at the end of the two-week controlled diet period using the [15N]-glycine end-product method. Nitrogen flux rates were determined in the fed state (1.3 g protein/kg) over a 9 h period after the dose of [15N]-glycine was given. RESULTS: After the 9 h of the test, the urinary ammonia excretion was significantly higher in the group receiving the diet AP than that in the group receiving the diet VP (P < 0.05). In contrast, there was no significant difference for both total nitrogen and urea nitrogen excretions. Both the protein synthesis and the protein breakdown were similar in both groups. In the same way, the net protein deposition measured in the fed state during 9 h was similar for both diets at 0.07 g/kg/h. CONCLUSIONS: Young adults fed 1.3 g/kg/d of either meat or vegetable protein-rich diet for two weeks did not show a different protein turnover.

Unlayered polymicrogyria: structural and developmental aspects.

Unlayered polymicrogyria was analyzed in four patients with established lesions and in one 19- to 20-week-old fetus with lesions in a formative stage whose mother had suffered a serious accident two weeks before. Polymicrogyria occurred at the banks of porencephalic, sylvian clefts in three cases, and bilaterally in the watershed areas of the parieto-occipital lobes in a fourth case. Periventricular neuronal heteropias were found in these cases. Cortical lesions in the fetus were distributed along the watershed zones of the middle cerebral artery. Serial sections revealed that the appearance of microgyria was the result of radial tissue cleavage of the cerebral cortex, as shown by the increased numbers of blood vessels and astrocytes forming a tissue scar. Golgi studies disclosed that the different neuronal types were positioned at the apropriate cortical depths in the microgyric cortex. On the other hand, heterotopic nodules were composed of pyramidal and non-pyramidal neurons usually found in the upper cortical layers in the normal cortex. These features indicate that unlayered polymicrogyria is produced by circulatory failure occurring before the end of the period of neuroblast migration to the cortical plate. Circulatory failure in the radial and unbranched arteries that penetrate from the meningeal surface and vascularize the cerebral cortex at midgestation may result in radial tissue necrosis of the cortical mantle, whereas failure in the distal, terminal territories of these blood vessels may damage radial glial fibres and impair the last migration of neuroblasts. The particular morphology of this cortical abnormality finally depends on the imbalance in the tangential growth of adjoining cortical areas variably destroyed by tissue necrosis.

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.

Cytologic diagnosis of salivary duct carcinoma: a review of seven cases.

The cytomorphologic findings in fine-needle aspirates from 7 cases of salivary duct carcinoma (SDC) are reviewed and correlated with the histologic features. Malignant cytologic characteristics are clear in this tumor, and no false-negative results were obtained. But the absence of cribriform or papillary groups suggests an inconclusive diagnosis and sometimes the need to establish a differential diagnosis with other salivary tumors, and in particular with adenocarcinoma not otherwise specified (ADC-NOS) and high-grade mucoepidermoid carcinoma (h-g MEC). The pitfalls in the cytologic diagnosis of this tumor are discussed. In addition, the literature on the subject is reviewed.

Intraoperative fine needle aspiration cytology of pancreatic lesions. A study of 90 cases.

Undiagnosed masses in the pancreas represent a problem at laparotomy. Intraoperative biopsy of pancreatic lesions frequently fails to detect carcinoma and may cause severe complications. The aim of the present study was to determine the diagnostic accuracy of intraoperative fine needle aspiration cytology (FNAC) of pancreatic lesions. Ninety patients were studied from January 1988 to June 1992. The cytologic diagnoses were correlated with histology, autopsy results or clinical follow-up. Aspirates were reported as benign, suspicious, malignant or unsatisfactory. Final diagnosis of malignant pancreatic disease (MPD) was established in 60 patients and of benign pancreatic disease in 30. Among the 60 cases with MPD, the cytologic diagnosis was concordant in 42 and interpreted as suspicious in 4. Seven patients with benign cytology and 7 with unsatisfactory cytology later proved to have malignant disease. A total of 30 patients had benign disease; 26 of them had benign cytology. The remaining four had "unsatisfactory" cytologic reports. No false positives were reported. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNAC results were 80%, 100%, 100%, 70% and 91%, respectively. No complications followed the procedure. Intraoperative FNA of the pancreas is a safe and highly accurate diagnostic method for pancreatic lesions at laparotomy.

Caroli's disease versus polycystic hepatic disease. Differential diagnosis with Tc-99m DISIDA scintigraphy.

Four patients with multiple hepatic cysts were studied: two were diagnosed with Caroli's disease (CD) and two with polycystic hepatic disease (PHD). In CD, hepatic scintigraphy with Tc-99m DISIDA showed areas of focally increased radiotracer accumulation that persisted more than 120 minutes, whereas in PHD, areas of focally decreased radiotracer accumulation were observed with normal liver washout and biliary excretion. When multiple hepatic cysts are shown by abdominal echography or CT scan, hepatic scintigraphy with Tc-99m DISIDA should be performed. This examination is safe and noninvasive, and permits differential diagnosis between CD and PHD.

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.