The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recentl... more The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower...
Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different como... more Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different comorbidities in OSA patients make it difficult to know their specific effects on the development of cardiovascular injury. The aim of the present study was to investigate whether recurrent obstructive apneas could lead to myocardial injury. Thirty-six male Sprague-Dawley rats (300-350 g) were either acutely (3 h) or sustainably (5 h/day, for 10 days) subjected to obstructive apneas with a pattern of 15 s each, 60 apneas/h. Corresponding control groups were formed for the acute and sustained models. To assess the induction of systemic inflammation, IL1-β was measured in plasma. Ventricular tissue injury was evaluated by histological techniques (presence of inflammatory cell infiltration, eosin autofluorescence, and detection of apoptosis). After 3h of obstructive apneas, a significant increase in IL1-β (64.9±29.6 ng/μl) were observed with respect to the controls (7.3±1.0 ng/μl), but no myocardial injury was present. Conversely to the acute model, the systemic inflammation triggered by obstructive apneas for 10 days was reduced. However, the percentage of area with enhanced eosin autofluorescence and of apoptotic cells (1.83±0.35% and 24.4±1.5%, respectively) was increased when compared to the control group (0.72±0.20% and 5.0±2.8%, respectively). This study suggests that obstructive apneas are a potential source of early systemic and ventricular inflammation and myocardial cell injury after sustained apneas application, which could represent an initial phase in the progression of heart disease associated with OSA.
The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-... more The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal- or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by β1 integrin mechano-sensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in β1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), β1 expression, and ERK1/2 (pT202/Y204) than ADC-TAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or β1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs. This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.
Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accu... more Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s automated scanning system. All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.
The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the H... more The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the Hospital Clinic, Barcelona (Catalonia, Spain) studied by a multidisciplinary committee. The clinicopathologic correlation of the primary underlying disease with the immediate cause of death was reviewed. Between 1991 and 2000, 2,495 autopsies were performed, 1933 of which were evaluated by the committee. The autopsy rate fell from 20% in 1993 to 9.1% in 2000. The clinicopathologic correlation in underlying primary disease was correct in 92.67% of the cases; there was a major discrepancy in 3.51% and a minor discrepancy in 3.82%. As regards the immediate cause of death, major errors were found in 5.89% of cases and minor errors in 6.17%. Despite the scientific and technologic advances in medicine, we have seen that there are still clinicopathologic discrepancies. The postmortem examination continues to play an important role in auditing clinical practice and diagnostic performance, and also for educational purposes. Evaluation by a multidisciplinary committee is the more reliable system for the study of the clinicopathologic correlation.
... P2-014 BSTB: Cancer Genetics Posters, Tue, Sept 4 Single nucleotide polymorphisms of Pim-1 in... more ... P2-014 BSTB: Cancer Genetics Posters, Tue, Sept 4 Single nucleotide polymorphisms of Pim-1 in Korean lung cancer patients Jung, Jun Seok; Han, Sle Gi Lo; Jo, Uk Hyun; Yoo, Won Beak; Choi, Hyo Seon; Sung, Jae Sook; Lee, Hyo Jung; Lee, Jae Won; Kim, Jun Suk; Kim ...
To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomog... more To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomography (CT) scan in clinical non-central cIA and cIB non-small-cell lung cancer (NSCLC) for mediastinal staging. Between January 2007 and December 2010, 402 patients with potentially operable NSCLC were assessed by thoracic CT scan and 18-fluoro-2-deoxy-d-glucose PET-CT for mediastinal staging and to detect extrathoracic metastases, of which 153 surgically treated patients (79 cIA and 74 cIB cases) were prospectively included in the study. Central tumours were excluded on the basis of CT scan criteria, defined as contact with the intrapulmonary main bronchi, pulmonary artery, pulmonary veins or the origin of the first segmental branches. CT scan was considered negative if lymph nodes were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 cm at the smaller diameter. 18FDG PET-CT was considered negative when the high maximum standard uptake value (SUVmax) was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.5. Non-invasive surgical staging was carried out in this group, and curative resection plus systematic mediastinal dissection was performed except in the event of unexpected oncological contraindication. Composite non-invasive staging (CT scan, PET-CT) showed a negative predictive value (NPV) of 92% (CI 83.6-96.8) in the cIA group and 85% (CI 74-92) in the cIB group. There were 6 of 79 (7.6%) false-negatives (FNs) in cIA and 11 of 74 (14.8%) in cIB. Multilevel pN2 were detected in four cases, all of them in the cIB group. The most frequently involved N2 was subcarinal (two cases) in cIA and right lower paratracheal (R4) and seven (five cases) in cIB. Occult (pN2) lymph nodes were more frequent in tumour sizes≥5 cm (pT2b, nine cases, four FNs, P=0.03), pN1, adenocarcinoma [excluding minimally invasive adenocarcinoma (MIA) and lepidic predominant growth (LPA)] (P=0.029) and female patients, but no other risk factors for mediastinal metastases were identified (age, clinical stage, tumour location, central or peripheral, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Multilevel pN2 was significantly more frequent in the cIB group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). In pT≤1 cm (T1a), NPV was significantly better (NPV=100%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) than the other subgroups studied (IA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 cm and IB). Composite results for non-invasive mediastinal staging (CT scan, PET-CT) showed 11% of FNs in cI stage (7.6% in non-central cIA and 14.8% in cIB). In tumours≤1 cm, NPV makes surgical staging unnecessary. In women with adenocarcinoma and non-central cIB, however, the high FN rate makes invasive staging necessary, particularly in pT2b to decrease the incidence of unexpected pN2 in thoracotomy.
... Lipid deposition during the long-term infusion of propofol. El-Ebiary, Mustafa MD; Torres, An... more ... Lipid deposition during the long-term infusion of propofol. El-Ebiary, Mustafa MD; Torres, Antoni MD; Ramirez, Josep MD; Xaubet, Antoni MD; Rodriguez-Roisin, Robert MD FRCP. ... 3. Lynch MJ: Nephrosis and fat embolism in acute hemorrhagic pancreatitis. ...
To validate sampling techniques (tracheobronchial aspirates, protected specimen brush, and bronch... more To validate sampling techniques (tracheobronchial aspirates, protected specimen brush, and bronchoalveolar lavage, both conventional and protected) for the detection of ventilator-associated pneumonia (VAP) and causative microorganisms according to different histologic and microbiological references. Immediate, multiple bilateral lung biopsy, postmortem study. Respiratory intensive care unit of a 1,000-bed teaching hospital. Twenty-five mechanically ventilated patients (&gt;72 hrs) who died in our intensive care unit. Lung tissue histologic examination and quantitative cultures (16 specimens/patient). The following four references for the diagnostic techniques were used: histology of guided lung biopsy, histology of blind lung biopsy, combined guided and blind lung biopsy histology and microbiology of lung tissue, and microbiology of lung tissue. Sensitivities when histologic reference tests were used ranged from 16% to almost 40%, whereas specificity rates were always &lt;80%. When we combined both lung histology of guided or blind specimens and microbiology of lung tissue, all diagnostic techniques achieved considerably higher but still limited diagnostic yields (sensitivity range 43% to 83%; specificity range 67% to 91%). Causative organisms were missed in a significant number of cases by all techniques (17% to 83%). The diagnostic performances of different diagnostic techniques strongly depend on the reference used. All techniques for detecting VAP are of limited value. Finding a balance between clinical judgment and microbiological results is crucial to appropriately manage patients with VAP.
To evaluate the clinical relevance of the presence of lymphocytes in transbronchial needle aspira... more To evaluate the clinical relevance of the presence of lymphocytes in transbronchial needle aspiration (TBNA) samples from pathological mediastinal lymph nodes in patients with suspected lung cancer. Retrospective observational study evaluating the negative predictive value (NPV) of TBNA samples containing lymphocytes but not malignant cells. A total of 266 TBNA were performed in 252 patients with pathological lymph nodes. One hundred and fifteen TBNA samples had evidence of malignant cells (43%), and 94 (35%) samples were considered as inadequate (absence of adequate cytological material or exclusive presence of bronchial epithelial cells). Out of the 57 TBNA samples remaining (21%), 15 could not be confirmed; in 32, TBNA samples were confirmed with alternative diagnostic techniques and in 10, they were confirmed after clinical and radiological follow-up. The NPV of the 32 samples that were confirmed with alternative diagnostic techniques was 84% decreasing down to 76% when the 10 TBNA samples confirmed after clinical and radiological follow-up were included. The presence of lymphocytes in the TBNA sample does not exclude the neoplasic invasion of the specific lymph node analyzed.
The relationship between microbiology and histology in patients with ventilator-associated pneumo... more The relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described. Twenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died with clinical suspicion of pulmonary infection. A total of 375 immediate postmortem pulmonary biopsies were obtained after death and processed for quantitative microbiology and histology. Four evolutionary stages of pneumonia were defined: early, intermediate, advanced, and resolution. At least one specimen with histologic evidence of pneumonia was found in all but two patients (92%). Histologic pneumonia was a widespread and frequent process (46%) of biopsies examined) involving predominantly the lower lobes (55% of all biopsies with pneumonia) and showing different histopathologic stages of progression coexisting in the same lung lobes. Lung cultures were frequently polymicrobial (149 of 375, 40% of the pulmonary biopsy cultures, and 20 of 25, 80% of the cases) and not always yielding the same pathogen (19 microorganisms) when comparing one lung to the other. Histopathology and microbiologic biopsy cultures showed a weak relationship (28% and 49% of species had counts &amp;amp;gt; or = 10(3) cfu/g in samples without pneumonia from patients with and without prior antibiotic treatment, respectively). Histopathologic evolutionary stages were not associated with any differences in quantitative culture results of pulmonary biopsies, independently of prior administration of antibiotics. Higher bacterial concentrations of biopsy cultures were associated with the absence of prior antibiotic treatment. Ventilator-associated pneumonia is a frequent diffuse and polymicrobial process showing different coexisting degrees of evolution and involving preferentially the lower lobes. Microbiology and histology can be dissociated even in the absence of prior antibiotic treatment. Lung histology appears more reliable than bacteriology as a diagnostic reference test.
American Journal of Respiratory and Critical Care Medicine, 1997
The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study o... more The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (&amp;amp;gt; 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. Lung tissue specimens were histologically examined. Respiratory samples were classified as having Candida or otherwise. Ten (40%) patients had at least one pulmonary biopsy yielding Candida spp. Among these 10 patients with Candida isolates, only two had definite pulmonary candidiasis. A total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy samples in all 25 patients. Candida species represented 9% (n = 40) of the isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida species was isolated from pulmonary biopsies, this was always associated with the isolation of the same microorganism from one of the sampling methods. Quantitative cultures of Candida species from different sampling methods correlated well among each other but could not discriminate the presence from absence of Candida pneumonia. A logistic regression model adjusted for the presence of antibiotics, days of antibiotic treatment, mechanical ventilation period, age, ARDS, parenteral nutrition, and gender did not show any independent risk factor for developing positive pulmonary samples for Candida species. The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.
The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recentl... more The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower...
Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different como... more Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different comorbidities in OSA patients make it difficult to know their specific effects on the development of cardiovascular injury. The aim of the present study was to investigate whether recurrent obstructive apneas could lead to myocardial injury. Thirty-six male Sprague-Dawley rats (300-350 g) were either acutely (3 h) or sustainably (5 h/day, for 10 days) subjected to obstructive apneas with a pattern of 15 s each, 60 apneas/h. Corresponding control groups were formed for the acute and sustained models. To assess the induction of systemic inflammation, IL1-β was measured in plasma. Ventricular tissue injury was evaluated by histological techniques (presence of inflammatory cell infiltration, eosin autofluorescence, and detection of apoptosis). After 3h of obstructive apneas, a significant increase in IL1-β (64.9±29.6 ng/μl) were observed with respect to the controls (7.3±1.0 ng/μl), but no myocardial injury was present. Conversely to the acute model, the systemic inflammation triggered by obstructive apneas for 10 days was reduced. However, the percentage of area with enhanced eosin autofluorescence and of apoptotic cells (1.83±0.35% and 24.4±1.5%, respectively) was increased when compared to the control group (0.72±0.20% and 5.0±2.8%, respectively). This study suggests that obstructive apneas are a potential source of early systemic and ventricular inflammation and myocardial cell injury after sustained apneas application, which could represent an initial phase in the progression of heart disease associated with OSA.
The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-... more The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal- or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by β1 integrin mechano-sensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in β1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), β1 expression, and ERK1/2 (pT202/Y204) than ADC-TAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or β1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs. This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.
Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accu... more Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s automated scanning system. All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.
The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the H... more The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the Hospital Clinic, Barcelona (Catalonia, Spain) studied by a multidisciplinary committee. The clinicopathologic correlation of the primary underlying disease with the immediate cause of death was reviewed. Between 1991 and 2000, 2,495 autopsies were performed, 1933 of which were evaluated by the committee. The autopsy rate fell from 20% in 1993 to 9.1% in 2000. The clinicopathologic correlation in underlying primary disease was correct in 92.67% of the cases; there was a major discrepancy in 3.51% and a minor discrepancy in 3.82%. As regards the immediate cause of death, major errors were found in 5.89% of cases and minor errors in 6.17%. Despite the scientific and technologic advances in medicine, we have seen that there are still clinicopathologic discrepancies. The postmortem examination continues to play an important role in auditing clinical practice and diagnostic performance, and also for educational purposes. Evaluation by a multidisciplinary committee is the more reliable system for the study of the clinicopathologic correlation.
... P2-014 BSTB: Cancer Genetics Posters, Tue, Sept 4 Single nucleotide polymorphisms of Pim-1 in... more ... P2-014 BSTB: Cancer Genetics Posters, Tue, Sept 4 Single nucleotide polymorphisms of Pim-1 in Korean lung cancer patients Jung, Jun Seok; Han, Sle Gi Lo; Jo, Uk Hyun; Yoo, Won Beak; Choi, Hyo Seon; Sung, Jae Sook; Lee, Hyo Jung; Lee, Jae Won; Kim, Jun Suk; Kim ...
To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomog... more To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomography (CT) scan in clinical non-central cIA and cIB non-small-cell lung cancer (NSCLC) for mediastinal staging. Between January 2007 and December 2010, 402 patients with potentially operable NSCLC were assessed by thoracic CT scan and 18-fluoro-2-deoxy-d-glucose PET-CT for mediastinal staging and to detect extrathoracic metastases, of which 153 surgically treated patients (79 cIA and 74 cIB cases) were prospectively included in the study. Central tumours were excluded on the basis of CT scan criteria, defined as contact with the intrapulmonary main bronchi, pulmonary artery, pulmonary veins or the origin of the first segmental branches. CT scan was considered negative if lymph nodes were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 cm at the smaller diameter. 18FDG PET-CT was considered negative when the high maximum standard uptake value (SUVmax) was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.5. Non-invasive surgical staging was carried out in this group, and curative resection plus systematic mediastinal dissection was performed except in the event of unexpected oncological contraindication. Composite non-invasive staging (CT scan, PET-CT) showed a negative predictive value (NPV) of 92% (CI 83.6-96.8) in the cIA group and 85% (CI 74-92) in the cIB group. There were 6 of 79 (7.6%) false-negatives (FNs) in cIA and 11 of 74 (14.8%) in cIB. Multilevel pN2 were detected in four cases, all of them in the cIB group. The most frequently involved N2 was subcarinal (two cases) in cIA and right lower paratracheal (R4) and seven (five cases) in cIB. Occult (pN2) lymph nodes were more frequent in tumour sizes≥5 cm (pT2b, nine cases, four FNs, P=0.03), pN1, adenocarcinoma [excluding minimally invasive adenocarcinoma (MIA) and lepidic predominant growth (LPA)] (P=0.029) and female patients, but no other risk factors for mediastinal metastases were identified (age, clinical stage, tumour location, central or peripheral, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). Multilevel pN2 was significantly more frequent in the cIB group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). In pT≤1 cm (T1a), NPV was significantly better (NPV=100%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) than the other subgroups studied (IA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 cm and IB). Composite results for non-invasive mediastinal staging (CT scan, PET-CT) showed 11% of FNs in cI stage (7.6% in non-central cIA and 14.8% in cIB). In tumours≤1 cm, NPV makes surgical staging unnecessary. In women with adenocarcinoma and non-central cIB, however, the high FN rate makes invasive staging necessary, particularly in pT2b to decrease the incidence of unexpected pN2 in thoracotomy.
... Lipid deposition during the long-term infusion of propofol. El-Ebiary, Mustafa MD; Torres, An... more ... Lipid deposition during the long-term infusion of propofol. El-Ebiary, Mustafa MD; Torres, Antoni MD; Ramirez, Josep MD; Xaubet, Antoni MD; Rodriguez-Roisin, Robert MD FRCP. ... 3. Lynch MJ: Nephrosis and fat embolism in acute hemorrhagic pancreatitis. ...
To validate sampling techniques (tracheobronchial aspirates, protected specimen brush, and bronch... more To validate sampling techniques (tracheobronchial aspirates, protected specimen brush, and bronchoalveolar lavage, both conventional and protected) for the detection of ventilator-associated pneumonia (VAP) and causative microorganisms according to different histologic and microbiological references. Immediate, multiple bilateral lung biopsy, postmortem study. Respiratory intensive care unit of a 1,000-bed teaching hospital. Twenty-five mechanically ventilated patients (&gt;72 hrs) who died in our intensive care unit. Lung tissue histologic examination and quantitative cultures (16 specimens/patient). The following four references for the diagnostic techniques were used: histology of guided lung biopsy, histology of blind lung biopsy, combined guided and blind lung biopsy histology and microbiology of lung tissue, and microbiology of lung tissue. Sensitivities when histologic reference tests were used ranged from 16% to almost 40%, whereas specificity rates were always &lt;80%. When we combined both lung histology of guided or blind specimens and microbiology of lung tissue, all diagnostic techniques achieved considerably higher but still limited diagnostic yields (sensitivity range 43% to 83%; specificity range 67% to 91%). Causative organisms were missed in a significant number of cases by all techniques (17% to 83%). The diagnostic performances of different diagnostic techniques strongly depend on the reference used. All techniques for detecting VAP are of limited value. Finding a balance between clinical judgment and microbiological results is crucial to appropriately manage patients with VAP.
To evaluate the clinical relevance of the presence of lymphocytes in transbronchial needle aspira... more To evaluate the clinical relevance of the presence of lymphocytes in transbronchial needle aspiration (TBNA) samples from pathological mediastinal lymph nodes in patients with suspected lung cancer. Retrospective observational study evaluating the negative predictive value (NPV) of TBNA samples containing lymphocytes but not malignant cells. A total of 266 TBNA were performed in 252 patients with pathological lymph nodes. One hundred and fifteen TBNA samples had evidence of malignant cells (43%), and 94 (35%) samples were considered as inadequate (absence of adequate cytological material or exclusive presence of bronchial epithelial cells). Out of the 57 TBNA samples remaining (21%), 15 could not be confirmed; in 32, TBNA samples were confirmed with alternative diagnostic techniques and in 10, they were confirmed after clinical and radiological follow-up. The NPV of the 32 samples that were confirmed with alternative diagnostic techniques was 84% decreasing down to 76% when the 10 TBNA samples confirmed after clinical and radiological follow-up were included. The presence of lymphocytes in the TBNA sample does not exclude the neoplasic invasion of the specific lymph node analyzed.
The relationship between microbiology and histology in patients with ventilator-associated pneumo... more The relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described. Twenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died with clinical suspicion of pulmonary infection. A total of 375 immediate postmortem pulmonary biopsies were obtained after death and processed for quantitative microbiology and histology. Four evolutionary stages of pneumonia were defined: early, intermediate, advanced, and resolution. At least one specimen with histologic evidence of pneumonia was found in all but two patients (92%). Histologic pneumonia was a widespread and frequent process (46%) of biopsies examined) involving predominantly the lower lobes (55% of all biopsies with pneumonia) and showing different histopathologic stages of progression coexisting in the same lung lobes. Lung cultures were frequently polymicrobial (149 of 375, 40% of the pulmonary biopsy cultures, and 20 of 25, 80% of the cases) and not always yielding the same pathogen (19 microorganisms) when comparing one lung to the other. Histopathology and microbiologic biopsy cultures showed a weak relationship (28% and 49% of species had counts &amp;amp;gt; or = 10(3) cfu/g in samples without pneumonia from patients with and without prior antibiotic treatment, respectively). Histopathologic evolutionary stages were not associated with any differences in quantitative culture results of pulmonary biopsies, independently of prior administration of antibiotics. Higher bacterial concentrations of biopsy cultures were associated with the absence of prior antibiotic treatment. Ventilator-associated pneumonia is a frequent diffuse and polymicrobial process showing different coexisting degrees of evolution and involving preferentially the lower lobes. Microbiology and histology can be dissociated even in the absence of prior antibiotic treatment. Lung histology appears more reliable than bacteriology as a diagnostic reference test.
American Journal of Respiratory and Critical Care Medicine, 1997
The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study o... more The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (&amp;amp;gt; 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. Lung tissue specimens were histologically examined. Respiratory samples were classified as having Candida or otherwise. Ten (40%) patients had at least one pulmonary biopsy yielding Candida spp. Among these 10 patients with Candida isolates, only two had definite pulmonary candidiasis. A total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy samples in all 25 patients. Candida species represented 9% (n = 40) of the isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida species was isolated from pulmonary biopsies, this was always associated with the isolation of the same microorganism from one of the sampling methods. Quantitative cultures of Candida species from different sampling methods correlated well among each other but could not discriminate the presence from absence of Candida pneumonia. A logistic regression model adjusted for the presence of antibiotics, days of antibiotic treatment, mechanical ventilation period, age, ARDS, parenteral nutrition, and gender did not show any independent risk factor for developing positive pulmonary samples for Candida species. The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.
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