RESUMEN
BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.
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Genómica , Mutación de Línea Germinal , Neoplasias , Humanos , Femenino , Biopsia Líquida , Neoplasias/genética , Neoplasias/patología , Masculino , Persona de Mediana Edad , Estudios de Cohortes , Mutación de Línea Germinal/genética , Genómica/métodos , Adulto , Anciano , Células Germinativas/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Predisposición Genética a la EnfermedadRESUMEN
Mismatch repair (MMR) testing on all new cases of colorectal cancer (CRC) has customarily been preferably performed on surgical specimens, as more tissue is available; however, new clinical trials for the use of immune checkpoint inhibitors in the neoadjuvant setting require MMR testing on biopsy samples. This study aims at identifying advantages, disadvantages and any potential pitfalls in MMR evaluation on biopsy tissue and how to cope with them. The study is prospective-retrospective, recruiting 141 biopsies (86 proficient (p)MMR and 55 deficient (d)MMR) and 97 paired surgical specimens (48 pMMR; 49 dMMR). In biopsy specimens, a high number of indeterminate stains was observed, in particular for MLH1 (31 cases, 56.4%). The main reasons were a punctate nuclear expression of MLH1, relatively weak MLH1 nuclear expression compared to internal controls, or both (making MLH1 loss difficult to interpret), which was solved by reducing primary incubation times for MLH1. A mean of ≥ 5 biopsies had adequate immunostains, compared to ≤ 3 biopsies in inadequate cases. Conversely, surgical specimens rarely suffered from indeterminate reactions, while weaker staining intensity (p < 0.007) for MLH1 and PMS2 and increased patchiness grade (p < 0.0001) were seen. Central artefacts were almost exclusive to surgical specimens. MMR status classification was possible in 92/97 matched biopsy/resection specimen cases, and all of these were concordant (47 pMMR and 45 dMMR). Evaluation of MMR status on CRC biopsy samples is feasible, if pitfalls in interpretation are known, making laboratory-specific appropriate staining protocols fundamental for high-quality diagnoses.
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Neoplasias Colorrectales , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias Colorrectales/genética , BiopsiaRESUMEN
BACKGROUND: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. MATERIALS AND METHODS: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. RESULTS: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. CONCLUSIONS: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).
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Carcinoma Neuroendocrino , Carcinoma de Células Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/patología , Humanos , Pulmón , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
Complete histopathologic tumor regression after neoadjuvant treatment is a well-known prognostic factor for survival among patients with adenocarcinomas of the esophagus and gastroesophageal junction. The aim of this international Delphi survey was to reach a consensus regarding the most useful tumor regression grading (TRG) system that could represent an international standard for histopathologic TRG grading of gastroesophageal carcinomas. Fifteen pathologists with special interest in esophageal and gastric pathology participated in the online survey. The initial questionnaire contained of 43 statements that addressed the following topics: (1) specimen processing, (2) gross examination, (3) cross sectioning, (4) staining, (5) Barrett's esophagus, (6) TRG systems, and (7) TRG in lymph node (LN). Participants rated the items using a 5-point Likert style scale and were encouraged to write comments for each statement. The expert panel recommended a 4-tiered TRG system for assessing the primary tumor: grade 1: No residual tumor (complete histopathologic tumor regression), grade 2: less than 10% residual tumor (near-complete regression), grade 3: 10%-50% residual tumor (partial regression), grade 4: greater than 50% residual tumor (minimal/no regression), combined with a 3-tiered system for grading therapeutic response in metastatic LNs: grade a: no residual tumor (complete histopathologic TRG), grade b: partial regression (tumor cells and regression), grade c: no regression (no sign of tumor response). This TRG grading system can be recommended as an international standard for histopathologic TRG grading in esophageal and gastroesophageal junction adenocarcinoma.
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Adenocarcinoma/patología , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Clasificación del Tumor/métodos , Adenocarcinoma/terapia , Consenso , Técnica Delphi , Neoplasias Esofágicas/terapia , Humanos , Terapia Neoadyuvante/métodos , Manejo de Especímenes/métodos , Manejo de Especímenes/normas , Resultado del TratamientoRESUMEN
Standardization in immunohistochemistry is a priority in modern pathology and requires strict quality control. Cost containment has also become fundamental and auditing of all procedures must take into account both these principles. Positive controls must be routinely performed so that their positivity guarantees the appropriateness of the immunohistochemical procedure. The aim of this study is to develop a low cost (utilizing a punch biopsy-PB-tool) procedure to construct positive controls which can be integrated in the patient's tissue slide. Sixteen frequently used control blocks were selected and multiple cylindrical samples were obtained using a 5-mm diameter punch biopsy tool, separately re-embedding them in single blocks. For each diagnostic immunoreaction requiring a positive control, an integrated PB-control section (cut from the appropriate PB-control block) was added to the top right corner of the diagnostic slide before immunostaining. This integrated control technique permitted a saving of 4.75% in total direct lab costs and proved to be technically feasible and reliable. Our proposal is easy to perform and within the reach of all pathology labs, requires easily available tools, its application costs is less than using external paired controls and ensures that a specific control for each slide is always available.
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Biopsia/normas , Técnicas de Preparación Histocitológica/normas , Inmunohistoquímica/normas , Control de Calidad , Biopsia/economía , Biopsia/instrumentación , Técnicas de Preparación Histocitológica/economía , Técnicas de Preparación Histocitológica/instrumentación , Humanos , Inmunohistoquímica/economía , Inmunohistoquímica/instrumentación , Estándares de ReferenciaRESUMEN
BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS: A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS: Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.
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Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/cirugía , Membrana Mucosa/fisiopatología , Cicatrización de Heridas , Adulto , Biopsia , Esomeprazol/uso terapéutico , Femenino , Reflujo Gastroesofágico/fisiopatología , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Membrana Mucosa/cirugía , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Segmental infarction (SI) of the testis is a rare condition that can masquerade as a mass lesion, thus requiring exclusion of tumour. If clinical exams do not exclude a neoplastic lesion with certainty, orchidectomy is usually performed. A case of SI of the testis is presented; the use of frozen section of the enucleated mass demonstrated the ischaemic nature of the lesion, so avoiding orchidectomy. The 8 year follow-up was uneventful. The use of frozen section in SI could permit the selection of cases in which testicular-sparing surgery should be considered.
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Secciones por Congelación , Infarto/patología , Orquiectomía , Neoplasias Testiculares/patología , Testículo/irrigación sanguínea , Testículo/patología , Procedimientos Innecesarios , Adulto , Diagnóstico Diferencial , Humanos , Infarto/cirugía , Masculino , Valor Predictivo de las Pruebas , Neoplasias Testiculares/cirugía , Testículo/cirugíaRESUMEN
PURPOSE: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Most (80 %) contain activating mutations in the KIT receptor tyrosine kinase, roughly 10 % in platelet-derived growth factor receptor-alpha (PDGFRA). In a small subset, BRAF mutations are an alternative molecular pathway. GISTs respond well to imatinib, but low response is seen in patients with wild-type KIT or PDGFRA. Resistance has also been reported as a result of mutations in downstream effectors such as BRAF. METHODS: We provide here a molecular characterization of a series of primary GISTs from Italian patients. Of 121 GIST cases diagnosed between 2000 and 2012, 83 were evaluated by PCR amplification and direct sequencing for mutations in KIT exons 8, 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and BRAF exon 15. Eighty-one GISTs also underwent K-RAS testing. RESULTS: Sixty-four GISTs were positive: 55 had mutations in KIT and 9 in PDGFRA; 16 patients were mutation negative. Three samples came from NF1 patients and were KIT- and PDGFRA negative. Overall, we identified six novel mutations in KIT (p.K550_M552delinsL, p.Q556_W557delinsG p.Q556_G575del, p.W557_V559delinsQ p.P573_R588dup, p.G592_K593dup) and one novel mutation in PDGFRA (p.D842_N848delinsVDV), thus contributing to widening the spectrum of known mutations in GIST tumors and confirming the most frequently altered regions underlying GIST development. CONCLUSIONS: Among the 64 KIT- and PDGFRA-positive sporadic patients in our series, no BRAF or KRAS mutations were identified, suggesting that co-occurrence of these mutations is likely to be rare in the northwestern Italian population and not a frequent cause of primary resistance to imatinib in KIT-positive GIST patients.
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Tumores del Estroma Gastrointestinal/genética , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Biomarcadores de Tumor/genética , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Reacción en Cadena de la Polimerasa , Pronóstico , Proteínas Proto-Oncogénicas p21(ras) , Pirimidinas/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals. AIMS: To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266). METHODS: Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy. RESULTS: Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin. CONCLUSIONS: Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.
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Antiulcerosos/uso terapéutico , Células Similares a las Enterocromafines/patología , Esomeprazol/uso terapéutico , Reflujo Gastroesofágico/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Inhibidores de la Bomba de Protones/uso terapéutico , Adolescente , Adulto , Anciano , Cromogranina A/sangre , Células Similares a las Enterocromafines/metabolismo , Femenino , Estudios de Seguimiento , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Gastrinas/sangre , Reflujo Gastroesofágico/complicaciones , Infecciones por Helicobacter/complicaciones , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility.
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Adenocarcinoma/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Eliminación de Gen , Mutación de Línea Germinal/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Proteína del Grupo de Complementación N de la Anemia de Fanconi , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/genética , LinajeRESUMEN
Lynch syndrome is an inherited cancer syndrome caused by germline mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. LS predisposes to high risk of early-onset colorectal, endometrial and other tumors. Patients with Lynch syndrome have also been shown to have an elevated risk for pancreatic cancer (PC). In this study, we aimed to estimate the frequency of suspected Lynch syndrome among a series of 135 PC patients. Further, we wanted to determine the frequency of MMR gene mutations in the suspected Lynch syndrome cases. We also aimed to verify the pathogenicity of any novel non-truncating variants we might detect with a functional assay. Based on personal and/or familial cancer history, 19 patients were classified as suspected Lynch syndrome cases. DNA material for mutation analysis was available for eleven of them. Four patients were found to carry a total of five MLH1 or MSH2 variants. Of these, MSH2-Q402X, MSH2-G322D, and MLH1-K618A had been previously reported, while the MSH2-E205Q and MSH2-V367I variants were novel. MSH2-Q402X is a known stop mutation and reported here for the first time here in association with PC. MLH1-K618A was found in the unaffected branch of a kindred, suggesting that it may be a polymorphism or a low penetrance variant. MSH2-G322D likely does not cause a MMR defect, although this variant has also been associated with breast cancer as indeed seen in our patient. The novel variants MSH2-E205Q and MSH2-V367I were found in the same patient. Both novel variants were however functional in the applied MMR assay. Our findings suggest that only a small subset of pancreatic cancer patients carry pathogenic MMR mutations.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Predisposición Genética a la Enfermedad , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Adulto , Secuencia de Bases , Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Reparación de la Incompatibilidad de ADN/genética , Análisis Mutacional de ADN , Femenino , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Italia , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Linaje , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Intestinal metaplasia is a risk factor for gastric carcinoma. So far few studies have focused on the efficacy of endoscopic biopsies in detecting intestinal metaplasia in relation with the site and number of biopsies performed. The present study is aimed to assess the efficacy of single and multiple gastric biopsies in the detection and staging of intestinal metaplasia. MATERIAL AND METHODS: The study was conducted on 455 gastrectomies. We defined the extent of intestinal metaplasia on surgical specimens sampled by the "Swiss roll" technique and assessed the efficiency of an increasing number of "virtual" biopsies performed on the same rolls in recognising the true extent of intestinal metaplasia in the antro-angular region. RESULTS: Seventy-four out of 455 cases showed intestinal metaplasia in more than 5% of the antro-angular mucosa. The correlation between antro-angular intestinal metaplasia on rolls and on virtual biopsies was always highly significant, both when a single biopsy was considered and when groups of multiple biopsies (from 2 to 6 samples) were taken into account (p
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Mucosa Gástrica/patología , Lesiones Precancerosas/patología , Antro Pilórico/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Femenino , Humanos , Masculino , Metaplasia/epidemiología , Metaplasia/patología , Persona de Mediana Edad , Lesiones Precancerosas/epidemiología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The microscopic assessment of squamous epithelium lesions in gastro-oesophageal reflux disease (GERD) is subjective. The Ki67 nuclear antigen expressed by proliferating cells provides an objective measure of regeneration in the squamous epithelium. AIM: To evaluate Ki67 expression in GERD patients and controls, in comparison with histological lesions, pH-metry and endoscopic data. METHODS: Eighty-seven patients with GERD symptoms and 20 symptom-free controls underwent endoscopy and 24-h pH monitoring. Oesophageal biopsies (4 cm, 2 cm and Z-line) were stained with Ki67/MIB-1 antibodies; the Ki67-positive nuclear area was assessed with an image analysis system and expressed as percentage of the whole epithelial area (Ki67-%). RESULTS: Ki67-% was significantly higher in 32 patients with erosive oesophagitis, 44 endoscopy-negative GERD and 11 patients with functional heartburn than in controls (P = 0.0001). Both controls and patients showed a progressive increase in Ki67-% from 4 cm to the Z-line (P < 0.0001). Ki67-% showed a significant correlation with other conventional histological lesions (P ranged between 0.0151 and <0.0001). CONCLUSIONS: Ki67 evaluation provides quantitative and objective data on squamous epithelium proliferative activity. This marker can be applied in the distinction of endoscopy-negative GERD from healthy controls.
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Endoscopía Gastrointestinal , Células Epiteliales/patología , Reflujo Gastroesofágico/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: There are conflicting reports on the role of gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection in the aetiology of carditis. AIM: The role of reflux and H. pylori infection in causing carditis was assessed in 113 consecutive patients with GERD and in 25 controls. METHODS: All subjects underwent endoscopy and pH test and carditis was diagnosed on biopsies taken across the squamocolumnar junction. Helicobacter pylori was assessed by histology and rapid urease test. GERD was diagnosed by endoscopic oesophagitis or abnormal pH test. RESULTS: Carditis was detected in 53 of 71 GERD patients and in 15 of 20 controls. Among patients, 18 showed absent, 39 mild and 14 marked cardia inflammation and their H. pylori infection rates were 17, 23 and 57%, respectively (P < 0.025). Most patients with carditis (68%) lacked H. pylori infection. pH-metry was abnormal in 15 of 18 patients with normal cardia, 33 of 39 with mild carditis and 12 of 14 with marked inflammation. CONCLUSIONS: Carditis is a frequent finding in GERD and controls. Mild, non-active carditis is frequent in GERD patients. Marked inflammation is associated with both H. pylori and abnormal pH testing. Thus, both GERD and H. pylori infection may play a role in inducing carditis.
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Cardias , Gastritis/etiología , Reflujo Gastroesofágico/complicaciones , Adulto , Anciano , Estudios de Casos y Controles , Esofagoscopía , Femenino , Gastritis/diagnóstico , Gastritis/microbiología , Reflujo Gastroesofágico/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Estudios ProspectivosRESUMEN
A case of parosteal ossifyng lipoma of femour in 67 years-old female patient is described. Review of literature (1966-1999) about parosteal lipoma reveals less then 70 referred cases; much less common is the ossifyng type; in our knowledge five cases of this very rare subtype are referred in last thirty years.
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Fémur , Lipoma/patología , Osificación Heterotópica/patología , Neoplasias de los Tejidos Blandos/patología , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: The majority of reflux patients have non-erosive reflux disease. AIM: To evaluate the influence of Helicobacter pylori on oesophageal acid exposure in patients with both non-erosive and erosive reflux disease and in a group of controls. The pattern and distribution of chronic gastritis were also assessed. METHODS: One hundred and twelve consecutive patients with symptoms of gastro-oesophageal reflux disease agreed to undergo both upper gastrointestinal endoscopy and 24-h oesophageal pH-metry. Patients were grouped as H. pylori-positive or H. pylori-negative on the basis of both CLO-test and histology, and as cases with or without oesophagitis on the basis of endoscopy. The controls consisted of 19 subjects without reflux symptoms and with normal endoscopy and oesophageal pH-metry. RESULTS: H. pylori was positive in 35 patients (31%) and in six controls (31%); oesophagitis was found in 44 patients (39%) and non-erosive reflux disease in 68 (61%). The prevalence of chronic gastritis in the antrum and corpus was higher in H. pylori-positive than in H. pylori-negative patients (P < 0.001), but was more frequently mild (P < 0.001) than moderate or severe. The percentage total time the oesophageal pH < 4.0 was higher in patients than in controls (P < 0.008-0.001), but there was no difference between H. pylori-positive and H. pylori-negative patients (12.3% vs. 12%, P = 0.43) or H. pylori-positive and H. pylori-negative controls (1.07% vs. 1.47%, P = 0.19). CONCLUSIONS: H. pylori infection had the same prevalence in reflux patients and in controls. It did not affect oesophageal acid exposure, as there was no difference between H. pylori-positive and H. pylori-negative individuals. The high prevalence of mild body gastritis in H. pylori-positive patients suggests that H. pylori eradication is unlikely to lead to gastric functional recovery, which might precipitate or worsen symptoms and lesions in patients with gastro-oesophageal reflux disease.
Asunto(s)
Reflujo Gastroesofágico/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Adolescente , Adulto , Anciano , Endoscopía Gastrointestinal/métodos , Femenino , Ácido Gástrico/fisiología , Reflujo Gastroesofágico/fisiopatología , Infecciones por Helicobacter/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty. AIMS: To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation. METHODS: Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients. RESULTS: Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels. CONCLUSIONS: Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.