RESUMEN
INTRODUCTION: In 2006 under the supervision of the French health authorities (HAS), recommendations for clinical practice (RCP) in the management of rectal cancers were first published. The primary objective of this study was to assess the impact of these guidelines on multidisciplinary management in terms of therapeutic strategies based on disease staging and quality indicators for surgical excision. Secondarily, we assessed the impact of the RCPs on postoperative and oncological outcomes. METHODS: All consecutive patients having undergone curative surgical excision for middle and low (subperitoneal) rectal cancer from 1995 to 2017 in the university hospital of Caen were included in accordance with the relevant French guidelines. They were divided into two groups: before (Gr1) and after (Gr2) 2006. For each group, a chart review was conducted on demographic variables, preoperative rectal tumor features, disease severity variables and quality of surgery variables. Postoperative and oncological outcomes were likewise assessed and compared between the two groups. RESULTS: Six hundred and four patients were included (Gr1, n=266; Gr2, n=338). Compliance with French guidelines significantly improved (i) use of magnetic resonance imaging (P<0.0001) and CT-scan (P<0.0001)]; (ii) organization of multidisciplinary tumor boards (P<0.0001) leading to suitable neo-adjuvant treatment plan classification (P<0.0001). Consequently, compliance improved widespread total mesorectal excision (P<0.0001), sphincter-sparing surgery (P=0,0005), and completeness of curative resection in the specimen (P<0.0001). Although postoperative 90-day mortality was similar, overall postoperative morbidity significantly increased in Gr2 (P<0.0001). Overall (P=0.0005) and disease-free survival (P=0.0016) of patients in Gr2 were significantly prolonged and correlated with a significant reduction in local and distant recurrences. CONCLUSION: Compliance with the relevant French guidelines improved the quality of multidisciplinary management of patients undergoing curative surgery for subperitoneal rectal cancer. However, further progress is still needed to render accession to the recommendations more comprehensive.
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Adhesión a Directriz/normas , Grupo de Atención al Paciente/normas , Neoplasias del Recto/cirugía , Anciano , Canal Anal , Femenino , Francia , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Tratamientos Conservadores del Órgano/normas , Grupo de Atención al Paciente/organización & administración , Complicaciones Posoperatorias/epidemiología , Mejoramiento de la Calidad , Calidad de la Atención de Salud , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Factores Sexuales , Tomografía Computarizada por Rayos X/normas , Resultado del TratamientoRESUMEN
The quality of pathologic assessment of rectal cancer specimens is crucial for treatment efficiency and survival. The Royal College of Pathologists (RCP) recommends evaluating the quality of the pathology report in routine practice using three quality indicators (QIs): the number of lymph nodes (LNs) analyzed (≥ 12), the rate of venous invasion (VI ≥ 30%), and peritoneal involvement (pT4a ≥ 10%). In this study, we evaluated the three QIs of the French national pathology reports and compared them with British guidelines and assessed the influence of neoadjuvant radiochemotherapy on QIs. From January 1 to December 31, 2016, all pathology reports for rectal adenocarcinoma were collected from French departments. Neoadjuvant radiochemotherapy included long-course radiotherapy with concomitant 5-FU-based chemotherapy. A total of 983 rectal cancer pathology reports were evaluated. A median of 15 LNs were analyzed and 81% of centers had ≥ 12 LNs. The rate of VI was 30% and 41% of centers had ≥ 30% VI. The rate of pT4a was 4% and 18% of centers reported ≥ 10% pT4a. None of the centers reached the threshold for the three QIs. All three QIs were lower after radiochemotherapy compared to surgery alone. In conclusion, in French routine practice, the values of two of the three QIs (LNs analyzed and VI) were globally in line with RCP guidelines. However, the rate of pT4a was very low, particularly after radiochemotherapy, suggesting its low value in rectal cancer.
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Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Anciano , Quimioradioterapia/métodos , Femenino , Francia , Humanos , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Radioterapia Adyuvante/métodos , Resultado del TratamientoRESUMEN
INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft rejection associated with HEV are available and are subject to discussion. CASE REPORT: Here we report the case of a 58-year-old male patient who underwent LT in July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a mismatch CMV (donor+ and recipient-). HEV serology was negative before LT. In February 2016, we noted abnormal liver function, with increased transaminases and cholestasis parameters, without functional complaints. The patient was immunosuppressed by tacrolimus (4mg) and everolimus (2mg). Abdominal ultrasound was normal and liver biopsy showed signs of acute rejection (Banff score 6/9). We dispensed 500mg of methylprednisolone before obtaining positive serological results for HEV genotype 3 infection. Ribavirin (1,200mg per day) for 3 months was started, leading to rapid improvement in liver tests. Viral load became negative one month later. To date, the patient is under LP 5mg tacrolimus with normal liver tests. CONCLUSION: We describe a case of HEV genotype 3 infection mimicking acute cellular rejection, with a favorable outcome due to ribavirin treatment. As intensive immunosuppressive therapy administered for graft rejection may promote viral replication and worsen liver damage, potential HEV infection must be considered in cases of pathological signs of acute cellular rejection, in order to avoid chronic graft hepatitis, cirrhosis and liver decompensation.
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Hepatitis E/diagnóstico , Trasplante de Hígado , Colestasis/virología , Diagnóstico Diferencial , Rechazo de Injerto/diagnóstico , Virus de la Hepatitis E/genética , Humanos , Huésped Inmunocomprometido , Pruebas de Función Hepática , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate long-term (5- and 10-year) survival and recurrence rates on the basis of the pathological complete response (pCR) in the specimens of patients with esophageal carcinoma, treated with trimodality therapy. METHODS: Between 1993 and 2014, all consecutives patients with esophageal locally-advanced non-metastatic squamous cell carcinoma (SCC) or adenocarcinoma (ADC) who received trimodality therapy were reviewed. According to histopathological analysis, patients were divided in two groups with pCR and with pathological residual tumor (pRT). The primary endpoint was overall survival (OS). The secondary endpoints included the disease-free survival (DFS), the recurrence rate, and the predictive factors of overall survival and recurrence. RESULTS: One hundred and three patients were included: 49 patients with pCR and 54 patients with pRT. The median OS was significantly longer in pCR group than in pRT group (132±22.3 vs. 25.5±4 months), with both 5- and 10-years OS rates of 75.2% vs. 29.1%, and 51.1% vs. 13.6%, respectively (P<0.001). Also, pRT, major postoperative complications (Dindo-Clavien grade>IIIb) and recurrence were the 3 independent predictive factors for worse OS. CONCLUSIONS: Patients with locally-advanced oesophageal carcinoma, who responded to trimodality therapy with a pCR, could be achieved a 10-year survival rate of 51%.
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Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Adenocarcinoma/patología , Análisis de Varianza , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Quimioradioterapia/estadística & datos numéricos , Terapia Combinada/métodos , Terapia Combinada/mortalidad , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Esofagectomía/estadística & datos numéricos , Femenino , Humanos , Quimioterapia de Inducción/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual , Cuidados Preoperatorios , Estudios Retrospectivos , Sobrevivientes , Factores de TiempoRESUMEN
BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency. So far, the treatment of choice is hemin which represses ALAS1. The main issue in the medical care of AIP patients is the occurrence of debilitating recurrent attacks. OBJECTIVE: The aim of this study was to determine whether chronic hemin administration contributes to the recurrence of acute attacks. METHODS: A follow-up study was conducted between 1974 and 2015 and included 602 French AIP patients, of whom 46 had recurrent AIP. Moreover, we studied the hepatic transcriptome, serum proteome, liver macrophage polarization and oxidative and inflammatory profiles of Hmbs-/- mice chronically treated by hemin and extended the investigations to five explanted livers from recurrent AIP patients. RESULTS: The introduction of hemin into the pharmacopeia has coincided with a 4.4-fold increase in the prevalence of chronic patients. Moreover, we showed that both in animal model and in human liver, frequent hemin infusions generate a chronic inflammatory hepatic disease which induces HO1 remotely to hemin treatment and maintains a high ALAS1 level responsible for recurrence. CONCLUSION: Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti-inflammatory therapies should be considered in patients with recurrent AIP.
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5-Aminolevulinato Sintetasa/sangre , Hidroximetilbilano Sintasa/fisiología , Hígado/fisiopatología , Porfiria Intermitente Aguda/fisiopatología , Enfermedad Aguda , Animales , Estudios de Cohortes , Estudios Transversales , Femenino , Estudios de Seguimiento , Hemo-Oxigenasa 1/metabolismo , Hemina/administración & dosificación , Hemina/efectos adversos , Humanos , Hígado/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Porfiria Intermitente Aguda/diagnóstico , Porfiria Intermitente Aguda/epidemiología , Porfiria Intermitente Aguda/terapia , Recurrencia , Factores de RiesgoRESUMEN
INTRODUCTION: Benign osteoblastoma is a rare fibrous bone tumour observed in children. Very few cases involving the paranasal sinuses have been reported. SUMMARY: A 10-year-old child presented with a 1-month history of right exophthalmos. Clinical and radiological assessment demonstrated a heterogeneous tumour with bone components occupying all of the maxillary sinus. Initial histology was in favour of fibrous dysplasia. Surgery was performed via a combined approach. After review of the histology slides, the final diagnosis was that of osteoblastoma. In view of the procedure performed and after consultation, no complementary treatment was proposed. A recurrence was observed 8months later. Right maxillectomy associated with total ethmoidectomy via a combined approach was performed to ensure complete resection of the tumour. A favourable course without recurrence was observed with a follow-up of 5 years. DISCUSSION: Osteoblastoma of the maxillary sinus is rare. CT assessment must be as precise as possible to avoid confusion with another tumour. The diagnosis can only be confirmed by histological examination. This case report is completed by a review of the literature with description of the main differential diagnoses.
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Exoftalmia/etiología , Neoplasias del Seno Maxilar/patología , Osteoblastoma/patología , Niño , Senos Etmoidales/cirugía , Exoftalmia/cirugía , Humanos , Masculino , Seno Maxilar/cirugía , Neoplasias del Seno Maxilar/cirugía , Osteoblastoma/cirugíaRESUMEN
The first step in the diagnosis of a metastatic brain lesion is to exclude a primary central nervous sytem tumour, followed by verification or identification of the primary tumor site, in order to guide the clinician to specific therapy. In addition to morphological features, ancillary immunohistochemical study is most effective for the evaluation of a metastatic neoplasm of unknown primary. Although the main principles are same, there are slight variations in the approach to the secondary lesion in the central nervous system versus other regions. Indeed, immunohistochemical approach focuses on the most common tumor types associated with secondary brain colonization: lung cancer, breast cancer and melanoma. Several studies have reported that targeted therapies are capable of reducing brain metastases in melanoma or non-small cell lung cancer, sometimes with a high dramatic response. These results have clearly impacted routine neuropathological practice. It is likely that molecular subtyping of central nervous system metastases will play an increasing role in the future. In accordance with the recommendations of Inca (French national cancer institute), the pathologist develops appropriate strategies for molecular and immunohistochemical analysis, in order to provide results as soon as possible. This article summarizes the diagnosic approach to brain metastases, with a focus on the recent emergence of targeted therapies.
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Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/secundario , Adulto , Neoplasias Encefálicas/química , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma/química , Carcinoma/clasificación , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/secundario , Diferenciación Celular , Femenino , Genes Relacionados con las Neoplasias , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Melanoma/química , Melanoma/diagnóstico , Melanoma/genética , Melanoma/secundario , Mutación , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , OncogenesRESUMEN
BACKGROUND: Hepatocellular carcinoma in noncirrhotic liver (HCCNC) is rare. This tumor has a particular epidemiology and presentation, and it requires specific treatment, compared with HCC in cirrhotic liver. The aims of this study were to determine the survival and recurrence rates, prognostic factors, and optimum treatment of HCCNC and to propose a follow-up protocol for patients who have undergone surgery for HCCNC. METHODS: This study included 131 patients who underwent surgical treatment for HCCNC from January 1992 to December 2010. Survival and recurrence rates were evaluated, and the prognostic factors and characteristics of recurrence were analyzed. Pathologic characteristics of the tumors and the nontumoral liver were examined. RESULTS: The mean survival time was 67.9 months. The 5- and 10-year overall survival rates were 72.9 and 36.7 %, respectively. In all, 54 patients (41.2 %) developed recurrence at a median interval of 30.96 months. Of these recurrences, 31.5 % occurred during the first year, and 24.1 % occurred more than 5 years after surgery. Macro- or microvascular invasion and tumor size >5 cm were significantly associated with a poor survival rate. The predictive factors for recurrence were multiple tumors, tumor diameter >5 cm, and satellite nodules. Patients who underwent surgical treatment for recurrence had a significantly longer survival time than those who did not (p < 0.0292). CONCLUSIONS: Recurrence is the most common cause of death after hepatectomy for HCC, and patients should undergo careful, long-term follow-up. Early detection and treatment of recurrence with curative intent should improve the prognosis of these patients.
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Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Hígado/patología , Recurrencia Local de Neoplasia/epidemiología , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Protocolos Clínicos , Femenino , Estudios de Seguimiento , Humanos , Hígado/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To characterize bone microarchitectural changes and to test the hypothesis that disrupting local cytokine equilibrium could modify cartilage degradation in a murine model of experimental osteoarthritis (OA). METHODS: Ten-week-old male C57BL/6 mice underwent medial meniscectomy of their right knees and a sham operation of their left knees. The mice received intraperitoneal injections of osteoprotegerin (OPG) (10 mg/kg), interleukin-1 receptor antagonist (IL-1Ra) (100 mg/kg), or phosphate buffered saline for 6 weeks. The microarchitecture of the trabecular bone, the OA score, and expression of ADAMTS-4 and ADAMTS-5 were assessed. Proteoglycan release was measured in cartilage explant cultures in the presence of IL-1Ra and OPG. RESULTS: In the meniscectomized knees, bone volume/tissue volume (BV/TV) was lower, whereas trabecular separation, the OA score, and aggrecanase expression were higher than in the sham-operated knees. After treatment with OPG, BV/TV was significantly increased and trabecular separation was reduced in the knees that underwent meniscectomy. The OA score and the number of ADAMTS-positive cells were significantly decreased by treatment with OPG but were not affected by IL-1Ra. Moreover, OPG did not directly reduce the release of proteoglycans from cartilage explant cultures. CONCLUSION: In an experimental model of OA, meniscectomy induced bone loss and cartilage degradation at 6 weeks. Systemic administration of OPG prevented bone and cartilage degradation in vivo but had no effect on cartilage in vitro. These data collectively indicate that bone could be a contributor in the early stages of OA pathogenesis. They further suggest that disruption of RANKL/OPG balance might result in the degradation of cartilage subjected to mechanical loading. Specific targeting of the bone cytokine network might help to prevent OA.
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Huesos/efectos de los fármacos , Enfermedades de los Cartílagos/prevención & control , Cartílago Articular/metabolismo , Osteoartritis de la Rodilla/metabolismo , Osteoprotegerina/fisiología , Proteínas ADAM/metabolismo , Proteína ADAMTS4 , Proteína ADAMTS5 , Animales , Huesos/metabolismo , Enfermedades de los Cartílagos/metabolismo , Modelos Animales de Enfermedad , Proteína Antagonista del Receptor de Interleucina 1/fisiología , Masculino , Meniscos Tibiales/cirugía , Ratones , Ratones Endogámicos C57BL , Osteoartritis de la Rodilla/patología , Procolágeno N-Endopeptidasa/metabolismo , Proteoglicanos/metabolismo , Ligando RANK/metabolismoRESUMEN
AIMS: Selection of the relevant combination from a growing list of candidate immunohistochemical biomarkers constitutes a real challenge. The aim was to establish the minimal subset of antibodies to achieve classification on the basis of 12 antibodies and 309 renal tumours. METHODS AND RESULTS: Seventy-nine clear cell (CC), 88 papillary (PAP) and 50 chromophobe (CHRO) renal cell carcinomas, and 92 oncocytomas (ONCO) were immunostained for renal cell carcinoma antigen, vimentin, cytokeratin (CK) AE1-AE3, CK7, CD10, epithelial membrane antigen, alpha-methylacyl-CoA racemase (AMACR), c-kit, E-cadherin, Bcl-1, aquaporin 1 and mucin-1 and analysed by tissue microarrays. First, unsupervised hierarchical clustering performed with immunohistochemical profiles identified four main clusters-cluster 1 (CC 67%), 2 (PAP 98%), 3 (CHRO 67%) and 4 (ONCO 100%)-demonstrating the intrinsic classifying potential of immunohistochemistry. A series of classification trees was then automatically generated using Classification And Regression Tree software. The most powerful of these classification trees sequentially used AMACR, CK7 and CD10 (with 86% CC, 87% PAP, 79% CHRO and 78% ONCO correctly classified in a leave-one-out cross-validation test). The classifier was also helpful in 22/30 additional cases with equivocal features. CONCLUSION: The classification tree method using immunohistochemical profiles can be applied successfully to construct a renal tumour classifier.