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INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.
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Bloqueo Nervioso , Dolor Postoperatorio , Cirugía Torácica Asistida por Video , Humanos , Método Doble Ciego , Cirugía Torácica Asistida por Video/métodos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Masculino , Bloqueo Nervioso/métodos , Femenino , Persona de Mediana Edad , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anciano , Bupivacaína/administración & dosificación , Anestésicos Locales/administración & dosificación , Músculos Paraespinales , Hidromorfona/administración & dosificación , AdultoRESUMEN
AIMS: To identify the bacteria nodulating Sulla spinosissima growing profusely in a lead and zinc mine tailings in Eastern Morocco. METHODS AND RESULTS: In all, 32 rhizobial cultures, isolated from root nodules of S. spinosissima growing in soils of the mining site, were tolerant to different heavy metals. The ERIC-polymerase chain reaction (PCR) fingerprinting analysis clustered the isolates into seven different groups, and the analysis of the 16S rRNA sequences of four selected representative strains, showed they were related to different species of the genus Mesorhizobium. The atpD, glnII and recA housekeeping genes analysis confirmed the affiliation of the four representative strains to Mesorhizobium camelthorni CCNWXJ40-4T , with similarity percentages varying from 96·30 to 98·30%. The sequences of the nifH gene had 97·33-97·78% similarities with that of M. camelthorni CCNWXJ40-4T ; however, the nodC phylogeny of the four strains diverged from the type and other reference strains of M. camelthorni and formed a separated cluster. The four strains nodulate also Astragalus gombiformis and A. armatus but did not nodulate A. boeticus, Vachellia gummifera, Prosopis chilensis, Cicer arietinum, Lens culinaris, Medicago truncatula, Lupinus luteus or Phaseolus vulgaris. CONCLUSIONS: Based on similarities of the nodC symbiotic gene and differences in the host range, the strains isolated from S. spinosissima growing in soils of the Sidi Boubker mining site may form a different symbiovar within Mesorhizobium for which the name aridi is proposed. SIGNIFICANCE AND IMPACT OF THE STUDY: In this work, we show that strains of M. camelthorni species nodulating S. spinosissima in the arid area of Eastern Morocco constitute a distinct phylogenetic clade of nodulation genes; we named symbiovar aridi, which encompasses also mesorhizobia from other Mediterranean desert legumes.
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Fabaceae/microbiología , Plomo/metabolismo , Mesorhizobium/fisiología , Minería , Simbiosis , Proteínas Bacterianas/genética , Genes Esenciales/genética , Especificidad del Huésped , Mesorhizobium/clasificación , Marruecos , Filogenia , Nodulación de la Raíz de la Planta/genética , ARN Ribosómico 16S/genética , Nódulos de las Raíces de las Plantas/microbiología , Microbiología del Suelo , Simbiosis/genéticaRESUMEN
AIM: To analyse the diversity of nodule-forming bacteria isolated from Lupinus cosentinii naturally grown in the Maamora cork oak forest (Rabat, Morocco). METHODS AND RESULTS: Of the 31 bacterial strains, four were selected based on their REP-PCR fingerprinting that were studied by sequencing and phylogenetic analysis of their 16S rRNA, gyrB, dnaK, recA and rpoB housekeeping genes as well as the nodC symbiotic gene. The nearly complete 16S rRNA gene sequence of the four representative strains showed that they are related to Tunisian strains of genus Microvirga isolated from L. micranthus with nucleotide identity values ranging from 98·67 to 97·13%. The single and concatenated sequences of the 16S rRNA, gyrB, dnaK, recA and rpoB housekeeping genes indicated that the L. cosentinii-isolated strains had 99·2-99·9% similarities with the Tunisian L. micranthus microsymbionts. The nodC gene phylogeny revealed that the Moroccan strains clustered in the newly described mediterranense symbiovar, and nodulation tests showed that they nodulated not only L. cosentinii but also L. angustifolius, L. luteus and L. albus. CONCLUSIONS: To the best of our knowledge, this is the first report concerning the isolation, molecular identification and phylogenetic diversity of L. cosentinii nodule-forming endosymbionts and of their description as members of the Microvirga genus. SIGNIFICANCE AND IMPACT OF THE STUDY: In this work, we show that Microvirga sp. can be isolated from root nodules of wild-grown L. cosentinii in Northeast Africa, that selected strains also nodulate L. angustifolius, L. luteus and L. albus, and that they belong to symbiovar mediterranense. In addition, our data support that the ability of Microvirga to nodulate lupines could be related to the soil pH, its geographical distribution being more widespread than expected.
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Lupinus/microbiología , Methylobacteriaceae/fisiología , Simbiosis , ADN Bacteriano/genética , Genes Esenciales/genética , Lupinus/clasificación , Methylobacteriaceae/clasificación , Methylobacteriaceae/genética , Methylobacteriaceae/aislamiento & purificación , Marruecos , Filogenia , ARN Ribosómico 16S/genética , Nódulos de las Raíces de las Plantas/microbiología , Análisis de Secuencia de ADNRESUMEN
Breast cancer (BC) is one of the most complex, diverse and leading cause of death in women worldwide. The present investigation aims to explore genes panel associated with BC in different African regions, and compare them to those studied worldwide. We extracted relevant information from 43 studies performed in Africa using the following criteria: case-control study, association between genetic variations and BC risk. Data were provided on mutations and polymorphisms associated with BC without fixing a specific date. Case-only studies and clinical trials were excluded. Our study revealed that the majority of African BC genetic studies remain restricted to the investigation of BRCA1 and BRCA2 genes and differences in their mutations spectrum. Therefore, it is necessary to encourage African researchers to characterize more genes involved in BC using methods generating global information such as next-generation sequencing in order to guide specific and more effective therapeutic strategies for the African community.
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Replicative senescence is a hallmark of chronic liver diseases including chronic hepatitis B virus (HBV) infection, whereas HBV-encoded oncoproteins HBx and preS2 have been found to overcome senescence. HBx possesses a C-terminal truncation mainly in hepatocellular carcinomas but also in noncancerous liver tissues. Here, by cell counting, BrdU incorporation, MTT proliferation assay, cell cycle analysis, SA-ßgal staining and Western blotting in primary and malignant cells, we investigated the effect of HBx C-terminal mutants on cellular senescence. HBx C-terminal mutants were found to trigger cellular senescence in primary MRC5 cells, and malignant liver cells Huh7, and SK-Hep1. In contrast, these mutants promoted the proliferation of HepG2 malignant liver cells. The pro-senescent effect of HBx relied on an increased p16(INK4a) and p21(Waf1/Cip1) expression, and a decreased phosphorylation of Rb. Together, these results suggest that the two main variants of HBx present in HBV-infected liver possess opposite effects on cellular senescence that depend on the phenotype of infected cells.
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Proliferación Celular/genética , Senescencia Celular/genética , Antígenos de Superficie de la Hepatitis B/genética , Neoplasias Hepáticas/patología , Precursores de Proteínas/genética , Transactivadores/genética , Ciclo Celular , Línea Celular Tumoral , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Hepatocitos/metabolismo , Humanos , Fenotipo , Fosforilación , Regiones Promotoras Genéticas/genética , Precursores de Proteínas/metabolismo , Proteína de Retinoblastoma/metabolismo , Transactivadores/metabolismo , Proteínas Reguladoras y Accesorias Virales , beta-Galactosidasa/metabolismoRESUMEN
INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.
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Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/patología , Nefrolitiasis/complicaciones , Nefrolitiasis/patología , Fosfatos de Calcio/metabolismo , Diagnóstico Diferencial , Humanos , Hiperparatiroidismo Primario/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Nefrolitiasis/diagnóstico por imagen , Nefrolitiasis/metabolismo , Radiografía , RecurrenciaRESUMEN
One of the side effects of the BCG vaccine is a local infection that may spread to the regional lymph nodes causing lymphadenitis, which can resolve spontaneously without treatment. We report the case of an immunocompetent infant who developed lymphadenitis after administration of the BCG vaccine, complicated with persistent symptomatic hypercalcemia in spite of the usual treatment including corticotherapy. Antituberculous treatment was necessary to reduce this hypercalcemia.
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Vacuna BCG/efectos adversos , Hipercalcemia/etiología , Linfadenitis/inducido químicamente , Linfadenitis/complicaciones , Femenino , Humanos , LactanteRESUMEN
Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical manifestations, but overt symptoms may be sparse. One unusual presentation is onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism. This situation can lead to delayed diagnosis, with inefficacity of the antiepileptic drugs. We report five cases of adolescence-onset epilepsy with unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical examination revealed signs of hypocalcemia, confirmed biologically. Full testing disclosed the origin of the seizures: hypoparathyroidism in three patients and pseudohypoparathyroidism in the other two. In four of five patients, computed tomography showed calcification of the basal ganglia, defining Fahr's syndrome. The patients were treated with oral calcium and active vitamin D (1-alphahydroxy vitamin D3). Seizure frequency progressively decreased and serum calcium levels returned to normal. These cases illustrate the importance of the physical examination and of routine serum calcium assay in patients with new-onset epileptic seizures in order to detect hypocalcemia secondary to hypoparathyroidism.
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Enfermedad Celíaca/diagnóstico , Epilepsia Tónico-Clónica/etiología , Hiperfosfatemia/etiología , Hipocalcemia/metabolismo , Hipoparatiroidismo/diagnóstico , Seudohipoparatiroidismo/diagnóstico , Adolescente , Anticonvulsivantes/uso terapéutico , Enfermedades de los Ganglios Basales/sangre , Enfermedades de los Ganglios Basales/etiología , Calcinosis/sangre , Calcinosis/etiología , Enfermedad Celíaca/complicaciones , Epilepsia Tónico-Clónica/tratamiento farmacológico , Femenino , Humanos , Hiperfosfatemia/metabolismo , Hipoparatiroidismo/complicaciones , Hipoparatiroidismo/congénito , Masculino , Seudohipoparatiroidismo/complicaciones , Deficiencia de Vitamina D/etiologíaRESUMEN
Urolithiasis is a frequent pathology with a constantly increasing prevalence in industrial countries. The relapse frequency is around 50 % with a risk of complications. The laboratory input is essential in the determination of the etiology and in the therapeutic monitoring. The morphoconstitutional analysis of the stone is the most important element. It comprises the examination of the stone with binocular loupes and the simultaneous analysis of its crystalline composition. This can be done by different techniques but infrared spectrophotometry is the most powerful. The chemical analysis should be definitely proscribed. The analysis of crystalluria includes the search, the identification and the counting of crystals in fresh morning urines. It is useful for the diagnosis and for the patient follow-up. Finally, the biochemical analyses in urine and serum, in first line or on the basis of the stone composition, are an important part of the etiological exploration and therapeutic monitoring.
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Cálculos Urinarios/química , Urolitiasis/etiología , Pruebas de Química Clínica , Humanos , Orina/químicaRESUMEN
INTRODUCTION: Acute catatonia is a non-specific, relatively frequent syndrome, which manifests itself through characteristic motor signs that enables its diagnosis. It occurs in association with mood disorders, psychotic disorders and several somatic or toxic diseases. Its short-term prognosis is of paramount importance. Without effective treatment, it is associated with high mortality. Despite the vital risk inherent in this disorder, it is not recognized as an independent diagnostic category by international rankings, which makes its diagnostic detection difficult and consequently does not allow adequate therapeutic care. However, if benzodiazepines and electroconvulsive therapy have proved effective in the treatment of acute catatonia, the role of atypical antipsychotics remains controversial. In fact, despite the progress made by the DSM-IV-TR and CIM 10 by the recognition of the etiologic diversity of catatonia, we deplore the absence to date of a consensus on clinical management and therapy of catatonia, which constitutes a source of confusion for practitioners in their approach to catatonic patients. To illustrate the difficulty in supporting these patients, we report here a clinical vignette. CLINICAL FEATURES: Mr. M. aged 21, without psychiatric history, has shown a functional acute psychotic episode involving a delirious and hallucinatory syndrome associated with a marked catatonic dimension. Olanzapine was initiated at a dose of 10mg/d on the nineth day of hospitalization; the clinical picture was complicated by a malignant catatonia justifying the halt of olanzapine and the institution, in intensive units, of 15mg per day of lorazepam. After 72hours, the patient has not responded to this treatment. ECT was expected, but the patient died on the 12th day. DISCUSSION: This case raises a threefold question: the crucial issue of immediate vital prognosis, that of the truthfulness of the positive diagnosis of this psychotic table and finally the issue of therapeutic care, primarily the well-founded or otherwise use of an atypical antipsychotic for the treatment of this type of psychotic disorder. For Mr. M., the clinical diagnosis that he has shown, according to the DSM IV-TR, is brief psychotic disorder "temporary diagnosis". This diagnosis - brief psychotic disorder - does not actually allow for a specific clinical approach to this type of psychotic table. The immediate vital prognosis inherent in the catatonic dimension may not be properly evaluated and the therapeutic conduct may miss the application of the specific treatment of the catatonic syndrome. The proper diagnosis for this type of psychotic disorder would be "catatonia" as proposed by Taylor and Fink, instead of "brief psychotic disorder" if the international rankings have included this disorder as a separate and independent diagnosis. The identification by international rankings of the catatonic syndrome as an independent diagnostic category seems essential for clinicians to allow: its clinical detection, the establishment of a syndromic diagnosis of catatonic disorder, appropriate prognostic evaluation and finally, the application of a suitable therapeutic strategy. Conventional treatment, benzodiazepine- and/or ECT-based, can solve the catatonic episode in a few days, irrespective of its etiology and its severity. Moreover, while all authors agree that conventional antipsychotics may induce a catatonic state or worsen a preexisting catatonia into a malignant catatonia and should thus be avoided for catatonic patients or with prior catatonic episodes, recent data from the literature emphasize the frequent and successful use of atypical antipsychotics, including olanzapine, in various clinical forms of benign catatonia. However, our patient did not respond to treatment with olanzapine and got even more complicated. Was the malignant catatonia that this patient has shown induced by olanzapine ? The answer to this question seems difficult since some authors report the efficacy of olanzapine in malignant catatonia. We wonder if we should have kept olanzapine and strengthen its dosage like Cassidy et al. in 2001 and Suzuki et al. in 2010 for the treatment of the malignant form constituted in this patient rather than having stopped it and used lorazepam as indicated by Taylor and Fink in 2003. IN CONCLUSION: The non-recognition of catatonia as an independent entity, the lack of a therapeutic consensus and the pending issue on the safety and efficacy of atypical antipsychotics in the treatment of catatonia are at the origin of the difficulties of therapeutic support of catatonic patients.
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Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Catatonia/inducido químicamente , Catatonia/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Enfermedad Aguda , Catatonia/diagnóstico , Catatonia/psicología , Resultado Fatal , Hospitalización , Humanos , Masculino , Olanzapina , Pronóstico , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
Hemangiomas are rare benign vascular tumors; there are several types including the capillary hemangiomas, we present the case of an exceptional localization of capillary hemangioma in the middle ear. We report the case of a 60-year-old female which consults for episodes of pulsatile tinnitus, otorragies, and hearing loss of the left ear. The clinical examination revealed a reddish polypoid mass in the left external auditory canal, the radiological tests showed a vascular mass in the middle left ear. The tumor was surgically removed, the histological study revealed a capillary hemangioma. The incidence of hemangiomas in the temporal bone, especially in the middle ear, is exceptional. Medical imaging guides to the vascular nature of these tumors that make confusion with other vascular tumors such as tympanic paragangliomas. The management is often surgical and the final diagnosis is histological.
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Vitamin B(12), or cobalamin, deficiency is often unrecognized because the clinical manifestations are subtle; they are also potentially serious. We report a case of pseudothrombotic microangiopathy related to cobalamin deï¬ciency. Vitamin B(12) deficiency, which is more commonly recognized in the context of malnutrition, should be considered in the context of microangiopathy.
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Microangiopatías Trombóticas/etiología , Deficiencia de Vitamina B 12/complicaciones , Adolescente , Algoritmos , Humanos , Masculino , Deficiencia de Vitamina B 12/diagnósticoAsunto(s)
Aneurisma de la Aorta Torácica/diagnóstico por imagen , Disección Aórtica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Diagnóstico Diferencial , Disnea/diagnóstico por imagen , Disnea/etiología , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Derrame Pleural/diagnóstico por imagenRESUMEN
INTRODUCTION: Primary biliary cirrhosis is a hepatic auto-immune disease which is rarely associated with respiratory complications. CASE REPORT: A 40-year-old woman had a 5-year history of primary biliary cirrhosis. Two years previously, she had begun to experience a chronic cough and dyspnea. On clinical examination, the patient had fever, jaundice and basal pulmonary crackles. Chest X-ray showed bilateral slowly migrating and spreading airspace consolidation refractory to antibiotics. Microbiological investigations evidenced no abnormalities. Routine biological studies revealed an inflammatory syndrome, a mild neutrophilic hyperleukocytosis without hypereosinophilia and a mild hepatitis picture with cholestasis. Antineutrophil cytoplasmic antibody testing and anti-nuclear factor testing were negative. Fibreoptic bronchoscopy showed diffuse bronchial inflammation with no specific pathological pattern at bronchial biopsy. The bronchoalveolar lavage revealed a mixed cellular pattern. The chest computed tomography revealed peribronchial pulmonary consolidation with septal and pleural thickening, suggestive of an organizing pneumonia. The patient was treated with oral corticosteroids which resulted in a prompt clinical improvement and complete resolution of radiographic pulmonary abnormalities within two months. Treatment continued for six months and no relapse was noticed during the six months following the end of treatment. CONCLUSIONS: This case of organizing pneumonia highlights the importance of physicians considering this condition in women with primary biliary cirrhosis complaining of respiratory symptoms in the context of unresolved pneumonia.
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Neumonía en Organización Criptogénica/complicaciones , Cirrosis Hepática Biliar/complicaciones , Adulto , Antiinflamatorios/uso terapéutico , Neumonía en Organización Criptogénica/diagnóstico por imagen , Neumonía en Organización Criptogénica/tratamiento farmacológico , Femenino , Humanos , Cirrosis Hepática Biliar/diagnóstico por imagen , Cirrosis Hepática Biliar/tratamiento farmacológico , Prednisona/uso terapéutico , Radiografía TorácicaRESUMEN
The ingestion of a foreign body (FB) is one of the most frequent childhood accidents requiring urgent care depending on the type and localization. Coins are the most frequent, and disk battery ingestion can lead to a significant risk of complications. FB stagnation in the esophagus entails a major risk of perforation. This article reports a retrospective study of 105 cases of foreign body ingestion admitted to the pediatric gastroenterology unit between November 2002 and June 2010. The average age of these patients was 4 years with a 1.5 sex ratio. Ten patients were followed for esophagus stenosis; the others had no considerable pathological histories. The fibroscopy performed on 104 patients allowed us to visualize the foreign body in 96 cases (91.4%). In the 8 remaining cases, the FB was not found (it had already migrated in the digestive tract). Coins were the most frequent (64.7%). Endoscopic extraction removed 83 FBs (86.4%). In 11 cases, it was pushed towards the stomach, split up in 1 case, and surgery was necessary in only 1 case. The progress of child digestive fibroscopy has decreased both the morbidity related to the ingestion of foreign bodies and the use of surgery. Prevention should be based on educating the parents by informing them about the risk of this kind of accident.
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Cuerpos Extraños , Tracto Gastrointestinal , Niño , Preescolar , Deglución , Femenino , Cuerpos Extraños/diagnóstico , Cuerpos Extraños/etiología , Cuerpos Extraños/terapia , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Right colonic diverticulitis is not a frequent disease and its management is still controversial. In this study we describe our experience. MATERIAL AND METHODS: We retrospectively reviewed all patients operated on because of a right colonic diverticulitis in our surgical unit. All patients were treated laparoscopically. Demographics, diagnostic and surgical results were recorded. RESULTS: Between January 1994 and January 2007, 11 patients (7 males and 4 females) mean age 53 +/- 9 years (range 39-68), ASA 1: 6 patients, ASA 2: 4 patients, ASA 3: one patient, and BMI 27.8 (range 25-31), had right colonic diverticulitis. Four patients underwent emergency operations: one for peritonitis and three with an erroneous diagnosis of acute appendicitis; seven were operated on electively. There were no deaths or complications. The mean postoperative hospital stay was 5.6 days (range, 3-9). After a mean follow-up of 6.3 years (range 1-13) all patients of this series are symptom-free. INTERPRETATION AND CONCLUSION: Right colon diverticulitis diagnosis remains difficult. A pre-operative imaging screening is necessary to successfully face this challenging disease. Laparoscopy is a safe and effective method to treat these patients. Colectomy should be considered a good therapeutic option for right colonic diverticulitis, although a conservative approach could be proposed in selected cases.