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OBJECTIVE: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). BACKGROUND: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. METHODS: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054). RESULTS: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. CONCLUSION: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.
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Trasplante de Hígado , Humanos , Muerte Encefálica , Preservación de Órganos , Supervivencia de Injerto , Donantes de Tejidos , Hígado , PerfusiónRESUMEN
Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
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Colangitis Esclerosante , Síndrome de Fatiga Crónica , Cirrosis Hepática Biliar , Trasplante de Hígado , Adulto , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/cirugía , Femenino , Humanos , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/cirugía , Trasplante de Hígado/efectos adversos , Masculino , Calidad de VidaRESUMEN
BACKGROUND AND AIMS: Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two-dimensional shear wave elastography (2D-SWE), are used to quantify liver fibrosis. Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D-SWE. Here, we compare liver and spleen 2D-SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH. METHODS: We analysed liver and spleen 2D-SWE in relation to liver TE in 90 patients treated ≥ 6 months for AIH. Liver and spleen 2D-SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18 months follow-up. RESULTS: Liver 2D-SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P < .001) but there was no link between spleen 2D-SWE and ALT. Liver 2D-SWE, but not spleen 2D-SWE, was associated with histopathological inflammatory score (P < .01). When compared to LB, the optimal cut-offs for detecting cirrhosis by liver and spleen 2D-SWE were 16.1 kPa (AUROC 0.93) and 29.8 kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D-SWE had significantly better AUROC for detecting cirrhosis than liver 2D-SWE alone. CONCLUSIONS: Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.
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Diagnóstico por Imagen de Elasticidad , Hepatitis Autoinmune , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/patología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , BazoRESUMEN
Immunoglobulin G4-related disease (IgG4-RD) is a comparatively new condition that may involve more than one organ. The lack of characteristic, pathognomonic clinical symptoms may delay the diagnosis of this disease. The diagnosis is based upon clinical manifestation, elevated serum levels of IgG4 and histopathologic examination with immunohistochemical staining to reveal infiltration of IgG4-positive plasma cells. The first line treatment is oral glucocorticoids. A CASE REPORT: 38-year-old woman with Hashimoto disease, chronic sinusitis and chronic hepatitis of unknown etiology was admitted to the Department of Endocrinology because of moderate eyelids swelling accompanied by redness for 3 years. Graves' orbitopathy and systemic vasculitis were suspected, however both were excluded (negative antibodies results: anty-TSHR, ANCA, ANA). Serologic investigation of Sjögren's syndrome was also negative. In Magnetic Resonance Imaging (MRI) of orbits there were described bilateral mild extension of lateral rectus muscles, normal signal of adipose tissue and bilateral lacrimal glands enlargement. Moreover, increased IgG4 serum levels were detected. The material derived from perinasal sinuses surgery was analyzed in histopathology examination with immunohistochemical staining, which revealed characteristic features of chronic inflammatory process and increased numbers of IgG4 - positive plasma cells (>50 in a large field of view). The diagnosis of IgG4-RD was established. Because of non-effective oral methylprednisolone therapy in the past, the patient was referred to Clinic of Rheumatology for further treatment. After the therapy with methylprednisolone and azathioprine there were observed the significant reduction of symptoms. CONCLUSIONS: Because of lack of characteristic symptoms of IgG4- RD, it should be always considered in differential diagnosis of chronic inflammatory diseases of various organs.
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Enfermedades Autoinmunes/complicaciones , Enfermedad de Hashimoto/etiología , Hepatitis/etiología , Inmunoglobulina G , Sinusitis/etiología , Adulto , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Azatioprina/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Metilprednisolona/uso terapéuticoRESUMEN
Leflunomide is a disease-modifying anti-rheumatic drug that is used in patients with rheumatoid arthritis (RA), who do not respond well to standard RA treatment. Leflunomide therapy may, however, be related with significant pulmonary complications in predisposed individuals. We present a patient with RA treated with leflunomide, in whom leflunomide lung injury had a fatal outcome. Potential risk factors for pulmonary complications of leflunomide treatment and the management of patients with leflunomide lung injury are discussed.
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Adyuvantes Inmunológicos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Isoxazoles/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/diagnóstico , Adyuvantes Inmunológicos/administración & dosificación , Resultado Fatal , Humanos , Isoxazoles/administración & dosificación , Leflunamida , Masculino , Persona de Mediana Edad , Radiografía TorácicaRESUMEN
INTRODUCTION: According to the WHO, almost a third of the world population are thought to be infected with Mycobacterium tuberculosis. Some studies of the prevalence of latent tuberculosis infection (LTBI) have already been performed in Poland, showing that almost a quarter of the Mazovia population could be infected. It also indicated a higher prevalence of LTBI among seniors. Those studies were based on indirect diagnostic methods. MATERIAL AND METHODS: We randomly collected hilar lymph nodes from decedents aged 40 years and older during post-mortem examination. We excluded patients with previous confirmed tuberculosis. In addition, an autopsy was performed in all patients. Finally, we used real-time PCR Xpert MTB/RIF (Cepheid, USA) for the specific capture of mycobacterial DNA. RESULTS: Twenty-two of 23 patients had a negative result of the real-time PCR examination and no signs of caseous necrosis in hilar lymph nodes. We found the only positive sample in a patient with histopathological signs of tuberculosis (the presence of caseous necrosis in the specimens obtained from lymph nodes and lung). Due to the change of cartridges from version G3 to G4, further reactions were inhibited and no more post-mortem samples were tested. CONCLUSIONS: Real-time PCR Xpert MTB/RIF was capable of detecting M. tuberculosis complex DNA in a patient with tuberculosis recognised on autopsy. In the remaining patients, no M. tuberculosis complex DNA was found, in accordance with negative results of histological examination. Since the technology of cartridges has changed, it is no longer possible to use real-time PCR Xpert MTB/RIF (Cepheid USA) on post-mortem material.
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ADN Bacteriano/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Tuberculosis/microbiología , Adulto , Autopsia , Femenino , Humanos , Masculino , Tuberculosis/diagnósticoRESUMEN
BACKGROUND: Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. The aim of this study was to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts. METHODS: This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. RESULTS: A total of 36 patients developed biliary complications (at least one event) - 6 events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7% vs. 43.4% [P=0.11]). No differences were found significant with respect to anastomotic (19.9% vs. 33.7% [P=0.20]) and non-anastomotic strictures (0% vs. 11.1% [P=0.10]) as well as biliary fistulas (11.7% vs. 12.2% [P=0.93]). Survival analysis did not show significantly different result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038). CONCLUSIONS: The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for benefits of dHOPE in low-risk grafts.
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Takotsubo syndrome (TTS) is associated with inflammatory response, therefore the aim of the study was to evaluate the presence and dynamics of inflammatory-associated forms of cell death, necroptosis, and pyroptosis in the female rat model of isoprenaline (ISO)-induced TTS. TTS was induced in female Sprague Dawley rats (n = 36) by ISO 150 mg/kg intraperitoneally. Animals were divided into four groups: TTSO (TTS+ovariectomy; n = 10), TTSP (TTS+sham operation; n = 10), CO (0.9% NaCl+ovariectomy; n = 8), CP (0.9% NaCl+sham operation; n = 8). Histopathological analysis, evaluation of plasma concentration, and myocardial expression of pyroptosis- and necroptosis-associated proteins were performed. TTSO and TTSP groups had higher plasma concentrations of interleukin-1ß in comparison with the controls. Low myocardial protein expression of mixed lineage kinase domain-like pseudokinase (MLKL), caspase-1 (Casp-1), and calcium/calmodulin-dependent kinase type II isoform delta (CAMKIIδ) was visible 6 and/or 12 h post-ISO. Twenty-four hours post-ISO, high myocardial and vascular protein expression of CAMKIIδ was visible in TTSO but not TTSP rats, while high myocardial expression of MLKL and Casp-1 was visible both in TTSO and TTSP rats. The course of TTS is associated with activation of inflammatory-associated programmed cell death, necroptosis, and pyroptosis, therefore inflammation may be a primary response occurring simultaneously with cardiomyocyte death in TTS.
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Introduction: Calcifying nested stromal epithelial tumor (CNSET) is an extremely rare diagnosis among patients treated for primary hepatic neoplasms. There are only 45 cases reported worldwide. Histopathological characteristics are well-demarcated nests of spindle and epithelioid cells in a dense desmoplastic stroma with variable calcification and ossification. It is mostly diagnosed in children and young females. Treatment strategies implemented for the management of CNSET include radiofrequency ablation, transarterial chemoembolization, surgical resection, adjuvant and neoadjuvant chemotherapy, and liver transplantation. Given the small number of available cases, there are still no established standards of treatment for this neoplasm. Case Presentation: A 28-year-old female diagnosed with CNSET presented mild abdominal pain, with normal laboratory values. The tumor was initially deemed unresectable, therefore, the patient was disqualified from liver resection. Further deterioration of the patient's clinical condition and local tumor progression led to qualification for liver transplantation. The patient underwent liver transplantation 1 year following initial diagnosis and a 12 months recurrence-free period was observed. During the course of treatment, she did not receive systemic chemotherapy, radiotherapy, or loco-regional treatment. Conclusion: Multiple strategies have been implemented for the treatment of CNSET, with liver resection providing the best outcomes. Transarterial chemoembolization, radiofrequency ablation, and radiotherapy are reported to be insufficient in the management of this tumor. Various chemotherapy regimens turned out to be ineffective as well. There have been only eight reported cases of patients undergoing liver transplantation for CNSET, with tumor recurrence in two cases. CNSET appears to be a neoplasm with low malignancy potential, although an aggressive progression has subsequently been reported. Further investigation is still required in this field.
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A 44-year-old woman was admitted to hospital with end-stage renal failure, productive cough, and decreased exercise tolerance. She had owned nine cats, which resulted in long-term exposure (18 years) to silica-containing bentonite cat litter. High-resolution computed tomography of the chest showed micronodular lesions in the lungs, and mild mediastinal lymphadenopathy. A lung biopsy revealed multinucleated giant cells, some of which had birefringent material and Schaumann bodies. X-ray photoelectron spectroscopy revealed the presence of silicon in the lung biopsy specimen, as well as in the patient's cat litter. The pulmonary condition was suggestive of sarcoid-like lung disease, rather than silicosis, sarcoidosis, or hypersensitivity pneumonitis, according to the clinicopathological findings. Renal failure appeared to be a result of chronic hypercalcemia due to extrarenal calcitriol overproduction in activated alveolar macrophages. Ultimately, the patient was diagnosed with sarcoid-like lung disease complicated by end-stage renal failure from exposure to bentonite cat litter. Therapy with steroids, in addition to elimination of the bentonite cat litter exposure, resulted in a significant improvement in the health condition. At a follow-up visit after 4 months, an almost complete resolution of the lung lesions and a significant improvement in renal function were observed.
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Fallo Renal Crónico , Enfermedades Pulmonares , Sarcoidosis , Enfermedades de la Piel , Bentonita , Calcitriol , Femenino , Humanos , Sarcoidosis/diagnóstico , Silicio , Dióxido de Silicio/toxicidadRESUMEN
BACKGROUND: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. METHODS: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. RESULTS: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084). CONCLUSIONS: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.
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Cardiomiopatía de Takotsubo , Animales , Ecocardiografía , Femenino , Humanos , Isoproterenol/efectos adversos , Masculino , Miocitos Cardíacos , Ratas , Ratas Sprague-Dawley , Cardiomiopatía de Takotsubo/inducido químicamente , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/diagnósticoRESUMEN
BACKGROUND: Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary neoplasm of the bile duct (IPN-B) are two different types of mucin-producing bile duct tumour that may complicate the course of pregnancy. To the best of our knowledge, we describe herein the first case of MCN-L with spontaneous rupture during pregnancy necessitating complex surgical treatment. CASE SUMMARY: A 24-year-old woman was initially admitted to another hospital in October 2018 with signs of jaundice (serum bilirubin level 12 mg/dL) and upper abdominal pain radiating to the left shoulder. Initial magnetic resonance imaging (MRI) of the abdominal cavity revealed a multilocular cystic tumour of the liver hilum (37 mm × 40 mm in diameter) located between segments 3 and 4 of the left liver lobe. Six weeks later (December 2018), the patient was found to be 12 wk pregnant and was referred to our institution for further diagnostics and treatment. At admission, a soft, palpable, and tender mass in the left upper abdomen was found. It was determined via MRI (with no intravenous contrast in view of the first-trimester pregnancy) to be a large collection of fluid (19 cm × 17 cm × 10 cm) located close to the liver hilum and below the left liver lobe. The patient did not undergo any diagnostic or therapeutic procedures nor did they have any abdominal trauma in the preceding weeks. The fluid collection proved to be of biliary origin following percutaneous drainage. Therefore, we concluded this was a spontaneous rupture of an MCN-L with the formation of a biloma. The MRI study also revealed the previously found cystic tumour of the liver hilum communicating with the left hepatic duct, which, together with left hepatic duct dilatation, suggested the diagnosis of IPN-B. The follow-up MRI with intravenous gadolinium contrast performed in the second trimester of pregnancy (week 14) showed, in turn, some features of MCN-L, including enhancement of the internal septations within the cystic liver mass. A precise preoperative differential diagnosis between IPN-B and MCN-L was therefore not possible. The patient was submitted to surgery in the second trimester of pregnancy (week 18). Surgery included a cholecystectomy, left hepatectomy, and concomitant resection of the extrahepatic bile ducts followed by anastomosis of the right hepatic duct with the Roux limb of the jejunum. The post-operative period was uneventful and the patient was discharged 8 days after surgery. The histopathological examination of the resected specimen revealed a final diagnosis of MCN-L with low-grade dysplasia and epithelium surrounded by ovarian-type stromal tissue. The patient delivered a healthy baby girl and both remain well at present, after 2 years of follow-up since surgery. CONCLUSION: The differential diagnosis and management of MCN-L and IPN-B may be very challenging, particularly in the setting of pregnancy. When indications for surgery are obvious, the final diagnosis is based on histopathological examination, with ovarian-type stroma being pathognomonic for MCN-L. We believe that the growth of this subepithelial stroma secondary to the high levels of sex hormones produced during pregnancy might have been the main causative factor leading to the tumour rupture with the formation of a biloma in our patient.
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OBJECTIVES: Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson's disease. To evaluate the accuracy of collagen proportionate area (CPA), transient elastography and shear wave elastography (SWE) in the assessment of liver fibrosis in adult patients with Wilson's disease. METHODS: In this retrospective study of 60 patients with Wilson's disease, results of percutaneous cutting liver biopsy assessed using the Ishak fibrosis score and CPA were compared with liver stiffness measured with transient elastography and SWE. RESULTS: CPA correlated with the Ishak score (r = 0.45; P = 0.001) and transient elastography results correlated with SWE measurements (r = 0.80; P = 0.0001). In contrast, transient elastography or SWE did not significantly correlate with the Ishak score or CPA. CONCLUSION: Collagen content assessment may be useful for estimation of liver fibrosis in patients with Wilson's disease. However, single time-point elastographic liver stiffness measurements have a limited diagnostic value in Wilson's disease.
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Diagnóstico por Imagen de Elasticidad , Degeneración Hepatolenticular , Adulto , Biopsia , Degeneración Hepatolenticular/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH.
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Antioxidantes/metabolismo , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Hepatitis Autoinmune/genética , Cirrosis Hepática/genética , Proteínas Mitocondriales/genética , Oxidorreductasas/genética , Polimorfismo Genético/genética , Polimorfismo Genético/fisiología , Adolescente , Adulto , Anciano , Niño , Femenino , Genotipo , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/metabolismo , Hepatitis Autoinmune/prevención & control , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/prevención & control , Masculino , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
BACKGROUND Central nervous system ischemia in acute pancreatitis is rare with only a handful of cases reported in the literature. We report a case of spinal cord ischemia due to microvascular thrombosis complicating acute on chronic pancreatitis. CASE REPORT A 37-year-old male was transferred to a university hospital intensive care unit with a diagnosis of acute onset chronic pancreatitis, paraplegia, and multi-organ failure. Laboratory studies showed elevated serum amylase activity and leukocytosis. The patient deteriorated quickly and anemia with thrombocytopenia and coagulation abnormalities developed. Computed tomography showed large pancreatic pseudocyst and ischemic lesions in abdominal organs. Symptoms of paraplegia preceded by the bilateral paresis were noted 7 days from the onset of his disease and magnetic resonance imaging showed ischemia involving the central part of the medullary cone resulting from microvascular thrombosis. The patient underwent endoscopic retrograde cholangiopancreatography and repeated surgery with a number of complications but 2 months later was discharged to rehabilitation center due to persistent neurologic deficit. CONCLUSIONS Patients with severe pancreatitis and multiorgan failure requiring intensive care should undergo routine neurological examination to identify and treat deficits early.
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Pancreatitis Aguda Necrotizante/complicaciones , Isquemia de la Médula Espinal/etiología , Microangiopatías Trombóticas/complicaciones , Adulto , Coagulación Intravascular Diseminada/complicaciones , Coagulación Intravascular Diseminada/etiología , Humanos , Masculino , Trombocitopenia/etiología , Microangiopatías Trombóticas/etiologíaRESUMEN
BACKGROUND: Extra-appendiceal colorectal neuroendocrine tumors are rare neoplasms with a variable biological behavior. MATERIALS AND METHODS: The study group consisted of 15 patients with an extra-appendiceal colorectal neuroendocrine tumor who underwent surgical resection (M/F=3:12, mean age=62.9 years). Lower-grade neuroendocrine tumors and neuroendocrine carcinomas were recognized in 5 and 10 patients, respectively. Data were evaluated retrospectively with regard to clinical and pathologic characteristics and outcomes. RESULTS: The median age of the patients with lower-grade NETs was significantly lower than that in patients with NECs (53 yr vs. 68 yr, p=0.03). NETs G1-G2 were significantly smaller than neuroendocrine carcinomas (4.0 cm vs. 6.4 cm, p=0.02). There were no differences between lower-grade NETs and NECs with regard to tumor location, rate of nodal involvement and distant metastases. All the patients underwent open segmental resection of the colon or rectum. Complete resection was achieved in 3 of 5 patients from the lower-grade NET group, and in 5 of 10 patients in the NEC group. Overall survival was significantly better for lower-grade NETs tumors (p=0.005). The median survival was 4.8 months in the NEC group. The median survival in the lower-grade NET group was not achieved after a median follow-up of 69 months. Three-year overall survival was 100% for lower-grade NETs, and only 27% for NECs. CONCLUSION: Lower-grade neuroendocrine tumors seem to exhibit comparable potential for dissemination as neuroendocrine carcinomas, but prognostic implications of metastases are distinct.
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Neoplasias del Apéndice/cirugía , Carcinoma Neuroendocrino/cirugía , Neoplasias Colorrectales/cirugía , Anciano , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/patología , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recto/patología , Tasa de SupervivenciaRESUMEN
AIMS: Toll-like receptors (TLR) and apoptosis were indicated as important factors in heart failure. Our aim was to characterize the morphological pattern of apoptosis, TLR2, TLR4, and TLR6 expression in female rat hearts in the model of takotsubo syndrome (TTS). MAIN METHODS: 60 Sprague-Dawley female rats were treated with a single dose of 150â¯mg/kg b.wt. of isoprenaline (ISO) or 0.9% NaCl (controls). Hearts were collected 24, 48, 72â¯h and 7â¯days post-ISO injection. 32/60 hearts were used in immunohistopathological studies and 28/60 in real time. KEY FINDINGS: Apoptosis was observed 24â¯h post-ISO in cardiomyocytes, 24, 48, 72â¯h and 7â¯days post-ISO in infiltrating inflammatory cells, 7â¯days post-ISO in endothelial cells of vessels. Diffuse TLR4CD68 (CD68, a macrophage marker) and TLR6CD68 positive cells and TLR2, TLR4, TLR6 mononuclear cells were observed in both acute and recovery phase of TTS. In the foci located in the neighborhood of damaged (necrotic/apoptotic) cardiomyocytes in TTS, high (strong) protein expression of TLR2 (TLR2high) was observed: 24, 48, 72â¯h post-ISO; TLR4high - 48 and 72â¯h post-ISO; TLR6high - 48â¯h post-ISO. Whereas in cardiomyocytes of remote myocardium: TLR2high - 72â¯h post-ISO; TLR4high - 24 and 72â¯h post-ISO; TLR6high - 24â¯h post-ISO. TLR2 mRNA was down-regulated 48 and 72â¯h post-ISO whereas TLR4 up-regulated 7â¯days post-ISO. SIGNIFICANCE: The expression pattern of apoptosis and TLR differs in the course of TTS in comparison with the control rats. We hypothesize that innate immunity and apoptosis may play a crucial role in TTS pathophysiology.
Asunto(s)
Apoptosis/fisiología , Isoproterenol/toxicidad , Miocitos Cardíacos/metabolismo , Cardiomiopatía de Takotsubo/diagnóstico por imagen , Cardiomiopatía de Takotsubo/metabolismo , Receptores Toll-Like/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Expresión Génica , Corazón/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-Dawley , Cardiomiopatía de Takotsubo/inducido químicamente , Receptores Toll-Like/genéticaRESUMEN
True epithelial-lined cysts are rare forms of adrenal cystic lesions, the pathogenesis of which is still not fully understood. In this report we present a case of an adrenal cyst diagnosed incidentally on imaging in a 31-year-old, previously healthy, obese woman. Due to non-specific hormonal disorders and enlargement of the lesion, a right-sided laparoscopic adrenalectomy was performed. The cyst was lined predominantly by ciliated cuboidal-to-columnar, Müllerian-type epithelium, and focally by flat-to-cuboidal, mesothelium-like lining. Immunohistochemistry demonstrated a strong positive reaction in the cells of both types of lining for CKAE1+E3, CK19, CK7 and WT1, and both had a negative reaction for CK20, CD34, Melan-A, SF1, TTF1, SMA and CDX2. The cells of the ciliated cuboidal-to-columnar epithelium were strongly positive for PAX8, ER, Ep-CAM and EMA, focally positive for PR, and were negative for calretinin, whereas the cells of the flat-to-cuboidal lining were positive for calretinin and podoplanin and showed only a weak positive response in individual cells for PAX8, EMA and Ep-CAM, but were negative for ER and PR. This is the first reported case of an adrenal ciliated epithelial cyst with Müllerian differentiation (confirmed immunohistochemically) in the English literature. The differences in morphology and immunophenotype of the two types of lining (epithelial Müllerian phenotype versus mesothelial phenotype), suggest that some adrenal epithelial cysts probably form due to metaplasia of mesothelium-derived lining. A similar mechanism may also be involved in the pathogenesis of at least some of the so-called Müllerian cysts (or inclusions) in other locations.
Asunto(s)
Enfermedades de las Glándulas Suprarrenales/patología , Quistes/patología , Adulto , Biomarcadores/análisis , Diferenciación Celular , Epitelio/patología , Femenino , Humanos , InmunohistoquímicaRESUMEN
Epithelial- lined (true) cysts are rare lesions and until now the only information we had about their histogenesis was based on the analysis of a few cases. We retrospectively reviewed 8 cases of cysts with a true epithelial lining (confirmed immunohistochemically). The pathological findings and immunohistochemical analysis of the epithelial linings allowed for categorization of the cysts into 3 groups. Five cysts had pure mesothelial lining, which was flattened to cuboidal, and demonstrated a positive reaction for mesothelial markers (eg. calretinin, WT1), and a negative reaction for EpCAM, EMA, PAX8 and ER. Two cysts had cuboidal to flattened lining, the cells of which were diffusely or focally positive for mesothelial markers, for some epithelial markers (eg. EpCAM and EMA) and despite a lack of müllerian-type epithelium demonstrated a positive reaction for PAX8 and focally for ER. A cyst derived from adreno-hepatic fusion (AHF)-related intra-adrenal bile ductules was diagnosed in a right adrenal gland which was directly adherent to the liver, microscopically features of AHF were visible with intermingling of adrenal and liver parenchymal cells. The immunoreactivity pattern was similar among the preserved cells of the cyst-lining, the intra-adrenal bile ductules and the normal bile ductules in the adjoining liver parenchyma. On the basis of this case series from a single institution (8 presented now and 1 reported before) we propose a new histogenetic categorization of adrenal epithelial cysts into: 1. pure mesothelial cysts (the most common type), 2. mesothelial cysts with incomplete or complete müllerian metaplasia 3. AHF-related cysts.