ABSTRACT
INTRODUCTION AND OBJECTIVES: The liver imaging reporting data system (LI-RADS) for hepatocellular carcinoma (HCC) was proposed to standardize and enhance consensus of reporting. However, clinical utility of LI-RADS has not been evaluated in Latin America. We therefore sought to compare LI-RADS categories with histopathology findings in liver transplant (LT) explants in a regional center. MATERIALS AND METHODS: Prospective cohort study conducted between 2012 and 2018 in a single center from Argentina including patients with HCC listed for LT. LI-RADS definitions were applied to magnetic resonance images (MRI) or computed tomography (CT) abdominal scans at time of listing and at final pre-LT reassessment and compared to explant pathology findings; specifically, major nodule (NOD1). RESULTS: Of 130 patients with HCC listed for LT (96.1% with cirrhosis and 35.6% with hepatitis C virus infection), 72 underwent LT. Overall, 65% had imaging HCC diagnosis based on MRI (nâ¯=â¯84), 26% with CT (nâ¯=â¯34) and 9% (nâ¯=â¯12) with both methods. Among LT patients with pre-transplant imaging at our institution (nâ¯=â¯42/72), 69% of the NOD1 were LR-5, 21% LR-4 and 10% LR-3. Definite HCC diagnosis was 50% in LR-3 NOD1 (CI 18-90); none presented microvascular invasion. In LR-4 NOD1, HCC was confirmed in 89% (CI 59-98), of which 11% showed microvascular invasion; whereas in LR-5 NOD1 77% (CI 64-87) had confirmed HCC, 17% with microvascular invasion. CONCLUSIONS: LI-RADS was useful to standardize reports; however, no significant differences were observed between LR-4 and LR-5 HCC probability when compared to explant pathology.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Aged , Argentina , Carcinoma, Hepatocellular/surgery , Clinical Decision-Making , Female , Humans , Liver Neoplasms/surgery , Liver Transplantation , Male , Middle Aged , Prospective StudiesABSTRACT
We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated the effects of LMW HA priming on human-tumor-pulsed monocytes-derived dendritic cells (DC/TL) obtained from healthy donors and patients with CRC. LMW HA treatment resulted in an improved maturation state of DC/TL and an enhanced mixed leucocyte reaction activity in vivo. Importantly, pre-conditioning of DC/TL with LMW HA increased their ability to migrate and reduced their attraction to human tumor derived supernatants. These effects were associated with increased CCR7 expression levels in DC. Indeed, a significant increase in migratory response toward CCL21 was observed in LMW HA primed tumor-pulsed monocyte-derived dendritic cells (DC/TL/LMW HA) when compared to LWM HA untreated cells (DC/TL). Moreover, LMW HA priming modulated other mechanisms implicated in DC migration toward lymph nodes such as the metalloproteinase activity. Furthermore, it also resulted in a significant reduction in DC migratory capacity toward tumor supernatant and IL8 in vitro. Consistently, LMW HA dramatically enhanced in vivo DC recruitment to tumor-regional lymph nodes and reduced DC migration toward tumor tissue. This study shows that LMW HA--a poorly immunogenic molecule--represents a promising candidate to improve human DC maturation protocols in the context of DC-based vaccines development, due to its ability to enhance their immunogenic properties as well as their migratory capacity toward lymph nodes instead of tumors.
Subject(s)
Cell Movement/drug effects , Colorectal Neoplasms/immunology , Dendritic Cells/drug effects , Hyaluronic Acid/pharmacology , Culture Media , Humans , Tumor Cells, Cultured , Tumor MicroenvironmentABSTRACT
Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.
ABSTRACT
Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.
Subject(s)
Antitubercular Agents/adverse effects , Isoniazid/adverse effects , Liver Failure, Acute/chemically induced , Pyrazinamide/adverse effects , Rifampin/adverse effects , Child , Female , HumansABSTRACT
La toxicidad hepática por isoniacida, sobre todo asociada a rifampicina, es un raro efecto adverso de la terapia antituberculosa. En EE.UU., es la causa de 0,2% de los trasplantes hepáticos pediátricos y del 14% de los trasplantes por toxicidad medicamentosa. Comunicamos el caso de una paciente de 10 años de edad con falla hepática fulminante que requirió trasplante hepático luego de cuarenta días de tratamiento tuberculostático con isoniacida, rifampicina y pirazinamida.
Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.
Subject(s)
Child , Female , Humans , Antitubercular Agents/adverse effects , Isoniazid/adverse effects , Liver Failure, Acute/chemically induced , Pyrazinamide/adverse effects , Rifampin/adverse effectsABSTRACT
La toxicidad hepática por isoniacida, sobre todo asociada a rifampicina, es un raro efecto adverso de la terapia antituberculosa. En EE.UU., es la causa de 0,2% de los trasplantes hepáticos pediátricos y del 14% de los trasplantes por toxicidad medicamentosa. Comunicamos el caso de una paciente de 10 años de edad con falla hepática fulminante que requirió trasplante hepático luego de cuarenta días de tratamiento tuberculostático con isoniacida, rifampicina y pirazinamida.(AU)
Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.(AU)
Subject(s)
Child , Female , Humans , Antitubercular Agents/adverse effects , Isoniazid/adverse effects , Liver Failure, Acute/chemically induced , Pyrazinamide/adverse effects , Rifampin/adverse effectsABSTRACT
La toxicidad hepática por isoniacida, sobre todo asociada a rifampicina, es un raro efecto adverso de la terapia antituberculosa. En EE.UU., es la causa de 0,2% de los trasplantes hepáticos pediátricos y del 14% de los trasplantes por toxicidad medicamentosa. Comunicamos el caso de una paciente de 10 años de edad con falla hepática fulminante que requirió trasplante hepático luego de cuarenta días de tratamiento tuberculostático con isoniacida, rifampicina y pirazinamida.(AU)
Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.(AU)
ABSTRACT
Se realizaron autotrasplante de riñón en 12 perros, divididos en dos grupos iguales: en el 1ro. se utilizó eurocollins como solución de preservación y en el 2do. la solución de la Universidad de Wisconsin. Se evaluaron la sobrevida, el volúmen urinario promedio en las 3 hs. posteriores a la nueva perfusión, la creatina sérica y el flujo en la arteria renal. Los resultados fueron estadísticamente significativos a favor del 2do. grupo. Se confirman los buenos resultados en el uso clínico en la preservación de riñones, páncreas e hígado con la solución Universidad de Wisconsin.
Subject(s)
Dogs , Animals , Male , Female , Renal Circulation , Nephrectomy , Kidney/transplantation , Freezing , Hypertonic Solutions , Organ Preservation/methodsABSTRACT
Se realizaron autotrasplante de riñón en 12 perros, divididos en dos grupos iguales: en el 1ro. se utilizó eurocollins como solución de preservación y en el 2do. la solución de la Universidad de Wisconsin. Se evaluaron la sobrevida, el volúmen urinario promedio en las 3 hs. posteriores a la nueva perfusión, la creatina sérica y el flujo en la arteria renal. Los resultados fueron estadísticamente significativos a favor del 2do. grupo. Se confirman los buenos resultados en el uso clínico en la preservación de riñones, páncreas e hígado con la solución Universidad de Wisconsin. (AU)
Subject(s)
Dogs , Animals , Male , Female , Kidney , Nephrectomy , Renal Circulation/drug effects , Organ Preservation/methods , Hypertonic Solutions , FreezingABSTRACT
Se estudió el efecto de la 16.16 dimetil PGE2 sobre la diferencia de potencial de la mucosa gástrica de la rata previamente tratada con aspirina, hipovolemia o ambas. Previamente se determinó la dosis máxima de PGE2 sin efecto sobre la secrección gástrica en ratas Shay de 4 horas, siendo de 50 ug/kg. La administración de la PGE2 a dosis no antisecretorias demostró su acción protectora sobre el efecto de la aspirina, no así en la rata hipoolémica en donde no se consigue elevar significativamente la caída de la diferencia de potencial transmucosa. Se discuten los diversos mecanismos citoprotectores involucrados que pudieran explicar los resultados obtenidos
Subject(s)
Rats , Animals , Gastric Mucosa/drug effects , Prostaglandins/pharmacologyABSTRACT
Se estudió el efecto de la 16.16 dimetil PGE2 sobre la diferencia de potencial de la mucosa gástrica de la rata previamente tratada con aspirina, hipovolemia o ambas. Previamente se determinó la dosis máxima de PGE2 sin efecto sobre la secrección gástrica en ratas Shay de 4 horas, siendo de 50 ug/kg. La administración de la PGE2 a dosis no antisecretorias demostró su acción protectora sobre el efecto de la aspirina, no así en la rata hipoolémica en donde no se consigue elevar significativamente la caída de la diferencia de potencial transmucosa. Se discuten los diversos mecanismos citoprotectores involucrados que pudieran explicar los resultados obtenidos (AU)
