RESUMEN
Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notch signaling pathway. Quinomycin treatment resulted in significant inhibition of proliferation and colony formation in pancreatic cancer cell lines, but not in normal pancreatic epithelial cells. Moreover, Quinomycin affected pancreatosphere formation. The compound also decreased the expression of CSC marker proteins DCLK1, CD44, CD24 and EPCAM. In addition, flow cytometry studies demonstrated that Quinomycin reduced the number of DCLK1+ cells. Furthermore, levels of Notch 1-4 receptors, their ligands Jagged1, Jagged2, DLL1, DLL3, DLL4 and the downstream target protein Hes-1 were reduced. The γ-secretase complex proteins, Presenilin 1, Nicastrin, Pen2, and APH-1, required for Notch activation also exhibited decreased expression. Ectopic expression of the Notch Intracellular Domain (NICD) partially rescued the cells from Quinomycin mediated growth suppression. To determine the effect of Quinomycin on tumor growth in vivo, nude mice carrying tumor xenografts were administered Quinomycin intraperitoneally every day for 21 days. Treatment with the compound significantly inhibited tumor xenograft growth, coupled with significant reduction in the expression of CSC markers and Notch signaling proteins. Together, these data suggest that Quinomycin is a potent inhibitor of pancreatic cancer that targets the stem cells by inhibiting Notch signaling proteins.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Equinomicina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Receptores Notch/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Antígeno CD24/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Quinasas Similares a Doblecortina , Resistencia a Antineoplásicos , Molécula de Adhesión Celular Epitelial/metabolismo , Citometría de Flujo , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Receptores de Hialuranos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Células Madre Neoplásicas , Páncreas/patología , Neoplasias Pancreáticas/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores Notch/metabolismo , Trasplante HeterólogoRESUMEN
BACKGROUND: There is a paucity of data on long-term management of type 1 autoimmune pancreatitis (AIP), a relapsing steroid-responsive disorder. OBJECTIVE: We describe our experience with treatment of relapses and maintenance of remission using steroid-sparing immunomodulators (IMs) and induction of remission using rituximab (RTX). METHODS: We obtained details of disease relapse and treatment in 116 type 1 AIP patients from clinic visits, medical records and telephone interviews. We compared relapse free survival in those treated with IMs versus those treated with steroids alone, assessed patients' response to RTX, and identified treatment-related complications. RESULTS: During a median follow-up of 47 months, 52/116 AIP patients experienced 76 relapse episodes. The first relapse was treated with another course of steroids in 24 patients, and with steroids plus IM in another 27 patients; subsequent relapse-free survival until a second relapse was similar in the two groups (p=0.23). 38 patients received an IM for >2 months; failure or intolerance of IM therapy occurred in 17 (45%). 12 patients with steroid or IM intolerance/resistance were treated with RTX, an antiCD20 antibody; 10 (83%) experienced complete remission and had no relapses while on maintenance therapy. Treatment-limiting side effects related to RTX were uncommon. CONCLUSIONS: In type 1 AIP relapses are common. Relapse-free survival is similar in those treated with steroids plus IM compared to those treated with steroids alone. Nearly half the patients on IMs will relapse during treatment. RTX is effective in the treatment of both IM resistant and steroid intolerant patients.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Pancreatitis Crónica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Enfermedades Autoinmunes/diagnóstico por imagen , Colangitis Esclerosante/tratamiento farmacológico , Evaluación de Medicamentos/métodos , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulina G/sangre , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pancreatitis Crónica/diagnóstico por imagen , Prednisona/uso terapéutico , Radiografía , Recurrencia , Inducción de Remisión , Rituximab , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Autoimmune pancreatitis (AIP) has been classified into type 1 and type 2 subtypes. Serum immunoglobulin G4 (IgG4) elevation characterizes type 1 AIP. Type 2 AIP and a subset of type 1 AIP are seronegative, i.e., have normal serum IgG4 levels. AIM: We compared the profiles of the three subsets of AIP to identify the unique characteristics of seronegative type 1 AIP and type 2 AIP. METHODS: We compared the clinical profiles of 69 seropositive type 1 AIP patients, 21 seronegative type 1 AIP patients and 22 type 2 AIP patients. RESULTS: Among type 1 AIP, seronegative group had similar clinical profiles when compared to seropositive group except that they were more likely to undergo surgical resection than seropositive patients (p = 0.001). Seronegative type I AIP patients were older (61.9 ± 13.7 vs 45.3 ± 17.4; p = 0.004), and differed in the occurrence of other organ involvement (OOI) (71.4% vs 0%; p < 0.001) and disease relapse (33.3% vs 0%; p = 0.005) when compared with type 2 AIP. All seronegative type 1 AIP patients had at least one of the following -OOI, disease relapse, and age >50 years while none of the type 2 AIP had OOI or disease relapse. CONCLUSIONS: Seronegative and seropositive type 1 AIP patients have similar clinical profiles, which are distinct from that of type 2 AIP. Among the seronegative AIP group, patients are more likely to have type 1 AIP rather than type 2 AIP if they are older than 50 years or have OOI or disease relapse.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Inmunoglobulina G/sangre , Pancreatitis/inmunología , Adulto , Factores de Edad , Anciano , Enfermedades Autoinmunes/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/inmunología , Páncreas/patología , Pancreatitis/patología , Pancreatitis/terapia , Células Plasmáticas/patología , Prednisona/uso terapéutico , RecurrenciaRESUMEN
Despite advances in molecular pathogenesis, pancreatic cancer remains a major unsolved health problem. It is a rapidly invasive, metastatic tumor that is resistant to standard therapies. The phosphatidylinositol-3-kinase/Akt and mTOR signaling pathways are frequently dysregulated in pancreatic cancer. Gemcitabine is the mainstay treatment for metastatic pancreatic cancer. P276 is a novel CDK inhibitor that induces G(2)/M arrest and inhibits tumor growth in vivo models. Here, we determined that P276 sensitizes pancreatic cancer cells to gemcitabine-induced apoptosis, a mechanism-mediated through inhibition of Akt-mTOR signaling. In vitro, the combination of P276 and gemcitabine resulted in a dose- and time-dependent inhibition of proliferation and colony formation of pancreatic cancer cells but not with normal pancreatic ductal cells. This combination also induced apoptosis, as seen by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies showed that this combination downregulated Akt-mTOR signaling pathway, which was confirmed by Western blot analyses. There was also a downregulation of VEGF and interleukin-8 expression suggesting effects on angiogenesis pathway. In vivo, intraperitoneal administration of the P276-Gem combination significantly suppressed the growth of pancreatic cancer tumor xenografts. There was a reduction in CD31-positive blood vessels and reduced VEGF expression, again suggesting an effect on angiogenesis. Taken together, these data suggest that P276-Gem combination is a novel potent therapeutic agent that can target the Akt-mTOR signaling pathway to inhibit both tumor growth and angiogenesis.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Animales , Antineoplásicos/administración & dosificación , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/metabolismo , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Desnudos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Oncogenes , Neoplasias Pancreáticas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
⢠AIP is a heterogeneous disease with two distinct subtypes, now called type 1 and type 2. The proportions of these subtypes vary in their distribution worldwide. ⢠Pancreatic cancer is the leading differential diagnosis for AIP, although AIP can mimic any other major pancreatobiliary disease. ⢠Cross-sectional abdominal imaging CT/MRI should form the cornerstone to the diagnosis of AIP. ⢠Serum IgG4 provides collateral evidence for the diagnosis of AIP and should not be the sole basis for the diagnosis. False-positive elevation in serum IgG4 can be seen in up to 10% of patients with pancreatic cancer. ⢠A steroid trial should be performed only in select situations after ruling out pancreatic cancer and by gastroenterologists experienced in treating AIP. ⢠Disease recurrence can be seen in up to 40% of patients after initial steroid therapy.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Pancreatitis/diagnóstico , Pancreatitis/terapia , Algoritmos , Humanos , Pancreatitis/inmunologíaRESUMEN
The purpose of this review is to provide a concise view of the existing knowledge of autoimmune pancreatitis (AIP) for practicing clinicians. AIP is a rare disease whose recognition and understanding are evolving. It is a type of chronic pancreatitis that often presents as obstructive jaundice, has a distinctive histology, and is exquisitely sensitive to steroid therapy. This form of chronic pancreatitis has a unique clinical, biochemical, and radiological profile. The term "AIP" encompasses two subtypes: types 1 and 2. Type 1 AIP is the pancreatic manifestation of a systemic fibro-inflammatory disease called immunoglobulin G4-associated systemic diseases. Type 2 AIP has been shown to be associated with inflammatory bowel disease. Existing criteria are geared towards the diagnosis of type 1 AIP. At present, pancreatic histology is a requirement for the definitive diagnosis of type 2 AIP. AIP can mimic most other pancreatic diseases in its presentation, but in clinical practice, it often has to be differentiated from pancreatic cancer. There are established criteria and algorithms not only to diagnose AIP, but also to differentiate it from pancreatic cancer. The utility of these algorithms and the approach to management are discussed here.
Asunto(s)
Enfermedades Autoinmunes , Pancreatitis Crónica , Algoritmos , Enfermedades Autoinmunes/clasificación , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Técnicas de Apoyo para la Decisión , Diagnóstico Diferencial , Humanos , Pancreatitis Crónica/clasificación , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/terapia , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
Colorectal polyps have been traditionally classified as either hyperplastic or adenomatous, with only the latter progressing to carcinoma. However, it is now recognized that certain subtypes of serrated polyps have a risk of malignant transformation via a serrated neoplasia pathway. Serrated polyps are a heterogeneous group of lesions with distinct morphologic, histologic and molecular genetics profiles. Based on available evidence, there are reasons to suspect that this pathway may contribute to interval or missed cancers because serrated lesions are more likely than conventional adenomas to be missed on colonoscopy, and the progression of serrated polyps to cancer may be more rapid. Therefore, it is paramount that physicians recognize the importance of serrated polyps and are aware of the latest surveillance guidelines.
Asunto(s)
Pólipos del Colon/patología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/fisiopatología , Lesiones Precancerosas/patología , Adenoma/epidemiología , Adenoma/patología , Adenoma/fisiopatología , Transformación Celular Neoplásica/patología , Colonoscopía , Neoplasias Colorrectales/epidemiología , Progresión de la Enfermedad , Humanos , Factores de RiesgoAsunto(s)
Hemorragia Gastrointestinal/etiología , Yeyuno/patología , Síndrome de Peutz-Jeghers/diagnóstico , Biopsia , Femenino , Hemorragia Gastrointestinal/cirugía , Humanos , Yeyuno/diagnóstico por imagen , Yeyuno/cirugía , Melena/etiología , Persona de Mediana Edad , Síndrome de Peutz-Jeghers/complicaciones , Síndrome de Peutz-Jeghers/patología , Síndrome de Peutz-Jeghers/cirugía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Characteristic pancreatic duct changes on endoscopic retrograde pancreatography (ERP) have been described in autoimmune pancreatitis (AIP). The performance characteristics of ERP to diagnose AIP were determined. METHODS: The study was done in two phases. In phase I, 21 physicians from four centres in Asia, Europe and the USA, unaware of the clinical data or diagnoses, reviewed 40 preselected ERPs of patients with AIP (n=20), chronic pancreatitis (n=10) and pancreatic cancer (n=10). Physicians noted the presence or absence of key pancreatographic features and ranked the diagnostic possibilities. For phase II, a teaching module was created based on features found most useful in the diagnosis of AIP by the four best performing physicians in phase I. After a washout period of 3 months, all physicians reviewed the teaching module and reanalysed the same set of ERPs, unaware of their performance in phase I. RESULTS: In phase I the sensitivity, specificity and interobserver agreement of ERP alone to diagnose AIP were 44, 92 and 0.23, respectively. The four key features of AIP identified in phase I were (i) long (>1/3 the length of the pancreatic duct) stricture; (ii) lack of upstream dilatation from the stricture (<5 mm); (iii) multiple strictures; and (iv) side branches arising from a strictured segment. In phase II the sensitivity (71%) of ERP significantly improved (p<0.05) without a significant decline in specificity (83%) (p>0.05); the interobserver agreement was fair (0.40). CONCLUSIONS: The ability to diagnose AIP based on ERP features alone is limited but can be improved with knowledge of some key features.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatitis Crónica/diagnóstico por imagen , Algoritmos , Colangiopancreatografia Retrógrada Endoscópica/normas , Competencia Clínica , Diagnóstico Diferencial , Educación Médica Continua/métodos , Humanos , Cooperación Internacional , Neoplasias Pancreáticas/diagnóstico , Radiología/educación , Sensibilidad y EspecificidadRESUMEN
PURPOSE OF REVIEW: To summarize the existing knowledge of autoimmune pancreatitis (AIP) and to review the progress made in the diagnosis and treatment of AIP in the past year. RECENT FINDINGS: The term 'AIP' appears to encompass at least two distinct subtypes, type 1 and type 2. Type 1 AIP is the pancreatic manifestation of a systemic fibroinflammatory disease called immunoglobulin G4-associated systemic disease. Type 2 AIP affects younger patients, does not have a gender predilection and is associated with normal serum immunoglobulin G4 levels. Existing criteria are geared toward diagnosis of type 1; type 2 AIP can be definitively diagnosed only on pancreatic histology. Both subtypes respond to corticosteroid therapy. However, there are no standardized protocols for initial treatment or management and prevention of relapses in AIP. A novel antibody for AIP has recently been identified and its performance needs validation from other centers. Newly published strategies for differentiating AIP from pancreatic cancer are available. SUMMARY: AIP is a rare disease whose recognition and understanding are evolving. Much needs to be elucidated with regard to its cause, pathogenesis, treatment of relapse and long-term outcomes. A multidisciplinary team, familiar with the disease, is critical in making the correct diagnosis.
Asunto(s)
Enfermedades Autoinmunes , Colangiopancreatografia Retrógrada Endoscópica/métodos , Endosonografía/métodos , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética/métodos , Pancreatitis , Biopsia con Aguja Fina , Diagnóstico Diferencial , Humanos , Pancreatitis/diagnóstico , Pancreatitis/tratamiento farmacológico , Pancreatitis/inmunología , Prevención Secundaria , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVES: In autoimmune pancreatitis (AIP), the prevalence, interrelationships, and significance of peripheral eosinophilia, allergic disorders, and eosinophil infiltration in the pancreas remain unclear. METHODS: From medical records, we obtained data on peripheral eosinophil counts at presentation and follow-up, and clinical diagnoses of allergic disorders in 97 AIP patients (78 type 1 and 19 type 2), which were compared with matched healthy controls. Available pancreatic histologic specimens were graded for eosinophils. Peripheral eosinophilia was defined as counts >0.5×10(9) per liter. We examined nature of and association between these parameters in AIP. RESULTS: Among 78 type 1 AIP patients (mean age 62±14 years, 77% men), peripheral eosinophilia at presentation was diagnosed in 12% and allergic disorders in 15% (vs. 0 and 4% in controls, P=0.0004 and 0.006, respectively). Allergic disorders were observed in 27 and 11% of type 1 AIP with and without eosinophilia, respectively (P=0.08). Patients with and without peripheral eosinophilia were similar in clinical profile. Moderate-to-severe eosinophil infiltration was present in 67% of pancreas resection specimens and did not correlate with peripheral eosinophilia. Type 2 AIP did not differ from type 1 AIP in any of these parameters. CONCLUSIONS: Peripheral eosinophilia, allergic disorders, and pancreatic eosinophil infiltration are associated with AIP. Eosinophilia in AIP may not reflect an allergic phenomenon, but appears to be consistent with autoimmune mechanism.
Asunto(s)
Enfermedades Autoinmunes/epidemiología , Eosinofilia/epidemiología , Hipersensibilidad/epidemiología , Pancreatitis/epidemiología , Adulto , Anciano , Enfermedades Autoinmunes/patología , Comorbilidad , Eosinofilia/patología , Eosinófilos/patología , Femenino , Humanos , Hipersensibilidad/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pancreatitis/patología , Prevalencia , Estadísticas no ParamétricasRESUMEN
Both autoimmune pancreatitis (AIP) and pancreatic cancer frequently present with obstructive jaundice. However, AIP is a rare disease and its diagnosis carries vastly different therapeutic and prognostic implications compared with that of pancreatic cancer. The clinical challenge is to distinguish AIP from pancreatic cancer, because the price of misdiagnosis can be heavy. Recently, two strategies for differentiating AIP from pancreatic cancer were published, one from Japan and the other from the United States. The Japanese strategy relies on cross-sectional imaging, endoscopic retrograde pancreatogram, and serum IgG4. The American strategy uses imaging (CT scan), serology (serum IgG4), and evidence of other organ involvement (on CT scan) as the first tier of tests. If the differentiation cannot be made by these methods, a core biopsy of the pancreas, steroid trial, or surgical resection is recommended. The two strategies reflect differences in clinical practice and local preferences in the use of certain diagnostic tests. However, both strategies require thorough familiarity with the diseases and the tests being used.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/métodos , Neoplasias Pancreáticas/diagnóstico , Pancreatitis/diagnóstico , Guías de Práctica Clínica como Asunto , Algoritmos , Enfermedades Autoinmunes/inmunología , Diagnóstico Diferencial , Errores Diagnósticos , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Pancreatitis/inmunología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. METHODS: We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. RESULTS: At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. CONCLUSIONS: Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.
Asunto(s)
Enfermedades Autoinmunes/clasificación , Pancreatitis Crónica/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/mortalidad , Enfermedades Autoinmunes/patología , Enfermedades Autoinmunes/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pancreaticoduodenectomía , Pancreatitis Crónica/mortalidad , Pancreatitis Crónica/patología , Pancreatitis Crónica/cirugía , Modelos de Riesgos Proporcionales , RecurrenciaRESUMEN
BACKGROUND & AIMS: Little is known about how many patients with features of acute pancreatitis (AP) or chronic pancreatitis (CP) have autoimmune pancreatitis (AIP); most information comes from case reports. We explored the clinical profiles and relationship between these diseases. METHODS: We evaluated 178 patients presenting to our Pancreas Clinic between January 2005 and June 2006 for evaluation of the etiology of their suspected pancreatitis; AIP was diagnosed when patients met HISORt (Histology, Imaging features, Serology, Other organ involvement and Response to steroid treatment) criteria. In a separate cohort of patients with AIP from our database, we identified patients who presented with features of AP (>/=2 of abdominal pain, increased pancreatic enzymes, pancreatic inflammation determined by imaging analyses) or CP (>/=1 of pancreatic calcification, irregular main pancreatic duct dilation, or marked atrophy) and determined their clinical profile. RESULTS: Only 7/178 (3.9%) patients evaluated for etiology of suspected pancreatitis had AIP. Among 63 AIP patients in our database, 22 (34.9%) had features of AP (n = 15) or CP (n = 7) at presentation (average age 53.4 +/- 19.0 years, all males). Patients with AIP and pancreatitis were characterized by presence of obstructive jaundice (59.1%), increased levels of liver enzymes (81.8%), increased levels of serum immunoglobulin G4 (80.9%), and other organ involvement (69.1%). All 19 patients presenting with pancreatitis who were treated with steroids responded to treatment. CONCLUSIONS: While AIP is an uncommon etiology for acute or chronic pancreatitis, >33% of AIP have features of acute or chronic pancreatitis at presentation.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Pancreatitis Aguda Necrotizante/diagnóstico , Pancreatitis Aguda Necrotizante/epidemiología , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/epidemiología , Adulto , Anciano , Enfermedades Autoinmunes/patología , Enzimas/sangre , Humanos , Inmunoglobulinas/sangre , Ictericia Obstructiva , Masculino , Persona de Mediana Edad , Pancreatitis Aguda Necrotizante/patología , Pancreatitis Crónica/patología , PrevalenciaRESUMEN
Warfarin is the most common oral anticoagulant prescribed around the world. Adverse drug interactions with warfarin are a huge problem especially in the elderly and in patients who take multiple medications. Most adverse drug interactions involve concomitantly prescribed oral or intravenous medications. Occasionally, topical or mucosally absorbed drugs can interact, leading to fluctuations in warfarin levels with adverse consequences. In this case report, we describe a case of intestinal intramural hematoma, a rare but known consequence of a supra therapeutic international normalized ratio (INR). The supra therapeutic INR was a consequence of mucosally absorbed miconazole, prescribed for vaginal candidiasis. We wish to highlight this rare and potentially fatal drug interaction, along with the need for frequent INR monitoring when new drugs are added or removed in patients taking warfarin.
RESUMEN
Until recently, colonic polyps were traditionally classified as either hyperplastic or adenomatous, and only the latter were believed to have the potential to progress to carcinoma. However, it is now appreciated that a subset of serrated polyps also appear to have malignant potential. Serrated polyps are a heterogeneous group of colon polyps that include hyperplastic polyps, sessile serrated adenomas (SSAs), traditional serrated adenomas, and mixed polyps. Insights into these polyps were derived, in part, from studies of patients with the hyperplastic polyposis syndrome. SSAs show a predilection for the right colon, have a distinct histology, and their molecular genetic profile has recently been linked to a pathway for colon tumorigenesis that is characterized by microsatellite instability. Based upon available evidence, it is recommended that patients with serrated adenomas undergo colonoscopic follow-up at the same frequency as for conventional adenomas. It is important that physicians are aware of serrated polyps, particularly serrated adenomas and their relationship to colon cancer, and their proper clinical management.
RESUMEN
BACKGROUND: Testicular cancer is a common neoplasm in young and middle-aged men. Although the most common presentation is a palpable testicular mass, it can present with atypical symptoms. There is a lack of awareness among primary-care physicians about the less common presentations of testicular tumors. Early detection is a key prognostic variable. This case demonstrates an unusual first presentation of testicular cancer with chylous ascites and abdominal pain. CASE REPORT: We report a case of a 19-year-old man who presented with severe atypical abdominal pain, which was initially diagnosed as acute appendicitis. He underwent laparoscopic appendectomy and was found to have chylous ascites and a normal-appearing appendix. As part of his work-up for chylous ascites, he was found to have mesenteric lymphadenopathy. These nodes were sampled and revealed a mixed germ cell tumor. The primary tumor was later traced to his right testis. CONCLUSIONS: The differential diagnosis of atypical abdominal pain in young men should include testicular tumors. A thorough testicular exam should be part of the routine physical exam in such situations.
Asunto(s)
Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/diagnóstico , Humanos , Masculino , Adulto JovenRESUMEN
Autoimmune pancreatitis is a rare disease which closely mimics pancreatic cancer in its presentation. It is important for clinicians to distinguish one from the other due to vastly different therapeutic and prognostic implications. We compared 2 recently proposed strategies, 1 from Japan and the other from the United States, to distinguish autoimmune pancreatitis from pancreatic cancer. While both strategies have inherent strengths and weaknesses, we believe that the best features of both need prospective validation. The strategy proposed from Japan is simple to use, but is based on a small number of patients and is heavily dependent on imaging criteria. The American strategy while based on a bigger sample of patients is complicated and is most useful in expert hands. Additionally, differences in clinical practice and local preference in the use of certain diagnostic tests need to be considered while adopting either strategy.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/patología , Diagnóstico Diferencial , Humanos , Japón , Estados UnidosRESUMEN
Autoimmune pancreatitis (AIP) is a rare but treatable form of pancreatic disease that is being increasingly recognized worldwide. The diagnosis of AIP remains a clinical challenge and the difficulty is compounded by the fact that there are no internationally agreed on diagnostic criteria for AIP. One of the reasons for the lack of consensus on diagnostic criteria could be that the term "AIP" likely refers to more than one distinct disease or subtype. This may explain the divide between European and other diagnostic criteria. Recent insights into AIP subtypes should help develop an evidence-based consensus on diagnostic criteria for the disease.