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المحددات
1.
Chinese Journal of Surgery ; (12): 590-595, 2023.
مقالة ي صينى | WPRIM | ID: wpr-985813

الملخص

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.


الموضوعات
Male , Female , Humans , Retrospective Studies , Acute Disease , Treatment Outcome , Calculi/pathology , Lithotripsy , Pancreatitis, Chronic/pathology , Pancreatic Diseases/complications , Pancreatic Ducts , Abdominal Pain/therapy
2.
Neuroscience Bulletin ; (6): 342-358, 2022.
مقالة ي الانجليزية | WPRIM | ID: wpr-929097

الملخص

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.


الموضوعات
Animals , Rats , Anxiety/etiology , Chronic Pain/etiology , GABAergic Neurons , Gyrus Cinguli/metabolism , Hyperalgesia/metabolism , Pancreatitis, Chronic/pathology , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Trinitrobenzenesulfonic Acid/toxicity
4.
Hist. ciênc. saúde-Manguinhos ; 22(1): 69-93, Jan-Mar/2015.
مقالة ي الانجليزية | LILACS, BDS | ID: lil-741522

الملخص

The article explores the ideas of Pan American Health Organization director Abraham Horwitz on the relations between health and development at the time the Alliance for Progress was established, in 1961. Taking development discourse as a public philosophy of international cooperation, the discussion centers on how Horwitz worked to mediate between health and development. Horwitz endeavored to establish arguments that highlighted the importance of social policy, especially in health; he also strove to reach different audiences and drew connections between elements like health, illness, and labor productivity, without ignoring the humanistic considerations so dear to the public health tradition.


O artigo examina as ideias de Abraham Horwitz, diretor da Organização Pan-americana da Saúde, sobre as relações entre saúde e desenvolvimento, quando da celebração da Aliança para o Progresso, em 1961. Toma-se o discurso do desenvolvimento como a filosofia pública da cooperação internacional e discute-se a forma pela qual Horwitz propõe uma mediação entre saúde e desenvolvimento. Verifica-se que ele preocupou-se em estabelecer um cardápio de argumentos favoráveis à importância das políticas sociais, em particular da saúde, ampliando adesões em diferentes audiências, afirmando conexões entre saúde, adoecimento e produtividade do trabalho, sem prescindir de um sentido humanístico, caro à tradição sanitarista.


الموضوعات
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , /analysis , /analysis , Pancreatic Neoplasms/chemistry , Pancreatitis, Chronic/metabolism , Biomarkers, Tumor/analysis , Diagnosis, Differential , Discriminant Analysis , Immunohistochemistry , Predictive Value of Tests , Pancreatic Neoplasms/pathology , Pancreatitis, Chronic/pathology , Up-Regulation
5.
مقالة ي الانجليزية | IMSEAR | ID: sea-157087

الملخص

Background & objectives: Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 −181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. Methods: A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (− 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). Results: The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 −181GG genotype and − 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 –2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. Interpretation &conclusions: The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.


الموضوعات
Adult , Case-Control Studies , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Matrix Metalloproteinase 7/genetics , Middle Aged , Pancreatitis, Chronic/genetics , Pancreatitis, Chronic/pathology , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Risk Factors
7.
GEN ; 65(3): 240-242, sep. 2011. ilus
مقالة ي الأسبانية | LILACS | ID: lil-664154

الملخص

La disección mucosal endoscópica (DME), surge a partir de la resección mucosal endoscópica (RME), permitiendo resecar lesiones malignas en estadio precoz, logrando tasas de curación de hasta el 99%, disminuyendo la morbi-mortalidad de la cirugía tradicional. Es importante la obtención de la pieza de forma completa, ya que de esta manera, el patólogo podrá informar los márgenes de la lesión en extensión y profundidad. Caso clínico: Se trata de paciente masculino de 40 años de edad, valorado por nuestro servicio (agosto 2009) por clínica de 4 meses de evolución, dado por cambios en el patrón evacuatorio (evacuaciones diarreicas) y rectorragia. Consulta a especialista, el cual realiza colonoscopia con hallazgo de tumor en recto medio, con biopsia positiva para Adenocarcinoma, por lo que refieren a nuestro centro. Antecedentes personales y familiares: no contributorios. Se realizó gastroscopia la cual reporta: Lesión en cara anterior de antro, elevada, fondo ulcerado, deprimido, amputación de pliegues; se concluye: Ca. Gástrico Precoz IIc. Ultrasonido Endoscópico: Engrosamiento de la mucosa y muscular de la mucosa en antro. Cara posterior. Biopsia: Sin atipias. Colonoscopia: Tu recto bajo. Poliposis colonica. Ultrasonido endoscópico transrectal: Tu. Recto bajo uT2N1. Biopsia: Adenocarcinoma Moderadamente diferenciado. En vista de las características de la lesión gástrica, se decide realizar disección mucosal endoscópica, cuya biopsia que reporta: Carcinoma intramucoso precoz, bordes de resección libres de lesión. Paciente recibe tratamiento oncológico neo-adyuvante y posteriormente se realiza ileoprocto anastomosis. Evolución actual satisfactoria. Discusión: La apariencia endoscópica de las lesiones juega un papel importante en la conducta a seguir por el médico y es clave al momento de plantearse la realización de DME, ya que es un procedimiento que conlleva riesgos y tiene indicaciones especificas, para obtener así los resultados planteados...


Endoscopic mucosal dissection (DME), arises from endoscopic mucosal resection (EMR), allowing resection malignant lesions in early stage, achieving cure rates of up to 99%, decreasing morbidity and mortality of traditional surgery. It is important to obtain the piece completely, as this way, the pathologist may report the margins of the lesion extent and depth. Case report: This male patient aged 40 years, valued for our service (August 2009) by clinical evolution of 4 months, changes in the pattern of voiding (bowel diarrhea) and bleeding rectal. Consulting specialist, performed colonoscopy finding means is rectal tumor, with positive biopsy for adenocarcinoma, so refer to our center. Personal and family history: no contributory. Gastroscopy was performed which reported: Injury anterior antrum, high background ulcerated, depressed, amputation of folds, it is concluded: IIc early gastric Ca. Endoscopic Ultrasound: Thickening of the mucosa and muscle of the antral mucosa. Posterior. Biopsy: No atypia. Colonoscopy: tu. lower rectum. Colonic polyposis. Transrectal endoscopic ultrasound: Tu. UT2N1 lower rectum. Biopsy: moderately differentiated adenocarcinoma. Given the characteristics of gastric injury is endoscopic submucosal dissection dedide perform, with biopsy reports: early intramucosal carcinoma, resection margins free of injury. patient receives Neoadjuvant cancer treatment and subsequently coloproctoanastomosis. Current developments satisfactory. Discussion: The endoscopic appearance of lesions plays an important role in the conduct to be followed by the doctor and is key to consider when conducting DME because it is a procedure that carries risks and has specific indications for and results obertener raised...


الموضوعات
Humans , Female , Child , Cholangiography/methods , Magnetic Resonance Imaging/methods , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/pathology , Choledochal Cyst/diagnosis , Ultrasonography , Gastroenterology
8.
GEN ; 65(3): 237-239, sep. 2011.
مقالة ي الأسبانية | LILACS | ID: lil-664161

الملخص

El quiste de colédoco es una malformación congénita de las vías biliares poco común, que suele presentarse en la infancia. La triada clásica de ictericia, masa y dolor abdominal no siempre esta presente. Caso clínico: escolar femenina de 9 años, con Pancreatitis Aguda de evolución tórpida, ecosonograma abdominal inicial sin alteraciones, y diagnóstico no concluyente de Colecistitis crónica o Colangitis alitiásica por tomografía abdominal y colangioresonancia, respectivamente. Referida para colangiopancreatografía retrograda endoscópica, estudio que fue omitido por ecosonograma abdominal control sugestivo de Quiste de colédoco. Se solicita nueva colangioresonancia, que no visualiza quiste y reporta dilatación de hepatocoledoco y colédoco terminal de aspecto afinado. Se mantiene conducta expectante. La paciente permanece asintomática, con reevaluación 3 meses después. El ecosonograma abdominal revelo: dilatación fusiforme del colédoco en toda su extensión, hallazgo compatible con quiste de colédoco tipo I. Se realiza resección del quiste, con buena evolución clínica. Se concluye que el uso de estudios por imágenes no invasivos son de utilidad en la evaluación hepatobiliar en niños, y el ultrasonido abdominal continua como método de elección para esta patología.


Choledochal cyst is a congenital malformation of the bile ducts rare, usually seen in childhood. The classic triad of jaundice, abdominal mass and pain is not always present. Case report: A school girl of nine years, with Acute Pancreatitis torpid, unaltered initial abdominal ultrasound, and no conclusive diagnosis of chronic cholecystitis or acalculous cholangitis abdominal and from magnetic resonance tomography, respectively. Referred for endoscopic retrograde cholangiopancreatography, a study that was omitted from control abdominal ultrasound suggestive of choledochal cyst. New requested from magnetic resonance, which displayed no reports cyst and bile duct dilation and terminal hepatocoledoco related aspects. Expectant management is maintained. The patient remains asymptomatic, with reassessment 3 months later. The abdominal ultrasound revealed: fusiform dilatation of the bile duct in its entirety, a finding compatible with type I choledochal cyst Resection was performed, the cyst, cholecystectomy and reconstruction of the bile duct through a hepato-jejunostomy Roux en Y no complications. Liver biopsy reported normal tissue. We conclude that the use of noninvasive imaging tests such as ultrasound is the method of choice due to its sensitivity to determine the presence of cyst and to demonstrate the anatomy of the pancreaticduct.


الموضوعات
Humans , Female , Child , Cholangiography/methods , Pancreatitis, Chronic/pathology , Choledochal Cyst/diagnosis , Ultrasonography , Gastroenterology , Pediatrics
9.
An. bras. dermatol ; 86(4,supl.1): 125-128, jul,-ago. 2011. ilus
مقالة ي البرتغالية | LILACS | ID: lil-604140

الملخص

A paniculite pancreática, condição patológica rara, acomete 2-3 por cento dos pacientes com doença do pâncreas. Em 40 por cento dos casos, precede manifestações de doença pancreática. Relata-se caso de paciente feminina, 71 anos, surgimento há 1 mês de nódulos eritematosos nas pernas que evoluíram para ulceração e saída de conteúdo amarelado. Sem sintomas abdominais. A biópsia revelou macrófagos vacuolizados e necrose gordurosa representada por áreas anfofílicas, de material amorfo. Exame laboratorial e TAC demonstraram pancreatite crônica. Presume-se que a liberação de enzimas pancreáticas, tais como a tripsina, pode aumentar a permeabilidade da microcirculação e, então, a lípase e a amilase causariam a necrose de gordura subcutânea observada nas lesões. Na histologia, observam-se "células fantasmas" e paniculite septal de início e posteriormente lobular. O tratamento direciona-se a resolução da doença base.


Pancreatic panniculitis is a rare pathological condition affecting 2-3 percent of patients with pancreatic disease. In 40 percent of cases the condition precedes manifestations of pancreatic disease. We report the case of a 71-year-old female who presented with an erythematous tender node which had appeared one month previously, progressing to ulceration and yellowish exudation. No abdominal symptoms. Biopsy revealed fat necrosis and vacuolated macrophages represented by amorphous amphophilic areas. Laboratory examination and CT scan revealed chronic pancreatitis. It is assumed that release of pancreatic enzymes such as trypsin may enhance the permeability of the microcirculation leading to lipase and amylase causing the subcutaneous fat necrosis observed in the lesions. Histology showed "ghost cells" and, firstly, septal panniculitis, followed later by lobular panniculitis. Treatment focused on resolution of the underlying pancreatic disease.


الموضوعات
Aged , Female , Humans , Pancreatitis, Chronic/pathology , Panniculitis/pathology , Subcutaneous Fat/pathology , Necrosis/etiology , Necrosis/pathology , Pancreatitis, Chronic/complications , Panniculitis/etiology
10.
RBM rev. bras. med ; 66(10)out. 2009.
مقالة ي البرتغالية | LILACS | ID: lil-532237

الملخص

A pancreatite crônica se caracteriza pela inflamação sustentada e substituição progressiva do parênquima pancreático por fibrose e calcificações. Clinicamente se manifesta por episódios de dor abdominal intensa, síndrome de má absorção e diabetes mellitus secundário. Em nosso país, o alcoolismo persiste como principal causa, porém a contribuição de outras formas de pancreatite crônica, particularmente as de causa genética, é reconhecida cada vez mais. O diagnóstico é, por vezes, difícil e requer a combinação de uma série de exames laboratoriais, radiológicos e endoscópicos, cuja sensibilidade e a especificidade variam amplamente de acordo com o estágio clínico em que se encontra a doença, sendo fundamental a formulação de adequadas hipóteses diagnósticas. O tratamento da insuficiência exócrina se baseia na reposição de enzimas pancreáticas exógenas, descartando-se doenças associadas que possam agravar a má absorção. O tratamento da dor é difícil, envolvendo profissionais da área clínica, endoscopistas, radiologistas e cirurgiões, uma vez que as decisões terapêuticas trazem importantes repercussões para a vida do paciente. Os pseudocistos, complicações habituais da pancreatite crônica, também são de tratamento multimodal, sendo importante conhecer a melhor forma de tratá-los de acordo com as características do paciente e as características da própria lesão no contexto da história natural da pancreatite crônica de cada indivíduo.


الموضوعات
Humans , Male , Female , Alcoholism/complications , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/pathology , Pancreatic Pseudocyst/therapy , Digestive System Abnormalities/etiology
11.
ACM arq. catarin. med ; 38(2): 116-120, abr.-jul. 2009. ilus
مقالة ي البرتغالية | LILACS | ID: lil-528907

الملخص

A pancreatite crônica hereditária é definida como uma doença autossômica dominante rara caracterizada porepisódios recorrentes de pancreatite aguda em dois ou mais membros de várias gerações da família. A maioriados pacientes possui mutações nos genes PRSS1, SPINK1 ou CFTR. Relata-se o caso de uma paciente com um quadro agudo de pancreatite secundário a um processo crônico calcificado subjacente, em que na investigação familiar seis membros já haviamapresentado episódios de pancreatite. A pesquisa das alterações genéticas características não foi possível porlimitações do serviço.


Chronic hereditary pancreatitis is defined as a rare autossomic dominant disease, characterized by recurrentepisodes of acute pancreattis in two or more members of several familiar generations. Most of these patientspresent mutation on genes PRSS1, SPINK1 or CFTR. It’s reported the case of a patient with an acute episodeof pancreatitis secondary to a chronic calcified underlying process, in which six cases of history of previous episodesof pancreatitis were found, through familiar investigation. The screening for genetic alterations was not possibledue to the lack of resources of the heath care service.


الموضوعات
Humans , Female , Adult , Genetic Diseases, Inborn , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/congenital , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/pathology
12.
J. bras. patol. med. lab ; 43(2): 115-120, abr. 2007. tab
مقالة ي البرتغالية | LILACS | ID: lil-450967

الملخص

INTRODUÇÃO: O abuso crônico do álcool é importante causa de cirrose hepática e de pancreatite crônica. OBJETIVO: Avaliar a frequência de pancreatite crônica (PC) em pacientes portadores de cirrose hepática alcoólica (CHA) por exame histopatológico. Casuística: Analisaram-se necropsias de 18 homens e sete mulheres portadores de CHA, com idade média e desvio padrão de 47,2 ± 13,8 anos (24 a 83 anos), que consumiam em média 239,6 ± 155,3 g de etanol/dia por um período médio de 16,7 ± 7,2 anos. MÉTODOS: O diagnóstico histopatológico de cirrose hepática baseou-se na fibrose sistematizada com formação de septos delimitando nódulos, associada à inflamação crônica inespecífica. O diagnóstico histológico de PC baseou-se na identificação de exsudato mononuclear (EM) em torno dos ductos e no tecido conjuntivo inter e intralobular, acompanhado de traves de fibrose. A PC foi classificada como leve quando havia discreto EM em região periductal, interlobular ou intralobular acompanhado por finas traves de fibrose; moderada, pelo aumento da intensidade do exsudato e da fibrose, ocasionalmente associado com pequena dilatação dos ductos; a forma grave caracterizou-se pelo EM, densa fibrose, presença de rolhas, dilatação dos ductos, atrofia glandular e, às vezes, calcificação. RESULTADOS: Observou-se PC em 20 pacientes portadores de CHA (80 por cento), que foi leve em 13 (52 por cento), moderada em dois (8 por cento) e grave em cinco (20 por cento). CONCLUSÃO: A pancreatite crônica está frequentemente associada à CHA, sendo histologicamente grave em aproximadamente 1/4 dos casos.


INTRODUCTION: The chronic alcohol abuse is an important cause of liver cirrhosis and chronic pancreatitis. OBJECTIVE: To evaluate the prevalence of chronic pancreatitis (CP) in patients with alcoholic liver cirrhosis (ALC) based on histopathological assays. Subjects: Autopsies of 25 patients with ALC, 18 men and seven women, age ranging from 24 to 83 years (mean ± standard deviation: 47.2 ± 13.8) were retrospectively analyzed. They ingested on average 239.6 ± 155.3 g ethanol/day for a mean period of 16.7 ± 7.2 years. METHODS: Liver cirrhosis histopathological diagnosis was based on the findings of systemized fibrosis with formation of septum-delimited nodules and nonspecific chronic inflammation. CP histopathological diagnosis was based on identification of mononuclear cell infiltration (MCI) around the ducts and in the inter- and intra-lobular connective tissue and presence of strands of fibrosis. CP was classified as mild (discrete MCI in the periductal, inter- or intra-lobular areas with thin strands of fibrosis), moderate (increased exudates and fibrosis, occasionally associated with small dilatation of ducts), and severe (evident MCI, dense fibrosis, presence of plugs in the ducts, irregular ductal dilatation, glandular atrophy and, sometimes, calcification). RESULTS: CP was observed in 20 patients (80 percent) with ALC, and was considered mild in 13 (52 percent), moderate in two (8 percent) and severe in five (20 percent) patients. CONCLUSION: CP is often associated with the ALC, and it can be histologically severe in approximately 1/4 of the cases.


الموضوعات
Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Liver Cirrhosis, Alcoholic/diagnosis , Liver Cirrhosis, Alcoholic/epidemiology , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/epidemiology , Alcoholism/complications , Cross-Sectional Studies , Liver Cirrhosis, Alcoholic/etiology , Liver Cirrhosis, Alcoholic/pathology , Pancreatitis, Chronic/etiology , Pancreatitis, Chronic/pathology
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