Tumor sólido pseudopapilar de páncreas. Reporte de caso / Solid pseudopapillary tumor of the pancreas. Case report

Introducción. La neoplasia sólida pseudopapilar de páncreas, también conocida como tumor de Frantz, es una patología poco frecuente, que comprende menos del 3 % de los tumores pancreáticos, y la mayor incidencia se observa en mujeres jóvenes entre la segunda y tercera década de la vida. Su etiología es desconocida. El tratamiento de elección es la resección quirúrgica sin linfadenectomía cuando se encuentra bien localizado. Inclusive aún cuando hay evidencia de metástasis o invasión local, el manejo quirúrgico sigue siendo el tratamiento de elección. Caso clínico. Mujer de 24 años de edad, con masa abdominal palpable, dolorosa, de tres semanas de evolución. La tomografía computarizada mencionó como presunción diagnóstica un tumor de origen pancreático. En la laparotomía se encontró una masa dependiente del cuerpo del páncreas. Se realizó pancreatectomía distal radical con esplenectomía y omentectomía parcial en bloque. Resultados. Durante la cirugía no se presentaron complicaciones y hasta el sexto mes de seguimiento, la evolución fue adecuada y sin recidiva tumoral. Conclusiones. Ante la presencia de masa abdominal, con compromiso pancreático documentado por tomografía computarizada, se debe considerar el diagnóstico de neoplasia sólida pseudopapilar de páncreas, o tumor de Frantz. El tumor de Frantz es una entidad poco frecuente que generalmente se diagnostica de forma incidental o por síntomas inespecíficos en estadios avanzados. El diagnóstico y manejo de esta neoplasia representa un reto y la resección quirúrgica continúa siendo el tratamiento indicado.

Introduction. Solid pseudopapillary neoplasia of the pancreas, also known as Frantz tumor, is a rare pathology, comprising less than 3% of pancreatic tumors, and the highest incidence is observed in young women between the second and third decades of life. Its etiology is unknown. The treatment of choice is surgical resection without lymphadenectomy when it is well located. Even when there is evidence of metastasis or local invasion, surgical management remains the treatment of choice. Clinical case. A 24-year-old woman presented with a palpable, painful abdominal mass of three weeks' duration. The computed tomography mentioned a tumor of pancreatic origin as a presumptive diagnosis. At laparotomy, a mass dependent on the body of the pancreas was found. Radical distal pancreatectomy with splenectomy and en bloc partial omentectomy was performed. Results. During the surgery there were no complications and until the sixth month of follow-up, the evolution was adequate and without tumor recurrence. Conclusions. In the presence of an abdominal mass, with pancreatic involvement documented by computed tomography, the diagnosis of solid pseudopapillary neoplasia of the pancreas, or Frantz tumor, should be considered, which must be treated surgically. Frantz tumor is a rare entity that is generally diagnosed incidentally or due to nonspecific symptoms in advanced stages. The diagnosis and management of this neoplasia represents a challenge and surgical resection continues to be the indicated treatment.

Esplenúnculo intrapancreático simulando neoplasia / Intrapancreatic splenunculus simulating neoplasia

Introducción. El esplenúnculo se ha descrito con una incidencia global del 10 al 30 %. Puede ser una entidad de origen congénito o adquirida, frecuentemente está asociada a trauma abdominal o antecedente de esplenectomía por diversas causas. Caso clínico. Mujer en edad media, con antecedente de trauma abdominal y esplenectomía por ruptura traumática, quien 30 años después presenta un cuadro de dolor abdominal. Los estudios imagenológicos identificaron una masa sólida intrapancreática. Resultados. Fue llevada a pancreatectomía distal. Los hallazgos histológicos e inmunohistoquímicos confirmaron que la masa pancreática correspondía a un esplenúnculo intrapancreático adquirido, asociado al evento traumático previo. Conclusión. Los esplenúnculos suelen constituir un "incidentaloma". Los estudios imagenológicos se encuentran limitados, pues la tomografía computarizada, la resonancia nuclear magnética y la ultrasonografía presentan características imagenológicas similares con los tumores pancreáticos hipervascularizados, por lo que se debe practicar el estudio histopatológico durante su valoración. Esta entidad se debe incluir dentro de los diagnósticos diferenciales, con mayor énfasis en aquellos pacientes con historia de trauma abdominal y esplenectomía asociada, un escenario en el que esta lesión puede simular una neoplasia sólida del páncreas, con características malignas.

Introduction. Splenunculus has been described with an overall incidence of 10 to 30%. It can be an entity of congenital or acquired origin, it is frequently associated with abdominal trauma or a history of splenectomy for various reasons. Clinical case. Middle-aged woman, with a history of abdominal trauma and splenectomy due to traumatic rupture, who 30 years later presents with abdominal pain. Imaging studies identified a solid intrapancreatic mass. Results. She was taken to OR for distal pancreatectomy. The histological and immunohistochemical findings confirmed that the pancreatic mass corresponded to an acquired intrapancreatic splenunculus, associated with the previous traumatic event. Conclusion. Splenuncles usually constitute an "incidentaloma". Imaging studies are limited, since computed tomography, magnetic resonance imaging, and ultrasonography present similar imaging characteristics with hypervascularized pancreatic tumors, so histopathological study must be included during their evaluation. This entity should be included in the differential diagnoses, with greater emphasis on those patients with a history of abdominal trauma and associated splenectomy, a scenario in which this lesion can simulate a solid neoplasm of the pancreas, with malignant characteristics.

Mortalidad post operatoria de la duodenopancreatectomía cefálica en una unidad de cuidados intensivos

Introducción: La duodenopancreatectomía cefálica o cirugía de Whipple ha sido el procedimiento quirúrgico electivo como tratamiento de las patologías neoplásicas de páncreas, duodeno y vías biliares. A pesar de los avances en técnicas quirúrgicas continúa siendo un gran desafío el manejo multidisciplinario. Materiales y Métodos: Estudio analítico, retrospectivo, de corte transversal, de pacientes postoperados de duodenopancreatectomía cefálica mayores de 18 años, ingresados a una unidad de Cuidados Intensivos, de enero de 2022 a julio de 2023. Variables evaluadas: características sociodemográficas (edad, sexo); comorbilidades asociadas; variables de interés en UCI (SOFA, APACHE, días de internación en UTI, días de internación hospitalaria, requerimiento de Intubación orotraqueal IOT, días de IOT, requerimiento de vasopresores), desenlace en UTI; variables de interés quirúrgicas: duración de la cirugía, complicaciones quirúrgicas. Resultados: Se incluyeron 24 pacientes. La media de edad: 66 años (mín:35; Máx: 85; RIC: 59-77); 14 (58%) sexo femenino. Comorbilidades más frecuentes: Hipertensión arterial 17 (71%), Diabetes Mellitus 26 (25%), Cardiopatía 3. SOFA al ingreso media de 4; (mín:1; Máx: 11; DS:3); APACHE al ingreso: media de 15; (mín:6; Máx: 24; DS: 4); media de internación en UTI fue de 6 días (mín:1; Máx: 68; DS: 14). Se constataron 5 (21%) óbitos. Factores asociados a la mortalidad el uso de vasopresores (p=0,013), insuficiencia renal aguda (p=0,009), infección del sitio quirúrgico (p=0,023), y una media de SOFA estimada en 9 (p=0,0012). Conclusión: Es fundamental el manejo multidisciplinario de pacientes sometidos a cirugía de Whipple a fin de optimizar los resultados, previniendo la aparición de complicaciones, y disminuyendo de esta forma la morbimortalidad de los mismos.

Introduction: Cephalic pancreaticoduodenectomy or Whipple surgery has been the elective surgical procedure as a treatment for neoplastic pathologies of the pancreas, duodenum and bile ducts. Despite advances in surgical techniques, multidisciplinary management continues to be a great challenge. Materials and Methods: Analytical, retrospective, cross-sectional study of postoperative cephalic duodenal-pancreatectomy patients over 18 years of age, admitted to an Intensive Care unit, from January 2022 to July 2023. Variables evaluated: sociodemographic characteristics (age, sex); associated comorbidities; variables of interest in the ICU (SOFA, APACHE, days of ICU admission, days of hospitalization, requirement for orotracheal intubation IOT, days of IOT, requirement for vasopressors), outcome in ICU; surgical variables of interest: duration of surgery, surgical complications. Results: 24 patients were included. Median age: 66 years (min: 35; Max: 85; IQR: 59-77); 14 (58%) female. Most frequent comorbidities: High blood pressure 17 (71%), Diabetes Mellitus 26 (25%), Heart disease 3. SOFA at admission average of 4; (min:1; Max: 11; DS:3); APACHE upon admission: average of 15; (min:6; Max: 24; DS: 4); Mean ICU stay was 6 days (min: 1; Max: 68; SD: 14). There were 5 (21%) deaths. Factors associated with mortality were the use of vasopressors (p=0.013), acute renal failure (p=0.009), surgical site infection (p=0.023), and a mean estimated SOFA of 9 (p=0.0012). Conclusion: Multidisciplinary management of patients undergoing Whipple surgery is essential in order to optimize results, preventing the appearance of complications, and thus reducing their morbidity and mortality.

Duodenopancreatectomía cefálica con resección vascular laparoscópica / Laparoscopic cephalic pancreaticoduodenectomy with laparoscopic vascular resection

RESUMEN Antecedentes: la duodenopancreatectomía cefálica (DPC) con resección vascular venosa está indicada para el tratamiento del adenocarcinoma ductal y de tumores neuroendocrinos de páncreas, tanto por laparoscopia como por laparotomía. Objetivo: describir los resultados de una serie de pacientes operados de DPC con resección vascular venosa y comparar la morbimortalidad entre los abordados por laparoscopia y por laparotomía. Material y métodos: se realizó un estudio observacional, comparativo, retrospectivo de pacientes con DPC con resección vascular entre enero de 2022 y agosto de 2023. El abordaje laparoscópico fue determinado en menores de 80 años, invasión venosa tumoral igual a 180° o menor en la tomografía, buen performance status, y no haber realizado tratamiento neoadyuvante. Resultados: fueron realizadas 23 DPC con resección vascular venosa: 11 por laparoscopia y 12 por laparotomía. Las 11 realizadas por laparoscopia fueron resecciones laterales, y, en los 12 abordados por laparotomía, se realizó resección total de vena porta en 5 y en el resto, resección lateral. El tiempo de "clampeo" (pinzamiento) portal y la necesidad de transfusiones fue similar en ambos grupos. El estudio patológico reveló R0 en el 78,2% de los pacientes e invasión venosa en el 40.9%. La morbilidad con laparoscopia y con laparotomía consistió, respectivamente, en: fístula pancreática en 7 (4 y 3), vaciamiento gástrico retardado en 4 (1 y 4), fístula biliar en uno (1 y 0), neumonía en dos (1 y 1) e infección de herida en uno (0 y 1). La mortalidad fue de 8,6% por el fallecimiento de dos pacientes, uno en cada grupo. Conclusión: de acuerdo con los criterios empleados, la morbimortalidad de la DPC con resección vascular fue similar por laparoscopia y por laparotomía.

ABSTRACT Background: Cephalic pancreaticoduodenectomy (CPD) with venous resection is indicated for the treatment of ductal adenocarcinoma and neuroendocrine tumors of the pancreas, either through laparoscopy or laparotomy. Objective: The aim of this study was to describe the results of a series of patients undergoing CPD with venous vascular resection and compare morbidity and mortality between the laparoscopic approach and open surgery. Material and methods: We conducted a retrospective, comparative and observational study of patients who underwent CPD with venous vascular resection between January 2022 and July 2023. Criteria for laparoscopic surgery were age < 80 years, interface between tumor and vein of 180° of the circumference of the vessel wall or less on computed tomography, good performance status, and no previous neoadjuvant treatment. Results: A total of 23 CPD procedures with venous vascular resection were performed: 11 by laparoscopy and 12 by laparotomy. The 11 laparoscopic procedures were lateral resections, and in the 12 patients approached by laparotomy, 5 were total portal vein resections and 7 were lateral resections. Portal vein clamping time and need for transfusion was similar in both groups. The pathological examination reported R0 resections in 78.2% and venous invasion in 40.9%. The complications associated with laparoscopy and laparotomy were pancreatic fistula in 4 and 3 patients, respectively, delayed gastric emptying in 1 and 4 patients, respectively, biliary fistula in 1 and 0 patients, respectively, aspiration pneumonia i 1 and 1 patients, respectively and surgical site infection in 0 and 1 patients, respectively. Mortality was 8.6% (n =2), one in each group. Conclusion: According to the criteria used, the morbidity and mortality of CPD with vascular resection were similar for laparoscopy and laparotomy.

Linfangioma Quístico del Páncreas. Un Tumor poco Frecuente / Pancreas Cystic Lymphangioma. A Rare Tumor

El linfangioma quístico del páncreas (LQP), es un tumor extremadamente raro y representa solo el 1% de los linfangiomas abdominales. El objetivo de este manuscrito fue reportar un caso de LQP intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Mujer de 67 años, con LQP operada en Clínica RedSalud Mayor Temuco en septiembre de 2023. Se verificó un tumor sólido-quístico de 16 cm de diámetro mayor, adherido al páncreas a nivel del cuerpo de la glándula, de 867 gramos de peso, con líquido amarillento en su interior; la que fue extirpada completamente. Después del estudio histológico, se realizaron tinciones inmunohistoquímicas complementarias para CD31, D2-40 y calretina. La paciente tuvo un curso postoperatorio sin incidentes, siendo dado de alta al tercer día postoperatorio. En el control alejado, se encontraba en buenas condiciones generales. El LQP es un tumor muy poco frecuente. Las características clínicas e imágenes de este tipo de lesiones son inespecíficas. Debe considerarse en el diagnóstico diferencial de las lesiones quísticas pancreáticas. La resección quirúrgica completa con márgenes libres es el tratamiento de elección; y el pronóstico del LQP es favorable si se reseca por completo.

SUMMARY: Pancreas cystic lymphangioma (PCL) are extremely rare, accounting for only 1% of abdominal lymphangiomas. The aim of this study was to report a rare case of PCL, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. 67-year-woman patient with PCL who underwent surgery at Clínica RedSalud Mayor Temuco in September 2023. In this case, a solid-cystic tumor with a major diameter of 16 cm was identified, adhering to the pancreas at the level of the body of the gland, weighing 867 grams and containing yellowish fluid in its interior. The tumor was completely excised. Subsequent to histological examination, additional immunohistochemical staining was performed for CD31, D2-40, and calretinin. The patient experienced an uneventful postoperative course and was discharged on the third postoperative day. During the follow-up, the patient remains in good general condition. LQP is a very rare tumor. Clinical features and images of this type of lesions are nonspecific. It should be considered in the differential diagnosis of pancreatic cystic lesions. Complete surgical resection with free margins is the treatment of choice; and the prognosis of LQP is favorable if it is completely resected.

Resección de metástasis pancreáticas: análisis de resultados quirúrgicos y oncológicos. Estudio de cohorte retrospectiva / Pancreatic resections for metastases in the pancreas: analysis of surgical and oncologic outcomes. A retrospective cohort study

RESUMEN Antecedentes: las metástasis pancreáticas, si bien son poco frecuentes, representan una entidad clínica cuyo diagnóstico probablemente se incrementará en el futuro por el aumento de los programas de seguimiento oncológico. Objetivo: describir los resultados quirúrgicos y oncológicos de una serie de pacientes operados por metástasis pancreáticas. Materiales y métodos: se realizó un estudio de cohorte retrospectivo, descriptivo, multicéntrico, de los pacientes sometidos a resecciones pancreáticas por metástasis entre enero de 2016 y diciembre de 2022, en tres efectores de salud por el mismo grupo quirúrgico. Resultados: fueron operados 19 pacientes, con una media de edad de 59 años (45-79), 11 de sexo femenino, en buen estado general y sin otra evidencia de enfermedad oncológica. El origen de los tumores primarios fue 14 en riñón (7 diagnosticados durante el seguimiento), uno carcinoma mamario, uno melanoma, uno testicular, uno colorrectal y uno de cuello de útero. Las técnicas quirúrgicas empleada fueron: 7 esplenopancreatectomías (5 videolaparoscópicas y 2 convencionales), 4 enucleaciones (3 convencionales y 1 videolaparoscópica), 3 duodenopancreatectomías cefálicas convencionales, 2 duodenopancreatectomías totales convencionales, 2 pancreatectomías centrales convencionales, y una pancreatectomía corporocaudal con preservación del bazo. No se registró mortalidad operatoria (dentro de los 90 días posoperatorios), y presentaron una supervivencia global y libre de enfermedad de 58 y 53 meses, respectivamente. Conclusión: la resección de metástasis pancreáticas, en casos seleccionados, con un abordaje multidisciplinario, y en centros de alto volumen de patología hepatobiliopancreática, es segura y permite buenos resultados oncológicos y de supervivencia global.

ABSTRACT Background: Pancreatic metastases are rare but are likely to be diagnosed more frequently in the future due to the increase in oncology surveillance programs. Objective: The aim of this study was to describe the surgical and oncologic outcomes of a series of patients undergoing surgery for pancreatic metastases. Materials and methods: We conducted a retrospective, descriptive, and multicenter cohort study on patients who underwent pancreatic resections for metastases in the pancreas by the same surgical group between January 2016 and December 2022 in three healthcare providers. Results: A total of 19 patients were operated on, mean age was 59 years (45-79), and 11 were women with good performance status and no other evidence of oncologic disease. Clear cell renal cell carcinoma was the primary tumor in 14 cases (7 diagnosed during surveillance), and the remaining primary tumors were one case of breast ductal carcinoma, one testicular cancer, one colorectal cancer, one melanoma and one cervical cancer. The surgical techniques used were pancreatectomies and splenectomies in 7 patients (5 via laparoscopy and 2 conventional procedures), 4 enucleations (3 conventional procedures and 1 laparoscopic surgery), 3 conventional cephalic pancreaticoduodenectomies, 2 conventional central pancreatectomies and one spleen-preserving distal pancreatectomy. No deaths were reported within 90 days of surgery, and overall survival and disease-free survival were 58 and 53 months, respectively. Conclusion: Resection of pancreatic metastases is safe and provides good oncologic outcomes and overall survival when performed with a multidisciplinary approach in centers with a high volume of hepatobiliary and pancreatic surgeries and in selected cases.

Which detergent is most suitable for the generation of an acellular pancreas bioscaffold?

Pancreatic bioengineering is a potential therapeutic alternative for type 1 diabetes (T1D) in which the pancreas is decellularized, generating an acellular extracellular matrix (ECM) scaffold, which may be reconstituted by recellularization with several cell types to generate a bioartificial pancreas. No consensus for an ideal pancreatic decellularization protocol exists. Therefore, we aimed to determine the best-suited detergent by comparing sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and Triton X-100 at different concentrations. Murine (n=12) and human pancreatic tissue from adult brain-dead donors (n=06) was harvested in accordance with Institutional Ethical Committee of the University of São Paulo Medical School (CEP-FMUSP) and decellularized under different detergent conditions. DNA content, histological analysis, and transmission and scanning electron microscopy were assessed. The most adequate condition for pancreatic decellularization was found to be 4% SDC, displaying: a) effective cell removal; b) maintenance of extracellular matrix architecture; c) proteoglycans, glycosaminoglycans (GAGs), and collagen fibers preservation. This protocol was extrapolated and successfully applied to human pancreas decellularization. The acellular ECM scaffold generated was recelullarized using human pancreatic islets primary clusters. 3D clusters were generated using 0.5×104 cells and then placed on top of acellular pancreatic slices (25 and 50 μm thickness). These clusters tended to connect to the acellular matrix, with visible cells located in the periphery of the clusters interacting with the ECM network of the bioscaffold slices and continued to produce insulin. This study provided evidence on how to improve and accelerate the pancreas decellularization process, while maintaining its architecture and extracellular structure, aiming at pancreatic bioengineering.

Fístula pancreática: una complicación temida. Experiencia en una unidad de cirugía hepatobiliopancreática de cuarto nivel / Pancreatic fistula: A feared complication. Experience in a fourth level hepatobiliopancreatic surgery unit

Introducción. La fístula pancreática postoperatoria es una de las complicaciones más importantes en la cirugía hepatobiliopancreática. Su diagnóstico se hace mediante la presencia de un nivel de amilasa en el líquido de drenaje al menos tres veces por encima del valor de la amilasa en suero a partir del tercer día postoperatorio. El objetivo de este estudio fue caracterizar los pacientes con fístula pancreática postoperatoria en nuestra institución, evaluando la importancia de la detección temprana y el establecimiento de un manejo oportuno. Métodos. Estudio descriptivo, retrospectivo, que incluyó los pacientes sometidos a pancreatoduodenectomía, con diagnóstico de fístula pancreática postoperatoria como complicación de cirugía hepatobiliopancreática, en el Hospital Internacional de Colombia, en Piedecuesta, entre enero del 2017 y diciembre de 2020. Se excluyeron los pacientes con otro tipo procedimiento quirúrgico y aquellos que decidieron no participar en el estudio. Resultados. Se evaluaron 69 pacientes, con un predominio del sexo femenino (n=38; 55,1 %) y mediana de la edad de 57 años. El 33,3 % (n=24) de los pacientes intervenidos desarrollaron fístula pancreática postoperatoria, siendo el 23,2 % fuga bioquímica, grado B 8,7 % y grado C 2,9 %, para quienes se indicaron manejo expectante, control ecográfico y reintervención, respectivamente. Fallecieron 5 pacientes (7,2 %). Conclusiones. La fístula pancreáticapostoperatoria es una complicación para tener en cuenta en todos los pacientes sometidos a pancreatoduodenectomía. Existen estrategias que pueden permitir disminuir la incidencia de esta complicación, con el fin de mejorar el desenlace, el pronóstico y la morbilidad posquirúrgica.

Introduction. Postoperative pancreatic fistula is one of the most important complications in hepatobiliopancreatic surgery. Its diagnosis is made by the presence of an amylase level in the drainage fluid at least three times above the serum amylase value from the third postoperative day. The objective of this study was to characterize patients with postoperative pancreatic fistula at our institution, evaluating the importance of early detection and to establish a timely management. Methods. Descriptive, retrospective study that included patients who underwent pancreatoduodenectomy with a diagnosis of postoperative pancreatic fistula as a complication of hepatobiliopancreatic surgery at the Hospital Internacional Colombia, between January 2017 and December 2020. Patients with another type of procedure performed by this specialty and those who did not decide to participate in the study were excluded. Results. A total of 69 patients were included, the median age was 57 years with a predominance of females (n=38; 55.1%). 33.3% (n=24) of the operated patients developed postoperative pancreatic fistula, with 23.2% having a biochemical leak, grade B in 8.7% and grade C in 2.9%, for whom expectant management, ultrasound control and reintervention were indicated, respectively. Five patients died (7.2%). Conclusions. Pancreatic fistula is a complication to take into account in all patients undergoing pancreatoduodenectomy. There are strategies that can reduce the incidence of this complication and thus improve not only the outcome but also the prognosis and postoperative morbidity.

Tumor pseudopapilar sólido de páncreas, una neoplasia inusual / Solid Pseudopapillary Tumor of the Pancreas, an Unusual Neoplasm

Presentación del caso. Se trata de una mujer de 26 años que presentó dolor en epigastrio e hipocondrio izquierdo, con aumento del perímetro abdominal y pérdida de 5 kg de peso corporal. En el examen físico se detectó una masa de gran tamaño en el epigastrio, con bordes regulares, ligeramente dolorosa al tacto y no móvil. Los estudios de imagen revelaron una neoplasia mixta en el cuerpo y cola pancreática. Intervención terapéutica. Se practicó una esplenopancreatectomía corpo-caudal, con extirpación completa del tumor. Evolución clínica. La paciente recibió cuidados especializados y vigilancia estrecha posquirúrgica en la unidad de cuidados intensivos, sin presentar complicaciones relevantes. Tras el alta hospitalaria, la paciente refirió un buen estado general en los controles de seguimiento, que incluyeron una tomografía realizada a los 12 meses, donde no se evidenciaron restos o recidivas tumorales

Case presentation. A 26-year-old woman who presented with pain in the epigastrium and left hypochondrium, with increased abdominal perimeter and loss of 5 kg of body weight. Physical examination revealed a large mass in the epigastrium, with regular borders, slightly painful to the touch and non-mobile. Imaging studies revealed a mixed neoplasm in the pancreatic body and tail. Treatment. A corpo-caudal splenopancreatectomy was performed, with complete removal of the tumor. Outcome. The patient received specialized care and close postoperative surveillance in the intensive care unit, with no relevant complications. After hospital discharge, the patient reported a good general condition in the follow-up controls, which included a computed tomography scan performed after 12 months, where no tumor remnants or recurrences were evidenced

Evaluation of Fine Needle Biopsy (FNB) for Endoscopic Ultrasound (EUS)-guided tissue acquisition of pancreatic masses to negate the need for rapid on-site evaluation: A randomized control trial

Background and Objectives@#The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in large, randomized trials. New equipment using EUS-guided fine needle biopsy (FNB) allows for more material to be acquired that may obviate the need for ROSE. This study aimed to evaluate if EUS-FNB without ROSE was non-inferior to EUS-FNA with ROSE in solid pancreatic masses (SPMs). @*Methods@#Patients with SPMs requiring tissue sampling were randomly assigned to undergo either EUS-FNA with ROSE or EUS-FNB without ROSE. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy and secondary endpoints were specimen quality, complication rates, and procedure time. @*Results@#Seventy-eight patients were randomized and analyzed (39 EUS-FNA with ROSE and 39 EUS-FNB without ROSE). Non-significantly different diagnostic accuracies were noted in both groups (97% with ROSE and 100% without ROSE, P < 0.371). The bloodiness of histologic samples and complication rates were not significantly different between groups. A significantly shorter mean sampling procedural time was noted for EUS-FNB over EUS-FNA with ROSE (30.4 ± 10.4 vs 35.8 ± 9.8 minutes, P < .02). @*Conclusions@#EUS-FNB demonstrated equal diagnostic accuracy with shorter procedure times in evaluating SPMs compared to EUS-FNA with ROSE. These new-generation FNB needles may obviate the need for ROSE.

Value of a nomogram model in early recurrence of pancreatic ductal adenocarcinoma after laparoscopic pancreaticoduodenectomy / 临床肝胆病杂志

ObjectiveTo investigate the risk factors for early tumor recurrence after laparoscopic pancreaticoduodenectomy （LPD） in patients with pancreatic ductal adenocarcinoma （PDAC）， and to establish a predictive model. MethodsA retrospective analysis was performed for the clinical data of 240 PDAC patients who underwent LPD in The First Hospital of Jilin University from April 2016 to July 2022， with early postoperative tumor recurrence （time to recurrence ≤12 months） as the study outcome. The patients were randomly divided into training group with 168 patients and validation group with 72 patients at a ratio of 7∶3. In the training group， there were 70 patients （41.67%） with early postoperative recurrence and 98 （58.33%） without early recurrence， and in the validation group， there were 32 （44.44%） with early postoperative recurrence and 40 （55.56%） without early recurrence. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a logistic regression analysis was used to investigate the risk factors for early postoperative recurrence； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to evaluate the discriminatory ability of the model， with AUC>0.75 indicating that the model had adequate discriminatory ability. The Bootstrap resampling method was used for validation after 1 000 times of random sampling， and the model was validated again in the validation group. The calibration curve and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the degree of calibration， and the decision curve analysis was used to evaluate clinical practicability. ResultsThe univariate and multivariate analyses showed that preoperative CA19-9 level≥37 U/mL （odds ratio ［OR］=6.265， 95% confidence interval ［CI］： 1.938‍ ‍—‍ ‍20.249， P<0.05）， maximum tumor diameter >3 cm （OR=10.878， 95%CI： 4.090‍ ‍—‍ ‍28.932， P<0.05）， poor tumor differentiation （OR=3.679， 95%CI： 1.435‍ ‍—‍ ‍9.433， P<0.05）， lymph node metastasis （OR=0.209， 95%CI： 0.080‍ ‍—‍ ‍0.551， P<0.05）， and absence of adjuvant chemotherapy after surgery （OR=0.167， 95%CI： 0.058‍ ‍—‍ ‍0.480， P<0.05）. A nomogram model was constructed based on these factors； the ROC curve analysis showed that the model had an AUC of 0.895 （95%CI： 0.846‍ ‍—‍ ‍0.943， P<0.001）， and the calibration curve and the Hosmer-Lemeshow test showed that the model had a good degree of calibration （P=0.173）. The decision curve analysis showed that the nomogram had a good clinical application value. ConclusionPreoperative CA19-9 level ≥37 U/mL， maximum tumor diameter >3 cm， poor tumor differentiation， lymph node metastasis， and absence of adjuvant chemotherapy after surgery are independent risk factors for the early recurrence of PDAC after LPD， and the nomogram model established based on these factors can effectively predict early postoperative recurrence.

The pathogenesis of hyperlipidemic acute pancreatitis caused by pancreatic duct hypertension / 临床肝胆病杂志

Compared with acute pancreatitis caused by other factors， hyperlipidemic acute pancreatitis often has a higher rate of severe conditions， greater difficulties in predicting prognosis， and a more complex and unclear pathogenesis. At present， the pathogenesis of hyperlipidemic acute pancreatitis may be associated with the elevation of serum free fatty acids， but the lipid-lowering treatment regimens do not reduce the incidence rate of this disease. Recent studies have further confirmed that pancreatic duct hypertension is an important pathogenesis of acute pancreatitis. The latest research advances have shown that hyperlipidemia can lead to pancreatic duct obstruction by causing pancreatic duct hyperplasia， forming protein embolism at the biliary-pancreatic junction， and damaging the secretory function of the pancreatic duct， while pancreatic duct obstruction can in turn cause pancreatic duct obstruction. This article reviews the latest research advances in hyperlipidemia in causing pancreatic duct obstruction and emphasizes that pancreatic duct hypertension is one of the important pathogeneses of hyperlipidemic acute pancreatitis， which will provide new ideas for exploring the pathogenesis of hyperlipidemic acute pancreatitis.

Jiedu Tongluo Tiaogan Prescription Protects Pancreatic β Cell by Targeting NLRP3 Inflammasome via TGR5/cAMP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Relationship between hsa_circ_401724 expression and inflammatory response and pancreatic islet cell function in type 2 diabetic patients / 国际检验医学杂志

Objective To analyze the relationship between the expression of hsa_circ_401724 and the in-flammatory response in type 2 diabetes mellitus(T2DM)patients and pancreatic islet cell function.Methods A total of 102 patients with T2DM treated in Linfen Central Hospital from April 2017 to December 2022 were selected as the observation group,and 100 healthy subjects with normal glucose tolerance were se-lected as the control group during the same period.The levels of tumor necrosis factor α(TNF-α),interleukin-6(IL-6)and intercellular adhesion molecule-1(ICAM-1)in the blood of the subjects were detected by en-zyme-linked immunosorbent assay to evaluate the levels of inflammatory factors in the subjects.The relative expression level of hsa_circ_401724/U6 was calculated according to the dissolution curve,and the pancreatic islet cell function of the subjects was assessed,including homeostasis model assessment of insulin resistance(HOMA-IR)and homeostatic model assessment beta cell function(HOMA-β)as assessed by homeostasis model.Pearson correlation was used to analyze the correlation between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function,and Logistics regression model was used to analyze the rela-tionship between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function.Results The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in observation group were significantly higher than those in control group,while the levels of HOMA-β in observation group were significantly lower than those in control group,with statistical significance(P＜0.05).The relative expression level of hsa_circ_401724 in observation group(0.75±0.13)was significantly higher than that in control group(0.24±0.06),and the difference was statistically significant(P＜0.05).The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in hsa_circ_401724 high expression group were significantly higher than those in hsa_circ_401724 low expres-sion group,and the levels of HOMA-β were significantly lower than those in hsa_circ_401724 low expression group.The difference was statistically significant(P＜0.05).The relative expression level of hsa_circ_401724 was positively correlated with the levels of HOMA-IR,TNF-α,IL-6 and ICAM-1(r=0.657,0.671,0.703,0.698,P＜0.05).hsa_circ_401724 expression level was negatively correlated with HOMA-β level(r=-0.611,P＜0.05).The high expression of hsa_circ_401724 was an independent risk factor affecting the levels of HOMA-IR,HOMA-β,TNF-α,IL-6 and ICAM-1 in T2DM patients(P＜0.05).Conclusion The high ex-pression of hsa_circ_401724 is related to the inflammatory response and the decline of pancreatic islet cell function in T2DM patients.

Research status and prospect of pancreatic fistula after laparoscopic pancreaticoduodenectomy / 国际外科学杂志

With the rapid development of laparoscopic techniques, the safety of laparoscopic surgery has gradually been recognized. Its advantages, including clear visualization, minimal trauma and faster recovery, are increasingly favored by surgeons and patients. Common postoperative complications of laparoscopic pancreaticoduodenectomy include pancreatic fistula, bleeding, gastric paresis, pancreatic insufficiency, and wound infection. Among them, postoperative pancreatic fistula and its related complications are the leading causes of mortality after laparoscopic pancreaticoduodenectomy. This article present an overview of the understanding of postoperative pancreatic fistula, combined with recent research progress in this field, to explore the potential mechanisms of pancreatic fistula occurrence and development, and also summarize the predictive models for postoperative pancreatic fistula and discuss the future trends in laparoscopic pancreaticoduodenectomy.

miR-139-5p enhances the inhibition effect of metformin on cell proliferation of pancreatic cancer cell line PANC-1 cultured in normal-glucose medium / 基础医学与临床

Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines / 基础医学与临床

Objective To study the effect of carboxyamidotriazole-orotate(CTO)on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells.Methods Human pancreatic cancer cell lines AsPC-1,AsPC-1/GEM(AR),PANC-1 and MiaPaCa-2 were used as the study subjects;cell survival rate was detected by sulfo-nylrhodamine B(SRB);the mRNA level of key genes for fatty acid synthesis was detected by qPCR;the protein level of the AMPK/ACC pathway was detected by Western blot;intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS).Results Comparing to control group,CTO significantly de-creased the cell viability of AsPC-1,AR,PANC-1,and MiaPaCa-2(P＜0.05).CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05).CTO significantly reduced the protein expression of AMPK,ACC and c-Myc(P＜0.05),while increasing the protein expression of p-AMPK and p-ACC(P＜0.05).CTO decreased lipid metabolite content in AR cells(P＜0.05).Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway,down-regulates the expression of fatty acid synthesis-related genes,and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1,AR,PANC-1 and MiaPaCa-2.

Effect of MSC-exo,a New Cell Delivery Tool,on Gene Delivery and Proliferation of Pancreatic Cancer / 昆明医科大学学报

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Expression of adhesion G protein-coupled receptor F1 in pancreatic ductal adenocarcinoma and its mechanism of promoting cancer progression / 上海交通大学学报（医学版）

Objective·To analyze the expression changes of adhesion G protein-coupled receptor F1(ADGRF1)in the occurrence and development of pancreatic ductal adenocarcinoma(PDAC),and explore the impact of ADGRF1 on the proliferation of PDAC cells and the potential molecular mechanisms that promote PDAC progression.Methods·The expression of ADGRF1 at mRNA level was analyzed based on the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database,respectively.The expression of ADGRF1 in normal pancreatic ductal epithelial cells(hTERT-HPNE)and various PDAC tumor cells was detected by using real-time fluorescence quantitative PCR(qPCR)and Western blotting.Immunohistochemical staining(IHC)was used to detect the differential expression of ADGRF1 in cancer tissues and adjacent tissues of PDAC patients.After knocking down ADGRF1 with small interfering RNA(siRNA)transfection,the changes in the proliferation ability of PDAC AsPC-1 and SW1990 cells were detected through CCK8 assay and plate cloning experiment.Stable overexpression of ADGRF1 was constructed in PDAC Patu8988 cell line,and the proliferation changes induced by overexpression of ADGRF1 were evaluated through CCK8 assay.RNA sequencing(RNA-seq),gene set enrichment analysis(GSEA),and immune infiltration analysis were utilized to predict signaling pathways associated with ADGRF1-mediated promotion of PDAC cancer progression.Results·Analysis of the TCGA database and GEO database revealed higher expression of ADGRF1 mRNA in PDAC tissues compared to normal pancreatic tissues(all P=0.000).qPCR and Western blotting results demonstrated up-regulation of ADGRF1 mRNA and protein levels in various PDAC cells compared to hTERT-HPNE cells(all P<0.05).IHC results confirmed higher ADGRF1 expression in PDAC cancer tissues compared to adjacent tissues.Furthermore,downregulation of ADGRF1 inhibited the proliferation of PDAC AsPC-1 and SW1990 cell lines,while overexpression of ADGRF1 promoted the proliferation of Patu8988 cells(all P<0.05).RNA-seq,GSEA enrichment analysis,and immune infiltration analysis revealed that ADGRF1 expression was related to signaling pathways such as interferon-α(IFN-α),tumor necrosis factor-α(TNF-α),and nuclear factor κB(NF-κB).Conclusion·ADGRF1 is highly expressed in PDAC cells and tissues,and promotes the proliferation of PDAC cells via immune-related signaling pathways.

Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors / 复旦学报（医学版）

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.