Progress and reflection of conversion therapy for locally advanced pancreatic cancer / 中华外科杂志

With the improvement of nonsurgical treatment in pancreatic cancer, the increasing accuracy of subclassification of anatomy, and the continuous refinement of surgical resection techniques, more and more locally advanced pancreatic cancer(LAPC) patients have the opportunity to undergo conversion surgery and achieve survival benefits,which has attracted the attention of scholars in this field. Despite the numerous prospective clinical studies conducted, there is still a lack of high-level evidence-based medical evidence in terms of conversion treatment strategies, efficacy evaluation, surgical timing and survival prognosis, and there are not yet specific quantitative standards and guiding principles for conversion treatment for these patients in clinical practice, and the indications for surgical resection rely more on the experience of each center or surgeon, lacking consistency. Therefore,the indicators for the evaluation of the efficacy of conversion treatment in patients with LAPC were summarized to reflect on the different modes of conversion treatment and clinical outcomes currently being explored, expecting to provide more accurate recommendations and guidance for the clinic.

Características y resultados del tratamiento aplicado a los pacientes con cáncer de páncreas / Rejuvenation Surgery with High-Superficial Musculoaponeurotic System Flap

Introducción: El cáncer de páncreas mantiene un pronóstico ominoso a pesar de los avances en técnicas quirúrgicas y cuidados perioperatorios. Objetivo: Caracterizar los resultados del tratamiento aplicado a los pacientes con cáncer de páncreas. Métodos: Se realizó un estudio observacional, descriptivo y transversal de una serie de 70 pacientes con diagnóstico de cáncer de páncreas. Se estudiaron las variables: localización, tamaño del tumor, procedimiento quirúrgico, estadificación preoperatoria, diagnóstico histológico, estancia hospitalaria, complicaciones posoperatorias y estado al egreso, mediante el análisis de frecuencias absolutas, relativas y la media así como la prueba de ji al cuadrado y el IC 95 por ciento. Resultados: El procedimiento quirúrgico más frecuente fue derivativo en 47 enfermos (67,1 por ciento). La operación de Whipple se realizó en 10 pacientes (14,3 por ciento) con tumores localizados en la cabeza del páncreas y la pancreatectomía corporocaudal en 11 (15,7 por ciento) con tumores de cuerpo y cola del páncreas. La mayoría correspondió a los estadios III y IV. El 47,1 por ciento de los pacientes presentó un adenocarcinoma poco diferenciado. La estadía fluctuó entre 15 y 30 días en el 54,3 por ciento de la serie. Las complicaciones se presentaron en 19 enfermos (27,1 por ciento). Fallecieron 15 pacientes (21,4 por ciento) del total. Conclusiones: El tratamiento debe ser individualizado mediante equipos multidisciplinarios, con protocolos de actuación uniformes en cada institución que permita realizar estudios multicéntricos, con el objetivo de obtener estadísticas propias en aras de disminuir la morbilidad y la mortalidad, así como aumentar la calidad de vida de estos pacientes(AU)

Introduction: Facial rhytidectomy is the technique for correcting facial aging features, but they are becoming increasingly complex due to the incorporation of deeper planes in the process. The superficial musculoaponeurotic system techniques have the advantage of providing a greater degree of naturalness and permanence in time. Objective: To evaluate the effectiveness of the high-superficial musculoaponeurotic system technique for facial rejuvenation. Methods: A prospective and longitudinal case series study was carried out in the plastic surgery service of Hospital General Universitario "Vladimir Ilich Lenin" with patients who requested facial rejuvenation and were treated with the high-superficial musculoaponeurotic system technique, from January 1, 2018 to June 30, 2020. The variables age, sex, skin type, degree of aging, operative complications, patient satisfaction and aesthetic outcomes were studied. Results: The female sex predominated, together with the age group 50-59 years, the degrees of aging II and III, as well as white and light brown skin colors, while the most frequent operative complication was wound dehiscence of the suture line at the auricle root. The patients' satisfaction with the aesthetic outcomes of the surgical intervention was verified and the aesthetic outcomes was assessed as favorable in 100 percent of the cases for the used surgical technique. Conclusions: The high-superficial musculoaponeurotic system surgical technique for rhytidectomy offers harmonic, long-lasting outcomes with a low percentage of complications, making it a valuable alternative for patients(AU)

Nimotuzumab combinado con un esquema de quimioterapia GEMOX en pacientes con cáncer pancreático avanzado / Nimotuzumab combined with GEMOX chemotherapy regimen in patients with advanced pancreatic cancer

Se realizó un estudio retrospectivo y observacional en pacientes con adenocarcinoma pancreático avanzado, tratados con Nimotuzumab combinado con un esquema de quimioterapia GEMOX, atendidos en el Servicio de Oncología Clínica del Hospital Clínico Quirúrgico Hermanos Ameijeiras entre 2013 y 2019 (n=118), cuyo objetivo fue evaluar la respuesta al tratamiento y la supervivencia global según variables clínicas, histopatológicas y tratamiento. Se utilizó método chi-cuadrado para la asociación de variables. Se evaluó la supervivencia global por el método de Kaplan Meier y se utilizó la prueba de Log-Rank y Breslow para la comparación de las curvas, con valor p<0.05. La tasa de control de la enfermedad fue 44,9. La mediana de supervivencia fue de 13,8 meses (IC95 por ciento:11,7-15,8). Las variables estadísticamente significativas asociadas con mayor respuesta al tratamiento y supervivencia fueron: no hábitos tabáquicos; índice plaquetas-linfocitos por debajo de 200; tumores primarios T2-T3, de localización predominantemente en cabeza pancreática; no presencia de metástasis al diagnóstico y más de seis dosis de quimioterapia o Nimotuzumab. Los pacientes con clasificación de bajo peso y albúmina sérica baja tuvieron peor supervivencia (p<0.05). En 42 pacientes se realizó una segunda línea de quimioterapia y se obtuvo supervivencia de 17,4 meses (IC95 por ciento:13,5-21,4). Las toxicidades clasificadas como grado 3-4 se reportaron en 27 pacientes (22,9 por ciento), las más frecuentemente observadas fueron: neuropatía (14,4 por ciento), neutropenia (10,2 por ciento) y trombopenia (9,3 por ciento). En condiciones de práctica clínica, con el Nimotuzumab combinado con quimioterapia GEMOX se obtuvieron óptimas tasas de control de la enfermedad y supervivencia con buen perfil de seguridad(AU)

A retrospective and observational study was carried out in patients with advanced pancreatic adenocarcinoma, treated with Nimotuzumab combined with a GEMOX chemotherapy scheme, in the Clinical Oncology Service at the Ameijeiras Hospital, between 2013 and 2019 (n =118), whose objective was to evaluate the response to the treatment and overall survival according to clinical, histopathological and treatment variables. The chi-square method was used for the association of variables. Overall survival was evaluated by the Kaplan Meier method and the Log-Rank and Breslow test for the comparison of the curves, with p <0.05. The disease control rate was 44.9. The median survival was 13.8 months (95 percent CI: 11.7-15.8). The statistically significant variables associated with greater response to treatment and survival were: no smoking habits; platelet-lymphocyte index below 200; T2-T3 primary tumors, predominantly located in the pancreatic head; no presence of metastases at diagnosis and greater than six doses of chemotherapy and Nimotuzumab. Patients classified as underweight and low serum albumin had worse survival (p <0.05). Second-line chemotherapy was performed in 42 patients and it was obtained SV of 17.4 months (95 percent CI: 13.5-21.4). Toxicities classified as grade 3-4 were reported in 27 patients (22.9 percent); the most frequently observed were: neuropathy (14.4 percent), neutropenia (10.2 perrcent) and thrombopenia (9.3 percent). Under clinical practice conditions, Nimotuzumab combined with GEMOX chemotherapy obtained optimal disease control and survival rates with a good safety profile(AU)

Páncreas ectópico en antro gástrico asociado a síntomas de reflujo. Reporte de un caso / Ectopic pancreas in gastric antrum associated to reflux symptoms. Report of a case

RESUMEN El páncreas ectópico es una entidad poco común. Como tumor submucoso de origen congénito, frecuentemente presenta un curso asintomático, aunque con posibles complicaciones. Su diagnóstico de certeza se basa en la endoscopia, el ultrasonido endoscópico y la histología, que permiten adoptar una conducta expectante o quirúrgica. El paciente estudiado presentó un páncreas ectópico localizado en antro gástrico asociado a síntomas de reflujo gastroesofágico rebeldes a tratamiento, los cuales motivaron el estudio endoscópico, con el consecuente hallazgo de dicha entidad (AU).

ABSTRACT Ectopic pancreas is a little common entity. As congenital-originated sub mucous tumor, it frequently presents an asymptomatic course, though with possible complications. Its definitive diagnosis is based in the endoscopy, endoscopic ultrasound and histology, allowing to adopt an expectant or surgical behavior. The current patient presented an unresponsive-to-treatment ectopic pancreas located in the gastric antrum associated to gastro-esophageal reflux symptoms. This motivated the endoscopic study consequently leading to finding this entity (AU).

Whether early stage pancreatic ductal adenocarcinoma patients could benefit from the post-operation chemotherapy regimens: a SEER-based propensity score matching study / 浙江大学学报·医学版

To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance，epidemiology，and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.

Pancreatitis aguda en carcinoma de célula pequeña de pulmón (CPCP) resuelta con quimioterapia / Acute pancreatitis in small-cell lung carcinoma (SCLC) resolved with chemotherapy

Resumen El carcinoma de célula pequeña (CPCP) o microcítico de pulmón es un subtipo de cáncer de pulmón que típicamente se ha asociado al tabaquismo y que se caracteriza por su agresividad y mal pronóstico a corto plazo. Como entidad, puede metastatizar en cualquier órgano, siendo las metástasis pancreáticas raras y la mayoría de las veces asintomáticas. Por ello, la presencia de una pancreatitis neoplásica, como en el caso presentado, es excepcional, y aún más cuando presenta refractariedad al tratamiento médico convencional y responde al tratamiento citotóxico sistémico. Por todo ello, se expone esta experiencia clínica y se debate la presencia de esta rara entidad y su manejo.

Abstract Small-cell lung carcinoma is a subtype of neoplasm that has been typically associated with smoking; it is characterized by its aggressiveness and poor prognosis in the short term. As an entity, it can metastasize in any organ, but pancreatic metastases are rare and most of the time asymptomatic. Therefore, the presence of neoplastic pancreatitis as in our case is exceptional; even more when it presents refractoriness to conventional medical treatment, responding instead to systemic cytotoxic treatment. Therefore, we expose our clinical experience and discuss the presence of this rare entity and its management.

Arginine metabolism: a potential target in pancreatic cancer therapy / 中华医学杂志(英文版)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.

Neurolisis del plexo celiaco en cáncer de páncreas / Neurolysis of the celiac plexus in pancreas cancer

Introducción: El cáncer en Cuba constituye la primera causa de mortalidad en edades de 15 a 64 años y la segunda en mayores de 65, los tumores digestivos ocupan la tercera posición en las neoplasias malignas y la afección pancreática el cuarto lugar dentro de estas. Objetivo: Presentar la evolución de un paciente con un tumor de páncreas y una supervivencia de más de 6 meses al cual se le realizó neurolisis del plexo celiaco. Presentación del caso: Paciente masculino de 64 años de edad con el diagnóstico de adenocarcinoma de cuerpo y cola de páncreas sin criterio quirúrgico con dolor de severa intensidad que imposibilita el inicio del tratamiento adyuvante para lo cual se le realizó neurolisis del plexo celiaco bilateral, con 7 mL de fenol al 10 por ciento por cada lado, vía posterior retrocrural bajo seguimiento con intensificador de imágenes, y se administró tratamiento coadyuvante vía oral a base de antidepresivos tricíclicos, analgésicos y ansiolíticos debido al componente mixto del dolor oncológico. Conclusiones: El bloqueo neurolitico del plexo celiaco asociado a terapia farmacológica analgésica convencional por vía oral proporcionó un alivio total del dolor por neoplasia de páncreas de forma inmediata y duradera, se logró mejorar el estado general del paciente lo cual facilitó el inicio de la terapia adyuvante oncológica(AU)

Introduction: In Cuba, cancer is the leading cause of death at ages 15-64 and the second at ages over 65, digestive tumors occupy the third position among malignancies and pancreatic affection the fourth place among these. Objective: To present the evolution of a patient with a pancreatic tumor and survival of more than 6 months who underwent neurolysis of the celiac plexus. Case presentation: A 64-year-old male patient diagnosed with adenocarcinoma of the body and tail of the pancreas without surgical criteria, with pain of severe intensity that made it impossible to start adjuvant treatment, for which he underwent neurolysis of the bilateral celiac plexus, with 7 mL of phenol-10 percent per side, through the retrocrural posterior space with follow-up with image intensifier, and oral adjuvant treatment was administered with tricyclic, analgesic and anxiolytic antidepressants due to the mixed component of oncological pain. Conclusions: The neurolytic block of the celiac plexus associated with conventional oral analgesic pharmacological therapy provided total relief of pain from pancreatic cancer in an immediate and lasting way. It was possible to improve the general state of the patient, which facilitates the start of adjuvant oncology therapy(AU)

Nimotuzumab y gemcitabina en el tratamiento del cáncer de páncreas y metástasis esplénica / Nimotuzumabe e gencitabina no tratamento do câncer de pâncreas e metástases esplênicas / Nimotuzumab and gemcitabine in the treatment of pancreatic cancer and splenic metastases

Se presentó un paciente masculino de 69 años con una colestasis extrahepática, pérdida de peso, astenia y anorexia, antecedentes de pancreatitis crónica, diabetes mellitus e hipertensión arterial, el cual fue diagnosticado con adenocarcinoma de páncreas con metástasis esplénica. Se le realizó colecistoyeyunostomía con yeyunoyeyunostomía por ser irresecable el tumor. Fue incluido en el ensayo clínico IIC RDEC166 y tratado con nimotuzumab y gemcitabina. En los estudios evolutivos no se apreciaron las imágenes metastásicas que se observaron antes del tratamiento lo que presupone la utilidad de estos fármacos para el control de éstas. No se encontraron referentes sobre el tema en la literatura nacional e internacional consultadas(AU)

A 69-year-old male patient presented with extrahepatic cholestasis, weight loss, asthenia and anorexia, a history of chronic pancreatitis, diabetes mellitus and arterial hypertension, who was diagnosed with adenocarcinoma of the pancreas with splenic metastases. A cholecystojejunostomy was performed with jejunum jejunostomy because the tumor was unresectable. It was included in the IIC RDEC166 clinical trial and treated with nimotuzumab and gemcitabine. In the evolutionary studies the metastatic images that were observed before the treatment were not appreciated, which presupposes the usefulness of these drugs for their control. No references on the subject were found in the national and international literature consulted(AU)

Paciente do sexo masculino, 69 anos, apresentou colestase extrahepática, perda de peso, astenia e anorexia, história de pancreatite crônica, diabetes mellitus e hipertensão arterial, diagnosticada com adenocarcinoma do pâncreas com metástases esplênicas. Uma colecistojejunostomia foi realizada com jejuno jejunostomia porque o tumor era irressecável. Foi incluído no ensaio clínico IIC RD-EC166 e tratado com nimotuzumab e gencitabina. Nos estudos evolutivos, as imagens metastáticas observadas antes do tratamento não foram apreciadas, o que pressupõe a utilidade desses medicamentos para seu controle. Não foram encontradas referências sobre o assunto na literatura nacional e internacional consultada(AU)

Neurotoxicidad orofacial en FOLFIRINOX: ¿Oxaliplatino o Irinotecán? / Oropharyngeal neurotoxicity in FOLFIRINOX: Oxaliplatin or Irinotecan?

El cáncer de páncreas resulta una de las patologías oncológicas con mayor índice de mortalidad en Argentina. Dadala importancia y prevalencia de esta afección, en los últimos años se han desarrollado varias alternativas de tratamiento que incluyen cirugía, radioterapia y quimioterapia endovenosa. El FOLFIRINOX es uno de los esquemas dequimioterapia de primera línea en los casos de neoadyuvancia y tumores avanzados. El esquema incluye dos drogasneurotóxicas: Oxaliplatino e Irinotecán. Se presentan dos casos de neurotoxicidad orofaríngea durante la infusiónde quimioterapia: un paciente masculino de 38 años y una femenina de 54. En ambos casos la neurotoxicidad fuereversible espontáneamente. Se plantea la disminución de la velocidad de infusión de oxaliplatino y la separación dela administración de ambas drogas como estrategia para la disminución de los efectos adversos(AU)

Pancreatic cancer is one of the oncological pathologies with the highest mortality rate in Argentina. Given the prevalenceof this condition, several treatments have been developed, including surgery, radiotherapy and intravenous chemotherapy.FOLFIRINOX is one of the first-line chemotherapy schemes in cases of neoadjuvant and advanced tumors. The schemeincludes two highly neurotoxic drugs: Oxaliplatin and Irinotecan. We present two cases of oropharyngeal neurotoxicityduring the chemotherapy infusion. A 38 years old male patient and 54 years old female patient. In both cases theoropharyngeal neurotoxicity was spontaneously reversible. The decrease in the rate of infusion of oxaliplatin and theseparation of the administration of both drugs was the strategy for the reduction of adverse effects(AU)

Acetato de lanreotida para o tratamento de tumores neuroendócrinos gastroenteropancreáticos / Lanreotide acetate for the treatment of gastroenteropancreatic neuroendocrine tumors

CONTEXTO: Os tumores neuroendócrinos gastrintestinais e do pâncreas constituem um grupo heterogêneo de tumores com origem no sistema neuroendócrino difuso do trato gastrintestinal e de células neuroendócrinas ou pluripotentes do pâncreas. A maioria ocorre no jejuno, íleo, cólon e reto. As prevalências variam de 20 a 35 por 100.000, enquanto as incidências entre 2,5 a 5,25 por 100.000 pessoas/ano. A histopatologia tumoral, o tamanho e a extensão, comprometimento locorregional e presença de metástases hepáticas são fundamentais para o diagnóstico, prognóstico e para o planejamento da conduta terapêutica. Essas características influenciam na sobrevida global. Dessa forma, os tumores podem ser classificados em diferenciados de grau 1 (G1) e grau 2 (G2) ou pouco diferenciados de grau 3 (G3) e ainda nos estádios I a IV de acordo com comprometimento locorregional e presença de metástase. Os tumores mais diferenciados, em estádios menores e sem metástases hepáticas tem melhor prognóstico com maior sobrevida global. Esses tumores em função de suas características geralmente não são diagnosticados até que a doença envolva outros órgãos (dor e obstrução) ou na presença de metástases hepáticas, com prejuízo ao funcionamento desse órgão. A mediana da sobrevida global em indivíduos com tumores bem ou moderadamente diferenciados e com metástases distantes é de 33 meses. TECNOLOGIA: Acetato de Lanreotida. INDICAÇÃO: Tratamento de tumores neuroendócrinos gastroenteropancreáticos irressecáveis metastáticos. PERGUNTA: "Análogos de somatostatina são eficazes e seguros no tratamento de adultos diagnosticados com tumores neuroendócrinos gastroenteropancreáticos irressecáveis localmente avançados ou metastáticos ou ativos após a cirurgia?" EVIDÊNCIAS CIENTÍFICAS: Foi construída estratégia e conduzida busca estruturada. Recuperaramse 7 estudos clínicos e outros estudos de extensão e de análise de subgrupos. Os participantes tinham tumores neuroendócrinos irressecáveis localmente avançados ou metastáticos de graus 1 ou 2, com as lesões primárias localizadas principalmente no intestino médio e pâncreas e com metástases majoritariamente hepáticas. Em dois estudos com melhor qualidade metodológica compararam-se os análogos de somatostatina (AS) lanreotida e octreotida com placebo em participantes não tratados anteriormente. Não há estudos de comparação direta entre esses dois medicamentos. Pode-se observar um efeito de ambos os AS na sobrevida livre de progressão, de forma que a chance de progressão tumoral ou morte foi 68% menor, a qualquer tempo, no grupo que recebeu octreotida LAR em relação ao grupo que recebeu placebo (HR 0,32; IC 95% 0,19 a 0,55; P=0,000015) e 53% menor no grupo que recebeu lanreotida em comparação com placebo (HR 0,47; IC 95% 0,30 a 0,73). Em indivíduos com progressão da doença em uso de análogos de somatostatina há evidência de qualidade metodológica mais limitada de que a associação de octreotida e everolimo traga maior benefício na sobrevida livre de progressão que o uso de octreotida isolado. Não foram relatados casos de regressão tumoral e poucos com resposta parcial sendo o principal efeito dos medicamentos o de estabilização dos tumores avaliado por critérios radiológicos. Pela análise de evidência de baixa qualidade metodológica não se observa efeito desses medicamentos na sobrevida global dos participantes. AVALIAÇÃO ECONÔMICA: Foi elaborado estudo de custo-efetividade para comparar o uso de lanreotida de liberação prologada com a conduta expectante em modelo de Markov. Os desfechos avaliados foram sobrevida global e anos de vida ajustados pela qualidade em 6 e 30 anos. As razões incrementais de custo-efetividade foram de R$ 52.775,13 e R$ 40.478,00 por ano de vida ganho nos horizontes temporais de 6 e 30 anos, respectivamente. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O demandante conduziu uma análise de impacto orçamentário na perspectiva do SUS projetando os gastos de uma possível incorporação de lanreotida de liberação prolongada (120 mg) para tratamento de tumores neuroendócrinos gastroenteropancreáticos no período de cinco anos em comparação com a conduta expectante. Utilizando-se o pressuposto de 100% de utilização do medicamento pelo sistema de saúde obteve-se como resultado impactos orçamentários incrementais de R$ 103,63 milhões no primeiro ano e de R$ 674,00 milhões como acumulado para os cinco anos. Aplicando-se taxas de difusão e pressupondo uma utilização gradual do medicamento obtêm-se impactos orçamentários incrementais de R$ 18,6 milhões para o primeiro ano e de R$ 252,00 milhões para os cinco anos. RECOMENDAÇÃO INICIAL DA CONITEC: Os membros do plenário da CONITEC decidiram na 62ª reunião ordinária da Comissão em 6 de dezembro de 2017, por unanimidade, não criar um novo procedimento específico para tratamento de tumores neuroendócrinos com lanreotida, entendendo que já existe procedimento no SUS para tratamento desses tumores. CONSULTA PÚBLICA: A consulta pública nº 02/2018 foi realizada entre os dias 18/01/2018 e 06/02/2018. Foram recebidas 75 contribuições, sendo 22 pelo formulário para contribuições técnico-científicas e 53 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições encaminhadas pela consulta pública, o plenário da CONITEC entendeu que não houve argumentação suficiente para alterar a sua recomendação inicial pela não incorporação do medicamento. Propôs-se como possibilidade a revisão do procedimento (quimioterapia paliativa de apudoma/tumor neuroendócrino) para que se avalie a real necessidade de alteração do valor e das especificações frente aos novos tratamentos aprovados para os tumores neuroendócrinos irressecáveis. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 64ª reunião ordinária, no dia 07 de março de 2018, deliberaram por unanimidade recomendar a não criação de procedimento quimioterápico específico para o uso da lanreotida para tratamento de tumores neuroendócrinos gastroenteropancreáticos. Foi assinado o Registro de Deliberação nº 336/2018 pela não incorporação da tecnologia. DECISÃO FINAL: O Secretário de Ciência, Tecnologia e Insumos Estratégicos do Ministério da Saúde, por meio da Portaria SCTIE/MS nº 16, de 27 de abril de 2018, publicada no DOU nº 82 de 30 de abril de 2018, Seção I, tornou pública a decisão de não criar procedimento quimioterápico específico para o uso do Acetato de Lanreotida para tratamento de tumores neuroendócrinos gastroenteropancreáticos.(AU)

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor

SUMMARY Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.

Cytotoxicity of Mycobacterium indicus pranii on Mia-Pa-Ca2 cells

Background: MIP is a cultivable, non-pathogenic organism, which shares several antigens with Mycobacterium tuberculosis and Mycobacterium leprae. It has several proposed clinical applications. However, its cytotoxic effect on pancreatic cancer has not been documented. Hence, the study was conducted to investigate MIP induced cytotoxicity on Mia-Pa-Ca2 cells. To determine the cytotoxic potential of heat killed Mycobacterium indicus pranii (MIP) on pancreatic cancer cells in vitro along with gemcitabine & 5-fluorouracil (5-FU). Mitogen-activated protein kinase (MAPK) level was also studied post MIP treatment. Methods: Cytotoxic effect of MIP, gemcitabine and 5-FU on Mia-Pa-Ca2 cells was determined. We have analyzed extent of apoptosis using flow cytometry and changes in p38 levels, c-Jun N-terminal kinases (JNK) and extracellular signal­regulated kinase (ERK) using ELISA. Results: MIP not only exhibits cell cytotoxicity in dose dependent manner, but also enhances efficacy of gemcitabine and 5-FU when used in combination. Flow cytometry analyses reveals apoptosis of Mia-Pa-Ca2 cells post MIP treatment compared to untreated cells. MAPK pathway study using ELISA shows that p38 and JNK levels are suppressed while there is no change in ERK level. Conclusion: With these results we conclude that MIP is a cytotoxic agent. Cytotoxicity is exhibited by apoptosis. Combining MIP with gemcitabine and 5-FU shows synergistic effect (AU)

Eficacia y seguridad del uso de everolimus en combinación a octreótide para el tratamiento de tumor neuroendocrino pancreático bien diferenciado en pacientes sintomáticos con enfermedad metastásica irresecable sin terapia sistémica previa / Efficacy and safety of the use of everolimus in combination with octreotide for the treatment of well differentiated pancreatic neuroendocrine tumor in symptomatic patients with unresectable metastatic disease without previous systemic therapy

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de everolimus en combinación a octreótide, para el tratamiento de pacientes adultos con tumor neuroendocrino pancreático bien diferenciado, sintomáticos, con enfermedad metastásica irresecable sin terapia sistémica previa. Aspectos Generales: Los Tumores neuroendocrinos gastroenteropancreáticos (TNEGEP) representan más del 50% de la totalidad de tumores neuroendocrinos (TNE), constituyéndose en el subgrupo más común (1). Estos tumores surgen de las células neuroendocrinas del sistema gastroenteropancreático y se caracterizan por la expresión de hormonas peptídicas de tipos celulares específicos y marcadores tumorales comunes para todos los TNE (sinaptofisina, cromogranina A). Tecnologia Sanitaria de Interés: Everolimus 10 mg: El Everolimus es un inhibidor de mTOR que se une con alta afinidad a la proteína de unión- FK506 12 (FKBP- 12), formando un complejo que inhibe la activación de mTOR. Esta inhibición reduce la actividad de los efectores de activación, lo que conduce a una obstrucción en la progresión de las células de la fase G1 a la fase S, y posteriormente la inducción de la detención del crecimiento celular y la apoptosis. Everolimus también inhibe la expresión del factor inducible por hipoxia, lo que lleva a una disminución en la expresión del factor de crecimiento endotelial vascular. El resultado de la inhibición de mTOR por everolimus es una reducción en la proliferación celular, la angiogénesis y la captación de glucosa. METODOLOGIA: Se realizó una estrategia de búsqueda sistemática de la evidencia científica con respecto a Everolimus asociado a octreótide en pacientes con TNEP bien diferenciado con enfermedad metastásica irresecable sin terapia sistémica previa. Las siguientes fuentes fueron consultadas y revisadas con la finalidad de encontrar la mejor evidencia disponible: MEDLINE, (PubMed), LILACS (Biblioteca Virtual en Salud - BVS), COCHRANE LIBRARY, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Guideline Clearinghouse (NGC), Ministerio de Salud y Protección Social ­ IETS Colombia,\r\nCMA Infobase de la Canadian Medical Association, Database of Abstracts of Reviews of Effectiveness (DARE). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda y la revisión. Así se consideraron los estudios que tuvieran como intervención everolimus en combinación a octreótide para el tratamiento de TNEP bien diferenciado, en pacientes sintomáticos con enfermedad metastásica irresecable sin terapia sistémica previa. CONCLUSIONES: La presente evaluación de tecnología sanitaria tuvo por objetivo la evaluación de la eficacia y seguridad de everolimus en combinación a octreótide en comparación con octreótide solo, para el tratamiento de pacientes adultos con tumor neuroendocrino pancreático bien diferenciado, sintomáticos, con enfermedad metastásica irresecable sin terapia sistémica previa. Fueron incluidos un total de 4 publicaciones científicas (1 guía de práctica clínica, 1 revisión sistemática, 1 evaluación de tecnología sanitaria y 1 ensayo clínico). El IETSI no aprueba el uso de everolimus en combinación con octreótide para el tratamiento de pacientes adultos con TNEP bien diferenciado, sintomáticos, con enfermedad metastásica irresecable sin terapia sistémica previa.

Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer

PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.

La neoplasia sólida-pseudopapilar del páncreas como entidad enigmática / The solid tumor-the pancreas pseudopapillary as enigmatic entity

El tumor sólido-pseudopapilar del páncreas, conocido también como tumor de Frantz, es una rara enfermedad. Afecta principalmente a mujeres jóvenes, no blancas. Tiene componentes sólidos y quísticos. Constituye una neoplasia maligna con un pronóstico, generalmente alentador. Realizamos una revisión de la literatura con el objetivo de actualizar algunos puntos clave acerca del tema. Se incluyeron para la búsqueda las siguientes palabras claves: tumor sólido-quístico, tumor quístico papilar, pseudopapilar, sólido y quístico, tumor de páncreas, tumor pancreático, neoplasia del páncreas, neoplasia pancreática, sólido pseudopapilar y tumor de Frantz. Los acápites que desarrollamos son patogénesis, biología molecular, patología, características clínicas, imaginología y diagnóstico, tratamiento y por último pronóstico. Existen algunos aspectos no bien dilucidados en estos tumores. Por ejemplo, se necesitan más investigaciones en áreas como patogénesis, biología molecular y tratamiento no quirúrgico(AU)

Solid-pseudopapillary of the pancreas, also known as Frantz tumor, is a rare disease. It mainly affects non-Caucasian young women; it has solid and cystic components and represents a malignant neoplasm with generally encouraging prognosis. To this end, a literature review was made to update some key points on the subject. The following keywords were used: solid-cystic turmor, papillary cystic tumor, pseudopapillary, solid and cystic, pancreas tumor, pancreatic tumor, pancreas neoplasm, pancreatic neoplasm, solid-pseudopapillary and Frantz' tumor. The sections that we further developed were pathogenesis, molecular biology, pathology, clinical characteristics, imaging and diagnosis, treatment and finally prognosis. There are some poorly clarified in these tumors, so more research work is needed in pathogenesis, molecular biology and non-surgical treatment(AU)

Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered / Maior sobrevida global em pacientes com câncer pancreático metastático: o impacto de onde e como o tratamento é realizado

Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center.Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded.Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy.Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival.

Objetivo Determinar a sobrevida global dos pacientes com câncer pancreático avançado e avaliar fatores com impacto prognóstico em um centro de câncer privado.Métodos Foram coletados retrospectivamente os dados do Registro de Câncer do Hospital Israelita Albert Einstein. Os pacientes incluídos apresentaram câncer metastático ao diagnóstico ou em estádio mais precoce com recorrência subsequente. Os casos de tumores neuroendócrinos foram excluídos.Resultados Foram avaliados 65 pacientes, incluindo 63 com adenocarcinoma. A sobrevida global mediana dos pacientes em todos os estádios foi 20,7 meses (IC95%: 15,6-25,7), enquanto a sobrevida global de doença metastática foi de 13,3 meses. Entre os 33 casos com câncer em estádio IV, não houve evidência de associação estatisticamente significativa entre a sobrevida mediana e CA19-9 ao diagnóstico (p=0,212), localização do tumor (p=0,482), primeiro tratamento realizado (p=0,337), invasão vasculo-linfática (p=0,286) e idade (p=0,152). No entanto, o número de linhas de quimioterapia foi significativamente associado com a sobrevida (log-rankp=0,013), com uma sobrevida mediana estimada de 10,2 meses para os pacientes que receberam até duas linhas de tratamento e de 23,5 meses para os que receberam mais de duas linhas.Conclusão A sobrevida dos pacientes tratados foi maior do que o relatado na literatura. O único fator estatisticamente significativo relacionado à maior sobrevida foi maior número de linhas de quimioterapia recebidas. Acreditamos que o nível socioeconômico dos pacientes pesquisados neste estudo, assim como seu maior acesso a opções de tratamento, pode ter influenciado em sua sobrevivência global.

Recent Advances in Palliative Chemotherapy for Unresectable Pancreatic Cancer / 대한소화기학회지

Pancreatic adenocarcinoma is one of the fatalist malignancies. A large proportion of patients are diagnosed with unresectable stage pancreatic cancer at the time of presentation. Gemcitabine is a standard chemotherapeutic agent since 1997, but survival benefit is not satisfactory. Recent clinical study proved that several new combination chemotherapy regimens are superior to gemcitabine single chemotherapy and extended overall survival. However, its prognosis still remains grim. Current research is taking a multidirectional approach in the hope of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. This article also reviews the current ongoing clinical trials, which include the use of molecular targeting agents and immune therapies.

Un desafío clínico: diagnóstico diferencial de pancreatitis autoinmune y cáncer de páncreas. El valor del tratamiento esteroidal de prueba / Focal autoimmune pancreatitis versus pancreatic cancer: value of steroid treatment in the diagnosis

Background: The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. Aim: To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. Material and Methods: Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. Results: The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. Conclusions: The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer.