Transcriptome-based classification to predict FOLFIRINOX response in a real-world metastatic pancreatic cancer cohort.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at metastatic stage and typically treated with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Few patients benefit from this treatment. Molecular subtypes are prognostic in particularly resectable PDAC and might predict treatment response. This study aims to correlate molecular subtypes in metastatic PDAC with FOLFIRINOX responses using real-world data, providing assistance in counselling patients. We collected 131 RNA-sequenced metastatic biopsies and applied a network-based meta-analysis using published PDAC classifiers. Subsequent survival analysis was performed using the most suitable classifier. For validation, we developed an immunohistochemistry (IHC) classifier using GATA6 and keratin-17 (KRT17), and applied it to 86 formalin-fixed paraffin-embedded samples of advanced PDAC. Lastly, GATA6 knockdown models were generated in PDAC organoids and cell lines. We showed that the PurIST classifier was the most suitable classifier. With this classifier, classical tumors had longer PFS and OS than basal-like tumors (PFS: 216 vs. 78 days, p = 0.0002; OS: 251 vs. 195 days, p = 0.049). The validation cohort showed a similar trend. Importantly, IHC GATA6low patients had significantly shorter survival with FOLFIRINOX (323 vs. 746 days, p = 0.006), but no difference in non-treated patients (61 vs. 54 days, p = 0.925). This suggests that GATA6 H-score predicts therapy response. GATA6 knockdown models did not lead to increased FOLFIRINOX responsiveness. These data suggest a predictive role for subtyping (transcriptomic and GATA6 IHC), though no direct causal relationship was found between GATA6 expression and chemoresistance. GATA6 immunohistochemistry should be seamlessly added to current diagnostics and integrated into upcoming clinical trials.

Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions.

OBJECTIVES: Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors. This study collected real-world data on demographics, clinical characteristics, and clinical outcomes in this patient population. MATERIALS AND METHODS: In this retrospective, multicenter, non-comparative cohort study, physicians in the US-based Cardinal Health Oncology Provider Extended Network collected data from medical records of patients with NRG1 fusion-positive solid tumors who received afatinib (afatinib cohort) or other systemic therapies (non-afatinib cohort) in any therapy line. Objectives included demographics, clinical characteristics, and outcomes (overall response rate [ORR], progression-free survival [PFS], and overall survival [OS]). RESULTS: Patients (N = 110) with a variety of solid tumor types were included; 72 received afatinib, 38 other therapies. In the afatinib cohort, 70.8 % of patients received afatinib as second-line treatment and Eastern Cooperative Oncology Group performance status (ECOG PS) was 2-4 in 69.4 % at baseline. In the non-afatinib cohort, 94.7 % of patients received systemic therapy as first-line treatment and ECOG PS was 2-4 in 31.6 % at baseline. In the afatinib cohort, ORR was 37.5 % overall (43.8 % when received as first-line therapy); median PFS and OS were 5.5 and 7.2 months, respectively. In the non-afatinib cohort, ORR was 76.3 %; median PFS and OS were 12.9 and 22.6 months, respectively. CONCLUSION: This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.

Artificial intelligence for assessment of vascular involvement and tumor resectability on CT in patients with pancreatic cancer.

OBJECTIVE: This study aimed to develop and evaluate an automatic model using artificial intelligence (AI) for quantifying vascular involvement and classifying tumor resectability stage in patients with pancreatic ductal adenocarcinoma (PDAC), primarily to support radiologists in referral centers. Resectability of PDAC is determined by the degree of vascular involvement on computed tomography scans (CTs), which is associated with considerable inter-observer variability. METHODS: We developed a semisupervised machine learning segmentation model to segment the PDAC and surrounding vasculature using 613 CTs of 467 patients with pancreatic tumors and 50 control patients. After segmenting the relevant structures, our model quantifies vascular involvement by measuring the degree of the vessel wall that is in contact with the tumor using AI-segmented CTs. Based on these measurements, the model classifies the resectability stage using the Dutch Pancreatic Cancer Group criteria as either resectable, borderline resectable, or locally advanced (LA). RESULTS: We evaluated the performance of the model using a test set containing 60 CTs from 60 patients, consisting of 20 resectable, 20 borderline resectable, and 20 locally advanced cases, by comparing the automated analysis obtained from the model to expert visual vascular involvement assessments. The model concurred with the radiologists on 227/300 (76%) vessels for determining vascular involvement. The model's resectability classification agreed with the radiologists on 17/20 (85%) resectable, 16/20 (80%) for borderline resectable, and 15/20 (75%) for locally advanced cases. CONCLUSIONS: This study demonstrates that an AI model may allow automatic quantification of vascular involvement and classification of resectability for PDAC. RELEVANCE STATEMENT: This AI model enables automated vascular involvement quantification and resectability classification for pancreatic cancer, aiding radiologists in treatment decisions, and potentially improving patient outcomes. KEY POINTS: • High inter-observer variability exists in determining vascular involvement and resectability for PDAC. • Artificial intelligence accurately quantifies vascular involvement and classifies resectability for PDAC. • Artificial intelligence can aid radiologists by automating vascular involvement and resectability assessments.

Differentiating pancreatic adenosquamous carcinoma from pancreatic ductal adenocarcinoma by CT radiomic and deep learning features / 中华胰腺病杂志

Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.

Sobrevida del adenocarcinoma ductal de páncreas

El objetivo de este trabajo es analizar la presentación epidemiológica y la sobrevida de los pacientes con adenocarcinoma ductal de páncreas de acuerdo con su estadío clínico y al tipo de intervención realizada, en una cohorte de pacientes atendidos en una clínica en Lima, Perú. Estudio de cohortes retrospectivas que evaluó desde enero del 2015 a febrero del 2021 a pacientes con diagnóstico de adenocarcinoma ductal de páncreas considerando diversos factores epidemiológicos, radiológicos, estadiaje oncológico, haber recibido quimioterapia neoadyuvante o adyuvante, haber sido sometidos a cirugía y la sobrevida posterior a alguna de las intervenciones realizadas. De los 249 pacientes analizados, se encontró que 75 de ellos requerían cirugía resectiva. Entre los principales resultados obtenidos, se observó que aquellos con un nivel de CA 19-9 menor a 200 U/mL presentaban una media de sobrevida más alta en comparación con aquellos cuyo nivel de CA 19-9 era superior a 200 U/mL (HR: 1,96; IC95%: 0,18-0,53; p≤0,001). Asimismo, al comparar a los pacientes según su etapa, se encontró que aquellos con tumores resecables tenían una media de sobrevida de 37,72 meses, mientras que aquellos con tumores localmente avanzados tenían una media de sobrevida de 13,47 meses y aquellos con tumores metastásicos tenían una media de sobrevida de 7,69 meses (HR: 0,87; IC95%: 0,31-0,25; p≤0,001). Igualmente, se observó que recibir tratamiento neoadyuvante se asociaba con un mejor pronóstico de sobrevida para los pacientes (HR: 0,32; IC95%: 0,19-0,53; p≤0,001). Asimismo, se llevaron a cabo 5 pancreatectomías con resección metastásica en pacientes oligometastásicos tratados con quimioterapia de rescate, y se encontró que la media de sobrevida para estos pacientes fue de 22,51 meses. Conclusión: La cirugía resectiva en un estadío clínico temprano , presentar valores de CA 19-9 por debajo de 200 U/mL y haber recibido quimioterapia neoadyuvante se correlaciona estadísticamente con una mayor esperanza de sobrevida.

The objective of this study is to analyze the epidemiological presentation and survival of patients with pancreatic ductal adenocarcinoma according to their clinical stage and the type of intervention performed, in a cohort of patients treated at a clinic in Lima, Peru. A retrospective cohort study evaluated patients diagnosed with pancreatic ductal adenocarcinoma from January 2015 to February 2021, considering various epidemiological factors, radiological findings, oncological staging, receipt of neoadjuvant or adjuvant chemotherapy, undergoing surgery, and post-intervention survival. Out of the 249 patients analyzed, 75 of them required resective surgery. Among the main findings, it was observed that those with a CA 19-9 level below 200 U/mL had a higher median survival compared to those with a CA 19-9 level above 200 U/mL (HR: 1.96; 95% CI: 0.18-0.53; p≤0.001). Furthermore, when comparing patients according to their stage, those with resectable tumors had a median survival of 37.72 months, while those with locally advanced tumors had a median survival of 13.47 months, and those with metastatic tumors had a median survival of 7.69 months (HR: 0.87; 95% CI: 0.31-0.25; p≤0.001). Additionally, receiving neoadjuvant treatment was associated with a better prognosis of survival for patients (HR: 0.32; 95% CI: 0.19-0.53; p≤0.001). Furthermore, 5 pancreatectomies with metastatic resection were performed in oligometastatic patients treated with salvage chemotherapy, and the median survival for these patients was 22.51 months. Conclusion: Resective surgery at an early clinical stage, CA 19-9 levels below 200 U/mL, and receiving neoadjuvant chemotherapy are statistically correlated with a higher overall survival.

Role of leukemia inhibitory factor in pancreatic ductal adenocarcinoma / 临床肝胆病杂志

Pancreatic ductal adenocarcinoma is a highly invasive malignant tumor of the digestive system with an extremely poor prognosis. Leukemia inhibitory factor is an important member of the interleukin-6 family and can regulate multiple physiological processes such as cell differentiation, growth, and renewing. This article reviews the mechanism of action of leukemia inhibitory factor in pancreatic ductal adenocarcinoma and the research advances in leukocyte inhibitory factor-targeted therapy based on literature evidence, and the analysis shows that leukemia inhibitory factor plays an important role in the progression, immune escape, and chemotherapy resistance of pancreatic ductal adenocarcinoma and may gradually become a potential biomarker and therapeutic target for pancreatic ductal adenocarcinoma.

Impact of segmentation methods on pathological grade prediction in pancreatic ductal adenocarcinoma based on 18F-FDG PET/CT radiomics / 中华核医学与分子影像杂志

Objective:To investigate the segmentation methods of pancreatic ductal adenocarcinoma (PDAC) tumor regions in 18F-fluorodeoxyglucose (FDG) PET/CT images, as well as their impact on radiomic features-based pathological grade prediction. Methods:A total of 72 patients (46 males, 26 females, age range: 25-87 years) with pathologically confirmed PDAC and a preoperative 18F-FDG PET/CT scan in Peking Union Medical College Hospital between September 2010 and January 2016 were enrolled retrospectively. The cohort of patients was classified as well differentiated group and non-well differentiated group based on the pathological grade of PDAC, and patients were divided into training set and validation set in the ratio of 3∶1 randomly. Two physicians performed manual contours in the tumor region (referred as region of interest (ROI)_M1 and ROI_M2) and semi-automatic ROIs based on standardized uptake value (SUV) gradient edge search (referred as ROI_G) and 40% threshold applied to the maximum SUV (SUV max; referred as ROI_S) were drawn. The four types of segmentation results were compared in terms of volume and Dice similarity coefficient (DSC). Shape, first-order, and texture features were extracted from PET/CT original and preprocessed images, and the interclass correlation coefficient (ICC) was used to assess each feature′s consistency across all segmentations. Kruskal-Wallis rank sum test, independent-sample t test or z test were used to analyze the data. The area under the receiver operating characteristic curve was used to assess model accuracy, and cross validation was used to assess generalization ability. Results:There were 55 patients in the training set (14 well differentiated cases and 41 non-well differentiated cases) and 17 patients in the validation set (4 well differentiated cases and 13 non-well differentiated cases). A total of 44 selected features were predictive of the pathological grade of PDAC among 20 feature groups. There was significant difference among the volumes of ROI_M1, ROI_M2, ROI_G and ROI_S (10.29(4.01, 19.43), 9.34(4.26, 17.27), 11.86(5.52, 19.74) and 15.08(9.62, 27.44) cm 3; H=18.641, P<0.05). The degree of contour coincidence and feature consistency between ROI_M1 and ROI_M2 were both higher (DSC=0.86 (0.76, 0.90), ICC=0.86 (0.74, 0.94)). Compared to manual contours, the degree of contour coincidence and feature consistency of ROI_G (DSC: 0.86(0.75, 0.91), 0.91(0.85, 0.96); ICC: 0.87(0.72, 0.94), 0.94(0.88, 0.98)) were better. There was no statistically significant difference in model accuracy or generalization ability between ROI_M1 and ROI_G ( z=1.052, t=0.712, both P>0.05). The accuracy of ROI_M2 was better than ROI_G ( z=3.031, P=0.002), but the generalization ability of ROI_M2 was insufficient ( t=3.086, P=0.012). Conclusions:Although the manual contour prediction models are highly accurate, their performance are unstable. Semi-automatic contouring based on gradient can achieve comparable accuracy to manual contouring, and the model′s generalization ability is stronger.

Existe un rol para la resección quirúrgica en los pacientes con cáncer de páncreas oligometastásicos / There is a role for surgical resection in patients with oligometastatic pancreatic cancer

RESUMEN Objetivo: El objetivo de este trabajo es analizar retrospectivamente la resección en pacientes con adenocarcinoma de páncreas en estadio IV oligometastásicos, luego de quimioterapia de primera línea para cáncer de páncreas metastásico evaluando la sobrevida de estos casos. Materiales y métodos: Entre enero del 2005 hasta diciembre del 2019 se evaluó de manera retrospectiva a 5 pacientes con diagnóstico de cáncer de páncreas oligometastásico sometidos a quimioterapia de primera línea luego de la cual se les efectuó cirugía resectiva. Resultados: La cirugía resectiva realizadas en estos pacientes fueron: Tres pancreatectomias distales con esplenectomía, una duodenopancreatectomia y una pancreatectomia total. Todos recibieron tratamiento con quimioterapia; tres pacientes recibieron tratamiento con Folfurinox, uno recibió 5 fluoruracilo y otro recibió gemcitabina más capecitabina. Los pacientes recibieron en promedio 4 meses de quimioterapia (3-6 meses) y luego de estos se programó la cirugía resectiva. La sobrevida media en estos pacientes fue de 23 meses (11 a 39 meses), solamente un paciente presento recidiva de la enfermedad y falleció a los 28 meses, los 4 restantes se encuentran vivos. Conclusión: La cirugía resectiva en pacientes con estadio IV con cáncer de páncreas se puede hacer de forma segura. Esta se podría considerar en pacientes seleccionados con una buena respuesta radiológica y bioquímica luego de un periodo adecuado de quimioterapia en los cuales no exista enfermedad a distancia evidente.

ABSTRACT Objective: The objective of this work is to retrospectively analyze the resection in patients with oligometastatic stage IV pancreatic adenocarcinoma, after first-line chemotherapy for metastatic pancreatic cancer, evaluating the survival of these cases. Materials and methods: Between January 2005 and December 2019, 5 patients diagnosed with oligometastatic pancreatic cancer undergoing first-line chemotherapy were retrospectively evaluated, after which resective surgery was performed. Results: The resective surgery performed in these patients were: three distal pancreatectomies with splenectomy, one duodenopancreatectomy and one total pancreatectomy. All received chemotherapy treatment; three patients received treatment with Folfurinox, one received 5-fluorouracil, and one received gemcitabine plus capecitabine. The patients received an average of 4 months of chemotherapy (3-6 months) and after this, resective surgery was scheduled. The average survival in these patients was 23 months (11 to 39 months), only one patient presented recurrence of the disease and died at 28 months, the remaining 4 are alive. Conclusion: Resective surgery in patients with stage IV pancreatic cancer can be done safely. This could be considered in selected patients with a good radiological and biochemical response after an adequate period of chemotherapy in whom there is no obvious distant disease.

Is there a link between non-alcoholic fatty liver disease aspects and pancreatic cancer? Results of a case-matched study / Existe ligação entre a doença hepática gordurosa não alcoólica e o câncer de pâncreas? Resultados de estudo caso-controle

ABSTRACT Background and Aims: An association between non-alcoholic fatty liver disease (NAFLD) and pancreatic ductal adenocarcinoma (PDAC) has been previously suggested. This study aims at investigating this association and at identifying potential links between variables of the NAFLD spectrum and PDAC. Methods: A cross-sectional case-matched analytical and comparative study was carried out to analyze patients undergoing surgical resection of PDAC and compare them to a control group of individuals undergoing cholecystectomy at a public tertiary teaching hospital, matched by sex, age and BMI. Hepatic histopathological examinations were compared between cases and controls. Results: Of 56 individuals, 36 were male (64.3%) and the median age was 61.5 years old (interquartile range: 57.5 - 70). The participants' median BMI was 24.3 kg/m2 (interquartile range: 22.1-26.2 kg/m2). Microvesicular steatosis (p=0.04), hepatocellular ballooning (p=0.02), fibrosis (p=0.0003) and steatohepatitis (p=0.03) were significantly more frequent in the group of cases. Odds ratios for hepatocellular ballooning (6.2; 95%CI: 1.2-31.8; p=0.03), fibrosis (9.3; 95%CI: 2.5-34.1; p=0.0008) and steatohepatitis (3.9; 95%CI: 1.1-14.3; p=0.04) were statistically significant in relation to the PDAC prevalence. Conclusions: Significant associations were identified between histopathological aspects of NAFLD (microvesicular steatosis, hepatocellular ballooning, fibrosis, and steatohepatitis) and PDAC.

RESUMO Histórico e objetivos: a associação entre a doença hepática gordurosa não alcoólica (DHGNA) e o adenocarcinoma ductal pancreático (ACDP) foi sugerida anteriormente. Este estudo visa investigar esta associação e identificar possíveis ligações entre as variáveis do espectro da DHGNA e o ACDP. Métodos: foi realizado estudo transversal caso-controle analítico e comparativo para analisar pacientes submetidos a ressecção cirúrgica de ACDP e compará-los a grupo controle de indivíduos submetidos a colecistectomia em hospital público terciário de ensino, pareados por sexo, idade e IMC. Os exames histopatológicos hepáticos foram comparados entre casos e controles. Resultados: dos 56 indivíduos, 36 eram do sexo masculino (64,3%) e a idade mediana era de 61,5 anos de idade (intervalo interquartil 57,5-70). A mediana do IMC dos participantes foi de 24,3 kg/m2 (intervalo interquartil 22,1 26,2). Esteatose microvesicular (p = 0,04), balonização hepatocelular (p = 0,02), fibrose (p = 0,0003) e esteato-hepatite (p = 0,03) foram significativamente mais frequentes no grupo de casos. As razões de chances para balonização hepatocelular (6,2; IC 95%: 1,2 - 31,8; p = 0,03), fibrose (9,3; IC 95%: 2,5 - 34,1; p = 0,0008) e esteato-hepatite (3,9; IC 95%: 1,1 - 14,3; p = 0,04) foram estatisticamente significativas em relação à prevalência de ACDP. Conclusões: houve associações significativas entre aspectos histopatológicos de DHGNA (esteatose microvesicular, balonização hepatocelular, fibrose e esteato-hepatite) e a ocorrência de ACDP.

One-stop pancreas perfusion CT combined with enhancement in evaluation on pancreatic neuroendocrine neoplasms / 中国医学影像技术

Objective: To explore the value of one-stop pancreas perfusion CT combined with enhancement in evaluation on pancreatic neuroendocrine neoplasms (pNEN). Methods: A total of 30 patients with histopathologically proved pNEN who underwent one-stop pancreas perfusion CT combined with enhancement scan were collected. Imaging features of pNEN were analyzed, the perfusion parameters (blood volume [BV], blood flow [BF], mean transit time [MTT] and capillary surface permeability [PS]) and tissue time density curve (TDC) were observed, the perfusion parameters were compared between different grades of tumors, and the efficacy of radiation dose was analyzed. Results: Pseudo-color images showed that compared with surrounding pancreatic tissue, significantly higher-perfusion was observed in pNEN tissue, with BV of (22.80±6.42)ml/100 g, BF of (237.38±134.86)ml/(min·100 g),significantly higher than those of surrounding pancreatic tissue (both P0.05). There was negative correlation between PS and tumor grade (r=-0.52, P<0.01). The total X-ray dose of whole scan was (19.88±3.03)mSv. Conclusion: One-stop pancreas perfusion CT combined with enhancement scan can diagnose pNEN according to morphological features and perfusion parameters with small radiation dose, and PS parameters may distinguish pNEN grading preoperation. One-stop pancreas perfusion CT combined with enhancement scan is helpful to choice of optimal scanning time of suspicious pNEN lesions during conventional enhanced CT.

Fatores prognósticos pré-operatórios em pacientes com adenocarcinoma ductal da cabeça do pâncreas / Preoperative prognostic factors in patients with ductal adenocarcinoma of the head of the pancreas

RESUMO Objetivos: Identificar fatores prognósticos pré-operatórios relacionados à sobrevida de pacientes com adenocarcinoma ductal da cabeça de pâncreas (ADCP) submetidos a tratamento cirúrgico com intenção curativa em uma única instituição brasileira. Método: No período de 2005 a 2018, dados clinicodemográficos e laboratoriais pré-operatórios foram prospectivamente coletados. A análise de sobrevida foi feita pelo método de Kaplan-Meier e a comparação entre as curvas pelo teste de log-rank. Para a análise multivariada utilizou-se o modelo de regressão de Cox. Resultados: Os fatores pré-operatórios com impacto significativo na sobrevida à análise univariada foram a idade maior ou igual a 70 anos (p=0,012) e história pessoal prévia positiva para câncer (p=0,026). A análise multivariada, pacientes com níveis séricos pré-operatórios de CA 19.9 de 38 a 554 U/ml apresentaram 3,15 vezes maior chance de óbito (HR 3,15; IC 95% 1,01 - 9,82; p=0,047), enquanto que os pacientes com o marcador acima de 554 U/ml evoluíram com chance 3,96 vezes maior de óbito que aqueles com a dosagem normal (HR 3,96; IC 95% 1,19 - 13,10; p=0,024). Pacientes com comorbidades prévias evoluíram com chance 2,90 vezes superior de óbito que doentes sem condições associadas (HR 2,90; IC 95% 1,10 - 7,67; p=0,032). Conclusão: O ADCP mostrou ser doença agressiva para a qual os fatores pré-operatórios de pior prognóstico foram idade avançada, presença de comorbidades, história prévia de câncer e nível sérico de CA 19.9 elevado no pré-operatório.

ABSTRACT Objective: To identify the preoperative prognostic factors influencing pancreatic cancer survival following curative resection in a single Brazilian institution. Methods: From 2005 to 2018, preoperative clinic, demographic and laboratory data were prospectively collected. Survival analysis was performed by the Kaplan-Meier method and the comparison between curves by the log-rank test. For multivariate analysis, the Cox regression model was used. Results: advanced age (p = 0.012) and previous history of cancer (p = 0.026) were the preoperative factors, according to the univariate analysis, that significantly impacted survival. Patients with preoperative serum levels of CA 19.9 from 38 to 554 U/mL had a 3.15 times higher chances of death (HR 3.15; 95% CI 1.01-9.82; p = 0.047), whereas patients with the marker above 554 U/mL were 3.96 times more likely than those with the normal level (HR 3.96; 95% CI 1.19-13.10; p = 0.024), by using the multivariate analysis. Patients with previous comorbidities had a 2.90 times higher chance of death than those without associated conditions (HR 2.90; 95% CI 1.10-7.67; p = 0.032). Conclusion: Preoperative factors related to the worst prognosis after pancreatic ductal adenocarcinoma resection were advanced age, presence of comorbidities, previous history of cancer and elevated preoperative serum CA 19.9.

Immunotherapy for pancreatic ductal adenocarcinoma: Challenges and opportunities / 临床肝胆病杂志

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and its micrometastases are commonly seen in clinical practice. Although great progress has been made in immunotherapy for malignancies in recent years, immune checkpoint blockade focusing on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has changed the clinical diagnosis and treatment of non-small cell lung cancer, melanoma, urothelial carcinoma, and renal carcinoma. However, the clinical effect of immunotherapy in PDAC is limited by the low immunogenicity and unique tumor microenvironment (TME) of PDAC. With the research advances in PDAC-TME, an in-depth analysis of the highly complex interaction network between immune system, tumor cell, and matrix signal may help to develop a rational combination of immunotherapies for PDAC. By elaborating on the unique immunological features of PDAC-TME, this article reviews the potential treatment opportunities for PDAC and the advances in clinical research.

Stage 1A Pancreatic Cancer Initially Manifesting as Clinical Acute Pancreatitis / 대한내과학회지

Pancreatic cancer has a poor prognosis due to the difficulty of early diagnosis. Observation is recommended for early diagnosis of pancreatic cancer in elderly patients with risk factors such as newly diagnosed diabetes and chronic pancreatitis. A 66-year-old male suffered from acute pancreatitis of uncertain etiology. Initial pancreatic imaging showed a main pancreatic duct stricture at the pancreas body/tail junction and minimal duct dilatation without a visible mass. Eight months later, however, pancreatic imaging revealed a pancreatic mass at the previous stricture site with progression of the upstream duct dilation. The patient underwent distal pancreatectomy, and a pathologic examination showed stage 1A pancreatic cancer with a predominantly intraductal spreading pattern. We report a case of stage 1A pancreatic cancer that initially manifested as acute obstructive pancreatitis, which enabled early diagnosis of pancreatic cancer.

Combination of multi-slice spiral CT with MRI in diagnosis of rare types of pancreatic tumors / 中华全科医师杂志

With the progress of pathology and imaging the detection rate of rare pancreatic tumors has gradually increased.This article reviews the epidemiology,pathology,imaging features and differential diagnosis of rare pancreatic tumors.

Combination of multi-slice spiral CT with MRI in diagnosis of rare types of pancreatic tumors / 中华全科医师杂志

With the progress of pathology and imaging the detection rate of rare pancreatic tumors has gradually increased. This article reviews the epidemiology, pathology, imaging features and differential diagnosis of rare pancreatic tumors.

Establishment of pancreatic cancer organoids with endoscopic ultrasonography-guided fine-needle aspiration specimen: a prospective pilot study / 中华消化内镜杂志

Objective@#To study the feasibility of establishing human 3D pancreatic cancer organoids with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimen.@*Methods@#A total of 9 patients with suspected pancreatic masses were prospectively included in this study from June 2017 to January 2018. EUS-FNA was performed for initial diagnosis. The biopsy tissues were obtained from a COOK 22-gauge FNA needle for organoid establishment, and the growth status in vitro was observed.@*Results@#Nine specimens of pancreatic lesions obtained from EUS-FNA were enrolled. Successful establishment of organoids was achieved in 5 cases, which were all confirmed to be pancreatic cancer histopathologically. In the process of generating, the growth rate of organoids increased correspondingly. The pathological morphology of these organoids was similar to the corresponding pancreatic tissues in HE staining.@*Conclusion@#Pancreatic cancer organoids can be successfully created by means of EUS-FNA. Establishment of these organoids can potentially provide excellent models for patients with pancreatic cancer in guiding precision treatment.

Study on cell matrix of pancreatic duct adenocarcinoma / 国际肿瘤学杂志

The occurrence of pancreatic duct adenocarcinoma (PDAC) is closely related to the biological immunological characteristics of the hematopoietic matrix of its cancer cells.The malignant characteristics of the cancer matrix play important roles in the malignant origin of tumors,avoiding immune surveillance,promoting tumor progression and growth,and increasing drug resistance and metastasis.Understanding the important roles of hyaluronic acid,Sonic Hedgehog signaling pathway,transforming growth factor-beta,CD40,Kras pathway and microRNA in the pathogenesis and development of PDAC,can provide new strategies for clinical treatment of PDAC.

The role of immunoinflammatory markers in the prognosis and resectability of pancreatic adenocarcinoma / O papel dos marcadores imunoinflamatórios no prognóstico e ressecabilidade do adenocarcinoma pancreático

ABSTRACT Background: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. Aim: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. Methods: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. Results: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). Conclusions: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

RESUMO Racional: O adenocarcinoma pancreático apresenta alta taxa de mortalidade. Uma ferramenta que possa predizer adequadamente o seu prognóstico é fundamental para melhor estratificação de risco. A razão neutrófilos/linfócitos e suas adaptações e a razão plaquetas/linfócitos tem se mostrado promissores para este fim. Objetivo: Avaliar o valor prognóstico das razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos, analisar os pontos de corte mais adequados e investigar sua utilidade como fator preditivo de ressecabilidade. Métodos: Foram coletados dados de pacientes com adenocarcinoma pancreático atendidos no Hospital de Clínicas de Porto Alegre entre 2003 e 2013. As razões estudadas foram determinadas com base nos hemogramas coletados na internação e após dois ciclos de quimioterapia paliativa. Resultados: As razões neutrófilos/linfócitos basal, neutrófilos/linfócitos derivada basal e plaquetas/linfócitos basal não tiveram impacto prognóstico na sobrevida (p=0,394, p=0,152, p=0,177 respectivamente). No subgrupo submetido a quimioterapia paliativa, as razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos após dois ciclos de tratamento mostraram-se fatores prognósticos para sobrevida global (p=0,003, p=0,009 e p=0,001 respectivamente). Os pontos de corte encontrados foram 4,11 para neutrófilos/linfócitos (sensibilidade 83% e especificidade 75%), 362 para plaquetas/linfócitos (sensibilidade 91% e especificidade 62,5%) e 2,8 para neutrófilos/linfócitos derivada (sensibilidade 87% e especificidade 62,5%). As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos não se mostraram estatisticamente significativas como preditores para ressecabilidade (p=0,88; p=0,99 e p=0,64 respectivamente). Conclusões: As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos são úteis como marcadores prognósticos de sobrevida global em pacientes com adenocarcinoma pancreático submetidos à quimioterapia paliativa. Seu uso como preditor de ressecabilidade não foi demonstrado.

Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement

PURPOSE: The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. METHODS: This study included eight and 37 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors. In the quantitative echo intensity evaluation, the two groups were compared with respect to the difference between the tumor intensity and the pancreatic intensity (TI-PI) and between the tumor intensity and the vascular intensity (TI-VI). In the quantitative contrast enhancement evaluation, the increase in echo intensity (ΔTI) and increase in echo intensity per unit of time (slope) were compared between the groups. The echo intensity and contrast enhancement were also compared between the two groups in patients with T3-T4 disease. In addition, the correlations of the histological type, tumor size, stromal type, and T factor with echogenicity and contrast enhancement were analyzed. RESULTS: IPMN-IC had significantly greater echo intensity and contrast enhancement than PDAC (TI-PI, P=0.004; TI-VI, P=0.001; ΔTI, P=0.012; slope, P=0.002). In T3-T4 disease, IPMN-IC also showed greater echo intensity and faster enhancement than PDAC. Echo intensity and contrast enhancement were correlated with histological type (TI-PI, P=0.003; TI-VI, P<0.001; ΔTI, P=0.007; slope, P<0.001). CONCLUSION: IPMN-IC and PDAC can be differentiated by the quantitative evaluation of echo intensity and contrast enhancement.

Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy

BACKGROUND/AIMS: Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients. METHODS: Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m² twice daily for 14 days; oxaliplatin, 130 mg/m² on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed. RESULTS: Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis. CONCLUSIONS: Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.