Integrating intratumoral and peritumoral radiomics with clinical risk factors for prognostic prediction in pancreatic ductal adenocarcinoma patients undergoing combined chemotherapy and HIFU ablation.

OBJECTIVE: A radiomics nomogram will be created utilizing MRI data from intratumoral and peritumoral areas to forecast survival outcomes in patients who have had treatment for pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 87 individuals diagnosed with PDAC were included in the study, with 60 patients in the training cohort and 27 patients in the validation cohort. A grand total of 2395 radiomics characteristics were extracted from the tumor region and the peritumoral region. The least absolute shrinkage and selection operator (LASSO) method was used to select features and create a radiomics score, also known as the Rad-score. A multivariate regression analysis was then conducted to build the radiomics nomogram. The evaluation of the nomogram included discrimination, calibration, and clinical utility assessments. RESULTS: Based on the conclusions derived from the multivariate Cox model, Rad-Score, jaundice, and tumor size were identified as independent risk factors for overall survival (OS). The inclusion of the Rad-score in the radiomics nomogram led to improved accuracy in predicting survival compared to the clinical model. Patients were categorized into high-risk and low-risk groups based on their Rad-Score. Kaplan-Meier analysis revealed a statistically significant difference between the two groups (p < 0.05). Furthermore, the radiomics nomogram demonstrated excellent ability to differentiate, calibrate, and provide clinical utility in both the training and validation groups. CONCLUSIONS: The MRI-based intratumoral and peritumoral radiomics nomogram, integrating the Rad-score and clinical data, provided better prognostic prediction for PDAC patients after HIFU treatment, which may hold great potential for guiding personalized care for these patients.

Evaluation of cryoablation using a prototype cryoablation needle in swine liver.

BACKGROUND/AIMS: Pancreatic cancer poses significant challenges due to its tendency for late-stage diagnosis and high mortality rates. Cryoablation, a technique used to treat various types of cancer, has shown potential in enhancing the prognosis of pancreatic cancer when combined with other therapies. However, its implementation is often limited by the need for lengthy procedures and specialized equipment. This study aims to develop a cryoablation needle optimized for endoscopic ultrasonography to simplify its application in treating pancreatic cancer. METHODS: The study involved conducting cryoablation experiments on swine liver tissue. It utilized cryo-needles to evaluate the extent of cell death across various temperatures and durations of cryoablation. RESULTS: The cryoablation system, which employed liquid carbon dioxide, achieved rapid cooling, reaching temperatures below -60 °C within 30 seconds and maintained the cryoablation process for 200 seconds. These conditions resulted in necrosis of the liver tissue. Notable cellular changes were observed up to 15 mm away from the cryoablation needle. CONCLUSIONS: This experimental study successfully demonstrated the efficacy of using a cryo-needle for cryoablation in swine liver tissue. Further trials involving pancreatic tissue are expected to verify its effectiveness, underscoring the importance of continued research to establish its role as a complementary therapy in pancreatic cancer treatment.

Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking. OBJECTIVE: The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings. METHODS: A total of 185 resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival. RESULTS: Subgroup A1 (ISL1+/ARX+/PDX-/CDX2-) was most frequent (46%), followed by type B (18%; ISL1+/ARX-/PDX+/CDX2-), A2 (15%; ISL1+/ARX+/PDX+/CDX2-), C (15%; ISL1-/ARX-/PDX-/CDX2-), and D (5%; ISL1-/ARX-/PDX+/CDX2+). Subgroups A1 and A2 showed a strong association with a trabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. Subgroup B was associated with insulin production (p < 0.001) and included all 17 insulinomas. Subgroup C was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). Subgroup D showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types. CONCLUSION: PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.

The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patients Survival: A Systematic Review and Meta-Analysis.

Background: In recent years, the incidence of early-onset pancreatic cancer (EOPC) has increased. Several studies comparing the survival of patients with EOPC to those with average-onset pancreatic cancer (AOPC) have reported mixed results. We aimed, therefore, to perform a meta-analysis summarizing the current evidence. Methods: We searched the MEDLINE and EMBASE databases for relevant articles published through March 2024. Articles comparing the survival of patients with EOPC - defined as pancreatic ductal adenocarcinoma (PDAC) diagnosed at ≤ 50 years of age - and AOPC were included in the present meta-analysis. The primary outcome was the pooled adjusted hazard ratio (aHR), and the risk of bias analysis was performed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using a random-effects model. Results: A total of 17 studies were eligible for the primary analysis, the results of which indicated that patients with EOPC had a longer overall survival than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74-0.86; P < 0.001). The rate of distant metastasis was higher in EOPC than AOPC; however, patients with EOPC also received more treatments than those with AOPC. Conclusions: Patients with EOPC had a better prognosis than those with AOPC. Clinicians must ensure that patients with PDAC receive early and appropriate treatment to improve their survival.

A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer.

BACKGROUND: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC. METHODS: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH-, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023. RESULTS: Intravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events. CONCLUSIONS: P-AscH- infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).

Efficiency evaluation of dual-energy CT to predict the postoperative early recurrence of pancreatic ductal adenocarcinoma.

OBJECTIVES: To evaluate the efficacy of quantitative parameters from dual-energy CT (DECT) and basic CT features in predicting the postoperative early recurrence (ER) of pancreatic ductal adenocarcinoma (PDAC). METHODS: In this study, patients with PDAC who underwent radical resection and DECT from 2018 to 2022 were enrolled and categorised into ER and non-ER groups. The clinical data, basic CT features and DECT parameters of all patients were analyzed. Independent predictors of ER were identified with Logistic regression analyses. Three models (model A: basic CT features; model B: DECT parameters; model C: basic CT features + DECT parameters) were established. Receiver operating characteristic curve analysis was utilized to evaluate predictive performance. RESULTS: A total of 150 patients were enrolled (ER group: n = 63; non-ER group: n = 87). Rim enhancement (odds ratio [OR], 3.32), peripancreatic strands appearance (OR, 2.68), electron density in the pancreatic parenchymal phase (P-Rho; OR, 0.90), arterial enhancement fraction (AEF; OR, 0.05) and pancreatic parenchyma fat fraction in the delayed phase (OR, 1.25) were identified as independent predictors of ER. Model C showed the highest area under the curve of 0.898. In addition, the corresponding ER risk factors were identified separately for resectable and borderline resectable PDAC subgroups. CONCLUSIONS: DECT quantitative parameters allow for the noninvasive prediction of postoperative ER in patients with PDAC, and the combination of DECT parameters and basic CT features shows a high prediction efficiency. Our model can help to identify patients with high-risk factors to guide preoperative decision making.

Diagnostic yield of endoscopic ultrasound in dilated common bile duct with non-diagnostic cross-sectional imaging.

BACKGROUND: Biliary dilatation without obvious etiology on cross sectional imaging warrants further investigation. This study aimed to assess yield of endoscopic ultrasound in providing etiologic diagnosis in such situation. METHODS: Prospective cohort of consecutive patients with biliary dilatation & non diagnostic computed tomography (CT) and /or magnetic resonance imaging (MRI) underwent endoscopic ultrasound (EUS) with/without fine needle aspiration cytology (FNAC) and were followed clinically, biochemically with/without radiology for up to six months. The findings of EUS were corroborated with histopathology of surgical specimens and endoscopic retrograde cholangiography (ERCP) findings in relevant cases. RESULTS: Median age of 121 patients completing follow up was 55 years. 98.2% patients were symptomatic and median common bile duct (CBD) diameter was 13 mm. EUS was able to identify lesions attributable for biliary dilatation in (67 out of 121) 55.4% cases with ampullary neoplasm being the commonest (29 out of 67 i.e. 43%). Multivariate logistic regression analysis identified jaundice as the predictor of positive diagnosis on EUS, of finding ampullary lesion and pancreatic lesion on EUS. EUS had sensitivity, specificity, positive predictive value and diagnostic accuracy of 95.65%, 94.23%, 95.65% and 95.04% respectively in providing etiologic diagnosis. Threshold value for baseline bilirubin of 10 mg%, for baseline CA 19.9 of 225 u/L and for largest CBD diameter of 16 mm were determined to have specificity of 98%, 95%, 92.5% respectively of finding a positive diagnosis on EUS. CONCLUSION: EUS provides considerable diagnostic yield with high accuracy in biliary dilatation when cross sectional imaging fails to provide etiologic diagnosis.

Concomitant or antecedent intraductal papillary mucinous neoplasm is not a prognostic factor in resected pancreatic cancer.

Background: Intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic cancer is becoming a common subtype of pancreatic cancer found in resected specimens. The prognostic of this subtype is still under evaluation. The study aims to evaluate the prognosis of IPMN-associated pancreatic adenocarcinoma compared to the conventional pancreatic adenocarcinoma. Methods: In this study, patients with resected pancreatic neoplasms and IPMN treated at Hospital Israelita Albert Einstein, from January 2016 to December 2020, were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method, and correlations between the variables of interest and the disease specific OS was assessed by multivariate analysis. Results: Of 187 patients undergoing resection for pancreatic adenocarcinoma or IPMN, 125 (67%) had pancreatic adenocarcinoma, 33 (18%) had IPMN-associated pancreatic adenocarcinoma, and 29 (16%) had IPMN. Resected IPMN was associated with long-term OS for most of the patients. Similar OS was identified in this study in upfront resected pancreatic cancer associated or not with IPMN. No statistical differences in median OS were identified between resected pancreatic adenocarcinoma and IPMN-associated pancreatic adenocarcinoma (48 vs. 44 months, P=0.44). Size of the tumor [hazard ratio (HR), 1.33], resected stage III (HR, 1.31), perineural invasion (HR, 1.58), lymphovascular invasion (HR, 1.44), positive lymph nodes (HR, 1.34), and neoadjuvant treatment (HR, 1.70) were associated with worse outcomes. Conclusions: Our findings confirm that resected pancreatic cancer has a poor prognosis and IPMN-associated pancreatic adenocarcinoma has the same prognosis as a conventional pancreatic adenocarcinoma. More than half of the cases of IPMN-associated adenocarcinoma already had positive lymph nodes. The impact of neoadjuvant treatment in this group of patients should be investigated in larger cohorts.

Performance of explainable artificial intelligence in guiding the management of patients with a pancreatic cyst.

BACKGROUND/OBJECTIVES: Pancreatic cyst management can be distilled into three separate pathways - discharge, monitoring or surgery- based on the risk of malignant transformation. This study compares the performance of artificial intelligence (AI) models to clinical care for this task. METHODS: Two explainable boosting machine (EBM) models were developed and evaluated using clinical features only, or clinical features and cyst fluid molecular markers (CFMM) using a publicly available dataset, consisting of 850 cases (median age 64; 65 % female) with independent training (429 cases) and holdout test cohorts (421 cases). There were 137 cysts with no malignant potential, 114 malignant cysts, and 599 IPMNs and MCNs. RESULTS: The EBM and EBM with CFMM models had higher accuracy for identifying patients requiring monitoring (0.88 and 0.82) and surgery (0.66 and 0.82) respectively compared with current clinical care (0.62 and 0.58). For discharge, the EBM with CFMM model had a higher accuracy (0.91) than either the EBM model (0.84) or current clinical care (0.86). In the cohort of patients who underwent surgical resection, use of the EBM-CFMM model would have decreased the number of unnecessary surgeries by 59 % (n = 92), increased correct surgeries by 7.5 % (n = 11), identified patients who require monitoring by 122 % (n = 76), and increased the number of patients correctly classified for discharge by 138 % (n = 18) compared to clinical care. CONCLUSIONS: EBM models had greater sensitivity and specificity for identifying the correct management compared with either clinical management or previous AI models. The model predictions are demonstrated to be interpretable by clinicians.

Embolize, supercharge, resect: Embolization to enhance hepatic vascularization prior to en-bloc pancreas and arterial resection.

INTRODUCTION: Embolization could increase the resectability of pancreatic tumors by supercharging visceral arterial perfusion prior to pancreatic surgery with arterial en-bloc resection. Its indications, however, are controversial. METHODS: We retrospectively analyzed the results of a single-center database of patients undergoing pancreatic surgery with arterial resection (AR) after preoperative arterial embolization (PAE) to increase hepatic vascular flow and spare arterial reconstruction. RESULTS: PAE was planned in 15 patients with arterial involvement due to pancreatic tumors. Three patients were excluded due to the finding of irresectable disease during surgery. Twelve cases were resected because of pancreatic cancer (10), distal cholangiocarcinoma (1), and pancreatic neuroendocrine tumor (1). Arterial involvement in these cases required embolization of the substitute right hepatic artery (RHA) (5), left hepatic artery (1), and common hepatic artery (CHA) (6) to enhance liver vascularization. Two patients presented migration of the vascular plug after PAE. Six pancreatoduodenectomies and 6 distal pancreatectomies were performed, the latter associated with en-bloc celiac trunk and CHA resection. R0 was achieved in 7 out of 12 patients, and pathological vascular involvement was confirmed in 8. Postoperative complications included one patient who developed gastric ischemia and underwent gastrectomy, and one patient who underwent reoperation for acute cholecystitis with liver abscesses. CONCLUSION: Preoperative arterial embolization before pancreatic surgery with hepatic arterial resection enables surgeons to precondition hepatic vascularization and prevent hepatic ischemia. In addition, this avoids having to perform arterial anastomosis in the presence of pancreatic suture.

Trends in the Care of Locally Advanced Pancreatic Cancer in the Modern Era of Chemotherapy.

INTRODUCTION: Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT. METHODS: Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function. RESULTS: In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS. CONCLUSIONS: Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

Endoscopic biliary drainage for distal bile duct obstruction due to pancreatic cancer.

Approximately 60% of pancreatic cancers occur in the pancreatic head and may present as obstructive jaundice due to bile duct invasion. Obstructive jaundice often leads to poor general conditions and acute cholangitis, interfering with surgery and chemotherapy and requiring biliary drainage. The first choice of treatment for biliary drainage is the endoscopic transpapillary approach. In unresectable tumors, self-expandable metal stents (SEMSs) are most commonly used and are classified into uncovered and covered SEMSs. Recently, antireflux metal stents and large- or small-diameter SEMSs have become commercially available, and their usefulness has been reported. Plastic stents are infrequently used in patients with resectable biliary obstruction; however, owing to the recent trend in preoperative chemotherapy, SEMSs are frequently used because of the long time to recurrent biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is often performed in patients who are not eligible for the transpapillary approach, and favorable outcomes have been reported. Different EUS-BD techniques and specialized stents have been developed and can be safely used in high-volume centers. The indications for EUS-BD are expected to further expand in the future.

Diminishing calcifications as a potential predictor of pancreatic ductal adenocarcinoma arising in association with IPMN in patients with chronic pancreatitis.

Chronic pancreatitis (CP) is a progressive benign fibroinflammatory condition involving repeated episodes of pancreatic inflammation, which lead to fibrotic tissue replacement and subsequent pancreatic insufficiency. A lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC) in patients with chronic pancreatitis is reported to be 1.5%-4%. However, diagnosis of PDAC in patients with CP can be challenging, in part due to overlapping imaging features. In rare instances, pancreatic parenchymal calcifications that are typically associated with chronic pancreatitis may diminish in the case of a developing PDAC. In this article, we present a patient with chronic pancreatitis in whom calcifications decreased at the time of pancreatic ductal adenocarcinoma diagnosis, as compared to prior CT imaging. The unique imaging features of "diminishing calcifications" associated with a hypoattenuating lesion can potentially be a useful sign of pancreatic ductal adenocarcinoma and may aid in early diagnosis and prompt treatment intervention.

Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer.

BACKGROUND: Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS: In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS: Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS: We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

The impact of myosteatosis on postoperative outcomes and survival of patients undergoing pancreatoduodenectomy for suspected/confirmed malignancy.

Backgrounds/Aims: While the effects of myosteatosis are emerging, the evidence for its use as a predictor of outcomes in patients undergoing pancreatoduodenectomy (PD) still needs to be established. The study aims to evaluate the effect of myosteatosis on the short- and long-term outcomes of PD. Methods: We analyzed the effect of myosteatosis on the short- and long-term outcomes of patients who underwent PD between July 2006 and May 2013. Myosteatosis was measured retrospectively from preoperative computed tomography (CT) at the L3 vertebra level, and dichotomized as a binary exposure variable as < 38.5 Hounsfield unit (HU) for males, and < 36.1 HU for females. Results: A total of 214 patient (median age 62 years, range: 41-80 years) CTs were analyzed for myosteatosis. Overall, 120/214 (56.1%) patients were classed as having myosteatosis. Both groups had similar comorbidity profiles. The presence of myosteatosis was not shown to increase the rate of any short- or long-term complication. However, pancreatic leak (29.8% vs. 13.3%; p = 0.006) and postoperative bleeding (13.8% vs. 5.0%; p = 0.034) were higher in the non-myosteatosis group. The median intensive care (2 days) and hospital stay (12 days) were the same in both groups. The 30-day mortality (myosteatosis: 3.3% vs. non-myosteatosis: 3.2%; p = 0.95), and 5-year overall survival (myosteatosis: 26.7% vs. non-myosteatosis: 31.9%; p = 0.5), were similar in both groups. Conclusions: We have found no evidence supporting myosteatosis affecting either the short-term or long-term outcomes of patients undergoing PD for suspected/confirmed malignant tumors.

The Initial Journey of Patients with Metastatic Pancreatic Cancer (PaCTO Project): A Nationwide Survey among Portuguese Specialist Physicians.

Introduction: We aimed to characterize the initial healthcare journey of metastatic pancreatic ductal adenocarcinoma (mPDAC) patients in Portugal, including healthcare provision and factors affecting therapeutic decisions, namely BRCA mutations testing. Methods: This is a descriptive cross-sectional, web-based survey using a convenience sampling approach. Portuguese oncologists and pathologists that routinely work with mPDAC patients from the different geographical regions and settings were invited to participate in the study via email (December 2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR) (Stata v.15.0). Results: Seventy physicians participated in the study (43 oncologists, 27 pathologists). According to the responses, a median of 28 patients per center (IQR 12-70) was diagnosed with PDAC in the previous year; 22 of them referring (IQR 8-70) to mPDAC. The pointed median time from patients' first hospital admission until disease diagnosis/staging is between 2 and 4 weeks. Endoscopic ultrasound with fine-needle biopsy is available in most hospitals (86%). Around 50% of physicians request BRCA testing; the assessment of additional biomarkers besides BRCA is requested by 40% of professionals. Half of them stated that BRCA testing should be requested earlier-upon histological diagnosis, especially because the median time for results is of 4.0 weeks (IQR 4-8). PARP inhibitors such as olaparib, when available, would be the therapy of choice for most oncologists (71%) if no disease' progression occurs after 4 months. Treatments' selection is usually grounded on clinical criteria (e.g., performance status, liver function). Around 45% of patients use FOLFIRINOX/mFOLFIRINOX as the first-line therapy. Gemcitabine + nab-paclitaxel is used by 35% of patients as the second-line therapy. Conclusions: Physicians in Portugal support the increasing role of patient-tailored treatments in mPDAC, whose selection should be grounded on tumoral subtyping and molecular profiling. Further efforts to develop multidisciplinary teams, standardized clinical practice, and optimize the implementation of new target therapies are needed.

Introdução: Este estudo teve como objetivo caracterizar o percurso inicial dos doentes com adenocarcinoma ductal pancreático metastático (ACDPm) em Portugal, incluindo a prestação de cuidados de saúde e determinação de fatores que afetam as decisões terapêuticas, nomeadamente o teste de mutações BRCA. Métodos: Trata-se de um estudo descritivo transversal (web-based) usando uma abordagem de amostragem por conveniência. Médicos oncologistas e anatomopatologistas portugueses dedicados ao ACDPm e de diferentes regiões geográficas e instituições foram convidados a participar do estudo por email (Dez-2020). Foram realizadas análises estatísticas descritivas, com variáveis categóricas relatadas como frequências absolutas e relativas, e variáveis contínuas com distribuição não-normal como mediana e intervalo interquartil (IIQ) (Stata v.15.0). Resultados: Setenta médicos participaram do estudo (43 oncologistas, 27 patologistas). De acordo com as respostas, uma mediana de 28 doentes por centro (IIQ 12­70) foi diagnosticada com ACDP no ano anterior; 22 deles (IIQ 8­70) referentes a ACDPm. O tempo médio desde a primeira admissão hospitalar dos doentes até o diagnóstico/estadiamento da doença foi entre 2­4 semanas. A ultrassonografia endoscópica com biópsia por agulha fina é realizada pela maioria dos hospitais (86%). Aproximadamente 50% dos médicos referem solicitar o teste BRCA; a avaliação de biomarcadores adicionais além do BRCA é solicitada por 40% dos profissionais. Metade dos médicos assume que o teste BRCA deveria ser solicitado mais precocemente ­ durante o diagnóstico histológico, principalmente porque o tempo médio para obtenção do resultado é de 4,0 semanas (IIQ 4­8). Os inibidores PARP, como o olaparibe, quando disponíveis, seriam a terapia de escolha para a maioria dos oncologistas (71%) caso não haja progressão da doença após quatro meses. A seleção dos tratamentos é usualmente baseada em critérios clínicos (por exemplo, performance status, função hepática). Em cerca de 45% dos doentes é utilizado FOLFIRINOX/mFOLFIRINOX como terapia de primeira linha. Um esquema com Gemcitabina + nab-paclitaxel é usado em 35% dos doentes como terapia de segunda linha. Conclusões: Os médicos em Portugal apoiam o papel crescente do tratamento individualizado no ACDPm, cuja seleção deve ser baseada na subtipagem tumoral e no perfil molecular. São necessários mais esforços para capacitar as equipas multidisciplinares, desenvolver práticas clínicas padronizadas e otimizar a implementação de novas terapias-alvo.

Association between pancreatic adenocarcinoma risk and concentration of organochlorine pesticides in adipose tissue and urine: A targeted-screening analysis case-control study (PESTIPAC).

BACKGROUND: Knowledge about environmental pancreatic adenocarcinoma (PA) risk factors, including pesticide exposure, remains limited. Organochlorine (OC) accumulates in adipose tissue and can help reflect long-term exposure. PATIENTS AND METHODS: Age and body mass index (BMI) of patients with PA were matched with those undergoing a surgery for a benign disease on age and BMI (1:1). Targeted analyses screened 345 pesticides and metabolites, including 29 OC, in adipose tissue and urine samples. The primary aim was to investigate the association between organochlorine concentrations in visceral fat or urine, and PA. Adjusted conditional logistic regressions were carried out accounting for multiple testing. RESULTS: Trans-nonachlor (odds ratio [OR] = 1.325, 95% confidence interval [CI] [1.108-1.586]), cis-nonachlor (OR = 15.433, 95% CI [2.733-87.136]), Mirex (OR = 2.853, 95% CI [1.213-6.713]) and 4,4 DDE (OR = 1.019, 95% CI [1.005-1.034]) in fat and a greater number of positive samples (OR = 1.758 95% CI [1.11-2.997]) were significantly associated with higher odds of PA. In contrast, as awaited, urine samples did not yield any statistically significant associations for all tested pesticides. CONCLUSION: Some OCs were associated with higher odds of PA. The underlying mechanisms of pancreatic aggression need to be investigated to refine these findings. TRIAL REGISTRATION: Clinicaltrials.gov NCT04429490.

Survival after vascular resections in patients with borderline resectable or locally advanced pancreatic head cancer: A systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, and the most common cause of cancer-related deaths. In the past, vascular infiltration of the tumor rendered the disease unresectable. However, today, venous or arterial involvement of a PDAC is classified as borderline resectable (BR) or locally advanced (LA) disease. Pancreaticoduodenectomy (PD) with vascular resections is a promising intervention intended for complete resection of BR- and LA-PDAC. This study aims to assess the overall survival of patients undergoing PD with vascular resections, compared to those without. A PubMed search was conducted for cohort studies that included patients with BR- or LA-PDAC treated with vascular resections. The retrieved publications were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The study protocol was registered at the International Prospective Register for Systematic Reviews (PROSPERO). Sixteen cohort studies were included in our systematic review. Fourteen of them included patients undergoing PD with venous-only resections for PDAC. The 5-year overall survival rates ranged from 8.0% to 22.2% for vascular resection patients, and 4.0% to 24.3% for standard PD patients. Three cohorts included patients with PDAC and arterial and/or venous involvement who were treated with arterial resections. Their median overall survival ranged from 13.7 to 17.0 months, similar to that of patients who did not undergo vascular resections. PD with vascular resections in patients with BR- and LA-PDAC could lead to similar overall survival to that after standard PD.

Pancreas Fine Needle Aspiration: Current and Future Impact on Patient Care.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.