Pancreatic cancer is one of the leading causes for cancer-related deaths in the United States. Majority of patients present with unresectable or metastatic disease. For those that present with localized disease, a multidisciplinary approach is necessary to maximize survival and optimize outcomes. The quality and safety of surgery for pancreatic cancer have improved in recent years with increasing adoption of minimally invasive techniques and surgical adjuncts. Systemic chemotherapy has also evolved to impact survival. It is now increasingly being utilized in the neoadjuvant setting, often with concomitant radiation. Increased utilization of genomic testing in metastatic pancreatic cancer has led to better understanding of their biology, thereby allowing clinicians to consider potential targeted therapies. Similarly, targeted agents such as PARP inhibitors and immune checkpoint- inhibitors have emerged with promising results. In summary, pancreatic cancer remains a disease with poor long-term survival. However, recent developments have led to improved outcomes and have changed practice in the past decade. This review summarizes current practices in pancreatic cancer treatment and the milestones that brought us to where we are today, along with emerging therapies.

Pancreatic Cancer: A Review of Current Treatment and Novel Therapies.

Importance Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Objective To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Design, Setting, and Participants This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Exposures Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Main Outcomes and Measures The main outcomes were DFS and patterns of recurrence. Results A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In multivariate analysis, gastric neuroendocrine carcinoma (HR, 2.22; 95% CI, 1.66-2.98) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.70; 95% CI, 1.24-2.34) were independent risk factors associated with distant recurrence. Additionally, T3 to T4 stage (odds ratio, 2.84; 95% CI, 1.57-5.14; P = .001) and lymph node metastasis (odds ratio, 2.01; 95% CI, 1.31-3.10; P = .002) were independent risk factors associated with distant recurrence of gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma. Conclusions and Relevance This cohort study found that patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma had worse prognoses and were more prone to distant recurrence than those with gastric adenocarcinoma. Thus, different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially patients with tumors penetrating into the subserosa or deeper layers or with lymph node metastasis.

/pdf/comparison-of-survival-and-patterns-of-recurrence-in-gastric-hemlh7c4sq.pdf

Comparison of Survival and Patterns of Recurrence in Gastric Neuroendocrine Carcinoma, Mixed Adenoneuroendocrine Carcinoma, and Adenocarcinoma.

Simple Summary Pancreatic cancer remains a major therapeutic challenge despite medical advances. The incidence of pancreatic cancer is increasing, and this disease is associated with a high mortality and morbidity rate. The poor prognosis of pancreatic cancer can be attributed to several factors, including the difficulty of early diagnosis due to the lack of specific symptoms and biomarkers in the early stages, the aggressiveness of the disease, and its resistance to systemic therapies. However, recent advances in the field have led to promising new therapeutic strategies, and endoscopists have assumed a key role in the multidisciplinary management of this disease. The aim of this article is to provide a comprehensive literature review focused on examining existing treatments for various stages of pancreatic cancer, with an emphasis on new and innovative therapeutic approaches. Abstract Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in the last two decades. The incidence of pancreatic cancer is increasing, and it continues to be associated with high mortality and morbidity rates. The difficulty of early diagnosis (the lack of specific symptoms and biomarkers at early stages), the aggressiveness of the disease, and its resistance to systemic therapies are the main factors for the poor prognosis of pancreatic cancer. The only curative treatment for pancreatic cancer is surgery, but the vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. Pancreatic surgery is among the most challenging surgical procedures, but recent improvements in surgical techniques, careful patient selection, and the availability of minimally invasive techniques (e.g., robotic surgery) have dramatically reduced the morbidity and mortality associated with pancreatic surgery. Patients who are not candidates for surgery may benefit from locoregional and systemic therapy. In some cases (e.g., patients for whom marginal resection is feasible), systemic therapy may be considered a bridge to surgery to allow downstaging of the cancer; in other cases (e.g., metastatic disease), systemic therapy is considered the standard approach with the goal of prolonging patient survival. The complexity of patients with pancreatic cancer requires a personalized and multidisciplinary approach to choose the best treatment for each clinical situation. The aim of this article is to provide a literature review of the available treatments for the different stages of pancreatic cancer.

/pdf/state-of-the-art-and-upcoming-innovations-in-pancreatic-3amfbbi5.pdf

State-of-the-Art and Upcoming Innovations in Pancreatic Cancer Care: A Step Forward to Precision Medicine

Abstract RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing regulation linked to PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis in a mouse model of pancreatic cancer. We demonstrate downregulation of RBFOX2, an RBP of the FOX family, promotes pancreatic cancer progression and liver metastasis. Specifically, we show RBFOX2 regulates exon splicing events in transcripts encoding proteins involved in cytoskeletal remodeling programs. These exons are differentially spliced in PDAC patients, with enhanced exon skipping in the classical subtype for several RBFOX2 targets. RBFOX2 mediated splicing of ABI1 , encoding the Abelson-interactor 1 adapter protein, controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells and promotes the relocalization of ABI1 from the cytoplasm to the periphery of migrating cells. Using splice-switching antisense oligonucleotides (AONs) we demonstrate the ABI1 ∆Ex9 isoform enhances cell migration. Together, our data identify a role for RBFOX2 in promoting PDAC progression through alternative splicing regulation. 

RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing

BACKGROUND
Undetectable occult liver metastases block the long-term survival of pancreatic ductal adenocarcinoma (PDAC). This study aimed to develop a radiomics-based model to predict occult liver metastases and assess its prognostic capacity for survival.


MATERIALS AND METHODS
Patients who underwent surgical resection and were pathologically proven with PDAC were recruited retrospectively from five tertiary hospitals between January 2015 and December 2020. Radiomics features were extracted from tumors, and the radiomics-based model was developed in the training cohort using LASSO-logistic regression. The model's performance was assessed in the internal and external validation cohorts using the area under the receiver operating curve (AUC). Subsequently, the association of the model's risk stratification with progression-free survival (PFS) and overall survival (OS) was then statistically examined using Cox regression analysis and the log-rank test.


RESULTS
A total of 438 patients (mean [standard deviation] age, 62.0 [10.0] years; 255 [58.2%] male) were divided into the training cohort (n = 235), internal validation cohort (n = 100), and external validation cohort (n = 103). The radiomics-based model yielded an AUC of 0.73 (95% confidence interval [CI]: 0.66-0.80), 0.72 (95% CI: 0.62-0.80), and 0.71 (95% CI: 0.61-0.80) in the training, internal validation, and external validation cohorts, respectively, which were higher than the preoperative clinical model. The model's risk stratification was an independent predictor of PFS (all P < 0.05) and OS (all P < 0.05). Furthermore, patients in the high-risk group stratified by the model consistently had a significantly shorter PFS and OS at each TNM stage (all P < 0.05).


CONCLUSION
The proposed radiomics-based model provided a promising tool to predict occult liver metastases and had great significance in prognosis.

Development of a radiomics-based model to predict occult liver metastases of pancreatic ductal adenocarcinoma: a multicenter study.

Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma.

Atrial Fibrillation and the Risk of Early-Onset Dementia an Cognitive Decline: An Updated Review.

BACKGROUND
Post-hemorrhoidectomy bleeding is a serious complication after hemorrhoidectomy. In the setting of a new wave of anticoagulants, we aimed to investigate the relationship of post-operative anticoagulation timing and delayed bleeding.


METHODS
We performed a retrospective analysis of all patients undergoing hemorrhoidectomy at a single institution over a 10-year period. Fisher's exact and Wilcoxon Rank Sum tests were utilized to test for association between delayed bleeding and anticoagulation use.


RESULTS
Between January 2011 and October 2020, 1469 hemorrhoidectomies were performed. A total of 216 (14.7%) were taking platelet inhibitors and 56 (3.8%) other anticoagulants. Delayed bleeding occurred in 5.2% (n = 76) of which 47% (n = 36) required operative intervention. Mean time to bleeding was 8.7 days (SD ±5.9). Time to bleeding was longer in those taking antiplatelet inhibitors vs. non-platelet inhibitors vs. none (11 vs. 8 vs. 7 days, P = .05). Among anticoagulants (n = 56), novel oral anticoagulants were more common than warfarin (57% vs 43%) and had a nonsignificant increase in delayed bleeding (31% vs 16%, P = .21). Later restart (>3 days) of novel anticoagulants after surgery was associated with increased bleeding (10.5% vs 61.5%, P=.005). On multivariable analysis, only anticoagulation use (OR 4.5, 95% CI: 2.1-10.0), male sex (OR 1.8, 95% CI: 1.1-2.9), and operative oversewing (OR 3.5, 95% CI: 1.8-6.9) were associated with delayed bleeding.


CONCLUSION
Post-hemorrhoidectomy bleeding is more likely to occur with patients on anticoagulation. Later restart times within the first week after surgery was not associated with a decrease in bleeding.

Bleeding After Hemorrhoidectomy in Patients on Anticoagulation Medications.

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Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma.

Atrial Fibrillation and the Risk of Early-Onset Dementia an Cognitive Decline: An Updated Review.

Bleeding After Hemorrhoidectomy in Patients on Anticoagulation Medications.