Seminars in diagnostic pathology 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30482417

Congenital and hamartomatous lesions of the gastrointestinal tract cause diagnostic challenges for surgical pathologists. Many of these are merely histologic curiosities, whereas others have substantial clinical implications because they herald cancer syndromes or associated anomalies. Although a comprehensive discussion of all developmental abnormalities that can occur in the gastrointestinal tract is beyond the scope of a single manuscript, some entities are more likely to be encountered by surgical pathologists, have important clinical consequences, or pose diagnostic difficulties. The purpose of this review is to discuss the more common malformations and choristomas, as well as hamartomatous lesions that may be clinically important due to their risk for cancer development, frequent associations with heritable cancer syndromes and other anomalies, or potential to simulate other entities.

Applied immunohistochemistry & molecular morphology : AIMM 2019 Jan;27(1):40-47

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30531392

BACKGROUND: Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers for the diagnosis, prediction of prognosis, and target therapy have not yet been identified. OBJECTIVE: To investigate the expression of aquaporin-1 (AQP1) and AQP3 protein and their clinicopathological significances in PDACs. MATERIALS AND METHOD: AQP1 and AQP3 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues was measured by immunohistochemistry. RESULTS: Western blot showed that AQP1 and AQP3 protein expression was significantly higher in PDAC tissues than that in benign pancreatic tissues (P<0.01). Immunohistochemistry showed that the percentages of positive AQP1 and AQP3 expressions were significantly higher in PDAC tumors than that in peritumoral tissues, benign, and normal pancreatic tissues (P<0.01). Benign pancreatic lesions with positive AQP1 and AQP3 expression exhibited a dysplasia or intraepithelial neoplasia. The percentage of cases with positive AQP1 and AQP3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion, and having low Tumor, Node and Metastasis (TNM) stage disease than in patients with lymph node metastasis, invasion, and high TNM stage disease (P<0.05 or <0.01). Kaplan-Meier survival analysis showed that positive AQP1 and AQP3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive AQP1 and AQP3 expression was independent poor prognosis factors in PDAC patients. The area under the curve of receiver operating characteristic curve was 0.669 for AQP1 and 0.707 for AQP3, respectively. CONCLUSIONS: Positive AQP1 and AQP3 expressions are associated with the tumorigenesis and progression of PDAC. Both AQP1 and AQP3 are a diagnostic marker of PDAC and a predictive marker of poor prognosis in PDAC patients.

Human pathology 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30537492

Mitogen-activated protein kinase kinase 4 (MKK4) and mitogen-activated protein kinase kinase 7 (MKK7) were shown to regulate biological behavior in many malignancies. In pancreatic ductal adenocarcinoma (PDAC), it remains controversial whether MKK4 and MKK7 have pro-oncogenic or tumor-suppressive activities. Furthermore, their clinicopathologic and prognostic implications are unknown. In the present study, we detected MKK4 and MKK7 expressions in the nucleus and cytoplasm of resected PDAC tissues from 321 patients by tissue microarray-based immunohistochemistry. Cytoplasmic MKK4 and MKK7 expressions were significantly down-regulated, while nuclear MKK4 expression was significantly up-regulated in tumor tissues compared with non-tumor tissues. Tumor cytoplasmic MKK4 and MKK7 expressions were significantly negatively associated with histological grade. Cytoplasmic MKK4 expression was also negatively correlated with CA19-9 level. By univariate analysis, high cytoplasmic MKK4 expression was significantly associated with longer cancer-specific survival (hazard ratio [HR]: 0.705; 95% confidence interval [95%CI]: 0.510-0.974), with a similar trend observed for MKK7 expression. High MKK4 and MKK7 mRNA expressions were significantly associated with longer overall survival in the TCGA database. Although MKK4 expression was not significant in a multivariate Cox regression analysis, combination of MKK4/MKK7 and pN stage was identified as an independent prognostic indicator and had the lowest HR (HR: 0.308; 95%CI: 0.126-0.752). Furthermore, combined analysis of MKK4 and MKK7 greatly increased the prognostic predictive power. In addition, down-regulation of MKK4 or MKK7 increased proliferation of pancreatic cancer cells in vitro. In conclusion, high MKK4 expression and its combination with high MKK7 expression both predicted favorable prognosis in resectable PDAC.

Pathology, research and practice 2018 Dec;214(12):2069-2074

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30477643

AIM: We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). METHODS: Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare　the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%). RESULTS: PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%). DISCUSSION: Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.

The American journal of pathology 2019 Jan;189(1):6-8

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30558724

This Guest Editorial introduces this month’s special Pancreatic Cancer Theme Issue, a series of reviews intended to highlight the pathologic to molecular profiles and diagnoses of benign and neoplastic pancreatic lesions.

The American journal of pathology 2019 Jan;189(1):9-21

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30558727

Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms with poor outcomes. At the time of diagnosis, the disease is usually at an advanced stage and only a minority is eligible for surgical resection. To improve the prognosis, it is essential to diagnose and treat the disease in an early stage before its progression into an invasive disease. This article reviews clinical features, histopathology, cytopathology, and molecular alterations of pancreatic ductal adenocarcinoma and its precursors. Moreover, we review a recently updated two-tier classification system for precursor lesions, new findings in premalignant cystic neoplasms, and recently updated staging criteria for invasive carcinoma based on the Cancer Staging Manual, eighth edition, from the American Joint Committee on Cancer. Finally, we discuss the potential clinical applications of the rapidly growing molecular and genetic information of pancreatic cancer and its precursors.

Annals of diagnostic pathology 2018 Nov;38():93-98

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30562721

Pancreas 2018 07;47(6):742-747

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=29851752

OBJECTIVES: Notable modifications have been made in the American Joint Committee on Cancer (AJCC) Staging eighth edition staging for pancreatic cancer for the consideration of the irreproducible and inapplicable of the AJCC seventh edition staging. However, the new staging classification has not been systemically verified. METHODS: A comparison was performed to evaluate the application of the AJCC seventh and eighth staging classifications using the Surveillance, Epidemiology, and End Results registry (18,450 patients) and an institutional series (2040 patients). RESULTS: For the eighth staging classification, patients with tumor diameter of greater than 4 cm (T3N0M0, IIA) had similar prognosis to patients with 1 to 3 positive nodes (T1-3N1M0, IIB). For patients who underwent tumor resection and without lymph node involvement, survival curves of T1 (≤2 cm), T2 (2-4 cm), and T3 (>4 cm) were well separated. Statistical difference in survival analyses was demonstrated in N0 (0 positive node), N1 (1-3 positive nodes), and N2 (≥4 positive nodes) patients underwent tumor resection. The AJCC eighth edition had better stage distribution than the AJCC seventh edition for pancreatic cancer. CONCLUSIONS: The eighth edition of AJCC staging is more applicable and accurate than the seventh edition for pancreatic adenocarcinoma.

Journal of surgical oncology 2018 Dec;118(8):1277-1284

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30380143

BACKGROUND: The incidence of occult metastatic disease (OMD) in pancreatic ductal adenocarcinoma (PDAC) and associated risk factors are largely unknown. METHODS: We identified all patients with PDAC, who had an aborted oncologic operation due to OMD within a 10-year period. The cases were matched to a cohort of resected PDAC patients on a 1:3 ratio, based on age and sex, for comparison of preoperative clinical characteristics and potential risk factors for OMD. RESULTS: In the studied period, 117 patients with OMD were identified in 1423 pancreatectomies performed for PDAC (8%). Liver metastases were the most common finding (79%) followed by peritoneal implants (16%). When compared with non-OMD cases, patients with OMD presented more often with abdominal pain (P < 0.001), and higher preoperative carbohydrate antigen 19-9 (CA 19-9) values ( P = 0.007). Additionally, indeterminate liver lesions on preoperative computed tomography (CT) were identified in 40% of OMD versus 17% of non-OMD patients ( P < 0.001). Multivariable analysis distinguished four independent predictors for OMD: indeterminate lesions on preoperative CT, tumor size > 30 mm, abdominal pain, and preoperative CA 19-9 > 192 U/mL. CONCLUSIONS: Occurrence of OMD in PDAC accounts for 8% of cases. Preoperative CA 19-9 > 192 U/mL, primary tumor size > 30 mm, and identification of indeterminate lesions in preoperative CT may indicate the need for diagnostic laparoscopy.

Annals of surgery 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30499803

OBJECTIVE: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types. BACKGROUND: No predictive model for malignant IPMN has been widely applied in clinical practice. METHODS: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. RESULTS: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725. CONCLUSION: This predictive model provides important information for physicians and patients in assessing an individual’s risk for malignancy and may help to identify patients who need surgery.

Pancreas 2019 Jan;48(1):135-138

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30531244

We report a case of pseudomyxoma peritonei (PMP) arising in a 62-year-old male patient with Lynch syndrome (LS). The patient’s medical history included an adenocarcinoma of the colon for which a right hemicolectomy was performed and a pancreatectomy due to an intraductal papillary mucinous neoplasm (IPMN) with invasive colloid carcinoma. It was considered that the PMP could be a metastasis of the earlier colonic or pancreatic carcinoma. The pancreatic carcinoma, colon carcinoma, and PMP tissues were examined, and immunohistochemical and molecular analyses were performed to determine the PMP origin. Histopathologic examination revealed morphological similarities with the pancreatic colloid carcinoma, and further immunohistochemical and molecular analyses, including a shared GNAS mutation, confirmed the pancreatic origin of the PMP. In conclusion, this is a unique case of a patient with LS presenting with PMP originating from an IPMN with invasive colloid carcinoma, several years after pancreatectomy. The present case has important diagnostic implications. The IPMN should be considered as a rare extracolonic manifestation of LS, and pancreatic carcinoma origin should be considered in patients presenting with PMP. This case report highlights the added value of molecular diagnostics in daily pathology practice.

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 2019 Jan;127(1):27-32

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30549137

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN-lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.

The American journal of pathology 2019 Jan;189(1):44-57

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30558722

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is projected to become the second leading cause of cancer death in the United States. Despite significant advances in understanding the disease, there has been minimal increase in PDAC patient survival. PDAC tumors are unique in the fact that there is significant desmoplasia. This generates a large stromal compartment composed of immune cells, inflammatory cells, growth factors, extracellular matrix, and fibroblasts, comprising the tumor microenvironment (TME), which may represent anywhere from 15% to 85% of the tumor. It has become evident that the TME, including both the stroma and extracellular component, plays an important role in tumor progression and chemoresistance of PDAC. This review will discuss the multiple components of the TME, their specific impact on tumorigenesis, and the multiple therapeutic targets.

Gut 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30530506

Pancreas 2019 Jan;48(1):e4-e6

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30531247

Gastroenterology 2018 11;155(5):1625-1639.e2

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30092175

BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.

Annual review of physiology 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30418798

Pancreatic cancer is characterized by an extensive fibroinflammatory reaction that includes immune cells, fibroblasts, extracellular matrix, vascular and lymphatic vessels, and nerves. Overwhelming evidence indicates that the pancreatic cancer microenvironment regulates cancer initiation, progression, and maintenance. Pancreatic cancer treatment has progressed little over the past several decades, and the prognosis remains one of the worst for any cancer. The contribution of the microenvironment to carcinogenesis is a key area of research, offering new potential targets for treating the disease. Here, we explore the composition of the pancreatic cancer stroma, discuss the network of interactions between different components, and describe recent attempts to target the stroma therapeutically. We also discuss current areas of active research related to the tumor microenvironment. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Gastroenterology 2018 12;155(6):1999-2013.e3

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30165049

BACKGROUND & AIMS: Genomic studies have revealed subtypes of pancreatic ductal adenocarcinoma (PDA) based on their molecular features, but different studies have reported different classification systems. It is a challenge to obtain high-quality, freshly frozen tissue for clinical analysis and determination of PDA subtypes. We aimed to redefine subtypes of PDA using a large number of formalin-fixed and paraffin-embedded PDA samples, which are more amenable to routine clinical evaluation. METHODS: We collected PDA samples from 309 consecutive patients who underwent surgery from September 1996 through December 2010 at 4 academic hospitals in Europe; nontumor tissue samples were not included. Samples were formalin fixed and paraffin embedded. DNA and RNA were isolated; gene expression, targeted DNA sequencing, and immunohistochemical analyses were performed. We used independent component analysis to deconvolute normal, tumor, and microenvironment transcriptome patterns in samples. We devised classification systems from an unsupervised analysis using a consensus clustering approach of our data set after removing normal contamination components. We associated subtypes with overall survival and disease-free survival of patients using Cox proportional hazards regression with estimation of hazard ratios and 95% confidence interval. We used The Cancer Genome Consortium and International Cancer Genome Consortium PDA data sets as validation cohorts. RESULTS: We validated the previously reported basal-like and classical tumor-specific subtypes of PDAs. We identified features of the PDA, including microenvironment gene expression patterns, that allowed tumors to be categorized into 5 subtypes, called pure basal like, stroma activated, desmoplastic, pure classical, and immune classical. These PDA subtypes have features of cancer cells and immune cells that could be targeted by pharmacologic agents. Tumor subtypes were associated with patient outcomes, based on analysis of our data set and the International Cancer Genome Consortium and The Cancer Genome Consortium PDA data sets. We also observed an exocrine signal associated with acinar cell contamination (from pancreatic tissue). CONCLUSIONS: We identified a classification system based on gene expression analysis of formalin-fixed PDA samples. We identified 5 PDA subtypes, based on features of cancer cells and the tumor microenvironment. This system might be used to select therapies and predict patient outcomes. We found evidence that the previously reported exocrine-like (called ADEX) tumor subtype resulted from contamination with pancreatic acinar cells. ArrayExpress accession number: E-MTAB-6134.

Gastroenterology 2018 12;155(6):1689-1691

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30419209

Archives of pathology & laboratory medicine 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30525934

CONTEXT.—: The cause of pancreatic acinar metaplasia (PAM) at the distal esophagus/esophagogastric junction is still controversial. Whereas some authors believe it is congenital, others believe it is acquired because of inflammation of the gastric cardia, and more recently it was proposed to be due to chronic proton pump inhibitor use based on a study in rats. OBJECTIVE.—: To determine whether there is correlation between chronic proton pump inhibitor use and PAM in humans. We also investigated the correlation between several clinical and pathologic factors and PAM. DESIGN.—: Four hundred forty-four consecutive biopsies from the distal esophagus/esophagogastric junction were reviewed for the presence of PAM, which was then correlated with several clinical and pathologic findings. RESULTS.—: Pancreatic acinar metaplasia was found in 71 patients (16%). Pancreatic acinar metaplasia was significantly associated with patient age younger than 51 years ( P < .001), chronic carditis ( P = .01), and chronic proton pump inhibitor use ( P = .008). Surprisingly, we also found significant association between PAM and chronic nonsteroidal anti-inflammatory drug use ( P < .001). These associations, including that with chronic nonsteroidal anti-inflammatory drug use, remained significant in multivariate analysis. CONCLUSIONS.—: Our findings confirm the previous reports of significant association between PAM and chronic carditis and the findings from animal studies of association with chronic proton pump inhibitor use. The strong association with chronic nonsteroidal anti-inflammatory drug use has not been previously reported and warrants further studies.

The American journal of pathology 2019 Jan;189(1):82-93

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30558726

Advances in the past two decades have resulted in the recognition of several tumefactive pancreatic lesions that, on histologic evaluation, show a varying combination of inflammation and fibrosis. Autoimmune pancreatitis, the prototypic tumefactive pancreatic fibroinflammatory lesion, is composed of two distinct diseases, type 1 autoimmune pancreatitis and the less common type 2 autoimmune pancreatitis. Although designated as autoimmune pancreatitis, the two diseases show little morphologic or pathogenic overlap. In type 1 disease, subsets of T lymphocytes (type 2 helper T cells, regulatory T cells, and T follicular helper 2 cells) are hypothesized to drive the inflammatory reaction. The B-cell response is characterized by an oligoclonal expansion of plasmablasts, with dominant clones that vary among patients and distinct clones that emerge at the time of relapse. Although the precise role of IgG4 in this condition remains uncertain, recent studies suggest that other IgG subclasses (eg, IgG1) may mediate the immune reactions, whereas IgG4 represents a response to dampen excessive inflammation. A recent study of type 2 autoimmune pancreatitis highlights the role of CXCL8 (alias IL-8), with duct epithelium and infiltrating T lymphocytes expressing this chemokine; the latter may contribute to the distinct form of neutrophilic inflammation in this disease. The review also highlights other forms of mass-forming chronic pancreatitis: follicular pancreatitis, groove pancreatitis, and those associated with rheumatologic diseases.

Histopathology 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30515871

AIM: Follicular pancreatitis is a recently recognized, distinct clinicopathological entity characterized by the presence of many intrapancreatic lymphoid follicles with reactive germinal centres. However, the clinicopathological and immunological features and causes have not yet been established. We assessed the clinicopathological and immunological profiles of patients with follicular pancreatitis who underwent surgery. METHODS AND RESULTS: This study included three patients with pancreatic masses (age range: 62-75 years; women:men: 1:2). A histopathological study of the resected pancreatic masses revealed abundant lymphoid follicles with reactive germinal centres in both periductal regions and diffusely within the parenchyma. No storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions were observed. The immunohistochemical examination revealed an IgG4/IgG-positive plasma cell ratio <30% in all patients. Podoplanin (Th17 marker)-expressing lymphocytes were present in the lymphoid follicles of those with follicular pancreatitis, whereas these were absent in normal lymph nodes and in lymphoid follicles of those with IgG4-related autoimmune pancreatitis (AIP). An RNA digital counting assay clearly demonstrated that the expression counts of 20 genes, including dendritic cells and lymphoid follicles markers, and related cytokines were significantly higher in follicular pancreatitis than in IgG4-related AIP (p<0.01). The expressions of CCR6 and IL23A, which are genes related to Th17, were high. CONCLUSIONS: This study shows that follicular pancreatitis is a histopathologically and immunologically distinct disease entity of pancreatitis and is characterized by upregulated Th17 expression. This article is protected by copyright. All rights reserved.

Pathology, research and practice 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497878

OBJECTIVES: Hepatobiliary system cancer, which includes hepatocellular carcinoma (HCC), cholangiocarcinoma, and gallbladder carcinoma, has an increase of incidence and mortality due to various risk factors. Epstein-Barr virus (EBV) is associated with various types of lymphomas and carcinomas, which is also acknowledged as the first-discovered human tumor virus. Despite this, there is no systematic analysis about the relationship between the infection of EBV and hepatobiliary system cancer. The aim of this meta-analysis is to explore the significance of EBV infection in the development of hepatobiliary system cancer by evaluating the EBV infection ratio. METHODS: A systematic search of PubMed, Embase, Cochrane Library, as well as China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wan Fang, and China Biology Medicine databases was conducted. The EBV infection ratio and 95% confidence intervals (CIs) in hepatobiliary system cancer was evaluated. The I2 statistic was used to represent heterogeneity. Through meta-regression, stratified analyses were applied to find out heterogeneity’s sources. Odds ratios (ORs), 95% CIs of EBV infection in case-control studies were calculated. RESULTS: Altogether, 15 studies were included containing a total of 918 cases and 157 controls. The whole infection ratio of EBV was 23% (95% CI: 13%, 33%, I2 = 95.7%, P < 0.001) among all the patients. Comparable EVB infection ratios were observed in hepatobiliary system cancer as divided into different subtypes. The five case-control studies were epitomized to a pooled OR of 9.35 (95%CI: 2.95, 29.61, I2 = 20.1%, P < 0.286). CONCLUSION: EBV may be a potentially risk factor in the process of hepatobiliary system cancer. The prospective molecular mechanism remains to be explored.

Journal of gastrointestinal oncology 2018 Oct;9(5):942-952

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30505597

Background: Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive disease with an increasing incidence in the United States, and there is no level 1 evidence to help guide treatment decisions. We sought to determine national trends in surgical and medical management of patients with resected ICC, and more specifically, the role of lymphadenectomy (LAD) and utilization of chemotherapy. Methods: An augmented version of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer database registry was used to identify all surgically resected ICC patients from 2000 to 2014. We evaluated the incidence and adequacy of LAD, and receipt of chemotherapy over time. Next, multivariable logistic regressions were performed to determine the predictors of LAD and receipt of chemotherapy. Overall survival (OS) was evaluated using Kaplan-Meier and Cox proportional hazard models. Results: We identified 1,263 patients who underwent resection for ICC. Lymph nodes (LNs) were removed in 49% of patients, however, only 10% of patients received adequate LAD by the American Joint Committee on Cancer (AJCC) criteria (≥6 nodes). LN metastases were found in 29% of patients who underwent nodal evaluation. Chemotherapy was administered to 40% of patients, was utilized more frequently over time (P<0.05), and was associated with improved survival in node positive patients (P<0.05). Patients who did not have LNs evaluated were significantly less likely to receive chemotherapy than those who did. Lastly, OS for the entire cohort improved over time (P<0.05). Conclusions: After analyzing the treatment and outcomes of resectable ICC, we concluded: (I) LN evaluation at the time of surgical resection remains inadequate; (II) utilization of chemotherapy has increased over time; (III) the lack of LAD likely results in under-staging and underutilization of chemotherapy; and (IV) despite less than ideal surgical and medical therapy median OS continues to improve.

Annals of surgical oncology 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30539494

BACKGROUND: The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously. METHODS: Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5 years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5 years were excluded from the study. RESULTS: The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5 years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P = 0.008) and a lower rate of lymph node involvement (42% vs. 15%; P = 0.027) and R1 margins (39% vs. 17%; P = 0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups. CONCLUSIONS: One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).

Journal of surgical oncology 2019 Jan;119(1):21-29

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30466151

BACKGROUND: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. METHODS: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). RESULTS: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P < 0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5; 95%confidence intervals [CI], 1.3-1.9; P < 0.001), but not OS (HR 1.1; 95%CI, 0.9-1.3; P = 0.379). While MiVI and MaVI patients had similar DFS (median, MiVI 14.0 vs MaVI 12.0 months, HR 0.9; 95%CI, 0.7-1.2; P = 0.377), OS was better among MiVI patients (median, MiVI 39.0 vs MaVI 21.0 months, HR 0.7; 95%CI, 0.5-0.8; P = 0.002). Whereas nodal metastasis, R1 margin, and postoperative morbidity were associated with early death (≤18 months) among patients with MiVI, only nodal metastasis was associated with late (>18 months) prognosis. CONCLUSIONS: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.

Journal of cancer research and therapeutics 2018 11;14(6):1325-1329

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488851

Introduction: Cholecystectomy performed for benign diseases of the gallbladder is important for the diagnosis of gallbladder cancer. This is done by pathological examination of the removed specimens for patients with no detected or suspected complications before surgery. Although some centers undertake selective approaches for histopathological examination of gallbladder specimens, many centers perform this examination routinely. In our study, we investigated results of pathological examinations carried out on cholecystectomy specimens, in respect to unexpected cases of gallbladder cancer. Methods: We reviewed cholecystectomy cases performed for benign diseases of gallbladder from January 2012 to February 2016 by investigating pathological specimens from the gallbladder. We evaluated demographical properties and their association with the pathological diagnosis and frequency of unexpected gallbladder cancer cases. We reported additional treatment and survival information of the malignancy cases after surgery. Results: We reviewed 1294 cases of cholecystectomy, and the mean patient age was 47.5 ± 14.3 years. The most frequent diagnosis was chronic cholecystitis (92.3%), and it was more prevalent among younger patients and female sex (P < 0.0001). Five patients (0.4%) were determined to have gallbladder cancer, and the mean age of these cases was 65.6 ± 18.2 years. Two cases were Stage 2, two cases were Stage 3B, and one case was Stage 3A. There was no T1 or Tis tumor. Conclusion: Routine histopathological examination of gallbladder is significant with respect to the determination of additional interventions at the postoperative period required for cancer cases coincidentally diagnosed.

Minerva gastroenterologica e dietologica 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488679

Journal of gastrointestinal cancer 2018 Sep;49(3):268-274

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=28367607

BACKGROUND: India has high incidence of gallbladder carcinoma with regional variation in incidence, the highest in Northern India. This study examines the patterns of presentation, treatment strategies, and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over a period of 2 years. METHODS: All patients presented to our institute with established tissue diagnosis of carcinoma gallbladder were accrued in our study over a time period of 2 years. Presentation, treatment modalities, and survival rates were analyzed. RESULTS: One hundred six patients were included: 80 females and 26 males (F: M = 3:1). Median age was 60 years. Eighty patients (75%) had gallstones and 20 patients (21%) had typical history of chronic cholecystitis. The common symptom and sign at presentation were pain in the right upper abdomen (81%) and lump abdomen (49%), respectively. Overall resectability rate was 19.8% (21/106). Eighty-five patients were unresectable or metastatic and treated with palliative intent. Stagewise distribution at diagnosis was stage I (0%), stage II (4%), stage IIIA (10%), stage IIIB (8%), stage IVA (17%), and stage IVB (61%). Estimated 1-year survival for stages II, IIIA, IIIB, IVA, and IVB was 100, 76, 47.4, 26, and 10.6%, respectively. Significant difference in OS was observed among different stages of GBC (p value <0.001). CONCLUSION: If proper investigations are done, radical surgery including multi-organ resection can be curative with acceptable morbidity and mortality. Stage at presentation and ability to perform curative resection are the most important prognostic factors predicting survival. Palliative chemotherapy should be considered for metastatic GBC.

Annals of surgical oncology 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30499077

BACKGROUND: Current guidelines recommend radical cholecystectomy with regional lymphadenectomy (RC-RL) for patients with T1b gallbladder cancer (GBC). However, the extent to which these guidelines are followed is unclear. This study aimed to evaluate current surgical practices for T1b GBC and their implications for overall management strategies and associated outcomes. METHODS: This retrospective cohort study investigated patients identified from the National Cancer Data Base (2004-2012) with non-metastatic T1b GBC. The patients were categorized according to type of surgical treatment received: simple cholecystectomy (SC) or RC-RL. Among the patients who had lymph nodes pathologically examined, nodal status was classified as pN- or pN+. Use of any adjuvant therapy was ascertained. Overall survival (OS) was compared based on type of surgical treatment and nodal status. RESULTS: The cohort comprised 464 patients (247 SC and 217 RC-RL cases). The positive margin status did not differ between the two groups (6.1% for SC vs 2.3% for RC-RL; p = 0.128). For RC-RL, the pN+ rate was 15%. Adjuvant therapies were used more frequently in pN+ (53.1% vs 9.4% for pN-). By comparison, 10.9% of the SC patients received adjuvant therapy. The OS for RC-RL-pN- (5-years OS, 64.4%) was significantly better than for RC-RL-pN+ (5-years OS, 15.7%) or SC (5-years OS, 48.3%) (p < 0.001). CONCLUSION: Less than 50% of the patients with a T1b GBC primary tumor undergo the recommended surgical treatment. Given that 15% of these patients have nodal metastasis and in light of the previously described benefits of adjuvant therapy for node positive GBC, failure to perform RC-RL risks incomplete staging and thus undertreatment for patients with T1b GBC.

Journal of hepato-biliary-pancreatic sciences 2018 Dec;25(12):533-543

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30562839

BACKGROUND: There is no consensus on the optimal treatment of T1b gallbladder cancer (GBC) due to the lack of evidence and the difficulty of anatomy and pathological standardization. METHODS: A total of 272 patients with T1b GBC who underwent surgical resection at 14 centers with specialized hepatobiliary-pancreatic surgeons and pathologists in Korea, Japan, Chile, and the United States were studied. Clinical outcomes including disease-specific survival (DSS) rates according to the types of surgery were analyzed. RESULTS: After excluding patients, the 237 qualifying patients consisted of 90 men and 147 women. Simple cholecystectomy (SC) was performed in 116 patients (48.9%) and extended cholecystectomy (EC) in 121 patients (51.1%). The overall 5-year DSS was 94.6%, and it was similar between SC and EC patients (93.7% vs. 95.5%, P = 0.496). The 5-year DSS was similar between SC and EC patients in America (82.3% vs. 100.0%, P = 0.249) as well as in Asia (98.6% vs. 95.2%, P = 0.690). The 5-year DSS also did not differ according to lymph node metastasis (P = 0.688) or tumor location (P = 0.474). CONCLUSIONS: SC showed similar clinical outcomes (including recurrence) and survival outcomes as EC; therefore, EC is not needed for the treatment of T1b GBC.

The American journal of case reports 2018 Sep;19():1063-1067

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30181528

BACKGROUND Duodenal and ampullary carcinoids are very rare tumors accounting respectively for 2% and 0.03% of all carcinoid tumors. Clinical findings vary according to the location of the tumor within the periampullary region; with epigastric pain being the most common presenting symptom in duodenal carcinoids and jaundice the most common clinical finding in ampullary carcinoids. Treatment options include pancreaticoduodenectomy, local excision, and endoscopic excision. CASE REPORT In this case report, we present a 60-year-old male who presented with a one-week history of intractable epigastric pain. He was diagnosed with duodenal periampullary carcinoid tumor and treated with local excision. CONCLUSIONS Although duodenal and ampullary carcinoid tumors may have different clinical presentations, as well as histochemistry characteristics and metastatic potential, they appear to benefit from the same surgical treatment.

Journal of surgical oncology 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30548547

OBJECTIVES: To investigate the function of immunomarkers CK7, CK20, CK17, CDX2, MUC1, and MUC2 in the identification of primary ampullary carcinoma mixed subtype. METHODS: Forty-two cases of primary ampullary carcinoma were performed by immunohistochemical studies. The correlation between the mixed subtype and the other two subtypes and patient survival data was analyzed using the SPSS 16.0 statistical software. RESULTS: Among 42 cases, 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns: 91.7% (11/12) for CK7, 83.3% (10/12) for CK20; 66.7% (8/12) for CK17, CDX2, and MUC1; and 50% (6/12) for MUC2. Ten (83.3%) mixed types coexpressed four or more immunomarkers. Eight (19%) intestinal subtypes mainly showed a positive expression of CK20, CDX2, and MUC2. Twenty-two (52.4%) pancreaticobiliary subtypes showed a positive expression of CK7, MUC1, and CK17. Stages III and IV diseases in mixed subtype (25%) and intestinal subtype (25%) were less than pancreaticobiliary subtype(63.6%) (p = 0.039). Follow-up data appeared to show a better survival rate for patients with mixed subtype than those with pancreaticobiliary subtypes. CONCLUSION: Immunohistochemical staining provided a more reliable means of diagnosing mixed ampulla carcinoma. Accurate subtyping of ampullary carcinoma is clinically important to select effective chemotherapy regimens and to assess disease prognosis.

Minerva gastroenterologica e dietologica 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488680

INTRODUCTION: Ampullary cancer accounts for only 0.2% of GI cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS: Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS: A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, Black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (Hazard Ration 4.5, 95% CI 3.93-5.09, P=0.000). CONCLUSIONS: The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier.

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Nov;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497875

BACKGROUND/OBJECTIVES: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component. METHODS: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed. RESULTS: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P < 0.05) and cystic PNETs were significantly larger than solid PNETs (25 mm vs. 17 mm, P < 0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P = 0.64), hepatic metastasis (7% vs. 3%, P = 0.54), or disease-free survival rate (both 86%, P = 0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P < 0.01). CONCLUSIONS: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively.

Cancer management and research 2018 11;10():5629-5638

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30519109

Background: Neuroendocrine tumors (NETs) are a group of heterogeneous cancers arising from a variety of anatomic sites. Their incidence has increased in recent years. This study aimed to analyze the prognosis of NETs originating from different anatomic sites. Methods: We identified 73,782 patients diagnosed with NETs from the Surveillance Epidemiology and Ends Results (SEER) database from 1973 to 2014. Clinical data were compared between patients with different primary tumor sites using the chi-squared test. Differences in survival among NET patients with different tumor sites were compared by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify the prognostic factors of overall survival. Results: In this cohort, the lung/bronchus was the most common site of NETs, accounting for 30.6%, followed by the small intestine (22.2%), rectum (16.2%), colon (13.4%), pancreas (10.8%), and stomach (6.8%). Totally, 73,782 patients were selected for this cohort from 1973 to 2014. The median survival duration was 41 months. The 1-, 3-, 5-, and 10-year overall survival rates for patients with NETs were 72.8%, 52.7%, 39.4%, and 18.1%, respectively. Patients with NETs located in the rectum had the best prognosis, followed by those with NETs in the small intestine (HR, 1.660, 95% CI, 1.579, 1.744), lung/bronchus (HR, 1.786, 95% CI, 1.703, 1.874), stomach (HR, 1.865, 95% CI, 1.755, 1.982), and colon (HR, 1.896, 95% CI, 1.799, 1.999). Patients with NETs in the pancreas had the highest risk of mortality (HR, 2.034, 95% CI, 1.925, 2.148). Conclusion: Significant differences in survival were found among various primary tumor sites. NETs in the rectum had the best prognosis, while those in the pancreas had the worst. Primary tumor sites might be one of the most useful outcome predictors in patients with NETs.

Annals of surgical oncology 2018 Dec;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30519760

Pancreas 2019 Jan;48(1):131-134

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30531243

Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient’s anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.

The American journal of pathology 2019 Jan;189(1):71-81

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30558725

Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A blood-based biomarker that can enable early detection of disease, monitor response to treatment, and potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. The origin of CTCs and the methods of detection are discussed and a decade of research examining CTCs in pancreatic cancer is summarized, including both levels of CTCs and analyzing their molecular characteristics and how they may affect survival in both advanced and early disease and allow for treatment monitoring. The origin of cfDNA is discussed, and the literature over the past 15 years is summarized. This includes analyzing cfDNA for genetic mutations and methylation abnormalities, which have the potential to be used for the detection and prognosis of pancreatic ductal adenocarcinoma. However, the research certainly remains in the experimental stage, warranting future large trials in these areas.

Pancreas 2019 Jan;48(1):1-8

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30531240

The last 5 years have seen a dramatic increased interest in the field of exosome biology. Although much is unknown about the role of exosomes in human health and disease, disparate scientific disciplines are recognizing the highly conserved role that exosomes play in fundamental biological processes. Recently, there have been intriguing discoveries defining the role of exosomes in cancer biology. We performed a structured review of the English-language literature using the PubMed database searching for articles relating to exosomes and pancreatic ductal adenocarcinoma (PDAC). Articles were screened for relevance and content to judge for inclusion. Evidence implicates exosomes in the pathogenesis, local progression, metastasis, immune evasion, and intercellular communication of PDAC. Basic science discoveries in exosome biology have the potential to change the clinical management of PDAC, where, despite advances in early detection, diagnosis, staging, chemotherapy, and surgery, survival rates have been stagnant for decades and PDAC remains the most deadly human gastrointestinal malignancy.