General Anesthetics in CAncer REsection Surgery (GA-CARES) randomized multicenter trial of propofol vs volatile inhalational anesthesia: protocol description.

BACKGROUND: Studies indicate that patients can be "seeded" with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality. Therefore, we designed a pragmatic phase 3 multicenter randomized controlled trial (RCT) called General Anesthetics in Cancer Resection (GA-CARES). METHODS: After clinical trial registration and institutional review board approval, patients providing written informed consent were enrolled at five sites in New York (NY) State. Eligible patients were adults with known or suspected cancer undergoing one of eight oncologic surgeries having a high risk of cancer recurrence. Exclusion criteria included known or suspected history of malignant hyperthermia or hypersensitivity to either propofol or volatile anesthetic agents. Patients were randomized (1:1) stratified by center and surgery type using REDCap to receive either propofol or volatile agent for maintenance of general anesthesia (GA). This pragmatic trial, which seeks to assess the potential impact of anesthetic type in "real world practice", did not standardize any aspect of patient care. However, potential confounders, e.g., use of neuroaxial anesthesia, were recorded to confirm the balance between study arms. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms (primary endpoint, minimum 2-year follow-up), power using a two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1800 subjects. Data sources include the National Death Index (gold standard for vital status in the USA), NY Cancer Registry, and electronic harvesting of data from electronic medical records (EMR), with minimal manual data abstraction/data entry. DISCUSSION: Enrollment has been completed (n = 1804) and the study is in the follow-up phase. This unfunded, pragmatic trial, uses a novel approach for data collection focusing on electronic sources. TRIAL REGISTRATION: Registered (NCT03034096) on January 27, 2017, prior to consent of the first patient on January 31, 2017.

Tumor Biomarker In-Solution Quantification, Standard Production, and Multiplex Detection.

The diagnosis and monitoring of cancer have been facilitated by discovering tumor "biomarkers" and methods to detect their presence. Yet, for certain cancers, we still lack sensitive and specific biomarkers or the means to quantify subtle concentration changes successfully. The identification of new biomarkers of disease and improving the sensitivity of detection will remain key to changing clinical outcomes. Patient liquid biopsies (serum and plasma) are the most easily obtained sources for noninvasive analysis of proteins that tumor cells release directly and via extracellular microvesicles and tumor shedding. Therefore, an emphasis on creating reliable assays using serum/plasma and "direct, in-solution" ELISA approaches has built an industry centered on patient protein biomarker analysis. A need for improved dynamic range and automation has resulted in the application of ELISA principles to paramagnetic beads with chemiluminescent or fluorescent detection. In the clinical testing lab, chemiluminescent paramagnetic assays are run on automated machines that test a single analyte, minimize technical variation, and are not limited by serum sample volumes. This differs slightly from the R&D setting, where serum samples are often limiting; therefore, multiplexing antibodies to test multiple biomarkers in low serum volumes may be preferred. This review summarizes the development of historical biomarker "standards", paramagnetic particle assay principles, chemiluminescent or fluorescent biomarker detection advancements, and multiplexing for sensitive detection of novel serum biomarkers.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.

ABSTRACT: This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management and surveillance of metastatic and unresectable pheochromocytoma and paraganglioma held on October 2 and 3, 2019. The panelists consisted of endocrinologists, medical oncologists, surgeons, radiologists/nuclear medicine physicians, nephrologists, pathologists, and radiation oncologists. The panelists performed a literature review on a series of questions regarding the medical management of metastatic and unresectable pheochromocytoma and paraganglioma as well as questions regarding surveillance after resection. The panelists voted on controversial topics, and final recommendations were sent to all panel members for final approval.

Development of cancer after bariatric surgery.

BACKGROUND: Although bariatric surgery has been associated with a reduction in risk of obesity-related cancer, data on the effect of bariatric interventions on other cancers are limited. OBJECTIVES: This study aimed to examine the relationship between bariatric interventions and the incidence of various cancers after bariatric surgery. SETTING: Administrative statewide database. METHODS: The New York Statewide Planning and Research Cooperative System database was used to identify all adult patients diagnosed with obesity between 2006 and 2012 and patients who underwent bariatric procedures without preexisting cancer diagnosis and alcohol or tobacco use. Subsequent cancer diagnoses were captured up to 2016. Multivariable proportional subdistribution hazard regression analysis was performed to compare the risk of having cancer among obese patients with and without bariatric interventions. RESULTS: We identified 71,000 patients who underwent bariatric surgery and 323,197 patients without a bariatric intervention. Patients undergoing bariatric surgery were less likely to develop both obesity-related cancer (hazard ratio.91; 95% confidence interval, .85-.98; P = .013) and other cancers (hazard ratio .81; 95% confidence interval, .74-.89; P < .0001). Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing cancers that are considered nonobesity related (hazard ratio .59; 95% confidence interval, .42-.83; P = .0029) compared with laparoscopic sleeve gastrectomy. CONCLUSIONS: Bariatric surgery is associated with a decreased risk of obesity-related cancers. More significantly, we demonstrated the relationship between bariatric surgery and the reduction of the risk of some previously designated nonobesity-related cancers, as well. Reclassification of nonobesity-related cancers and expansion of bariatric indications for reducing the risk of cancer may be warranted.

Correction: Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Comparative Analysis of Survival and Funding Discrepancies in Cancers With High Mortality.

OBJECTIVE: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. BACKGROUND: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. RESULTS: Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) hijacks innate cellular processes to promote cancer growth. We hypothesized that PC exploits PD-1/PD-L1 not only to avoid immune responses, but to directly enhance growth. We also hypothesized that immune checkpoint inhibitors (ICIs) have direct cytotoxicity in PC. We sought to elucidate therapeutic targeting of PD-1/PD-L1. METHODS: PD-1 was assessed in PC cells, patient-derived organoids (PDOs), and clinical tissues. Then, PC cells were exposed to PD-L1 to evaluate proliferation. To test PD-1/PD-L1 signaling, cells were exposed to PD-L1 and MAPK was examined. Radio-immunoconjugates with anti-PD-1 drugs were developed to test uptake in patient-derived tumor xenografts (PDTXs). Next, PD-1 function was assessed by xenografting PD-1-knockdown cells. Finally, PC models were exposed to ICIs. RESULTS: PD-1 expression was demonstrated in PCs. PD-L1 exposure increased proliferation and activated MAPK. Imaging PDTXs revealed uptake of radio-immunoconjugates. PD-1 knockdown in vivo revealed 67% smaller volumes than controls. Finally, ICI treatment of both PDOs/PDTXs demonstrated cytotoxicity and anti-MEK1/2 combined with anti-PD-1 drugs produced highest cytotoxicity in PDOs/PDTXs. CONCLUSIONS: Our data reveal PCs innately express PD-1 and activate druggable oncogenic pathways supporting PDAC growth. Strategies directly targeting PC with novel ICI regimens may work with adaptive immune responses for optimal cytotoxicity.

Development of Patient-Derived Gastric Cancer Organoids from Endoscopic Biopsies and Surgical Tissues.

BACKGROUND: Organoids are three-dimensional in vitro models of human disease developed from benign and malignant gastrointestinal tissues with tremendous potential for personalized medicine applications. We sought to determine whether gastric cancer patient-derived organoids (PDOs) could be safely established from endoscopic biopsies for rapid drug screening. METHODS: Patients underwent esophagogastroduodenoscopy (EGD) for surveillance or staging and had additional forceps biopsies taken for PDO creation. Cancer tissues from operative specimens were also used to create PDOs. To address potential tumor heterogeneity, we performed low-coverage whole-genome sequencing of endoscopic-derived PDOs with paired surgical PDOs and whole-tumor lysates. The stability of genomic alterations in endoscopic organoids was assessed by next-generation sequencing and nested polymerase chain reaction (PCR) assay. The feasibility and potential accuracy of drug sensitivity screening with endoscopic-derived PDOs were also evaluated. RESULTS: Gastric cancer PDOs (n = 15) were successfully established from EGD forceps biopsies (n = 8) and surgical tissues (n = 7) from five patients with gastric adenocarcinoma. Low-coverage whole-genomic profiling of paired EGD and surgical PDOs along with whole-tumor lysates demonstrated absence of tumor heterogeneity. Nested PCR assay identified similar KRAS alterations in primary tumor and paired organoids. Drug sensitivity testing of endoscopic-derived PDOs displayed standard dose-response curves to current gastric cancer cytotoxic therapies. CONCLUSIONS: Our study results demonstrate the feasibility of developing gastric cancer PDOs from EGD biopsies. These results also indicate that endoscopic-derived PDOs are accurate surrogates of the primary tumor and have the potential for drug sensitivity screening and personalized medicine applications.

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years.

BACKGROUND: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. MATERIALS AND METHODS: All Phase 2-4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. RESULTS: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). CONCLUSIONS: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. FUNDING: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).

Case report of intestinal non-rotation, heterotaxy, and polysplenia in a patient with pancreatic cancer.

RATIONALE: Heterotaxy with polysplenia is an extremely rare congenital condition resulting from abnormal arrangement of organs in the abdominal and thoracic cavities during embryologic development. When a malignancy such as pancreatic cancer develops under these conditions, surgical resection becomes particularly complex. This case report demonstrates successful pancreatic cancer resection despite the patient's complicated anatomy. PATIENT CONCERNS: An 82-year-old female presented to our institution with complaints of mild right upper quadrant pain radiating to the mid-epigastric region. DIAGNOSES: Physical examination revealed jaundice with scleral icterus consistent with obstructive jaundice. Radiographic imaging revealed hepatic duct dilation with several anatomic anomalies including small bowel location in the right upper abdomen, cecum, and appendix in the left lower quadrant, reversed superior mesenteric artery and superior mesenteric vein positions, and right-sided duodenal-jejunal flexture as well as an entirely right-sided pancreas, and left lower pelvis with ≥6 separate splenules. These findings resulted in a diagnosis of heterotaxy syndrome with polysplenia. INTERVENTIONS: Careful preoperative planning and total pancreatectomy was performed without complication. OUTCOMES: The patient recovered well. Pathologic examination of the pancreatic mass revealed moderately/poorly differentiated invasive pancreatic duct adenocarcinoma. The patient remains alive and well without signs of recurrent disease at the 2-year follow-up. LESSONS: Given the wide range of anatomical variants observed in patients with heterotaxy syndrome, a thorough radiologic assessment is necessary before engaging in any surgical procedure. In our case, preoperative identification of the various anatomic anomalies, such as the short and vertically oriented pancreas, the porta hepatis position anterior to the duodenum, the nonrotation of the intestines and the anomalous origin of the right hepatic artery allowed us to perform a safe and uncomplicated total pancreatectomy.

De Novo Lipid Synthesis Facilitates Gemcitabine Resistance through Endoplasmic Reticulum Stress in Pancreatic Cancer.

Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single-agent therapy for pancreatic cancer. Although the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging The Cancer Genome Atlas dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients. Furthermore, we investigated the relationship between alterations in lipogenesis pathway and gemcitabine resistance by utilizing tissues from the genetically engineered mouse model and human pancreatic cancer patients. We observed a significant increase in fatty acid synthase (FASN) expression with increasing disease progression in spontaneous pancreatic cancer mouse model, and a correlation of high FASN expression with poor survival in patients and poor gemcitabine responsiveness in cell lines. We observed a synergistic effect of FASN inhibitors with gemcitabine in pancreatic cancer cells in culture and orthotopic implantation models. Combination of gemcitabine and the FASN inhibitor orlistat significantly diminished stemness, in part due to induction of endoplasmic reticulum (ER) stress that resulted in apoptosis. Moreover, direct induction of ER stress with thapsigargin caused a similar decrease in stemness and showed synergistic activity with gemcitabine. Our in vivo studies with orthotopic implantation models demonstrated a robust increase in gemcitabine responsiveness upon inhibition of fatty acid biosynthesis with orlistat. Altogether, we demonstrate that fatty acid biosynthesis pathway manipulation can help overcome the gemcitabine resistance in pancreatic cancer by regulating ER stress and stemness. Cancer Res; 77(20); 5503-17. ©2017 AACR.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage.

OBJECTIVE: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer.

Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming. Targeting HIF-1α or de novo pyrimidine biosynthesis, in combination with gemcitabine, strongly diminishes tumor burden. Finally, reduced expression of TKT and CTPS, which regulate flux into pyrimidine biosynthesis, correlates with better prognosis in pancreatic cancer patients on fluoropyrimidine analogs.

Duodenal gangliocytic paraganglioma with lymph node metastases: A case report and comparative review of 31 cases.

Gangliocytic paraganglioma (GP) is a rare tumor of uncertain origin most often located in the second portion of the duodenum. It is composed of three cellular components: Epithelioid endocrine cells, spindle-like/sustentacular cells, and ganglion-like cells. While this tumor most often behaves in a benign manner, cases with metastasis are reported. We describe the case of a 62-year-old male with a periampullary GP with metastases to two regional lymph nodes who was successfully treated with pancreaticoduodenectomy. Using PubMed, EMBASE, EBSCOhost MEDLINE and CINAHL, and Google Scholar, we searched the literature for cases of GP with regional lymph node metastasis and evaluated the varying presentations, diagnostic workup, and disease management of identified cases. Thirty-one cases of GP with metastasis were compiled (30 with at least lymph node metastases and one with only distant metastasis to bone), with age at diagnosis ranging from 16 to 74 years. Ratio of males to females was 19:12. The most common presenting symptoms were abdominal pain (55%) and gastrointestinal bleeding or sequelae (42%). Twenty-five patients underwent pancreaticoduodenectomy. Five patients were treated with local resection alone. One patient died secondary to metastatic disease, and one died secondary to perioperative decompensation. The remainder did well, with no evidence of disease at follow-up from the most recent procedure (except two in which residual disease was deliberately left behind). Of the 26 cases with sufficient histological description, 16 described a primary tumor that infiltrated deep to the submucosa, and 3 described lymphovascular invasion. Of the specific immunohistochemistry staining patterns studied, synaptophysin (SYN) stained all epithelioid endocrine cells (18/18). Neuron specific enolase (NSE) and SYN stained most ganglion-like cells (7/8 and 13/18 respectively), and S-100 stained all spindle-like/sustentacular cells (21/21). Our literature review of published cases of GP with lymph node metastasis underscores the excellent prognosis of GP regardless of specific treatment modality. We question the necessity of aggressive surgical intervention in select patients, and argue that local resection of the mass and metastasis may be adequate. We also emphasize the importance of pre-surgical assessment with imaging studies, as well as post-surgical follow-up surveillance for disease recurrence.

Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a prospective clinical trial.

PURPOSE: Prospectively assess relationships between dosimetric parameters and histopathologic/clinical duodenal toxicities in patients on a phase I trial for pancreatic cancer. METHODS: Forty-six borderline resectable/unresectable patients were enrolled on a prospective trial testing neoadjuvant gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5-8Gy) and concurrent nelfinavir. Post-SBRT surgery was performed in 13 resectable patients, which constituted the patient population herein. Pathologic duodenal damage was assessed using predetermined criteria: 1, no/minimal; 2, moderate; and 3, marked damage. Clinical toxicities were assessed per the Clinical Terminology Criteria for Adverse Events (CTCAE). Duodenal dosimetric parameters included V5-V40 and mean/maximum doses. Spearman correlation and linear regression evaluated associations between dosimetric parameters and clinical/pathologic duodenal toxicity. RESULTS: The median duodenal mean and maximum doses were 20 and 37Gy. Median duodenal V5-V40 were 64, 62, 52, 39, 27, 14, 5 and 0cc, respectively. The median duodenal damage score was 2 (four 1, eight 2, and one 3). Higher duodenal damage scores correlated with higher duodenal mean doses (r=0.75, p=0.003), V35 (r=0.61, p=0.03), V30 (r=0.67, p=0.01), V25 (r=0.68, p=0.01), V20 (r=0.56, p=0.05), and the planning target volume (PTV) mean (r=0.59, p=0.03) and maximum (r=0.61, p=0.03) doses. Clinical toxicities did not correlate with dosimetric parameters or duodenal pathologic damage. CONCLUSIONS: Duodenal histologic damage correlates with mean duodenal dose, V20-V35, and PTV mean/maximum doses.

A Combination of MUC5AC and CA19-9 Improves the Diagnosis of Pancreatic Cancer: A Multicenter Study.

OBJECTIVES: Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets. METHODS: The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321). RESULTS: Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9-382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7-948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4-26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5-19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls. CONCLUSIONS: MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Surgical Management of Liver Metastases From Colorectal Cancer.

Surgical resection remains one of the major curative treatment options available to patients with colorectal liver metastases. Surgery and chemotherapy form the backbone of the treatment in patients with colorectal liver metastases. With more effective chemotherapy regimens being available, the optimal timing and sequencing of treatments are important. A multidisciplinary approach with the involvement of medical oncologists and surgical oncologists from the beginning is crucial. Identification of the clinical and molecular prognostic factors may help personalize the treatment approaches for these patients. This article provides an overview of the surgical management of colorectal liver metastases.

Clinical presentation and outcome of nonfunctional pancreatic neuroendocrine tumors in a modern cohort.

BACKGROUND: The natural history of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is largely unstudied due to its rarity. The primary goal of this study was to characterize clinical features and outcomes of incidental NF-PNETs. METHODS: An institutional review board-approved retrospective study of patients with NF-PNET evaluated by the Surgical Oncology of University of Nebraska Medical Center was performed. Patients were evaluated with dedicated pancreatic and liver imaging using multiphasic computed tomographic scan and dedicated magnetic resonance imaging protocols. RESULTS: Forty-six patients (male, 47.8%) were evaluated, and 35 ultimately resected. Of these, 16 tumors were discovered incidentally. The median age was 62 and 59 years in incidental and symptomatically discovered, respectively. Incidental median size was 2.4 cm vs 6 cm in the symptomatic group, with a P value of .037. The presence of lymphatic and liver metastases was 10% and 25% incidental and 45% and 67% for those with symptoms (lymphatic involvement, P = .05; liver metastases P = .07). Median overall survival was 45 and 76 months (P = .03). CONCLUSIONS: Incidentally discovered NF-PNETs represent a malignancy with more questions than answers. Our series indicates that these cancers are more indolent than previously believed.