Intratumoral Cell Neighborhoods Coordinate Outcomes in Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes. METHODS: Here, using automated chromogenic multiplex immunohistochemistry and unsupervised computational image analysis of human PDA tumors, we investigated cell neighborhoods in surgically resected tumors from patients with chemotherapy-naïve PDA (n = 59) and neoadjuvant chemotherapy-treated PDA (n = 57). Single cells were defined by lineage markers (CD3, CD8, Foxp3, CD68, CK19), proliferation (Ki67), and neighboring cells. RESULTS: Distinct intratumoral immune and tumor cell subsets were defined by neighboring cells. Higher content of stromal-associated macrophages was seen in chemotherapy-naïve tumors from long-term survivors (overall survival >3 years) compared with short-term survivors (overall survival <1 year), whereas immune-excluded tumor cells were higher in short-term survivors. Chemotherapy-treated vs -naïve tumors showed lower content of tumor-associated T cells and macrophages but similar densities of stromal-associated immune cells. However, proliferating tumor cell subsets with immune-rich neighborhoods were higher in chemotherapy-treated tumors. In a blinded analysis of tumors from patients treated with neoadjuvant chemotherapy, a composite index comprising lower quantities of immune-excluded tumor cells and higher spatially distinct immune cell subsets was associated with prolonged survival. CONCLUSIONS: Together, these data provide new insights into discrete cell communities in PDA and show their clinical relevance.

Hospital Costs Following Surgical Complications: A Value-driven Outcomes Analysis of Cost Savings Due to Complication Prevention.

OBJECTIVE: Surgical complications have substantial impact on healthcare costs. We propose an analysis of the financial impact of postoperative complications. SUMMARY OF BACKGROUND DATA: Both complications and preoperative patient risk have been shown to increase costs following surgery. The extent of cost increase due to specific complications has not been well described. METHODS: A single institution's American College of Surgeons National Surgical Quality Improvement Program data was queried from 2012 to 2018 and merged with institutional cost data for each encounter. A mixed effects multivariable generalized linear model was used to estimate the mean relative increase in hospital cost due to each complication, adjusting for patient and procedure-level fixed effects clustered by procedure. Potential savings were calculated based on projected decreases in complication rates and theoretical hospital volume. RESULTS: There were 11,897 patients linked between the 2 databases. The rate of any American College of Surgeons National Surgical Quality Improvement Program complication was 11.7%. The occurrence of any complication resulted in a 1.5-fold mean increase in direct hospital cost [95% confidence interval (CI) 1.49-1.58]. The top 6 most costly complications were postoperative septic shock (4.0-fold, 95% CI 3.58-4.43) renal insufficiency/failure (3.3-fold, 95% CI 2.91-3.65), any respiratory complication (3.1-fold, 95% CI 2.94-3.36), cardiac arrest (3.0-fold, 95% CI 2.64-3.46), myocardial infarction (2.9-fold, 95% CI 2.43-3.42) and mortality within 30 days (2.2-fold, 95% CI 2.01-2.48). Length of stay (6.5 versus 3.2 days, P < 0.01), readmission rate (29.1% vs 3.1%, P < 0.01), and discharge destination outside of home (20.5% vs 2.7%, P < 0.01) were significantly higher in the population who experienced complications. CONCLUSIONS: Decreasing complication rates through preoperative optimization will improve patient outcomes and lead to substantial cost savings.

Value Analysis of Methods of Inguinal Hernia Repair.

OBJECTIVE: Value is defined as health outcomes important to patients relative to cost of achieving those outcomes: Value = Quality/Cost. For inguinal hernia repair, Level 1 evidence shows no differences in long-term functional status or recurrence rates when comparing surgical approaches. Differences in value reside within differences in cost. The aim of this study is to compare the value of different surgical approaches to inguinal hernia repair: Open (Open-IH), Laparoscopic (Lap-IH), and Robotic (R-TAPP). METHODS: Variable and fixed hospital costs were compared among consecutive Open-IH, Lap-IH, and R-TAPP repairs (100 each) performed in a university hospital. Variable costs (VC) including direct materials, labor, and variable overhead ($/min operating room [OR] time) were evaluated using Value Driven Outcomes, an internal activity-based costing methodology. Variable and fixed costs were allocated using full absorption costing to evaluate the impact of surgical approach on value. As cost data is proprietary, differences in cost were normalized to Open-IH cost. RESULTS: Compared to Open-IH, VC for Lap-IH were 1.02X higher (including a 0.81X reduction in cost for operating room [OR] time). For R-TAPP, VC were 2.11X higher (including 1.36X increased costs for OR time). With allocation of fixed cost, a Lap-IH was 1.03X more costly, whereas R-TAPP was 3.18X more costly than Open-IH. Using equivalent recurrence as the quality metric in the value equation, Lap-IH decreases value by 3% and R-TAPP by 69% compared to Open-IH. CONCLUSIONS: Use of higher cost technology to repair inguinal hernias reduces value. Incremental health benefits must be realized to justify increased costs. We expect payors and patients will incorporate value into payment decisions.

County-level Variation in Use of Surgery and Cancer-specific Survival for Stage I-II Pancreatic Adenocarcinoma.

OBJECTIVE: The aim of the study was to describe county-level variation in use of surgery for stage I-II pancreatic ductal adenocarcinoma (PDAC) and the association between county surgery rates and cancer-specific survival (CSS). BACKGROUND: The degree of small geographic area variation in use of surgery for stage I-II PDAC and the association between area surgery rates and CSS remain incompletely defined. METHODS: This is a retrospective cohort study of patients aged 18 to 80 years in the 2007 to 2015 Surveillance, Epidemiology, and End Results database with stage I-II PDAC without contraindications to surgery or refusal. Multilevel models were used to characterize county-level variation in use of surgery and CSS. County-specific risk- and reliability-adjusted surgery rates and CSS rates were calculated. RESULTS: Of 18,100 patients living in 581 counties, 10,944 (60.5%) underwent surgery. Adjusted county-specific surgery rates varied 1.5-fold from 49.9% to 74.6%. Median CSS increased in a graded fashion from 13 months [interquartile range (IQR) 13-14] in counties with surgery rates of 49.9% to 56.9% to 18 months (IQR 17-19) in counties with surgery rates of 68.0% to 74.6%. Results were similar in multivariable analyses. Adjusted county 18-month CSS rates varied 1.6-fold from 32.7% to 53.7%. Adjusted county surgery and 18-month CSS rates were correlated (r = 0.54; P < 0.001) and county surgery rates explained approximately half of county-level variation in CSS. Only 18 (3.1%) counties had adjusted surgery rates of 68.0% to 74.6%, which was associated with the longest CSS. CONCLUSIONS: County-specific rates of surgery varied substantially, and patients living in areas with higher surgery rates lived longer. These data suggest that increasing use of surgery in stage I-II PDAC could lead to improvements in survival.

Size and Importance of Socioeconomic Status-Based Disparities in Use of Surgery in Nonadvanced Stage Gastrointestinal Cancers.

BACKGROUND: The size and importance of socioeconomic status (SES)-based disparities in use of surgery for non-advanced stage gastrointestinal (GI) cancers have not been quantified. METHODS: The exposure in this study of patients age 18-80 with one of nine non-advanced stage GI cancers in the 2007-2015 SEER database was a census tract-level SES composite. Multivariable models assessed associations of SES with use of surgery. Causal mediation analysis was used to estimate the proportion of survival disparities in SES quintiles 1 versus 5 that were mediated by disparities in use of surgery. RESULTS: Lowest SES quintile patients underwent surgery at significantly lower rates than highest quintile patients in each cancer. SES-based disparities in use of surgery were large and graded in esophagus adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma. Smaller but clinically relevant disparities were present in stomach, ampulla, and small bowel adenocarcinoma, whereas disparities were small in colorectal adenocarcinoma. Five-year all-stage overall survival (OS) was correlated with the size of disparities in use of surgery in SES quintiles 1 versus 5 (r = - 0.87; p = 0.003). Mean OS was significantly longer (range 3.5-8.9 months) in SES quintile 5 versus 1. Approximately one third of SES-based survival disparities in poor prognosis GI cancers were mediated by disparities in use of surgery. The size of disparities in use of surgery in SES quintiles 1 versus 5 was correlated with the proportion mediated (r = 0.98; p < 0.001). CONCLUSIONS: Low SES patients with poor prognosis GI cancers are at substantial risk of undertreatment. Disparities in use of surgery contribute to diminished survival.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

OBJECTIVE: To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. BACKGROUND: Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. METHODS: Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. RESULTS: Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. CONCLUSIONS: Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Pancreatic cancer as a sentinel for hereditary cancer predisposition.

BACKGROUND: Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) predisposition have been shown to play a role in pancreatic cancer susceptibility. Growing evidence suggests that pancreatic cancer may be useful as a sentinel cancer to identify families that could benefit from HBOC or CRC surveillance, but to date pancreatic cancer is only considered an indication for genetic testing in the context of additional family history. METHODS: Preliminary data generated at the Huntsman Cancer Hospital (HCH) included variants identified on a custom 34-gene panel or 59-gene panel including both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer cases, unselected for family history. Given the strength of preliminary data and corresponding literature, 61 sequential pancreatic cancer cases underwent a custom 14-gene clinical panel. Sequencing data from HCH pancreatic cancer cases, pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clinic were combined in a meta-analysis to estimate the proportion of carriers with pathogenic and high probability of pathogenic variants of uncertain significance (HiP-VUS). RESULTS: Approximately 8.6% of unselected pancreatic cancer cases at the HCH carried a variant with potential HBOC or CRC screening recommendations. A meta-analysis of unselected pancreatic cancer cases revealed that approximately 11.5% carry a pathogenic variant or HiP-VUS. CONCLUSION: With the inclusion of both HBOC and CRC susceptibility genes in a panel test, unselected pancreatic cancer cases act as a useful sentinel cancer to identify asymptomatic at-risk relatives who could benefit from relevant HBOC and CRC surveillance measures.

Factors associated with improved survival after resection of pancreatic adenocarcinoma: a multivariable model.

BACKGROUND: Several retrospective studies suggest that perioperative care and anesthetic management for cancer resection may influence cancer recurrence or patient survival. Various intraoperative techniques such as paravertebral blocks, decreased opioid use, immunomodulation, and perioperative antiinflammatory administration, have previously been assessed for improved patient survival. The aim of this study was to assess associations between perioperative management and survival in patients undergoing resection of pancreatic adenocarcinoma. METHODS: Survival data and anesthetic records for 144 patients who had surgical resection of pancreatic adenocarcinoma from 2001 to 2012 were obtained and associations were sought between survival and 19 predefined variables. The authors performed a propensity weighted multivariable statistical analysis using Cox proportional hazards. RESULTS: Median length of survival was 562 days with 95% confidence interval (471, 680). In a multivariable Cox proportional hazard model of survival, the authors found increased survival in patients who received perioperative epidural analgesia and/or intraoperative dexamethasone. There was a 44% hazard ratio reduction, hazard ratio = 0.56, 95% confidence interval (0.38, 0.87), with dexamethasone. Adjuvant postoperative chemotherapy was associated with longer survival. A decrease in survival was noted in patients who received intraoperative blood transfusions, had poorer histologic grade, and advanced tumor stage. CONCLUSIONS: The authors report an association between perioperative dexamethasone administration and improved survival in human pancreatic adenocarcinoma patients. An association between use of epidural anesthesia during primary pancreatic cancer surgery and prolonged survival was also observed. Previously identified associations between perioperative blood transfusions and poor tumor histologic grade and decreased survival were confirmed. Further investigations regarding the use of perioperative dexamethasone and neuraxial anesthesia in this patient population are warranted.

HR-MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer.

The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five-year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS-detectable metabolic changes provide useful biomarkers for tumor detection and response-monitoring in other cancers. The goal of this study was to identify MRS-detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used (1) H high-resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide-induced inflammation, in pancreata with pre-cancerous metaplasia (4 week old p48-Cre;LSL-Kras(G12D) mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48-Cre LSL-Kras(G12D) mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre-cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p < 0.00001) of controls, respectively. Importantly, analysis of patient biopsies was consistent with the mouse findings. Lipids dropped in pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer-associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring.

Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines.

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

Prospects for developing an accurate diagnostic biomarker panel for low prevalence cancers.

BACKGROUND: Early detection screening of asymptomatic populations for low prevalence cancers requires a highly specific test in order to limit the cost and anxiety produced by falsely positive identifications. Most solid cancers are a heterogeneous collection of diseases as they develop from various combinations of genetic lesions and epigenetic modifications. Therefore, it is unlikely that a single test will discriminate all cases of any particular cancer type. We propose a novel, intuitive biomarker panel design that accommodates disease heterogeneity by allowing for diverse biomarker selection that increases diagnostic accuracy. METHODS: Using characteristics of nine pancreatic ductal adenocarcinoma (PDAC) biomarkers measured in human sera, we modeled the behavior of biomarker panels consisting of a sum of indicator variables representing a subset of biomarkers within a larger biomarker data set. We then chose a cutoff for the sum to force specificity to be high and delineated the number of biomarkers required for adequate sensitivity of PDAC in our panel design. RESULTS: The model shows that a panel consisting of 40 non-correlated biomarkers characterized individually by 32% sensitivity at 95% specificity would require any 7 biomarkers to be above their respective thresholds and would result in a panel specificity and sensitivity of 99% each. CONCLUSIONS: A highly accurate blood-based diagnostic panel can be developed from a reasonable number of individual serum biomarkers that are relatively weak classifiers when used singly. A panel constructed as described is advantageous in that a high level of specificity can be forced, accomplishing a prerequisite for screening asymptomatic populations for low-prevalence cancers.

Screening for pancreatic cancer.

Even with improved cancer care generally, the incidence and death rate is increasing for pancreatic cancer. Concern exists that a further increase in deaths caused by pancreatic cancer will be seen as other causes of death, such as heart disease and other cancers, decline. Critical exploration of screening high-risk patients as a tool to reduce deaths from pancreatic cancer should be considered. Technological advances and improved understanding of pancreatic cancer biology provides an opportunity to identify and test a panel of early detection biomarkers easily, accurately, and inexpensively measured in blood, urine, stool, or saliva samples. These biomarkers may have additional usefulness in staging, stratification for treatment, establishing prognosis, and assessing response to therapy in this disease. Screening may prove to be one of several strategies to improve outcomes in a disease that has otherwise been difficult to defeat.

Does travel distance influence length of stay in elective pancreatic surgery?

BACKGROUND: Length of stay (LoS) following elective surgery is being reported as an outcomes quality measure. Regional referral centres may care for patients travelling significant distances. The effect of travel distance on LoS in pancreatic surgery patients was examined. METHODS: National Surgical Quality Improvement Program data on pancreatic surgery patients, operated during the period from 2005 to 2011, were reviewed. Demographics, surgical variables and distance travelled were analysed relative to LoS. The LoS was log-transformed in general linear models to achieve normality. RESULTS: Of the 243 patients, 53% were male. The mean ± standard deviation (SD) age of the total patient sample was 60.6 ± 14 years. The mean ± SD distance travelled was 203 ± 319 miles (326.7 ± 513.4 km) [median: 132 miles (212.4 km); range: 3-3006 miles (4.8-4837.7 km)], and the mean ± SD LoS was 10.5 ± 7 days (range: 1-46 days). Univariate analysis showed a near significant increase in LoS with increased distance travelled (P = 0.05). Significant variables related to LoS were: age (P = 0.002); relative value units (P < 0.001), and preoperative American Society of Anesthesiologists class (P = 0.005). In a general linear model, for every 100 miles (160.9 km) travelled there is an associated 2% increase in LoS (P = 0.031). When the distance travelled is increased by 500 miles (804.7 km), LoS increases by 10.5%. CONCLUSIONS: Increased travel distance from a patient's home to the hospital was independently associated with an increase in LoS. If LoS is a reportable quality measure in pancreatic surgery, travel distance should be considered in risk adjustments.

Serum IGFBP2 and MSLN as diagnostic and prognostic biomarkers for pancreatic cancer.

BACKGROUND: Identification of diagnostic and prognostic biomarkers is a research priority for the improved management of pancreatic ductal adenocarcinoma (PDAC). Insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) have shown potential as serum biomarkers in other cancers, but have not been adequately studied in PDAC. METHODS: Serum IGFBP2 and MSLN levels were quantified by enzyme-linked immunosorbent assay (ELISA) in a cohort of 84 PDAC patients, 84 healthy control subjects and 40 chronic pancreatitis (ChPT) patients. Regression models related IGFBP2 and MSLN levels to diagnosis, gender, age, stage and survival. RESULTS: IGFPB2 and MSLN serum levels were diagnostic for PDAC in age-adjusted models (P = 0.032 and P = 0.002, respectively) when compared with ChPT and healthy control samples. At a 95% specificity threshold, the sensitivity for IGFBP2 was 22% and the sensitivity for MSLN was 17%. Neither protein approached the diagnostic accuracy of CA 19-9. However, IGFBP2 or MSLN or both correctly identified 18 of the 28 samples misidentified by CA 19-9. In age-adjusted models, neither serum IGFBP2 (P = 0.36) nor MSLN (P = 0.29) were significant predictors of survival. DISCUSSION: Serum IGFBP2 and MSLN are weak diagnostic classifiers individually, but may be useful in a diagnostic biomarker panel.

Comparison of intraoperative versus delayed enteral feeding tube placement in patients undergoing a Whipple procedure.

BACKGROUND: The intraoperative placement of an enteral feeding tube (FT) during pancreaticoduodenectomy (PD) is based on the surgeon's perception of need for postoperative nutrition. Published preoperative risk factors predicting postoperative morbidity may be used to predict FT need and associated intraoperative placement. METHODS: A retrospective review of patients who underwent PD during 2005-2011 was performed by querying the National Surgical Quality Improvement Program (NSQIP) database with specific procedure codes. Patients were categorized based on how many of 10 possible preoperative risk factors they demonstrated. Groups of patients with scores of ≤ 1 (low) and ≥ 2 (high), respectively, were compared for FT need, length of stay (LoS) and organ space surgical site infections (SSIs). RESULTS: Of 138 PD patients, 82 did not have an FT placed intraoperatively, and, of those, 16 (19.5%) required delayed FT placement. High-risk patients were more likely to require a delayed FT (29.3%) compared with low-risk patients (9.8%) (P = 0.026). The 16 patients who required a delayed FT had a median LoS of 15.5 days, whereas the 66 patients who did not require an FT had a median LoS of 8 days (P < 0.001). CONCLUSIONS: In this analysis, subjects considered as high-risk patients were more likely to require an FT than low-risk patients. Assessment of preoperative risk factors may improve decision making for selective intraoperative FT placement.

Screening for pancreatic cancer: why, how, and who?

Pancreatic cancer is the fourth most common cause of cancer mortality in the United States, with 5-year survival rates for patients with resectable tumors ranging from 15% to 20%. However, most patients presenting with distant metastases, are not resectable, and have a 5-year survival rate of close to 0%. This demonstrates a need for improved screening to identify pancreatic cancer while the tumor is still localized and amenable to surgical resection. Studies of patients with pancreatic tumors incidentally diagnosed demonstrate longer median survival than tumors discovered only when the patient is symptomatic, suggesting that early detection may improve outcome. Recent evidence from genomic sequencing indicates a 15-year interval for genetic progression of pancreatic cancer from initiation to the metastatic stage, suggesting a sufficient window for early detection. Still, many challenges remain in implementing effective screening. Early diagnosis of pancreatic cancer relies on developing screening methodologies with highly sensitive and specific biomarkers and imaging modalities. It also depends on a better understanding of the risk factors and natural history of the disease to accurately identify high-risk groups that would be best served by screening. This review summarizes our current understanding of the biology of pancreatic cancer relevant to methods available for screening. At this time, given the lack of proven benefit in this disease, screening efforts should probably be undertaken in the context of prospective trials.

Association between postoperative complications and clinical cancer outcomes.

INTRODUCTION: The treatment for a majority of solid organ tumors is surgical resection; 10-20 % of patients suffer a perioperative complication. Perioperative complications may contribute to cancer recurrence. This study examined the relationship between postoperative complications and risk-adjusted patient overall survival. METHODS: Data from 2003 to 2009 were linked from our clinical cancer registry, the National Surgery Quality Improvement Project (NSQIP), and medical records. Patients who had tumor extirpation for cure were included. The NSQIP was used to identify complications. Patients with a complication were matched to patients without a complication. χ (2) tests and Cox proportional hazard regression models were used. RESULTS: A total of 415 patients were included for survival analysis. The hazard ratio (HR) for mortality associated with having a complication was 2.17. The HR for mortality after 200 days postoperatively was 2.47. Infectious complications were associated with the highest association with increased mortality (HR = 3.56). Noninfectious complications were not associated with an increased risk of mortality. CONCLUSIONS: This study investigated the relationship of surgical infectious complications in cancer patients with long-term survival for patients who had a number of different types of cancer. After taking into account the site, histology, and stage of the cancer, we found that patients with infectious complications had earlier death.

Toward development of a surface-enhanced Raman scattering (SERS)-based cancer diagnostic immunoassay panel.

Proteomic analyses of readily obtained human fluids (e.g., serum, urine, and saliva) indicate that the diagnosis of complex diseases will be enhanced by the simultaneous measurement of multiple biomarkers from such samples. This paper describes the development of a nanoparticle-based multiplexed platform that has the potential for simultaneous read-out of large numbers of biomolecules. For this purpose, we have chosen pancreatic adenocarcinoma (PA) as a test bed for diagnosis and prognosis. PA is a devastating form of cancer in which an estimated 86% of diagnoses resulted in death in the United States in 2010. The high mortality rate is due, in part, to the asymptomatic development of the disease and the dearth of sensitive diagnostics available for early detection. One promising route lies in the development of a serum biomarker panel that can generate a signature unique to early stage PA. We describe the design and development of a proof-of-concept PA biomarker immunoassay array coupled with surface-enhanced Raman scattering (SERS) as a sensitive readout method.

Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma.

PURPOSE: We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. RESULTS: A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. CONCLUSION: Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.