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Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer (Panc Met) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1.787 (SD ± 0.336), and immunohistochemistry confirmed the expression of MUC5AC within tumor cells. MUC5AC-IR800 provides distinct visualization of pancreatic cancer liver metastasis in a PDOX mouse model, demonstrating its potential utility in staging laparoscopy and fluorescence-guided surgery.

Biliary tract cancers have dismal prognoses even when cytotoxic chemotherapy is administered. There is an unmet need to develop precision treatment approaches using comprehensive genomic profiling. A total of 121 patients with biliary tract cancers were analyzed for circulating-tumor DNA (ctDNA) and/or tissue-based tumor DNA (tissue-DNA) using clinical-grade next-generation sequencing: 71 patients (59%) had ctDNA; 90 (74%), tissue-DNA; and 40 (33%), both. Efficacy of targeted therapeutic approaches was assessed based upon ctDNA and tissue-DNA. At least one characterized alteration was detected in 76% of patients (54/71) for ctDNA [median, 2 (range, 0-9)] and 100% (90/90) for tissue-DNA [median, 4 (range, 1-9)]. Most common alterations occurred in TP53 (38%), KRAS (28%), and PIK3CA (14%) for ctDNA vs TP53 (44%), CDKN2A/B (33%) and KRAS (29%) for tissue-DNA. In 40 patients who had both ctDNA and tissue-DNA sequencing, overall concordance was higher between ctDNA and metastatic site tissue-DNA than between ctDNA and primary tumor DNA (78% vs 65% for TP53, 100% vs 74% for KRAS and 100% vs 87% for PIK3CA [But not statistical significance]). Among 80 patients who received systemic treatment, the molecularly matched therapeutic regimens based on genomic profiling showed a significantly longer progression-free survival (hazard ratio [95%confidence interval], 0.60 [0.37-0.99]. P = .047 [multivariate]) and higher disease control rate (61% vs 35%, P = .04) than unmatched regimens. Evaluation of ctDNA and tissue-DNA is feasible in biliary tract cancers.

BackgroundThe role of laterality for patients with synchronous metastatic colon cancer (SMCC) is not well-defined.MethodsUsing the National Cancer Database (2010-2015), we compared patients with metastatic right- (RCC) versus left-sided colon cancer (LCC). We performed Kaplan-Meier analysis to compare overall survival (OS) for each metastatic site and utilized adjusted Cox proportional hazard analysis to identify predictors of OS.ResultsPatients with RCCs were more likely to be older, female, and have more comorbidities. LCCs were more likely to metastasize to liver and lung, whereas RCCs were more likely to metastasize to peritoneum and brain. There was equal likelihood to metastasize to bone. OS was significantly longer for LCCs for all metastatic sites. After controlling for multiple variables, RCC (HR 1.426, p

BackgroundA significant proportion of patients with rectal cancer will present with synchronous metastasis at the time of diagnosis. Overall survival (OS) for these patients are highly variable and previous attempts to build predictive models often have low predictive power, with concordance indexes (c-index) less than 0.70.MethodsUsing the National Cancer Database (2010-2014), we identified patients with synchronous metastatic rectal cancer. The data was split into a training dataset (diagnosis years 2010-2012), which was used to build the machine learning model, and a testing dataset (diagnosis years 2013-2014), which was used to externally validate the model. A nomogram predicting 3-year OS was created using Cox proportional hazard regression with lasso penalization. Predictors were selected based on clinical significance and availability in NCDB. Performance of the machine learning model was assessed by c-index.ResultsA total of 4098 and 3107 patients were used to construct and validate the nomogram, respectively. Internally validated c-indexes at 1, 2, and 3 years were 0.816 (95% CI 0.813-0.818), 0.789 (95% CI 0.786-0.790), and 0.778 (95% CI 0.775-0.780), respectively. External validated c-indexes at 1, 2, and 3 years were 0.811, 0.779, and 0.778, respectively.ConclusionsThere is wide variability in the OS for patients with metastatic rectal cancer, making accurate predictions difficult. However, using machine learning techniques, more accurate models can be built. This will aid patients and clinicians in setting expectations and making clinical decisions in this group of challenging patients.

This study surveys surgeons’ cost knowledge and ability to distinguish subtle price variations between surgical tools with similar functions or indications.

BACKGROUND:Surgical supplies occupy a large portion of health care expenditures but is often under the surgeon's control. We sought to assess whether an automated, surgeon-directed, cost feedback system can decrease supply expenditures for five common general surgery procedures. MATERIALS AND METHODS:An automated "surgical receipt" detailing intraoperative supply costs was generated and emailed to surgeons after each case. We compared the median cost per case for 18 mo before and after implementation of the surgical receipt. We controlled for price fluctuations by applying common per-unit prices in both periods. We also compared the incision time, case length booking accuracy, length of stay, and postoperative occurrences. RESULTS:Median costs decreased significantly for open inguinal hernia ($433.45 to $385.49, P

Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer.

BackgroundA scholar's h-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists.MethodsWe utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science.ResultsWe identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p

A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p < 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy.

Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1×104 colony forming units (CFU)/100 μl) or, for comparison, intra-venous injection (iv; 5×107 CFU/100 μl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5×103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p

Background and objectivesDelineation of adequate tumor margins is critical in oncologic surgery, particularly in resection of metastatic lesions. Surgeons are limited in visualization with bright-light surgery, but fluorescence-guided surgery (FGS) has been efficacious in helping the surgeon achieve negative margins.MethodsThe present study uses FGS in a mouse model that has undergone surgical orthotopic implantation (SOI) of colorectal liver metastasis tagged with green fluorescent protein (GFP). An anti-CEA antibody conjugated to DyLight 650 was used to highlight the tumor.ResultsThe fluorescent antibody clearly demarcated the lesion at deeper tissue depth compared to GFP. Fluorescence of the anti-CEA-DyLight650 showed maximal tumor-to-liver contrast at 72 hr. Fifteen mice underwent bright-light surgery (BLS) versus FGS with GFP versus FGS with anti-CEA-DyLight650. Mice that underwent FGS had a significantly smaller area of residual tumor (P

The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs) that could localize to tumor in situ. One of the selected molecules is an aptamer that binds to the protein DHX9, an RNA helicase that is known to be upregulated in colorectal cancer. Upon systemic administration, the aptamer preferentially localized to the nucleus of cancer cells in vivo and thus has the potential to be used for targeted delivery.