Quan P. Ly

Preoperative Nomogram to Predict Risk of Perioperative Mortality Following Pancreatic Resections for Malignancy

IntroductionThe majority of pancreatic resections for malignancy are performed in older patients with major comorbidities. The aim of this study was to develop a preoperative nomogram based on the presence of comorbidities to predict risk of perioperative mortality.Materials and MethodsThe National Inpatient Sample database was queried to identify patients that underwent pancreatectomy for malignancy. The preoperative comorbidities identified as predictors were used, and a nomogram was created. Sample A (2000–2004) was utilized to develop the model, and sample B (2005) was utilized to validate this model.ResultsThe overall actual observed perioperative mortality rate for samples A and B was 6.3% and 5.2%, respectively. The mean total points calculated for sample A by the nomogram was 131.7 that translates to a nomogram-predicted mortality rate of 4.9%, which is similar to the actual mortality. The mean total points for sample B was 128.1, which translates to a nomogram-predicted mortality rate of 4.6%. The similarity of mortality rates as predicted by the nomogram and a concordance index of 0.76 shows good agreement between the data and the nomogram.ConclusionThis preoperative nomogram has been shown to accurately predict the risk of perioperative mortality following pancreatectomy for malignancy.

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.

Management of the primary tumor in patients with metastatic pancreatic neuroendocrine tumor: a contemporary single-institution review.

BACKGROUND Pancreatic nonfunctioning neuroendocrine tumors (PNFNETs) are an uncommon malignancy and often present with metastatic disease. There is a lack of information on the management of the primary tumor in patients who present with unresectable synchronous hepatic metastases. METHODS A retrospective review (2001-2008) of PNFNETs was conducted. Patients were divided into 3 groups: PNFNET without evidence of hepatic metastasis (group A), PNFNET with metastatic disease involving less than 50% of the liver (group B), and PNFNET with metastatic disease involving more than 50% of the liver (group C). Clinical data and outcomes were analyzed. RESULTS Thirty-five patients with PNFNET were identified (group A = 15, group B = 11, group C = 9). Resection of the pancreatic tumor was performed in 26 patients. With a mean follow-up period of 30 months, death from disease progression occurred in 1 patient in group A, none in group B, and in 7 in group C. CONCLUSIONS In selected patients, resection of the primary pancreatic tumor even in the setting of unresectable but limited hepatic metastases may be indicated.

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.

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.

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.

Erratum: MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer (Cancer Cell (2017) 32(1) (71–87.e7) (S1535610817302544) (10.1016/j.ccell.2017.06.004))

Surendra K. Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V. Chaika, Enza Vernucci, Ryan J. King, Jaime Abrego, Gennifer D. Goode, Aneesha Dasgupta, Alysha L. Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J. Augustine, Divya Murthy, Kuldeep S. Attri, Oksana Mashadova, Paul M. Grandgenett, Robert Powers, Quan P. Ly, Audrey J. Lazenby, Jean L. Grem, Fang Yu, José M. Matés, John M. Asara, Jung-whan Kim, Jordan H. Hankins, Colin Weekes, Michael A. Hollingsworth, Natalie J. Serkova, Aaron R. Sasson, Jason B. Fleming, Jennifer M. Oliveto, Costas A. Lyssiotis, Lewis C. Cantley, Lyudmyla Berim, and Pankaj K. Singh* *Correspondence: pankaj.singh@unmc.edu http://dx.doi.org/10.1016/j.ccell.2017.08.008

Fluorescence Guidance in Surgical Oncology: Challenges, Opportunities, and Translation

Surgical resection continues to function as the primary treatment option for most solid tumors. However, the detection of cancerous tissue remains predominantly subjective and reliant on the expertise of the surgeon. Surgery that is guided by fluorescence imaging has shown clinical relevance as a new approach to detecting the primary tumor, tumor margins, and metastatic lymph nodes. It is a technique to reduce recurrence and increase the possibility of a curative resection. While significant progress has been made in developing this emerging technology as a tool to assist the surgeon, further improvements are still necessary. Refining imaging agents and tumor targeting strategies to be a precise and reliable surgical strategy is essential in order to translate this technology into patient care settings. This review seeks to provide a comprehensive update on the most recent progress of fluorescence-guided surgery and its translation into the clinic. By highlighting the current status and recent developments of fluorescence image-guided surgery in the field of surgical oncology, we aim to offer insight into the challenges and opportunities that require further investigation.