Curtis R. Hall

Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors

PURPOSE The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs. METHODS We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival. RESULTS The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths. CONCLUSION Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size.

Optical Markers in Duodenal Mucosa Predict the Presence of Pancreatic Cancer

Purpose: Pancreatic cancer remains one of the most deadly cancers and carries a dismal 5-year survival rate of <5%. Therefore, there is urgent need to develop a highly accurate and minimally invasive (e.g., without instrumentation of the pancreatic duct given high rate of complications) method of detection. Our group has developed a collection of novel light-scattering technologies that provide unprecedented quantitative assessment of the nanoscale architecture of the epithelium. We propose a novel approach to predict pancreatic cancer through the assessment of the adjacent periampullary duodenal mucosa without any interrogation of the pancreatic duct or imaging of the pancreas. Experimental Design: Endoscopically and histologically normal-appearing periampullary duodenal biopsies obtained from 19 pancreatic cancer patients were compared with those obtained at endoscopy from 32 controls. Biopsies were analyzed using our newly developed optical technologies, four-dimensional elastic light-scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering (LEBS) spectroscopy. Results: 4D-ELF– and LEBS-derived optical markers from normal-appearing periampullary duodenal mucosa can discriminate between pancreatic cancer patients and normal controls with 95% sensitivity and 91% specificity. Moreover, the diagnostic performance of these optical markers was not compromised by confounding factors such as tumor location and stage. Conclusions: Here, we showed, for the first time, that optical analysis of histologically normal duodenal mucosa can predict the presence of pancreatic cancer without direct visualization of the pancreas.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART I: Diagnosis‐clinical staging and pathology

Biliary tract cancers (gallbladder cancer, intra‐ and extra‐hepatic cholangiocarcinoma, and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol. 2012; 106:332–338.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part II: multidisciplinary management.

Biliary tract cancers (gallbladder cancer, intra‐ and extra‐hepatic cholangiocarcinoma and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol. 2012; 106:339–345.

Spectral Slope from the Endoscopically-Normal Mucosa Predicts Concurrent Colonic Neoplasia: A Pilot Ex-Vivo Clinical Study

PurposeWe previously reported that analysis of histologically normal intestinal epithelium for spectral slope, a marker for aberrations in nanoscale tissue architecture, had outstanding accuracy in identifying field carcinogenesis in preclinical colorectal cancer models. In this study, we assessed the translatability of spectral slope analysis to human colorectal cancer screening.MethodsSubjects (n = 127) undergoing colonoscopy had spectral slope determined from two endoscopically normal midtransverse colonic biopsies using four-dimensional elastic light-scattering fingerprinting and correlated with clinical findings.ResultsFour-dimensional elastic light-scattering fingerprinting analysis showed the submicron particles size progressively shifted toward larger sizes in subjects harboring neoplasia. There was a corresponding decrease in spectral slope values from the endoscopically normal mucosa in subjects harboring adenomas (n = 41) and advanced adenomas (n = 10), compared to neoplasia-free subjects (P ≤ 0.00001). These factors did not appear to be confounded by either age or adenoma location. For detecting advanced adenomas, spectral slope had a negative and positive predictive value of 95 percent and 50 percent respectively.ConclusionsWe demonstrate, for the first time, that spectral slope in “normal” mucosa can accurately risk-stratify patients for colonic neoplasia. This proof of concept study serves to underscore the promise of four-dimensional elastic light-scattering fingerprinting analysis for colorectal cancer screening.

Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors

BACKGROUND This study compares the predictability of 5 tumor markers for distant metastasis and mortality in pancreatic neuroendocrine tumors (PNETs). METHODS A total of 128 patients who underwent pancreatectomy for nonfunctioning PNETs between 1998 and 2011 were evaluated. Tumor specimens were stained via immunochemistry for cytoplasmic and nuclear survivin, cytokeratin 19 (CK19), c-KIT, and Ki67. Univariate and multivariate regression analyses and receiver operating characteristics curve were used to evaluate the predictive value of these markers. RESULTS A total of 116 tumors (91%) were positive for cytoplasmic survivin, 95 (74%) for nuclear survivin, 85 (66.4%) for CK19, 3 for c-KIT, and 41 (32%) for Ki67 >3%. Twelve (9%) tumors expressed none of the markers. Survivin, CK19, and c-KIT had no substantial effect on distant metastasis or mortality. Age >55 years, grade 3 histology, distant metastasis, and Ki67 >3% were associated with mortality (P < .05). A cut-off of Ki67 >3% was the best predictor (83%) of mortality with an area under the curve of 0.85. Ki67 >3% also predicted occurrence of distant metastases with odds ratio of 9.22 and 95% confidence interval of 1.55-54.55 (P < .015). CONCLUSION Of the 5 markers studied, only Ki67 >3% was greatly associated with distant metastasis and death. Survivin, CK19, and c-KIT had no prognostic value in nonfunctioning PNETs.