QS113. Differentiating Benign Versus Malignant Nodules in Patients With Cirrhosis
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QS113. DIFFERENTIATING BENIGN VERSUS MALIGNANT NODULES IN PATIENTS WITH CIRRHOSIS. Amanda Cooper 1 , Nagana Gowda 2 , Yuliana Suryani 2 , Carl Murphy 2 , Dan Raftery 2 , Mary Maluccio 1 ; 1 Indiana University, India- napolis, IN; 2 Purdue University, West Lafayette, IN Introduction: Contemporary methods for diagnosing patients with hepatocellular carcinoma are suboptimal, particularly in patients with underlying cirrhosis. Although cross sectional imaging has im- proved, detecting cancer within a cirrhotic liver remains a challenge. Non-invasive biomarkers of cancer risk would help identify patients early for curative treatment. Recent interest in NMR-based meta- bolic profiling of intact tumors stems from the fact that biomarkers resulting from pathophysiological stress are anticipated to be highly concentrated in the tissue. Moreover, the latest technological ad- vancements have reduced the required amont of tissue to as little as a few milligrams, so that even the biopsy speciments are sufficient to obtain NMR spectra with good sensitivity. In the present study, we used 1 H and 31 P NMR spectroscopy to evaluate metabolomic differ- ences between cirrhotic liver and hepatocellular circinoma (HCC) to determine unique metabolites that accurately distinguish benign and malignant disease. Methods: Tissue was collected prospectively from cirrhotic patients undergoing surgical resection or transplan- tation for HCC. Proton and phosphorus NMR on 37 paired samples from liver tumors and tumor adjacent tissue were performed. The tissue spectra were obtained by magic angle spinning at 3 kHz to remove line-broadening caused by dipolar coupling or chemical shift anisotrophy. Both 1 H and 31 P NMR data were analyzed using mul- tivariate statistical analysis. Results: 1 H NMR spectra of the tissue specimens were dominated by triglycerides, phospholipids and car- bohydrates in addition to several other small molecular weight me- tabolites. Significantly altered metabolites were observed in the tu- mor samples. Specifically, choline-containing metabolites and carbohydrates were high in tumors relative to adjacent tissue and triglycerides were high in adjacent liver tissue relative to tumor tissue (figure). The altered metabolic profiles in cancerous tissue were also evident from the 31 P NMR spectra. Statistical analysis of 31 P NMR spectra distinctly separated tumor from adjacent liver tissue and the differences in phospholipids contributed to the statis- tical separation of tumors from non-cancerous tissues. Conclusions: Distinct metabolite differences between cancer and adjacent liver tissue are measurable using NMR spectroscopy. Alter- ations in choline metabolites within a high risk liver may help delineate benign from malignant areas, which might eventually im- prove diagnostic accuracy for suspicious lesions within a cirrhotic liver. In light of recent evidence that phosphocholine-containing metabolites have potential as cancer biomarkers in several other solid tumors, our findings from the 1 H and 31 P NMR study of intact tissue extend these findings to patients at risk for hepatocellular carcinoma. QS113-A. EXTENT OF LYMPH NODE DISSECTION IM- PACTS DISEASE SPECIFIC SURVIVAL IN MELA- NOMA PATIENTS. Yan Xing, Brian Badgwell, Janice N. Cormier; M. D. Anderson Cancer Center, Houston, TX Background: Extent of lymph node (LN) dissection has been de- fined as a potential indicator of surgical quality for patients with various solid tumors. The objective of the current analysis was to determine: (1) the most relevant measure of extent of LN dissection, (2) identify the threshold value of the most relevant measure, and (3) examine its impact on disease specific survival (DSS) in melanoma patients undergoing therapeutic LN dissection. Methods: Patients with pathologically confirmed, node positive, cutaneous melanoma who underwent completion LN dissection were identified from the SEER database (1988-2004). Those with primary tumors of the head/ neck, upper extremity, and lower extremity were selected to examine the specific outcomes associated with LN dissection of the neck, axilla, and groin, respectively. Cox multivariate analyses were per- formed to determine the significance of various indicators including total number of LN removed, number of negative LN removed, and LN ratio (number of positive LN / total number of LN removed) on DSS. Multivariate cut-point analyses were then conducted for each anatomic region to define threshold values. Kaplan Meier Methods were used to estimate 5-year DSS. Comparisons among groups (above threshold value versus below threshold value) were per- formed using log rank tests. Results: The LN ratio was determined to be significantly associated with DSS for all anatomic regions. Variables related to the LN dissection Neck (n 465) Axilla (n 530) Groin (n 700) Median no. of positive LN removed (IQR) 1 (1–3) 1 (1–2) 2 (1–2) Median no. of negative LN removed (IQR) 19 (7–33) 15 (9–22) 9 (5–13) Total no. of LN removed (IQR) 22 (9–38) 17 (11–24) 11 (7–16) Median LN ratio (positive/ total) 0.09 0.08 0.17 Minimum no. of LN removed per positive node 9 8 5 Optimal no. of LN removed per positive node 15 10 8 IQR: interquartile range 313 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
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Transcript of QS113. Differentiating Benign Versus Malignant Nodules in Patients With Cirrhosis
QS113. DIFFERENTIATING BENIGN VERSUS MALIGNANTNODULES IN PATIENTS WITH CIRRHOSIS. AmandaCooper1, Nagana Gowda2, Yuliana Suryani2, Carl Murphy2,Dan Raftery2, Mary Maluccio1; 1Indiana University, India-napolis, IN; 2Purdue University, West Lafayette, IN
Introduction: Contemporary methods for diagnosing patients withhepatocellular carcinoma are suboptimal, particularly in patientswith underlying cirrhosis. Although cross sectional imaging has im-proved, detecting cancer within a cirrhotic liver remains a challenge.Non-invasive biomarkers of cancer risk would help identify patientsearly for curative treatment. Recent interest in NMR-based meta-bolic profiling of intact tumors stems from the fact that biomarkersresulting from pathophysiological stress are anticipated to be highlyconcentrated in the tissue. Moreover, the latest technological ad-vancements have reduced the required amont of tissue to as little asa few milligrams, so that even the biopsy speciments are sufficient toobtain NMR spectra with good sensitivity. In the present study, weused 1H and 31P NMR spectroscopy to evaluate metabolomic differ-ences between cirrhotic liver and hepatocellular circinoma (HCC) todetermine unique metabolites that accurately distinguish benignand malignant disease. Methods: Tissue was collected prospectivelyfrom cirrhotic patients undergoing surgical resection or transplan-tation for HCC. Proton and phosphorus NMR on 37 paired samplesfrom liver tumors and tumor adjacent tissue were performed. Thetissue spectra were obtained by magic angle spinning at 3 kHz toremove line-broadening caused by dipolar coupling or chemical shiftanisotrophy. Both 1H and 31P NMR data were analyzed using mul-tivariate statistical analysis. Results: 1H NMR spectra of the tissuespecimens were dominated by triglycerides, phospholipids and car-bohydrates in addition to several other small molecular weight me-tabolites. Significantly altered metabolites were observed in the tu-mor samples. Specifically, choline-containing metabolites andcarbohydrates were high in tumors relative to adjacent tissue andtriglycerides were high in adjacent liver tissue relative to tumortissue (figure). The altered metabolic profiles in cancerous tissuewere also evident from the 31P NMR spectra. Statistical analysis of31P NMR spectra distinctly separated tumor from adjacent livertissue and the differences in phospholipids contributed to the statis-tical separation of tumors from non-cancerous tissues.
Conclusions: Distinct metabolite differences between cancer andadjacent liver tissue are measurable using NMR spectroscopy. Alter-ations in choline metabolites within a high risk liver may helpdelineate benign from malignant areas, which might eventually im-prove diagnostic accuracy for suspicious lesions within a cirrhoticliver. In light of recent evidence that phosphocholine-containing
metabolites have potential as cancer biomarkers in several othersolid tumors, our findings from the 1H and 31P NMR study of intacttissue extend these findings to patients at risk for hepatocellularcarcinoma.
QS113-A. EXTENT OF LYMPH NODE DISSECTION IM-PACTS DISEASE SPECIFIC SURVIVAL IN MELA-NOMA PATIENTS. Yan Xing, Brian Badgwell, JaniceN. Cormier; M. D. Anderson Cancer Center, Houston, TX
Background: Extent of lymph node (LN) dissection has been de-fined as a potential indicator of surgical quality for patients withvarious solid tumors. The objective of the current analysis was todetermine: (1) the most relevant measure of extent of LN dissection,(2) identify the threshold value of the most relevant measure, and (3)examine its impact on disease specific survival (DSS) in melanomapatients undergoing therapeutic LN dissection. Methods: Patientswith pathologically confirmed, node positive, cutaneous melanomawho underwent completion LN dissection were identified from theSEER database (1988-2004). Those with primary tumors of the head/neck, upper extremity, and lower extremity were selected to examinethe specific outcomes associated with LN dissection of the neck,axilla, and groin, respectively. Cox multivariate analyses were per-formed to determine the significance of various indicators includingtotal number of LN removed, number of negative LN removed, andLN ratio (number of positive LN / total number of LN removed) onDSS. Multivariate cut-point analyses were then conducted for eachanatomic region to define threshold values. Kaplan Meier Methodswere used to estimate 5-year DSS. Comparisons among groups(above threshold value versus below threshold value) were per-formed using log rank tests. Results: The LN ratio was determinedto be significantly associated with DSS for all anatomic regions.
Variablesrelated to theLN dissection
Neck(n � 465)
Axilla(n � 530)
Groin(n � 700)
Median no. ofpositive LNremoved(IQR)
1 (1–3) 1 (1–2) 2 (1–2)
Median no. ofnegativeLNremoved(IQR)
19 (7–33) 15 (9–22) 9 (5–13)
Total no. ofLNremoved(IQR)
22 (9–38) 17 (11–24) 11 (7–16)
Median LNratio(positive/total)
0.09 0.08 0.17
Minimum no.of LNremovedper positivenode
9 8 5
Optimal no.of LNremovedper positivenode
15 10 8
IQR: interquartile range
313ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
