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High price of endocrine surgery in octogenarians HeatherYeo, MD, Pritesh Mehta, Leon Boudourakis, TracyWang, MD, Sanziana Roman, MD, Julie Ann Sosa, MD, MA Yale University School of Medicine, New Haven, CT INTRODUCTION: There has been a 38% increase in the number of octogenarians in the last decade. Incidence of endocrine diseases also has risen dramatically. Increasingly, we are operating on older pa- tients. Small institutional series show parathyroidectomy and thy- roidectomy to be safe in octogenarians in high-volume centers; a population-based study has not been performed. METHODS: We performed a cross-sectional analysis using 2003-2004 discharge information from the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS). The database was searched by ICD-9 procedure codes for thyroidectomy, parathyroidectomy, adrenal- ectomy, and pancreatectomy for endocrine tumors. Independent vari- ables included patient age (18-44, 45-64, 65-79, 80years), gender, race, comorbidities, and procedure. Univariate analysis was performed with mean length-of-stay (LOS), hospital costs, in-hospital mortality, complications and discharge disposition. RESULTS: There were 32,507 discharges for endocrine proce- dures; 1,313 (4%) were in octogenarians. They were more often female (78%), and white (83%); 47% had at least moderate se- verity of illness, and 17% had non-elective admissions. Compared to younger patients, octogenarians had longer LOS (3.9days, p0.001), higher cost ($8319, p0.001), higher mortality (0.9%, p0.001) and less frequent routine discharge (79%, p0.001). Even for parathyroidectomy, complication rates for octogenarians were higher (9%vs.6% for 65-79years, 5% for 45- 64years, 5% for 18-44years, p0.001); 20% required home- health services or transfer to another facility. Table. Endocrine Procedures HCUP DATA 2003-2004 Age Groups (years) Patient Outcomes 18-44 45-64 65-79 80 p-value Length of stay (days) 2.1 2.3 2.8 3.9 p.001 Mean cost ($) 5924 6307 6991 8319 p.001 Mortality (%) 0.1 0.2 0.3 0.9 p.001 Non-routine disposition (%) 1.4 2.5 7.0 20.0 p.001 CONCLUSIONS: These data suggest that endocrine procedures in octogenarians are more expensive, with higher morbidity/mortality. Even for safe procedures (parathyroidectomy), there are significant outcomes differences. Additional studies are needed to assess long- term outcomes, quality-of-life, and cost-effectiveness of endocrine procedures in octogenarians. Endothelial nitric oxide synthase (eNOS) mediates aneurysm formation in aged mice Jose M Pimiento, MD, Stephen Maloney, MD, PaulTang, MD, Akihito Muto, MD, PhD, Tamara Fitzgerald, MD, PhD, Tiffany Fancher, MD, Stanley Dudrick, MD, FACS, GeorgeTellides, MD, PhD, Alan Dardik, MD, PhD, FACS Yale University School of Medicine, New Haven, CT INTRODUCTION: Regulation of eNOS expression has been associ- ated with inflammatory vascular diseases, but has not been defini- tively linked with a mechanistic role in the pathophysiology of aortic aneurysms. To determine whether eNOS plays a mechanistic role in aneurysm formation we examined the role of eNOS in human pa- tients and an age-appropriate mouse model. METHODS: Normal and aneurysmal human ascending thoracic aortic surgical specimens (n24) were analyzed for PECAM-1, VE-Cadherin and eNOS expression by qPCR (normalized to GAPDH) and immunohistochemistry. Inflammatory aneurysms were induced in young adult (3m) and aged (18m) C57Bl/6 and eNOS-knockout (eNOS-KO) mice by periadventitial CaCl2 ap- plication (0.5M) to the carotid artery. Vessel diameter was mea- sured in-vivo and compared with the contralateral untreated ca- rotid artery after 5 weeks. RESULTS: eNOS transcript expression and immunoreactive protein were significantly reduced in human thoracic aneurysms compared with controls (0.030.01 vs. 0.130.05 transcripts; p0.03), in spite of preserved endothelium. Aged wild-type mice had significantly larger aneurysm diameter when compared with young adult wild-type mice (47%5% vs. 31%4%;p0.005). Aged wild-type mice had reduced intimal eNOS immunoreactive protein compared with young adult wild-type mice. Aged eNOS-KO mice had similar size, not larger, aneurysms compared with young eNOS-KO mice (33%1% vs. 27%2%;p0.1) and young wild-type mice. CONCLUSIONS: eNOS expression is reduced in both aged human and aged mouse endothelium. eNOS is mechanistically linked to aneurysm progression in aged but not young adult mice, suggesting the relevance of age-associated changes in eNOS expression in the pathophysiology of aneurysmal disease. Hypoxia-inducible factor-1 alpha deficiency correlates with impaired dermal wound healing in older diabetic mice Lixin Liu, PhD, Xianjie Zhang, MD, PhD, Guy Marti, MD, Parsa Mohebi, MD, Sherwin Brown, Huafeng Zhang, PhD, Lindsey Savino, BS, Tomoharu Miyashita, MD, PhD, Gregg Semenza, MD, PhD, John Harmon, MD Johns Hopkins University, Baltimore, MD INTRODUCTION: We explored the possibility that age induced impairment in cutaneous wound healing in diabetic mice would correlate with reduced production of the transcription factor Hypoxia Inducible Factor-1 Alpha (HIF-1 Alpha) and its down- stream targets. Brem et al recently showed that the impairment does not correlate with increased levels of glycosylated hemoglo- bin in the same mouse model (H Brem et al, Exptl Gerontology 2007, in press). METHODS: Two 5 mm punch biopsy wounds were created on the dorsum of each mouse. Real time reverse transcriptase PCR assess- ment was carried out at intervals in wounds from young (6-8 week) and older (18-21 week) mice. cDNA was synthesized (iScript cDNA S41 Vol. 205, No. 3S, September 2007 Surgical Forum Abstracts

Hypoxia-inducible factor-1 alpha deficiency correlates with impaired dermal wound healing in older diabetic mice

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High price of endocrine surgery in octogenariansHeather Yeo, MD, Pritesh Mehta, Leon Boudourakis,Tracy Wang, MD, Sanziana Roman, MD, Julie Ann Sosa, MD, MAYale University School of Medicine, New Haven, CT

INTRODUCTION: There has been a 38% increase in the number ofoctogenarians in the last decade. Incidence of endocrine diseases alsohas risen dramatically. Increasingly, we are operating on older pa-tients. Small institutional series show parathyroidectomy and thy-roidectomy to be safe in octogenarians in high-volume centers; apopulation-based study has not been performed.

METHODS: We performed a cross-sectional analysis using 2003-2004discharge information from the Healthcare Cost and Utilization ProjectNational Inpatient Sample (HCUP-NIS).The database was searched byICD-9 procedure codes for thyroidectomy, parathyroidectomy, adrenal-ectomy, and pancreatectomy for endocrine tumors. Independent vari-ables included patient age (18-44, 45-64, 65-79, ��80years), gender,race, comorbidities, and procedure. Univariate analysis was performedwith mean length-of-stay (LOS), hospital costs, in-hospital mortality,complications and discharge disposition.

RESULTS: There were 32,507 discharges for endocrine proce-dures; 1,313 (4%) were in octogenarians. They were more oftenfemale (78%), and white (83%); 47% had at least moderate se-verity of illness, and 17% had non-elective admissions. Comparedto younger patients, octogenarians had longer LOS (3.9days,p�0.001), higher cost ($8319, p�0.001), higher mortality(0.9%, p�0.001) and less frequent routine discharge (79%,p�0.001). Even for parathyroidectomy, complication rates foroctogenarians were higher (9%vs.6% for 65-79years, 5% for 45-64years, 5% for 18-44years, p�0.001); 20% required home-health services or transfer to another facility.

Table. Endocrine Procedures HCUP DATA 2003-2004

Age Groups (years)

Patient Outcomes 18-44 45-64 65-79 80� p-value

Length of stay (days) 2.1 2.3 2.8 3.9 p�.001Mean cost ($) 5924 6307 6991 8319 p�.001Mortality (%) 0.1 0.2 0.3 0.9 p�.001Non-routine disposition (%) 1.4 2.5 7.0 20.0 p�.001

CONCLUSIONS: These data suggest that endocrine procedures inoctogenarians are more expensive, with higher morbidity/mortality.Even for safe procedures (parathyroidectomy), there are significantoutcomes differences. Additional studies are needed to assess long-term outcomes, quality-of-life, and cost-effectiveness of endocrineprocedures in octogenarians.

Endothelial nitric oxide synthase (eNOS) mediatesaneurysm formation in aged miceJose M Pimiento, MD, Stephen Maloney, MD, Paul Tang, MD,Akihito Muto, MD, PhD, Tamara Fitzgerald, MD, PhD,Tiffany Fancher, MD, Stanley Dudrick, MD, FACS,George Tellides, MD, PhD, Alan Dardik, MD, PhD, FACSYale University School of Medicine, New Haven, CT

INTRODUCTION: Regulation of eNOS expression has been associ-ated with inflammatory vascular diseases, but has not been defini-tively linked with a mechanistic role in the pathophysiology of aorticaneurysms. To determine whether eNOS plays a mechanistic role inaneurysm formation we examined the role of eNOS in human pa-tients and an age-appropriate mouse model.

METHODS: Normal and aneurysmal human ascending thoracicaortic surgical specimens (n�24) were analyzed for PECAM-1,VE-Cadherin and eNOS expression by qPCR (normalized toGAPDH) and immunohistochemistry. Inflammatory aneurysmswere induced in young adult (3m) and aged (18m) C57Bl/6 andeNOS-knockout (eNOS-KO) mice by periadventitial CaCl2 ap-plication (0.5M) to the carotid artery. Vessel diameter was mea-sured in-vivo and compared with the contralateral untreated ca-rotid artery after 5 weeks.

RESULTS: eNOS transcript expression and immunoreactiveprotein were significantly reduced in human thoracic aneurysmscompared with controls (0.03�0.01 vs. 0.13�0.05 transcripts;p�0.03), in spite of preserved endothelium. Aged wild-type micehad significantly larger aneurysm diameter when compared withyoung adult wild-type mice (47%�5% vs. 31%�4%;p�0.005).Aged wild-type mice had reduced intimal eNOS immunoreactiveprotein compared with young adult wild-type mice. AgedeNOS-KO mice had similar size, not larger, aneurysms comparedwith young eNOS-KO mice (33%�1% vs. 27%�2%;p�0.1)and young wild-type mice.

CONCLUSIONS: eNOS expression is reduced in both aged humanand aged mouse endothelium. eNOS is mechanistically linked toaneurysm progression in aged but not young adult mice, suggestingthe relevance of age-associated changes in eNOS expression in thepathophysiology of aneurysmal disease.

Hypoxia-inducible factor-1 alpha deficiencycorrelates with impaired dermal wound healing inolder diabetic miceLixin Liu, PhD, Xianjie Zhang, MD, PhD, Guy Marti, MD,Parsa Mohebi, MD, Sherwin Brown, Huafeng Zhang, PhD,Lindsey Savino, BS, Tomoharu Miyashita, MD, PhD,Gregg Semenza, MD, PhD, John Harmon, MDJohns Hopkins University, Baltimore, MD

INTRODUCTION: We explored the possibility that age inducedimpairment in cutaneous wound healing in diabetic mice wouldcorrelate with reduced production of the transcription factorHypoxia Inducible Factor-1 Alpha (HIF-1 Alpha) and its down-stream targets. Brem et al recently showed that the impairmentdoes not correlate with increased levels of glycosylated hemoglo-bin in the same mouse model (H Brem et al, Exptl Gerontology2007, in press).

METHODS: Two 5 mm punch biopsy wounds were created on thedorsum of each mouse. Real time reverse transcriptase PCR assess-ment was carried out at intervals in wounds from young (6-8 week)and older (18-21 week) mice. cDNA was synthesized (iScript cDNA

S41Vol. 205, No. 3S, September 2007 Surgical Forum Abstracts

Synthesis system BioRad), and Real-time PCR was performed (iCy-cler Real-time PCR Detection System, BioRad).

RESULTS: HIF-1 Alpha mRNA levels (fold increase over older an-imal baseline) after wounding were greater in younger as compared toolder diabetic animals; Unwounded 26�7 vs 1� 0, day 3 afterwound 41� 3 vs 15� 9, and day 5 after wound 168� 55 vs 13� 4(ANOVA andTukey p� .05).The mRNA levels for HIF-1-regulatedgene products, including vascular endothelial growth factor, Angio-poietin 1, Angiopoietin 2, platelet derived growth factor B and pla-cental growth factor, were also diminished in the older animals.However, the glucose levels were not significantly different in youngand older (84 week) animals at 290�33 (N�17) and 334�41(N�12), respectively.

Relative fold induction of HIF-1 Alpha mRNAlevels in wound tissue

Day 0 Day 3 Day 5

Young 26 � 7� 41 � 3� 168 � 55�

Old 1 � 0 15 � 9 13 � 4

�p � 0.05, ANOVA and post test, young vs. old.

CONCLUSIONS: Inadequate production of HIF-1 Alpha may ex-plain the impairment in wound healing in older diabetic mice.

Do the elderly benefit from identifying 12 lymphnodes for colon cancer?Karl Bilimoria, MD, Andrew Stewart, MA, David Bentrem, MD,Bryan Palis, MD, Mark Talamonti, MD, Clifford Ko, MDAmerican College of Surgeons and Northwestern UniversityMedical School, Chicago, IL

INTRODUCTION: Studies have demonstrated improved survivalwhen ��12 lymph nodes are examined for colon cancer. Oversightagencies have discussed implementing the 12 Node Measure as aquality indicator. The elderly comprise a significant proportion ofcolon cancer patients. Our objective was to assess differences in nodalevaluation by age and to determine whether examining ��12 nodesis associated with improved survival in the elderly

METHODS: From the National Cancer Data Base (1998-2004), weidentified N0M0 patients who underwent colectomy for adenocar-cinoma. Logistic regression was used to determine whether compli-ance with the 12 Node Measure differed with age. Cox ProportionalHazards modeling stratified by age was used to determine whethernodal evaluation affected survival.

RESULTS: 142,009 patients underwent colectomy for cancer:40.6% were �75 years old. Patients �75 years old had fewer nodesexamined than younger patients: median 11 vs. 13 nodes(P�.0001).. Patients �75 years old underwent evaluation of �� 12nodes less frequently than younger patients: 43.4% vs. 52.2%(P�.0001). When adjusted using multivariate analysis, patients �75years old were less likely to have �� 12 nodes examined (OR 0.48,95% CI 0.40’0.60). Regardless of age, patients who had �� 12nodes examined had better survival than those with �12 nodes ex-amined (P�.0001).

Table. Cox Proportional Hazards Model Assessing the Effect onSurvival of Having �12 Nodes Evaluated for Colon Cancer in Com-parison to �12 Nodes Examined

AgeOddsRatio

95% ConfidenceInterval Significance

� 55 years 0.62 (0.50 – 0.78) P�.000155-75 years 0.73 (0.67 – 0.79) P�.0001�75 years 0.80 (0.75 – 0.84) P�.0001

Adjusted for gender, race, socioeconomic status, primary payer, T stage,grade, lesion location, adjuvant chemotherapy administration, adjuvant radi-ation therapy administration, hospital volume, and facility type.�Having �12 nodes evaluated is the reference category.

CONCLUSIONS: This study demonstrates that older patientshave fewer nodes examined. Examination of ��12 nodes in theelderly is associated with better survival. Improving nodal evalu-ation will result in better colon cancer outcomes for the elderly.

Should we offer lung transplantation to patientsover 60 years of age? An analysis of the UNOSdatabaseEric Weiss, MD, Lois Nwakanma, MD, Ashish Shah, MDJohns Hopkins Univerisity School of Medicine, Baltimore, MD

INTRODUCTION: Elderly patients are increasingly referred for lungtransplantation evaluation. Prior outcome studies in this cohort arelimited by sample size. The United Network for Organ Sharing(UNOS) database provides an opportunity to examine survival in alarge cohort of elderly patients.

METHODS: We retrospectively reviewed UNOS data to identify7,285 non pediatric (�18) patients who underwent lung transplan-tation between 1989 and 2005. Patients were stratified by age (�60yrs). Our primary endpoint was all cause mortality during the studyperiod. Post transplant survival was compared using Cox propor-tional hazard regression.

RESULTS: Of patients who met inclusion criteria, 6% (n�445)were elderly (��60). The two most common indications for trans-plantation were chronic obstructive pulmonary disease (32% young,60% elderly, p�0.001) and idiopathic pulmonary fibrosis (IPF)(18% young, 28% elderly, P�0.001) Survival rates at 30 days, 1 yearand 5 years were, 94%, 81% and 53% for the young group, and 95%,77%, and 44% for the elderly group. Age greater than 60 was asso-ciated with lower survival during the entire 5 year study period(p�0.001) however, similar 30 day mortality was noted (P�0.22).The lowest 5 year survival was noted among elderly IPF patients(38%) Multivariate analysis showed elderly age to be an independentpredictor of mortality.

CONCLUSIONS: The UNOS database has provided the single larg-est series examining survival after lung transplantation in the elderly.Lung transplantation is safe in elderly patients, but should be usedwith caution in carefully selected candidates.

S42 Surgical Forum Abstracts J Am Coll Surg