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The aim of this study was to investigate bacterial translocation and its possible role in the development of post-resuscitation inflammatory response following Cardio-Pulmonary Resuscitation (CPR) after cardiac arrest.Munich female swine were employed for a model of cardiac arrest via application of electrical current. After 7 min, CPR was initiated, and animals were either successfully return to spontaneous circulation (ROSC) within 40 min or not (no-ROSC). At the end of experimental period and prior to sacrifice, samples from the intestine, mesenteric lymph nodes (MLN), liver and portal vein blood were obtained. Evaluation of inflammation and gut permeability was performed; MLN, liver and portal vein samples were analyzed for 16 s rRNA detection and cytokine mRNA expression.A decreased expression of the tight junction protein Occludin, with higher levels of inflammation, greater epithelial disintegration, ulceration, loss of crypts and villi height were found in the intestines of the ROSC swine in comparison to no-ROSC. The macrophage surface antigen CD-14 staining was relatively more intense in the ROSC than in no-ROSC. Higher levels of TNF-α mRNA expression were present in the liver of the ROSC group. Finally, despite the inflammatory response and the gut mucosal alterations in ROSC group, no bacterial translocation was detected in liver, MLN and portal vein.We show that resuscitation from cardiac arrest induces inflammatory response and intestinal permeability in swine 4h after resuscitation, but not a bacterial translocation. Bacterial translocation is not an early phase phenomenon but probably part of the pathophysiologic sequelae.

BACKGROUND: The objective of this study was to examine the influence of Surgical Society Oncology (SSO) membership and National Cancer Institute (NCI) status on the academic output of surgical faculty. METHODS: NCI cancer program status for each department of surgery was identified with publically available data, whereas SSO membership was determined for every faculty member. Academic output measures such as NIH funding, publications, and citations were analyzed in subsets by the type of cancer center (NCI comprehensive cancer center [CCC]; NCI cancer center [NCICC]; and non-NCI center) and SSO membership status. RESULTS: Of the surgical faculty, 2537 surgeons (61.9%) were from CCC, whereas 854 (20.8%) were from NCICC. At the CCC, 22.7% of surgeons had a history of or current NIH funding, compared with 15.8% at the NCICC and 11.8% at the non-NCI centers. The academic output of SSO members was higher at NCICC (52 ± 113 publications/1266 ± 3830 citations) and CCC (53 ± 92/1295 ± 4001) compared with nonmembers (NCICC: 26 ± 78/437 ± 2109; CCC: 37 ± 91/670 ± 3260), respectively, P < 0.05. Multivariate logistic regression revealed that SSO membership imparts an additional 22 publications and 270 citations, whereas NCI-designated CCC added 10 additional publications, but not citations. CONCLUSIONS: CCCs have significantly higher academic output and NIH funding. Recruitment of SSO members, a focus on higher performing divisions, and NIH funding are factors that non-NCI cancer centers may be able to focus on to improve academic productivity to aid in obtaining NCI designation.

Many surgical departments in the United States lack endocrine surgery faculty. Although endocrine surgeons can provide worthwhile clinical services, it is unclear how they contribute to the overall academic mission of the department. The present study aims to evaluate the academic productivity of endocrine surgeons, as defined by the American Association of Endocrine Surgeons (AAES) membership, when compared with other academic surgical faculty.An established database of 4081 surgical department faculty was used for this study. This database includes surgical faculty of the top 50 National Institutes of Health (NIH) funded universities and faculty from five outstanding hospital-based surgical departments. Academic metrics including publication, citations, H-index, and NIH funding were obtained using publically available data from websites. The AAES membership status was gathered from the online membership registry.A total of 110 AAES members were identified in this database, accounting for 2.7% of this population. Overall, the AAES members outperformed other academic surgical faculty with respect to publications (66 ± 94 versus 28 ± 91, P 0.001), publication citations (1430 ± 3432 versus 495 ± 2955, P 0.001), and H-index (19 ± 18 versus 10 ± 13, P 0.001). In addition, the AAES members were more likely to have former/current NIH funding and hold divisional or departmental leadership positions than their non-AAES member colleagues.Based on these data, the AAES members excelled with respect to publications, citations, and research funding compared with nonendocrine surgical faculty. These results demonstrate that endocrine surgeons can contribute enormously to the overall academic mission. Therefore, more surgical departments in the United States should consider establishing an endocrine surgery program.

To determine the effects of patient demographics, socioeconomic status (SES) and clinical variables on outcomes for patients with salivary and parotid gland tumors.Florida cancer registry and inpatient hospital data were queried for cancer of the salivary glands diagnosed between 1998-2002.A total of 1573 patients were identified. Women were diagnosed at a younger age (median age (years): women 60.8 versus men 64.3, P=0.003). Men were more often diagnosed with high grade tumors (65.1% versus 41.9% for women, P0.001) and advanced disease stage (stage III: 60.2 versus 49.4%, P0.001), but underwent surgical extirpation and received radiation at equal rates compared with women. Overall 5-year survival rates was superior in women (67.4% versus 55.6%, P=0.001). By multivariate analysis, adjusted for patient comorbidities, age over 65 (HR 3.43 P=0.008), advanced disease stage (HR 8.05 P0.001), and high tumor grade (HR 2.33, P0.001) were independent predictors of worse prognosis. Improved outcomes were observed for female gender (HR 0.68, P=0.011). Tumors located in the parotid gland (HR 0.631 P=0.003) and receiving both surgical extirpation and radiation were predictors of improved survival.Salivary gland tumors carry a worse prognosis than tumors of the parotid. Male patients have worse outcomes.

Lung cancer is the second most common neoplasm and the leading cause of cancer deaths in the United States. In cancer, weight loss and obesity are associated with reduced survival. However, the effect of obesity or weight loss at presentation on lung cancer survival has not been well studied.Using an extensive cancer dataset, we identified 76,086 patients diagnosed with lung cancer during the period of 1998-2002, of which 14,751 patients presented with obesity and/or weight loss. We examined the relationship between survival and weight loss or obesity at diagnosis using univariate and multivariate analysis.Median survival time (MST) for all lung cancer patients was 8.7 mo. Patients presenting with weight loss (15.8%) had shorter MST versus those who did not (6.4 versus 9.2 mo, P0.001) and patients with weight loss had significantly shortened MST for all stages and histologic subtypes. In contrast, obese patients at presentation (5.4%) had longer MST relative to non-obese patients (13.0 versus 8.6 mo, P0.001), which was significant across all stages and histologic subtypes. Multivariate analysis revealed that the absence of weight loss was an independent, positive predictor of improved survival (HR = 0.087, P0.001), while the absence of obesity was an independent predictor of worsened survival in lung cancer (HR = 1.16, P0.001).Our results demonstrate an inverse relationship between survival and weight loss at presentation and a potentially protective effect of obesity in lung cancer survival, which could be due to greater physiologic reserves, thereby prolonging life by slowing the progress of cancer cachexia.

To determine the outcomes and predictors of survival for pediatric non-Wilms renal tumors (NWRT).The SEER database (1973-2005) was queried for all patients20 y of age.Overall, 349 cases of NWRT were identified. The major histologic groups included renal cell carcinoma (RCC) (44%), clear cell sarcoma of the kidney (CCSK) (17%), and malignant rhabdoid tumor (MRT) (12%). A bimodal age distribution was observed, with tumors commonly presenting in patients ≤4 y of age and ≥15 y of age. More than 50% of RCC presented at ≥15 y of age, whereas ≥80% of CCSK or MRT patients were ≤4 y of age. Most RCC (57%) and CCSK (53%) were locally staged while most MRT presented with distant disease (51%, P0.001). Overall 10-y survival was 63% with improved survival observed in patients with CCSK (79%) and RCC (70%) versus MRT (29%, P 0.001). By univariate analysis, surgical resection was associated with improved overall 10-y survival (68% versus 30%, P0.001), while no benefit was observed for radiotherapy (60% versus 63%, P = 0.8). By multivariate analysis, worse overall survival was observed for patients ≥ 10 y old (HR 4.01, P = 0.013) and those with advanced disease (HR = 12.78, P0.001). Patients with MRT (HR = 11.61, P0.001) and CCSK (HR = 3.68, P = 0.038) had significantly worse prognosis compared with those with RCC. Surgical resection improved overall survival (HR = 0.36, P = 0.001).For pediatric NWRT, younger patients and those with RCC have improved survival, while a diagnosis of MRT portends a worse prognosis. Surgical extirpation significantly improves survival for all patients.

Objective To study the outcomes of solid tumors of the colon and rectum in pediatric patients. Methods The Surveillance, Epidemiology, and End Results (SEER) database (1973–2005) was queried for patients less than 20 y of age. Results Overall, 270 patients with malignant tumors of the lower gastrointestinal tract were identified. The annual incidence was 1.04 cases per million in 2005. Overall, equal distribution between boys (50.7%) and girls (49.3%) was observed. The majority of tumors arose in adolescents (68.1% were older than 15 y). Tumors were more commonly seen in white (77.8%) and non-Hispanic (78.9%) patients. Tumors were identified in the right colon (45.9%), transverse colon (9.3%), left colon (20.4%), rectum (15.2%), and anal canal (1.1%). The most common histology of these tumors was adenocarcinoma (35.6%), followed by carcinoid (34.1%). Disease specific 5- and 10-y-survival for the entire cohort was 61.0% and 57.9%, respectively. Multivariate analysis of the cohort identified tumor stage (HR 8.39, P < 0.001 for distant disease), tumor type (signet ring HR 2.12, P = 0.025, and carcinoid HR = 0.14, P = 0.001), and surgical resection (no surgery HR 2.98, P = 0.010) as independent predictors of worse outcome. Conclusion In the pediatric population, solid tumors of the colon and rectum occur more frequently in the right side of the colon in teenagers. Surgical resection significantly improves survival for most pediatric tumors of the lower gastrointestinal tract.

We sought to define current incidence trends and outcomes for children with lung and bronchus tumors.The SEER registry was queried from 1973 to 2004 for all patients with pulmonary tumors less than 20 y of age.Overall, 160 patients were identified. The age-adjusted incidence has remained stable at 0.049 per 100,000 persons. The median age at diagnosis was 16 y. Whites had the highest age-adjusted population incidence at 0.056 per 100,000. Most tumors arose in the lower lobe (37%), followed by the upper lobe (31.2%). The most common histology was endocrine tumor (51.6%), followed by sarcoma (11%), and mucoepidermoid tumor (9%). Overall survival was greater than 381 mo with a 15-y survival of 65%. Males had better survival (381 versus 288 months). Endocrine and mucoepidermoid tumors had the best survival. Small cell carcinoma had the worst median survival at less than 5 mo. Squamous cell carcinoma and adenocarcinoma both had a 14-mo median survival. Median survival for nonsurgically treated patients was 14 mo with a 10-y survival rate of 32%. Surgery improved the 10-y survival to 75% (P0.0001). Multivariate analysis demonstrated nonsurgical treatment and nonendocrine tumor histology to be independent prognostic factors of death.The incidence of pediatric lung cancer remains stable. Several factors, including nonsurgical treatment and nonendocrine tumors confer a poor prognosis. Early diagnosis and surgical therapy provide the best chance for survival.

BACKGROUND: Determine the role of surgery and radiation therapy for patients with malignant CNS ependymomas. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1973–2005) was queried. RESULTS: Overall, a total of 2408 cases of malignant ependymomas were identified. Of these, 2132 cases (88.5%) were identified as WHO grade II ependymomas and 276 cases (11.5%) as WHO grade III (anaplastic) ependymomas. The annual incidence of ependymomas was approximately 1.97 cases per million in 2005. Overall median survival for all patients was 230 mo, with a significant difference between women and men (262 mo versus l96 mo, respectively) (P = 0.004). Median age at diagnosis was 37 y among females and 34 y in males. Patients who successfully underwent surgical resection had a considerably longer median survival (237 mo versus 215 mo, P < 0.001) as well as a significantly improved five-year survival (72.4% versus 52.6%, P < 0.001). Univariate analysis demonstrated that age, gender, ethnicity, primary tumor site, WHO grade and surgical resection were significant predictors of improved survival for ependymoma patients. Multivariate analysis identified that a WHO grade III tumor, male gender, patient age, intracranial tumor locations and failure to undergo surgical resection were independent predictors of poorer outcomes. Multivariate analysis of partially resection cases revealed that lack of radiation was a sign of poor prognosis (HR 1.748, P = 0.024). CONCLUSION: Surgical extirpation of ependymomas is associated with significantly improved patient survival. For partially resected tumors, radiation therapy provides significant survival benefit.

Background The outcomes of pediatric intestinal foregut and small bowel solid tumors have never been studied on a population scale. Materials and Methods The Surveillance, Epidemiology, and End Results database (1973–2005) was queried for all patients under 20 y of age. Results A total of 105 cases of pediatric intestinal foregut and small bowel solid tumors were identified. Tumors occurred in the esophagus (8.6%), stomach (61%), and small bowel (30.5%). The most common histologies include sarcoma (43.8%), which consisted mostly of gastrointestinal stromal tumors (GIST), carcinoma (41.0%), which consisted mostly of adenocarcinomas, and neuroendocrine tumors (NET) (10.5%). Most tumors were poorly differentiated and presented with advanced disease. The overall median survival time was 207 mo. Gastric solid tumors had significantly worse 5- and 10-y survival compared with their small bowel counterparts, though this difference disappeared in those who received surgical resection. Patients with carcinoma had significantly worse survival compared with those with sarcoma or NET, regardless of site and surgical intervention. Univariate analysis identified race, differentiation, stage, and surgery as significant predictors of survival. Multivariate analysis revealed that African American race, advanced stage of disease, carcinoma histology, and failure to undergo surgical extirpation were all independent predictors of worse outcome. In patients with carcinoma, failure to undergo radiotherapy was also a predictor of worse outcome. Conclusion Surgery is associated with a significantly improved survival for pediatric patients with solid tumors of the intestinal foregut and small bowel. Radiotherapy appears to be an important adjuvant therapy for patients with carcinoma.

Objective To examine outcomes and predictors of survival for pediatric patients with thyroid carcinoma. Methods The Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2004 was queried for all patients with thyroid carcinoma less than 20 y of age. Results A total of 1753 patients with malignant thyroid neoplasms were identified with an age-adjusted annual incidence of 0.54 cases per 100,000 persons. There has been a significant increase in the annual incidence by 1.1% per y. Female patients outnumbered males 4 to 1. Tumors were classified as papillary ( n = 1044, 60%), follicular variant of papillary ( n = 389, 23%), follicular ( n = 165, 10%), and medullary ( n = 87, 5%). The majority of patients presented with localized and regional disease. Overall mean survival time (MST) was 30.5 y. The MST for females was 40 y, whereas males survived an average of 20.4 y ( P = 0.0001). Patients with medullary cancer had significantly shorter mean survival than those with papillary cancer ( P = 0.006). Surgical treatment significantly improved outcome. Multivariate analysis demonstrated that male gender, nonpapillary histology, distant disease, and no surgery were all independent prognostic factors of worse outcome. For patients with medullary thyroid carcinoma, radiation therapy was also identified as an independent predictor of lower survival. Conclusion The incidence of pediatric thyroid cancer is increasing. Females have a higher incidence than males, but enjoy longer survival. Papillary thyroid cancer has overall excellent survival. Male gender, nonpapillary tumor, distant metastases, and nonsurgical treatment all predict worse outcome.

Background Accurate determination of body surface area (BSA) in experimental animals is essential for modeling effects of burn injury or drug metabolism. Two-dimensional surface area is related to three-dimensional body volume, which in turn can be estimated from body mass. The Meeh equation relates body surface area to the two-thirds power of body mass, through a constant, k , which must be determined empirically by species and size. We found older values of k overestimated BSA in certain mice; thus we determined empirically k for various strains of normal, obese, and hypermuscular mice. Materials and methods BSA was computed from digitally scanned pelts and nonlinear regression analysis was used to determine the best-fit k . Results The empirically determined k for C57BL/6J mice of 9.82 was not significantly different from other inbred and outbred mouse strains of normal body composition. However, mean k of the nearly spheroid, obese lepr db/db mice ( k = 8.29) was significantly lower than for normals, as were values for dumbbell-shaped, hypermuscular mice with either targeted deletion of the myostatin gene ( Mstn ) ( k = 8.48) or with skeletal muscle specific expression of a dominant negative myostatin receptor ( Acvr2b ) ( k = 8.80). Conclusions Hypermuscular and obese mice differ substantially from normals in shape and density, resulting in considerably altered k values. This suggests Meeh constants should be determined empirically for animals of altered body composition. Use of these new, improved Meeh constants will allow greater accuracy in experimental models of burn injury and pharmacokinetics.

Objective To evaluate the scientific impact of women in the surgical literature. Methods Gender of the principal investigator of every abstract presented at the 2002, 2003, and 2004 annual meetings of the Association for Academic Surgery and Society of University Surgeons was identified by internet search. Resulting publications were identified using PubMed. Journal impact factor and number of article citations were determined using ISI Web of Knowledge. Results The principal investigator's gender was identified for 649 (98.8%) of the 657 abstracts presented at the 2002–2004 AAS meetings. Women authored 9.1% of abstracts and 11.8% of total resulting publications. The publication rate of abstracts by women was significantly higher than that of men (69.5% versus 52.4%, P = 0.0132). There was a trend toward higher average impact factors of journals in which female authors published (3.265 versus 2.673, P = 0.0626). There was no significant difference in mean number of citations per publication. The principal investigator's gender was identified for all 337 (100%) abstracts presented at the 2002–2004 SUS meetings. Women authored 11.0% of abstracts and 11.2% of resulting publications. Publication rates and average citation numbers were similar for female and male authors. The average impact factors of journals in which women published were significantly higher (4.741 versus 3.348, P = 0.0082). Conclusions Although women comprise a small proportion of principal investigators on abstracts presented at these conferences, the quality of their presented work is equal to or better than those of their male counterparts.

Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse cell functions including proliferation and differentiation. Within the liver IL-6 signaling plays a central role during normal hepatic growth and regeneration yet can inhibit the proliferation of hepatocellular carcinoma (HCC) cells. The aim of the current study was to identify underlying mechanisms whereby IL-6 induces cell-cycle arrest in HCC cells. These studies demonstrate that IL-6 inhibits cell-cycle progression at the G(0)/G(1) interface through inhibition of cyclin-dependent kinase (cdk) 2 and cdk4 activity in the absence of changes in total cyclin (A, D1, D3, and E) or cdk (cdk2, 4, and cdc2 p34) expression. Inhibition of signal transduction pathways associated with IL-6 receptor activation demonstrates that IL-6-dependent inhibition of G(0)-G(1) progression occurs via Janus tyrosine kinase-signal transducers and activators of transcription-3 (Jak-STAT3)-dependent induction of p21(waf1/cip1) and is independent of ERK-MAPK signaling. These data demonstrate that, while IL-6 plays a central role in hepatocyte priming and proliferation in vivo, the pronounced inhibition of proliferation observed in HCC cells occurs due to IL-6-STAT3-dependent regulation of cdk2/cdk4 activity and p21(waf1/cip1) expression.

Objective To determine incidence trends and outcomes for pediatric patients with malignant breast disease. Methods The Surveillance, Epidemiology, and End Results registry was examined for all females 19 years of age and younger diagnosed with a malignant breast tumor between 1973 and 2004. Results A total of 75 patients with malignant breast tumors were identified. Overall, 14.5% of patients had in situ tumors, and 85.5% had invasive disease. Tumors were classified as being either carcinomas (n = 41, 54.7%) or sarcomas (n = 34, 45.3%). The majority of sarcomatous lesions were phyllodes tumors (n = 29, 85.5%), whereas most carcinomas were of a ductal etiology (n = 19, 46.3%). The age-adjusted incidence of all malignant pediatric breast tumors in 2003 was 0.08 cases per 100,000 people (0.03 carcinoma and 0.06 sarcoma cases per 100,000 people). In the carcinoma group, regionally advanced disease was present in 11 patients (26.8%), whereas only 3 patients (7.3%) presented with metastatic disease. All patients with sarcomatous tumors presented with localized disease. Adjuvant radiation therapy was administered in only 9.8% of carcinomas and 8.8% of sarcomas, and 85.4% of carcinoma patients and 97.1% of sarcoma patients underwent surgical resection for their primary disease. Subgroup analysis revealed 5- and 10-year survival rates of 89.6% for patients with sarcomatous tumors and 63.1% and 54.3% for carcinomas. Conclusions Malignant pediatric breast malignancies remain relatively rare. The two most common histologies of breast neoplasms in children are malignant carcinomas followed by sarcomas. Although uncommon, malignant disease must be considered in the differential diagnosis of the pediatric patient with a breast mass.

Expression of macrophage inhibitory cytokine-1 (MIC-1), a divergent transforming growth factor-beta family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15), is induced in hepatocytes by surgical and chemical injury and heat shock. Here, we demonstrate that the regulation of GDF-15/MIC-1 expression may be evolutionarily conserved because MIC-1 was induced in diseased human livers. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although tumor necrosis factor (TNF) induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtypes. Furthermore, although the stress sensor p53 is known to induce GDF-15/MIC-1 expression, injury-elicited Gdf15 expression was unchanged in p53 null mice. Our results demonstrate that GDF-15 induction is an immediate early response to liver injury that can occur through TNF and p53 independent pathways.

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent TGF-β family member overexpressed in numerous malignancies. Expression of MIC-1 correlates with disease stage in pancreatic and colon cancer and has been proposed as a potential diagnostic and prognostic biomarker. We have previously shown that the murine ortholog of MIC-1, Growth/Differentiation Factor-15 (GDF-15), is highly expressed in response to various acute liver injuries including those associated with subsequent carcinogenesis. Here we show that MIC-1 is overexpressed in chronic human liver disease, and furthermore, that GDF-15 is expressed in liver, kidney, and lung in various models of acute organ injury, including toxic/genotoxic, ischemic, surgical, and hyperoxic. We also show that Gdf15 is an immediate-early gene. GDF-15 expression after injury may be induced by the inflammatory response, since administration of TNF and, to a lesser extent IL-6, induced expression of Gdf15. Injury-induced Gdf15 expression was not reduced in mice deficient for both TNF receptor subtypes, however, suggesting that cytokine signaling is not required for GDF-15 expression. As well, although the stress sensor p53 is widely recognized to induce MIC-1 expression, injury-induced Gdf15 expression was unchanged in p53 null mice. Our results demonstrate that GDF-15 expression following injury is regulated by both paracrine (cytokine) and autocrine (p53) mechanisms, and in more tissues than previously recognized. Taken together with its described activities, these data suggest that MIC-1/GDF-15 production may regulate inflammation, cell proliferation, apoptosis, and perhaps migration in injured tissues, and moreover, may influence carcinogenesis and cancer progression in settings of genotoxic injury.

Objective. To determine which etiologies of lower gastrointestinal bleeding (LGIB) may best be treated with super-selective embolization. Methods. A meta-analysis was undertaken of all 25 identified publications reporting the use of embolization and 12 consecutive cases of LGIB from the authors’ institution. Seven series met selection criteria for further analysis. Results. Multiple regression analysis demonstrated no significant difference in pooled outcomes when varying the included study, age, or embolization method on the outcome of rebleeding. The pooled odds ratio for rebleeding up to 30 days postlocalization and embolization for arteriovenous malformations (AVM) and other diseases was 3.53 compared to re-bleeding after localization and embolization for diverticular disease [95% Confidence Interval OR (1.33, 9.41), P < 0.01]. Embolization for diverticular bleeding demonstrated was successful in 85% of cases. Moreover, the vast majority of cases that rebled did so within 48 h. In contrast, rebleeding after embolization for nondiverticular bleeding occurred in greater than 40% of cases and over a more protracted period. Conclusion. Embolization for LGIB is most effective for the treatment of diverticular bleeding. Given the low observed complication rate, minimal post-procedure recovery time, and low failure rate, super-selective embolization may be considered first-line therapy for severe diverticular LGIB regardless of age. Caution should be used when applying embolization therapy for non-diverticular causes due to the considerably higher associated failure rate. Figure options Download full-size image Download as PowerPoint slide