Role of FDG-PET in the evaluation and staging of hepatocellular carcinoma with comparison of tumor size, AFP level, and histologic grade.

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has proven to be a valuable tool in the initial diagnosis, staging, and restaging of a variety of cancers. The potential use of FDG-PET in the evaluation and management of hepatocellular carcinoma (HCC) continues to evolve. The purpose of this study was to investigate the effectiveness of FDG-PET for the detection and staging of HCC. In addition, we also assessed the correlation between FDG-PET positivity, tumor size, a-fetal protein level (AFP), and histologic grade. All patients on the hepatobiliary and liver transplant service with biopsy proven HCC that underwent FDG-PET between January 2000 and December 2004 were selected for a retrospective review. Results of the FDG-PET scan were compared with other imaging studies [computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography], intraoperative findings, tumor size, AFP levels, and histologic grade. Of the 20 patients who underwent 18F-FDG PET, increased FDG uptake was noted in 14 scans (70%). These 20 patients fell into 2 groups: 1 for detecting HCC (Group A) and 1 for staging HCC (Group B). There were 7 patients in Group A; only 2 scans (28.6%) showed increased uptake. There were 13 patients in Group B; 12 scans (92.3%) showed increased uptake. In Group B, 11 of the 13 scans (84.6%) provided an accurate representation of the disease process. Two scans failed to accurately portray the disease; one scan failed to show any increase in uptake, and the other scan failed to detect positive nodes that were found during surgery. FDG-PET detected only 2 of 8 tumors (25%) < or = 5 cm in size. All 12 PET scans (100%) in tumors > or = 5 cm and/or multiple in number were detected by FDG-PET. FDG-PET scans with AFP levels < 100 ng/ml were positive in 5 of 9 patients (55.6%). In patients with levels > 100 ng/ml, 6 of 7 patients (85.7%) had positive scans. Histologically, there were 6 well-differentiated, 6 moderately differentiated, and 2 poorly differentiated HCCs. FDG-PET detected 4 of 6 for both well- and moderately differentiated HCCs. Both poorly differentiated HCCs were detected. The intensity was evenly distributed between the different histologic grades. There was a strong correlation of FDG uptake with tumor size. There were 5 HCCs with primary tumors >10 cm in size; 4 showed intense uptake on the scan. In contrast, of the 8 tumors < or = 5 cm in size, 6 were negative for uptake. The sensitivity of FDG-PET in detecting HCC < or = 5 cm in size is low and therefore may not be helpful in detecting all of these tumors. For larger tumors, there is a strong correlation of sensitivity and uptake intensity with tumor size and elevated AFP levels. FDG-PET sensitivity and uptake intensity did not correlate with histologic grade. In the setting of extrahepatic disease, FDG-PET seems to be an effective accurate method for HCC staging; however, whether PET offers any benefit over traditional imaging has yet to be determined.

Comparison of surgical outcomes between teaching and nonteaching hospitals in the Department of Veterans Affairs.

OBJECTIVE: To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings. SUMMARY BACKGROUND DATA: The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows. METHODS: The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated. Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity. RESULTS: Teaching hospitals performed 81% of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals. CONCLUSION: Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.

The diagnostic accuracy of mammography in the evaluation of male breast disease.

BACKGROUND: The role of mammography in the evaluation of male patients presenting with breast disease is controversial. This controversy is a function of the lack of specific data concerning the diagnostic accuracy of mammography when used in this clinical setting. The purpose of this study was to define the diagnostic accuracy of mammography in the evaluation of male breast disease. METHODS: One hundred and four prebiopsy mammograms from 100 patients with tissue diagnoses were read blindly by two independent radiologists, and placed into one of five predetermined categories: definitely malignant, possibly malignant, gynecomastia, benign mass, and normal. Radiologic/pathologic correlation was performed and the sensitivity (Sn), specificity (Sp), positive (Ppv) and negative predictive value (Npv), and accuracy (Ac) for each of the mammographic diagnostic category determined. RESULTS: The pathologic diagnoses were 12 cancers, including 1 patient with bilateral breast cancer, 70 cases of gynecomastia, 16 benign masses, and 6 normals. The accuracy data for the mammographic diagnostic categories are as follows: malignant (combined definitely and possibly malignant), Sn 92%, Sp 90%, Ppv 55%, Npv 99%, Ac 90%; and overall benignity (combined gynecomastia, benign mass, and normal), Sn 90%, Sp 92%, Ppv 99%, Npv 55%, Ac 90%. Six cancers (50%) coexisted with gynecomastia. CONCLUSIONS: Mammography can accurately distinguish between malignant and benign male breast disease. Although not a replacement for clinical examination, its routine use could substantially reduce the need for biopsy in patients whose mammograms and clinical examination suggest benign disease.

FAK induction in keratinocytes in an in vitro model of reepithelialization.

During reepithelialization, keratinocytes must become activated in order to migrate over the provisional extracellular matrix of the wound. Previously we have shown that focal adhesion kinase (FAK) is induced in activated keratinocytes. The mechanisms responsible for keratinocyte activation are unknown. Here we use an organ culture system to investigate FAK up-regulation and regulation of keratinocyte activation. Normal human skin was cultured on type I collagen. Keratinocytes migrated out of the explant onto the supporting collagen. Immunostaining for FAK showed induction in the migrating epithelium and also in the center of the explant some distance from the cut edge. Cells from the center of the explant expressed FAK and showed the activated phenotype as defined by their ability to spread on collagen. Since FAK is a tyrosine kinase, the tyrosine kinase inhibitors genistein or herbimycin A were added to the explant medium for 24 h. Inhibition of tyrosine kinase activity delayed epithelial migration, but keratinocytes were able to begin migrating after removal of the inhibitors. We conclude that FAK is up-regulated in keratinocytes in this whole skin explant model. Furthermore FAK up-regulation and keratinocyte activation are not confined to the migrating cells but are found in cells some distance from the skin margin. These data suggest that (1) cell migration, contact with wound matrix molecules, loss of cell-cell contact, or loss of basement membrane contact is not necessary for FAK up-regulation or keratinocyte activation; and (2) tyrosine kinase signaling pathways are important for reepithelialization.

Burn-activated neutrophils and tumor necrosis factor-alpha alter endothelial cell actin cytoskeleton and enhance monolayer permeability.

BACKGROUND: This study examined the hypothesis that exposure of an endothelial cell (EC) monolayer to tumor necrosis factor-alpha (TNF-alpha) and that burn-activated neutrophils alter EC actin cytoskeleton and enhance the permeability of the monolayer. METHODS: Neutrophils were harvested from rats that had undergone a 45% surface area burn (BURN-neutrophil) or uninjured control rats. ECs were grown on polyester filters or fibronectin-coated glass slides and exposed for 4 hours to media, TNF-alpha (100 ng/mL), or TNF-alpha plus BURN-neutrophil or uninjured control rats (10(7) cells). Monolayer permeability was assessed by measuring the flux of albumin across the cells. EC surface area and microfilament number and length were determined by the staining of actin microfilaments with rhodamine phalloidin followed by fluorescent microscopy. RESULTS: The amount of albumin that moved across the monolayer in response to TNF-alpha plus BURN-neutrophil was twice that of media alone (P <.05) or TNF-alpha alone (P <.05). The number and length of actin microfilaments in ECs exposed to TNF-alpha plus BURN-neutrophil were significantly less than that of cells exposed to media alone or TNF-alpha alone. CONCLUSIONS: These data are consistent with a hypothesis that TNF-alpha plus BURN-neutrophil affect endothelial monolayer permeability by altering EC actin cytoskeletal organization.

Identification of high-risk residents.

BACKGROUND: Identification of high-risk residents allows remediation and support for administrative action when necessary. This study characterizes differences in documentation of marginally performing residents in a general surgery residency. METHODS: High-risk residents were identified by the former program director. Twenty-four of one hundred fifteen residents over a 10-year period had one to four problematic areas: cognitive, synthetic, family/health, and interpersonal skills. Outcomes included finished (18), voluntary withdrawal (1), and involuntary withdrawal (5). A case-control study matching controls to cases by date of entry into the training program was used. Records were reviewed for demographics, preentry qualifications, American Board of Surgery In-Training Exam (ABSITE) scores, letters of complaint or praise, events of counseling, and monthly ratings. The records of 48 residents were reviewed. Ward evaluations were on eight categories with a 5-point Leikert scale (3-unacceptable to 7-outstanding). The evaluation score assigns points only to low ratings. High scores represent progressively poorer performance. A Wilcoxon signed ranks test was used to compare the cases and controls for continuous variables. The McNemar test was used in comparisons of categorical data with binary outcomes. Exact P values are reported. RESULTS: Objective data were similar for both groups. Study residents tended to score higher on monthly evaluations at Year 2 and by Year 3 this achieved significance (0.026). Study residents were more likely to have negative faculty letters (0.016) and events of counseling by a faculty member (0.017) and the program director (0.005). CONCLUSIONS: Identification of residents at risk should begin as early as possible during training. A combination of faculty evaluations and evidence of letters of counseling can detect high-risk residents. Programs may use such indicators to support decisions regarding remedial work or administrative action.

Focal adhesion kinase up-regulation and signaling in activated keratinocytes.

BACKGROUND: During wound healing keratinocytes undergo a process called "activation" that enables the cells to spread and migrate on wound matrix molecules. Focal adhesion kinase (FAK) is a key component of integrin-mediated intracellular signaling. We investigated the induction of FAK and its signaling activity during keratinocyte activation. MATERIALS AND METHODS: Keratinocytes were harvested from normal human skin. Previous work has shown that culture of keratinocytes causes activation in a manner similar to reepithelialization. Freshly isolated, unactivated cells were compared with cultured, activated cells. Activated cells were further examined either as growing colonies or after replating on type I collagen. FAK content was assessed by Western blotting. FAK distribution was shown using indirect immunofluorescence. FAK signaling activity was assessed using an antiphosphotyrosine antibody. RESULTS: FAK was not detectable by Western blotting in freshly isolated cells. In contrast FAK was detected in activated cells. FAK was up-regulated between Days 2 and 4 after cell isolation from skin. Immunostaining of activated, growing keratinocyte colonies in vitro showed a diffuse, cytoplasmic pattern. When these cells were replated on collagen, FAK became concentrated in focal adhesions. Lysates from replated cells showed increased tyrosine phosphorylation of FAK. CONCLUSIONS: In summary FAK is induced in keratinocytes in a time course comparable to that of activation. FAK is phosphorylated and undergoes redistribution to focal adhesions when cells are plated on the beta(1) integrin ligand collagen. These data suggest that induction of FAK and subsequent FAK-induced signaling may be responsible for changes in integrin-mediated behavior of activated keratinocytes during reepithelialization.

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction.

The induction of cyclooxygenase is an important event in the pathophysiology of acute lung injury. The purpose of this study was to examine the synergistic effects of various cyclooxygenase products (PGE(2), PGI(2), PGF(2alpha)) on thromboxane A(2) (TxA(2))-mediated pulmonary microvascular dysfunction. The lungs of Sprague-Dawley rats were perfused ex vivo with Krebs-Henseleit buffer containing indomethacin and PGE(2) (5 x 10(-8) to 1 x 10(-7) M), PGF(2alpha) (7 x 10(-9) to 5 x 10(-6) M), or PGI(2) (5 x 10(-8) to 2 x 10(-5) M). The TxA(2)-receptor agonist U-46619 (7 x 10(-8) M) was then added to the perfusate, and then the capillary filtration coefficient (K(f)), pulmonary arterial pressure (Ppa), and total pulmonary vascular resistance (RT) were determined. The K(f) of lungs perfused with U-46619 was twice that of lungs perfused with buffer alone (P = 0.05). The presence of PGE(2), PGF(2alpha), and PGI(2) within the perfusate of lungs exposed to U-46619 caused 118, 65, and 68% increases in K(f), respectively, over that of lungs perfused with U-46619 alone (P < 0.03). The RT of lungs perfused with PGE(2) + U-46619 was approximately 30% greater than that of lungs exposed to either U-46619 (P < 0.02) or PGE(2) (P < 0.01) alone. When paired measurements of RT taken before and then 15 min after the addition of U-46619 were compared, PGI(2) was found to attenuate U-46619-induced increases in RT (P < 0.01). These data suggest that PGE(2), PGI(2), and PGF(2alpha) potentiate the effects of TxA(2)-receptor activation on pulmonary microvascular permeability.

A clinical pathway for inguinal hernia repair reduces hospital admissions.

BACKGROUND: Clinical pathways have been advocated as a means to improve and standardize patient care while reducing costs through improved efficiency. This study examines the hypothesis that development of a clinical pathway reduces hospital admissions in a Veterans Affairs (VA) medical center. MATERIALS AND METHODS: For the year prior to June 1997, 168 elective inguinal herniorrhaphies were performed. This constituted the prepathway (pre-P) group. One hundred ninety-six elective inguinal herniorrhaphies were performed during the year following institution of the clinical pathway-the postpathway (post-P) group. RESULTS: Hospital admissions were compared between the two groups. In the pre-P group 61 of the 168 patients (36%) were admitted while 29 of the 196 patients (15%) in the post-P group were admitted (P < 0.001). In the pre-P group 27 of the 53 patients reviewed (51%) had either no justification or inadequate justification for admission. In the post-P group 8 of the 29 patients admitted (28%) had inadequate justification (pre-P vs post-P, P = 0.124). Common reasons for admission included pain, perioperative complications, and concurrent medical problems or surgical procedures. The most common single cause other than pain was urinary retention. The average age of patients requiring admission was greater both pre-P and post-P. CONCLUSIONS: We conclude that institution of a clinical pathway for inguinal herniorrhaphy decreased hospital admissions. The reasons for this decrease are probably multifactorial and include improvements in physician and staff awareness. The decrease in unnecessary admissions should result in more efficient use of hospital resources.

Factors affecting recurrence following incisional herniorrhaphy.

The purpose of this study was to determine the influence of chronic illness, obesity, and type of repair on the likelihood of recurrence following incisional herniorrhaphy. The medical records of 77 patients who underwent elective repair of a midline incisional hernia at the Dallas Veterans Affairs Medical Center between 1991 and 1995 were reviewed. Demographic data, presence of chronic illnesses, type of repair, and presence of recurrence were noted. Ninety-six percent of the patients were men, with an average age of 59 years. More than 50% of the patients had chronic lung or cardiac diseases and more than 40% weighed > or = 120% of their ideal body weight and had a body mass index (BMI) > or = 30. Sixty-two percent of the patients underwent primary reapproximation of the fascia (tissue repair), whereas 38% underwent repair with prosthetic material (prosthetic repair). The overall recurrence rate was 45%, with a median follow-up of 45 months (range 6-73). Seventy-four percent of the recurrences presented within 3 years of repair. The recurrence rate for those patients undergoing a tissue repair was 54%, whereas the recurrence rate following prosthetic repair was 29%. The incidence of recurrence for patients with pulmonary or cardiac disease or diabetes mellitus was similar to that of patients without these illnesses. The percent ideal body weight and BMI of patients who developed a recurrent hernia, particularly following a prosthetic repair, were significantly greater than those of patients whose repairs remained intact. These data strongly support the use of prosthetic repairs for incisional hernias, particularly in patients who are overweight.

Effect of diabetes mellitus on endotoxin-induced lung injury.

OBJECTIVE: To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation. HYPOTHESIS: Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs. DESIGN: Zucker diabetic fatty (ZDF) rats (genotype fa/fa) were used as a model of diabetes mellitus, while their normoglycemic heterozygous littermates served as controls. Lipopolysaccharide (Escherichia coli 0111: B4; 100-200 microg) or vehicle (0.25 mL of isotonic sodium chloride solution) was instilled into the airways of ZDF and control rats. Four hours later, pulmonary microvascular dysfunction was assessed by measuring the extravasation of Evans blue dye into the lung. Lipopolysaccharide-induced neutrophil recruitment was assessed by counting the number of neutrophils within the bronchoalveolar lavage fluid and measuring their expression of CD11b/CD18 by fluorescence-activated cell analysis sorting. RESULTS: The LPS (200 microg) induced a 32% increase in Evans blue dye extravasation into the lungs of controls (P = .008) but had no such effect in diabetic animals. Pulmonary extravasation of Evans blue dye in controls was greater than that of ZDF rats both at baseline (P = .002) and in response to 200 microg of LPS (P<.001). The LPS upregulated neutrophil CD11b/CD18 expression in diabetic and nondiabetic groups and induced a greater than 50-fold increase in the number of neutrophils within the airways of both control and diabetic groups (P<.001). CONCLUSION: Despite the recruitment of a large number of neutrophils into the lung, the LPS-induced change in pulmonary microvascular permeability in diabetic animals is substantially less than that of nondiabetic controls.

Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction.

OBJECTIVES: To examine whether the lung releases nitric oxide (NO) in response to thromboxane A2 and to examine the local release of NO as a protective compensatory mechanism by which the lung responds to the proinflammatory and vasoactive effects of thromboxane A2. DESIGN: The lungs of anesthetized Sprague-Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an inhibitor of NO synthase (nitroglycerinenitro-L-arginine methyl ester [L-NAME]) (10(-4) mol/L), an NO donor (sodium nitroprusside) (10(-8) mol/L), or perfusate alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha(U-46619) (7.1 X 10(-8) mol/L) was added to the perfusate. Fifteen minutes later, the capillary filtration coefficient, pulmonary arterial pressure, and vascular resistance were measured. Pulmonary NO release was assessed by quantitating the release of cyclic guanosine monophosphate into the perfusate. RESULTS: The capillary filtration coefficient of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused with buffer alone (P<.05). The addition of sodium nitroprusside reduced the increase in capillary filtration coefficient associated with U-46619 by 50% (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused lung caused a 3.0+/-0.4 mm Hg increase in pulmonary artery pressure (P<.01) with a corresponding rise in total vascular resistance (P<.05). This effect was exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05). Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic guanosine monophosphate levels within the perfusate. CONCLUSION: These data are consistent with the hypothesis that NO release may be an important protective mechanism by which the lung responds to thromboxane A2.

The effect of sequential injuries on splanchnic perfusion and eicosanoid release.

BACKGROUND: This study examines the hypothesis that sequential burn injury followed by intraabdominal sepsis induces significantly greater splanchnic hypoperfusion and reduced intestinal PGI2 release than either injury independently. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats were randomized to one of four groups: BURN (45% body surface area scald burn) + cecal ligation and puncture (CLP); BURN alone; CLP alone; or uninjured controls (SHAM). Twenty-four hours following injury, superior mesenteric artery (SMA) blood flow was measured with a doppler flow probe. Splanchnic eicosanoid release (6-keto-PGF1alpha, metabolite of PGE2; TxB2, metabolite of TxA2; and PGE2) was measured in mesenteric venous effluent utilizing an isolated, perfused bowel preparation. RESULTS: SMA blood flow was no different than that of controls 72 h following BURN injury alone; whereas CLP alone resulted in a 80% reduction in splanchnic blood flow when compared with controls (P < 0.001). SMA blood flow in animals sustaining BURN + CLP was only modestly reduced from controls (P = 0.04) and 3.6 times greater than that of animals sustaining CLP alone (P < 0.001). PGI2 was the dominant eicosanoid released by the intestine with levels 10 times greater than TxB2 and nearly 50 times greater than PGE2. CLP either alone or when combined with BURN was associated with a 60% decrease in splanchnic PGI2 release when compared to controls (P < 0.05). CONCLUSIONS: These data suggest that moderate BURN injury in rats attenuates the severe reduction in splanchnic perfusion associated with intraabdominal sepsis and that this occurs despite profound reductions in the release of the endogenous splanchnic vasodilator PGI2.

Integrin alpha v promoter activity in keratinocytes.

BACKGROUND: During reepithelialization keratinocytes show increased expression of the integrin subunit alpha-v. We have investigated the promoter region of the alpha-v integrin subunit to learn more about its regulation. METHODS: The promoter region of the human integrin alpha-v gene was cloned into a luciferase reporter vector. Deletional mutants were created using PCR. Computerized sequence analysis was performed using the Wisconsin Package. Gel-shift analysis was performed using keratinocyte nuclear extracts and oligonucleotides spanning th regions of interest. RESULTS: Deletion from -522 bp to -235 resulted in no discernible effect on promoter activity. In contrast deletion of the next 22 bp, which included a putative ets binding site, reduced activity by approximately half. Further deletion to -139 bp essentially abolished promoter activity. Computer searching of this region of the integrin alpha-v promoter revealed two tandemly repeated motifs, TCCTCCTCC, that had previously been implicated in the function of the epidermal growth factor receptor (EGFR) promoter. Comparison of the alpha-v integrin promoter to the EGFR promoter revealed an area of high homology in this region. Gel-shift analysis revealed binding of a single-strand specific DNA binding protein to single stranded oligos comprising these motifs, but no binding of factors to the double- stranded oligo containing the ets binding site. CONCLUSIONS: In keratinocytes alpha-v integrin expression is controlled by a region of the promoter with high homology to the epidermal growth factor receptor promoter This region binds single-strand specific DNA binding proteins that are likely to be important in controlling transcription.

Gender-related attrition in a general surgery training program.

BACKGROUND: Attracting and retaining highly qualified applicants to careers in surgery is a goal of residency training programs. Few studies of attrition in residency exist. This study examines the hypothesis that reasons for attrition during general surgery training are different for male and female trainees. MATERIALS AND METHODS: NRMP matching information was used to evaluate attrition rates in a categorical general surgery (CGS) residency program from 1984 through 1996. The records of all matched residents were examined to determine the association between gender and attrition outcomes. Outcome variables included: voluntary vs involuntary withdrawal and the reasons for withdrawal. RESULTS: During the study period 132 candidates matched (103 men and 29 women) into CGS positions. Of that group, 18 residents, 11 (10.7%) from the male and 7 (24.1%) from the female cohorts withdrew. Only three involuntary withdrawals occurred. Women were 2.26 times more likely to withdraw than men, a finding that is not statistically significant (P = 0. 073). Women rarely left for preference of other specialty (relative risk 0.25), whereas men were 4 times more likely to leave for this reason. CONCLUSION: These numbers suggest that women are at higher risk of leaving general surgery training than men. When women do leave, it is more likely for family reasons such as lifestyle considerations or to join a spouse in another geographic location. Such findings support the conclusion that fundamental differences exist in decisions regarding attrition between genders. National studies of attrition and the reasons for leaving are needed to develop specific strategies promoting retention for both genders.

Intestinal reperfusion-induced pulmonary edema is related to increased pulmonary inducible nitric oxide synthase activity.

BACKGROUND: This study examines the hypothesis that specific inhibition of the inducible isoform of nitric oxide synthase (iNOS) will attenuate intestinal reperfusion-induced pulmonary microvascular dysfunction. METHODS: Sprague-Dawley rats underwent intestinal ischemia-reperfusion (IR) or sham operation (SHAM). Before injury, the animals received a selective inhibitor of iNOS (S-methylisothiourea sulfate, SMT: L-N6-[1-iminoethyl] lysine L-NIL), a nonselective inhibitor of NOS (NG-nitro-L-arginine methylester, L-NAME) or vehicle (0.9% saline). IR-induced changes in pulmonary microvascular permeability were assessed by quantitating the extravasation of Evans blue dye (EBD)-bound protein into the lung. Pulmonary iNOS activity and content were assessed by radiochemical analysis and Western blot, respectively. RESULTS: There was 60% more EBD within the lungs of animals sustaining IR when compared with controls (P < .05). Pretreatment with SMT or L-NIL totally prevented the increase in EBD extravasation associated with IR. In contrast, pretreatment with L-NAME resulted in a 10% increase in dye extravasation in those animals sustaining IR when compared with similarly injured animals receiving saline (P > .05). There was significantly greater iNOS activity and enzyme content within the lungs of animals sustaining IR compared with controls. CONCLUSIONS: These data are consistent with the hypothesis that the release of nanomolar quantities of nitric oxide generated by iNOS contributes to IR-induced pulmonary microvascular dysfunction.

Alveolar macrophage response to remote organ injury.

Intestinal reperfusion (IR)-induced pulmonary edema has been related to endogenous pulmonary thromboxane A2 (TxA2) release. This study examines the hypothesis that alveolar macrophages (aMphis) activated during IR are an important cellular source of TxA2 in this model. Anesthetized Sprague Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR) or sham operation (Sham). aMphis were isolated by bronchoalveolar lavage and incubated in Krebs buffer for 30 min, after which the supernatant was analyzed for TxB2 (metabolite of TxA2) and prostaglandin E2. Other parameters of aMphi activation measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O2-) release, and procoagulant activity. aMphis from animals sustaining IR generated more than twice as much TxA2 and prostaglandin E2 as did those isolated from controls (p < .05). Other evidence of aMphi activation included a nearly 100-fold increase in procoagulant activity, a 7-fold increase in beta-glucuronidase release, and a 2.5-fold increase in O2- release over that of controls (p < .05). These data suggest that TxA2 is a major eicosanoid product of aMphis during IR and that aMphis may be an important cellular participant in IR-induced pulmonary microvascular injury, either directly by releasing O2-, lysosomal enzymes, and pro-coagulant factors, or indirectly by generating TxA2.

Abdominal aortic aneurysms and malignant neoplasia: double jeopardy.

BACKGROUND: This study was performed to determine whether there is a significant association between abdominal aortic aneurysms (AAAs) and malignancy and to determine the impact of malignancy on late survival in patients with AAA. METHODS: We studied 126 men undergoing AAA repair and compared them with 99 men undergoing aortofemoral bypass (AFB) for occlusive disease and with 100 men undergoing herniorrhaphy during the same period. RESULTS: Fifty-one (40%) patients with AAA, 23 (23%) patients undergoing AFB, and 21 (21%) patients undergoing herniorrhaphy were diagnosed with cancer (p = 0.002). By life table analysis the proportion of subjects remaining cancer free at 5 years was 0.60 +/- 0.05 for AAA, 0.83 +/- 0.04 for AFB, and 0.81 +/- 0.04 for herniorrhaphy (p = 0.004). Multivariate analysis selected four independent risk factors for cancer: presence of AAA (p = 0.003, odds ratio 1.4, confidence interval [CI] 1.2 to 1.7), age (p = 0.001, odds ratio per year 1.1, CI 1.0 to 1.1), smoking (p = 0.04, odds ratio 1.5, CI 1.0 to 2.2), and hypertension (p = 0.04, odds ratio 0.73, CI 0.5 to 1.0). Cancer deaths accounted for 32% of late deaths in patients with AAA, which was not different compared with 26% of late deaths in patients undergoing AFB and 36% of late deaths in patients undergoing herniorrhaphy. Five-year cancer-free survival was 0.44 +/- 0.05 for patients with AAA, 0.64 +/- 0.05 for patients undergoing AFB, and 0.70 +/- 0.05 for patients undergoing herniorrhaphy (p < 0.001, AAA versus herniorrhaphy only). CONCLUSIONS: Cancer is more prevalent in men with AAA than in men undergoing AFB or herniorrhaphy. The presence of AAA appears to be an independent risk factor for cancer. Despite the higher cancer prevalence in patients with AAA, cardiovascular disease accounted for the largest number of late deaths in this series, minimizing differences in cancer-free survival between patients with AAA and patients undergoing AFB.

Physiologic basis of pulmonary edema during intestinal reperfusion.

This study quantitates the physiologic forces governing the movement of fluid and protein into the lungs during intestinal reperfusion (IR) and describes the anatomic pattern of protein extravasation. Sprague-Dawley rats underwent IR after which pulmonary microvascular dysfunction was assessed in vivo by measuring the concentration of protein within the airways and by quantitating the extravasation of Evans blue dye (EBD). Pulmonary microvascular dysfunction was quantitated in vitro by determining the capillary filtration coefficient (Kf), protein reflection coefficient (final sigma), and vascular resistance (Rt) using an isolated, perfused lung model. The morphologic pattern of protein extravasation into the lung was qualitatively assessed by fluorescence microscopy following the intravenous administration of fluorescent-labeled proteins of varying molecular weight. Sham-operated animals served as controls. The EBD content of lungs of IR animals was 48% greater than that of controls (P = 0.02). There was no difference in the protein concentration within the airways of these two groups. IR was associated with changes in pulmonary microvascular function favoring the movement of plasma fluid and protein into the interstitium (Kf = 0.02 +/- 0.006 vs 0.005 +/- 0.0005 g/min/mm Hg/100 g body wt; final sigma = 0.95 +/- 0.02 vs 0.99 +/- 0.005; and Rt = 0.94 +/- 0.08 vs 0. 53 +/- 0.04 mm Hg/ml/min/100 g body wt; IR vs SHAM, respectively, P < 0.05). Fluorescence microscopy demonstrated the focal extravasation of labeled proteins into the lungs of animals sustaining IR. These data suggest that both enhanced microvascular permeability and increased hydrostatic pressure contribute to the pulmonary edema associated with IR. Furthermore, the extravasation of protein is relatively focal in nature in contrast to the diffuse leak that characterizes more severe models of lung injury.