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Objective: To test whether or not the association between inflammation and pancreatic ductal adenocarcinoma (PC) is facilitated by host susceptibility, specifically by genetic polymorphisms in inflammation-related genes., Summary Background Data: Inflammation has been linked to PC. Reports have cited an increased expression of proinflammatory mediators, such as NF-κB and COX, in PC but not in normal adjacent tissue, suggesting a possible role in carcinogenesis. We sought to further understand the role that genetic variants in the NF-κB inflammatory pathway play in the development and progression of PC., Methods: We genotyped 1536 tag single nucleotide polymorphisms (SNPs) in 102 candidate genes of multiple inflammatory pathways in 1308 white patients with PC who were divided into 3 groups on the basis of the extent of disease: resected for cure (n = 400), locally advanced/unresected (n = 443), and metastatic (n = 465). Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression models. Statistical significance was set at less than 0.001 to control for multiple testing., Results: Median age was 67 (28.0-91.0) years, and 57% were men. Median survival for each of the 3 groups (resected, locally advanced, and metastatic) was 23.7, 9.4, and 6.6 months, respectively (P < 0.0001). In the resected group, carriers of a minor allele for either rs3824872 (MAPK8IP1) or rs8064821 (SOCS3) were associated with a 10- and 6-month survival advantage compared with noncarriers in patients with resected disease, with an additional 2-year survival if both minor alleles were present. With locally advanced disease, SNP rs1124736 (IGF1R) was associated with improved survival if they had a copy of the G allele, hazard ratio of 0.57 (95% confidence interval: 0.42-0.77); P = 0.0002. In addition, 4 SNPs in patients with metastatic disease were found to be associated with worse survival and 2 associated with improved overall survival, but the differences in survival were deemed not clinically significant., Conclusions: SNPs in the inflammatory pathway genes MAPK8IP1 and SOCS3 were associated with increased overall survival in patients undergoing potentially curative resection and may be used in the future as markers to predict survival. Future research is needed to determine the functional relevance of these loci.

Objective: To estimate the frequency of extrapancreatic neoplasms in patients with IPMN compared with those with ductal pancreatic cancer and a general referral population., Summary Background Data: Several studies have reported an increased risk of extrapancreatic neoplasms in patients with IPMN, but these studies focused only on those patients who underwent resection and excluded those patients treated nonoperatively., Methods: All patients diagnosed with IPMN at Mayo Clinic from 1994 to 2006 were identified. Two control groups consisting of Group 1-patients with a diagnosis of ductal pancreatic adenocarcinoma (1:1) and Group 2-a general referral population (3:1) were matched for gender and age at diagnosis, year of registration, and residence. Logistic regression was used to assess the risk of a diagnosis of extrapancreatic neoplasms among cases versus controls., Results: There were 471 cases, 471 patients in Group 1, and 1413 patients in Group 2. The proportion of IPMN patients having any extrapancreatic neoplasm diagnosed before or coincident to the index date was 52% (95% CI, 47%-56%), compared with 36% (95% CI, 32%-41%) in Group 1 (P < 0.001), and 43% (95% CI, 41%-46%) in Group 2 (P = 0.002). Benign neoplasms most frequent in the IPMN group were colonic polyps (n = 114) and Barrett's neoplasia (n = 18). The most common malignant neoplasms were nonmelanoma skin (n = 35), breast (n = 24), prostate (n = 24), colorectal cancers (n = 19), and carcinoid neoplasms (n = 6)., Conclusions: Patients with IPMN have increased risk of harboring extrapancreatic neoplasms. Based on the frequency of colonic polyps, screening colonoscopy should be considered in all patients with IPMN.

We developed a dextran-glucose-based extracellular perfusion solution (DGX) that supports limited aerobic metabolism to maintain cellular integrity of an inflated donor lung during long-term ischemia and a storage temperature of 10 degrees C. In a dog model, we compared respiratory and hemodynamic function of orthotopically transplanted left lungs preserved using this method (DGX, group I, n = 6) with function of those preserved with EuroCollins solution (EC) stored at a temperature of 4 degrees C (group II, n = 6). All lungs were inflated with room air and stored for 12 hr. Pulmonary function was monitored for 5 hr of reperfusion. Values expressed below are group means with standard deviation. Statistical significance was calculated using a two-tailed t test. For PO2 (mmHg) (FiO2 = 0.4), group I (EC): control = 193 +/- 8, 30 min p.o. = 87 +/- 20*, 300 min p.o. = 174 +/- 13*; and group II (DGX): control = 217 +/- 28, 30 min p.o. = 184 +/- 46*, 300 min p.o. = 248 +/- 5*. For pulmonary vascular resistance (dynes), group I: control = 389 +/- 22, 30 min p.o. = 1209 +/- 301, 300 min p.o. = 1025 +/- 204*; and group II: control = 401 +/- 31, 30 min p.o. = 522 +/- 129, 300 min p.o. = 458 +/- 137* (*P < 0.05 DGX vs. EC). Gas analysis performed on air samples taken from the ischemic donor lung immediately after harvest and after 12-hr storage showed (calculated as group means) a significant decrease of PO2 and a significant increase of PCO2, respectively. Histology of the lungs after 5 hr of reperfusion showed essentially normal-appearing lungs in the DGX group, whereas lungs in the EC group showed thickening of the intra-alveolar septi, marked cellular infiltration, and accumulation of protein-like material in the alveoli. In this study, preservation with DGX resulted in satisfactory respiratory and hemodynamic function of the transplanted lung even after 12 hr of ischemia. It does not cause an increase of pulmonary vascular resistance as seen after preservation with EC. Data from the intrabronchial air analysis of the donor lung suggest that aerobic metabolism continues even under preservation conditions.

This study reports the evaluation of the validity and utility of the Medicare heart transplant center selection process, as outlined in its 1986 Heart Coverage Regulations. A total of 9401 heart transplants performed in the U.S. between 1986 and 1991 were analyzed. The outcomes assessed were mortality and the occurrence of infection during the hospital stay. Outcomes experienced by centers with and without Medicare approval were compared directly and following adjustment for patient risk factors. Patients at centers that satisfied the Medicare criteria experienced lower mortality. The risk-adjusted hazard ratio for death over the five years of observation was 0.874 (P = 0.005). The probability of death following a transplant at a Medicare-approved center was 7.0 +/- 0.4% at 30 days and 16.2 +/- 0.6% at one year, and 9.2 +/- 0.4% and 19.2 +/- 0.6%, respectively, at centers without Medicare approval (P = 0.001). The difference appeared to be principally associated with death within 30 days of admission due to nonspecific graft failure. The posttransplant infection rate at Medicare-approved centers was 0.743 (P < 0.001) but this result is strongly confounded with differences in reporting patterns of the two types of centers. Criteria used by HCFA identify medical centers where outcomes of heart transplantation, as measured by mortality, are superior. This difference is established early, persists over time, and is not attributable to the numerous risk factors considered in our models. Overall, the results of the present study suggest that "centers of excellence" can be identified through the evaluation of center characteristics and outcomes, and that this approach chosen by HCFA may have broad health care systems applications.

From June 1984 to September 1989, 43 patients with large vena caval tumor thrombi from retroperitoneal malignancies underwent surgical treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). The primary malignancies were renal cell carcinoma (RCC) (n = 39), renal pelvic transitional cell carcinoma (n = 1), adrenal pheochromocytoma (n = 1), and renal (n = 1) or retroperitoneal (n = 1) sarcoma. The level of the caval thrombus was either suprahepatic (n = 27), intrahepatic (n = 14), or subhepatic (n = 2). In all cases the primary tumor and caval thrombus were completely removed. Concomitant procedures included coronary artery bypass grafting (n = 5), pulmonary resection (n = 2), and hepatic lobectomy (n = 1). The time of circulatory arrest ranged from 10 to 44 minutes (mean, 23.5 minutes). There were two operative deaths (4.7%), neither of them due to to the use of DHCA. Major postoperative complications occurred in 13 patients (30.2%). There were no ischemic or neurologic complications and no cases of perioperative tumor embolization. The median postoperative hospital stay was 9 days. Twenty-two patients (51%) are alive and enjoying a good quality of life. The 3-year patient survival rates in patients with localized (n = 24) versus metastatic (n = 15) RCC are 63.9% and 10.9%, respectively (p = 0.02). We conclude that CPB with DHCA facilities excision of retroperitoneal malignancies with large caval thrombi and provides the potential for cure with low morbidity and mortality rates.

Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in 11 dogs was observed noninvasively by use of 111In-labeled platelets and quantified after sacrifice at one (n = 3), 14 (n = 3), and 30 (n = 5) days postimplantation (300-400 microCi of labeled platelets having been injected 24 hours previously). Thrombosis on the sewing ring and pericardial leaflets at one and 14 days and on the leaflets at 30 days was delineated in scintiphotos. In vitro quantification (% injected dose) indicated that the leaflets, sewing ring, and perivalvular tissue retained 0.904% of labeled platelets at one day postimplantation, 0.198% at 14 days, and 0.040% at 30 days. Platelet half-life was reduced to 38 hours at 21 days postimplantation but returned toward the normal (50 hours) with fibrous ingrowth in the sewing ring. Microembolism in lung and kidney, as measured by tissue/blood radioactivity ratio, also was decreased significantly at 30 days. 111In-labeled platelets thus provide a sensitive marker for noninvasive imaging and in vitro quantification of platelet deposition on valvular prostheses and microemboli trapped in viscera, although histochemical confirmation will be necessary to correlate the increase in tissue/blood ratio with the presence of microembolism.

Autologous femoral vein segments were implanted as aortocoronary bypass grafts in 50 dogs, 25 of which were treated with dipyridamole and aspirin to inhibit platelet deposition and 25 that were not. Autologous platelets labeled with indium-111 were injected into some dogs 48 hr before they were killed on the first day after surgery; other dogs were injected 24 hr before they were killed (3, 7, 30, and 90 days after surgery). Radioactivity on the grafts and on control specimens of contralateral femoral veins was converted to quantification of platelets adhering to the vessel wall (platelets/cm2). The treated group had fewer graft platelets per square centimeter than the untreated group on postoperative days 3, 7 (p less than .01), and 30 (p less than .05). Graft and control vein platelets per square centimeter were nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy revealed deendothelialization at 1 and 7 days after grafting and reendothelialization at 30 and 90 days. The data suggest that indefinite prolongation of therapy to inhibit platelet deposition after bypass grafting may be unnecessary (although other atherosclerotic vessels may benefit from therapy).

Fetal intracardiac tumors are rare but, when present, are a common cause of poor or uninterpretable fetal heart tracings due to fetal arrhythmias. The most frequently encountered tumor, the rhabdomyoma, is associated with tuberous sclerosis. We present a case demonstrating this difficulty of fetal monitoring in a fetus with an arrhythmia later found to be due to multicentric intracardiac rhabdomyomas. The appropriate evaluation and management of such fetal heart tracings are discussed.

Six samples of various thicknessess of Gore-Tex compounds were fashioned into trileaflet valves. A radiopaque marker was placed on the center of the free margin of each cusp, and the prostheses were implanted in the tricuspid position of dogs. Two Hancock valves were studied for comparison. Catheterization revealed that the hemodynamic function was normal in all valves tested. High-speed radiography permitted analysis of leaflet movement throughout the cardiac cycle. Of the six Gore-Tex valves, five opened completely. The cusps of these five valves were fabricated from 4, 6, 8, 10, and 12 layers of Gore-Tex film. The remaining valve, which was fabricated from 15 layers of Gore-Tex film, and both porcine xenograft aortic valves did not open completely. We postulate that the laminates of 12 layers or less of Gore-Tex film are suitable for further study to evaluate their potential applicability in trileaflet cardiac valve prostheses.

A continuing program has been conducted since 1970 to determine levels of radioactive nuclides in adults and children from families residing in communities and ranches surrounding the Nevada Test Site. Twice each year these persons receive a whole-body count and physical examination; a urine sample from each is also submitted for radionuclide analyses. The only fission-product radionuclide routinely found in whole-body counting has been 137Cs at concentrations similar to those in persons living in other areas of the United States. The physical examinations reveal a generally healthy population, and urine samples have shown no remarkable radionuclide content.

In a long-term prospective study, five normal control pigs and five pigs with homozygous von Willebrand's disease received a nonfatty diet from age 3 months to 4 years; then the aortas were analyzed. The fibrous arteriosclerotic plaques in the distal abdominal aortic region involved an average of 28% of the surface area in control pigs and only 7% of the surface area in pigs with von Willebrand's disease (P less than 0.01). In a subsequent study of 3-month-old pigs, the distal abdominal aortic segments from nine normal pigs were cross-transplanted with segments from nine other normal pigs (control study), and aortic segments from four normal pigs were transplanted into four host pigs with von Willebrand's disease (exchange study). All pigs received a 2% cholesterol diet for up to 6 months; then the transplanted aortic segments were analyzed. The donor normal aortic segments in the host normal pigs developed arteriosclerosis that involved an average of 20% of the surface; the endothelial fluorescent pattern of von Willebrand factor was identified. In contrast, the donor normal aortic segments in the host pigs with von Willebrand's disease had arteriosclerosis that involved an average of only 4% of the surface (P less than 0.01); the endothelial cell von Willebrand factor was not identified. The long-term prospective study indicates that pigs with von Willebrand's disease are resistant to the development of spontaneous arteriosclerosis. The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis.

A retrospective study was undertaken to examine the prognosis of gastric outlet obstruction with specific reference to patients with obstruction due to peptic ulcer. During the 10-year period 1970-1979, 68 patients with gastric outlet obstruction were admitted to our hospital. Obstruction was caused by peptic ulceration in 55 of these patients, all of whom initially were managed conservatively. Thirty-four, however, required surgical decompression during their first admission for obstruction, and 11 needed surgery for a subsequent episode of obstruction. Of the ten patients who have not undergone surgery, six died within 3 years of their first episode of obstruction and three of the four survivors continue to have recurrent obstructive symptoms. Overall, 92% (45/49) of patients who have lived for more than 3 years after their presentation with gastric outlet obstruction due to peptic ulcer have required surgery for relief of obstruction.

At 8 and 32 hours after saphenous vein bypass graft surgery in six dogs, in vivo images of the graft were obtained with a gamma camera after intravenous injection, 2 hours postoperatively of autologous platelets labeled with indium-111. Platelet deposition in the grafts could be imaged in vivo from the scintiphotos. In vitro images of the excised heart showed saphenous vein graft uptake confirming the in vivo image. In vitro determination of radioactivity in the graft averaged 17 +/- 14 times greater than in blood and 33 +/- 26 times greater than in the lung. Under identical conditions, in eight dogs treated with dipyridamole (55 mg/day) plus aspirin (325 mg/day), the grafts appeared to have considerably less platelet deposition as estimated by imaging. In vitro determination of radioactivity in the graft averaged 5 +/- 2 times greater than in blood and 8 +/- 4 times greater than in the lung (p less than 0.01). This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man and its prevention with platelet inhibotors.

Oxygen-derived free radicals (O2-, H2O2, OH.) are produced during oxidative metabolism, ischemia and reperfusion, and cardiopulmonary bypass (CPB). When oxygen free radical production exceeds scavenging capacity, peroxidation of structural lipids in cell membranes can occur with potentially injurious consequences. In this prospective study, 45 patients were evaluated to determine the effect of CPB on oxygen free radical generation. Twenty patients in group I were controls. Exogenous oxygen free radical antioxidants were administered before bypass to patients in group II (n = 15, mannitol) and group III (n = 10, allopurinol). In group I, plasma H2O2 increased during extracorporeal circulation from 65 +/- 6.0 to 125 +/- 12 microM/ml (p less than .001). At similar sampling intervals, plasma H2O2 levels were significantly lower in group II (p less than .03) and group III (p less than .05) when compared with those in group I. Red blood cell H2O2 did not change in group I or group II. White blood cell H2O2 levels decreased in group I (p less than .04) and group II during CPB. (Intracellular concentrations of H2O2 were not obtained in group III patients). We conclude that cytotoxic oxygen radicals are generated during CPB and that pretreatment with free radical antioxidants, mannitol or allopurinol, may minimize the free radicals available for lipid peroxidation of biomembranes.