Search

In this paper, we analyze approaches to assess the effectiveness of decision analyses. We develop an effectiveness framework, categorized in metrics to assess the quality of the decision process ('process [...]

Employing Pt(111) supported 2D Pt-core Au-shell model catalysts, we demonstrate that 2D core–shell surfaces prepared under ultrahigh vacuum (UHV) conditions constitute excellent model systems to determine the activity of step sites in electrocatalysis, especially because UHV-scanning tunneling microscopy (STM) enables control of the quality of narrow step modifications with high accuracy on such systems. As verified with STM, cyclic voltammetry (CV), and temperature-programmed desorption (TPD) measurements, this approach allows us (i) to increase the step density by homoepitaxial growth of monolayer high islands on the respective single crystal and (ii) to modify the step sites for adsorption of reactants by selective deposition of a guest metal. Herein, STM imaging in combination with electrochemical characterization provides a direct control to ascertain a selective modification of the entire steps. Comparing the electrocatalytic activity of 2D core–shell systems with and without the shell enables us to identify the activity of step sites for electrocatalytic reactions, as demonstrated for the bulk CO electro-oxidation.

To prospectively determine the influence of variations of surgical radicality and surgical quality on long-term outcome in patients with stage I-III colon cancer.

Prostheto-ureteral fistula after aortic graft surgery is a potentially life-threatening, rare pathology. We report the successful treatment of a prostheto-ureteral fistula that caused hematuria with hemorrhagic shock in two patients by explantation of aortic prosthetic grafts and implantation of a silver-bonded prosthetic graft (Intergard S, Intervascular®). These cases show that this surgical procedure is effective, and that straightforward diagnostic procedures are necessary to initiate correct therapeutic approach without delay. Various different possible risk factors for the formation of a prostheto-ureteral fistula are also discussed.

Background Endotoxemia is well known to be associated with an excessive host response to bacteria or microbial compounds, resulting in systemic inflammation and organ injury. The aim of the present study was to examine the effects of simvastatin on endotoxemic liver injury.Methods Male C57BL/6J mice were challenged intraperitoneally with 0.5 mg/kg Escherichia coli-lipopolysaccharide (LPS) and 0.9 g/kg d-galactosamine (Gal). Mice were pretreated with 0.2 mg/kg simvastatin. Lipopolysaccharide/d-Gal-injected mice without simvastatin served as endotoxemic controls, and sham mice served as negative controls. Additional mice were challenged with LPS/d-Gal and co-treated with simvastatin and 10 mg/kg mevalonate to determine the role of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. After 6 hours of endotoxemia serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as caspase-3 and myeloperoxidase activity were determined.Results Endotoxemia caused a substantial hepatocellular injury as indicated by significantly elevated serum ALT and AST levels and hepatocellular apoptosis. Leukocyte infiltration in the liver was significantly elevated in endotoxemic mice. Simvastatin significantly reduced endotoxin-induced hepatocellular damage and apoptosis. Moreover, hepatic accumulation of leukocytes was attenuated by simvastatin in endotoxemic animals. Co-administration of mevalonate abolished protective effects of simvastatin on endotoxin-provoked increases in ALT, AST, and hepatocellular apoptosis as well as leukocyte recruitment.Conclusions Simvastatin has the capacity to prevent endotoxemic liver injury by inhibiting leukocyte infiltration and hepatocellular apoptosis. These protective effects exerted by simvastatin are dependent on the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase pathway. Thus, simvastatin may represent a potential approach to prevent endotoxemia-associated liver dysfunction.

HYPOTHESIS Laryngeal dysfunction after thyroidectomy is a common complication. However, few data are available to differentiate whether these complications result from injury to the recurrent nerve or to the vocal folds from intubation. SETTING University medical center. PATIENTS Seven hundred sixty-one patients who underwent surgery to the thyroid gland from 1990 to 2002. Of these patients, 8.4% underwent a revision thyroidectomy. INTERVENTION Preoperative and postoperative laryngostroboscopic examination. MAIN OUTCOME MEASURE Laryngostroboscopic evaluation of laryngeal complications. RESULTS The overall rate of laryngeal complications was 42.0% (320 patients). Complications from an injury to the vocal folds occurred in 31.3% of patients. Weakness or paresis of the recurrent nerve was initially present in 6.6% and was related to the nerves at risk. This rate was higher in revision thyroidectomies than in primary surgical interventions (6.2% vs 11.6%; P = .04). The rate of laryngeal injuries was higher in patients older than 65 years (39.8% vs 30.8%; P = .03). CONCLUSIONS These data suggest that laryngeal complications after thyroidectomies are primarily caused by injury to the vocal folds from intubation and to a lesser extent by injury to the laryngeal nerve. We recommend documentation of informed consent, especially for patients who use their voice professionally, such as singers, actors, or teachers.Arch Surg. 2009;144(2):149-153--

Background/Aim:Pancreatic cancer is characterized by perineural invasion, early lymph node and liver metastases, and an extremely dismal prognosis. In the present study we aimed at investigating the expression profile of pro-inflammatory and angiogenic CXC chemokines as potential factors contributing to the aggressive biology of this gastrointestinal malignancy. Methods:Protein expression profiles of the CXC chemokines growth-related oncogene alpha (GRO-a/ CXCL1), epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5), granulocyte chemoattractant protein-2 (GCP-2/CXCL6), neutrophil-activating protein-2 (NAP-2/CXCL7), and interleukin-8 (IL-8/CXCL8) were assessed by enzyme-linked immunosorbent assay in pancreatic carcinoma, cancer of the papilla of Vater, pancreatic cystadenoma, and chronic pancreatitis specimens. Results: IL-8 and ENA-78 protein expression was most pronounced in pancreatic carcinoma specimens, showing an 11-fold and 17-fold over-expression in comparison with non-affected neighbouring tissues, a 66-fold and 24-fold upregulation compared to pancreatic cystadenoma, and a 6-fold and 9-fold overex-pression with respect to chronic pancreatitis, respectively (p <0.05 between all groups). In addition, a close correlation between IL-8 and ENA-78 protein expression and advanced pancreatic carcinomas in relation to the T category was evident (p < 0.05). Conclusion:Our results demonstrate that ELR+ CXC chemokines are differentially expressed in malignant and non-malignant human pancreatic specimens, suggesting a potential contribution of these chemokines to the pathogenesis of pancreatic carcinoma.

AbstractBackground/Aim:Pancreatic cancer is characterized by perineural invasion, early lymph node and liver metastases, and an extremely dismal prognosis. In the present study we aimed at investigating the expression profile of pro-inflammatory and angiogenic CXC chemokines as potential factors contributing to the aggressive biology of this gastrointestinal malignancy. Methods:Protein expression profiles of the CXC chemokines growth-related oncogene alpha (GRO-α/CXCL1), epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5), granulocyte chemoattractant protein-2 (GCP-2/CXCL6), neutrophil-activating protein-2 (NAP-2/CXCL7), and interleukin-8 (IL-8/CXCL8) were assessed by enzyme-linked immunosorbent assay in pancreatic carcinoma, cancer of the papilla of Vater, pancreatic cystadenoma, and chronic pancreatitis specimens. Results:IL-8 and ENA-78 protein expression was most pronounced in pancreatic carcinoma specimens, showing an 11-fold and 17-fold overexpression in comparison with non-affected neighbouring tissues, a 66-fold and 24-fold upregulation compared to pancreatic cystadenoma, and a 6-fold and 9-fold overexpression with respect to chronic pancreatitis, respectively (p < 0.05 between all groups). In addition, a close correlation between IL-8 and ENA-78 protein expression and advanced pancreatic carcinomas in relation to the T category was evident (p < 0.05). Conclusion:Our results demonstrate that ELR+ CXC chemokines are differentially expressed in malignant and non-malignant human pancreatic specimens, suggesting a potential contribution of these chemokines to the pathogenesis of pancreatic carcinoma.Copyright © 2008 S. Karger AG, Basel and IAP

HYPOTHESIS Infections and sepsis are major complications in secondary peritonitis and still represent a diagnostic challenge. We hypothesized that the laboratory marker procalcitonin would provide an early and reliable assessment of septic complications. DESIGN Prospective, international, multicenter inception cohort study. SETTING Five European surgical referral centers. PATIENTS Eighty-two patients with intraoperatively proven secondary peritonitis were enrolled within 96 hours of symptom onset. MAIN OUTCOME MEASURES Procalcitonin and the laboratory routine marker C-reactive protein (CRP) were prospectively assessed and monitored for a maximum of 21 consecutive days. RESULTS Procalcitonin concentrations were most closely correlated with the development of septic multiorgan dysfunction syndrome (MODS), with peak levels occurring early after symptom onset or during the immediate postoperative course. No such correlation was observed for CRP. According to receiver operating characteristic analysis, a procalcitonin value of 10.0 ng/mL or greater on 2 consecutive days was superior to a CRP level of 210 mg/L or greater for predicting septic MODS, with sensitivity, specificity, and positive and negative predictive values of 65%, 92%, 83%, and 81% for procalcitonin and 67%, 58%, 49%, and 74% for CRP, respectively (P&lt;.001). Assessment of septic MODS was already possible on the first 2 postoperative days, with similar sensitivity and specificity. Persisting procalcitonin levels greater than 1.0 ng/mL beyond the first week after disease onset strongly indicated nonsurvival and were significantly better than CRP in assessing overall prognosis (P&lt;.001). CONCLUSIONS Procalcitonin monitoring is a fast and reliable approach to assessing septic MODS and overall prognosis in secondary peritonitis. This single-test marker improves stratification of patients who will develop clinically relevant complications.Arch Surg. 2007;142:134-142--

Acute pancreatitis is associated with substantial alterations of the immunologic host response which has been claimed to promote remote organ dysfunction, septic complications, and mortality. Treatment with immunomodulating substances has been subject of few experimental studies with still conflicting results.

During the last decade, cryosurgery became an interesting alternative in the treatment of nonresectable liver neoplasms. The freeze–thaw procedure, however, may be associated with life-threatening thrombocytopenia due to local platelet trapping, and success of neoplasm ablation may be compromised by inadequate parenchymal cell destruction.

During recent decades, the understanding of the segmental-oriented liver anatomy has enabled development of resection of isolated liver segments or sectors as dictated by the localization and extent of the mass lesion. These newer surgical procedures provide the advantage of maximal preservation of functional parenchyma, therefore minimizing the occurrence of postoperative liver failure and, at the same time, expanding the indications for surgery. We analyzed the results after classical hemihepatectomies and segment-based resections in a consecutive, nonselected patient group. During the 7-year period between November 1993 and November 2000, 270 patients with primary or secondary liver tumors were treated in our hospital; 167 of these patients underwent curative resections and their relevant data were entered into a statistical database. There were 77 classical hemihepatectomies and 90 tissue-preserving resections. Total mortality and morbidity for the series was 3.6% and 29.9%, respectively. Morbidity but not mortality was significantly lower after tissue-preserving resections than after classical hemihepatectomy. Median follow-up was 36 months. Survival was comparable for the two different surgical approaches for patients with secondary liver malignancies. In contrast, patients with hepatocellular carcinomas lived significantly longer after tissue-preserving resections. Tissue-preserving liver resection is a safe technique allowing maximal preservation of functional parenchyma without compromising radicality. Therefore, tissue-preserving resection is especially useful for patients with hepatocellular carcinomas and cirrhosis.

Stage IV circular hypopharyngeal cancer is a disease with poor long-term survival, and the only means of cure—surgery—is associated with high morbidity. All patients admitted with circular hypopharyngeal cancer and extension to the esophagus were enrolled in a multidisciplinary treatment protocol, including circular laryngopharyngoesophagectomy with tracheostomy, neck dissection, and pull-up of a fundus rotation gastric tube that was anastomosed to the oropharynx. Five weeks postoperatively high-dose radiotherapy (60 Gy) was given to the cervical region. Altogether, 18 qualifying patients were explored cervically, were found to have resectable lesions (i.e., without carotid artery infiltration), and were included in the protocol. After laryngopharyngoesophagectomy, an elongated gastric tube was pulled up to the oropharynx. The average distance bridged with the tube was 32±4 cm. No anastomotic leaks were found on postoperative Gastrografin swallow, and oral feeding was started between days 5 and 8. Patients were discharged with normal oral feeding on day 21 (±17 days). Diarrhea, postprandial fullness, and reflux resolved within 6 months postoperatively. Five patients died during the follow-up period of 42 months (range 3–63 months): three due to cardiac events 18 and 38 months postoperatively and two within 12 months with residual disease and tumor recurrence, respectively. The estimated 5-year survival was 60%. We concluded that an aggressive multidisciplinary approach including circular laryngopharyngoesophagectomy, neck dissection, and high-dose radiotherapy ascertains good long-term survival and good functional results in patients with advanced hypopharyngeal cancer when the intestinal continuity is reconstructed with a fundus rotation gastroplasty. En cas de cancer circonférentiel de l’hypopharynx stade IV, la survie est médiocre. Le seul moyen de cure possible, la chirurgie, est grevé d’une morbidité élevée. Tous les patients admis pour cancer circonférentiel de l’hypopharynx avec envahissement de l’œsophage ont été enregistrés dans un protocole de traitement multidisciplinaire, comprenant une laryngopharyngo-oesphagectomie avec trachéostomie, une lymphadénectomie cervicale et une gastroplastie tubulisée au dépens du fundus gastrique anastomosé à l’oropharynx. Cinq semaines après, une radiothérapie à haute dose (de 60 Gy) a été délivrée à la région cervicale. Dix-huit patients remplissant ces conditions ont eu une exploration cervicale et ont été considérés comme potentiellement résecables (c’est-à-dire sans infiltration de l’artère carotide). Après laryngo-pharyngo-esophagectomie, un tube gastrique a été monté à l’oropharynx. La distance moyenne du tube a été de 32±4 cm. Aucune fistule anastomotique n’a été retrouvée sur l’examen postopératoire à la gastrografine et on a pu commencer l’alimentation orale entre les jours postopératoires 5 et 8. Les patients ont pu quitter l’hôpital s’alimentant normalement au jour 21 (±17 jours). En ce qui concerne la morbidité postopératoire, diarrhée, sensation de plénitude postprandiale et reflux se sont résolus en moins de six mois après l’opération. Cinq patients sont décédés pendant la période de suivi de 42 mois (extrêmes 3–63 mois), trois, d’événements cardiaques, 18 et 38 mois postopératoire et deux patients, respectivement, de maladie résiduelle et de récidive tumorale, en moins de 12 mois. La survie à 5 ans a été de 60%. Chez les patients atteints de cancer de l’hypopharynx avancé, une approche multidisciplinaire agressive comprenant une laryngo-pharyngoesophagectomie circulaire, la lymphadénectomie cervicale et la radiothérapie à haute dose, assurent une bonne survie à long terme et de bons résultats fonctionnels lorsque la continuité intestinale est rétablie par une gastroplastie de rotation fundique. El cáncer hipofaríngeo de los pliegues circulares, estadio IV, es una afección con escasa supervivencia a largo plazo y cuya curación, exclusivamente quirúrgica cursa con elevada morbilidad. Todos los pacientes con dicho tipo de cáncer que además, se propaga al esófago, fueron incluidos en un protocolo de tratamiento multidisciplinario consistente en una laringo-faringo-esofagectomía circular con traqueostomía y vaciamiento ganglionar del cuello, anastomosándose un tubo del fundus gástrico rotado a la orofaringe. Transcurridas 5 semanas de la intervención se aplicó sobre la región cervical, radioterapia, a dosis altas: 60 Gy. En 18 pacientes en los que la cervicotomía exploradora demostró la resecabilidad (i.e., sin infiltración de la arteria carótida) se incluyeron en el mencionado protocolo. Tras la laringo-faringoesofagectomía un elongado tubo gástrico se ascendió para anastomosarlo a la orofaringe. La deglución de gastrografin no reveló ninguna dehiscencia anastomótica y la alimentación oral se instauró entre los días 5 y 8 del postoperatorio. Los pacientes fueron dados de alta con alimentación oral normal a los 21 días (±17 días). Diarreas, pesadez postprandial y reflujo desaparecieron a lo largo de los primeros seis meses del postoperatorio. 5 pacientes fallecieron durante el seguimiento, superior a 42 meses (rango 3–63 meses); tres, a los 18 y 38 meses de la intervención por problemas cardiacos; los otros dos murieron antes de 12 meses por enfermedad residual o recidivante. La supervivencia estimada a los 5 años fue del 60%. En pacientes con cáncer hipofaríngeo avanzado un tratamiento agresivo multidisciplinario que incluye no sólo la resección laringo-faringo-esofágica sino también el vaciamiento ganglionar del cuello y radioterapia postoperatoria a dosis altas permite un elevado porcentaje de supervivencia a largo plazo con buenos resultados funcionales, cuando la continuidad del tubo digestivo se restablece con una gastroplastia de rotación fúndica.

Spontaneous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (SP-LCLs) can be easily obtained from latently EBV-infected cancer patients and used as a source of antigen-presenting cells (APCs) for immunotherapy. Using point-mutated (codon 12) p21ras (muRas) as a model tumor antigen, we evaluated the practicability of using genetically modified SP-LCLs as cancer vaccines for patients with pancreatic cancer expressing mutated Ras (muRas). The repeated stimulation of peripheral blood mononuclear cells (PBMCs) from patients with muRas-LCLs elicited a strong, muRas-specific T cell response. A significant cytotoxic activity against EBV virus proteins or components of the expression vector was not observed. The T cells were able to recognize naturally presented muRas, as shown by their cytotoxicity against muRas (Gly-12 to Val-12 or Asp-12)-expressing tumor cells. The T cell response was mainly MHC class I restricted, and peptides containing amino acids 5 to 14 of muRas-Val-12 and muRas-Asp-12 were identified as immunogenic peptides for HLA-A2. In contrast to the situation in patients with putatively muRas-primed T cells, muRas-LCLs were not able to prime naive T lymphocytes from healthy controls. Vaccination of a pancreatic cancer patient with muRas-LCL induced muRas-specific T cells in PBMCs after 4 weeks. We conclude that genetically modified muRas-LCLs can efficiently present tumor antigens to the immune system and induce antigen-specific cytotoxic T cell responses in vitro and in vivo.

Background:Evidence indicates that hyperthermia preconditioning (HP) can be protective in kidney transplantation, possibly through increased heat shock protein (HSP) expression. A detailed study about individual HSPs and functional preservation is lacking, however. Therefore, we studied the effects of HP on kidney graft survival, function and HSP expression. Methods:Male Lewis rats were or were not subjected to whole-body hyperthermia 24 h prior to kidney procurement. Kidneys were stored in UW solution at 4°C for 32, 40 or 45 h. Recipient kidneys were both removed and single isografts transplanted orthotopically. Results:HP strongly induced HSP72 and HSP32 expression. Following 32-hour cold ischemia, most animals survived even without prior HP. However, HP strongly reduced functional impairment induced by cold ischemia. Following 40-hour cold ischemia, kidneys from donors without HP did not recover function and all animals died within 3 days. In contrast, HP-exposed kidneys tolerated 40-hour storage significantly better, with 44% of rats surviving until sacrifice on day 7. In these animals, renal function was still better compared to animals with 32-hour-stored kidneys without HP. Histological alterations were also diminished following HP. Conclusion:Our data show that HP induces renal HSP72 and, for the first time, HSP32. HP increases survival following transplantation and acts by improving several parameters of kidney function including proteinuria, volume output and creatinine clearance.

Abstract In liver preservation, the substitution of the anion Cl by lactobionic acid (LB) prevents reperfusion edema and extends the preservation time for human livers. We studied the effect of compounds that are structurally related to lactobionic acid: anionic polycarbohydrates (sulfated anionic polysaccharide, SAP, and pentosan polysulfate, PPS) on liver function and leukocyte‐endothelial cell interaction in isolated perfusion and liver transplant models. Rat livers, coldstored (24 h) in a Cl ‐containing control solution, became edematous during 1 h of reperfusion. Substitution of Cl‐by either LB, SAP, or PPS decreased reperfusion edema in a Cl‐concentration‐dependent fashion. Reperfusion edema was abolished completely after preservation in 100 mM SAP solution or PPS solution. Also hepatic lactic dehydrogenase (LDH) and aspartate aminotransferase (ASAT) release was lowest after preservation in those solutions. After preservation in LB or anionic polycarbohydrate solutions, portal venous resistance was significantly higher than after preservation in Cl‐‐containing control solution. Capillary blood flow was 391 ± 83 pl/s and 398 ± 174 pl/s after preservation in SAP solution (SAPs) and PPSs, and 803 ± 117 pl/s and 641 ± 219 pl/s after preservation in LB or Cl ‐containing control solution. The number of leukocytes sticking to the vascular wall was lower (P<0.05) after preservation in SAPs or PPSs (109 ± 31 cells/mm2and 108 ± 60 cells/mm2, respectively), when compared with preservation in Cl ‐containing control or LB solutions (429 ± 63 cells/mm2and 277 ± 59 cells/mm2). In rat liver preservation, anionic polysaccharides are antiedematous compounds, with a higher potency than LB and additional antiadhesive properties.

Abstract.: Transient sublethal hyperthermia followed by recovery from heat stress, referred to as heat shock preconditioning, exerts a protective effect on ischemia/reperfusion-induced injury in many systems. This effect is considered to be correlated to heat shock proteins (HSPs) and might be a critical factor in kidney graft function and survival. This study was designed to examine the impact of heat shock preconditioning on kidney isograft function and survival in a model utilizing non-heart-beating (NHB) donors. Four groups of male Lewis rats (n = 10/group) subjected either to whole body hyperthermia (groups A and C) or to sham anesthesia (groups B and D) were allowed 24 h recovery. Thereafter, 20 min of warm ischemia (A/B), and in a separate set of experiments 40 min of warm ischemia (C/D), were induced by suprarenal aortic cross clamping before renal procurement. After 24-h preservation with University of Wisconsin solution at 4 �C, orthotopic kidney transplantations were performed to syngeneic bilaterally nephrectomized recipients. Tissue specimens were taken to determine HO-1/HSP32, 72, and 90 induction by Western blot analysis. Renal function was measured by means of serum creatinine and creatinine clearance on days 0, 3, and 7 as well as urine volume, protein content, and creatinine levels daily. HO-1/HSP32 and HSP72 were found to be expressed constitutively. Moreover, heat shock strongly induced renal HSP72 and HSP32/HO-1, and to a lesser extent HSP90, expression. For recipients of group A grafts, the graft survival rate was 10/10, whereas it was 7/10 (70 %) in recipients of group B grafts (log rank p < 0.05). Following 40 min of warm ischemia, 6/10 (60 %) recipients survived, whereas all sham treated animals died with anuria within 6 days (log rank p = 0.01). Heat shock preconditioning strongly improved graft viability and reduced functional impairment. Creatinine clearance (CRC) on day 3 post Tx was 0.43 � 0.24 ml/min in preconditioned animals (group A) and 0.07 � 0.09 ml/min (p < 0.001) in sham preconditioned (group B), whereas it was 0.91 � 0.33 ml/min and 0.03 � 0.02 ml/min (p < 0.00 001) on day 7 post Tx. Following 40 min NHB time, CRC in survivors of preconditioned graft recipients (group C) was 0.32 � 0.2 ml/min (day 3 post Tx) and 0.23 � 0.08 ml/min (day 7 post Tx) and was significantly better than CRC of group B (p < 0.01 and p < 0.00001, respectively). CRCs prior to NHB procedures were comparable in all animals ranging between 1.31 and 1.72 ml/min. Serum creatinine as well as proteinuria were significantly increased after transplantation in both groups but recovered within 5 days in recipients of preconditioned grafts, whereas kidneys from donors without HP did not recover function. Histological alterations were also diminished following HP. Hyperthermic preconditioning induces strong and long lasting HO-1/HSP32, HSP72, and HSP90 expression in rat kidneys. HP increases survival following transplantation and improves renal graft function including proteinuria, volume output, and creatinine clearance. HSP induction might be used to develop novel approaches in clinical transplantation.

Low flow or no flow is a prefinal step after reperfusion of hepatic allografts. Adenosine is an intrinsic key regulator of physiological and pathological hepatic blood flow.

Background:With the advent of stage-adapted multimodal regimens for many gastrointestinal malignancies, accurate staging has become of utmost importance. In esophageal cancer, endoscopic ultrasonography (EUS) emerged as standard to determine T and N stage. Objective:Since growth patterns of squamous carcinoma (SC) differs from adenocarcinoma (AC) and lymph nodes are located at various distances from the esophagus in a horizontal plane, we studied the accuracy of esophageal EUS as a function of tumor type and localization of the tumor within the esophagus. Results:Overall staging accuracy was 79% for T and for N staging. Staging was more accurate for T3/4, when compared to T1/2 tumors, and for SC when compared to AC. Histological T1/2 stages were overstaged by EUS in 8/17 patients, mostly in patients with AC (6/10). The sensitivity of retrosternal pain and of dysphagia for extramural disease was 57 and 92% respectively, the specificity of pain for extramural disease was 73%, and of dysphagia 36%. Preoperative weight loss in this series correlated linearly with tumor stages. Conclusions:The accurate preoperative staging of T2 esophageal endodermal malignancies is crucial for treatment stratification but difficult to achieve by visual analysis of endosonography alone. Postacquisition processing of echoendosonographic images might further increase the accuracy of echoendosonography and aid in the critical differentiation of T2 versus T3 esophageal malignancies. Preoperative weight loss and retrosternal pain are good clinical indicators of extramural disease.

Abstract: Premalignant lesions of the gastroesophageal junction are treated conservatively or by antireflux surgical procedures. We describe a novel technique that replaces the distal esophagus after resection of the gastroesophageal junction. After resection of the gastroesophageal junction, 16 pigs were divided into two groups. In group 1 (n = 9) the gastroesophageal junction was replaced with a 3 cm wide horizontal gastric corpus tube, pedicled at the lesser curvature. In group 2 (n = 7) the tube was pedicled at the greater curvature. Tube length, volume, and compliance of the gastric remnant and blood flow in the tube (by laser Doppler flowmetry given in perfusion units [PU]) were measured before and after tube formation and 2 weeks postoperatively. Group 1 tubes were 9.5 ±1.5 cm long and group 2 tubes were 8.2 ± 0.7 cm long. Tube formation decreased volume and compliance of the gastric remnant. After tube formation, blood flow at the tip of the tube decreased from 254 PU to 64 ±22 PU (group 1) and 87 ±36 PU (group 2). Volume, compliance, and blood flow returned to baseline values 2 weeks postoperatively. No anastomoric leakage was found on postmortem examination. Horizontal gastric corpus tubes might offer an alternative to replace the distal esophagus and proximal stomach after resection of premalignant lesions of the gastroesophageal junction.

Experimental chronic pancreatitis is associated with microcirculatory disturbances but can also be induced or aggravated by perfusion changes. Microcirculatory alterations in human chronic pancreatitis are poorly defined. In this clinical study we investigated pancreatic microcirculation in the normal human pancreas and in chronic pancreatitis by laser Doppler flowmetry. Laparotomy was performed on 13 patients with nonpancreatic disease and on nine patients with chronic alcoholic pancreatitis for pancreatic head resection. Blood flow was measured over the pancreatic head, the uncinate process, over the mesenteric vein, the pancreatic corpus, and over the pancreatic tail by laser Doppler flowmetry. Blood flow was highest in the head of a normal pancreas with a mean of 436 ± 34 perfusion units (PU), 399 ± 43 PU in the uncinate process, 286 ± 30 PU in the pancreatic corpus, and 351 ±46 PU in the tail of the pancreas. In the normal pancreas, lowest blood flow was measured over the mesenteric vein (228 ± 23 PU). In chronic pancreatitis, blood flow in the pancreas was significantly decreased across the whole pancreas (p <0.01). Furthermore flow-wave pattern was altered in chronic pancreatitis as compared with the normal pancreas. The normal human pancreas has a spatial variation in blood flow, correlating with the pancreatic arterial blood supply. In the chronically inflamed human pancreas, blood flow is significantly diminished, with a lower flow toward the pancreatic head.

Renal transplantation in infants is frequently complicated by graft thrombosis and accelerated rejection reactions. We herein tested the hypothesis that the amount of blood required to sustain normal perfusion of an adult renal allograft transplanted into a pediatric recipient would surpass the cardiac output and aortic blood flow of the recipient and that the ensuing low flow in full-size grafts (FSG) would induce a release of thrombogenic substances.

Abstract: Background: Graft rejection and infection remain major problems following liver transplantation; both are heavily influenced by the immunosuppressive regimen. Despite the disparity in the primary disease leading to transplantation, all patients receive the same post-transplant immunosuppressive treatment in a given center. The aim of this study is to detect a possible effect of the underlying disease on the incidence of early acute rejection episodes after orthotopic liver transplantation (OLT). Patients and Methods: Retrospective analysis on all 101 consecutive liver transplants performed in 95 patients between 1983 and March 1998; five of these patients, surviving less than 30 days, were not included. The immunosuppressive regimen was based on conventional triple therapy during the whole study period. The diagnosis and treatment of acute rejection within the first 30 days post-OLT was uniform throughout the whole study period. Results: Though there were no differences with respect to patients' characteristics [age, child classification, number of HLA-mismatches or cytomegalovirus (CMV)-serocompatibility], patients with primary biliary cirrhosis (PBC) showed a significant increase of acute rejection after OLT compared with the other patients transplanted for other liver diseases (P = 0.024). The incidence of infection was not elevated in patients transplanted for PBC when compared with other diagnoses. Conclusion: Our results indicate that primary liver disease may be a determinant for acute graft rejection in PBC. Furthermore, these results suggest that immunosuppressive regimens based on the underlying disease should be considered.

Abstract. In this experimental study we measured microcirculatory and anatomic differences among a newly developed technique of gastroplasty—fundus rotation gastroplasty (FRG)—and conventional (CG) and reversed (RG) gastric tubes as substitutes for the thoracic and cervical esophagus. After transhiatal esophageal resection, 36 large white pigs were randomly assigned to have an FRG, CG, or RG. Tube length, gastric volume, and compliance as well as blood flow in the tube and the remaining gastric reservoir (by laser Doppler flowmetry) were measured. The FRG tubes were 35.9 ± 3.1 cm long, RG 38.7 ± 3.3 cm, and CG 27.3 ± 2.1 cm (: p < 0.05). Gastric compliance was 20.8 ml in the FRG and 3.2 ml and 2.9 ml in the CG and RG, respectively ( p < 0.001). Blood flow was significantly higher in FRG tubes than in RG tubes or CG tubes, resulting in a lower anastomotic failure rate (2/12 FRG, 6/12 CG, 7/12 RG). Hence a rotation flap of the gastric fundus (FRG) yields a long, well perfused tube by maintaining the blood supply of the gastric lesser curvature. FRG appears to be a good alternative to CG or RG as a substitute for the thoracic and cervical esophagus.

Cyclosporine A (CyA)-induced nephrotoxicity is a well-known complication of this potent immunosuppressive drug. It is caused by an elevation in renovascular resistance and impairment of renal blood flow. Currently, one of the principal experimental settings to assess renal hemodynamics has been using thein vivofluorescent videomicroscopy (IVFV) method on hydronephrotic rat kidneys, which is expensive, time-consuming, not physiological, and not applicable to humans. In the present paper we have been able to confirm our working hypothesis that laser Doppler flowmetry (LDF) is a valuable tool for assessing microcirculatory changes in the rat kidney during CyA administration. Total subcapsular blood flow decreased to approximately 70% of baseline values (P< 0.05) and mean arterial pressure (MAP) increased initially to 113% of baseline values (P< 0.05) compared to only minor changes for cremophor (carrier substance) or no changes for sodium chloride solution 0.9%. LDF provides an easy and rapid technique and its major advantage is the potential use in assessing microcirculatory changes after kidney transplants in humans.

Poor perfusion of the gastric substitute in esopha- geal replacement frequently causes anastomotic break down. In thisin vivostudy we assessed gastric microperfusion before, during, and after gastric tube formation by means of laser Doppler flowmetry in 11 patients undergoing esophagectomy for esophageal cancer. Baseline blood flux along the greater curvature was 323 ± 57, 167 ± 28, and 190 ± 44 perfusion units (PU) and along the lesser curvature 222 ± 44 and 227 ± 46 PU. Blood flux was significantly higher in close proximity to tumor-infiltrated areas (819 ± 172 and 879 ± 119 PU,P< 0.03 andP< 0.008 compared to normal stomach). Dissection of the gastrocolic ligament and the left gastric artery reduced gastric blood flux along the greater curvature to 69 ± 21, 79 ± 19, and 155 ± 61 PU. Elongation and transformation of the stomach to a gastric tube further reduced blood flux in the stomach especially at the fundus. In this study laser Doppler flowmetry was a valuable tool to assess microcirculatory changes during gastric tube formation as well as pathological blood flow in tumor bearing areas of the stomachin vivo.Quantification of the perfusion of gastric tubes in esophageal replacement might help prevent ischemia-induced anastomotic breakdown.

Ischemic colitis is a well known complication following surgery of ruptured abdominal aortic aneurysms, occurring in up to 60% of these patients. It is caused by failure to restore adequate blood flow to the watershed areas of the sigmoid colon. The purpose of this prospective study was to investigate erythrocyte flux to defined areas of the colon immediately after repair of ruptured abdominal aortic aneurysms using laser Doppler flowmetry (LDF) and to determine the critical level of erythrocyte flux below which revascularization of the colon is indicated. A group of 22 patients with a ruptured infrarenal aortic aneurysm in whom the inferior mesenteric artery was ligated at surgery were studied prospectively. Multiple LDF measurements of bowel blood flow (four per bowel segment) were performed on 103 intestinal segments intraoperatively using a Periflux 4001 Master with a PF 415:1 probe. In addition, histologic findings of ischemically injured intestine biopsied at routine postoperative endoscopy or postmortem examination were compared with the LDF records. There was a 41% incidence (9/22 patients) of postoperative colonic ischemia with a significant decrease in colonic erythrocyte flux below 50 perfusion units (PU) intraoperatively in all nine patients (100%). Four patients had transmural colon necrosis, and two patients died, for an overall mortality of 27%. Five patients were identified as having mild or moderate intestinal ischemia and were treated conservatively. Another 14 patients had no clinical or endoscopic signs of ischemic colitis. Erythrocyte flux in those colonic segments were > 50 PU. An intraoperative LDF recording of < 50 PU achieved a sensitivity of 100% (32/32 colon segments) and a positive prediction value of 100% in patients who developed ischemic colitis after surgery for ruptured abdominal aortic aneurysms. The results of this study demonstrate that LDF is a sensitive guide to and feasible method for evaluating critical colonic blood flow during repair of ruptured abdominal aortic aneurysm. The critical level of microvascular perfusion of the colon wall was found to be around 50 PU, below which revascularization of the colon should be considered to reduce the risk of subsequent ischemic colitis.

Activation of the serine proteinase system is an important mechanism that contributes to tissue remodeling. In the present study, we analyzed the expression of urokinase plasminogen activator uPA, urokinase plasminogen activator receptor uPAR, and plasminogen activator inhibitor type 1 PAI1 in samples of chronically rejected human kidneys.

Human bronchi were taken from the lungs of a single asthmatic and 5 nonasthmatic organ donors. The tissues were slowly frozen to -70°C and stored for 1-28 months in liquid nitrogen (-196°C) while suspended in Krebs-Henseleit solution containing 1.8 M dimethyl sulfoxide and 0.1 M sucrose as cryoprotectants. After thawing, bronchial rings were suspended in 10 ml organ baths for isometric tension recording. Spontaneously developed tone (1.13 ± 0.12, n = 22, vs. 0.56 ± 0.07 g, n = 33, p < 0.001) and maximal contractile responses to histamine (1.93 ± 0.12, n = 34, vs. 1.02 ± 0.14 g, n = 30, p < 0.001) were significantly stronger in asthmatic than in nonasthmatic bronchi. The potency of histamine was 4 times less in asthmatic than in nonasthmatic bronchi (p < 0.001). Comparison of the maximal responses to histamine after storage at -196°C for up to 28 months revealed no significant reduction of the contractile function by time of cryostorage. Salbutamol and the potassium channel opener SDZ PCO 400 were 3-4 times less potent in asthmatic than in nonasthmatic bronchi. For antagonism of histamine by ketotifen in asthmatic bronchi (pD'2 = 8.04 ± 0.13, n = 5) 4 times higher concentrations were necessary than in nonasthmatic bronchi (pD'2 = 8.63 ± 0.06, n = 15, p < 0.001). These data support the contention that in spite of a diminished sensitivity to histamine after fatal asthma, isolated bronchi show enhanced spontaneous and agonist-induced contractile responses whereas relaxant responses appear to be impaired.

Only 34 cases of primary cystic duct carcinoma have previously been published in the literature. Most of these cases presented with upper abdominal pain and a palpable mass in the right upper quadrant due to gallbladder hydrops or cholecystitis. We report a case of cystic duct carcinoma with the clinical presentation of obstructive jaundice. The patient was treated by cholecystectomy, resection of the common bile duct and a Roux-en-Y hepaticojejunostomy. An extended lymph node dissection was not performed. Fourteen months after the operation the patient died with local carcinoma recurrence. A literature review comparing clinical signs, surgical treatment, and outcome of 14 Japanese and 21 reported Western cases, including ours, was performed. Extended lymph node dissection in addition to combined resection of the gallbladder and ductus hepaticocholedochus appears to offer a better prognosis and larger survival, including the chance of potential cure.

Mesenteric ischemia following intestinal infarction caused by occlusion of the superior mesenteric artery is a rare and devastating disease. The overall mortality is a high as 80%. The purpose of this prospective study was to investigate erythrocyte flux to defined areas of the intestine immediately after laparotomy by using laser Doppler flowmetry (LDF) assessment. We tried to predict the intestinal viability and recovery of the small bowel, and further tried to define the level of critical perfusion below which intestinal resection is indicated. 13 patients undergoing surgery for acute mesenteric ischemia were prospectively studied. Multiple LDF assessment of bowel blood flow (4 records/segment) were performed on 48 ischemically injured bowel segments intraoperatively. All patients underwent a second-look procedure within 48 h to define the viability of the previously suspicious segments. All 18 resected bowel segments were histologically evaluated for the extent of ischemia. In addition clinical judgement as well as histological findings were compared with the laser Doppler records. There was a 19% (9 of 48) incidence of histologically proven nonviable bowel segments with a significant decrease in intestinal erythrocyte flux below 50 perfusion units intraoperatively in all those patients. But there was a 50% (9 of 18) incidence of nonviable segments among the clinically proven viable and subsequently resected segments, only. Therefore, clinical judgement alone had a overall accuracy of 87% and a predictive value of only 69%, compared to the 100% overall accuracy, sensitivity and predictive values of LDF assessment. The results of this study demonstrate that LDF is a sensitive guide and feasible method to evaluate and define the viability of ischemically injured intestine.

Transforming growth factor-β (TGF-β)signal transduction is mediated via specific cellsurface signaling TGF-β receptors, most notably thetype I ALK5 (TβR-IALK5)and the type II(TβR-II). We evaluated TβR-IALK5andTβR-II expression in 41 human pancreatic cancertissue samples and correlated these findings withclinical data of the patients. Northern blot analysisindicated that, in comparison with the normal pancreas,pancreatic adenocarcinomas exhibited 8.0-fold and4.5-fold increases (P < 0.01), respectively, in mRNAlevels encoding TβR-IALK5andTβR-II. In situ hybridization showed that both TβR-IALK5mRNAwere highly expressed in the majority of pancreaticcancer cells. Immunohistochemical analysis ofTβR-IALK5and TβR-II revealedpositive immunostaining in 73% and 56% of the tumors, respectively. Both receptorswere concomitantly present in 54% of the pancreaticcancer samples. The presence ofTβR-IALK5or TβR-II and theconcomitant presence of TβR-IALK5and TβR-II in the cancer cells was associatedwith advanced tumor stage (P < 0.01). These findingsshow that in many human pancreatic cancers, increasedlevels of the two signaling TβRs are present. The presence of the signaling TβRs inadvanced tumor stages indicates a role in diseaseprogression.

Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-1 might prevent cell–cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes. Int. J. Cancer (Pred. Oncol.) 79:76–81, 1998. © 1998 Wiley-Liss, Inc.

Multimodale Therapieansätze und stadienadaptierte, radikale Resektionsverfahren haben die Kurabilität des Ösophaguskarzinoms deutlich erhöht. In nachfolgendem Artikel werden Vor- und Nachteile der verschiedenen chirurgischen Zugangsverfahren, des Resektionsausmaßes sowie der Ösophagusersatzverfahren dargestellt.