The most significant advances in the management of small-bowel obstruction are developments in imaging modalities available to assist in the diagnosis itself, as well as to possibly assist in the early identification of those cases requiring urgent operative decompression. The most marked of these have been in the use and interpretation of contrast-enhanced CT. This has decreased the use of barium studies and has largely supplanted ultrasound and magnetic resonance imaging in the management of these patients. Diagnostic and therapeutic laparoscopic techniques are also growing in both capability and popularity. Laparoscopic adhesiolysis and the adjuvant of bioresorbable membranes each hold promise but have yet to become established as standard treatment. Further progress is needed in the detection of early, reversible strangulation. As a consequence, the fundamentals of the surgical management of small-bowel obstruction have evolved little over the past 15 years. With our persistent inability to detect reversible ischemia, a substantial risk of progression to irreversible ischemia remains when surgery is delayed, particularly in the setting of suspected complete obstruction.

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4 + T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.

Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H2O2stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC.

The hepatic reticuloendothelial system (RES) is the primary mechanism for removing circulating bacteria from the systemic circulation. While Kupffer cells are important for this process, leukocytes appear to play a significant role as well. Hepatic leukocyte accumulation following ischemia/reperfusion or cytokine stimulation is well documented, but its contribution to phagocytic killing by the hepatic RES is not fully understood. We evaluated the role of leukocytes in general, and leukocyte-endothelial adhesion in particular, in hepatic RES function. This was done by inducing confirmed leukopenia with cyclophosphamide or by blocking leukocyte-endothelial adhesion molecules with specific blocking antibodies. Hepatic phagocytic clearance (HPC) and hepatic phagocytic killing (HKE) of systemically intravenously injected E. coli were assayed and quantitated by a validated dual isotope label technique. HPC among the various experimental groups and respective controls varied only slightly, with no statistically significant differences observed. Leukopenia or CD11b blockade each significantly decreased the HKE relative to the controls. Antibody blockade of certain other adhesion molecules had no significant effect on HKE (or HPC). The role of leukocytes in killing systemically circulating bacteria is an integral component of hepatic RES function. This capability of the leukocyte appears to be dependent, in part, on the adhesion molecule, Mac-1.

Septic complications are common in patients with biliary obstruction. This is thought to be related, in part, to dysfunction of the hepatic reticuloendothelial system (RES). It has been reported that nearly 80% of circulating microorganisms are phagocytosed and killed within the liver and that clearance of circulating pathogens is significantly impaired in patients with jaundice. However, the effect of biliary obstruction specifically on phagocytic killing within the liver is less well described. Therefore this study was designed to quantify the effect of biliary obstruction, simultaneously and discriminately, on two important components of hepatic RES function (phagocytosis and phagocytic killing). Rats were divided into three experimental groups: control, sham, and jaundiced (common bile duct ligation). At 7, 10, 14, and 21days after operation, E. coli labeled with both 125I and 51Cr were injected intravenously. Using the previously validated double-labeled in vivo E. coli technique, hepatic phagocytic clearance (HPC), hepatic killing efficiency (HKE), and net hepatic killing (NHK) were measured. Common bile duct ligation resulted in a significant decrease in the HPC of E. coli 10, 14, and 21days postoperatively. Similarly, HKE was significantly decreased in jaundiced animals by postoperative day 10, but returned to baseline values by day 14. The net effect of these changes in HPC and HKE values were reflected in a significant reduction in NHK in jaundiced animals. Results of the present study suggest that obstructive jaundice impairs both phagocytosis and phagocytic killing within the liver. These findings may help to explain the susceptibility of patients with biliary tract obstruction to the morbidity and mortality of septic complications.

The relationship between hepatic ischemia-reperfusion (I-R) and subsequent injury through neutrophil accumulation is well described. Although alterations in reticuloendothelial system (RES) function (specifically Kupffer cell function) after I-R have been delineated, the degree to which discrete components of RES function (phagocytosis and killing) are independently modulated under these conditions has not been quantified. A hepatic segmental I-R model was established in mice, in which blood supply to the left lateral lobe of the liver was occluded for 45 minutes, the liver was reperfused, and the laparotomy incision was closed. Experimental animals were pretreated with either vinblastin (1.5 mg/kg) to induce neutropenia or anti-P-selectin monoclonal antibody (mAb; 50 μg/mice) 4 days and 5 minutes before ischemia, respectively. We previously reported that after intravenous injection of chromium 51 (51Cr) and iodine 125 (125I) double-labeled Escherichia coli, hepatic 51Cr levels could be used to reliably quantify hepatic phagocytic clearance (HPC) of bacteria from blood, whereas the subsequent release of 125I from the liver accurately paralleled hepatic bacterial killing efficiency (HKE). Using this double-label bacteria clearance assay, HPC and HKE were depressed after I-R, in association with hepatic neutrophil accumulation. Segmental I-R resulted in decreased HPC and HKE activity in both ischemic and nonischemic hepatic lobes. Depressions in HPC and HKE were attenuated by either vinblastin-induced neutropenia or blocking neutrophil adhesion to the hepatic endothelium with anti-P-selectin mAb. These findings support the hypothesis that I-R induces hepatic RES dysfunction, at least in part, through P-selectin-mediated neutrophil accumulation.

Purpose of reviewThe mesenteric hemodynamic response to circulatory shock is substantial and asymmetrical; the vasoconstrictive response disproportionately affects the mesenteric organs. The cardiac output is sustained partially, at no cost in nutrient flow to the mesenteric organs, by vasoconstriction of the mesenteric veins, resulting in the “autotransfusion” of up to 30% of the circulating blood volume into the systemic circulation. Recent findingsHemorrhagic or cardiogenic shock also results in decreased perfusion pressure, prompting selective vasoconstriction of the mesenteric arterioles to maintain perfusion pressure of the vital organs, here at the selective expense of the mesenteric organs. Septic shock may be associated with increased or decreased mesenteric blood flow but is characterized by increased oxygen consumption, exceeding the capability of mesenteric oxygen delivery. SummaryThe response to any of these conditions can, variably and unpredictably, cause hemorrhagic gastric stress erosions, nonocclusive mesenteric ischemia of the small bowel, ischemic colitis, ischemic hepatitis, acalculous cholecystitis, and/or ischemic pancreatitis. Injury to the mesenteric organs can also initiate the systemic inflammatory response syndrome and, consequently, multiple organ failure.

Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical. Nearly 100 years of study has documented the physiologic role of XD in urate catabolism. However, the rapid, posttranslational conversion of XD to the oxidant-generating form XO provides a possible physiologic mechanism for rapid, posttranslational, oxidant-mediated signaling. XO-generated reactive oxygen species (ROS) have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury and multisystem organ failure. More recently, the concept of physiologic signal transduction mediated by ROS has been proposed, and the possibility of XD to XO conversion, with subsequent ROS generation, serving as the trigger of the microvascular inflammatory response in vivo has been hypothesized. This review presents the evidence and basis for this hypothesis.

Surgery 2002;131:601-12.

Chen, Herbert MD, FACS*, **; Doty, John R MD†; Schlossberg, Leon*, †; Bulkley, Gregory B MD, FACS† Author Information

BACKGROUND: The distress imposed on family members of a patient with chronic disease, such as the inflammatory bowel disease, may predispose to mental disorders.Conversely, mental disorders in household members could contribute to stress-triggersd recurrences of the disease.Thus, our hypothesis was that.household-member of patients with inflammatory bowel disease have an increased frequency of mental disorders.AIM: to determine the prevalence of non-psychotic mental disorders in household-members of patients with inflammatory bowel disease.The 12-items version of the General Health Questionnaire (GHG) was administered to a group of 106 subjects from 52 families (53m/53w; mean age of 42 _+ 13 years) who lived with patients with inflammatory bowel disease.The 12-items GHQ is a standard questionnaire that assesses the predisposition to develop psychiatric non-psychotic disorders, and has been previously validated to Spanish.Its sensibility and specificity are 87 % and 91% respectively.The score of the GHQ ranges from 0 to 12 points.A score higher than 2 it is considered suggestive of mental disorder.Prevalence of mental disorders in household-members of patients with inflammatory bowel disease was compared with a previously analyzed unselected reference group of 12.245 controls who live in Catalunya (Gac Sanlt 1998;12:153).RESULTS: Prevalence of mental disorders in the 106 household-members was 39.0 %, whereas in the reference-control group was 17.4 %.In both groups, mental disorders were more prevalent in women (48.9 % in household-women vs 28.3 % in householdmen and 18.6 % in control-women vs 15.7 % in control-men).With regard to age, prevalence of mental disorders was higher (50.1%) in the subgroup of household-members 40 to 60 years old.In household-members younger than 40 years and older to 60 years the frequency of mental disorders was 30.0 %.Prevalence of mental disorders was similar for householdmembers of patients with Crohn's disease and ulcerative colitis (39.4 % vs 39.8% respectively).CONCLUSIONS: Household-members of patients with inflammatory bowel disease have an increased prevalence of non-psychotic mental disorders, specially affecting women and middleage household.These results reinforce the concept that global care of patients with inflammatory bowel disease should also include their household-members.

ABSTRACTChronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47phox−/−mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance ofBurkholderia cepacia, a major pathogen in CGD, was reduced in p47phox−/−mice compared to that in wild-type mice and was further inhibited in p47phox−/−mice by pretreatment with the specific XO inhibitor allopurinol. HepaticB. cepaciaburden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47phox−/−mice. Clearance and killing of intravenousEscherichia coliwas intact in p47phox−/−mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.

Department of Surgery The Johns Hopkins University School of Medicine Baltimore, Maryland Correspondence: Gregory B. Bulkley, MD, Blalock 685, The Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287-4685. Supported by NIH Grant KD 31764. E-mail: [email protected]

Aim: To determine whether fasting serum levels of progastrin, amidated gastrin and glycine-extended gastrin are elevated in patients with colorectal cancer or colorectal polyps compared to controls.Background: It has been shown that fasting serum amidated gastrin levels are elevated in patients with colorectal cancer and decrease after apparently curative resection of the tumor.However, these studies failed to control for H.Pylori infection (a known cause of hypergastrinaemia).When confounding factors which increase serum gastrin levels are taken into account, it has been shown that serum gastrin levels are not elevated in patients with colorectal cancer.These studies have only measured amidated gastrin and not the more immature forms of gastrin.Total gastrin, which includes all unprocessed, partially processed and mature forms of gastrin has been shown to be elevated in patients with colorectal cancer.Methods: This study included 57 patients with colorectal cancer, 29 patients with colorectal polyps and 53 controls.Controls included symptomatic patients who underwent colonoscopy and were found to have normal mucosa or mild diverticular disease.Patients and controls with factors known to raise plasma gastrin levels were excluded from the study.Fasting serum levels of progastrin, amidated gastrin and glycine-extended gastrin were measured by radioimmunoassay.H.Pylori antibodies were measured by ELISA test.Statistical analysis was by Kruskal Wallis test.Results: This study shows that patients with colorectal cancers have elevated median levels of progastrin (27.5 pM) compared to polyps (:515 pM) or controls (:515 pM), (p=O.OOOI).

Post-ischemic hepatic injury is observed commonly following cardiogenic or hypovolemic shock. We evaluated the putative roles of the alpha-adrenergic sympathetic nervous system and the renin-angiotensin axis in the pathogenesis of hepatic injury following cardiogenic shock. Previous studies have characterized the hepatic hemodynamic response to shock, while the relationship of these hemodynamic changes to ischemic hepatic injury has not been defined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrhage) followed by 2 h of resuscitation generated a reproducible model of cardiogenic shock and consequent post-ischemic hepatic injury in anesthetized pigs. In a separate group of pigs, the alpha-adrenergic component of the sympathetic nervous system was ablated with phenoxybenzamine or, in other groups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with teprotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selective splanchnic vasospasm and consequent biochemical and histological evidence of classic post-ischemic liver injury (centrilobular necrosis involving about a third of each hepatic lobule). These manifestations of splanchnic vasospasm and the consequent ischemic injury were not ameliorated by confirmed alpha-adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained cardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings consistent with previous, short-term, hemodynamic studies. The major mediator of this response, and the consequent hepatic injury, is the selective hypersensitivity of the mesenteric vasculature to the renin-angiotensin axis.

The safe performance of a right hepatic lobectomy requires adequate exposure of the hepatic veins and of the suprahepatic vena cava. An extended subcostal or midline incision is commonly used to provide exposure for this operation. The technique for an extended subcostal incision that uses the natural hinge mechanism of the rib cage to provide exposure to the right upper quadrant is described. This approach provides adequate exposure during a difficult hepatectomy, avoiding the need for a thoracotomy or sternotomy.