Patient colon and rectal operative outcomes when treated with immune checkpoint inhibitors.

There is limited data about the safety of colorectal surgery after immune checkpoint inhibitors (ICI). We aimed to share our experience about postoperative outcomes of colorectal surgery for patients treated with ICI. Overall, 31 patients were identified, 22 (71%) underwent elective and nine (29%) underwent emergent/urgent surgery. The 30-day Clavien Dindo class ≥ III complication rates were 27.3% (n = 6) for elective and 55.5% (n = 5) for emergent/urgent cases. Four patients underwent emergency surgery for immune-related colonic perforation and developed postoperative septic shock; two died. Considering patients' comorbidities, cancer stage, and surgical complexity, elective colorectal surgery after ICI seems relatively safe. However, emergent/urgent colorectal surgery was associated with high postoperative morbidity. Indeed, colonic perforation in the setting of ICI treatment has a significant risk of postoperative mortality. Therefore, for patients on ICI with any acute abdominal symptoms, surgical consult should be involved, and colon perforation should be ruled out.

Intraperitoneal Phototherapy Suppresses Inflammatory Reactions in a Surgical Model of Peritonitis.

BACKGROUND: Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS: Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. RESULTS: As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability. CONCLUSIONS: Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.

Gastrointestinal Injury Related to Antiangiogenesis Cancer Therapy.

BACKGROUND: Data on gastrointestinal toxicities related antiangiogenesis cancer therapy is very limited. We aim to describe the clinical, endoscopic, and histologic features and outcomes of antiangiogenesis-associated colitis and diarrhea (ACD) at a tertiary-care cancer center. PATIENTS AND METHODS: We performed a retrospective study of cancer patients who received antiangiogenesis therapy (AAT) and underwent endoscopy for ACD symptoms during 2000-2018. RESULTS: A total of 12,045 patients received AAT during the study period. Of these, 552 patients underwent lower gastrointestinal tract endoscopic evaluation after AAT. Among them, we identified 41 patients who developed ACD. The median time from AAT initiation to ACD onset was 20 weeks. Most patients received bevacizumab (83%). The median duration of ACD symptoms was 6 days. On endoscopy, 7 patients (17%) had mucosal ulceration, and 16 (39%) had nonulcerative inflammation. Active histologic inflammation was evident in 8 patients (20%). Thirteen patients (32%) received treatment for ACD: antibiotics in 5 (12%) and antimotility agents in 11 (27%). Sixteen patients (39%) were hospitalized for ACD, and 2 were admitted to the intensive care unit. One colonic perforation (2%) related to underlying malignancy was reported after colonoscopy. Patients with enterocolitis symptoms had more frequent abnormal endoscopic findings (P = .024) and less frequently received antimotility agents (P = .011) compared to those with diarrhea only. Abnormal endoscopic findings were associated with more hospitalizations (P = .063) compared to normal group. CONCLUSION: ACD is a rare adverse event of AAT and is usually mild. Despite its rarity, complications of ACD can be serious, requiring intensive care unit and surgery. Colonic perforation occurred after routine endoscopy after AAT in 2% of our cohort.

Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report.

Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage).There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered.

Emergency surgery for perforated diverticulitis in the immunosuppressed patient.

AIM: Immunosuppression is believed to worsen outcomes for patients who require surgery for perforated diverticulitis. The aim of this study was to compare surgical outcomes between immunocompromised and immunocompetent patients undergoing surgery for complicated diverticulitis. METHOD: All patients who underwent emergency surgery for complicated diverticulitis between 2004 and 2012 in a single unit were studied. Patients were classified as immunosuppressed (group I) or immunocompetent (group II). Operation type and postoperative morbidity and mortality were compared between groups. The impact of operating surgeons' specialization and the Peritonitis Severity Score (PSS) were also evaluated to determine their impact on the restoration of gastrointestinal (GI) continuity. RESULTS: One-hundred and sixteen patients (mean age: 63.7 years), 41.4% women, were included. Fifty-three (45.7%) patients were immunosuppressed (group I): 42 underwent Hartmann's procedure (HP) (79.2%), nine (17.0%) underwent resection and primary anastomosis (RPA) with ileostomy (IL) and two (3.8%) underwent RPA without IL. In group II, 15 HP (23.8%), nine RPA with IL (14.3%) and 39 RPA without IL (61.9%) were performed. Postoperative morbidity and mortality were 79.2% and 26.4%, respectively, in group I and 63.5% and 6.3%, respectively, in group II. The overall mean PSS was 9.5, with a mean PSS of 11.1 in group I and of 8.1 in group II. The decision to perform a primary anastomosis differed significantly between colorectal surgeons and general surgeons in the patients with a PSS of 9-10-11. CONCLUSION: In immunocompromised patients, RPA with IL can be a safe surgical option, whereas HP should be reserved for patients with a PSS of > 11. Colorectal surgical specialization is associated with higher rates of restoration of GI continuity in patients with perforated diverticulitis, especially in patients with an intermediate PSS score. Evaluation of each patient's PSS facilitates decision making in surgery for perforated diverticulitis.

Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants.

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment of neutrophils in abdominal sepsis.

We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP). Lung levels of myeloperoxidase (MPO) and histological tissue damage were determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1 expression and F-actin formation were also determined in isolated neutrophils up to 3h after stimulation with CXCL2. Labeled and activated neutrophils co-incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively transferred to CLP mice. Y-27632 reduced the CLP-induced pulmonary injury and MPO activity as well as Mac-1 on neutrophils. Neutrophil F-actin formation peaked at 6h and returned to baseline levels 24h after CLP induction. Rho-kinase inhibition decreased CLP-provoked F-actin formation in neutrophils. CXCL2 rapidly increased Mac-1 expression and F-actin formation in neutrophils. Co-incubation with Y-27632 abolished CXCL2-induced Mac-1 up-regulation and formation of F-actin in neutrophils. Notably, co-incubation with cytochalasin B inhibited formation of F-actin but did not reduce Mac-1 expression on activated neutrophils. Adoptive transfer experiments revealed that co-incubation of neutrophils with the anti-Mac-1 antibody or cytochalasin B significantly decreased pulmonary accumulation of neutrophils in septic mice. Our data show that targeting Rho-kinase effectively reduces neutrophil recruitment and tissue damage in abdominal sepsis. Moreover, these findings demonstrate that Rho-kinase-dependent neutrophil accumulation in septic lung injury is regulated by both adhesive and mechanical mechanisms.

IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.

Immunoblot analysis of sera in uncomplicated typhoid fever & with typhoid ileal perforation.

BACKGROUND & OBJECTIVE: Ileal perforation is a serious complication of typhoid fever. The exact reasons for the development of perforation in only a few of those infected with Salmonella Typhi is unknown, and it is likely that immunological factors are involved. Therefore we undertook this study to compare the antibody profile in patients with uncomplicated typhoid fever with those having ileal perforation by immunoblotting. METHODS: Two groups of patients were included in the study. Group II comprised patients with uncomplicated typhoid fever (n=47), and group I with typhoid ileal perforation (n=33). The flagellar (H), lipopolysaccharide (LPS) and outer membrane protein (OMP) antigens of Salmonella Typhi were extracted and used to test patient sera for antibodies by immunoblotting RESULTS: Immunoblotting using S. Typhi antigens enabled the detection of S. Typhi antibodies in the two groups of patients. A significant difference was seen in the response of these two groups of patients with respect to antibodies to flagella, lipopolysaccharide and outer membrane proteins. Antibodies to flagella were more pronounced among patients with uncomplicated typhoid fever, while anti-OMP antibodies were significantly associated with typhoid ileal perforation. INTERPRETATION & CONCLUSION: A comparison of antibodies in patients with uncomplicated typhoid fever and with ileal perforation revealed the differences in the antibody profiles of the two groups. Our study suggests that the difference in antibody response may in some way play a role in the pathogenesis of typhoid ileal perforation which can also potentially be exploited to develop suitable diagnostic tests.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

Severe proctitis, perforation, and fatal rectal bleeding secondary to cytomegalovirus in an immunocompetent patient: report of a case.

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in immunocompromised patients. In immunocompetent individuals, the infection is usually subclinical but it can sometimes be life threatening. We describe a case of fatal CMV proctitis in a 71-year-old man following an Ivor-Lewis esophagectomy. After surgery he developed renal failure, methicillin-resistant Staphylococcus aureus pneumonia, and acute respiratory distress syndrome. He recovered but developed melena and massive fresh rectal bleeding. Sigmoidoscopy revealed severe proctitis and a biopsy was consistent with ischemia. Despite undergoing a proctectomy he continued to bleed and died despite every effort. The final histological examination of the rectum revealed a CMV infection.

The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis.

BACKGROUND: The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the "cholinergic inflammatory pathway." Through stimulation of the acetylcholine receptors located upon the macrophages, the "unspecific" immune system can be directly influenced. METHODS: The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. RESULTS: After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. CONCLUSION: The vagal nerve is therefore an important modulator of the immune system.

Laparoscopic bowel injury in an animal model: monocyte migration and apoptosis.

BACKGROUND: Unrecognized laparoscopic bowel injury has a delayed and covert presentation. Differences in monocyte migration and apoptosis between laparoscopic and open bowel injury were determined. METHODS: For this study, 24 rabbits were divided into laparoscopic (n = 9) and open surgical (n = 9) bowel injury groups and a control group (n = 6) without bowel injury. Bowel injury was created using monopolar electrocautery. The animals were killed 1 day, 1 week, and 2 weeks after surgery. Monocyte migration assay was performed across a modified Boyden chamber. Apoptosis was assessed by DNA fluorescent stain H-33342. RESULTS: In laparoscopy, monocyte apoptosis was decreased (p < 0.001), and migration was increased (p < 0.05), as compared with the open group. Apoptosis increased over time in both study groups, and was higher than in the control group (p < 0.001). Migration was decreased in both study groups as compared with the control group (p < 0.05) CONCLUSIONS: These results suggest decreased immune system priming with laparoscopic bowel injury, which may contribute to the masking of relevant signs and symptoms of peritonitis.

Peritoneal and systemic inflammatory mediators of laparoscopic bowel injury in a rabbit model.

PURPOSE: Unrecognized bowel injury following laparoscopy has a subtle and delayed clinical presentation compared with that after open surgery. We determined peritoneal and systemic immune function in laparoscopic and open bowel injury cases. We propose that laparoscopy does not activate immune responses to the same extent as open surgery. MATERIALS AND METHODS: A total of 40 rabbits were divided into 4 groups. Two study groups were subjected to laparoscopic and open bowel injury, and 2 control groups underwent pneumoperitoneum and sham open surgery, respectively, without bowel injury. Animals were sacrificed 1 day, 3 days and 1 week postoperatively. Macroscopic and histological findings were analyzed. Peritoneal fluid, systemic white blood count (WBC) and differentials were done with a hemocytometer. Peritoneal fluid and serum interleukin (IL)-8 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Macroscopic and histological findings were indistinguishable in the 2 study groups. However, study groups demonstrated higher peritoneal WBCs than their respective controls at 1 and 3 days (p <0.05). Peritoneal WBC was lower in the laparoscopy than in the open study group at 3 days (p <0.05). There was a significant decrease in peritoneal lymphocytes and monocytes in the laparoscopic vs the open study group at 3 days. No differences were found in systemic WBC or differentials among all groups. Peritoneal IL-8 concentrations were higher in the laparoscopic bowel injury than in the laparoscopic control group at 1 and 3 days (p <0.05). However, there were no differences in peritoneal or serum IL-8 concentrations between both study groups. CONCLUSIONS: Laparoscopic surgery seems to be unable to sustain peritoneal immune responses, which may mask reliable clinical signs and symptoms of peritonitis associated with bowel injury.

[The pathogenesis of the systemic inflammatory response syndrome and compensatory antiinflammatory response syndrome following surgical stress].

The inflammation charge cells such as the macrophages, neutrophils, endothelial cells, and fibroblasts are activated in surgical sites when tissue injury occurs due to the operation. Proinflammatory cytokines such as tumor necrosis factor alpha, interleukin (IL)-1, IL-6, and IL-8 are induced from the activated inflammation charge cells. These cytokines amplify the information by autocrine and paracrine action, induce the production of other cytokines, and send the information to the whole body. Increases in body temperature, pulse rate, and leukocyte counts are then observed. This condition is called the systemic inflammatory response syndrome (SIRS) clinically. On the other hand, the production of antiinflammatory cytokines against SIRS is induced simultaneously. The condition in which antiinflammatory cytokines are produced in excess and become dominant systemically is called the compensatory antiinflammatory response syndrome (CARS). No standard concrete diagnosis for CARS has been established, although CARS is a pathogenetic concept. However, recently the analysis of cytokine production and various types of surface molecules in the inflammation charge cells became possible with the development of molecular biological methods. As a result, it was found that the immune system is controlled by the balance between proinflammatory and antiinflammatory cytokine production, and if the compensatory antiinflammatory reaction is sufficiently severe, it will manifest clinically as anergy, with increased susceptibility to infection. In this manuscript, we explain the pathogenesis of SIRS and CARS following surgical stress by analyzing cytokine production and surface membrane molecules in the inflammation charge cells.

Immune response to laparoscopic bowel injury.

BACKGROUND AND PURPOSE: Laparoscopic bowel injuries are rare but potentially fatal if recognition is delayed. Unlike the situation after open surgery, patients with unrecognized bowel injury after laparoscopy do not present with the typical "acute surgical abdomen." We investigated monocyte, neutrophil, and lymphocyte apoptosis as indicators of the immune response and whether this response is stimulated or suppressed by laparoscopic bowel injury compared with bowel injury induced during open surgery. MATERIALS AND METHODS: After an animal protocol was approved, laparoscopy was performed in a rabbit model. A total of 44 animals were divided into four groups of 11 rabbits each. Laparoscopic bowel injury was created using 30-W electrocautery at 0 (control), 1, and 5 hours after induction of pneumoperitoneum. Bowel injury was created in the fourth group during open laparotomy. Animals were euthanized at 0, 1 day, 1 week, or 2 weeks after surgery. Apoptosis was assessed by staining the nuclei of blood cells with H-33342 dye. RESULTS: At 1 week, neutrophil, monocyte, and lymphocyte apoptosis levels were 2.4- to 5-fold lower after laparoscopy (1-hour pneumoperitoneum) compared with open surgery. However, at 2 weeks, the percentage of apoptosis had equalized in the two groups. Interestingly, with longer laparoscopic procedures (5 hours), the percentage of apoptosis at 0 and 1 day more closely approached that seen after open surgery. At 2 weeks, there was a significant difference in apoptosis levels in all cell types between the experimental groups compared with controls (P < 0.001). No animals undergoing a 5-hour open procedure survived to 2 weeks after bowel injury. CONCLUSIONS: Open surgery resulted in a significant increase in programmed cell death compared with controls in the immediate postoperative period following bowel injury. Laparoscopic surgery produced a delayed response and after 2 weeks with bowel perforation approached open surgery levels. The difference in the degree of cellular death may be secondary to a smaller degree of stimulation of the immune response in laparoscopic surgery.

Perforation of toxic megacolon in non-typhoid Salmonella enterocolitis spares young infants and is immune-mediated.

Intestinal perforation, a life-threatening complication of toxic megacolon (TM) following non-typhoid Salmonella infection, is relatively uncommon in infants less than 1 year of age. The situation, also found in typhoid fever, appears to be cytokine-mediated. This finding may justify immunotherapy for older children with TM associated with non-typhoid Salmonella infection in order to prevent this complication.

Anti-interleukin-8 autoantibodies in patients at risk for acute respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that elevated concentrations of interleukin-8 associated with anti-interleukin-8 autoantibodies (anti-interleukin-8:interleukin-8 complexes) are found in patients at risk for acute respiratory distress syndrome who developed the disease. DESIGN: Measurement of anti-interleukin-8:interleukin-8 complex concentrations in previously collected bronchoalveolar lavage fluids. These fluids were obtained from patients at risk for acute respiratory distress syndrome who subsequently either recovered or developed acute respiratory distress syndrome. PATIENTS: A unique population of patients at risk for acute respiratory distress syndrome was studied. There were 26 patients at risk for acute respiratory distress syndrome who were divided into three groups. Group I patients had high interleukin-8 concentrations and developed acute respiratory distress syndrome, group II had high interleukin-8 concentrations and did not develop acute respiratory distress syndrome, and group III had low interleukin-8 concentrations and did not develop acute respiratory distress syndrome. These patients were selected to test the hypothesis that presence of elevated concentrations of anti-interleukin-8:interleukin-8 complexes differentiates patients at risk for acute respiratory distress syndrome who developed acute respiratory distress syndrome from patients who did not. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid concentrations of interleukin-8 associated with the anti-interleukin-8 autoantibodies were significantly different between groups (p <.03). The amount of interleukin-8 bound to the anti-interleukin-8 autoantibody was higher in group I than in group II and group III. CONCLUSIONS: Bronchoalveolar lavage fluid concentration of anti-interleukin-8:interleukin-8 complexes may serve as a marker of disease progression in patients at risk for acute respiratory distress syndrome.