Inflammation affects sufentanil consumption in ulcerative colitis.

BACKGROUND: Previous studies have demonstrated an increased perioperative opioid requirement during inflammatory disease. To evaluate the influence of the inflammatory process, we studied in the same patient the sufentanil requirement during procedures that occur during two distinct phases of ulcerative colitis with different inflammatory profiles: (1) left colectomy for major colitis unresponsive to medical treatment during acute inflammation and (2) coloprotectomy with ileoanal anastomosis, three months after recovery of the acute inflammatory episode. METHODS: Sixteen patients with clinical and histological evidence of ulcerative colitis scheduled for colectomy with ileoanal anastomosis were included. For each surgical procedure, anaesthesia was induced with sufentanil 0.5 microg kg(-1) and propofol 2 mg kg(-1). Patients were ventilated with 50% nitrous oxide and oxygen, and tidal volume was adjusted to keep end-tidal CO2 at 30 mmHg. Anaesthesia was maintained with end-tidal isoflurane at 0.5%. Analgesia was achieved with continuous infusion of sufentanil at 0.3 microg kg(-1) h(-1). Additional boluses of sufentanil and increases in infusion rates were used when haemodynamic variables increased to more than 20% of preoperative values. Sufentanil consumption during surgery was analysed by Wilcoxon signed rank sum test. P < 0.05 was considered significant. RESULTS: Total intra-operative sufentanil requirement was significantly larger during colectomy performed for acute inflammatory colitis than during ileoanal anastomosis performed after the inflammatory process (1.24 +/- 0.48 microg kg(-1) h(-1) vs. 0.62 +/- 0.3 microg kg(-1) h(-1); P < 0.05). CONCLUSION: For the same patient, inflammatory status influences opioid requirements during surgery for ulcerative colitis.

[Severe blunt liver injury: reappraisal of criteria for nonoperative management decision. Experience with 88 cases]. / Traumatismes graves fermés du foie: à la recherche de critères décisionnels pour le choix du traitement non-opératoire. A propos d'une série de 88 cas.

AIM OF THE STUDY: To analyze the predictive value of computed tomography (CT) and initial physiologic and laboratory data findings in the immediate operative (OP) or non-operative (NOP) management of blunt liver injury (BL). METHODS: Eighty-eight BL, grade III (51), grade IV (28) and nine grade V (9), aged 26.2 years (16-75) were identified. Hemoperitoneum on CT, hemodynamic status, physiologic and laboratory data <24 hours or preoperative (transfusion, vascular filling) and follow-up >48 hours were analyzed. RESULTS: Data of 71/88 (80%) NOP and 17/88 (20%) OP patients were reviewed. A secondary laparotomy or laparoscopy was necessary in 11/71 TNO. Six OP (35%) and 1 NOP patients died. Blood units transfused were 1.33 (0-10) vs 5.9 (0-22) and vascular filling 1.45 (0.5-5.5) vs 3.6L (2-12) (P<10(-6), P<4.10(-3) respectively). NOP patients had less severe hemoperitoneum (31 vs 94%, P<10(-5)) and hemodynamic instability (8.5 vs 94%, P<10(-4)). But, there was an overlap of values of blood units transfused, amount of vascular filling and initial haemoglobin levels between NOP and OP patients and among CT grades of liver injury. No cut-off values could be determined: 33% NOP received >4 blood units and >3 L vascular filling; 30% had severe hemoperitoneum. In OP group 23.5% patients had lower values and no severe hemoperitoneum. CONCLUSION: In the management of BL, vascular filling and blood transfusion increased with the grade of CT liver injury and were globally more elevated in the operative group but did not individually correlate with hemodynamic stability and did not authorize, by themselves, to decide between operative versus non-operative management.

Inflammation increases sufentanil requirements during surgery for inflammatory bowel diseases.

BACKGROUND AND OBJECTIVE: Inflammation promotes hyperalgesia and increases opioid binding protein (alpha1-acid glycoprotein) inducing increased opioid requirement. To investigate the influence of an acute episode of inflammatory bowel disease in opioid requirement during major abdominal surgery, 17 patients with Crohn's disease, 12 patients with ulcerative colitis and seven patients without any inflammatory process (control group) were prospectively studied. Sufentanil requirements were assessed during surgery. METHODS: Sufentanil administration was adjusted when haemodynamic variables changed more than 20% of preoperative values. In a subgroup of 20 patients (Crohn's disease: 7, ulcerative colitis: 7, control group: 6), plasma concentrations of alpha1-acid glycoprotein and unbound sufentanil were measured. Total plasma clearance of sufentanil was also determined. Data presented as median (25-75 per thousand) were analysed by non-parametric and ANOVA tests. RESULTS: Despite similar surgery duration, intraoperative sufentanil requirements were significantly larger in both the Crohn's disease group (0.9 (0.6-1.6) microg kg(-1) h(-1)) and the ulcerative colitis group (1.1 (0.6-1.7) microg kg(-1) h(-1)) than in the control group (0.5 (0.4-0.5) microg kg(-1) h(-1)). Total plasma clearance of sufentanil was larger in patients with inflammatory bowel disease than in the control group. The plasma alpha1-acid glycoprotein concentration was increased in the inflammatory bowel disease group. However, the free fraction of sufentanil was similar in all three groups. The largest sufentanil consumption in patients with inflammatory bowel disease was observed during time of pain stimulation in the area of referred hyperalgesia from the affected viscus. In the control group, the sufentanil requirement was constant throughout surgery. CONCLUSION: Inflammatory bowel disease increases opioid requirement during major abdominal surgery.

[Management of duodenal adenomatosis in patients with familial adenomatous polyposis]. / Prise en charge et traitement de l'adénomatose duodénale de la polypose adénomateuse familiale.

AIM OF THE STUDY: To review our global management of duodenal adenomas in patients with familial adenomatous polyposis and report the results of different therapeutic approaches. To present the outcome and possible sequels of pancreaticoduodenectomy. PATIENTS AND METHODS: We identified five cases of duodenal adenomas in patients with familial adenomatous polyposis over a period of 10 years (1992-2001), we followed the progression of their Spigelman score. Results of conservative and surgical treatment were collected. RESULTS: Duodenal adenomas were discovered 5-33 years after the first operation for colonic polyposis. The score of Spigelman was as follows: 2, stage 2; 3, stage 3; 1, stage 4. Endoscopic laser therapy followed by Sulindac prescription was proposed in three cases, with only one success. Duodenopancreatectomy was performed in four patients: once the diagnosis of adenoma was made in one patient, due to Spigelman stage 4 with severe dysplasia, because development of intramucosal carcinoma under surveillance in one patient, and after failure or complication of conservative treatment in two others. Worsening of Spigelman score was observed in two out of four patients submitted to conservative therapy. Correlation between Spigelman score and final examination of the specimen was correct in two cases. There was neither significant morbidity nor long-term nutritional sequel after pancreaticoduodenectomy. CONCLUSION: Duodenal adenomas may recur or progress into malignant degeneration under conservative treatment. The pancreaticoduodenectomy is an acceptable solution for stage 4 of Spigelman, especially when severe dysplasia is present.

[Gastric conservation in severe caustic lesions of the digestive tract: is it legitimate?]. / Conservation gastrique dans les lésions caustiques sévères du tube digestif: est-elle légitime?

OBJECTIVE: To evaluate advantages and drawbacks of a controlled conservative management of patients with severe gastric caustic injuries. METHODS: Among 40 patients with severe caustic gastric burns (> IIb), 28 with stade III lesions (mosaic necrosis: n = 10, extensive or circumferential necrosis: n = 18) were managed prospectively from 1990 to 1998. Twenty-two patients had associated stage III oesophageal lesions and 6 had stage III duodenal lesions. All patients were followed up by daily surgical examination. Total gastrectomy with esophageal exclusion or stripping was performed in case of perforation. RESULTS: Five immediate and 7 secondary total gastrectomies, two associated esophagectomies and two jejunal resections were performed. Mortality rate was 18% (5/28). Sixteen gastric preservations (60%) were achieved, including 7 complete and 9 partial because of gastric stricture. Eighteen esophagoplasties for oesophageal strictures or after gastrectomy were performed without mortality. CONCLUSION: Stage III caustic injuries of the stomach, when they are not immediately life-threatening, do not systematically require total gastrectomy. A strict conservative attitude can be done with significant morbidity and acceptable mortality and significantly raises the numbers of preserved stomach.

Prolongation of cardiac allograft survival by selective injection of donor liver leukocytes in non-immunosuppressed rats.

Liver grafts are spontaneously accepted in several animal combinations and are able to induce acceptance of another organ originating from the same donor, which would be rejected when transplanted alone. However, the exact mechanism of this unique tolerance induction capability remains unclear. The aim of our study was to investigate the ability of nonparenchymal liver cells to induce tolerance when they were separated from their parenchymal environment. In the murine combination we used (BN --> LEW), heart transplants were constantly tolerated after combined liver plus heart grafting, but rejected when transplanted alone. Nonparenchymal liver cells were isolated from BN rat livers by enzymatic digestion and injected, at different times, to LEW rats, which were recipients of BN heart transplants. The average number of mononuclear cells obtained after isolation was 20 x 10(6)/5 g of rat liver. Immediate trypan-blue exclusion test showed more than 95% of viable cells. Phenotypic studies showed a predominant (47%) lymphocyte population, 7% were monocytes and 46% were cellular debris. Among the lymphocyte population, the majority of cells were bearing the NKR-P1 receptor and about 30% CD3 receptors. Inoculation of nonparenchymal liver cells 7 and 30 days prior to heart transplantation significantly prolonged graft survival compared to controls (14.6 and 12.7 vs. 8.1 days; p = 0.0008 and 0.0059, respectively), whereas simultaneous injection (day 0) had no effect. Injection of donor splenocytes or nonparenchymal liver cells from a third party, at any time, had no effect on rejection. These results provide some more evidence about the specific role of liver lymphocytes in allogenic unresponsiveness. They also suggest that the hepatic parenchymal environment is necessary for the optimal development of this phenomenon.

Enhanced production of IL-8 in chronic but not in early ileal lesions of Crohn's disease (CD).

Distinct Th1/Th2 patterns have been observed during the evolution of CD. The aim of this study was to compare neutrophil involvement and IL-8 mRNA and protein expression during early recurrent lesions and chronic phases of CD. Twenty-nine patients with CD having ileocolonic resection with anastomosis were studied. Biopsies were obtained during surgery from the non-inflamed ileal mucosa and from chronic ileal lesions. Endoscopic ileal biopsies were also taken from early recurrent ileal lesions occurring 3 months after surgery. Neutrophil counts were performed and mucosal IL-8 levels were evaluated by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry. Early recurrent ileal lesions were characterized by low neutrophil counts and IL-8 production at the mRNA and protein levels compared with the ileal chronic lesions. The main cellular sources of IL-8 in the early recurrent lesions were neutrophils, while in chronic lesions the majority of IL-8-stained cells were CD3+ T cells and macrophages. These results confirmed that the nature of the inflammatory infiltrate and the expression of cytokine profiles may differ between the acute and chronic phases of CD.

Impaired contractile response of mesenteric arteries in Crohn's disease.

BACKGROUND: Crohn's disease is associated with vascular injury and dysregulation of the intestinal immune system which together can provide disturbance of mesenteric circulation functional properties. AIM: To evaluate the vascular reactivity of mesenteric arteries from patients with Crohn's disease. METHODS: Phenylephrine-induced contractions were assessed from 10 patients with Crohn's disease and 8 control organ donors. NG-nitro-L-arginine-methyl-ester (L-NAME) was used to test the presence of inducible NO synthase. Endothelium dependent and independent relaxation was assessed using acetylcholine, bradykinin, calcium ionophore A23187 and sodium nitroprusside. RESULTS: The contractile response to phenylephrine was significantly decreased in arteries without endothelium from patients with Crohn's disease. Exposure to the NO synthase inhibitor L-NAME restored the contractile response to phenylephrine. Relaxation remained unaltered in both groups. CONCLUSION: These data provide direct evidence for fading of contraction caused by phenylephrine in Crohn's disease. The restored mesenteric artery tone by a specific NO synthase inhibitor suggests that an increased production for NO in vascular smooth muscle might be responsible of this altered vascular reactivity.

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10.

BACKGROUND: Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil recruitment and is down-regulated by IL-10. AIM: To look for an imbalance between IL-8 and IL-10 in patients with pouchitis. PATIENTS/METHODS: 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of > or =7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction. RESULTS: IL-8, IL-10, and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01). CONCLUSION: Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for pouchitis.

[Malignant mesenchymoma of mesentery. A controversial entity]. / Mésenchymome malin du mésentère. Une entité controversée.

We report a case of malignant mesenchymoma developed in the mesentery in a 62-year-old man with no past history. It was an huge mass in the mesentery of the ileum. The tumor was composed of areas of chondrosarcoma and rhabdomyosarcoma in addition to an undifferentiated fusiform component. Malignant mesenchymoma is a rare sarcoma occurring preferentially in the retroperitoneum or the thigh. The location in the mesentery is exceptional. Malignant mesenchymoma is discussed more particularly with dedifferentiated liposarcoma with heterologous elements. The patient is alive without recurrence three years after surgery.

Acute inflammatory intestinal vascular lesions and in situ abnormalities of the plasminogen activation system in Crohn's disease.

OBJECTIVES: The distribution of the intestinal vascular lesions and their relation with the fibrinolysis process are poorly known in Crohn's disease (CD). The mediators of the plasminogen activator system, namely urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1), are a key complex involved in fibrinolysis. The aims of this study were: (1) to further define vascular lesions and their distribution in the intestine; and (2) to study concomitantly the qualitative in situ expression and the levels of u-PA, t-PA and PAI-1 in the ileum of patients with CD. PATIENTS AND METHODS: Histological, immunohistochemical and ultrastructural studies of vascular lesions in the resected ileum of 27 patients with CD were performed and compared with 36 control patients. Levels of u-PA, t-PA and PAI-1 measured by ELISA methods were compared in healthy and inflamed ileal tissues of 17 patients with CD. RESULTS: Acute vascular lesions involving mainly serosal venules and capillaries were present in 63% of patients with CD vs 3/36 controls and were associated with PAI-1 expression. They were prominent on the mesenteric border beneath macroscopically normal mucosa. In contrast, chronic vascular lesions were present in all layers beneath mucosal ulcerations, where a significant increase of PAI-1 levels was found. CONCLUSIONS: These results suggest that vascular involvement associated with abnormalities of PAI-1 expression is an early and widespread event in CD. Their prominence on the mesenteric border might explain the characteristic location of CD ulceration along the mesenteric margin.

[Excluded rectum during Crohn's diseases: what is the risk of dysplasia?]. / Rectums exclus au cours de la maladie de Crohn: quel est le risque de dysplasie?

OBJECTIVES: An excluded rectum may be at risk of carcinoma in the course of Crohn's disease. Surveillance of patients requires detection of dysplasia. The aim of our study was to determine the frequency of dysplasia from secondary proctectomy specimens in active rectal Crohn's disease. METHODS: Twenty three patients (13 women and 10 men, median age 38 years) were studied. The median duration of rectal exclusion was four years. Detection of dysplasia relied upon histopathology. Immunohistochemistry with MIB-1 (Ki-67) and anti-p53 (clone DO7) antibodies was performed as well. RESULTS: Frequency of dysplasia was 30%. This was low grade dysplasia, focally observed in proctectomy specimens. MIB-1 was positive on 46% of dysplastic cells. There was no expression of p53 protein. CONCLUSIONS: These results must be taken into account for decision of secondary proctectomy, in patients having an excluded rectum for Crohn's disease, when ileorectal anastomosis is not possible. Rectal endoscopic surveillance is advisable with multiple biopsies according to focal distribution of dysplasia.

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease.

BACKGROUND & AIMS: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS: These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.

Abnormalities in mucin gene expression in Crohn's disease.

Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.

[Laparoscopic ileo-colic resection in Crohn's disease]. / Résection iléo-colique coelio-assistée pour maladie de Crohn.

UNLABELLED: The objective was to evaluate the reliability and safety of laparoscopic ileocolic resection for Crohn's disease. PATIENTS AND METHODS: From June 1995 to February 1999, 40 patients underwent a laparoscopic ileocolic resection for Crohn's disease. Fistulizing disease, phlegmons and patients with previous laparotomy were excluded. Early morbidity, postoperative comfort and clinical recurrence were rates evaluated. RESULTS: No intra-operative incident or conversion occurred. Mean operating time was 163 min. Complications occurred in three patients: 1 pelvic hematoma with super-infection, 1 protracted ileus (7 days), 1 venous thrombosis. Opiate analgesics were used for a mean period of 3.1 days. Delay before bowel movements was 3.2 days. Post-operative hospital stay was 8 days. Mean size of the wound was 4.1 cm. Twelve patients (30%) developed long-term clinical recurrence; the mean disease-free interval was 10 months. No patient required secondary re-operation. CONCLUSION: Laparoscopic ileocolic resection was reliable and safe in the treatment of Crohn's ileal strictures. The possible role of this method in the treatment of fistulizing disease or recurrence has to be evaluated.