Martin Hiele

Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test

BACKGROUND The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. METHODS A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. RESULTS There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. CONCLUSIONS It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.

Controlled trial of metronidazole treatment for prevention of crohn's recurrence after ileal resection☆

BACKGROUND/AIMS New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohns ileitis. A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection. METHODS Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery. Thirty patients received metronidazole (20 mg/kg body wt) daily for 3 months, and 30 patients received placebo. Treatment was then discontinued. Nine patients dropped out during treatment, 7 in the metronidazole group and 2 in the placebo arm. RESULTS At 12 weeks, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients (52%) in the metronidazole group (P = 0.09). The incidence of severe endoscopic recurrence was significantly reduced by metronidazole (3 of 23; 13%) as compared with placebo (12 of 28; 43%; P = 0.02). Patients in the metronidazole arm had more frequent side effects. Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year (4% vs. 25%). Reductions at 2 years (26% vs. 43%) and 3 years (30% vs. 50%) were not significant. CONCLUSIONS Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohns disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence.

Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum

Aphthous lesions recur in the neoterminal ileum within the first few months after curative resection of the distal ileum in patients with Crohns disease. These lesions do not originate from microscopic disease that is already present at the time of surgery. To investigate the importance of faecal stream in the pathogenesis of recurrent Crohns lesions, we have studied 5 patients with Crohns disease who had ileal resection. After curative resection and ileocolonic anastomosis, a diverting terminal ileostomy was constructed 25-35 cm proximal to the anastomosis thereby excluding the neoterminal ileum, the anastomosis, and the colon from intestinal transit. After six months of exclusion, endoscopy of the ileocolon was undertaken and biopsy specimens were taken. Transit was then restored. Six months after reanastomosis further biopsy specimens were taken. These patients were compared with a control group of 75 patients with Crohns disease who underwent a one-step ileal resection and ileocolonic anastomosis. None of the 5 patients had endoscopic lesions in the neoterminal ileum after six months of exclusion and biopsies did not show inflammatory changes characteristic of Crohns disease. By contrast, 53 of 75 patients with one-step surgery had endoscopic recurrence in the neoterminal ileum within six months of surgery. All 5 patients had an important recurrence of disease, both endoscopically and histologically, at ileocolonoscopy six months after reanastomosis. Our findings strongly support the view that recurrence of Crohns disease in the neoterminal ileum after curative ileal resection is dependent on faecal stream.

Utility of Positron Emission Tomography for the Staging of Patients With Potentially Operable Esophageal Carcinoma

PURPOSE A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Tumor necrosis factor α antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis

BACKGROUND & AIMS Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohns disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohns ileocolitis were studied. METHODS Thirteen patients with steroid-refractory Crohns disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. RESULTS Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. CONCLUSIONS Infliximab dramatically decreases histological disease activity in Crohns ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.

Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis.

BACKGROUND AND AIMS Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC. METHODS Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects. RESULTS Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08). CONCLUSIONS High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction : a prospective study based on primary surgery with extensive lymphadenectomy

ObjectiveTo assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. Summary Background DataFDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. MethodsForty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). ResultsThe FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1–2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1–2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. ConclusionsFDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Appendectomy protects against ulcerative colitis

BACKGROUND/AIMS Defining risk factors for ulcerative colitis (UC) is important to better understand the pathogenesis of this idiopathic disease. One factor modulating the disease is smoking. A pilot study showed the absence of appendectomy in the medical history of patients with ulcerative colitis. The aim of the present case control study was to compare the relative risk of developing UC after appendectomy with the relative risk of developing UC with an intact appendix. METHODS One hundred seventy-four (84 females and 90 males, mean age 34.9 years) consecutive UC patients examined at our inflammatory bowel disease clinic or hospital ward, were included. Fifty-six had pancolitis (32%) and 118 (68%) suffered from left-sided colitis. The control group consisted of 161 consecutive patients examined at the orthopedic clinic (86 females and 75 males, mean age 40.9 years). RESULTS Two parameters, absence of appendectomy and smoking, were closely related to the development of UC. Before the onset of UC, only 1 of the 174 patients (0.6%) had undergone an appendectomy. Of the 161 controls, 41 (25.4%) had undergone an appendectomy. The difference between the two groups was highly significant with an odds ratio of 59.1 (95% CI, 18-189; P < 0.001). The relative risk of getting the disease associated with nonsmoking was 2.95 (95% CI, 1.69-5.17). CONCLUSIONS Appendectomy is a protective factor against UC.

Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis

ObjectivesIV cyclosporin A (CSA) is an effective therapy in patients with severe ulcerative colitis (UC). It remains unclear if this treatment affects the course of the disease in the long run. We investigated the long-term efficacy and safety in 86 patients with ulcerative colitis treated with IV CSA at our center. MethodsThe records of all patients treated with IV CSA between 11/1992 and 11/2000 were reviewed. ResultsSeventy-two of 86 patients (83.7%) responded to IV CSA therapy, administered for a mean of 9 ± 2 days. Following the initial treatment, 69 patients (96%) were discharged on oral CSA with mean blood CSA concentrations of 192 ± 55 ng/mL. Azathioprine was added in 64 (89%) patients. A second treatment with CSA was necessary in 11 patients; 1 patient received three courses of IV treatment.The duration of follow-up averaged 773 ± 369 days. Patients who were responders but were still having certain symptoms at discharge had a higher incidence of colectomy during follow-up. Of all initial responders, 18 (25%) underwent colectomy after a mean interval of 178 ± 141 days. The life-table predicts that of all treated patients, 55% will avoid a colectomy during a period of 3 years.Complications of CSA treatment were mostly reversible, but 3 patients (3.5%) died of opportunistic infections (1 of Pneumocystis carinii pneumonia and 2 of Aspergillus fumigatus pneumoniae). One patient with anaphylactic shock caused by the CSA solvent was successfully resuscitated. ConclusionsCSA is an effective treatment of the majority of patients with severe attacks of UC, although the toxicity and even mortality associated with its use necessitates careful evaluation, selection, and follow-up.

Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn's strictures: a prospective longterm analysis.

Preliminary reports have suggested that dilatation using hydrostatic through the scope balloons may be useful for the treatment of Crohns strictures, A prospective longterm follow up (mean (SD) 33.6 (11.2) months) was carried out in 55 Crohns patients with 59 ileocolonic strictures submitted to 78 dilatation procedures. Hydrostatic balloons were used (Rigiflator, Microvasive) with a diameter of 18 mm on inflation. As soon as the balloons became available dilatation up to a diameter of 20 and 25 mm was attempted. The dilatations were performed under general anaesthesia using propofol (Diprivan). The patients were kept for one night in the hospital after dilatation. Seventy (90%) procedures were technically successful and passage of the stricture with a 13.6 mm diameter colonoscope was possible after 73% of the dilatations. Complications occurred in six patients (11%; 8% of procedures), including sealed perforations (n = 2), retroperitoneal perforations (n = 2), and intraperitoneal perforations (n = 2). Two of the patients were treated surgically with a one stage resection of the stricture and recovered uneventfully. Four patients were treated conservatively with intravenous fluids and antibiotics. There was no mortality. Dilatation completely relieved obstructive symptoms in 20 patients after one procedure, in another 14 patients after two (n = 13) or three (n = 1) dilatations. Total longterm success rate was 34 of 55 patients (62%). Nineteen patients (38%) were operated on because of persistent obstructive symptoms. The data show that endoscopic dilatation using the through the scope hydrostatic balloon system relieves obstructive symptoms resulting from ileocolonic Crohns strictures. The procedure, however, carries a definite risk of perforation.