A NEW APPROACH IN THE MANAGEMENT OF CROHN’S DISEASE: OBSERVATIONS IN
20 CONSECUTIVE CASES.
del Gaudio A; Bragaglia RB; Boschi L; del Gaudio GA; Accorsi D Address
Department of Surgery, University of Bologna, School of Medicine, Italy.
Hepatogastroenterology, 1997 Jul, 44:16, 1095-103
Although the “modern history” of Crohn’s disease dates back to 1932,
the etiology is still nebulous, the medical treatment inefficient and resective
surgery results in a high recurrence rate. Twenty consecutive patients
with terminal ileitis underwent ileo-cecal resection and mesenteric-epiploonplasty
to enhance collaterals and lymphatic drainage. This approach was advised
by experimental observations (the ligation of colonic lymphatic ducts in
rabbits), by the intraoperative use of optics to better appreciate the
details of the diseased bowel before and after injecting dye and by the
angiographic results in one patient. In rabbit experiments, the obliteration
of lymphatic drainage led to Crohn’s disease-like macroscopic and microscopic
patterns, while diffusion of the dye injected in the diseased segment showed
altered lymph flow. The angiographic study in one patient confirmed the
presence of vascular anomalies. Direct observation through optics revealed
large vessels in the serosa with milky contents and the oozing of sticky
exudate. In the 8 patients who underwent this procedure over 5 years
ago, there were no recurrences. We strongly believe in the vasculo-lymphatic
etiology of Crohn’s disease and in mesentery-epiploonplasty as the only
actual indirect approach to resolve hemolymphatic obstructions.
SURGERY IN CROHN'S DISEASE: WHEN, WHERE AND WHY THE RECURRENCES?
Del Gaudio A, Bragaglia RB, Boschi L, Del Gaudio GA, Fuzzi N, Department
of Surgery, University of Bologna, School of Medicine, S.Orsola-Malpighi
Hospital, Italy. Hepatogastroenterology 1998 Jul-Aug;45(22):978-84
One frustrating feature in the surgical management of Crohn’s disease
is the high recurrence rate
which may lead to reoperation. It is common opinion that relapses occur
haphazardly both in time
and in site, and the causes remain unknown. When does a recurrence
really arise after surgery? Is
the site of recurrence determined by definite causes? Is there a relapsing
factor? Between 1965 and
1995, 177 patients underwent surgery for Crohn’s disease. The procedures
performed in 145 cases were those popular at the time, while a recent series
of 20 selected patients was managed following a new approach based on epiploonplasty.
This strategy stems from the strong conviction that Crohn’s disease is
not a primary bowel disease but the result of stasis and superimposed infection
due to a primary hemolymphatic disorder of the mesentery. The five-year
recurrence rate was 62% in patients operated on according to standard procedures,
while no recurrences were reported in the epiploonplasty group.
Among 12 remaining patients with recurrent disease, two cases are reported
in detail because they provide evidence in favor of the hemolymphatic theory.
This study also maintains that recurrences, viewed with the hemolymphatic
disorder in mind, occur immediately after surgery, while the superimposed
intestinal inflammatory process and stricturing events may appear clinically
at different time intervals during follow-up. The site of recurrences usually
corresponds to the mesenteric region subjected to compression. Altered
mesenteric microcirculation appears to be the true essence of the disease.
COMBINATION CIPROFLOXACIN AND METRONIDAZOLE FOR ACTIVE CROHN’S
DISEASE.
Greenbloom SL; Steinhart AH; Greenberg GR; Division of Gastroenterology,
Mount Sinai Hospital,
Toronto, Ontario. Can J Gastroenterol, 1998 Jan, 12:1, 53-6
Recent experimental evidence underscores the contribution of intestinal
bacteria to the inflammatory
process of Crohn’s disease. This open study examined the efficacy and
safety of combination
ciprofloxacin and metronidazole for patients with active Crohn’s disease
of the ileum and/or colon.
Seventy-two patients with active Crohn’s disease of the ileum (n =
27), ileocolon (n = 22) or colon
(n = 23) were treated with ciprofloxacin 500 mg bid and metronidazole
250 mg tid for a mean of 10
weeks. Clinical remission was defined as a Harvey-Bradshaw index of
three points or less; an index
reduction of at least three points indicated a clinical response. Clinical
remission was observed in 49
patients (68%), and 55 patients (76%) showed a clinical response. A
clinical response was noted in
29 of 43 patients (67%) who were not taking concurrent prednisone treatment
and in 26 of 29
patients (90%) receiving prednisone (mean dose of 15 mg/day). A clinical
response also occurred in
a greater proportion of patients with colonic disease, with or without
ileal involvement (84%),
compared with patients with ileal disease alone (64%), and in patients
without resection (86%)
compared with those with previous resection (61%). Five patients discontinued
antibiotics because
of adverse events. After a mean follow-up of nine months, clinical
remission was maintained in 26
patients off treatment and in 12 patients who continued antibiotic
therapy. Ciprofloxacin in
combination with metronidazole is well tolerated and appears to play
a beneficial role in achieving
clinical remission for patients with active Crohn’s disease, particularly
when there is involvement of
the colon.
ORAL BUDESONIDE IS AS EFFECTIVE AS ORAL PREDNISOLONE IN ACTIVE
CROHN'S DISEASE. THE GLOBAL BUDESONIDE STUDY GROUP.
Campieri M; Ferguson A; Doe W; Persson T; Nilsson LG; Medical and Gastroenterological
Clinic, University of Bologna, Italy. Gut, 1997 Aug, 41:2, 209-14
BACKGROUND: The use of corticosteroids in active Crohn’s disease often
becomes limited by side effects. Budesonide is a potent corticosteroid
with low systemic bioavailability due to an extensive first pass liver
metabolism. AIMS: To compare the efficacy and safety of two dosage regimens
of budesonide and prednisolone in patients with active Crohn’s disease
affecting the ileum and/or the ascending colon. PATIENTS AND METHODS: One
hundred and seventy eight patients were randomised to receive budesonide
controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice
daily, or prednisolone tablets 40 mg once daily. The treatment period was
12 weeks. The primary efficacy variable was clinical remission,
defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less. RESULTS:
After eight weeks of treatment, remission occurred in 60% of patients
receiving budesonide once daily or prednisolone and in 42% of those receiving
budesonide twice daily (p = 0.062). The presence of glucocorticoid
associated side effects was similar in all groups; however, moon face was
more common in the prednisolone group (p = 0.0005). The highest frequency
of impaired adrenal function, as measured by a short ACTH test, was
found in the prednisolone group (p = 0.0023). CONCLUSIONS: Budesonide
CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable
to prednisolone in inducing remission in active Crohn’s disease. The single
dose administration is as promptly effective as prednisolone and represents
a simpler and safer therapeutic approach, with a considerable reduction
in side effects.
TREATMENT OF ACTIVE AND POSTACTIVE ILEAL AND COLONIC CROHN'S DISEASE
WITH ORAL PH-MODIFIED-RELEASE BUDESONIDE. GERMAN BUDESONIDE STUDY
GROUP.
Caesar I; Gross V; Roth M; Andus T; Schmidt C; Raedsch R; Weber A;
Gierend M; Ewe K; Schölmerich J Department of Internal Medicine
University of Regensburg. Hepatogastroenterology, 1997 Mar, 44:14,
445-51
BACKGROUND/AIMS: Budesonide is a glucocorticoid with a high topical
anti-inflammatory but low systemic activity due to its rapid hepatic inactivation.
The aim of this open, multicenter study was to investigate efficacy and
safety of oral pH-modified-release budesonide in patients with active Crohn’s
disease of the ileum and colon and in maintaining budesonide-induced remission
in postactive Crohn’s disease. MATERIALS AND METHODS: 81 patients (intention-to-treat)
received 3 x 3 mg budesonide/day for 6 weeks, followed by 3 x 2 mg budesonide
for another 6 weeks in case of response to initial treatment. Clinical
and laboratory parameters were assessed at study entry as well as after
2, 4, 6 and 12 weeks of treatment. RESULTS: On an intention-to-treat basis
remission was induced in 54.3% of 81 patients with active Crohn’s
disease, 71.4% of 35 patients stayed in remission after the acute-phase
treatment until the end of the trial. Typical steroid-related side effects
were observed during the acute-phase treatment in only 18% of the patients.
Duration, severity and extent of disease at study entry played no significant
role in the outcome of the trial, but there was a tendency towards better
results during the acute-phase treatment in patients with moderate disease
activity and affection of the terminal ileum and proximal colon. CONCLUSIONS:
Budesonide could be an alternative to conventional steroid treatment in
patients with active Crohn's disease.
AN INTRAVENOUS LOADING DOSE OF AZATHIOPRINE DECREASES THE TIME TO RESPONSE
IN PATIENTS WITH CROHN'S DISEASE.
Sandborn WJ; Van O EC; Zins BJ; Tremaine WJ; Mays DC; Lipsky JJ; Inflammatory
Bowel Disease Clinic, Mayo Clinic, Rochester, Minnesota, USA. Gastroenterology,
1995 Dec, 109:6, 1808-17
BACKGROUND & AIMS: Azathioprine, an effective therapy for Crohn’s
disease, is limited by a prolonged time to response. The aim of this study
was to determine the safety and utility of a loading dose of azathioprine
to decrease the time to response in patients with Crohn’s disease. METHODS:
Twelve patients were studied: 6 with 13 fistulae and 6 with inflammatory
disease. All patients received an intravenous infusion of azathioprine
(50 mg/h for 36 hours). Response was determined by physical and radiographic
examination for fistulae and by the Crohn’s Disease Activity Index for
inflammatory disease. Erythrocyte concentrations of azathioprine metabolites
were measured by chromatography. RESULTS: Seven of 13 fistulae closed by
week 4, and three had a temporary decrease in drainage. One fistula improved
at week 16. Two fistulae failed to improve. Four of 6 patients with inflammatory
disease achieved remission, and 1 improved temporarily. Improvement was
rapid (< or = 4 weeks). Peak concentrations of azathioprine metabolites
occurred within 3 days. Clinical response did not correlate with azathioprine
metabolite concentrations at the azathioprine dose studied. No adverse
events occurred. CONCLUSIONS: An 1800-mg intravenous loading dose of
azathioprine is safe and may decrease the time to response to < or =
4 weeks in patients with Crohn’s disease. Correlation between clinical
response and azathioprine metabolite concentrations at larger azathioprine
doses should be determined.
TREATMENT OF THERAPY-RESISTANT PERINEAL METASTATIC CROHN’S DISEASE AFTER
PROCTECTOMY USING ANTI-TUMOR NECROSIS FACTOR CHIMERIC MONOCLONAL ANTIBODY,
CA2: REPORT OF TWO CASES.
van Dullemen HM; de Jong E; Slors F; Tytgat GN; van Deventer SJ; Department
of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
Dis Colon Rectum, 1998 Jan, 41:1, 98-102
PURPOSE: Two young females with well-documented Crohn’s disease and
nonhealing perineal wounds following proctectomy compatible with “metastatic
Crohn’s disease” are described. We hypothesized that metastatic Crohn’s
disease would be a tumor necrosis factor-dependent inflammatory reaction
and have treated these two patients with the anti-tumor necrosis factor
chimeric monoclonal antibody, cA2. MAIN FINDINGS: Administration of
cA2 was followed by a rapid reduction of subjective and objective parameters
of inflammation and caused a substantial reduction of the wound size.
CONCLUSION: These preliminary data are consistent with a tumor necrosis
factor-dependent inflammatory cause of Crohn’s disease and its extraintestinal
manifestations and provide support for targeting tumor necrosis factor
in this condition.
INTERLEUKIN 10 SUPPRESSES EXPERIMENTAL CHRONIC, GRANULOMATOUS
INFLAMMATION INDUCED BY BACTERIAL CELL WALL POLYMERS.
Herfarth HH; Mohanty SP; Rath HC; Tonkonogy S; Sartor RB; Department
of Medicine, University of North Carolina, Chapel Hill 27599-7080, USA.
Gut, 1996 Dec, 39:96, 836-45
BACKGROUND AND AIMS: Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions. This study examined the effect of systemically administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis, and arthritis in a rat model. METHODS: Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection, rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days. RESULTS: IL10 attenuated acute enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were more profound in the chronic granulomatous phase with decreased enterocolitis and markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes were downregulated in IL10 treated animals. CONCLUSIONS: These results indicate that exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new therapeutic approach in human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.