We were fascinated to read the paper by Cruz-Correa et al. [1] describing cases of mucosal tearing at colonoscopy in
patients subsequently found to have collagenous colitis. We were
particularly interested in their postulated mechanism for these tears
being a disruption of colonic mural integrity by the sub-mucosal collagen
layer. We would like to present two cases which add further weight to t...
We were fascinated to read the paper by Cruz-Correa et al. [1] describing cases of mucosal tearing at colonoscopy in
patients subsequently found to have collagenous colitis. We were
particularly interested in their postulated mechanism for these tears
being a disruption of colonic mural integrity by the sub-mucosal collagen
layer. We would like to present two cases which add further weight to this
theory as well as possibly providing information as to the pathogenesis of
diarrhoea in this condition.
A 60-year-old woman presented to her general practitioner with a two-
month history of profuse watery diarrhoea. A barium enema examination was
reported as showing evidence of a mild colitis only. The general
practitioner commenced corticosteroids resulting in complete resolution of
her symptoms. On referral to our department a gastrointestinal radiologist
reviewed her radiographs. It was noticed that, throughout the films, there
was a radiolucent border outlining the colonic mucosa (see figure 1 Erect radiographs from a double contrast barium enema series. Sub
mucosal tracking of gas is arrowed. [click here]) suggesting
the presence of a submucosal layer of gas for which no explanation could
be found. Although endoscopic examination of the colon was macroscopically
normal, serial biopsies revealed the presence of a subepithelial collagen
band up to 100µm thick and a diagnosis of collagenous colitis was made.
There was no evidence of pneumatosis or of sub mucosal barium on the small
amount of submucosa included. She has since remained well on mesalazine.
The second patient was a 68-year-old woman with a four-week history
of profuse watery diarrhoea. An emergency admission was required as a
result of deranged clotting secondary to warfarin, which she was taking
for a mechanical aortic valve. Following correction of her coagulopathy
she underwent a colonoscopy. The instrument was advanced to the caecum
without difficulty by a very experienced endoscopist who had performed in
excess of 10,000 procedures. Macroscopically there was evidence of a mild
colitis. Standard serial biopsies were taken. Shortly following the
procedure she complained of right shoulder tip pain. On examination she
was neither distressed nor haemodynamically compromised. Her abdomen was
soft. Chest and abdominal radiographs showed significant free gas under
the diaphragm and in the peritoneum. At laparotomy she was found to have
pneumoperitoneum without faecal contamination. No perforation was
identified but there was considerable emphysema within the caecal wall
extending proximally along the terminal ileum and distally to the mid
ascending colon. No further operative procedure was performed. Endoscopic
biopsies showed mild active inflammation and a subepithelial collagen
band. None of the biopsies were full thickness. A diagnosis of collagenous
colitis was made and her symptoms settled on a short course of
corticosteroids.
We suggest that the complications seen in the investigation of these
two patients result from a weakness within the colonic wall caused by the
collagen layer. In the first case it appears that cleavage or dissection
of the colonic wall alongside the collagen layer may have occurred. It is
unclear whether this has happened as a result of air insufflation at the
time of the examination or whether it was already present. In the second
case we postulate that air insufflated at the time of the colonoscopy
tracked alongside the collagen layer perforating into the peritoneum
remote from its original point of entry; possibly a proximal biopsy site.
If a true weakness in the integrity of adhesion of the elements of
the colonic wall does exist and such “dissection” can happen spontaneously
then it may provide some incite into the pathogenesis of the diarrhoea in
this condition, especially as there appears to be no correlation between
the width of the collagen band and the severity of symptoms.
Reference
(1) M Cruz-Correa, F Milligan, F M Giardiello, T M Bayless, M Torbenson, J H Yardley, Frank W Jackson, and F Wilson Jackson. Collagenous colitis with mucosal tears on endoscopic insufflation: a unique presentation. Gut 2002; 51:600.
I was interested to read the paper by Cruz-Correa et al. [1]
describing mucosal tears at colonoscopy in patients with collagenous
colitis. I was then interested to read letters from Mitchell et al.[2] and Komuro et al.[3] describing their experience with mucosal
tears in patients with collagenous colitis and diversion colitis, respectively. I would like to present a case of an elde...
I was interested to read the paper by Cruz-Correa et al. [1]
describing mucosal tears at colonoscopy in patients with collagenous
colitis. I was then interested to read letters from Mitchell et al.[2] and Komuro et al.[3] describing their experience with mucosal
tears in patients with collagenous colitis and diversion colitis, respectively. I would like to present a case of an elderly lady who
turned out to have collagenous colitis and who also developed mucosal
tears from what appeared to be simply the air insufflated at colonoscopy.
A 75-year-old woman presented with three months of chronic
nonspecific diarrhoea with her passing up to six loose motions each day in
association with significant urgency and episodes of faecal incontinence.
There was no weight loss. There were no upper gastrointestinal symptoms.
Previously, she had undergone appendicectomy and several years before this
presentation a diagnosis of angina was made although there were no ongoing
symptoms after the initial diagnosis. She was a nonsmoker, nondrinker.
She had been on atenolol, aspirin and isosorbide mononitrate ever since
the purported diagnosis of angina had been made. There were no other
medications. Two faecal samples were sent for microbiology and these
revealed unformed faecal matter with no abnormalities on culture with one
specimen showing occasional polymorphs on microscopy. The stools were
negative for Clostridium difficile toxin. A full blood count, CRP,iron
studies, renal function, liver tests, thyroid tests,endomysial
antibody,vitamin B12 and red blood cell folate were all normal.
At colonoscopy, the colonoscope was passed to the caecum with a
little difficulty in negotiating the scope slowly through the sigmoid
colon. Air insufflation was not excessive and the patient's abdomen
remained quite soft and lax throughout the entire procedure. Once the
scope was in the distal descending colon, it could be seen that there was
a 1.5 centimetre shallow, transverse mucosal split in the proximal
descending colon. As the scope was being passed across the transverse
colon, five shorter mucosal tears with associated oozing of blood were
seen to be present along the transverse colon proximal to the tip of the
scope. The colon otherwise appeared normal. Four biopsies were taken from
the right hemi-colon and four biopsies were taken along the left hemi-colon
and these showed classic features of collagenous colitis with increased
inflammatory cells in the lamina propria including plasma cells,
lymphocytes and polymorphs and there was also a variable but quite
definite increase in the sub-epithelial collagen layer with the thickness
often exceeding 10 µm. The patient was perfectly well after the procedure
with no pain, abdominal distension or tenderness.
I have had a similar occurrence with one other patient who had
collagenous colitis. My experience and the letters and articles in Gut
would all indicate that this complication is not rare in patients with
collagenous colitis. The appearance at colonoscopy can be somewhat
alarming and the letter from Mitchell, Teague et al. indicates that these
tears can sometimes result in more than just a worrying appearance through
the scope. In patients who are undergoing colonoscopy for chronic
diarrhoea, the finding of mucosal tears in segments of otherwise
unremarkable looking colon, through which the scope has not yet passed ,
could suggest the presence of underlying collagenous colitis.
References
1. M Cruz-Correa, F Milligan, F M Giardiello, T M Bayless, M Torbenson, J H Yardley, Frank W Jackson, and F Wilson Jackson. Collagenous colitis with mucosal tears on endoscopic insufflation: a unique presentation. Gut 2002; 51: 600.
2. Mitchell JD et al. Submucosal "dissection" in collagenous colitis [electronic response to Cruz-Correa, et al. Collagenous colitis with mucosal tears on endoscopic insufflation: a unique presentation] gutjnl.com 2004http://gut.bmjjournals.com/cgi/eletters/51/4/600#71
3. Komuro Y et al. Diversion colitis with a mucosal tear on endoscopic insufflation [electronic response to Cruz-Correa, et al. Collagenous colitis with mucosal tears on endoscopic insufflation: a unique presentation] gutjnl.com 2004http://gut.bmjjournals.com/cgi/eletters/51/4/600#69
The article by Ransford and Langman [1] on
suspected serious adverse drug reactions for sulphasalazine and mesalazine
reported in the UK from 1991 to 1998 revealed significant differences
between both drugs. Pancreatitis and interstitial nephritis were reported
more frequently for mesalazine in comparison with sulphasalazine. The
authors’ conclusion that mesalazine would not offer a safety benefit over
s...
The article by Ransford and Langman [1] on
suspected serious adverse drug reactions for sulphasalazine and mesalazine
reported in the UK from 1991 to 1998 revealed significant differences
between both drugs. Pancreatitis and interstitial nephritis were reported
more frequently for mesalazine in comparison with sulphasalazine. The
authors’ conclusion that mesalazine would not offer a safety benefit over
sulphasalazine, however, appears unjustified for several reasons.
Sulphasalazine is an older compound used for the treatment of both
rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). For 30
years, the adverse event (AE) profile of sulphasalazine has been well
known [2]. It often induces
oligoteratozoöspermy in male patients and frequently causes nausea,
vomiting, headache, and folic acid deficiency. Although not ‘serious’
AEs, these often lead to low compliance, incorrect use and early
discontinuation. In addition, it is more than likely that the many
adverse reactions, identified in the 1970s, were not reported again to
the medical authorities in the nineties.
The introduction of mesalazine in the 1980s enabled effective treatment
(often at higher doses) without the numerous adverse effects attributed to
the sulphapyridine moiety of sulphasalazine.[3] Focus on the risk of
interstitial nephritis caused by mesalazine preparations in the mid
nineties undoubtedly led to a low threshold for reporting. However, the
incidence of renal insufficiency was recently studied in a large cohort of
1449 European IBD patients (more than 70 % on mesalazine/sulphasalazine)
and did not exceed the expected incidence in the general population.[4]
Furthermore, pooling the data of all pure mesalazine products (as
done by Ransford and Langman, 2002)[5] does not seem appropriate, since the different
release mechanisms of the various products could bring along different AE
profiles. PENTASA® has less frequently been associated with interstitial
nephritis than other 5-ASAs.[6] Unlike PENTASA®, Asacol®, Claversal® and Salofalk®
indeed have a relative dose dumping effect with higher peak serum
concentrations, allegedly contributing to potential nephrotoxicity.[7]
In addition, reporting serious AEs in relation to the number of
prescriptions is an unusual approach. Dosage and duration of therapy would
have been more relevant, since the risk of side effects is dose-dependent
with sulphasalazine but not with mesalazine. Physicians may prefer to
prescribe mesalazine to patients who are susceptible to side effects
caused by sulphasalazine.
For an unclear reason, adverse events with fatal outcome were not
mentioned separately in Ransford and Langman’s report.[1] Based on the
British CSM database, 18 fatal events occurred in patients taking
sulphasalazine, versus 12 in the pooled pure mesalazine group during the
same observation period. Moreover, PENTASA® mortality rate was zero in an
earlier French pharmacovigilance report revealing an incidence of reported
adverse events with this product (the most commonly used mesalazine
preparation in France with a market share > 70%) between 6 and 9 per
million days of therapy.[8]
In conclusion, based on all available data on mortality, serious
irreversible adverse events and tolerability of both drugs, mesalazine
should be preferred to sulphalsalzine in the treatment of IBD. Eighty per
cent of the patients intolerant to sulphasalzine will tolerate mesalazine
without problems. [9-11]
References
(1) Ransford RAJ, Langman MJS. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 2002;51: 536-539.
(2) Das KM, Eastwood MA, McManus JP, Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype.
New Engl J Med 1973:289:491-5.
(3) Forbes, A. Clinicians' guide to inflammatory bowel disease. London: Chapman & Hall, 1997.
(4) G D'Haens, M Elseviers, L Lemmens, C Plane, E Lerebours, JC Stolear, G Riegler, M Van Outryve, P Mishevska, S Djuranovica and M De Broe. Absence of renal impairment with longstanding use of aminosalicylates in
chronic inflammatory bowel disease. 8th UEGW, Bruxelles. GutSuppl 2000.
(5) Ransford RAJ, Langman MJS. Sulphasalazine and mesalazine: serious adverse
reactions re-evaluated on the basis of suspected adverse reaction reports to
the Committee on Safety of Medicines. Gut 2002;51:536-539.
(7) Corrigan G, Stevens PE. Review article: interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease. Aliment Pharmacol Ther 2000; 14:1-6.
(8) Marteau P, Nelet F, Le Lu M, Devaux C. Adverse events in patients treated with 5-aminosalicyclic acid: 1993-1994 pharmacovigilance report for Pentasa in France.
Aliment Pharmacol Ther 1996;10:949-956.
(9) Dew MJ, Harries AD, Evans BK, Rhodes J. Treatment of ulcerative colitis with oral 5-aminosalicyclic acid in patients unable to take sulphasalazine. Lancet 1983;2:801
(10) Turunen U, Elomaa I, Anttila VJ, Seppala K. Mesalazine tolerance in patients with inflammatory bowel disease and previous intolerance or allergy to sulphasalazine or sulphonamides. Scand J Gastroenterol 1987;22: 798-802.
(11) Rao SS, Cann PA, Holdsworth CD. Clinical experience of the tolerance of mesalazine and olsalazine in patients intolerant of sulphasalazine. Scand J Gastroenterol 1987; 22:332-336.
The Therapy Update in the May issue highlighted the potential role for
antibiotic therapy in Crohn's disease [1]. Dr Colombel
indicated the need for appropriate antibiotics that are based on current
theories of pathogenesis, namely that they be effective against both
extracellular and intracellular bacteria. The possible role of
Mycobacterium paratuberculosis, although controversial, also should not be
overl...
The Therapy Update in the May issue highlighted the potential role for
antibiotic therapy in Crohn's disease [1]. Dr Colombel
indicated the need for appropriate antibiotics that are based on current
theories of pathogenesis, namely that they be effective against both
extracellular and intracellular bacteria. The possible role of
Mycobacterium paratuberculosis, although controversial, also should not be
overlooked. The review also emphasised that trials of antibiotics should
be of sufficiently long duration to demonstrate any possible benefit.
Based on the observational study of Gui et al,[2] in August 1999 we
commenced a suitably powered Australian multicentre, placebo-controlled,
double-blind trial of clarithromycin, rifabutin and clofazimine in active
Crohn's disease. All subjects receive a tapering regimen of prednisolone
on entry in addition to either antibiotics or matching placebos. If
remission is achieved at 16 weeks, and prednisolone withdrawn, subjects
continue their trial medications for 2 years. There is then a further one
year of clinical and colonoscopic follow-up. The aim of the study is to
determine whether this antibiotic therapy has a long-term benefit for
patients with Crohn's disease. The primary endpoints are relapse rates at
one, two and three years. The latter is particularly important to see if
there is an effect on the natural history of the disorder. Secondary
endpoints include remission at 4 months, safety and quality of life.
As of May 2001, 171 of the 212 subjects required have been enrolled.
Recruitment will continue until the end of July. To date, the likelihood
of being in remission at 16 weeks and continuing in the study is 60%. Once
past this point, 92% are ongoing. Only five patients have been withdrawn
for probable reactions to the trial medication, four with elevated liver
enzymes and one who developed a rash. An Independent Data Monitoring
Committee, which recently conducted the first interim analysis,
unanimously recommended that the trial continue.
Because of the necessary length of therapy the results will not be known
until 2004. The IDMC will continue to assess the progress. We believe this
study will answer the important questions in the treatment of Crohn's
disease raised by Dr Colombel.
W Selby
B Crotty
T Florin
P Pavli
Steering Committee for the Australian IBD Interest Group
References
(1) Colombel J-F, Cortot A, Van Kruiningen HJ. Antibiotics in
Crohn's disease.
(2) Gui GPH, Thomas PRS, Tizard MLV, Lake J, Sanderson JD,
Hermon-Taylor J. Two-year-outcomes analysis of Crohn's disease treated
with rifabutin and macrolide antibiotics. J Antimicrobial chemotherapy
1997;39:393-400.
Various therapeutic approaches for unresectable hepatocellular
carcinoma (HCC) have been suggested during recent years. However, major
advances concerning tumor regression or patient survival were not
achieved. Few trials assessed the effect of the somatostatin analogue
octreotide in advanced HCC with divergent results.[1,2] The latter might
be due to the expression of somatostatin receptor type 2 (SSTR...
Various therapeutic approaches for unresectable hepatocellular
carcinoma (HCC) have been suggested during recent years. However, major
advances concerning tumor regression or patient survival were not
achieved. Few trials assessed the effect of the somatostatin analogue
octreotide in advanced HCC with divergent results.[1,2] The latter might
be due to the expression of somatostatin receptor type 2 (SSTR2) in some
but not all patients with HCC.[3,4]
Herein, we describe a patient with
advanced HCC who was treated with long-acting octreotide, which resulted
in complete and prolonged regression of the tumor.
The patient was diagnosed with HCC after a suspect nodule was detected in
the abdominal ultrasound. Laboratory testing revealed a highly increased a
-fetoprotein (AFP) and positive HCV antibodies. Computed tomography (CT)
of the liver displayed multiple tumors (maximum diameter 5 cm) in segment
seven and two smaller nodules in segments six and one. Histology of an
ultrasound-guided biopsy revealed hepatocellular carcinoma. Due to the
advanced stage of the tumor a surgical resection was not feasible. As the
patient refused local ablative therapies a therapy with octreotide was
initiated (initially 250 µg twice daily, followed by long-acting
octreotide, Sandostatin LAR®, 10 mg monthly). Four months later a 50-70%
reduction in the size of the multifocal tumors was demonstrated by CT.
Furthermore, a complete regression of the formerly described tumors was
noted ten months after initiation of octreotide therapy. This was
paralleled by a normalization of the formerly elevated AFP values (33,1
ng/ml vs. 7615,3 ng/ml). Octreotide receptor scintigraphy performed after
12 months and 19 months of therapy did not reveal any suspicious
enhancement. However, after 13 and 19 month a gradual increase of the AFP
levels from 37 to 223 ng/ml and a new suspicious liver nodule by CT scans
were observed. The patient has so far not experienced any tumor-associated
symptoms or any drug-related side effects and up to now has been in
excellent condition during the 22 months of treatment.
The survival-improving treatment effects of octreotide described by
Kouroumalis et al. [1] were not confirmed in a subsequent randomized
placebo-controlled trial.[2] Of the octreotide receptors expressed in the
liver, octreotide has the highest affinity to SSTR2 compared with the four
other isoforms of the somatostatin-receptors.[3] SSTR2 is expressed in
HCC [3,4] and has been shown to play a major role in mediating cell cycle
arrest.[5] Although we were not able to proof SSTR expression in our
patient due to tissue preparation in another hospital, a high SSTR2
expression in our patient might be the reason for the unusual beneficial
clinical course. The recent increase in AFP levels could reflect the
ability of the tumor cells to escape somatostatin receptor treatment,
possibly by down regulation or mutation of the respective receptor.
To the best of our knowledge, the complete and prolonged regression
of advanced HCC with normalized AFP levels during octreotide treatment has
not been described before. Based on our observation and the divergent
results of recent studies, forthcoming trials evaluating the effect of
octreotide in advanced HCC might additionally stratify patients according
to the respective somatostatin receptor expression profile of the tumor
cells.
References
(1) Kouroumalis E, Skordilis P, Thermos K, et al. Treatment of
hepatocellular carcinoma with octreotide: a randomised controlled study. Gut 1998;42:442-447.
(2) Yuen MF, Poon RT, Lai CL, et al A randomized placebo-controlled study
of long-acting octreotide for the treatment of advanced hepatocellular
carcinoma. Hepatology 2002;36:687-691
(3) Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-
sst5 expression in normal and neoplastic human tissues using receptor
autoradiography with subtype-selective ligands. Eur J Nucl Med 2001;28:836-846
(4) Reubi JC, Zimmermann A, Jonas S, et al. Regulatory peptide receptors in
human hepatocellular carcinomas. Gut 1999;45:766-774
(5) Benali N, Cordelier P, Calise D, et al. Inhibition of growth and
metastatic progression of pancreatic carcinoma in hamster after
somatostatin receptor subtype 2 (sst2) gene expression and administration
of cytotoxic somatostatin analog AN-238. Proc Natl Acad Sci USA
2000;97:9180-9185
Editor,
Thoracic outlet syndrome is frequently undiagnosed in patients with
non-cardiac ,non-coronary chest pains.
See www.tos-syndrome.com. Patients with depression or panic attacks can
have associated Thoracic Outlet Syndrome. The diagnosis will remain ignored
unless the symptoms and physical findings are elicited in these patients.
We would like to draw the attention of Murray et al.[1] to the
objectives set out clearly in the introductory section of our paper.
Our
study was not designed to address the question of whether ghrelin is
involved in long-term regulation of body weight. Furthermore, the duration
of the study was too short to see any change in BMI. More importantly,
waist circumference would be a better...
We would like to draw the attention of Murray et al.[1] to the
objectives set out clearly in the introductory section of our paper.
Our
study was not designed to address the question of whether ghrelin is
involved in long-term regulation of body weight. Furthermore, the duration
of the study was too short to see any change in BMI. More importantly,
waist circumference would be a better anthropometric measure of change in
body fat composition supported by sequential dual energy Xray
absorptiometry or MRI. The results of our study were unexpected and there
was nothing in the literature that gave us forewarning. We would have
designed the study to follow-up the subjects for at least one year,
monitoring their plasma ghrelin and assessing changes in body composition
using the techniques described above.
The authors refer to “physiological feasibility” and thereby miss the
point that Helicobacter pylori-infected stomachs exhibit distortion of
normal physiological mechanisms. For example, the tight reciprocal
relationship between gastrin and intragastric acidity seen in Helicobacter
pylori negative subjects is modified in Helicobacter pylori positive
subjects. We believe that an Helicobacter pylori-infected stomach produces
less ghrelin leading to decreased appetite and food intake. The
physiological response should be that the resulting weight loss leads to a
compensatory increase in ghrelin, increased appetite, and weight gain and
so on. We believe that this “physiological” mechanism is altered by the
presence of Helicobacter pylori, possibly by resetting a putative “ghrelin
thermostat” at a lower level, allowing thinness and hypo-ghrelinaemia to
occur together. Proof will come only from further experimentation.
The authors cite a study comparing spot measurements of plasma
ghrelin in women with and without Helicobacter pylori gastritis;[2] this
does not amount to a robust challenge to our hypothesis on Helicobacter pylori, ghrelin and children.
The authors repeat the widely-held, though unproven belief that the
increase in intragastric acidity after Helicobacter pylori cure can be
attributed to the recovery of parietal cells from inflammation. They
ignore our observation of a positive correlation between ghrelin and 24-
hour intragastric acidity.
We accept that the relationship between gastrin and ghrelin is
unproven in man, but this emphasises the paucity of human data and the
need for more studies.
References
(1) Murray CDR, Emmanuel AV. Ghrelin and Helicobacter pylori [electronic response to Nwokolo CU et al. Plasma ghrelin following cure of Helicobacter pylori] gutjnl.com 2003 http://gut.bmjjournals.com/cgi/eletters/52/5/637#94
(2) Gokcel A, Gumurdulu Y, Kayaselcuk F, et al. Helicobacter pylori
has no effect on plasma ghrelin levels. Eur J Endocrinol 2003;148(4):423-6.
We commend the BSG and the authors for the excellent recent
publication of guidelines for the management of inflammatory bowel disease
in adults.[1] However we feel that their recommendation for routine
terminal ileal biopsying is inappropriate. Although it is important to
biopsy the terminal ileum if there is macroscopic evidence of an
abnormality, their statement that “a terminal ileal biopsy perfor...
We commend the BSG and the authors for the excellent recent
publication of guidelines for the management of inflammatory bowel disease
in adults.[1] However we feel that their recommendation for routine
terminal ileal biopsying is inappropriate. Although it is important to
biopsy the terminal ileum if there is macroscopic evidence of an
abnormality, their statement that “a terminal ileal biopsy performed at
colonoscopy documents the extent of examination” is not recommended
practice, due to the potential risk of variant Creutzfeld-Jacob disease
transmission from prion proteins which are prevalent in the lymphoid
tissue of Peyer’s patches in the ileum. Although the use of disposable
forceps may reduce the risk of transmission, there could still be
contamination of the intubation channel of the colonoscope and prion
protein is resistant to the standard endoscopic cleaning process.[2] If
the extent of examination needs to be documented, then a photograph of the
ileocaecal valve or ileal mucosa is preferable.
It is worth emphasising that prion protein may be present in any part
of the gastrointestinal tract [3] and random biopsy of gastrointestinal
mucosa for reasons other than confirming an endoscopic abnormality or
excluding microscopic colitis is not acceptable. Similarly for
surveillance colonoscopy where multiple biopsy is recommended, the risk
benefit ratio of this policy must be supported by the clinical
indications.
References
1. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of
inflammatory bowel disease in adults. Gut 2004; 53(suppl 5) 1.
2. Bramble MG, Ironside JW. Creutzfeld-Jakob disease: implications
for gastroenterology. Gut 2002; 50:888-90.
3. Herzog C, Sales N, Etchegaray N et al. Tissue distribution of
bovine spongiform encephalopathy agent in primates after intravenous or
oral infection. Lancet 2004; 363:422-8.
We read with interest the article by Eckardt et al regarding long-term results of pneumatic dilatation in achalasia.[1]
Fifty-four patients were followed up for a median of 14 years after a
single pneumatic dilatation using the Browne-McHardy dilator. The 5- and 10-year remission rates were 40 and 36% respectively and repeated
dilatations only mildly improved the clinical response. Most of the
rela...
We read with interest the article by Eckardt et al regarding long-term results of pneumatic dilatation in achalasia.[1]
Fifty-four patients were followed up for a median of 14 years after a
single pneumatic dilatation using the Browne-McHardy dilator. The 5- and 10-year remission rates were 40 and 36% respectively and repeated
dilatations only mildly improved the clinical response. Most of the
relapses occurred within one year of the dilatation. Patients with post-
dilatation lower oesophageal sphincter pressure of <_10 mmhg="mmhg" had="had" a="a" significantly="significantly" better="better" outcome.="outcome." the="the" authors="authors" suggest="suggest" that="that" failure="failure" to="to" respond="respond" first="first" dilatation="dilatation" should="should" lead="lead" consideration="consideration" of="of" alternative="alternative" therapy.="therapy." p="p"/> We disagree with this conclusion and we would like to bring to your
attention a recent prospective study on the long term effects of pneumatic
dilatation in 11 patients with achalasia.[2] A different approach was
chosen, ie treatment consisted of one or more pneumatic dilatations
under conscious sedation in order to achieve stable clinical remission,
defined as persisting 1 year after dilatation. To this purpose, a closer
follow-up was performed in the first year after dilatation (scheduled
assessments at 3 and 12 months). Thereafter clinical and manometric
assessments were performed yearly for 6 years. The clinical score was
according to Eckardt et al. Five patients needed one (30 mm diameter
Rigiflex dilator) and six needed two (30 and 35 mm diameter) dilatations.
No complications occurred. All patients remained in clinical remission and
their lower oesophageal sphincter pressure decreased to <_10 mmhg="mmhg" and="and" remained="remained" unchanged="unchanged" over="over" time.="time." p="p"/> There are similarities in the results between the two studies. 1) The
outcome of our 11 patients is in line with that of the 8 patients of
Eckardt et al with a lower oesophageal sphincter pressure of <_10 mmhg="mmhg" who="who" had="had" a="a" remission="remission" rate="rate" of="of" _75="_75" at="at" _6="_6" years.="years." _2="_2" the="the" observation="observation" that="that" six="six" patients="patients" in="in" our="our" series="series" needed="needed" second="second" dilatation="dilatation" all="all" relapsed="relapsed" within="within" one="one" year="year" first="first" agrees="agrees" with="with" data="data" by="by" eckardt="eckardt" i="i"/>et al
showing that most relapses occurred in the first 12 months. However,
our dilatations were more successful and above all a second dilatation led
to a sustained remission in all patients. We do not know the reasons for
this difference, but we think it may be at least partly related to our use
of the non compliant Rigiflex dilator, which is currently considered the
best choice,[3] although there are no adequately powered comparisons with
the Browne-McHardy dilator in the literature.[4] Similarly to our result,
a recent paper has shown very good efficacy of a second dilatation with
the Rigiflex dilator in patients who had relapsed.[5] Another possible
additional reason is the use of conscious sedation during the procedure
which allowed us to complete all dilatations; Eckardt et al, who used
topical anesthesia only, had to prematurely terminate 17% of the
procedures.
In conclusion, our published experience and our current clinical
practice, involving treatment and follow-up of 10-15 new achalasia
patients each year, suggest that performance of one or two dilatations
until stable clinical remission is a valuable strategy, and that pneumatic
dilatation under conscious sedation with the Rigiflex dilator is an
effective long-term treatment in most patients with achalasia.
References
1. Eckardt V F, Gockel I, Bernhard G. Pneumatic dilation for achalasia: late results of a prospective follow up investigation. Gut 2004;53:629-633
2. Penagini R, Cantù P, Mangano M, Colombo P, Bianchi PA. Long-term
effects of pneumatic dilatation on symptoms and lower oesophageal
sphincter pressure in achalasia. Scand J Gastroenterol 2002;37:380-384.
3. Vaezi MF, Richter JE. Current therapies for achalasia: comparison and
efficacy. J Clin Gastroenterol 1998;27:21-35.
4. Stark GA, Castell DO, Richter JE, Wu WC. Prospective randomized
comparison of Brown-McHardy and Microvasive balloon dilators in treatment
of achalasia. Am J Gastroenterol 1990;85:1322-1326.
5. Mikaeli J, Bishehsari F, Montazeri G, Yaghoobi M, Malekzadeh R.
Pneumatic balloon dilatation in achalasia: a prospective comparison of
safety and efficacy with different balloon diameters. Aliment Pharmacol
Ther 2004;20:431-436.
We read with great interest the paper by Jenkins et
al.[1] regarding screening guidelines for colorectal
cancer and polyps in patients with acromegaly and the
subsequent discussion by Renehan addressing
screening inconsistencies as compared to other high
risk groups.[2,3]
The optimal colorectal screening modality and
frequency in this group however requires clarification.
Colonoscopy...
We read with great interest the paper by Jenkins et
al.[1] regarding screening guidelines for colorectal
cancer and polyps in patients with acromegaly and the
subsequent discussion by Renehan addressing
screening inconsistencies as compared to other high
risk groups.[2,3]
The optimal colorectal screening modality and
frequency in this group however requires clarification.
Colonoscopy in this patient group is technically
demanding and often complicated by inadequate
bowel preperation.[1,4] However, despite current
controversies regarding true colorectal cancer risk
categorization in acromegaly, previous data from the
largest published series showed a trend for adenoma
and carcinoma formation in the right-hemi-colon.[5] This
is an important observation for many reasons.
Flat adenomas and carcinomas can be difficult to
detect by conventional colonoscopy alone, often
presenting as subtle mucosal erythema, mucosal
pallor, fold convergence, interruption of innominate
grooves, air-induced deformation or loss of vascular
net pattern.[6] The neoplastic risk for this
morphologically distinct group has additionally been
shown by many authors to be higher when compared
to exophytic polypoid lesions and exhibit a propensity
for the right colon.[7-10] De novo neoplastic lesions and
‘minute’ colorectal cancers are also associated with an
increased risk of lymph node metastasis due to early
invasion of the submucosal layer.[11] Tada et
al. found
extensive submucosal invasion in a cohort of flat
colorectal neoplasms,[12] with Shimoda’s series
corroborating this data with submucosal invasion
demonstrable in 69% of flat carcinomas compared to
only 35% of sessile and broad based polypoid
carcinomas.[13]
Morphologically flat and depressed lesions are also
known to occur in chronic ulcerative colitis (CUC)[14]
where the need for colorectal cancer screening with
total colonoscopy and now adjunctive chromoscopy is
adopted by many centers. Failure to detect such
lesions may impart account for those cases of CRC
which occurred in Winawers study, despite clearance
of all exophytic polyps and thus stresses the
requirement for accurate diagnosis and definitive
treatment of these high risk lesions.[15]
Given the lack of standardized and uniform reporting
regarding morphology of colorectal lesions in many of
the existing prevalence studies of adenomas and CRC
in acromegaly however, at present we can only
hypothesis that the high incidence of right-hemi-colonic
neoplasia may be an indicator of an alternative
morphologically distinct lesion such as the flat
adenoma and carcinoma with a trend toward a de novo
pathogenic sequence.
In our prospective study, 38 patients with acromegaly
underwent total colonoscopy by a single endoscopist
using the Olympus C240Z magnifying colonoscope.
Preparation was with 4 litres of Kleanprep 24 hours
prior to procedure. Pan-colonic chromoscopy using
0.5% indigo carmine sprayed onto the colonic mucosa
using an Olympus diffusion catheter (CS12890) was
applied. Identified lesions were morphologically
grouped according to the Japanese Research Society
Classification (JRSC).[16,17] A flat lesions was defined
as mucosal change with a flat or rounded surface
combined with a height of less than half the diameter of
the lesion.[18] High magnification views of all suspected
lesions were then obtained and reported according to
the modified Kudo criteria.[19] Tissue sampling was
performed with cold biopsy or endoscopic mucosal
resection (EMR) following exclusion of a Kudo type
V(n)/IIIs invasive crypt pattern which suggests deep
submucosal invasion. Mean intubation and extubation
times were recorded. Neoplastic change was
classified according to Vienna criteria.[20]
Caecal intubation was achieved in 37/38 (97%) of
patients with 36/38(94%) receiving confirmatory
terminal-ileal biopsies. Males represented 14/37 (37%
of the cohort, mean age 64 years (range 40-75). The
mean duration of intubation to the caecum was 16.5
minutes (range 3-31) and extubation (excluding
interventional procedures) 35 minutes (range 20-55).
There were no complications.
A total of 28 lesions were identified in 15 patients. A
total of 22 hyperplastic lesions were identified (79%) of
which 17(77%) were flat (JRSC II). Twenty (91%) were
located in the left colon and rectum. Of the 5 adenomas
identified, 4(80%) were present in the right colon with 4/
5(80%) being of JRSC II morphology. A single
adenoma with high-grade dysplasia was present in the
right colon and was flat with a small area of central
depression. No invasive carcinomas were diagnosed.
Results are summarized in table 1.
Table 1 Lesion demographics
Histology
N
Morphology
(JRSC)
Dominant
crypt pattern
Mean
size
(mm)
Anatomical
location
I
II
R. Colon
L. Colon/ rectum
Hyperplastic
22
5
17
I/II
6
2
20
Adenoma LGD
5
1
4
IIIL
6.5
4
1
Adenoma HGD
1
0
1
V(a)
5
1
0
Invasive neoplasia (T2 or beyond)
0
0
0
Nill
0
0
Total
28
6(21%)
22(79%)
7(25%)
21(75%)
Low grade Dysplasia (LGD)
High grade Dysplasia (HGD)
Although the numbers entering this study are small,
our results show a clear prevalence for JRSC class II
lesions in this select patient group. Although only one
adenoma with HGD was detected, it was small (5mm)
and was not identified prior to chromoscopic and
magnification enhancement, and therefore carries
major clinical connotations.
We suggest that further large prospective studies are
required to establish the true prevalence of flat and
depressed colorectal lesion in acromegaly, so the
optimal screening modality and frequency can finally be
established. Furthermore colonoscopists require
training in chromoscopic techniques if a higher
endoscopically ‘treatable’ lesional frequency is to be
detected at a screening level, so as to avoid the high
apparent incidence of interval neoplasms.
References
(1) Jenkins PJ, Fairclough PD. Screening guidelines for
colorectal cancer and polyps in patients with
acromegaly. Gut 2002;51:V13-14.
(2) Renehan AG, O'Dwyer ST, Shalet SM. Colorectal
neoplasia in acromegaly: the reported increased
prevalence is overestimated. Gut 2000;46:440.
(3) Renehan AG, O'Dwyer ST, Shalet SM. Guidelines for
colonoscopic screening in acromegaly are inconsistent
with those for other high risk groups. Gut
2003;52:1071-1072.
(4) Veysey MJ, Mills TD, Thomas LA et al. Prolonged
large bowel transit increases serum deoxycholic acid:
a risk factor for octreotide induced gallstones. Gut
1999;44:675-681.
(5) Jenkins PJ, Fairclough PD, Richards T et al.
Acromegaly, colonic polyps and carcinoma. Clin
Endocrinol 1997;47:17-22.
(6) Hurlstone DP, Fujii T, Lobo AJ. Early detection of
colorectal cancer using high-magnification
chromoscopic colonoscopy. Br J Surg 2002;89:272-82.
(7) Rembacken BJ, Fujii T, Cairns A et al. Flat and
depressed colonic neoplasms: a prospective study of
1000 colonoscopies in the UK. Lancet 2000;355:1211-
1214.
(8) Tsuda S, Veress B, Toth E et al. Flat and depressed
colorectal tumours in a southern Swedish population: a
prospective chromoendoscopic and histopathological
study. Gut 2002;51:550-555.
(9) Saitoh Y, Waxman I, West AB et al. Prevalence and
distinctive biologic features of flat colorectal adenomas
in a North American population. Gastroenterology
2001;120:1657-1665.
(10) Adachi M, Okinaga K, Muto T. Flat adenoma of the
large bowel: re-evaluation with special reference to
central depression. Dis Colon Rectum 2000;43:782-
787.
(11) Kudo S, Tamura S, Hirota S et al. The problem of de
novo colorectal carcinoma. Eur J Cancer
1995;31A:1118-20.
(12) Tada S, Yao T, Iida M et al. A clinicopathologic study
of small flat colorectal carcinoma. Cancer
1994;74:2430-2435.
(13) Shimoda T, Ikegami M, Fujisaki J et al. Early
colorectal carcinoma with special reference to its
development de novo. Cancer 1989;64:1138-1146.
(14) Kiesslich R, Fritsch J, Holtmann M et al. Methylene
Blue-Ailed Chromoendoscopy for the Detection of
Intraepitheial Neoplasia and Colon Cancer in
Ulcerative Colitis. Gastroenterology 2003;124:880-888.
(15) Winawer SJ, Zauber AG, Ho MN et al. Prevention of
colorectal cancer by colonoscopic polypectomy. The
National Polyp Study Workgroup. N Engl J Med
1993;329:1977-1981.
(16) General rules for clinical and pathological studies
on cancer of the colon, rectum and anus. Part I. Clinical
classification. Japanese Research Society for Cancer
of the Colon and Rectum. Jpn J Surg 1983;13:557-73.
(17) General rules for clinical and pathological studies
on cancer of the colon, rectum and anus. Part II.
Histopathological classification. Japanese Research
Society for Cancer of the Colon and Rectum. Jpn J Surg
1983;13:574-98.
(18) Kudo S, Kashida H, Tamura T et al. Colonoscopic
diagnosis and management of nonpolypoid early
colorectal cancer. World J Surg 2000;24:1081-1090.
(19) Kudo S, Rubio CA, Teixeira CR et al. Pit pattern in
colorectal neoplasia: endoscopic magnifying view.
Endoscopy 2001;33:367-373.
(20) Schlemper RJ, Riddell RH, Kato Y et al. The Vienna
classification of gastrointestinal neoplasia. Gut
2000;47:251-255.
Dear Editor
We were fascinated to read the paper by Cruz-Correa et al. [1] describing cases of mucosal tearing at colonoscopy in patients subsequently found to have collagenous colitis. We were particularly interested in their postulated mechanism for these tears being a disruption of colonic mural integrity by the sub-mucosal collagen layer. We would like to present two cases which add further weight to t...
Dear Editor
I was interested to read the paper by Cruz-Correa et al. [1] describing mucosal tears at colonoscopy in patients with collagenous colitis. I was then interested to read letters from Mitchell et al.[2] and Komuro et al.[3] describing their experience with mucosal tears in patients with collagenous colitis and diversion colitis, respectively. I would like to present a case of an elde...
Dear Editor
The article by Ransford and Langman [1] on suspected serious adverse drug reactions for sulphasalazine and mesalazine reported in the UK from 1991 to 1998 revealed significant differences between both drugs. Pancreatitis and interstitial nephritis were reported more frequently for mesalazine in comparison with sulphasalazine. The authors’ conclusion that mesalazine would not offer a safety benefit over s...
The Therapy Update in the May issue highlighted the potential role for antibiotic therapy in Crohn's disease [1]. Dr Colombel indicated the need for appropriate antibiotics that are based on current theories of pathogenesis, namely that they be effective against both extracellular and intracellular bacteria. The possible role of Mycobacterium paratuberculosis, although controversial, also should not be overl...
Dear Editor
Various therapeutic approaches for unresectable hepatocellular carcinoma (HCC) have been suggested during recent years. However, major advances concerning tumor regression or patient survival were not achieved. Few trials assessed the effect of the somatostatin analogue octreotide in advanced HCC with divergent results.[1,2] The latter might be due to the expression of somatostatin receptor type 2 (SSTR...
Editor,
Thoracic outlet syndrome is frequently undiagnosed in patients with non-cardiac ,non-coronary chest pains. See www.tos-syndrome.com. Patients with depression or panic attacks can have associated Thoracic Outlet Syndrome. The diagnosis will remain ignored unless the symptoms and physical findings are elicited in these patients.
Dear Editor
We would like to draw the attention of Murray et al.[1] to the objectives set out clearly in the introductory section of our paper.
Our study was not designed to address the question of whether ghrelin is involved in long-term regulation of body weight. Furthermore, the duration of the study was too short to see any change in BMI. More importantly, waist circumference would be a better...
Dar Editor
We commend the BSG and the authors for the excellent recent publication of guidelines for the management of inflammatory bowel disease in adults.[1] However we feel that their recommendation for routine terminal ileal biopsying is inappropriate. Although it is important to biopsy the terminal ileum if there is macroscopic evidence of an abnormality, their statement that “a terminal ileal biopsy perfor...
Dear Editor
We read with interest the article by Eckardt et al regarding long-term results of pneumatic dilatation in achalasia.[1] Fifty-four patients were followed up for a median of 14 years after a single pneumatic dilatation using the Browne-McHardy dilator. The 5- and 10-year remission rates were 40 and 36% respectively and repeated dilatations only mildly improved the clinical response. Most of the rela...
Dear Editor
We read with great interest the paper by Jenkins et al.[1] regarding screening guidelines for colorectal cancer and polyps in patients with acromegaly and the subsequent discussion by Renehan addressing screening inconsistencies as compared to other high risk groups.[2,3]
The optimal colorectal screening modality and frequency in this group however requires clarification. Colonoscopy...
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