We read with interest the article by Ehrer A J, et al.[1] the authors have conclusively proven the benefit of
sildenafil citrate in reducing the lower oesophageal sphincter pressure
and propulsive forces in the body of oesophagus in both healthy subjects
and patients with esophageal dysmotility disorders. The beneficial effect
was shown to last for upto 8 hours after a single, daily dose of 50...
We read with interest the article by Ehrer A J, et al.[1] the authors have conclusively proven the benefit of
sildenafil citrate in reducing the lower oesophageal sphincter pressure
and propulsive forces in the body of oesophagus in both healthy subjects
and patients with esophageal dysmotility disorders. The beneficial effect
was shown to last for upto 8 hours after a single, daily dose of 50 mg.
We have done a similar study in patients with irritable bowel
syndrome (IBS) and wish to share our results.
Irritable bowel syndrome is characterized by disturbances of
gastrointestinal functions that occur in everybody from time to time in
response to dietary indiscretions or psychological upheavals, but present
to a greater extent and with greater frequency in patients with IBS.[3] the
abnormal patterns of motor activity have been demonstrated in colon [4] but
also in jejunum, ileum [5] and esophagus.[6]
Nitric oxide (NO) is a major inhibitory neurotransmitter in
gastrointestinal tract.[2] NO activates soluble guanylate cyclase thereby
enhancing the production of guanosine 3’, 5’- cyclic mono phosphate
(cGMP). Sildenafil blocks the degradation of NO by blocking
phosphodiesterase type 5. This results in increased levels of NO, leading
to increased level of cGMP and cGMP dependent protein kinase. This
causes relaxation of smooth muscles in various organs. We thought of
utilizing this effect of sildenafil citrate and study its effects on IBS
patients having colonic dysmotility.
A prospective, open label, intention to treat study was planed. 58
married male, patients with irritable bowel disease, diagnosed on the
basis of Rome II criterion,[7] were screened. Out of these 18 reported
erectile dysfunction (ED) along with symptoms of IBS. These 18 patients
were enrolled for the study. They were aged between 20-40 years with mean
age of 29 ±9.54 years. After explaining the nature of the study 17 patients
consented for participation in the study. All the drugs were discontinued
for a period of 2 weeks run in period, except fiber supplements, which
were continued throughout the study period. Baseline characteristics were
recorded along with the symptoms. The patients were asked to score theirs
symptoms (IBS and ED symptoms) on a scale of 1 to 10 at the beginning of
the study and on every follow up, to compare the improvement after
treatment. The patients were started on 12.5 mg of sildenafil citrate once
daily at bed time. They were asked to note down improvement in their
symptoms and any untoward effects. The patients were followed up at 2
weekly intervals for 6 weeks and the drug dose was increased at every
follow up. The maximum dose given was 37.5 mg / day. Compliance was
measured by pill count. All the patients complied with the therapy. Only
2 patients reported minor side effects like headache and flushing with
37.5 mg dose. All the patients experienced significant improvement in
their ED but none of them reported any improvement in any IBS symptoms.
Though sildenafil citrate in known to relax smooth muscle cells in
various organs and has been found to be effective in improving esophageal
dysmotility1 patients of IBS with erectile dysfunction did not report any
improvement in their symptoms with 37.5 mg/day dose. The reason for this
lack of response could be the lower dose used by us in the study group.
Since there are no studies available till date regarding the use of
sildenafil in IBS and no guidelines are available regarding the minimum /
maximum dose of sildenafil to be used in gastrointestinal dysmotility, we
gradually hiked up the dose so as to avoid significant side effects.
References
(1) Ehrer AJ, Schwartz I, Hammer HF, Petnehazy T, Scheidl SJ, Weber K,
Krejs G. Effect of sildenafil on oesophageal motor function in healthy
subjects and patients with esophageal motor disorders. Gut 2002;50:758-64.
(2) Sanders KM, Ward SM. Nitric oxide as a mediator of non adrenergic, non
cholinergic neurotransmitter. Am J Physiol 1995;489: 735-43.
(3)Read NW. Irritable bowel syndrome, (Chapter 91). In Feldman M, Friedman LS,
Sleisenger (Eds) Gastrointestinal and liver disease, 7th edition. London: Saunders, 2002. Pp.1794-1806.
(4) McKee DP, Quigley EMM. Intestinal motility in irritable bowel syndrome:
Is IBS a motility disorder? Dig Dis Sci 1993;38:1761-82.
(5) Kellow JE, Gill RC, Wingate DL. Prolonged ambulant recording of small
bowel motility demonstrates abnormality in irritable bowel syndrome. Gastroenterology 1990;98:1208-18.
(6) Read NW. Visceral afferent information and functional bowel disease:
Evidence of dyssensation and altered reflux function. In Mayer EA,
Raybould NE (Eds) Basic and clinical aspects of chronic abdominal pain. Amstredum: Elsevier, 1993. Pp.87-96.
(7) Drossman DA. Rome II: The functional intestinal disorders. McLean, Va,
Degnan Associates, 2002.
We read the study by Prantera and colleagues, with great interest.
As the authors assert, there have been few good quality and well designed
clinical trials, with sufficient power, to examine the effects of
probiotics on inflammatory bowel disease.
This trial unfortunately also has a number of weaknesses both in its
reporting and methodology.
We read the study by Prantera and colleagues, with great interest.
As the authors assert, there have been few good quality and well designed
clinical trials, with sufficient power, to examine the effects of
probiotics on inflammatory bowel disease.
This trial unfortunately also has a number of weaknesses both in its
reporting and methodology.
The report does not make clear the exact time point at which patients
were recruited to the trial and randomized. As such recruitment bias may
be introduced. The issue of allocation concealment is also ignored in the
paper. Furthermore, at no point do the authors fully address the difficult
issue of standardisation, be it regarding the patient's disease, the
surgeon, the endoscopist or the assessors of clinical outcome.
The authors do not report any attempt to estimate the necessary
sample size for the study. The absence of a power calculation or
confidence intervals leaves the authors open to the same criticism that
they have levelled at other studies. The statistical analysis used is not
an intention to treat analysis. We also question whether a chi-squared
test was used to compare differences in proportions rather than a z test
as stated in the paper.
The study concludes that probiotics are ineffective in preventing
recurrence after curative resection. Indeed endoscopic recurrence was 25%
greater in the probiotic group, although this was not statistically
significant. However this conclusion is based on the analysis of just 37
patients. Clearly, the possibility of a type II error must be acknowledged.
The authors do accept that this must be considered a pilot study.
Given the possible biases and lack of power in this study, it should
not be considered to be Class Ib evidence. We feel this study re-inforces
the fact that a well designed, multi-centre randomised controlled trial is
needed to test the hypothesis of the whether probiotics are of any benefit
in Crohn's Disease.
We read with interest the British Society of Gastroenterology
guidelines for the diagnosis and treatment of cholangiocarcinoma (Gut
2002:51(Suppl VI): 1-9).
The authors recommend that routine biliary drainage before assessing
resectability or preoperatively should be avoided except in the context of
acute cholangitis. They do not state the rationale for this approach.
Presumably the a...
We read with interest the British Society of Gastroenterology
guidelines for the diagnosis and treatment of cholangiocarcinoma (Gut
2002:51(Suppl VI): 1-9).
The authors recommend that routine biliary drainage before assessing
resectability or preoperatively should be avoided except in the context of
acute cholangitis. They do not state the rationale for this approach.
Presumably the argument against preoperative biliary drainage is the
possible increased risk for perioperative complications, increased risk of
bile leakage of chole-enteric anastomosis because of stent-induced
inflammatory response or increased mortality. On the other hand, the
argument for preoperative biliary drainage is equally persuasive. There
may be improvement in nutritional and metabolic function, including
restoration of enterohepatic circulation and improvement in hepatic
synthetic function and coagulation; improvement in immune function,
reduced risk for perioperative complications or reduced mortality. The
authors quote two studies to support their recommendation (Nakeeb et al.,
Hochwald et al.[1,2]). However they ignore two other prospective randomized
controlled trials comparing preoperative biliary drainage with no
preoperative biliary drainage (Lai et al.; Lygidakis et al.[3,4]). Lai et al.[3]
revealed no difference in morbidity and mortality while Lygidakis et al.[4]
found that there was significantly reduced operative morbidity and
mortality with preoperative biliary drainage. They also ignore at least
eight retrospective studies comparing preoperative biliary drainage with
no preoperative biliary drainage which have conflicting results. These
individual studies are flawed by the heterogeneous nature of the patients
included; whether a sphincterotomy was performed alone or in combination
with stent; insufficient sample sizes and varying types of surgical
procedures used. A recent meta-analysis of these prospective and
retrospective studies found no evidence of either a positive or adverse
effect of preoperative endoscopic biliary stent placement on the outcome
of surgery (Saleh et al.[5]). We therefore feel that there is insufficently
robust data to justify the recommendation by the guidelines that
preoperative biliary drainage or before assessing resectability should be
avoided. In practice, because of the delay in the work up of a patient
for resectability and especially with the limited resources of the NHS,
there is a danger that these patients may develop complications from their
obstructed biliary system in the interim. The recommendations are not
based on level A evidence but are in fact level D evidence.
In the algorithm for the management of cholangiocarcinoma, the
authors state that if the lesion is resectable, patients should not have
ERCP (unless infected) or percutaneous biopsy of the lesion. The
implication is that patients will undergo major surgery which has a
significant risk of mortality and morbidity without any prior attempt to
obtain histology and therefore a definitive diagnosis. Discrimination of
malignant from benign bile duct strictures is difficult although benign
strictures are rare. However, up to 10% of bile duct strictures may turn
out to be benign and may not be distinguishable from a malignant stricture
even at surgery (Nakayama, et al.[6]).
In summary, there is insufficient evidence to justify the recommendation
that routine biliary drainage prior to resection or assessment for
resection should be avoided. With the present data available, there is
neither a positive or adverse effect of preoperative endoscopic biliary
stent placement on the outcome of surgery. We also feel that prior to
resection, attempts should be made to obtain histological confirmation
with ERCP and brushings for cytology. If not, patients should be made
aware that they may undergo resection for benign disease.
References
(1) Nakeeb A, Pitt HA. The role of preoperative biliary decompression in
obstructive jaundice. Hepatogastroenterol 1995;42:332-7.
(2) Hochwald SN, Burke EC, Jarnagin WR, et al. Association of preoperative
biliary stenting with increased postoperative infectious complications in
proximal cholangiocarcinoma. Arch Surg 1999;134:261-6.
(3) Lai ECS, Mok FPT, Fan ST, Lo CM, Chu KM, Liu CL, et al. Preooperative
endoscopc drainage for malignant obstructive jaundice. Br J Surg
1994;81:1195-8.
(4) Lygidakis NJ, van der Heyde MN, Lubbers MJ. Evaluation of preoperative
biliary drainage in the surgical management of pancreatic head ccarcinoma.
Acta Chir Scand 1987;153:665-8.
(5) Saleh MA, Norregaard P, Jorgensen HL, Andersen PK, Matzen P.
Preoperative endoscopic stent placement before pancreaticododenoectomy: a
meta-analysis of the effect on morbidity and mortality. Gastrointest
Endosc 2002;56:529-34.
(6) Nakayama A, Imamura H, Shimada R, Miyagawa S, Makuuchi M, Kawasaki S.
Proximal bile duct stricture disguised as malignant neoplasm. Surgery
1999;125:514-21.
The UK Guidelines on Acute pancreatitis by the BSG Working party (Gut
1998; 42(suppl 2): S1-13) recommends cefuroxime as the preferred
antibiotic in patients with acute severe pancreatitis. This is based on
the study by Saino et al.[1] In this randomised, prospective study even
though less people in the cefuroxime group died there were 67% of the
patients who started treatment with ce...
The UK Guidelines on Acute pancreatitis by the BSG Working party (Gut
1998; 42(suppl 2): S1-13) recommends cefuroxime as the preferred
antibiotic in patients with acute severe pancreatitis. This is based on
the study by Saino et al.[1] In this randomised, prospective study even
though less people in the cefuroxime group died there were 67% of the
patients who started treatment with cefuroxime who were converted to
imipenem plus vancomycin and flucanazole in a mean of 9 days. This makes
the study rather difficult to interpret with regard to whether cefuroxime
is the best antibiotic as the better mortality could have been due to the
change in antibiotic. Many surgeons in UK and Ireland prefer cefuroxime to
other antibiotic [2] but antibiotics like imipenem, 4-quinolones, third
generation cefalosporins have much better tissue penetration.[3]
References
(1) Sainio V, Kemppainen E, Puolakkaien P, et al. Early antibiotic
treatment in acute necrotising pancreatitis. Lancet 1995; 346:663.
2.Powell JJ, Campbell E, Johnson CD, et al. Survey of antibiotic
prophylaxis in acute pancreatitis in UK and Ireland. British Journal of
Surgery 1999;86:320.
3.Powell JJ, Miles R, Siriwardena AK, Antibiotic prophylaxis in the
initial management of acute severe pancreatitis. British Journal of
Surgery 1998;85:582.
I read Dr Travis’ Therapy Update [1] with interest, the topic is timely in a market about to be challenged by new generic mesalazine brands. I note the choice of time dependent mesalazine (Pentasa), but, if mesalazine is to be relied upon exclusively, some evidence suggests pentasa may not be the best choice. The recent study by Kruis et al.[2] in the maintenance of remission in ulcerative colitis fo...
I read Dr Travis’ Therapy Update [1] with interest, the topic is timely in a market about to be challenged by new generic mesalazine brands. I note the choice of time dependent mesalazine (Pentasa), but, if mesalazine is to be relied upon exclusively, some evidence suggests pentasa may not be the best choice. The recent study by Kruis et al.[2] in the maintenance of remission in ulcerative colitis found that with pentasa 1.5g per day the 6 month remission rate was 56.8% compared to 77.5% with balsalazide 3g twice daily (p= 0.045).
The assertion that the advantages of the azo-bond delivery to the distal colon can be matched by simply increasing the dose of pH dependent (asacol), or time dependent release (pentasa), has not been born out by laboratory or clinical studies. Tissue level studies have indicated that double dose mesalazine is delivered to the kidney, not the colon.[3] A large clinical trial of pentasa in mild to moderate active ulcerative colitis found remission rates of 29% for both 2g/day and 4g/day.[4] This latter study highlights the lack of efficacy of mesalazine released by a time dependent delivery system in active UC. In contrast three studies comparing balsalazide with mesalazine (pH dependent release),[5-7] containing a total of 426 patients, all found balsalazide to be superior in active UC, with rapid resolution of symptoms (median 10 days in one study[5]) and superior sigmoidoscopic scores (in all three studies). Plasma concentrations of 5ASA were 4.5 fold lower in patients treated with balsalazide than mesalazine (p=0.018).[6] The patients with most to benefit are new patients with distal disease.[7] The use of 5ASA in the initial treatment of UC does not require mega doses as Dr Travis suggests, indeed mega doses of mesalazine delivered by asacol or pentasa are ineffective, but it does require a reliable delivery system, such as the azo-bond, and an inert carrier as with balsalazide. The clinical implication of this efficacy in mild to moderate active UC is that the threshold for the use of steroids can be raised. Of interest in the North American trials of balsalazide vs mesalazine, 60 patients failing mesalazine treatment were treated after the trial with balsalazide open label, with 60% response.[8]
The advocates of sulphasalazine (SASP) and those wishing to use the least expensive treatment cite trials of SASP vs. newer agents [9] and conclude that SASP is the most cost effective, these trials are in patients with known UC and specifically exclude patients who are SASP intolerant. In two recently published studies,[10,11] patients, with newly diagnosed, or previously untreated UC, were randomised to SASP or balsalazide, 34% were intolerant of SASP at the modest dose of 3g daily compared to 5% for balsalazide 6.75g daily. The number needed to treat to avoid SASP intolerance at this rate is only 3, and in new patients it seems particularly important to use well tolerated effective treatment first line and avoid the loss of confidence that drug intolerance produces.
It seems a sad reflection on the pharmaceutical industry sponsored research that the most recent trial on UC treatment with 5ASA quoted in the therapy update is from 1998. Large clinical trials of one 5ASA brand against another are expensive and the advent of generic mesalazine preparations is unlikely to improve this situation. My interpretation of recently published evidence is that the mesalazine release mechanism is important for the efficacy, reliability of delivery, and safety of the oral preparations and that balsalazide is now the gold standard for other agents to be judged against.
The author has accepted hospitality from the manufactures of all the current 5ASA preparations, and sat on an advisory panel for Shire.
References
(1) Travis SPL. Therapy update. Which 5ASA? Gut 2002;51:548-9
(2) Kruis W, Schreiber S, Theuer D, et al. Low does balsalazide (1.5g twice daily) and mesalazine (0.5g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3g twice daily) was superior in preventing relapses. Gut 2001;49:783-89
(3) Hussain FN, Ajjan RA, Riley SA. Dose loading with delayed release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters. Br J Clin Pharmacol 2000;49:323-30
(4) Hanauer S, Schwartz J, Robinson M, et al. Mesalamine capsules for treatment of active ulcerative colitis: Results of a controlled trial. Am J Gastroenterol 1993;88:1188-1197
(5) Green JRB, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. Gastroenterology 1998;114:15-22
(6) Levine DS, Riff DS, Pruitt R, et al. A randomized double blind dose response comparison of balsalazide 6.75g, balsalazide 2.25g and mesalamine 2.4g in the treatment of active mild-to-moderate ulcerative colitis. Am J Gastroenterol2002;97:1398-1407
(7) Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute ulcerative colitis. Gastroenterology 2000;118:A756
(8) Data on file. Shire pharmaceuticals Ltd.
(9) Sutherland L, Roth D, Beck P, May G, Makiyama K. Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis.(Cochrane review) In the Cochrane Library, Issue 4. Oxford: Update software, 2000.
(10) Green JRB, Mansfield JC, Gibson JA, Kerr GD, Thornton PC. A double blind comparison of balsalazide 6.75g daily and sulfasalazine 3g daily in patients with newly diagnosed or recently relapsed active ulcerative colitis. Aliment Pharmacol Ther 2002;16:61-68
(11) Mansfield JC, Giaffer MH, Cann PA, et al. A double blind comparison of balsalazide 6.75g and sulfasalazine 3g as sole therapy in the management of ulcerative colitis. Aliment Pharmacol Ther 2002;16:69-77
We read with interest the eLetter of Laghi et al. (14 August 2002).
We
agree with the first comment of Laghi et al. concerning the experience of
the investigators. At the beginning of this study, our experience was
limited to the cases done for the study published in Gut[1] and to a
couple of multidetector computed tomography colonography (MDCT-
colonography) in patients with in...
We read with interest the eLetter of Laghi et al. (14 August 2002).
We
agree with the first comment of Laghi et al. concerning the experience of
the investigators. At the beginning of this study, our experience was
limited to the cases done for the study published in Gut[1] and to a
couple of multidetector computed tomography colonography (MDCT-
colonography) in patients with incomplete conventional colonoscopy. We
were entirely aware about the limits of our clinical experience in CT-
colonography.[1,2] Independent of this fact, we were able to demonstrate
the advantages of MDCT colonography in the detection of colorectal
lesions.
We do not agree with the second comment in the eLetter of Laghi et al.
As described in the methods section the image reconstructions were
performed with a slice thickness of 2.5 mm with reconstruction intervals
of 2 mm (overlap 0.5 mm) that means that we used an optimal technical
setting. But it is true that we have been using only 5 mm slices in our
first study.[1]
Aware about our limited experience we included in our paper a
retrospective analysis of all missed lesions. If we add lesions not
detected due to perception errors to our first view results we reach
sensitivities as good as those of more experienced investigators:[3,4]
lesions 10 and more mm 100 % sensitivity, lesions 6 to 9 mm 80 %
sensitivity.
In conclusion, we showed clearly that the moderate results in detection of
small polyps is due to the limited experience and not to intrinsic
limitations of MDCT colonography.
References
(1) Pescatore P, Gluecker T, Delarive J, et al. Diagnostic accuracy and
interobserver agreement of CT colonography (virtual colonoscopy). Gut
2000; 47: 126-30.
(2) Gluecker T, Meuwly JY, Pescatore P, Schnyder P, Delarive J, Jornod P,
Meuli R, Dorta G. Effect of investigator experience in CT colonography.
Eur Radiol 2002;12:1405-9.
(3) Laghi A, Iannaccone R, Carbone I, et al. Computed tomographic
colonography (virtual colonoscopy): blinded prospective comparison with
conventional colonoscopy for the detection of colorectal neoplasia.
Endoscopy 2002;34: 441-6.
(4) Macari M, Bini EJ, Xue X et al. Colorectal Neoplasms: Prospective
Comparison of Thin-Section Low-Dose Multi-Detector Row CT Colonography and
Conventional Colonoscopy for Detection. Radiology 2002;224: 383-92.
We read with interest the recent article by Gluecker et al. (Gut 2002;
51: 207-211) investigating the performance of multidetector computed
tomography (MDCT) colonography in the detection of colorectal lesions in
comparison with that of conventional colonoscopy. The authors concluded
that MDCT colonography provides good sensitivity and specificity for the
detection of colonic lesions la...
We read with interest the recent article by Gluecker et al. (Gut 2002;
51: 207-211) investigating the performance of multidetector computed
tomography (MDCT) colonography in the detection of colorectal lesions in
comparison with that of conventional colonoscopy. The authors concluded
that MDCT colonography provides good sensitivity and specificity for the
detection of colonic lesions larger than 10 mm in diameter, but certain
weaknesses in the study design should be emphasised. We would like to
comment further on two of these weaknesses, as they are potentially
important in interpreting the results of Gluecker et al. (Gut 2002; 51: 207
-211).
First, the evaluation of MDCT colonographic data sets was performed
by two observers with little (radiologist with experience of approximately
60 CT colonographic examinations) or no (gastroenterologist) experience in
the procedure. We believe that this represents a major limitation to the
study. It is already well known from the literature [1,2] that data
interpretation of CT colonography requires a long learning process. The
authors too acknowledged this key issue in the manuscript (Gluecker et al.
Gut 2002; 51: 207-211). Indeed, the first reading of the MDCT colonography
images identified 1/41 lesions 5 mm in diameter or smaller, 5/15 lesions
between 6 and 9 mm, and 9/11 lesions 10 mm or larger. However,
retrospective evaluation of the same data (i.e., a second reading) already
allowed the authors to detect many of the lesions missed in the first
reading session (18/40 lesions 5 mm or smaller; 7/10 lesions between 6 and
9 mm; 2/2 lesions 10 mm or larger). All lesions identified retrospectively
were missed due to perceptive errors. Although perceptive errors may occur
with MDCT, the high incidence of this type of errors in the study by
Gluecker et al. (Gut 2002;51: 207-211) is best explained with the low
experience of the observers, and should not be construed as an intrinsic
limitation of MDCT colonography.
Second, it should be noted that one of the major advantages
introduced by MDCT technology is represented by the ability of combining
thin beam collimation (1 or 2.5 mm) with short acquisition times.[3] The
use of 5 mm beam collimation considerably reduces this advantage and could
explain the poor performance of MDCT in the detection of small lesions
(lesions 6-9 mm, sensitivity 33 %; lesions 5 mm or smaller, sensitivity 4 %)
in the hands of the authors. In particular, the use of a thin beam
collimation would have significantly increased the spatial resolution of
CT images with consequent improvement in image quality, while still
allowing for short acquisition time and only slightly higher radiation
exposure delivered to patients.[3,4]
In recent years, several studies have demonstrated that CT
colonography has a performance similar to that of conventional colonoscopy
in the detection of colorectal lesions 6 mm in diameter or larger.[5-7]
In particular, with regard to CT colonography as peformed with thin-beam-
collimation MDCT, both published[8,9] and unpublished [Laghi A, et al.
Multi-slice spiral CT colonography for the detection of colorectal polyps
and neoplasms, RSNA 2001, personal communication] data have shown that
MDCT colonography can increase the detection rate of small lesions. In
addition, the use of thin-beam-collimation MDCT colonography can reduce
the number of false positive findings by enabling better assessment of the
morphology and CT density of suspected lesions, thus allowing to better
differentiate residual stool or hypertrophic colonic folds from colorectal
lesions.[10]
We therefore believe that MDCT colonography can reliably detect
lesions smaller than 10 mm (in particular those in the 6 to 9 mm range),
provided that experienced readers interpret the results and that the
technological potential of the current devices is fully exploited with the
use of thin-beam-collimation protocols.
References
(1) Pescatore P, Gluecker T, Delarive J, et al. Diagnostic accuracy and
interobserver agreement of CT colonography (virtual colonoscopy). Gut
2000; 47: 126-30.
(2) Spinzi G, Belloni G, Martegani A, et al. Computed tomographic
colonography and conventional colonoscopy for colon diseases: a
prospective, blinded study. Am J Gastroenterol 2001; 96: 394-400.
(4) Laghi A, Iannaccone R, Mangiapane F, et al. Experimental colonic
phantom for the evaluation of the optimal scanning technique for CT
colonography using a multidetector spiral CT equipment. Eur Radiol 2002
(in press).
(5) Fenlon HM, Nunes DP, Schroy PC, et al. A comparison of virtual and
conventional colonoscopy for the detection of colorectal polyps. N Engl J
Med 1999; 341: 1496-503.
(6) Laghi A, Iannaccone R, Carbone I, et al. Computed tomographic
colonography (virtual colonoscopy): blinded prospective comparison with
conventional colonoscopy for the detection of colorectal neoplasia.
Endoscopy 2002; 34: 441-6.
(7) Laghi A, Iannaccone R, Carbone I, et al. Detection of colorectal
lesions with virtual computed tomographic colonography. Am J Surg 2002;
183: 124-31.
(8) Rogalla P, Meiri N, Rückert JC, et al. Colonography using
multislice CT. Eur J Radiol 2000; 36: 81-5.
(9) Wessling J, Fischbach R, Domagk D, et al. Colorectal polyps:
Detection with multi-slice CT colonography. Rofo Fortschr Geb Rontgenstr
Neuen Bildgeb Verfahr 2001; 173: 1069-71.
(10) Macari M, Bini EJ, Xue X, et al. Colorectal neoplasms: prospective
comparison of thin-section low-dose multi-detector row CT colonography and
conventional colonoscopy for detection. Radiology 2002 (in press).
For decades, surgical operation has been considered as the only ideal
therapeutic method in the treatment of hydatid cyst/cystic echinococcosis,
a parasitic zoonosis that still remains prevalent in a number of
countries, and especially PR China where the estimated number of cases is
over 500,000.[1] The ultrasound (US)-guided Puncture-Aspiration-Injection
-Reaspiration (PAIR) technique [2,3] has now ga...
For decades, surgical operation has been considered as the only ideal
therapeutic method in the treatment of hydatid cyst/cystic echinococcosis,
a parasitic zoonosis that still remains prevalent in a number of
countries, and especially PR China where the estimated number of cases is
over 500,000.[1] The ultrasound (US)-guided Puncture-Aspiration-Injection
-Reaspiration (PAIR) technique [2,3] has now gained international
recognition and dissemination [4,5]. Schipper et al. [6] recently
reported their experience of 12 multivesicular or complicated cysts
treated with the 'PEVAC' technique. We think that the experience gained in
People Republic of China for the past decade is worth reporting.
Since 1986, after a series of experiments and researches [7,8], we
eventually designed the dilatable-multi-function trocar (DMFT, patent
number 92 2 38136.4, registered in PR China) to treat hepatic and
abdominal CE by using an original technique, the 'percutaneous puncture, drainage and curettage' (PPCD).[9, 10] We studied US-guided treatment of
CE on a total of 1614 cysts in 1409 patients (table 1). Under US-guidance, punctures were performed through the intercostal, dorsolumbar,
or abdominal route; for vesico-rectal cysts we adopted a trans-anal, -
rectal or -vaginal route. A usual PAIR needle (#14-16 gauge; inside
diameter 1.2-2.0 mm, outside diameter 1.4-2.2 mm, length 20cm) and the
DMFT (inside diameter 4-9mm, outside diameter 6-12 mm, length 12-30cm)
were used for 740 and 699 punctures respectively; a secondary puncture was
necessary in 175 cases. PAIR was performed for small to middle-sized
unilocular cysts with no cysto-biliary fistula.[5] PPCD was used for
multivesicular and complicated cysts, as a primary procedure or as a
second step when PAIR was inefficient.
The DMFT is inserted under local anesthesia, through a 0.8-1 cm skin
incision. It is linked to an aspiration apparatus, with a slightly
negative pressure from the beginning of the procedure; the negative
pressure is then increased when the trocar is in the cyst cavity, after
its air balloon has been inflated. Hydatid endocyst, daughter cysts and
other cyst content are extracted through aspiration, and cyst cavity is
repeatedly irrigated with 10-20 % saline. If necessary, curettage of the
cystic cavity using the suction curette is done until the irrigated
solution becomes clear. The cavity is left as empty as possible. The
external tube remains in the cavity for the drainage of the cystic cavity.
If necessary an inner drainage tube is inserted through the external tube
which is then removed, and the drainage tube is fixed onto the abdominal
skin and left for 2-3 days according to the local evolution of the
drainage fluid.
All the procedure was done in a surgical environment. Albendazole (20
mg/kg/day orally) was given for an average of 3 days before and 6 months
after the procedure. A careful follow-up of the patients was ensured
within the days after PAIR or PPDC, then at 3, 6, 12, 24 and 36 months.
The puncture procedure failed in 1.8 % of cases. In 62 cases, with a
volume of the cystic cavity over 2000 mL and with obvious venous
hypertension, the puncture treatment followed a two-stage procedure. No
patient died. Anaphylactic manifestations occurred in only 4 patients
(facial oedema and acute dyspnea). Thirteen patients had fever because of
improper drainage of the cystic cavity; they recovered after further
curettage of the cystic cavity. Bile leakage of various degrees occurred
in 392 cysts, of which 17 had a drainage volume of over 400 mL / per day,
and the drainage lasted for 4-17 weeks. In 16 cases with a long-lasting
fistula, a surgical omentoplasty was necessary and successful. A 3-yr
follow-up showed that the cysts relapsed in 2.3 % of the patients in situ,
and in only 1 % of cases in other locations. A tumour was misdiagnosed in
4 patients; they were operated on afterwards. Results of the follow-up
showed that the all symptoms disappeared in 98 % of the patients.
This experience based on the US-guided treatment of CE in more than
1400 cases with a 3 yr-follow-up fully supports the efficiency and
usefulness of the technique of percutaneous evacuation of cyst content
using a technique similar to that reported by Schipper et al. in 12 cases.
The specifically adapted DMFT that makes the technique easier and safer
may, in addition, be proposed as an aid to surgeons and interventional
radiologists involved in the treatment of CE.
Acknowledgements
The authors thank Ms Wu Xiaohong, from the Agriculture High School of
Qinghai Province, PR China and University of Franche-Comté Department of
Linguistics, France, for the Chinese-English translation of the data, and
Prof. Philip Craig, from Salford University, UK, for the revision of the
manuscript. Wang Xiao Zhi participates in the 'PAIR' network of the WHO
Informal Working Group on Echinococcosis(C Filice, Pavia, Italy,
coordinator) and has contributed to the booklet on PAIR published by WHO.[5]
References
(1) Wang YY, Rogan MT, Vuitton DA, Wen H, Giraudoux P, Bartholomot B,
Macpherson C, Zou PF, Ding ZX, Zhang XF, Luo J, Fu Y, Xiong HB, Mcvie A,
Yang WG, Craig PS. Cystic Echinococcosis in Semi-Nomadic Pastoral
Communities in Northwest China.ActaTropica 2001;95:153-8.
(2) Ben Amor N, Gargouri M, Gharbi HA, Golvan YJ, Ayachi K, Kcouck H.
Essai de traitement par ponction des kystes hydatiques abdominaux
inopérables. Ann Parasitol Hum Comp 1986;61:689.
(3) Filice , Pirola F, Brunetti E, Dughetti S, Strosseli M, Scotti-
Foglieni C. A new therapeutic approach for hydatid cysts of the liver.
Aspiration and alcohol injection under sonographic guidance.
Gastroenterology 1990;98:1366-8.
(4) WHO-Informal Working Group on Echinococcosis. Guidelines for
treatment of cystic and alveolar echinococcosis in humans. Bull WHO, 1996,
74: 213-42.
(5) WHO-Informal Working Group on Echinococcosis. PAIR: an alternative
treatment in cystic echinococcosis. 2002. Geneva: WHO/CDS.
(6) Schipper H G, Laméris J S, van Delden O M, Rauws E A and Kager P
A. Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts
with or without cystobiliary fistulas which contain non-drainable
material: first results of a modified PAIR method. Gut 2002;50:718-23.
(7) Wang XZ, Shao XL, Liang TZ.Li YS, Wei WH, Gao GM, Cheng YH.
Elementary research on Percutaneous Puncture treatment guided by B-
ultrasound for cystic echinococcosis. Chin J Ultrasound Med1991;7:54-5 (in Chinese).
(8) Wang XZ, Li YS, Lu HK, Jia GQ, Wei WH, Wang LQ. Observations on
the experimental treatment of echinococcosis in sheep by using puncture. Qinghai Med J 1994:144:1-3 (in Chinese).
(9) Wang XZ, Fen SL, Zhao HN. A new type of multi-functional trocar
for percutaneous puncture in hydatidosis. Arch Int Hidatidosis, Beijing
1993;30:404. (abstract)
(10) Wang XZ, Changming Y, Shengli F, Jinshen C, Hui M, Shufang L,
Qunke T, Jun W, Tingxshang L, Zailu G, Qiang J, Yangbao M. Therapy of
liver and abdominal cavity with percutaneous drainage and curettage
(report of 1002 cases). Arch Int Hidatidosis, Lisbon 1997;32:254 (abstract).
Table Main characteristics of the population of 1409 patients with
cystic echinococcosis
and of the hydatid cysts treated by PAIR and/or PPCD.
The recent report by MacDonald et al., despite provides promising
findings for an effective adjuvant chemoradiotherapy of gastric cancer
patients after gastrectomy has raised a numerous of questions and
criticisms.[1,2]
The weakness of this randomized trial and the lack of a surgical quality
control have currently been extensively described
[1,2,...
The recent report by MacDonald et al., despite provides promising
findings for an effective adjuvant chemoradiotherapy of gastric cancer
patients after gastrectomy has raised a numerous of questions and
criticisms.[1,2]
The weakness of this randomized trial and the lack of a surgical quality
control have currently been extensively described
[1,2,www.gastriccancer.net].
To avoid repetition, here we are focused on
the importance of quality of surgery in prolonging survival. Undoubtedly,
curative resection (R0) is generally accepted as the treatment of choice
in gastric cancer and it has been repeatedly recognized in multivariate
analyses as the most important and independent predictor of survival.[3]
Although the aim of an R0 resection is primarily depended on patient's
tumor stage, quality of surgery plays also an important role towards this
goal.
Because 90 % of the patients in this trial received a limited D0 or D1 node
dissection, a substantial proportion of patients, approximately 30 %,[3]
had residual disease in the level II lymph nodes (around the celiac axis),
which were left behind. It is likely therefore that chemoradiotherapy
prolonged survival only in these certain patients. The study raises
important questions:
(a) should all patients after limited node
dissection, even those with node-negative cancer, receive adjuvant
chemoradiotherapy?
(b) can D0/D1 dissection plus chemoradiotherapy work
better than standardized extended (D2) node dissection alone?
(c) should patients after D2 dissection receive this adjuvant regimen? Further phase III trials are needed for an evidence-based treatment-decision about
chemoradiotherapy in the various subgroups of gastric cancer patients.
References
(1) Cuschieri A. Does chemoradiotherapy after intended curative surgery
increase survival of gastric cancer patients? Gut 2002;50:751.
(2) Roukos DH. Adjuvant chemoradiotherapy in gastric cancer: wave goodbye to extensive surgery? Ann Surg Oncol 2002 Apr-May;9(3):220-1.
(3) Roukos DH. Current status and future perspectives in gastric cancer management. Cancer Treat Rev 2000 Aug;26(4):243-55.
We are very grateful for the interest shown and comments made by Dr
Beales regarding our study [1]. We agree with him that it would have been
interesting to study the effects of H. pylori infection on the responses
to other physiological agonists. Unfortunately, the number of cells
obtained from the human stomach with endoscopic biopsies is much lower
than that obtained from the entire stomach in expe...
We are very grateful for the interest shown and comments made by Dr
Beales regarding our study [1]. We agree with him that it would have been
interesting to study the effects of H. pylori infection on the responses
to other physiological agonists. Unfortunately, the number of cells
obtained from the human stomach with endoscopic biopsies is much lower
than that obtained from the entire stomach in experimental conditions. In
this way the number of aliquots available for each experiment and each
agonist does not allow us to study this point that far.
Regarding the variability in the stimulatory effects of H. pylori in
our experiments, we should say that many studies on pepsinogen secretion
in experimental conditions always show some interassay variability, but
this has been found to be greater in all experiments carried out in
isolated human peptic cells [1,2]. The reason for this is not known and
this question has not been specifically investigated. We have reported
that factors such as the presence of peptic ulcer and/or the presence of
H. pylori infection does not seem to be relevant, but other factors might
be considered in future studies, including the method of cell isolation,
experimental conditions of experiments, age of patients, etc. We have
included different H. pylori strains since our experiments were carried
out over different periods of time and it was not possible to maintain the
same strains for the entire proccess of the study. Although we have
demonstrated that H. pylori-induced pepsinogen secretion was not affected
by the absence/presence of the cagA gene, other bacterial factors could
explain the differences in the magnitude of the stimuli. On the other
hand, the results of Beil et al [3] with three different cagA (+) strains
and one cagA (-) strain, showed that all H. pylori strains significantly
increased pepsinogen release but the effect was quite variable (9% to
27.9% of total pepsinogen content).
With regard to the Ca++/NO/cGMP-dependent pathway, we verified that the
absence of extracellular calcium inhibited H. pylori-induced pepsinogen
secretion, as well as the stimulus observed with carbachol, which was also
reduced by the addition of the nitric oxide synthase inhibitor L-NMMA
(data not published). In our study we have not determined the effect of
calcium removal on histamine or db-cAMP-stimulated release. However, the
results reported by Beil et al. [3], where both calmodulin antagonists and
lantanum inhibited both calcium-mediated pepsinogen agonists and db-AMP-
stimulated pepsinogen secretion, may also suggest an interaction or “cross
-talk” between signal-transduction pathways in chief cells, which could be
similar to what has been published elsewhere in different experimental
conditions [4].
As previously discussed [5], the reasons for the EGF potentiation of
CCK-pepsinogen secretion reported by our group are not clear and suggest
that, in human peptic cells, different calcium independent mechanisms
might be involved. Furthermore, in our system, the pepsinogen secretion
obtained with the combination of both CCK and acetylcholine was even
higher than the addition of the secretion obtained with each one of them
separately [5].
Finally, our results showed that H. pylori further increased the
secretion of pepsinogen in the presence of db-AMP-stimulated pepsinogen
secretion. This effect was not additive and, as was expressed in the
discussion section of our article, we think that it may be explained by
the interaction or “cross-talk” between these signal-transduction
pathways. We agree that H2-receptor stimulation may also activate the
phosphoinositide signaling cascade but this event has been published only
in a rat hepatoma-derived cell line [6].
Although during the past years much information about chief cell receptors
and signal-transduction mechanisms has been obtained, further and more
extensive research is needed for a better knowledge of the
pathophysiological regulation of pepsinogen secretion. The use of isolated
human peptic cells is challenging, but, in some way, it is in a better and
closer model to human physiology, where many of the questions raised can
be unravelled.
Sara Lorente
Angel Lanas
Service of Gastroenterology, University Hospital, Zaragoza, Spain
References
(1) Lanas AI, Anderson JW, Uemura N, et al. Effects of cholinergic,
histaminergic and peptidergic stimulation on pepsinogen secretion by
isolated human peptic cells. Scand J Gastroenterol 1994; 29: 678-83
(2) Lanas AI, Nerin J, Esteva F, et al. Non-steroidal anti-inflammatory
drugs and prostaglandin effects on pepsinogen secretion by dispersed human
peptic cells. Gut 1995; 36: 657-63.
(3) Beil W, Wagner S, Piller M, et al. Stimulation of pepsinogen secretion
release from chief cells by Helicobacter pylori: evidence for a role of
calcium and calmodulin. Microb Pathog 1998; 25: 181-7.
(4) Raufman JP, Cosowsky L. Protein kinase C modulates effects of
prostanoids on cyclic adenosine monophosphate in guinea pig chief cells. J
Cell Physiol 1989; 140: 91-97.
(5) Serrano MT, Lanas AI, Lorente S, et al. Cytokine effects on pepsinogen
secretion from human peptic cells. Gut 1997; 40: 42-48.
(6) Delvalle J, Wang L, Gantz I, et al. Characterization of H2 histamine
receptor: linkage to both adenylate cyclase and [Ca2+]i signaling systems.
Am J Physiol 1992; 263: G967-72.
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For decades, surgical operation has been considered as the only ideal therapeutic method in the treatment of hydatid cyst/cystic echinococcosis, a parasitic zoonosis that still remains prevalent in a number of countries, and especially PR China where the estimated number of cases is over 500,000.[1] The ultrasound (US)-guided Puncture-Aspiration-Injection -Reaspiration (PAIR) technique [2,3] has now ga...
Dear Editor
The recent report by MacDonald et al., despite provides promising findings for an effective adjuvant chemoradiotherapy of gastric cancer patients after gastrectomy has raised a numerous of questions and criticisms.[1,2] The weakness of this randomized trial and the lack of a surgical quality control have currently been extensively described [1,2,...
Dear Editor
We are very grateful for the interest shown and comments made by Dr Beales regarding our study [1]. We agree with him that it would have been interesting to study the effects of H. pylori infection on the responses to other physiological agonists. Unfortunately, the number of cells obtained from the human stomach with endoscopic biopsies is much lower than that obtained from the entire stomach in expe...
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