In a recent issue of the Journal[1], Biancone et al.
showed a comparable frequency of new diagnosis of neoplasia in
inflammatory bowel disease (IBD) patients treated with infliximab and in
patients who never received infliximab. These data seem to confirm
reassuring message from clinical trials.[2,3] A peculiar situation may
be IBD patients having had liver transplantation for primary sclerosing
ch...
In a recent issue of the Journal[1], Biancone et al.
showed a comparable frequency of new diagnosis of neoplasia in
inflammatory bowel disease (IBD) patients treated with infliximab and in
patients who never received infliximab. These data seem to confirm
reassuring message from clinical trials.[2,3] A peculiar situation may
be IBD patients having had liver transplantation for primary sclerosing
cholangitis and in whom an increased risk of colon cancer has been
reported. We here report a case of rapidly progressing colon cancer in a
liver transplant recipient suffering from Crohn’s disease treated with
infliximab.
A 23-year-old man had a 12-year long history of Crohn’s disease
characterized by ileitis, pancolitis and oral aphthous ulcers. He was
treated with mesalasine (2 g/day) since 1991 and azathioprine (2.5 mg/kg/day) since 1994. In September 2003, he underwent orthotopic liver
transplantation (OLT) for primary sclerosing cholangitis (PSC) complicated
by several angiocholitis. Tacrolimus and steroids were introduced after
transplantation to prevent organ rejection. In November 2004, he has a
flare-up of colitis despite maintenance treatment with azathioprine,
tacrolimus and steroids. Colonoscopy showed moderate inflammation of the
whole colon and mild ileitis. The random biopsy pattern including biopsies
of the caecum (total of 45 biopsies) did not reveal any evidence of
dysplasia. Infliximab therapy was thus initiated. From December 2004 to
July 2005, he received a total of six infliximab infusions at 5 mg/kg
(weeks 0, 2, 6 and then every 8 weeks) and was in clinical remission after
three infusions. In July 2005, two weeks after his last infliximab
infusion, he presented with a small bowel obstruction.
Computed tomography
showed a stenosis of the caecum related to a bulky tumor with multiple one
centimeter regional lymph nodes. Colonoscopy confirmed mucosal healing and
showed a tumor of the caecum (Fig. 1), with a poorly differentiated
adenocarcinoma on biopsies. The endoscopist could not reach the terminal
ileum. The patient underwent a coloproctectomy in August 2005. Macroscopic
examination revealed an exophytic mass with extension through the bowel
wall and the pericolonic fat and the tumor size was 5-cm. Histologic
examination showed a poorly differentiated adenocarcinoma of the caecum
with a mucinous component (10%) and 19 of the 126 regional lymph nodes
removed during surgery were positive for metastatic disease. Microscopic
examination also found venous and nerve invasion. As staging of the cancer
was pT4N2M0, adjuvant chemotherapy with oxaliplatin, fluorouracil and
leucovorin was started in September 2005.
Figure 1. Endoscopic view of the tumor:
A colonoscopy performed in July 2005 showed an exophytic lesion of the caecum responsible for a colon stenosis. The ileo-caecal valve was not visible and the endoscopist could not reach the terminal ileum.
Almost 30 cases of colon cancer have been described in liver transplant
recipients with ulcerative colitis, but no case has yet been reported to
our knowledge in Crohn’s disease.[4-10] Similarly to former reports,
colon cancer was diagnosed within 30 months of transplantation with a
duration of colitis of more than 9 years. While the youngest patient in
these case reports was 39 years old[10] (mean age:c46[6]) and some
patients had a history of colorectal neoplasia[5], our patient was only
25 years old and had neither personal nor family history of colon
neoplasia. Previous reports indicated that the risk of colorectal
carcinoma in IBD patients is related to the extent and duration of disease
and might be increased by the coexistence of PSC. In the present case, the
combination of these factors might be necessary but not sufficient to
explain the development of colon cancer, as a colonoscopy with random
biopsies performed just before the first infliximab infusion was normal.
Given the development in only seven months of a bulky cancer of the caecum
with multiple regional lymph metastases, infliximab therapy might have
promoted and/or accelerated colon carcinogenesis in this young patient.
This case advocates for a cautious use of infliximab in IBD patients with
liver transplant.
Acknowledgments:
We are grateful to Mathias Chamaillard for helpful discussions, and to
Professor Colombel for critical reading of this manuscript.
References
1. Biancone L, Orlando A, Kohn A, et al. Infliximab does not increase
the risk of newly diagnosed neoplasia in Crohn’s disease: a multicenter
matched-pair study. Gut doi:10.1136/gut.2005.075937
2. Present DH, Rutgeerts P, Targan S, et al.. Infliximab for the treatment
of fistulas in patients with Crohn's disease. N Engl J Med 1999;340:1398-
1405.
3. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance
therapy for fistulizing Crohn's disease. N Engl J Med 2004;350:876-885.
4. Higashi H, Yanaga K, Marsh JW, et al. Development of colon cancer after
liver transplantation for primary sclerosing cholangitis associated with
ulcerative colitis. Hepatology 1990;11:477-480.
5. Narumi S, Roberts JP, Emond JC, et al. Liver transplantation for
sclerosing cholangitis. Hepatology 1995;22:451-457.
6. Fabia R, Levy MF, Testa G, et al. Colon carcinoma in patients
undergoing liver transplantation. Am J Surg 1998;176:265-269.
7. Loftus EV Jr, Aguilar HI, Sandborn WJ, et al. Risk of colorectal
neoplasia in patients with primary sclerosing cholangitis and ulcerative
colitis following orthotopic liver transplantation. Hepatology 1998;27:685
-690.
8. Vera A, Gunson BK, Ussatoff V, et al. Colorectal cancer in patients
with inflammatory bowel disease after liver transplantation for primary
sclerosing cholangitis. Transplantation 2003;75:1983-1988.
9. Knechtle SJ, D'Alessandro AM, Harms BA, et al. Relationships between
sclerosing cholangitis, inflammatory bowel disease, and cancer in patients
undergoing liver transplantation. Surgery 1995;118:615-619.
10. Bleday R, Lee E, Jessurun J, et al. Increased risk of early colorectal
neoplasms after hepatic transplant in patients with inflammatory bowel
disease. Dis Colon Rectum 1993;36:908-912.
Dr Gupte and colleagues conclude that our article "does not
acknowledge the contribution of the paediatric experience in this
developing field" Nonetheless, the article does outline the development
of small intestinal transplantation internationally for both adults and
paediatrics and includes all of the paediatric outcome data submitted to
the international registry, which we believe does include t...
Dr Gupte and colleagues conclude that our article "does not
acknowledge the contribution of the paediatric experience in this
developing field" Nonetheless, the article does outline the development
of small intestinal transplantation internationally for both adults and
paediatrics and includes all of the paediatric outcome data submitted to
the international registry, which we believe does include the Birmingham
cases. The mission of the article was to orientate the general reader as
to the global situation and lay emphasis upon certain aspects of the UK
provision which might be improved by their increased awareness, rather
than enhance the knowledge of the transplant specialist. One of the
specific local UK problems is the poor referral rate of adults in
particular which may stem from an overly conservative approach to the
management of sudden intestinal failure requiring salvage surgery and
parenteral nutrition as well as late referral of adults to the intestinal
failure centres. It was not the aim of the article to cover the details of
the UK adult or paediatric transplantation centres' experiences which have
been published elsewhere. We feel that the article largely satisfies its
mission to inform the generalist and that inclusion of a detailed
comprehensive description of aspects such as post operative infection,
PTLD and the surgical reduction techniques commonly needed in paediatric
practice would have steered away from our aim. We agree however that the
type of information provided in Dr Gupte's letter is of great importance
but more so to the specialists undertaking the procedure that to the non
transplant specialist who might wish to refer a patient for consideration
of intestinal transplantation.
Yours sincerely,
Dr S J Middleton, Gastroenterologist
Mr N V Jamieson, Hepatobiliary and Transplant Surgeon
We read with interest the paper by Foucher et al.[1] where the
authors assess the accuracy of transient elastography for the detection of
cirrhosis. Its use to assessing the severity of chronic liver disease in
other clinical scenarios warrant further evaluations. According to large
population studies, the prevalence of chronically hepatitis C virus (HCV)
infected patients who have persistently normal...
We read with interest the paper by Foucher et al.[1] where the
authors assess the accuracy of transient elastography for the detection of
cirrhosis. Its use to assessing the severity of chronic liver disease in
other clinical scenarios warrant further evaluations. According to large
population studies, the prevalence of chronically hepatitis C virus (HCV)
infected patients who have persistently normal serum aminotransferase (PN-ALT) levels is most likely around 30-50%.[2] A major problem is to define
whether these patients may suffer a progressive disease; additionally,
although no consensus exists regarding who must be treated and when
antiviral therapy must be initiated, positive decisions have been
reinforced by the recent results of a large clinical trial indicating that
pegylated interferon plus ribavirin combination therapy is effective and
safe in these patients with PN-ALT.[3] In a recent review the schedule of
antiviral combination treatment of patients with chronic hepatitis C and
normal aminotransferases is described and indication of antiviral therapy
in some cases might be decided on the basis of histological findings[2];
hence, liver biopsy seems to be a key in this decision and a patient must
be treated if there is significant fibrosis (>OR= F2). However,
meanwhile liver biopsy remains the “gold standard” for the assessment of
hepatic fibrosis, it represents an invasive procedure with some risks and
limitations[1], and is not well accepted by all patients. Non-invasive
methods such as Fibrotest, Forns’ index (FI) and APRI have been designed
to assess liver fibrosis.[4] Fibroscan® (FS), a new transient
elastography technique to measure liver stiffness or elasticity[5,6],
have rised great expectancy as an alternative method for staging liver
disease. Stiffness insignificantly correlates to fibrosis stage and is a
promising, reproducible and independent of the operator, method for the
detection of cirrhosis.[1,6] Our aim was the assessment by FS of hepatic
fibrosis in patients infected by HCV and PN-ALT, comparing the accuracy of
FS to that previously described for biomarkers.
We analysed prospectively 28 chronically HCV infected patients (18
females) with PN-ALT (at least three determinations yearly), assessing
hepatic fibrosis by FS. Concordances and correlations between FS and FI
and APRI were also evaluated. Almost all consecutive patients were
asymptomatic and none of them have had the well known complications of
advanced liver disease or cirrhosis.[7] Patients’ characteristics (mean ±
SD) were as follow: age 44.3 ± 10 years, BMI 24.1± 2.8 Kg/m2, platelets
count 249.6 ± 58 /mm3, serum cholesterol levels 190.5 ± 26 mg/dL, serum
AST levels 25 ± 5 IU/L, serum ALT levels 27.7 ± 6.7 IU/L and serum GGT
levels 23.2 ± 21 IU/L. Results of the study were as follow: 26 (92.8%)
patients had HCV-genotype 1. Mean value of FS was 6.35 ± 3.3 KPa,
indicating absence or mild stage of fibrosis (<8.5 KPa); as expected,
mean values of FI (3.35 ± 1.4) and APRI (0.27 ± 0.09) also reflects
minimal or no fibrosis (<4.5 and <0.5, respectively). These
provocative findings show that this cohort of PN-ALT chronically HCV
infected patients have a low stage of fibrosis according to three non-
invasive methods. A previous study has compared and validated these
methods in chronic hepatitis C patients with elevated ALT.[8]
Liver biopsy has been used as the “gold standard” for the assessment
of hepatic fibrosis. It has been used for staging the liver damage in
chronic viral hepatitis and for decision analysis as to the need of
treatment in patients with chronic hepatitis C. The limitations of biopsy
such as patient acceptability, sampling error or diagnostic inaccuracy,
and the remote risk of complications, have led clinical investigators to
study alternative methods to stage chronic viral hepatitis.[1,4,9] Serum
biological markers determination is the most widely used procedure for
stimation of liver fibrosis[9]; combining serum biomarkers with FS may
increase the accuracy of these non-invasive methods, suggesting that it
may be valid to circumvent the limitations of hepatic histology.[8,9] FS
is an objective and safe technique, enthusiastically accepted by patients.
Hence, periodical examinations can be performed as a follow-up protocol
for assessment of hepatic fibrosis progression or improvement. Moreover,
it is a precise method for the detection of cirrhosis and promising in
order to predict complications of cirrhosis.[1] Accordingly, our data may
suggest that therapeutic management of PN-ALT patients could be
established according to fibrosis stage detected along successive FS
examinations. Those PN-ALT patients with evidence of fibrosis by FS would
need to start an early antiviral treatment. Although with the
inconvenience of less effectivity in obese subjects, transient
elastography may be very helpful in a better diagnostic and therapeutic
management of PN-ALT chronically HCV infected patients, questioning the
leading role of biopsy.[8,9] Further studies on this topic may be
warranted in order to evaluate the diagnostic accuracy for staging hepatic
fibrosis, the natural history of disease and the optimised response to
combination antiviral therapy. Additionally, it has been demonstrated that
combining a FS measurement with biomarkers may increase the diagnostic
accuracy of both tests.[8,9] In conclusion, repeated stiffness assessment
appears to be a good and safe alternative method to indicate antiviral
combination therapy in PN-ALT patients reluctant to liver biopsy. (Grant ISC III 03/02).
References
1. Foucher J, Chanteloup E, Vergniol J, et al. Diagnosis of
cirrhosis by transient elastography (Fibroscan®): a prospective study. Gut
online 14 Jul 2005.
2. Alberti A. Towards more individualised management of hepatitis C
virus patients with initially or persistently normal
alanineaminotransferase levels. J Hepatol 2005;42:266-74.
3. Zeuzem S, Diago M, Gane E, et al. Peginterferon alfa-2a (40
kilodaltons) and ribavirin in patients with chronic hepatitis C and normal
aminotransferase levels. Gastroenterology 2004;127:1724-32.
4. Wai CT, Greenson JK, Fontana RJ, et al. A simple non-invasive
index can predict both significant fibrosis and cirrhosis in patients with
chronic hepatitis C. Hepatology 2003; 38:518-26.
5. Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient
elastography : a new noninvasive method for assessment of hepatic
fibrosis. Ultrasound Med Biol 2003; 29:1705-13.
6. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment
of liver fibrosis by measurement of stiffness in patients with chronic
hepatitis C. Hepatology 2005;41:48-54.
7. Benvegnù L, Gios M, Bocato S et al. Natural history of compensated
viral cirrhosis: a prospective study on the incidence and hierarchy of
major complications. Gut 2004; 53:744-9.
8. Castera L, Vergniol J, Foucher J, et al. Prospective comparison of
transient elastography, fibrotest, APRI, and liver biopsy for the
assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005; 128:
343-50.
9. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise
review. Am J Gastroenterol 2004;99:1160-74.
Maria Trapero-Marugan, Jorge Mendoza and Ricardo Moreno-Otero.
Gastroenterology and Hepatology Service (ISC III 03/02) Hospital Universitario de La Princesa Autonomous University of Madrid Spain
We read with interest the article on ‘The current status of small
bowel transplantation in the UK and internationally’ by Middleton et
al.[1] This is a timely article about the improving worldwide outcome
following small bowel transplantation, but does not fully reflect the
status of small bowel transplantation in the UK. In the UK, the Department
of Health through NSCAG (National Specialist Commissio...
We read with interest the article on ‘The current status of small
bowel transplantation in the UK and internationally’ by Middleton et
al.[1] This is a timely article about the improving worldwide outcome
following small bowel transplantation, but does not fully reflect the
status of small bowel transplantation in the UK. In the UK, the Department
of Health through NSCAG (National Specialist Commissioning Advisory Group)
recognises and funds three units for small bowel transplantation [two adult
centres- Addenbrooke’s Hospital, Cambridge; St James Hospital, Leeds; and
single paediatric centre- Birmingham Children’s Hospital (BCH)] since
1997. The majority of transplants in the UK to date have been carried out
in children, which also reflects the international situation. Thirty eight
intestinal transplants have been performed in children at BCH since 1993
compared to 14 transplants in the adult population in the last 15 years at
two adult centres.[1]
The paediatric experience has taught us many useful lessons which
also benefit adult recipients, such as : reduction of graft size[2],
increased awareness about post-transplant infectious enteritis and Epstein
Barr virus (EBV) related post-transplant lympho-proliferative disease
(PTLD), which are risk factors for death following small bowel
transplantation in both adults and children.[3,4]
Since the introduction of graft reduction techniques, we have
performed 21 en-bloc reduced combined liver and small bowel transplants
thus extending the donor pool and facilitating transplantation of small
children from older donors.[2]
In a recent report from the UCLA group, infectious enteritis (IE)
with viruses (adenovirus, EBV and rotavirus) and protozoa (Giardia
Lamblia, Cryptosporidium) has been reported in 3 adults and 10 children
following small bowel transplantation. This is an under-reported and under
-diagnosed complication following intestinal transplantation. A high index
of suspicion and prompt laboratory investigations are necessary to arrive
at an early diagnosis as the clinical features can mimic acute cellular
rejection (ACR) and the treatment of IE is very different to ACR.[3]
Epstein Barr Virus (EBV) related post-transplant lymphoproliferative
disease (PTLD) is seen more commonly in children who unlike adults are
EBV seronegative pre-transplant, but also occurs in adults following small
bowel transplantation.[4] The diagnosis of EBV related PTLD is based on
high viral EBV PCR loads and histopathological examination. Treatment
modalities such as reduction of immunesuppresssion , surgical resection
for control of local complications, anti CD20 monoclonal antibody
(Rituximab), adoptive immunotherapy, cytotxic chemotherapy are helpful in
treatment of this invasive disease.[5] Awareness about PTLD and serial
EBV PCR monitoring has reduced the incidence of PTLD in the last
Decade.[4,5]
In conclusion, this article does not acknowledge the contribution of
paediatric experience in this developing field.
Reference List
1. Middleton SJ,.Jamieson NV. The current status of small bowel
transplantation in the UK and internationally. Gut 2005;54:1650-7.
2. de Ville dG, Mitchell A, Mayer AD, Beath SV, McKiernan PJ, Kelly
DA et al. En block combined reduced-liver and small bowel transplants:
from large donors to small children. Transplantation 2000;69:555-9.
3. Ziring D, Tran R, Edelstein S, McDiarmid SV, Gajjar N, Cortina G
et al. Infectious enteritis after intestinal transplantation: incidence,
timing, and outcome. Transplantation 2005;79:702-9.
4. Grant D, Abu-Elmagd K, Reyes J, Tzakis A, Langnas A, Fishbein T
et al. 2003 report of the intestine transplant registry: a new era has
dawned. Ann Surg 2005;241:607-13.
5. Green M,.Webber S. Posttransplantation lymphoproliferative
disorders. Pediatr Clin.North Am. 2003;50:1471-91.
I enjoyed the article by Albert et al. comparing newly emerging
imaging modalities for the assessment and detection of small bowel Crohn’s
disease, an area of the gastro-intestinal tract that is often difficult to
adequately image, assess and biopsy.[1]
However, their article failed to mention 99mTc HMPAO labelled white
cell scanning at all as a method of imaging the small (and large) bowel...
I enjoyed the article by Albert et al. comparing newly emerging
imaging modalities for the assessment and detection of small bowel Crohn’s
disease, an area of the gastro-intestinal tract that is often difficult to
adequately image, assess and biopsy.[1]
However, their article failed to mention 99mTc HMPAO labelled white
cell scanning at all as a method of imaging the small (and large) bowel.
Planar white-cell scintigraphy is a well-established, non-invasive method
of assessing intestinal inflammation.[2] While histological assessment is
considered to be the gold standard method of detecting intestinal
inflammation planar white-cell scintigraphy accurately reflects disease
extent and histological activity.[3] The new imaging methods discussed by
Albert et al. also suffer from this disadvantage of not allowing
histological assessment.
In addition to planar white cell scanning single photon emission
computerised tomography (SPECT) white cell scanning has been shown to
correlate very well with histology (r=0.8 p<0.0001) in subjects with
active IBD.[4]
We have previously shown that both white cell scanning techniques are
valuable not only in assessing extent and severity of inflammation but in
following up response to treatment in subjects with ulcerative colitis and
Crohn’s disease.[5,6]
When evaluating newly emerging imaging techniques it is vital not to
forget previously established techniques.
References
1. Albert JG, Martiny F, Krummenerl A et al.Diagnosis of small bowel
Crohn’s disease: a prospective comparison of capsule endoscopy with
magnetic resonance imaging and fluoroscopic enteroclysis. Gut
2005;52(12):1721-1727.
2. Danpure HJ. Osman S. Carroll MJ. The development of a clinical
protocol for the radiolabelling of mixed leucocytes with 99Tcm-
hexamethylpropyleneamine oxime. Nuclear Medicine Communications
1988;9(6):465-75.
3. Lantto E, Jarvi K, Krekla I, et al. Technetium-99m hexamethyl
propylene anime oxine leucocytes in the assessment of disease activity in
inflammatory bowel disease. Eur J Nucl Med 1992;19(1):14-18.
4. Weldon MJ, Masoomi AM, Britten AJ et al. Quantification of
inflammatory bowel disease activity using technetium-99m HMPAO labelled
leucocyte single photon emission computerised tomography (SPECT). Gut
1995; 36(2)243-50.
5. Poullis A, Irwin AG, Dearing M, et al. Methodological study to
assess repeat planar white cell scanning in monitoring the efficacy of
treatment in inflammatory bowel disease. Gut 2003;52 (Suppl I):A87.
6. Poullis A, Irwin AG, Dearing M, et al. Methodological study to
assess repeat SPECT white cell scanning in monitoring the efficacy of
treatment in inflammatory bowel disease. Gastroenterology 2003:Suppl
(1):A267.
Dental erosion can be considered as an extraoesophageal manifestation
of gastro-oesophageal reflux disease (GORD). Many reports have implicated
refluxed gastric acid as a cause or contributory factor in the development
of extraoesophageal disorders (“atypical” symptoms related to GORD), but
the presence of lesions in oral cavity in patients with acid reflux has
been less studied. The association between...
Dental erosion can be considered as an extraoesophageal manifestation
of gastro-oesophageal reflux disease (GORD). Many reports have implicated
refluxed gastric acid as a cause or contributory factor in the development
of extraoesophageal disorders (“atypical” symptoms related to GORD), but
the presence of lesions in oral cavity in patients with acid reflux has
been less studied. The association between acid reflux and dental erosion
was firstly described by Howden in 1971 and was confirmed in other studies
later, both in the adult population and in children.
We had studied two groups of subjects: 181 patients with GORD and 72
healthy volunteers. Clinical assessment including sex, age, body mass
index, and consumption of tobacco and alcohol was performed in all
subjects, as well as a dental examination performed by a dentist
physician, blind as to the diagnosis of subjects. Parameters evaluated
were the presence and number of dental erosion, location and severity,
according to the Eccles and Jenkins index, modified by Hattab. Clinical
parameters were similar in both groups (p>0.05). Compared with control
group, the percentage of dental erosion was significantly higher in GORD
group (12.5% vs. 47.5%, p<0.001, Chi-square test), as was the number
and severity of dental erosions (p<0.001, Student’s t test). Location
of dental erosion was significantly different between groups.
Given the high prevalence of dental erosion in patients with acid reflux,
the collaboration between gastroenterologists and dentists is necessary in
order to identify dental involvement in patients diagnosed of GORD. On the
contrary, subjects with unexplainable presence of dental erosion should be
referred to gastroenterologists to investigate the presence of a probable
GORD.
We read with great interest the guideline for gastroenteropancreatic
neuroendocrine (including carcinoid) tumors by Ramage et al.[1] In this
excellent guideline, they reported that appendix is the most frequent site
of gastrointestinal primary endocrine tumors, consisting 35% of the total
tumors, while colon and rectal carcinoids consisted only 7% and 10%,
respectively. One important aspect not ment...
We read with great interest the guideline for gastroenteropancreatic
neuroendocrine (including carcinoid) tumors by Ramage et al.[1] In this
excellent guideline, they reported that appendix is the most frequent site
of gastrointestinal primary endocrine tumors, consisting 35% of the total
tumors, while colon and rectal carcinoids consisted only 7% and 10%,
respectively. One important aspect not mentioned, however, is the fact
that the site distribution of gastrointestical carcinoids differs among
races.
Modlin et al previously reported a marked predominance of white
Caucasians population in carcinoids of the colon and appendix based upon
the nationwide surveillance in the United States.[2] In contrast, the
incidence of rectal carcinoids was 3- to 4-fold higher in African-
Americans than in white Caucasians. Accordingly, the site distribution of
colorectal carcinoids markedly differs among these two races.
Regarding carcinoids in Asian population, there have been few reports
based upon a large database. In order to provide such evidence, we
analyzed colorectal carcinoids in the Japanese population using the
Multi-Institutional Registry of Large Bowel Cancers in Japanh, a
nationwide database which covers approximately 10% of the Japanese
population, from 1984 to 1998.[3] Among 90,057 cases of colorectal tumors
registered during this period, a total of 345 cases of colorectal
carciniods were identified. All cases were from the Asian population. The
site distribution consisted of the ileum 3 (0.9%), appendix 8 (2.3%),
colon 28 (8.2%) and rectum 304 (88.6%). Thus, carcinoids in the Japanese
population exhibited much higher distribution in the rectum than in the
colon and appendix. This over-representation of rectal carcinoids is
compatible with a previous report from Taiwan in which 33 cases (89.2%)
out of 37 colorectal carcinoids originated from the rectum.[4]
The difference in the distribution of colorectal carcinoids among
races suggests that race-related genetic factors play an important role in
the development of gastrointestinal carcinoids. With acceptance on this
point, racial disparity could be a point to consider in the diagnosis of
carcinoids, and further investigation using a larger database is needed to
clarify these points.
References
1. Ramage JK, Davies AH, Ardill J, et al. Guidelines for the
management of gastroenteropancreatic neuroendocrine (including carcinoid)
tumours. Gut 2005;54 Suppl 4:iv1-16.
2. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid
tumors. Cancer 2003;97(4):934-59.
3. Kotake K, Honjo S, Sugihara K, et al. Changes in colorectal cancer
during a 20-year period: an extended report from the multi-institutional
registry of large bowel cancer, Japan. Dis Colon Rectum 2003;46(10
Suppl):S32-43.
4. Weng YJ, Wang SS, Yang WG, et al. Carcinoid tumors of the
gastrointestinal tract in Chinese of Taiwan: an analysis of fifty cases.
Zhonghua Yi Xue Za Zhi (Taipei) 1996;58(4):254-8.
Institutions of the authors:
T. Konishi, T. Watanabe and H. Nagawa, Department of Surgical Oncology, University of Tokyo, Tokyo, Japan
T. Muto,
Department of Surgery, Cancer Institute Hospital, Tokyo, Japan
K. Kotake,Department of Surgery, Tochigi Cancer Center, Tochigi, Japan
All Correspondence to:
Dr. Toshiaki Watanabe
Department of Surgical Oncology
University of Tokyo
7-3-1 Hongo Bunkyo-ku
Tokyo 113-8655
Japan
TEL: +81-3-5800-8653
FAX: +81-3-3811-6822
E-mail: toshwatanabe@yahoo.co.jp
We read with interest the article by Israeli et al. on Anti-
Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as
predictors of inflammatory bowel disease as they concluded that ASCA and
pANCA may predict development of inflammatory bowel disease years before
the disease is clinically diagnosed.[1]
Anti-Saccharomyces cerevisiae antibodies (ASCA) are known as specific
markers i...
We read with interest the article by Israeli et al. on Anti-
Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as
predictors of inflammatory bowel disease as they concluded that ASCA and
pANCA may predict development of inflammatory bowel disease years before
the disease is clinically diagnosed.[1]
Anti-Saccharomyces cerevisiae antibodies (ASCA) are known as specific
markers in Crohn's disease albeit the clinical relevance of these
antibodies to some oligomannose epitope of the Saccharomyces cerevisiae is
not clear. Neither the origin and nor the clinicopathological role are
clarified. It is also known that ASCA positivity correlates principally
with small intestines. Crohn's disease and in these cases both the IgG and
IgA type antibodies are present.[2,3]
Gluten-sensitive enteropathy (GSE) or, as it is more commonly called,
celiac disease, is another immune-mediated enteropathic condition
(specified as an autoimmune inflammatory disease of the small intestine)
that is precipitated by the ingestion of gluten, a component of wheat
protein, in genetically susceptible persons.
In 2003, we examined whether there was ASCA positivity in our patients
with biopsy-confirmed celiac disease in a pilot study and found a
relatively high incidence of ASCA in GSE. Our and other’s results also
foreshadows that ASCA positivity predicts both CD and celiac disease.[4-6]
Both celiac disease and Crohn’s disease are characterized by the presence
of distinct (auto) antibodies. Theoretically and practically it is
thinkable that ASCA positivity is not only a specific marker of Crohn’s
disease but correlates with the (auto-) immune inflammation of the small
intestines. Oligomannosids of Saccharomyces cerevisiae with modification
by ASCA can change their immunopathogenicity and trigger a process that
results in specific inflammation. The antibodies in the sera of the
analyzed ASCA positive cases proved a systemic immune response against
Saccharomyces cerevisiae and suggested the end of the oral tolerance
against the yeast’s antigens.
The diet restriction (elemental diet, total parenteral nutrition, and
faecal diversion) may ameliorate the status of the patients with Crohn’s
disease. It can also be speculated that the yeast-free diet as a part of
the therapy for the ASCA positive patients can be reasonable, moreover the
permanent "forbidding" of the yeast can be an acceptable alternative in
case of getting well.[7]
Reference List
(1) Israeli E, Grotto I, Gilburd B et al. Anti-Saccharomyces
cerevisiae and antineutrophil cytoplasmic antibodies as predictors of
inflammatory bowel disease. Gut 2005;54(9):1232-6.
(2) Bernstein CN, Orr K, Blanchard JF et al. Development of an assay
for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for
Crohn's disease. Can J Gastroenterol 2001;15(8):499-504.
(3) Quinton JF, Sendid B, Reumaux D et al. Anti-Saccharomyces
cerevisiae mannan antibodies combined with antineutrophil cytoplasmic
autoantibodies in inflammatory bowel disease: prevalence and diagnostic
role. Gut 1998;42(6):788-91.
(4) Barta Z, Csipo I, Szabo GG et al. Seroreactivity against
Saccharomyces cerevisiae in patients with Crohn's disease and celiac
disease. World J Gastroenterol 2003;9(10):2308-12.
(5) Tursi A, Giorgetti GM, Brandimarte G et al. High prevalence of
celiac disease among patients affected by Crohn's disease. Inflammatory
Bowel Diseases 2005;11(7):662-6.
(6) Yang A, Chen Y, Scherl E et al. Inflammatory bowel disease in
patients with celiac disease. Inflammatory Bowel Diseases 2005;11(6):528-
32.
(7) Barclay GR, McKenzie H, Pennington J et al. The effect of
dietary yeast on the activity of stable chronic Crohn's disease. Scand J
Gastroenterol 1992;27(3):196-200.
Re: Stratification by gender and subgroup is necessary for RCT on IBS by Prof. Bian
Thank you for the communication of your interesting study results.
Your findings highlight a problem especially for acupuncture research.
Many experimental trials are pointing out the efficacy of acupuncture,
also regarding problems of the gastrointestinal tract.[1-4] However, many
of these trials are not a...
Re: Stratification by gender and subgroup is necessary for RCT on IBS by Prof. Bian
Thank you for the communication of your interesting study results.
Your findings highlight a problem especially for acupuncture research.
Many experimental trials are pointing out the efficacy of acupuncture,
also regarding problems of the gastrointestinal tract.[1-4] However, many
of these trials are not always controlled by appropriate placebo. Thus it
is difficult to explain the positive result with specific effects.
Acupuncture and placebo-acupuncture seem to have the same positive effect
in many RCTs.[5-8] That does not mean that an acupuncture effect is
always a placebo effect. Especially in musculoskeletal diseases
acupuncture seem to be stronger than placebo.[9-12] Indeed, in functional
diseases the efficacy of acupuncture seems to rely on placebo effects. In
our study, we placed the “Streitberger-needle”[13] 2 cm apart the real
points to avoid acupressure effects. Nevertheless, we had definitive
effects of the placebo acupuncture.[14] Thus, it seems that the
identified physiological effects seem to play an ancillary role. Our
results are supported by another recently published trial.[15] They used
a sham acupuncture on non-acupuncture-points. As a consequence, it was not
sure if the effects are due to some unspecific effects. The sham
acupuncture trials have the disadvantage that the unspecific effect could
always be due to some hypothesized unspecific needling effects. It will be
always questioned: “Was that really a non-acupuncture point? How do you
know that a sham acupuncture will not cause any effect?”. This is excluded
with our study design.
The question arises why placebo-acupuncture and placebo in general[16]
are so effective in irritable bowel syndrome. And the second question is
whether the results of experimental trials are really due to specific
effects. And if they are: why is this not reflected in clinical trials?
What role does the cognitive processing play in this context? Further
research is required to shed light on this phenomenon.
It was not possible to do a subgroup analysis from a statistical point of
view as we had only 9 males in our study. This is the same for the
clinical subgroups. However, the placebo-effect was so strong that almost
526 patients would be necessary to prove some effect. Such an effect could
be interesting, but it must be questioned if it is clinically relevant.
References:
(1) Cui KM, Li WM, Gao X et al. Electro-acupuncture relieves chronic
visceral hyperalgesia in rats. Neurosci Lett 2005;376(1):20-3.
(2) Jin HO, Zhou L, Lee KY et al. Inhibition of acid secretion by
electrical acupuncture is mediated via beta-endorphin and somatostatin. Am
J Physiol 1996;271(3 Pt 1):G524-G530.
(3) Li P, Rowshan K, Crisostomo M et al. Effect of electroacupuncture on
pressor reflex during gastric distension. Am J Physiol Regul Integr Comp
Physiol 2002;283(6):R1335-R1345.
(4) Li Y, Tougas G, Chiverton SG et al. The effect of acupuncture on
gastrointestinal function and disorders. Am J Gastroenterol
1992;87(10):1372-81.
(5) Linde K, Jobst K, Panton J. Acupuncture for chronic asthma. Cochrane
Database Syst Rev 2000;(2):CD000008.
(6) Linde K, Streng A, Jürgens S et al. Acupuncture for Patients with
Migraine. JAMA 2005;293:2118-25.
(7) Melchart D, Streng A, Hoppe A et al. Acupuncture in patients with
tension-type headache: randomised controlled trial. BMJ 2005;331(7513):376
-82.
(8) White AR, Rampes H, Ernst E. Acupuncture for smoking cessation.
Cochrane Database Syst Rev 2002;(2):CD000009.
(9) Kleinhenz J, Streitberger K, Windeler J et al. Randomised clinical
trial comparing the effects of acupuncture and a newly designed placebo
needle in rotator cuff tendinitis. Pain 1999;83(2):235-41.
(10) Manheimer E, White A, Berman B et al. Meta-analysis: acupuncture for
low back pain. Ann Intern Med 2005;142(8):651-63.
(11) White P, Lewith G, Prescott P et al. Acupuncture versus placebo for
the treatment of chronic mechanical neck pain: a randomized, controlled
trial. Ann Intern Med 2004;141(12):911-9.
(12) Witt C, Brinkhaus B, Jena S et al. Acupuncture in patients with
osteoarthritis of the knee: a randomised trial. Lancet 2005;366(9480):136-
43.
(13) Streitberger K, Kleinhenz J. Introducing a placebo needle into
acupuncture research. Lancet 1998;352(9125):364-5.
(14) Schneider A, Enck P, Streitberger K et al. Acupuncture treatment in
irritable bowel syndrome. Gut 2005. Epub ahead of print.
(15) Forbes A, Jackson S, Walter C et al. Acupuncture for irritable bowel
syndrome: a blinded placebo-controlled trial. World J Gastroenterol
2005;11(26):4040-4.
(16) Enck P, Klosterhalfen S. The placebo response in functional bowel
disorders: perspectives and putative mechanisms. Neurogastroenterol Motil
2005;17(3):325-31.
In 1994, Helicobacter pylori was declared a type 1 carcinogen—a
definite cause of human cancer—by the International Agency for Research on
Cancer (IARC).[1]
We read with interest the study by Mera et al.[1] on the effect of
eradicating H. pylori infection on precancerous gastric lesions. Here the
author Mera et al conclude that “Preneoplastic gastric lesions regress at
a rate equal to the squ...
In 1994, Helicobacter pylori was declared a type 1 carcinogen—a
definite cause of human cancer—by the International Agency for Research on
Cancer (IARC).[1]
We read with interest the study by Mera et al.[1] on the effect of
eradicating H. pylori infection on precancerous gastric lesions. Here the
author Mera et al conclude that “Preneoplastic gastric lesions regress at
a rate equal to the square of time in patients rendered free of H pylori
infection. Our findings suggest that patients with preneoplastic gastric
lesions should be treated and cured of their H pylori infection”. I would
like to focus other studies done before to find out the association of H
pylori and gastric neoplasm.
In Fujian Province, China a large study[2] was conducted by Benjamin
Chun-Yu Wong at el on 1630 healthy carriers of H pylori infection. The
Objective was to determine whether treatment of H pylori infection reduces
the incidence of gastric cancer. The study was Prospective, randomized,
placebo-controlled, recruited in July 1994 and followed up until January
2002. Benjamin Chun-Yu Wong at el concluded that “the incidence of
gastric cancer development at the population level was similar between
participants receiving H pylori eradication treatment and those receiving
placebo during a period of 7.5 years in a high-risk region of China. In
the subgroup of H pylori carriers without precancerous lesions,
eradication of H pylori significantly decreased the development of gastric
cancer. Further studies to investigate the role of H pylori eradication in
participants with precancerous lesions are warranted”.
Information of the individual metaplasia and atrophy scores at
baseline and at twelve years in both groups also needed to find out
independent analysis and interpretation of this important study, which is
unavailable here in this study. This is important as these are the lesions
most strongly associated with cancer risk.
References:
1. International Agency for Research on Cancer Working Group on the
Evaluation of Carcinogenic Risks to Humans. Schistosomes, Liver Flukes and
Helicobacter pylori: Views and Expert Opinions of an IARC Working Group on
the Evaluation of Carcinogenic Risks to Humans. Lyon, France: IARC Press;
1994:177-240.
2. Benjamin Chun-Yu Wong; Shiu Kum Lam; Wai Man Wong; Jian Shun
Chen; Ting Ting Zheng; Rui E. Feng; Kam Chuen Lai; Wayne Hsing Cheng Hu;
Siu Tsan Yuen; Suet Yi Leung; Daniel Yee Tak Fong; Joanna Ho; Chi Kong
Ching; Jun Shi Chen Helicobacter pylori Eradication to Prevent Gastric
Cancer in a High-Risk Region of China: A Randomized Controlled Trial
JAMA, January 14, 2004; 291: 187 - 194.
Dear Editor,
In a recent issue of the Journal[1], Biancone et al. showed a comparable frequency of new diagnosis of neoplasia in inflammatory bowel disease (IBD) patients treated with infliximab and in patients who never received infliximab. These data seem to confirm reassuring message from clinical trials.[2,3] A peculiar situation may be IBD patients having had liver transplantation for primary sclerosing ch...
Dear Editor,
Dr Gupte and colleagues conclude that our article "does not acknowledge the contribution of the paediatric experience in this developing field" Nonetheless, the article does outline the development of small intestinal transplantation internationally for both adults and paediatrics and includes all of the paediatric outcome data submitted to the international registry, which we believe does include t...
Dear Editor,
We read with interest the paper by Foucher et al.[1] where the authors assess the accuracy of transient elastography for the detection of cirrhosis. Its use to assessing the severity of chronic liver disease in other clinical scenarios warrant further evaluations. According to large population studies, the prevalence of chronically hepatitis C virus (HCV) infected patients who have persistently normal...
Dear Editor,
We read with interest the article on ‘The current status of small bowel transplantation in the UK and internationally’ by Middleton et al.[1] This is a timely article about the improving worldwide outcome following small bowel transplantation, but does not fully reflect the status of small bowel transplantation in the UK. In the UK, the Department of Health through NSCAG (National Specialist Commissio...
Dear Editor,
I enjoyed the article by Albert et al. comparing newly emerging imaging modalities for the assessment and detection of small bowel Crohn’s disease, an area of the gastro-intestinal tract that is often difficult to adequately image, assess and biopsy.[1]
However, their article failed to mention 99mTc HMPAO labelled white cell scanning at all as a method of imaging the small (and large) bowel...
Dear Editor,
Dental erosion can be considered as an extraoesophageal manifestation of gastro-oesophageal reflux disease (GORD). Many reports have implicated refluxed gastric acid as a cause or contributory factor in the development of extraoesophageal disorders (“atypical” symptoms related to GORD), but the presence of lesions in oral cavity in patients with acid reflux has been less studied. The association between...
Dear Editor,
We read with great interest the guideline for gastroenteropancreatic neuroendocrine (including carcinoid) tumors by Ramage et al.[1] In this excellent guideline, they reported that appendix is the most frequent site of gastrointestinal primary endocrine tumors, consisting 35% of the total tumors, while colon and rectal carcinoids consisted only 7% and 10%, respectively. One important aspect not ment...
Dear Editor,
We read with interest the article by Israeli et al. on Anti- Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease as they concluded that ASCA and pANCA may predict development of inflammatory bowel disease years before the disease is clinically diagnosed.[1]
Anti-Saccharomyces cerevisiae antibodies (ASCA) are known as specific markers i...
Dear Editor,
Re: Stratification by gender and subgroup is necessary for RCT on IBS by Prof. Bian
Thank you for the communication of your interesting study results. Your findings highlight a problem especially for acupuncture research. Many experimental trials are pointing out the efficacy of acupuncture, also regarding problems of the gastrointestinal tract.[1-4] However, many of these trials are not a...
Dear Editor,
In 1994, Helicobacter pylori was declared a type 1 carcinogen—a definite cause of human cancer—by the International Agency for Research on Cancer (IARC).[1]
We read with interest the study by Mera et al.[1] on the effect of eradicating H. pylori infection on precancerous gastric lesions. Here the author Mera et al conclude that “Preneoplastic gastric lesions regress at a rate equal to the squ...
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