ST. JMC JOURNAL OF MEDICINE ISSN 0970-4221VOL.III NO. 1 MARCH 1990
Item
- Title
- ST. JMC JOURNAL OF MEDICINE ISSN 0970-4221VOL.III NO. 1 MARCH 1990
- extracted text
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ISSN 0970-4221
ST. JOHN’S MEDICAL COLLEGE
JOURNAL OF MEDICINE
VOL III No 1
March 1990
EDITORIAL
1
REVIEWS
Treatment of Chronic Hepatitis B infection
4
An update on treatment of hepatocellular carcinoma
7
GASTROENTEROLOGY SYMPOSIUM - ACUTE COLITIS
10
Medical management of ulcerative colitis
11
Surgery in ulcerative colitis
17
Acute bacterial colitis
19
- An update
Intestinal amoebiasis persisting problems & challenges
25
CASE REPORT
Endoscopic cord lateralisation for bilateral vocal cord palsy
28
INFORMATION FOR CONTRIBUTORS
EDITOR-IN-CHIEF
Ashley. J. D'Cruz
Submitting the Manuscript
EDITORIAL BOARD
The St John's Medical College Journal of Medicine accepts scientific contributions from all fields of
modern medicine and from all institutions and health care professionals. The journal is a quarterly
publication which will be published in March, June, September and December. It is owned by the
C.B.C.I. Society for Medical Education and published by the Principal, St. John's Medical College. The
journal is a part of it's commitment to continuing medical education. Articles and all editorial
communications should be addressed to the Editor, Alumni Office, St. John's Medical College,
Bangalore-560 034.
Rajini Macaden
Ravi C. Nayar
Mario Vaz
Original articles, short case reports and review articles are accepted for publication. Review articles
and editorials are usually on invitation by the Editorial Board. Letters to the Editor will be considered
for publication only if received at least six weeks prior to the next publication.
A.B. Kilpadi
PREPARING THE MANUSCRIPTS
A.S. Arvind
Anil Abraham
All manuscripts should be submitted in 3 copies (including the glossy prints). They should be neatly
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500 words. INDEX WORDS for the purpose of indexing and computer programming, should appear
on the same page.
The format for articles suggested is as follows: INTRODUCTION, MATERIALS AND METHODS,
RESULTS, DISCUSSION, REFERENCES.
Measurements should be in metric system.
OVERSEAS
R.R. Baliga
A.V. Kurpad
ILLUSTRATIONS AND TABLES
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REFERENCES
PUBLISHER
Prof. A.F.A. Mascarenhas
Principal
References should be compiled at the end of the articles according to the order of citation in the text,
not alphabetically. They should be typewritten, double-spaced under the heading REFERENCES.
Abbreviation for titles of medical periodicals should conform to those used in the latest edition of Index
Medicus. Give inclusive page numbers.
EXAMPLES OF REFERENCES
Journal Articles upto six authors, list ail names:
Kurpad AV, Shetty PS: Dietary Fibre and the colon. St.John’s J Med, 1988;1.5-12.
r*
,
..
...
_...
•-“v'rs followed by et al:
.Appleton, 1966; pp 208-215
□liege Journal of Medicine, I Floor,
034.
PUBLICATION COMMITTEE
C. Ramachandra
00/-
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Community Health Cell
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on
in 1988
St. John's
Medical
EDITORIAL
College Journal
of Medicine
“
CURRENT ISSUES IN ELECTROCONVULSIVE THERAPY
Electroconvulsive therapy (ECT) originated in Rome in 1938. Introduced for the treatment of schizophrenia, its usefulness
in other psychiatric disorders rapidly became apparent. Today, while depression, mania and schizophrenia continue to
comprise the major indicationes for ECT, its efficacy in other psychiatric (e.g. certain paranoid, reactive psychotic and
delirious states), neurological (e.g. Parkinson’s disease, tardive dyskinesia) and even medical (e.g. panhypopituitarism,
hypothyroidism, mild glucose intolerance) disorders is also known or mooted.1
At the time of inception of ECT, the electrical part of the treatment was solely intended to induce a convulsion, and was
considered to have no inherent therapeutic effect. This was because subconvulsive electrical stimuli were non-therapeutic and because convulsions, whether spontaneous, chemically-induced or electrically-induced, all ameliorated psychosis.2
The importance of the cerebral seizure was soon clarified with the finding that suppression of the peripheral convulsion (with
muscle relaxants) was not associated with loss of therapeutic potency, while lidocaine induced abbreviation of the
(electroencephalographic) cerebral seizure activity comprised the antidepressant action of the treatment.3
The electrical component of ECT was nevertheless accorded attention as it was realized that ECT-induced post
ictal confusion as well as cognitive impairment were probably linked to the elctrical dose delivered. Therefore, as early as
between 1940 and 1945 attempts were made to develop electrical stimuli that were low in dose yet retaining convulsant
properties.
Originally, the ECT stimulus was of sinusoidal waveform, stepped down in voltage from the electricity mains. With this
waveform, stimulus intensity waxes and wanes from and to the isoelectric point; since the process alternates on positive
and negative sides of the baseline, the wave resembles an‘S’lying on its side-hence its name. With the sinusoidal waveform,
current is flowing continuously (except momentarily, at the isoelectric points). Progressive modifications of this waveform
led to the brief-pulse stimulus, which comprises rectangular-shaped pulses of current, 0.5-2 msec, induration, 10-40 msec
apart (on average). With the brief-pulse stimulus, current flows only during the brief tenure of each pulse, resulting in
considerable stimulus economy. Ergometric and coulometric methods are both described to quantify the ECT stimulus.4
Attempts to identify progressively lower dose convulsant ECT stimuli continue5, but the wisdom of this is questionable6
as studies have shown that the pulse waveform may be therapeutically inferior to the sinusoidal waveform7 8 and that low dose
pulse stimuli are therapeutically inferior to high dose pulse stimuli.9 A possible explanation for these findings is that the cerebral
seizure is not an all or none phenomenon10, and hence that supra-seizure threshold electrical stimuli may be more
therapeutic11 perhaps due to the elicitation of more diffuse, intense and/or prolonged cerebral seizure activity.
Both subjective12 and objective13 measures have suggested that the therapeutic gain with high dose stimuli is not at the cost
of increased cognitive and other side effects; at the most, high dose stimuli are more likely to cause/prolong post-ictal
confusion14, and to increase cognitive adverse effects in the early hours after ECT but not thereafter.15 Thus,the benefit
risk trade-off seems to favour high dose stimuli.
In the context of the preceding discussion, an issue that warrants attention is the comparison of high energy pulse and
sinusoidal waveforms. It is possible that the former, by virtue of lesser stimulus dose, may produce lesser adverse effects
without compromised therapeutic efficacy.9 If such transpires, the entire spectrum of sinusoidal wave ECT stimulus
generators (such as are in use in India) may-become obsolete; until this time, however, the sinusoidal waveform should
rightfully continue to hold sway.
Dr. Chittaranjan Andrade, M.D.
Dept of Psychopharmacology
Dr. B.N. Gangadhar M.D.
Dept, of Psychiatry
National Institute of Mental Health and Neurosciences
Bangalore 560 029. INDIA.
REFERENCES:
1.
Weiner RD,
2.
Gangadhar BN. Andrade C, Janakiramaiah. N: Electroconvulsive therapy: Theory and practice. In: Vyas JN (Ed.): Postgraduate Psychiatry (in press).
MARCH
Coffey CE : Indications for use of electroconvulsive therapy. Annual Rev Psychiatry 1988;7:458-481.
1990
1
St. John’s Medical College Journal of Medicine
3. Cronholm B, Ottoson, J-O: Experimental studies of the therapeutic action of electroconvulsive therapy in endogenous depression. Acta Psychiatr Scand
1960;Suppl.145:69-141.
4.
Gangadhar BN,
5.
Hyrman V, Palmer LH, Cernik J, Jetelina, J: ECT: The search for the perfect stimulus. Biol Psychiatry 1985;20:634-645.
6. Gangadhar BN,
1989;12:61-66.
Andrade C: Electrical aspects of electroconvulsive therapy: A review. I. Electrical issues. Indian J Psychol Med 1989; 12:53-60.
Andrade C: Electrical aspects of electroconvulsive therapy: A review. II. Clinical and practical issues. Indian J Psych ol Med
7. Price TRP, McAllister TW, Peltier D. Kraft A: Positive response to bilateral sinusoidal ECT in unilateral and bilateral brief-pulse *ECT-resistanf depressive
illness. Convulsive Ther 1986;2:277-284.
8. Andrade C, Gangadhar BN, Subbakrishna DK, Channabasavanna SM, Pradhan N: A double-blind comparison of sinusoidal wave and brief-pulse
electroconvulsive therapy in endogenous depression. Convulsive Ther 1988;4:297-305.
9. Robin A, Tissera S: A double-blind controlled comparison of the therapeutic effects of low and high energy electroconvulsive therapies. Br J Psychiatry
1982:141:357-366.
10. Robin A, Binnie CD, CopasJB: Electrophysiological and hormonal responses to three types of electroconvulsive therapy. Br. J. Psychiatry 1985;147:707712.
11. MalitzS, Sackeim Ha, DecinaP, KanzlerM, Kerr B: The efficacy
Ny Acad Sci 1986;462:56-64.
12.
of
electroconvulsive
therrapy:
dose-response interactions with modality. Ann
Andrade, C, Gangadhar BN, Subbakrishna DK, Channabasavanna SM, Pradhan N. Subjective side effects and electroconvulsive therapy (submitted).
13. Swaminath G, Andrade C, Gangadhar BN, Rao SL, Narayan HS: The influence of ECT stimulus parameters on
endogenous depression (in preparation).
14.
Consensus Conference : Electroconvulsive therapy. JAMA 1985; 254:2103-2108.
15.
Squire LR, Zouzounis JA: ECT and memory: Brief-pulse versus sine wave. Am J Psychiatry 1986;143:596-601.
neuropsychological functioning in
COLITIS - WHAT’S NEW ?
Ulcerative colitis is an inflammatory disease of unknown etiology affecting the colon. Since its description by Wilks and Moxon
in 1875 ulcerative colitis is being recognized with increasing frequency worldwide, even in India.
Many exciting new developments have taken place in the understanding and treatment1 of ulcerative colitis, though
at present the etiology is unknown and therapy largely symptomatic. It has been recognized that current smokers are at a
reduced risk for developing ulcerative colitis2, but it is not clear how this observation is compatible with the theory that
inflammatory bowel disease is a mucosal energy deficiency disease3. Newer methods of delivering 5-aminosalicylic acid to
the colon4 have made therapy safer though serious side effects still occur5.
The risk of malignancy in patients with ulcerative colitis has recently been addressed6-7. While the risk of colon cancer in
long standing ulceration colitis is not as high as was thought earlier8 it is still of sufficient concern to warrant screening
programmes for malignancy of the colon. Certain points need emphasis. The risk of cancer developing in ulcerative colitis
is about 1% per year, the risk increasing over time6. High grade dysplasia is a precursor of colon cancer and identification
can reduce cancer risk by over a half. Because surveillance is time consuming and expensive a practical approach might
be prophylactic colectomy for young persons because the duration of risk is long, surveillance may fail and surgery is less
hazardous at a younger age. For persons with onset of disease over 60 years neither surgery nor surveillance is recommended
and for persons wiht onset of disease between 40 and 60 years surveillance may be most worthwhile9. The relationship
between chromosome deletions and colon cancer10 as applied to ulcerative colitis needs further study.
Spinctre saving surgery for ulcerative colitis has been authoritatively reviewed11. Patients come to surgery for life
threatening complications, risks of malignancy or intractability. Intractability or failure of medical therapy remains
to be defined. There is no strict definition, but it is important that the patient decides that the condition is intractable. Of
the various surgical procedures possible for ulcerative colitis the ileoanal anastomosis with construction of a pouch seems
the most viable option.
Advances have taken place int he study of infective colitis. The mechanism for antibiotic associated colitis has been identified
as being due to alteration of mucosal permiability12; the relationship between hemorrhagic colitis and Escherichia coli has
2
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been reviewed13. Patients with AIDS have a high rate of infection with Entamoeba histolytica trophozoites, yet symptomatic
illness is not common14. The interaction between immune status of the patient and pathogenic mechanisms15 is work for
the future.
An acute colitis presents as a bloody diarrhea. Identification of the etiology is important because the illness can be life
threatening. It cannot be overemphasized that the work-up of a patient with bloody diarrhea is simple and consists of a good
history and physical examination, microscopic study of the stool for trophozoites, red cells and pus cells, a bacterial culture
and finally a sigmosdoscopy and biopsy. Therapy of acute colitis, even ulcerative colitis, is most often rewarding.
Dr. P.S. Kamath
Associate Professor
Department of Gastroenterology
St. John'sMedical College Hospital, Bangalore
References
1.
Hanauer SB, Kirsner JB, Medical Management of Ileitis and Colitis Pract Gastroent 1988;12:18-29
2.
Jick H, Walker AM, Cigarette Smoking and Ulcerative Colitis. N Engl J Med 1986;308:261-5
3.
Editorial. Short - chain Fatty Acids in the Colon. NMJI 1989;2:209-10
4. Mulder CJJ, Tytgat GNJ, WEterman IT et al. Double blind comparison of slow release 5-Aminosalicylate and Sulfasalazine in remission maintenance in
ulcerative colitis. Gastroenterology 1988;95:1449-53
5.
Novis B, Korzets Z, Chen P et al, Nephrotic syndrome after treatment with 5 - aminosalicylic acid. Br Med J 1988;1:1442
6.
Ransohoff DF. Colon cancer in ulcerative Colitis. Gastroenterology 1988,95.1089-91
7.
Fozard JBJ, Dixon MF. Colonic Surveillance in Ulcerative Colitis-dysplasia through the looking glass Gut 1989;30:285-392
8. Gilat T, Fireman Z, Grossman A, et al, Colorectal cancer in patients with ulcerative colitis. A population study in Central Israel. Gastroenterology
1988;94:870-7
9.
Lennard-Jones JE. Compliance, cost and common sense limit cancer control in Colitis. Gut 1986;27:1403-6
10.
Fearon ER, Cho KR, Nigro JM. Identification of a chromosome 18Q gene that is altered in colorectal cancers. Science 1990;247:49-56
11.
Beart RW. Sphincter saving operations for chronic ulcerative Colitis. Adv. Surg 1990;23:195-210
12. Hecht G, PolhoulakisC, La Mont JT, Madara JL. Clostridium difficle Toxin A perturbs structure and tight junction permiability of cultured human intestinal
epithelial monolayers. J Clin Invest 1988;82:1516-24
13. Griffin PM, Ostroff SM, Tauxe RV et al. Illnessess associated with Escherichia coli 0157:H7 infection: A broad
1988;109:705-12
clinical spectrum Ann Intern Med
14. Allason - Jones E, Mindel A, Sargeaunt PG, Williams P. Entamoeba histolytica in a commensal intestinal parasite in homosexual man. N Engl J Med.
1986,315:352 - 5
15. Sargeaunt PG, Jackson TFHJ. Biochemical homogeneity of Entamoeba histolytica isolates, especially
1982;1:1386-8.
MARCH
1990
those
from
liver
abscess . Lancet
3
REVIEWS
St. John’s Medical College Journal or Medicine
TREATMENT OF CHRONIC HEPATITIS B INFECTION
MERON R JACYNA
INTRODUCTION:
Chronic Hepatitis B virus (HBV) is a major cause of morbidity
and mortality in man and 50% of chronic carriers can be
expected to die, either as a result of chronic inflammatory
liver disease (as a consequence of replicating intra-hepatic
HBV) or secondary to the development of hepato-cellular
carcinoma.1
Successful elimination of replicating virus from the liver thus
is of prime importance in preventing the development of
these potentially fatal complications. In order to design
successful treatment regimes for chronic viral infection, some
understanding of the mechanisms of viral persistence must
be gained. This review looks at the possible reasons for the
development of. the chronic carrier state, and also at
strategies of antiviral therapy that have been used in an
attempt to eliminate virus and prevent subsequent complica
tions.
REASONS FOR CHRONIC VIRAL CARRIAGE :
There are many possible reasons why chronic viral carriage
occurs in individuals, but epidemiologically there are two
large groups of carriers who are strikingly different. First,
there are those patients with chronic carriage who acquire
their infection during the neonatal period, and second, there
are those patients who are infected in later childhood or
adulthood.
1.
Infection during the Neonatal Period
This large group of patients is largely representaitve of
chronic HBV carriers from South-East Asia and China, who
acquire their infection during the neonatal period and who
are by far the largest group of chronic carriers. Ninety
percent of babies born to HBV ‘e’ antigen-positive mothers
become infected with HBV; most of these will develop a
chronic carrier state2. These infants probably receive a large
innoculum of virus from maternal blood before or during birth,
and also by close contact with secretions during birth.
Normally, elimination of infected hepatocytes is achieved
by natural killer cells and cytotoxic T cells, which recognise
infected heptocytes displaying HBV antigens on the cell
MERON R JACYNA MD MRCP
LECTURER IN MEDICINE
DEPARTMENT OF HEPATOLOGY
ST. MARYS HOSPITAL MEDICAL SCHOOL
IMPERIAL COLLEGE
UNIVERSITY OF LONDON.
4
surface.3 In the immunologically immature neonate, circulat
ing serum HBV ‘e’ antigen may function to induce tolerance to
those epitopes that are usually the target of the cytotoxic
cellular response.
A further factor that may lead to the development of chronicity in neonates is the passage of maternal IgG anti-HBc
via the placenta. In the case of HBV-infected hepatocytes,
anti-HBc and anti-HBe inhibit the lysis of infected
hepatocytes by the cytotoxic T cells.4
2.
Infection after the neonatal period
This is the group of patients mostly seen in Western Europe
and the USA who usually acquire their infection in adulthood
as a result of intravenous drug abuse or homosexual
activity. In contrast to the situation at birth, only 5%-10% of
these infected individuals will develop chronic infection. The
reasons for development of chronicity in this group are
different from those of patients who acquire their infection
around the time of birth. There is good evidence that some of
the adult-acquired carriers have a deficiency in alpha and
gamma interferon production.5 The interferons are essential
for successful elimination of virus infections; they enhance
MHO class I display and induce an intracellular antiviral
state which blocks virus replication. Thus a deficiency of
interferon or interference with the hepatocyte response to
interferon may lead to the establishment of a chronic carrier
state. There is also data to suggest that the virus itself may
be partly to blame for the interferon deficiency, and also
that it may interfere with the interferon response. It has been
shown that the HBV-core protein directly suppresses the
expression of human interferon.6 In addition, there is a region
of gene homology in the core gene of the HBV genome which
competes with the hepatocyte genome, making the cell less
responsive to interferon.7 Thus qualitative and quantitative
disturbances in interferon mediated virus clearance may be
the reason for the chronicity of HBV infection in this group
of carriers.
Antiviral therapy:
It is now clear that the disappearance of HBV‘©’antigen from
the serum and the development of anti-HBe is usually
associated with the elimination of replicating HBV from the
liver and results in a biochemical and histological remission
in the majority of infected individuals.8
Thus the goalof anti-viral therapy should be to increase the
chances of seroconversion from HBe to anti-HBe. However,
there are two distinctly different groups of chronic carriers
as illustrated above, who have different reasons for the
development of the chronic carrier state. Rationally therefore
it would seem logical that different approaches to treatment
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St. John’s Medical
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between these two groups would be required, and it might
be predicted that different responses to the same treatment
would be seen between the two carrier groups. This turns out
to be the case as will be seen in the studies reviewed below.
with HIV infection, are less responsive. Neonatallyacquired carriers (usually children and patients from China
and the Far East) also do not respond to alpha-interferon as
well as adult-acquired carriers.9
Single agent therapies :
Combination therapies
In both adult and neonatally acquired carriers, combination
therapy seems to offer a greater chance of anti-HBe
seroconversion than any single agent currently available.
The most promising combination therapies at the present are
those that involve a pre-treatment period of corticosteroids.
In chronic HBV-induced hepatitis, the liver damage is
1. Adenine arabinoside and adenine arabinoside mono
immunologically
mediated,
but immunosuppressive
phosphate
therapy is hazardous and may cause serious hepatic
decompensation when withdrawn in patients with more
The clinical usefulness of adenine arabinoside (ARA-A) is
advanced liver disease.11 However, a short course of
* limited by its poor aqueous solubility, which results in it having
steroid
pre-treatment can provide a rebound immunostimu
to be given by intravenous infusion. Controlled studies in
latory
effect
which, when the steroids are stopped and in as
carriers who acquired their HBV infection in adulthood have
sociation
with
other anti-viral therapies, may increase the
indicated that a 10 day course produces a 40%
chances
of
seroconversion.
In adult-acquired carriers, 2
seroconversion rate9. Inneonatally-acquired HBV carriers,
however, controlled studies have now shown that the controlled studies of prednisolone pre-treatment followed by
either interferon 12 or ARA-AMP 13 resulted in seroconver
seroconversion rate of treated patients is no higher than that
sion rates of 44% and 73% respectively. In neonatally
of untreated patients. Most of the recent clinical trials on
acquired carriers, a case controlled study of prednisolone
ARA-A have focussed on its highly water-soluble derivative
followed by ARA-A gave seroconversion rates of 55%,
adenine arabinoside monophosphate (ARA-AMP) which can
be given by intra-muscular injection and is thus easier to self compared to only 20% in the untreated patients 14. Other
studies of prednisolone followed by interferon in neonatally
administer. In adult-acquired carriers, controlled trials have
acquired carriers have also shown much higher seroconver
demonstrated a seroconversion rate of 10%-55% in treated
sion rates than placebo and there seems no doubt that this
patients given one month’s therapy with ARA-AMP, although
form of combination therapy at present is the best treatment
the seroconversion rate appears to be lower in homosexual
option
for this large goup of patients. Patients with
patients. Unfortunately no controlled trials of ARA-AMP in
advanced
or serious hepatic diseases must, however, be
neonatally-acquired HBV infection have been published.
excluded
from
this form of therapy.
ARA-AMP is also associated with significant neuromuscular
toxicity and therefore cannot be recommended as single
Conclusions :
agent therapy.
Only 3 single agent anti-viral compounds have been
properly studied in randomised controlled clinical trials.
These are; adenine arabinoside and adenine arabinoside
monophosphate, acyclovir and lastly alpha-interferon.
2.
Acyclovir
Only one controlled study in adult-acquired carriers has
been published 10 which showed no advantage of this agent
over no treatment. No controlled studies in neonatallyacquired carriers have yet been published.
3.
Alpha-Interferon
There are two types of alpha-interferon commercially avail
able; lymphoblastoid interferon, which consists of a mixture
of alpha-interferon subtypes and is produced by stimulation
of a lymphoblastoid cell line with Sendai virus, and
recombinant alpha-interferon which consists of one subtype,
alpha-2a, and is manufactured by molecular cloning technol
ogy. Both types of interferon seem equally efficacious in
HBV-carriers, with loss of ‘e’ antigen and a ‘seroconversion
hepatitis’ occuring about 2 months after the initiation of
therapy in a proportion of patients. In adult-acquired
carriers, a three month course of thrice weekly alpha
interferon will produce seroconversion rates of 20%-50%9,
although once again homosexual patients, particularly those
MARCH
1990
In adult-acquired chronic HBV infection, the best single
agent therapy is lymphoblastoid or recombinant alpha
interferon which offers upto a 50% chance of seroconver
sion. For the large group of carriers who acquired their
infection during the neonatal period, single agent therapy
is relatively ineffective and combination therapy, in the form
of a pretreatment period with prednisolone followed by either
alpha-interferon (preferably) or by ARA-AMP, is the only
treatment that has been shown to significantly improve the
chances of seroconversion from‘e’ toanti-e. Further studies
of newer single agents and also of different combination
therapies are still required.
REFERENCES
1. Beasley RP. Hwang L, Lin CC, Chien CS Hepatocellular carcinoma and
hepatitis B virus. Lancet 1981 :ii;1129-1132
2. Beasley RP. Hwang L, Lin C et al Hepatitis B immune globulin efficacy in
the interruption of perinatal transmission of hepatitis B virus carrier state.
Lancet 1981:ii;387-393.
3. Thomas HC, Jacyna MR, Waters J, Main J Virus-Host Interaction in
Chronic Hepatitis B virus Infection. Sem Liv Dis 1988:8,No.4.
5
St. John’s Medical College Journal or Medicine
4.
Pignatelli M, Waters J, Lever AML et al Cytotoxic T-cell responses to the
nucleocapsid proteins of HBV in chronic hepatitis. J Hepatol. 1986.4;15-21.
5. Abb J, Zachoval R, Eisenberg J et al Production of interferon alpha and
gamma by peripheral blood leucocytes from patients with chronic hepatitis
B virus infection. J.Med. Virol 1985:15:171 -176.
6. Twu JS, Lee CH, Lin PM, Schloemer RH Hepatitis B virus suppresses
expression of human beta-interferon. Proc. Natl. Acad.Sci. 1988.85:252-256.
7. Thomas HC, Pignatelli M, Lever AML Homology between HBV-DNA and
a sequence regulating the interferon-induced antiviral system possible
mechanism of persistent infection. J.Med. Virol 1986 19:63-69.
8. Hoofnagle JH, Dusheiko GM, Seeff LB et al Seroconversion from hepatitis
B e antigen to antibody in chronic hepatitis B infection Ann.lntern.Med.
1981:94:744-748.
9. Thomas HC, Scully LJ. Antiviral therapy in hepatitis B infection
Bull 1985:41:374-380.
Brit Med
10. Alexander GJM, Fagan EA, Hegarty JE, Yeo J, Eddleston ALWF
Williams R. Controlled clinical trial of acyclovir in chronic hepatitis B virus
infection. J. Med. Virol 1987'21;81-87.
11. Nair PV, Tong MJ, Stevenson D, Roskamp D, Boone C Effects of short
term high dose prednisone treatment of patients with HBsAg-positive chronic
active hepatitis. Liver 1985:5:8-12.
12. Perillo R, Regenstein FG, Peters M et al Prednisone withdrawal followed
by recombinant alpha-interferon in the treatment of chronic hepatitis B infec
tion Ann. Intern. Med. 1988:109:95-100.
13. Perillo R, Regenstein F, Bodicky C et al Comparative efficacy of ARAAMP and prednisolone withdrawal followed by ARA-AMP in the treatment
of chronic active hepatitis type B-Gastroenterology 1985:88:780-786.
14. Yokosuka O, Omata M, Imazeki F et a! Combination of short-term predni
solone and adenine arabinoside in the treatment of chronic hepatitis B
Gastroenterology 1985:98,246-251.
6
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REVIEWS
of Medicine
AN UPDATE ON TREATMENT OF HEPATOCELLULAR
CARCINOMA
DR. SPYROS. P. DOURAKIS
AN UPDATE ON TREATMENT OF HEPATOCELLULAR
CARCINOMA
Although relatively rare in the United States of America and
Europe, HEPATOCELLULAR CARCINOMA (HCC) is proba
bly the commonest malignant tumor in males in the world.
The annual incidence is estimated to be 1,000,000 cases’.
There is a strong evidence of an etiologic role for hepatitis B
virus infection in the etiology of HCC <2*3-4-5). Carriers of the
virus are 100 times more at risk for HCC than non-carriers6.
The natural history of the majority of HCC patients is
predictable. Survival is usually short, with death occurring
within a few weeks to months after diagnosis. There is no
effective medical therapy for HCC. Surgery offers the best
hope of cure in patients suffering from this highly lethal
disease.
SURGERY
The resectability of the tumor depends on its size, and the
absence of any local or distant invasiveness. Less than one
third of patients have resectable malignanacy at the time of
the first detection of the disease7.
After resection, the liver has a remarkable ability for
regeneration, by hypertrophy and hyperplasia of the
remaining liver cells. It is well known that local invasive
ness, as manifested by invasion of the inferior vena cava,
portal vein or adjacent structures, is a contraindication for
resection0. The resection of the tumor is also contraindicated
when there is multicentric involvement of both lobes9.
Cirrhosis by itself is not a contraindication, provided the liver
function is preserved, to compensate the resected
region00-11-12).
The ethnic origin of the patient plays an important role,
because encapsulated, small tumors seen in Japan, are
more easily resected than the Western-type tumors with the
explosive clinical manifestations and rapid downhill progres
sion03’1^.
DR. SPYROS. P.DOURAKIS MD.
CONSUL TANT PHYSICIAN,
HIPPOKRA TION HOSPITAL
ACADEMIC DEPT OF MEDICINE
AMPELDKIP111523
ATHENS
GREECE.
MARCH
1990
Before surgery the tumor must be localized by CT scanning
and arteriography. The liver function must be tested using the
serum albumin level and prothrombin time. Intraoperatively,
hepatic ultrasound can detect tiny metastasis or multicentric
growth, which would contraindicate liver resection.
The left lobe can be resected more easily than the right lobe8.
The overall operative mortality is 3-36%, the three-year
survival rate 11-42% and the five-year survival rate 528%(7A14>. There is a trend in recent years to investigate
regularly cirrhotics for early detection of tumors at a re
sectable stage, using four-monthly serum alpha-fetoprotein
levels and ultrasound. The recruitment of patients at
different stages of the disease and the differences in the
preoperative performance status, can explain the discrep
ancies in the above figures.
CHEMOTHERAPY
For unresectable tumors, single agent or multi-drug chemo
therapy have been proposed. Most of the studies have
been done uncontrolled and the results are difficult to
interpret. Only objective parameters must be used as an
indication of a drug’s potential in treating atumor. Ultimately,
however, increased survival is the end point of interest.
Doxorubicin (Adriamycin) has had the best results so far, as
a single agent chemotherapy. It induces partial or complete
remission in one fourth of treated patients, without improving
the survival15. Patients with well preserved liver function
respond better. Hepatitis B antigen negative patients
respond better than antigen positive ones. The response to
treatment can be monitored by imaging technique (ultra
sound, CT scan) and by testing serially alpha-fetoprotein or
des-gamma-carboxyprothrombin levels. The dose is 60 mg/
m2 body surface, given IV every three weeks, the maximum
dose is 550 mg/m2. The dose must be halved in jaundiced
patients. The full blood count and ECG are followed
regularly. Side-effects include nausea, vomiting (which can
be prevented by the appropriate treatment), reversible
alopecia and cardiotoxicity.
The newer anthracyclin derivatives Mitozantrone and Epirubicinhave given similar results16. It is claimed that some
side effects (vomiting, hair loss) are diminished. The dose
of Mitozantrone is 12mg/m2 every three weeks.
It has been attempted to improve the poor results seen with
single agent chemotherapy by using a combination of 5FU,
methyl-CCNU and doxorubicin. This has been found to be as
effective as doxorubicin alone but with more side effects.07-18*
To date, no therapy has been shown to increase the median
7
St. John’s Medical
College Journal of Medicine
survival of the treated patients19. There is no role for
chemotherapy in the nonprotocol treatment of HCC.
HEPATIC ARTERIAL THERAPY
The HCC is a hypervascular tumor which is largely supplied
by the hepatic artery. After percutaneous catheterization of
the hepatic artery via the femoral artery and coeliac axis, em
bolization or intra-arterial chemotherapy has been at
tempted. The aim is to reduce or possibly to eradicate the
tumor by interfering with its vascular supply and to deliver high
dose of toxic drugs locally, preventing the systemic side
effects.
Embolization is done using gel foam. Preoperatively, the
portal vein must be carefully checked for patency. There are
a few serious complications of this form of treatment such as
abscess formation, misplaced injection & severe pain.
Fever may be present due to tumor necrosis. Theone-year
survival rate is42%20. As the tumor rapidly regains a fresh
arterial supply, embolization may have to be done repeatedly.
The whole procedure can be followed by systemic chemo
therapy or resection. This is the proposed treatment for
spontaneous rupture of HCC, a lethal complication of the
disease. The same treatment has been proposed for the
closure of intratumor arterio-portal shunting which can aggra
vate seriously the pre-existing portal hypertension.
Microcapsular form of Mitomycin-C has been delivered to the
tumor by selective hepatic arterial infusion21. The combina
tion of the drug with lipiodol can give long-lasting results*22-23-24*. The drug is slowly released from the iodized oil,
which remains in the tumor and can be used as a marker of
treatment response and disease progression25.
Hepatic arterial infusion of floxuridine, doxorubicin and
Mitomycin-C gave better results compared with IV
treatment. Unfortunately, the mean survival of the patients
was less than 9 months26. The poor response to this form of
chemotherapy makes it rather difficult to recommend this
treatment.
RADIATION
Radiation treatment has been limited by dose-related
radiation hepatitis. In the few studies done so far, the results
are disappointing27.
HORMONALTHERAPY
Estrogen receptors have been demonstrated in some HCC
tumor specimens.
Hormonal manipulation has been
attempted with equivocal results28.
ALCOHOL INJECTION
Another treatment option is the direct percutaneous injection
within the tumor, of absolute alcohol. This can lead to tumor
necrosis and can be followed by a wide resection of the
remaining tumor29.
8
IMMUNOTHERAPY
The recent progress in immunotherapy has been used in
trials for novel cancer therapy. Radio-isotopes bound to
antibodies raised against neoplastic cell epitopes, may be
given IV or intra-arterially with the expectation that they
will be delivered directly to neoplastic cells and kill them.
1131-ferritin and alpha-fetoprotein antibodies have been
used similarly*30-31*. The study was uncontrolled and 50%
of the treated patients showed a partial response.
Unfortunately, systemic chemotherapy was given concur
rently and the results are difficult to interpret.
A novel approach of targeted HCC therapy has been
developed, following the observation that normal, but not
neoplastic cells, bear receptors for asialoglycoproteins. A
hepatotoxin, galactosamine, can be added to cells in culture
to produce a high mortality in neoplastic cells, whereas, the
normal cells can be protected by the simultaneous usageof
the specific antidote chemically linked to an asialoglycopro
tein. Results of these trials are expected shortly32.
Chemotherapeutic agents can be combined to antibodies
raised against a HCC membrane epitope33.
The growth of any malignancy may be related to the host
defences inability to lyse the tumor cells. An attempt has been
made to overcome this lack of efficiency by stimulating LAK
(lymphokine activated killer) cells formation after treatment of
patients’s mononuclear cells with inteleukin-2.34.
Alpha-interferon needs to be given in high dose to achieve
tumor regression in animals.35. Human studies have been
limited because of the systemic toxicity. The addition of
moderate doses of alpha-interferon to systemic chemother
apy gave poor results and is not recommended*36-37*. Recom
binant human gamma-interferon has been used unsuccess
fully too38.
Due to the gloomy results of the different forms of treatment,
hepatic transplantation has been proposed. Recurrence
and metastases are usual and can be enhanced by the
immunosuppressive treatment*39-40-41*. The median survival is
120 months in highly selective groups. Others, have claimed
5-year survival of 20%42 This treatment is extremely costly
and can be recommended only in clinical trials43.
PREVENTION :
Only by eradication of the B virus, can one expect a decline
of the prevalence of HCC. The appropriate vaccine is
highly recommended worldwide, especially in places with
high hepatitis B carriage rate. The newly described hepatitis
C virus seems to have an oncogenic potential and needs to
be further investigated. Elimination of mycotoxins from foods
by better agricultural methods and improved storage of
cereals may contribute to HCC prevention44.
VOL III No. i —
St. John’s
Medical
College Journal
of Medicine
REFERENCES :
23. Takayasu K.Shina V, Muramatsu Yetal: HCC: treatment with intraarterial
iodized oil with and without chemotherapeutic agents. Radiology
1. Alward WL, McMahon BJ, Hall DB et al: The long-term serologic course of 1987;162:345-349.
asymptomatic hepatitis B virus carriers and the development of primary
HCC.J Jnfect. Dis. 1985; 151:604-609.
24. KasugaiH, KojimaJ, Tatsuta Metal treatment of HCC by transcatheter
arterial embolization combined with intraarterial infusion of a mixture of
2. Beasley RP, Hwang LY, Lin CC et al : HCC and hepatitis B virus:a
cisplatin and ethiodized oil. Gastroenterology 1989;97:965-971.
prospective study of 22707 men in Taiwan. Lancet 1981;2:1129-113.
25. Maki S, Konno T, Maede H : Image enhancement in a computerized
3. Heyward WL, Lanier AP.BenderTR, etal: Primary HCC in Alascan natives, tomography for sensitive diagnosis of liver cancer and semi-quantitation of
1969-1979. IntJ.Cancer 1981;28:47-50.
tumor.
Selective drug targeting with oily contrast medium. Cancer
1985;56:751-757.
4. Prince AM, Alcabes P:The risk of development of HCC in hepatitis B
virus carriers in New York: a preliminary estimate using death-records
26. Ensminger WD, Rosowsky A, Raso V et al : A clinical pharmacological
matching. Hepatology 1982;2:15S-20S.
evaluation of hepatic arterial infusion of FUDR and 5-FU. Cancer Research
1978;38:3784-3792.
5. Shafritz DA, ShouvalD, Sherman H let al: Integration of hepatitis B virus
DNA into the genome of liver cells in chronic liver disease and HCC:studies
27. Cochrane A, Muray-Lyon I, Brincly D et al: Quadruple chemotherapy
in percutaneous liver biopsies
and post-mortem tissue specimen.
versus radiotherapy in treatment of HCC. Cancer 1977;40:609-614.
NewEngl. J.Med. 1981;305:1066.
28. Freidman M, Damanes D, Hoffman P : HCC: Hormone receptors and
6. London WT.Primary HCC Etiology, pathogenesis and prevention.
therapy. Amer.J.Med. 1982;73:362-366.
Hum. Pathol. 1981; 12.1085-1097.
29. Ocuda K Early recognition of HCC.Hepatology 1986;6:729-735.
7. Iwatsuki S, Shaw B, Starzl T:Experience with 150 liver resections.
Ann.surg. 1987;97:247-253.
30. LinYK, Zang KZ.Wn YD, etal: Treatment of advanced HCC by l’”-antiAFP. Lancet 1983;1:531-533.
8. Kinami V, Takashima S, Miyamaki I:Hepatic resection for hepatocellular
carcinoma associated with liver cirrhosis. World J.Surg. 1986;10:294-301.
31. Order SE, Stillwagon GB, Klein JL, etal: Iodine 131 antiferritin, a new
treatment modality in HCC.J.CIin.Oncol. 1985;3:1573-1582.
9. LeeCS, SungJL, Wang LY etal: Surgical treatment of 109 patients with
symptomatic and asymptomatic HCC.Surgery. 1986;99:481-490.
32. Wn GV, Keegan-Rogers V, Franklin S, et al : Targeted antagonism
10. Bismuth H, Houssin D, Ornowski J et al : Liver resections in cirrhotic
patients-a Western experience. World J.Surg. 1986;10:311-317.
11. Lannois B, Bourdonnec P, Nguyen T, et al: Surgical treatment of HCC on
cirrhosis: Press Med 1986;15:2235-2238.
12. Nasague N, Yukaye H, Chang Y : Appraisal of hepatic resection in the
treatment
of
minute
HCC
associated
with
liver
cirrhosis. Br.J .Surg. 1987;74:836-838.
13. Lotze M: Surgical management of HCC. Gastroenterol. Clin. North
Am.:1987;16:613-626.
14. Scudamore CH, Ragaz J, Kluflinger AM et al: Heptaocellular carcinoma
: a comparison of oriental and Caucasian patients. Am.J.Surg. 1988;155:659662.
15. Johnson PJ, Williams R, Thomas Het al: Induction of remission in HCC
with doxorubicin. Lancet 1978;1:1006-1009.
16. Dunk AA, Scott SC, Johnson PJet al: Mitozantrone as a single agent
therapy in hepatocellular carcinoma. A phase 2 study. J. Hepa
tol. 1985;1:395-4.
17. Falkon G, Morte! CG, Lavin P: Chemotherapy studies in primary liver
cancer: a prospective randomized clinical trial. Cancer 1985;42:2149-2156.
18. DourakisS, Stathopoulos G, StergiouSetal: Combination chemotherapy
of HCC with cisplatin and epirubicin. latriki (GK) 1989;87:564-567.
19. Dourakis S, Stergiou G stathopoulos G et al: Prognosis and treatment of
HCC. Nosocomiaka Chronica. (GK) 1988;45:543-550.
20. Allison DJ, Jordon H, Hennessy O:Therapeutic embolisation of the
hepatic artery:-a review of 75 procedures. Lancet 1985;1:595-598.
21. Ohnishi K, Tsuchiya S, Nakayama T et al: Arterial chemoembolisation
of HCC with mitomycin C microcapsules. Radiology 1984;152:151-155.
22.
Ocuda K:Primary liver cancer in Japan. Cancer 1980;45:2663-2669.
MARCH
1990
of galactosamine
toxicity
in
vitro. J. Biol .chem.1988;263:4719-4723.
normal
rat
hepatocytes
in
33. Baldwin RW, Byres Vs:Monoclonal antibodies in cancer treatment.
Lancet 1986;1:603-606.
34. Hsieh KH, Shu S, LeeCS, etal: Lysis of primary HCC by lymphokine
activated killer cells. Gut 1987;28:117-124.
35. Dunk AA, Keda T, Pignatelli M: Human lymphoblastoid interferon. In
vivo and in vitro studies in HCC.J. Hepatol. 1986;2:419-429.
36. Sachs ED, Bisceglie AM, DusheikoGM, etal: Treatment of hepatocel
lular carcinoma with recombinant leucocyte interferon: a pilot study. Br.
J.Cancer 1985;52:105-109.
37. Brook MG, Dunk AA, McDonald JA.et al : Human lymphoblastoid
interferon does not increase survival when added to mitozantrone in the
treatment of HCC.Aliment.PharmacoLTherap. 1987;1:315-320.
38. Forbes A, Johnson PJ, Williams R. Recombinant human gamma
interferon in primary HCC.J R. Soc.Med. 1985;78:826-831.
39. Ringe B, Wittekind C, Bechstein WO, et al: The role of liver transplantation
in HCC.Ann.Surg.1989;1:88-98.
40. Konery B, Cassavilla A, Bowman J, et al: Liver transplantation for
malignant tumors. Gastroenterol. Clin. North. Am. 1988;17:177-193.
41. Patt YZ, Claghorn L, Charnsangavej C, et al: HCC: a retrospective
analysis pf treatments to manage disease confined to the liver. Cancer
1988;61:1884-1888.
42. Iwatsuki S, Gordon RD, Shaw BW, etal:Role of liver transplantation
in cancer therapy. Ann. surg. 1985;202:401-407.
43. Pichlmayr R, Ringe B, Wittekind C, et al : Liver grafting for malignant
tumors. Trasplant Proc.1989;21:2403-2405.
44. Lutwick LT:Relationship between aflatoxin, hepatitis B virus and HCC.
Lancet 1979;1:755-757.
9
St. John’s Medical College Journal of Medicine
—p——HMM ■IHIWI ............ ■ ■........ .. ■!■ I mm—O—— —■—■—
GASTROENTEROLOGY SYMPOSIUM - ACUTE COLITIS
INTRODUCTION
Acute colitis presenting as bloody diarrhea is a common clinical problem in
patients of all ages. While infective colitis is considered in all cases of bloody
diarrhea a high index of suspicion is required to identify a patient with ulcerative
colitis. A long history can help recognize the condition, but a diagnosis of
ulcerative colitis can be difficult in the patient who presents for the first time. The
aim of symposium is to put acute colitis in perspective with emphasis being on
understanding the more difficult situation.
The symposium has been divided into four parts:
1. Medical management of ulcerative colitis
2. Surgical management of ulcerative colitis
3.
Bacillary colitis
4- Amoebic colitis
Each of the articles has been written by experts. The authors of the sections on
bacillary colitis and amoebic colitis are widely recognized as authorities in their
field.
*DR. P.S. KAMATH
M.D., D.M.
Guest Editor
* Associate Professor,
Head of the Dept, of Gastroenterology
St. John's Medical College Hospital, Bangalore.
io
VOL in No. i-—
GE-SYMPOSIUM
St. John's Medical College Journal of Medicine
MEDICAL MANAGEMENT OF ULCERATIVE COLITIS
ANAND JALIHAL
Ulcerative Colitis is an inflammatory disease of the colon of
unknown etiology. It is a disease with remissions and
esacerbations with serious local and systemic complications.
Treatment involves use of various drugs whicfh can compro
mise the immune status of the patient, which means that this
form of therapy is dangerous in infectious disorders of the
colon. Thus a proper diagnosis is the corner stone in
management of ulcerative colitis.
THE CORRECT DIAGNOSIS
In a patient with ‘chronic’ or ‘recurrent’ watery diarrhoea
and mixed with blood and mucous often with crampy lower
abdominal pain and extracolonic manifestations (uveitis,
aphthous stomatitis, arthritis, pyoderma gangrenosum) a firm
diagnosis is easily made based on sigmoidoscopic findings
and a rectal biopsy.
The situation becomes different when dealing with a patient
with the ‘first’ attack of a severe bloody diarrhoea and
sigmoidoscopy demonstrates ‘colitis’. Immediate tests to
rule out infections are mandatory. It is suggested that the
following tests be done immediately.
(1) Microsopic Examination of fresh stool samples (at least
three) to rule out Hematophagic Entamoeba Histolytica.
(2) Stool Culture to look for Shigella, Campylobacter and
Salmonella using proper culture techniques.
(3) Sigmoidoscopic suction of mucopus from uIcerated areas
and “wet mounted" in saline to look for amoebae.
(4) Sigmoidoscopic biopsy specimen to be examined for
amoebae in the tissue and also to look for characteristic
features of mucosal architectural distortion typical of
ulcerative colitis.
With the above tests it takes only 48 hours to rule out
ANAND JALIHAL M.D., D.M
DEPARTMENT OF GASTROENTEROLOGY
ST. JOHNS MEDICAL COLLEGE & HOSPITAL
BANGALORE 560 034.
REPRINT REQUESTS :
DR. ANAND JALIHAL
ASST. PROF. DEPT. OF GASTROENTEROLOGY
ST.JOHNS MEDICAL COLLEGE & HOSPITAL
BANGALORE 560034.
MARCH 1990
infectious causes of Colitis.
SIGMOIDOSCOPY
There is marked alteration of mucosa in ulcerative colitis.
Involvement of the rectosigmoid is seen in 90 to 95% of
patients with ulcerative colitis1 and sigmoidoscopy is often
the only test needed to diagnose this condition. The char
acteristic changes seen are loss of vascular pattern, loss of
the normal glistening surface, granularity, friability and
pseudopolyps. Involvement characteristically starts just
within the anal verge and is‘difuse’, with no mucosal sparing
unlike Crohn’s disease or amoebic colitis.
When rigid instruments are used biopsy should be taken
below the peritoneal reflection and along a Rectal valve
to prevent perforation. Biopsies may be at any site when
flexible instruments are used. Rectal biopsy typically
shows
mixed Cellular infiltration, (lymphocytes, plasma
cells, polymorphs and eosinophils). Goblet cells are de
pleted; microscopic erosions and crypt abscesses are often
noted. Atrophic changes in the mucosa such as diminution
in the number of mucous glands and branching of glands are
characteristic features.
Colonoscopy and/or Barium Enema are not usually indicated
in the innitial diagnosis of ulcerative Colitis. They howeiver
are necessary to determine the extent ofinnvolvementof the
colon and in long term surveillance programmes to screen
for colon cancer.
CLINICAL PRESENTATIONS
The clinical course, severity and ultimate prognosis are
highly variable. The course most often takes the following
forms.2
(1) Intermittent attacks of symptoms with complete remis
sions between attacks (60-75%)
(2) Single attack with no subsequent symptoms for as long
as 15 years (5-10%)
(3) continuous symptoms without any remission (5-10%)
Any of these courses may present with a fulminant Colitis
which involves toxic dilatation of the Colon ( toxic mega
colon) which may be life threatening and may warrant
emergent Surgery (1-3% of all cases of Ulcerative Colitis)
The severity of presentation is arbitrarily divided into three
categories but has prognostic value.(3,4)
11
St. John’s Medical
College Journal of Medicine
No. of bowel movements
Fever
Hematocrit %
Leucocyte count
Serum Albumin
Heart Rate
ESR mm/hr
Incidence
Mortality
Mild Disease
Moderate Disease
<4
Nil
Normal
Normal
Normal
<90
Normal
60%
0.4%
4-6
<101°F
30-40
<12,000
3 - 3.5 gm%
90-100
20-30
25%
2.4%
Ulcerative Colitis is also classified based on the extent of
Colonic involvement as proctitis, proctosigmoiditis, left sided
colitis (upto splenic flexure) or pan colitis.
5-15% of patients with limited disease may show ultimate
progression to involve the whole colon.5 Mild disease usually
is segmental and severe disease is usually diffuse. Excep
tions to the above however occur.
Treatment
General Measures
Patients with severe colitis tend to be dehydrated. They lose
potassium in Stool (compounded by steroid use which causes
renal potassium loss). Loss of bicarbonate results in
systemic acidosis. In addition, loss of blood and protein in the
exudatecauses anemia and hypoalbuminemia. All the above
complications should be treated appropriately with fluids,
blood and plasma. There is some evidence to suggest that
uncorrected electrolyte abnormalities are associated with the
development of a toxic megacolon.
There is no evidence that any dietary restriction or regimen
alters the course of the disease. Cow’s milk allergy has not
been shown to be important in the causation of disease.
Lactose intolerence could well aggravate diarrhoea and
milk should be withheld only if the above condition is docu
mented. Parenteral hyperalimentation certainly improves
nutritional status of patients with severe colitis;6 there is no
evidence that it alters the course of severe colitis. However
a chronic and debilitating disease such as ulcerative colitis
is associated with a great psychological trauma to patients.
There is no evidence that psychiatric abnormalities are
important in causation of disease. An understanding physi
cian can manage most patients with the disease with
psychiatric care reserved for those who are psychotic.
Severe Disease
>6
> 101°F
<30
> 12,000
< 3 gms%
> 100
>30
15%
26.8%
remissions in colitis associated with arthritis. Several well
controlled trials during the next three decades established the
efficacy of sulfasalazine (SASP) in the treatment of
inflammatory bowel disease.(7-8,9)
SASP is a compound of 5 Amino Salicylic acid (5-ASA)
and sulfapyridine linked by an azo bond. Only 20 to 30% of
orally administered SASP is absorbed from the upper
gastrointestinal tract. About 75% reaches the colon un
changed where bacterial azo reductase enzymes metabolize
SASP to Sulfapyridine (SP) and 5-ASA. Most of the SP is
absorbed and acetylated in the liver and this is genetically
determined. Most 5-ASA remains unabsorbed in the colon
and 80% is excreted in stools unchanged. The small quantity
of 5-ASA absorbed is also acetylated in the liver. This is not
genetically determined.
When 5-ASA or SP are administered as single agents orally,
each is promptly absorbed in the proximal Gl tract and thus
neither of the metabolites reaches the ileum and/or colon.
Mode of Action
Though the mechanism of action of the drug remains
unclear, elegant studies have shown that SASP serves as the
vehicle for the delivery of active metabolites especially 5ASA to the colon.10. Topical action of 5-ASA on arachidonic
acid metabolism both the cyclo-oxygenase and lipo oxyge
nase inhibition, seem to be important for therapeutic
efficacy. Its action as reactive oxygen scavenger, and
alteration of local or systemic immunity also seem to play a
role in its efficacy.
Side Effects : Side effects of SASP are noted in 10 to 40%
of patients with IBD. Many studies have confirmed that
toxicity is related to the acetylator status and serum SP
levels. There are two major groups of side effects, dose
related and hypersensitivity.
Drug Therapy
SULFASALAZINE
SALAZOPYRINE)
(SALICYL AZO
SULFAPYRIDINE/
Discovered by Dr. Nanna Svartz in 1940, it was initially used.
in treating Rheumatoid Arthritis and Dr. Svartz noticed
12
Dose related : Side effects depend on acetylator status
being frequent in the slow acetylators who tend to accumu
late SP in the serum. These include nausea, vomiting,
anorexia, dyspepsia, headache, reticulocytosis, bluish
discoloration of skin and oligospermia. Most side effects
VOL in No. i —
St. John’s Medical
College Journal of Medicine
Mild Disease
Moderate Disease
<4
Nil
Normal
Normal
Normal
<90
Normal
60%
0.4%
4-6
<101°F
30-40
< 12,000
3 - 3.5 gm%
90-100
20-30
25%
2.4%
No. of bowel movements
Fever
Hematocrit %
Leucocyte count
Serum Albumin
Heart Rate
ESR mm/hr
incidence
Mortality
Ulcerative Colitis is also classified based on the extent of
Colonic involvement as proctitis, procto sigmoiditis, left sided
colitis (upto splenic flexure) or pan colitis.
5-15% of patients with limited disease may show ultimate
progression to involve the whole colon.5 Mild disease usually
is segmental and severe disease is usually diffuse. Excep
tions to the above however occur.
Treatment
General Measures
Patients with severe colitis tend to be dehydrated. They lose
potassium in Stool (compounded by steroid use which causes
renal potassium loss). Loss of bicarbonate results in
systemic acidosis. In addition, loss of blood and protein in the
exudate causes anemia and hypoalbuminemia. All the above
complications should be treated appropriately with fluids,
blood and plasma. There is some evidence to suggest that
uncorrected electrolyte abnormalities are associated with the
development of a toxic megacolon.
There is no evidence that any dietary restriction or regimen
alters the course of the disease. Cow’s milk allergy has not
been shown to be important in the causation of disease.
Lactose intolerence could well aggravate diarrhoea and
milk should be withheld only if the above condition is docu
mented. Parenteral hyperalimentation certainly improves
nutritional status of patients with severe colitis;6 there is no
evidence that it alters the course of severe colitis. However
a chronic and debilitating disease such as ulcerative colitis
is associated with a great psychological trauma to patients.
There is no evidence that psychiatric abnormalities are
important in causation of disease. An understanding physi
cian can manage most patients with the disease with
psychiatric care reserved for those who are psychotic.
Severe Disease
>6
> 101°F
<30
> 12,000
< 3 gms%
> 100
>30
15%
26.8%
remissions in colitis associated with arthritis. Several well
controlled trials during the next three decades established the
efficacy of sulfasalazine (SASP) in the treatment of
inflammatory bowel disease.(7,8-9)
SASP is a compound of 5 Amino Salicylic acid (5-ASA)
and sulfapyridine linked by an azo bond. Only 20 to 30% of
orally administered SASP is absorbed from the upper
gastrointestinal tract. About 75% reaches the colon un
changed where bacterial azo reductase enzymes metabolize
SASP to Sulfapyridine (SP) and 5-ASA. Most of the SP is
absorbed and acetylated in the liver and this is genetically
determined. Most 5-ASA remains unabsorbed in the colon
and 80% is excreted in stools unchanged. The small quantity
of 5-ASA absorbed is also acetylated in the liver. This is not
genetically determined.
When 5-ASA or SP are administered as single agents orally,
each is promptly absorbed in the proximal Gl tract and thus
neither of the metabolites reaches the ileum and/or colon.
Mode of Action
Though the mechanism of action of the drug remains
unclear, elegant studies have shown that SASP serves as the
vehicle for the delivery of active metabolites especially 5ASA to the colon.10. Topical action of 5-ASA on arachidonic
acid metabolism both the cyclo-oxygenase and lipo oxyge
nase inhibition, seem to be important for therapeutic
efficacy. Its action as reactive oxygen scavenger, and
alteration of local or systemic immunity also seem to play a
role in its efficacy.
Side Effects : Side effects of SASP are noted in 10 to 40%
of patients with IBD. Many studies have confirmed that
toxicity is related to the acetylator status and serum SP
levels. There are two major groups of side effects, dose
related and hypersensitivity.
Drug Therapy
SULFASALAZINE
SALAZOPYRINE)
(SALICYL
AZO
SULFAPYRIDINE/
Discovered by Dr. Nanna Svartz in 1940, it was initially used
in treating Rheumatoid Arthritis and Dr. Svartz noticed
12
Dose related : Side effects depend on acetylator status
being frequent in the slow acetylators who tend to accumu
late SP in the serum. These include nausea, vomiting,
anorexia, dyspepsia, headache, reticulocytosis, bluish
discoloration of skin and oligospermia. Most side effects
VOL III No. i —
St. John’s
Medical
College Journal
of Medicine
occur in the first 8 to 12 weeks of therapy, when doses of
SASP exceed 4 gm/dayand when serum SP level exceeds
50 Ugm/ml.
Idiosyncratic : Side effects are not dose related and do not
depend on acetylator status. These include skin rash,
hepatotoxicity, brohchospasm, .pulmonary eosinophilia,
neutropenia, granulocytosis, aplastic aneamia, autoim
mune hemolytic aneamia, peripheral neuropathy, bloody
diarrhoea with fever and rash, serum sickness like-illness
and megaloblastic anaemia. If the acetylator status of the
patient is not known, the dose of SASP should not exceed
4 gm/day.
‘Desensitization’ to SASP is possible in most patients with
side effects starting at 125 mg per day with gradual incre
ments weekly by 125 mg till a dose of 2 gm/day is achieved.
If SASP suspension is available, a dose of 25 mg/day may be
started and increased by 25 mg every 2-3 days till 125 mg/
day is reached and then the above regimen can be followed.
However, when sensitivity to SASP is documented, a
change over to the new 5-ASA preparations is advisable
which brings down the side effects by 75%.
TOPICAL AND ORAL SALICYLATES
Two salicylate enema preparations, 5-ASXA, the active
component of SASP, and 4-ASA have been studied and
appearto be effective in ulcerative colitis. 5-ASXA enemas
have
undergone
many controlled trials in Left side
colitis12’13-14 and has been found effective both in inducing
remission at 4 gm/day and in maintaining remission at 2 gm/
day for a year.15
4-ASXA is more stable, economical and clinical trials have
found this compound beneficial.16Topical enemas should be
used in patients who have left sided colitis only. Side effects
described have been anal irritation and diarrhoea.
ORAL 5-ASXAX is rapidly abosrbed and preparations to
Preparation
Product
1. Pentasa
5 ASA encapsulated in ethyl
cellulose Micro granules
5 ASA coated with eudragit - S
5 ASA in Sodium/Glycine buffer
coated with Eudragit - L
5 ASA in enteric coated
compressed tablets
Enteric coated with Eudragit
compound
Olsalazine
2. Asacol
3. Claversal
4. Rowasa
5. 4-ASA
6. Dipentum
7. Balsalazide
MARCH
1990
4-amino benzoyl - B-alanine
5-ASA
prevent its degradation in upper Gl tract and release in
terminal ileum and colon have come forth recently. Two
general approaches have been utilized, conjugated azobond
preparations like olsalazine and the coated forms of 5-ASXA.
OLSALAZINE contains two molecules of 5-ASXA linked by
an azo bond. Other preparations undergoing trial are IPSALAZIDE and BALSALAZIDEJ
The coated preparations include (a) PENTASA which is en
capsulated 5-ASA in Ethyl cellulose in micro granules. Slow
dissolution of granules occurs in a time dependent fashion
in the small bowel and colon.
(b) ASACOL 5-ASA covered with a 100 to 130 micron thick
cover of acrylic polymer.
The coated preparations resist acid pH and are degraded
in alkaline pH with the optimal pH varying for different drugs.
(see table)
Clinical trials show that oral salicylates are as effective as
SASP.18-19 Unfortunately 25% of patients intolerant to SASP
may be intolerant to 5 ASA as well, though changing over
to a different form of 5-ASA has helped.
Topical Salicylates for limited diseases and oral salicylates
for pan colitis are likely to become the drugs of choice con
sidering the incidence of side effects of SASP. However,
more studies on the pH status of different regions in the gut
need to be done in ulcerative colitis before acceptings the
ideal oral salicylate. The cost factor too may limit their
general acceptance in our country.
CORTICO STEROIDS
Corticosteroids were first used for ulcerative colitis in the
early 1950’s. The Oxford trial in 195220 clearly showed that
cortisone benefits patients with UC. Later trials compared
cortisone with ACTH and found ACTH not to be
particularity advantageous. Newer steroids like Predniso
lone were then tested and found beneficial.21 Steroids in
topical form are beneficial in limited disease.22
Dose
Delivery
250 mg
Time/pH release
400 mg
Release at pH > 7
250, 500 mg
Release at pH > 6
250, 500 mg
Release pH >4.5
500 mg
250 mg
Time/pH release
Released in Colon
(azo reductase)
Inert carrier delivers
5-ASA into colon
500 mg
1 3 —
St. John's Medical
College Journal of Medicine
f) Combined oral Prednisolone (20mg) and Hydro Cortisone
enemas (100 mg) show efficacy equal to oral Prednisolone
40-60 mg a day with decreased steroid related side effects.
should be admitted to the hospital.The Oxford trials have
clearly shown the benefit of intravenous steroids in this group.
Hydrocortisone 400 mg daily is required. Patients are gener
ally kept nil per oral intravenous, alimentation and correction
of fluid, electrolyte and hemato crit disturbances should be
instituted. Seventy to seventy five percent of patients
achieve a remission on the above regime by 7-10 days.
Continuation of symptoms despite the above is a clear
indication for surgery. A sub-group of patients with severe
colitis (about 2-3%) develop dilatation of colon which heralds
impending perforation. X-ray of the abdomen shows the
transverse colon diameter to be above 6 to 7 cm. This group
of patients should be carefully monitored fora period of 2448 hours with 12 hourly x-rays. Intravenous steroids,
antibiotics and correction of fluid and electrolyte distur
bances should continue. Persistant toxicity and dilatation
for 48 hrs., warrants an urgent colectomy. If perforation
occurs, prognosis is very grave with about 50 to 80% mortal
ity in spite of surgery.
NEWER STEROIDS
Moderate Disease
In view of significant systemic absorption and adrenal
suppression even with steroid enemas, formulations which
were less absorbed or not at all have been discovered and
show promising results. Betamethasone Valerate (5mg)
Retention Enema is as effective as Prednisolone enemas
with less adrenal suppression.23 Prednisolone metasul
fobenzoate, commonly used int he UK, has been shown to
have negligile adrenal suppression when given as Enema.24
TIXOCORTOLPIVULATE is derived from cortisol.lt has no
effect on plasma cortisol or glucose levels or inexcrection
of sodium and potassium in urine. Clinical trials have shown
it to be effective in active distal colitis in an Enema form.25
Budenoside has been studied in Sweden and found effective
as an enema in distal colitis.26
Patients in this group should receive oral prednisolone 40 to
60 mg daily. Steroid retention enema may be started simul
taneously. Patients generally achieve remission by about 2
weeks. Steroids are tapered off over 6 to 8 weeks period and
patient started on sulfasalazine to maintain the remission.
Review of clinical studies on Steroids in UC reveal the
following:
a) Steroids are the drug of choice to manage an acute attack
(especially if moderate or severe in nature).
b) Steroids are of no value in maintaing remission
ulcerative colitis.
in
c) Dose response studies show that 40 to 60 mg prednisolone
is required initially to bring about remission.
d) Steroids in enema form show significant systemic absorp
tion.
e) Disease limited to the Rectum can be managed with ster
oids as foams.
IMMUNO SUPRESSIVES
Azathioprine and 6-mercaptopurine (6-MP) have been widely
studied though trials using Cyclosporine are in progress in
recent times. So far four controlled trials using Azathioprine
for resistant UC have been published with a total number of
134 patients roughly half of whom received the active drug.
The conclusions are that they might bring down the dose of
steroids in patients who are‘Steroid dependant’. There is no
conclusive evidence that they consistently induce remission
in steroid resistant cases. The propensity for serious side
effects such as Leucopenia, pancreatitis, hepatitis and
allergic phenomena is another cause for non acceptance of
this form of therapy. The decision to use the above drugs
should not be arbitrarily made, but by explaining to the patient
about their risks and the unpredictable chance of attaining a
remission.
Regimens of Therapy
(1)
Severe, Fulminant Colitis
Patients who present with a severe or Fulminant course
14
MILD DISEASE
This group by definition has less than four stools and no
biochemical or hematological disturbances. Systemic ster
oids are not required in this group. Steroid Enemas wholly
suffice to bring about remission by about 4 weeks. An
alternative approach is to start them on Sulfasalazine without
systemic or topical steroids. Once remission is achieved,
sulfasalazine is continued to maintain remission. Patients
who have proctitis or left sided colitis usually require steroid
foams or enemata irrespective of whether the presentation
is of mild or moderate severity. Salazoprine is required
along with to maintain remission once achieved. Rarely this
pattern of involvement causes severe colitis which has to
be managed with systemic steroids.
It is important to realise that management of ulcerative colitis
in pregnancy and childhood follows the same regimen.The
dangers of steroids and sulfasalazine have been overempha
sized in these groups of patients and the experience of all
major centres treating such patients tells us that achieving a
remission should be the main goal.
Systemic Complications of Ulcerative Colitis
Complications which parallel gut inflammation subside on
attaining a remission from colitis. These include aphthous
ucers, uveitis, episcleritis, erythema nodosum, pyoderma
gangrenosum and peripheral arthritis. Complications such
as sclerosing cholangitis, sacroileitis, ankylosing spondylitis
VOL III No. 1-----
St. John’s
Medical College Journal of Medicine
usually run an indolent course inspite of remissions from
colitis.
Indications for Surgery
(1) Complications such as perforation, stricture either benign
or malignant and colon cancer are unquestionable indica
tions for surgery.
(2) A fulminant course not responding to medical manage
ment and Toxic Megacolon which shows no signs of medical
remission are indications for surgery. As discussed previ
ously the time factor is not clearly laid out but 7 to 10 days
of fulminant course or 48 hours of toxicity with megacolon
clearly favour surgical approaches. Patients who bleed
profusely despite, intensive medical management also come
under consideration for surgery.
REFERENCES
1. Matts, S.F. The value of rectal biopsy in the diagnosis of ulceratk
colitiQ.J.Med. 1961;30:3932. Edwards, F.C. Truelove, S.C. The Course and Prognosis of Ulcerative
Colitis, 11. Long term Prognosis Gut 1964;4:3093. Truelove, S.C. Witts, L.J. Cortisone in Ulcerative Colitis Report on
Therapeutic trial Br. Med J. 1954,2:375
4. Kambe H, Yoshida T, Haraguchi Y:Quantification of disease activity in
Patients with ulcerative colitis J.CIin Gastroenterol 1986;89:1005-1013
5. Sparbergm, Fennergy J, Kirsner J.B. Ulcerative Proctitis and mild
ulcerative colitis: A study of 220 patients Medicine 1966;45:3916. Mullen J.L. Hargrove W.C. Dudrick SJ, Fitts W.T., Rosato, E.F: Ten years
experience with intravenous hyperalimentation and inflammatory bowel
disease. Ann. Surg 1978;187:523-
7.
Baron JH, connell AM, Lennard Jones JE, et al : Sulpha salazine in
(3) ‘Steroid dependance’ for maintenance of remission espe ulcerative colitis. Lancet 1962; 1094-1096
cially if causing stunted growth in children might warrant
8. Dick AP, Grayson MJ, Carpenter RG et al: Controlled trial of Sulphasalazsurgery.
ine in the treatment of ulcerative colitis Gut 1964, 5:437-442
(4) ‘Intractable Disease’ with frequent exacerbations affect
ing patients life style would warrant surgery which is curative
but the label of intractability should clearly be the opinion of
the patient as well as the physician.
PROGNOSIS
There has been a dramatic fall in mortality from ulcerative
colitis after 1950. Many factors might be operative, steroids
and sulfasalazine among the foremost. Early diagnosis, right
timing of surgery and improved surgical techniques also
contribute. Mortality of 4 to 6% is expected in the first attack
of ulcerative colitis, the majority of those who die have
severe disease, are elderly or have developed complications
such as perforation or haemorrhage. Considering the long
term out come, about 75% of all patients with ulcerative
colitis attain remission and are managed medically. Twenty
five percent will have had surgery 5 to 10 yrs. after the first
attack.
Since mortality is excessive in severe first attacks and the rate
of surgery high in patients with severe disease, it is salubrious
to note that only about 15% of patients with ulcerative colitis
present with severe colitis. Hence in absolute numbers the
mortality and morbidity of ulcerative colitis is less than is
inferred from the above data.
9. Misiewicz J.J, Lennard - Jones JE, Connell AM et al: conttrolled trial
of Sulphasalazine in maintenance therapy for Ulcerative Colitis. Lancet
1965;1:185-188
10. Klotz U, Maier K, Fischer C and Heinkal K Therapeutic efficacy of
Sulfasalazine and its metabolites in patients with ulcerative colitis and
Crohn’s disease. N.Engl J Med 1980;303;149911. Taffet SL, Das KM: Sulfasalazine: adverse effects and densensitization.
Dig DIS Sci 1983;28:833-842
12. Azad Khan AK, PirisJ, Truelove SC: An experiment to determine the
active therapeutic moiety of Sulphasalazine. Lancet 1977;2:892-895
13. Campieri M, Lanfranchi GA, Bazzochi G, etal: Treatment of ulcerative
Colitis, with high dose 5-Amino Salicylic acid enemas. Lancet 1981 ;2:270-271
14. Sutherland LR, Martin F, GreerS. etal: 5-amino Salicylic acid enema in
the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis.
Gastroenterology 1987;92:1894-1898
15. Biddle WL, Greenberger J. Swan T. etal: 5 amino Salicylic acid enemas:
Effective agent in maintaining remission in left-sided ulcerative colitis.
Gastroenterology 1988;94:1705-1709
16. Ginsberg AL, Beckls, MC Intosh TM, et al : Treatment of left sided
ulcerative colitis with 4-amino Salicylic add enemas. A double blind placebo
controlled trial. Ann Intern Med 1988;108:195-199
17. Myers B, Evans DNW, Rhodes J. et al: metabolism and urinary excretion
of 5-ASA in healthy voluntteers when given intravenously or released
for absorption at different sites in the gastrointestinal tract Gut 1987;28:196200
Conclusions:
Ulcerative colitis is eminently managed medically in upwards
of 75% of patients. Newer salicylates and steroids show
promising results at reducing morbidity from medical
therapy. Prompt diagnosis and judicious timing of surgery
and the surgical advances in maintaining continence after
colectomy clearly make this chronic, disabling disease easier
to manage.
MARCH
1990
18. Schroeder KW, Tremaine WJ, llstrup DM: Coated oral 5-ASA therapy
for mild-to-moderately active ulcerative colitis: A randomized study N Engl
J Med 1987;317:1625-1629
19. Mulder CJJ, Tytgat GNJ, Weterman IT, etal: Double blind comparison
of slow release 5-ASA and Sulfasalazine in remission maintenance in
ulcerative colitis. Gastroenterology 1988;95:1449-1453.
20. Trulove SC, Witts LJ; Cortisone in Ulcerative Colitis Report on therapeutic
trial Br. Med J 1955;2; 1041
1 5 —
St, John’s Medical College Journal Of Medicine
21. Lennard Jones JE, Misie wicz JJ, Connell AM, et al’ Prednisone as
maintenance treatment for ulcerative colitis. Lancet 1965;1:188
24. McIntyre PB, Macrae F, Berghouse L, et al: Therapeutic benefits from
a poorly absorbed prednisolone Enema in distal colitis Gut 1985;26.822-
22. Trulove SC; Treatment of ulcerative colitis wiht Hydrocortisone
hemisuicinate Sodium Br Med J 1957;1:1437
25. Hanauer SB, KirsnerJB. Barret WE: The treatment of left sided Colitis
with tixocortol pivalate Gastro Enterology 1986.90:1449-
23. Multi centre trial: Betamethasone 17-valerate and Prednisolone 21
- phosphate retention enema in proctocolitis Br. Med J 1971 ;2:84
16
26. Danidsson A, Hellers G. LyrenasE.et al : A controlled randomized trial
ofbudenoside versus Prednisolone retention enemas in active distal colitis.
Scand J Gastroenterol 1987;22S87
VOL III No- 1-----
GE - SYMPOSIUM
St. John’s Medical College Journal of Medicine
SURGERY IN ULCERATIVE COLITIS
N.K.JAIRAM
Most patients with ulcerative colitis remain under control with
medical therapy. The remaining small number need
surgery. Therefore only this small number ultimately requires
removal of the entire colon and rectum which is curative in
ulcerative colitis.
Surgery may be indicated in the elective or emergency
situation (table 1). The indication for elective surgery includes
malignant transformation and failure of medical treatment.
The need for emergency surgery is perforation, toxic
megacolon not responding to urgent medical measures and
uncontrolled haemorrhage.
TABLE - 1
INDICATIONS FOR SURGERY
EMERGENCY
ELECTIVE
FAILED MEDICAL
TREATMENT
PERFORATION
UNCONTROLLED BLEED
MALIGNANT TRANS
FORMATION
TOXIC DILATATION
PRE-OPERATIVE PREPARATION :
The preparation of a patient for surgery includes psychologi
cal preparation and advice from a stoma therapist, when
ever a temporary or permanent stoma is planned. The
colon needs preparation as for any large bowel surgery. Most
patients also require preioperative steroid cover as they
would have been on long term steroids prior to surgery.
CHOICE OF SURGICAL PROCEDURES (TABLE - 2)
There are basically five options :
1. Proctocolectromy with ileostomy:
The combination of proctocolectomy and ileostomy continues
N.K.JAIRAM
MS.
DEPARTMENT OF GENERAL SURGERY
ST.JOHN’S MEDICAL COLLEGE & HOSPITAL
BANGALORE 560034
REPRINT REQUESTS:
DR.N.K.JAIARAM
DEPARTMENT OF GENERAL SURGERY
ST.JOHN'S MEDICAL COLLEGE & HOSPITAL
BANGALORE 560034
MARCH
1990
to be an excellent operation. The procedure is safe, cures
the patient’s disease and has few serious sequelae, with
perfected technique and modern appliancesthe quality of life
is quite satisfactory. However some 20% of ileostomates
cannot adjust to their protruding stoma because of inconti
nence, because of the external appliance or because the
ileostomy interferes with professional, social and sexual
life.1
2. Total colectomy with rectal preservation:
In view of the problems with an ileostomy an attempt was
made to preserve the rectum by doing a subtotal or total
colectomy and ileorectal an anastamosis in the early 1960’s.
The approach has got the major drawback of persistent
symptoms. Further cancer can develop in the rectal stump.
While there are centres still performing this procedure, it
cannot be universally accepted as a surgical alternative for
the reasons quoted above.
3. Proctocolectomy with reservoir ileostomy(Kock)
Kockof Sweden was responsiible fora “Continent Ileostomy.”
A continent ileostomy is a pouch of the terminal ileum. The
pouch itself stores gas and faecal matter which can be
emptied only by intubation through a stoma and outflow track
which is created during formation of the pouch. Axiologi
cal valve", created prevents the contents from emptying
except when intubated.
While the mortality of this procedure is less than around 1 %]
the morbidity is high. The Mayo experience necessiated
removal of 10%1 of such pouches for various reasons includ
ing dysfunction, infection and patient dissatisfaction.
Further surgical revision of the valve was required in 22%
within 1 year.1
The procedure therefore is not suitable in all patients. Its use
today is perhaps restricted only to a small group of patients
who do not accept a conventional ileostomy and who cannot
undergo an ileo anal (pouch) anastamosis or in whomileo anal
anastamosis has failed.
4.
Proctocolectomy with ileoanal anastamosis:
A proctocolectomy with a straight ileo anal anastomosis, i.e.
without an intervening pouch, was attempted earlier to the
development of the pouch. Though certain reports indicate
adequate continence and stool frequency, it is probably
a procedure which offer’s little advantage over the creation of
the pouch. The only group in which this procedure has had
acceptable results is in young adults and children.
5. Proctocolectomy with an intervening pouch:
Park and Nicholls2 in 1978 published their experience with
total colectomy, rectal mucosectomy and ileo anal anasto17 —
GE-SYMPOSIUM
St. John’s Medical College Journal or Medicine
SURGERY IN ULCERATIVE COLITIS
N.K.JAIRAM
Most patients with ulcerative colitis remain under control with
medical therapy. The remaining small number need
surgery. Therefore only this small number ultimately requires
removal of the entire colon and rectum which is curative in
ulcerative colitis.
Surgery may be indicated in the elective or emergency
situation (table 1). The indication for elective surgery includes
malignant transformation and failure of medical treatment.
The need for emergency surgery is perforation, toxic
megacolon not responding to urgent medical measures and
uncontrolled haemorrhage.
TABLE - 1
INDICATIONS FOR SURGERY
ELECTIVE
EMERGENCY
FAILED MEDICAL
TREATMENT
PERFORATION
UNCONTROLLED BLEED
MALIGNANT TRANS
FORMATION
TOXIC DILATATION
PRE-OPERATIVE PREPARATION :
The preparation of a patient for surgery includes psychologi
cal preparation and advice from a stoma therapist, when
ever a temporary or permanent stoma is planned. The
colon needs preparation as for any large bowel surgery. Most
patients also require preioperative steroid cover as they
would have been on long term steroids prior to surgery.
CHOICE OF SURGICAL PROCEDURES (TABLE - 2)
There are basically five options :
1. Proctocolectromy with ileostomy:
The combination of proctocolectomy and ileostomy continues
N.K.JAIRAM MS.
DEPARTMENT OF GENERAL SURGERY
ST.JOHNS MEDICAL COLLEGE & HOSPITAL
BANGALORE 560034
REPRINT REQUESTS:
DR.N.K.JAIARAM
DEPARTMENT OF GENERAL SURGERY
ST.JOHNS MEDICAL COLLEGE & HOSPITAL
BANGALORE 560034
MARCII
1990
to be an excellent operation. The procedure is safe, cures
the patient’s disease and has few serious sequelae, with
perfected technique and modern appliances the quality of life
is quite satisfactory. However some 20% of ileostomates
cannot adjust to their protruding stoma because of inconti
nence, because of the external appliance or because the
ileostomy interferes with professional, social and sexual
life.1
2. Total colectomy with rectal preservation:
In view of the problems with an ileostomy an attempt was
made to preserve the rectum by doing a subtotal or total
colectomy and ileorectal an anastamosis in the early 1960’s.
The approach has got the major drawback of persistent
symptoms. Further cancer can develop in the rectal stump.
While there are centres still performing this procedure, it
cannot be universally accepted as a surgical alternative for
the reasons quoted above.
3. Proctocolectomy with reservoir ileostomy(Kock)
Kockof Sweden was responsiible fora “Continent Ileostomy."
A continent ileostomy is a pouch of the terminal ileum. The
pouch itself stores gas and faecal matter which can be
emptied only by intubation through a stoma and outflow track
which is created during formation of the pouch. A “biologi
cal valve”, created prevents the contents from emptying
except when intubated.
While the mortality of this procedure is less than around 1 %'
the morbidity is high. The Mayo experience necessiated
removal of 10%1 of such pouches for various reasons includ
ing dysfunction, infection and patient dissatisfaction.
Further surgical revision of the valve was required in 22%
within 1 year.1
The procedure therefore is not suitable in all patients. Its use
today is perhaps restricted only to a small group of patients
who do not accept a conventional ileostomy and who cannot
undergo an ileo anal (pouch) anastamosis or in whomileo anal
anastamosis has failed.
4.
Proctocolectomy with ileoanal anastamosis:
A proctocolectomy with a straight ileo anal anastomosis, i.e.
without an intervening pouch, was attempted earlier to the
development of the pouch. Though certain reports indicate
adequate continence and stool frequency, it is probably
a procedure which offer’s little advantage over the creation of
the pouch. The only group in which this procedure has had
acceptable results is in young adults and children.
5. Proctocolectomy with an intervening pouch:
Park and Nicholls2 in 1978 published their experience with
total colectomy, rectal mucosectomy and ileo anal anasto
17 —
St. John’s Medical
College Journal of Medicine
mosis in combination with a reservoir. This procedure, with
several modifications has become a popular alternative to a
conventional ileostomy or kock pouch in selected groups
of patients.
The procedure as it is carried out currently involves removal
of the entire colon and rectum upto the levator sling, excision
of the mucosa of the remaining rectum upto the dentate line,
the creation of a pouch, and anastomosis of the pouch to the
anal canal endoanally. Most surgeons perform a back up loop
ileostomy which is subsequently closed.
Several types of pouchees have been used but the optimal
size and configuration of the pouch is still unclear. Park and
others have used the S pouch3, Utsunomyia the J pouch4
and Fonkalsrud & Peck the lateral side to side pouch 5.
Todate no pouch has proven superior to the other and long
term follow up is necessary to decide the efficacy of one or
other pouch.
The procedure of total proctocolectomy with ileal pouch is
an operation that has a low mortality. However there are
post operative problems that may be associated. These
include pelvic sepsis, perineal excoriation, sexual dysfunc
tion, inflammation of the pouch or pouchitis, frequency of
stool and intestinal obstruction amongst others. The
incidence of these complications is however within accept
able levels. The procedure offers the greatest advantage in
that it cures the disease yet maintains continence. However
it is to be undertaken only by the experienced surgeon
in view of the difficult techniques entailed.
Newer Options?
Currently at the Mayo Clinic an artificial valve which acts as
an indwelling stomal occlusive device is under clinical trial.
This device made of moulded silastic occludes the ileum in
a manner permiting periodic emptying. The final outcome of
the use of this device following a conventional Brooke ileo
stomy or Kock pouch may revolutionise the surgical
management of Ulcerative colitis. However, initial results
have not been satisfactory1.
18
TABLE - 2
TYPES OF SURGERY
1.
Proctocolectomy with ileostomy
2.
Total colectomy with rectal preservation
3.
Proctocolectomy with Resovior ileostomy
(Knocks continent ileostomy)
4.
Proctocolectomy with ileo anal anastamosis
5.
Procto colectomy with an intervening pouch
Conclusion:
From the varous options given it appears that the Surgeon
has fairly wide choice of procedures. In fact, the simplest
and safest procedure amongst all these remains a proc
tocolectomy with Brooke ileostomy. For the experienced
surgeon and the intelligent patient who understands the
various aspects of the pouch, the pouch with ileo anal
anastamosis is a satisfactory alternative. These are perhaps
the most commonly performed procedures today for
Ulcerative colitis. The other
procedures mentioned are
used less frequently. In the emergency situation, however,
it would not be wise to perform any procedure other than a
total proctocolectomy and ileostomy. If a pouch is planned
for a later date the distal rectum may be preserved.
REFERENCES
1. R.R. Dozois * Alternatives to conventional Ileostomy, Year Book Medical
Publisher 1985.
2.
Park, Nicholls : British Medical Journal 1978:2:85.
3.
Parks : British Journal of Surgery 1980;67:533
4.
Utsunomyia : Dis. colon & Rechim 1980;23:459
5.
Fonkalsrud : Ann.Surg. 1980:191:294.
VOL HI No. 1-----
St. John's Medical College Journal
GE - SYMPOSIUM
of Medicine
ACUTE BACTERIAL COLITIS - AN UPDATE
NARENDRA BHARGAVA ,
DAVID D.K. ROLSTON.
INTRODUCTION :
Shigella
In India, acute diarrhoea causes some 500,000 deaths per
year in children under the age of 5 years. About 25% of these
deaths are due to acute bacterial colitis. Acute diarrhoea
may be caused by toxins elaborated by the bacteria or by
organisms which penetrate the mucosal surface as the pri
mary event but also produce toxins (Table 1). Bacterial toxins
may be enterotoxic, cytotoxic or neurotoxic. Enterotoxins
cause fluid secretion primarily by activation of intracellular
enzymes, and do not produce gross morphologic changes in
the enterocytes, for example cholera. Cylotoxins cause
injury to the intestinal epithelial cells and may induce fluid
secretion as well, while neurotoxins are implicated in
non-gastrointestinal manifestations, e.g. peripheral neuropa
thy sometimes observed in patients with dysentery.
Shigellae are non-motile, non-encapsulated, small gram
negative bacilli. These bacilli are the most important cause
of blood and mucus diarrhoea in our country because of the
severity of the disease and the associated high morbidity
and mortality. S.dysenteriae, S.flexneri, S.boydii, and
S.sonnei are the most important pathogens. Shigellosis is the
most highly communicable of the bacterial diarrhoeas,
because as few as 200 viable bacteria can produce illness2.
Humans are the only natural hosts although experimental
infection can be produced in monkeys and guinea pigs.
Table 1 : Classification of bacterial diarrhoeas
Invasive/cytotoxic*
Toxigenic*
Vibrio cholerae
Shigella
E.Coli - enterotoxigenic,
- enteropathogenic
E.Coli - enterohemorrhagic
- enteroinvasive
Bacillus cereus
Campylobacter
Aeromonas
Clostridium difficile
Y. enterocolitica
Non typhoidal salmonellosis
* effect the small intestine predominantly
Shigellae cause intestinal disease by penetrating the
mucosal surface and multiplying within the epithelial cells
from where cell to cell invasion by bacilli occur resulting
in extension of infection3. These organisms rarely penetrate
beyond the intestinal mucosa and generally do not invade the
blood stream. Although the initial lesions are confined to the
epithelial layers, the local inflammatory response is severe.
Mucosal oedema, microabscess formation, loss of goblet
cells, degeneration of normal cellular architecture and
mucosal ulceration occur. These events give rise to the
characteristic clinical picture of bloody, mucopurulent
diarrhoea.
It is now recognized that S.dysenteriae elaborate a toxin
which is cytotoxic, neurotoxic (in mice), and enterotoxic
and may be responsible for the watery diarrhoea which
sometimes precedes the bloody diarrhoea.
Shigellosis is a disease primarily of children (6 months to
5 years). Infection occurs by faeco-oral spread.
* invade the distal ileum and colon
Clinical features
The non-invasive toxigenic organisms primarily affect the
upper small intestine and produce watery diarrhoea while
invasive organisms commonly invade the colon and distal
ileum and produce bloody diarrhoea or dysentery. At times,
particularly in the West, the bloody diarrhoea is preceded by
watery diarrhoea, which may be related to products of a
arachadonic acid metabolism.1 The organisms causing
bloody diarrhoea will be discussed in this review.
NARENDRA BHARGAVA. MD
DAVID D.K, ROLSTON. MD. DM. MNAMS
DEPARTMENT OF GASTROENTEROLOGY
CHRISTIAN MEDICAL COLLEGE & HOSPITAL
VELLORE - 623 004
TAMIL NADU
MARCH
1990
Typically shigellosis presents as fever which is followed by
watery diarrhoea of variable duration, and then blood and
mucus diarrhoea which is accompanied by crampy abdomi
nal pain, rectal burning, and tenesmus4. The stools are small
volume and frequent. However, this constellation of symp
toms is seen only in the minority of patients.
S. dysenteriae type I characteristically produces a more
severe form of diarrhoea with a higher mortality rate than the
other shigella species. This organism has been associated
with several complications5 (Table 2). The leukemoid reac
tion is associated with a three-fold increase in mortality. The
presence of the hemolytic uremic syndrome (HUS) does
not increase mortality further. However, in HUS survival is
correlated with early dialysis. There is an increased risk
of fatal illness in uncomplicated shigellosis if the patient is
under one year of age, the febrile response is lacking or low
19 —
St. John’s Medical College Journal of Medicine
Table 2 : Complications of Shigellosis
Respiratory
Cough, rarely pneumonia
Nervous system
Meningismus, seizures, peripheral
neuropathy
Haematologic
Haemolytic uremic syndrome,
thrombocytopenia, leukemoid
reaction
Musculoskeletal
Arthritis, Reiter’s syndrome
Eye
Conjunctivitis, iritis, corneal
ulcers.
Miscellaneous
Urinary tract infection,
septicaemia
grade (< 39.4°C), the nutrition is poor (<70% of the standard),
lack of breastfeeding or vascular collapse at the outset of
disease. In developing countries death associated with
non-dehydrating diarrhoeal illness is most commonly due to
shigellosis6.
patients, while abdominal pain and bloody stools occur in
70% and 50% of all patients respectively. Other constitu
tional symptoms such as headache, myalgia, backache,
malaise, anorexia and vomiting are frequently observed.
Campylobacter infection should be suspected if the pro
drome (coryza, headache and generalised malaise) is
severe, the diarrhoeal illness is prolonged and biphasic (initial
diarrhoea, followed by slight improvement and then increas
ing severity of diarrhoea) and white and red blood cells are
present in faeces in abundance. The duration of illness is
usually less than one week, although symptoms can persist
for longer and relapses occur in as many as 25% of all cases.
Diagnosis of Campylobacter gastroenteritis can only be
made by stool culture. However, these strictly microaerophilic organisms require selective medium such as Skirrow’s,
Butzler’sor Campy BAP to ensure their growth. Dark field
or phase contrast microscopy of fresh diarrhoeal stool
shows curved, motile rods with darting, corkscrew move
ments. Recently a direct fluorescent antibody test has been
developed to screen Campylobacter. Unfortunately this
test while highly specific, lacks sensitivitiy11.
Escherichia coli
Chronic carriers of Shigella are known. Microscopic exami
nation of faeces reveals numerous polymorphonuclear leu
kocytes and red blood cells. The organism can be
recovered from faeces by culture.
AlthoOgh E.coli are part of the normal gut flora they are
potential enteric pathogens. Of the four major groups of
E.coli pathogenic to humans, enteroinvasive E.coli (ElEC)
and enterohemorrhagic E.coli (EHEC) can cause dysentery.
Campylobacter
The number of organisms necessary to produce infection is
large (>108)12, but these numbers can be found in contami
nated food. The attack rate is high13. Clinically ElEC-induced
dysentery is indistinguishable from that caused by shigella.
The illness is characterized by fever, severe abdominal
cramps, malaise and toxemia. Watery diarrhoea may occur
in some 20% of individuals and precedes the onset of
dystentery. Microscopic examination of the dysenteric stool
reveals white and red blood cells caught in clumps of mucus
and fibrin, the so called ‘bacillary exudate’.
Five species produce disease in humans. C.jejuni, C.laridis,
C.coli and C.hypointestinalis cause diarrhoea in normal
individuals while C.fetus causes systemic infection in the
immunocompromised host. Recently Campylobacter like
organisms (CLO) have been found to be associated with
proctocolitis in homosexual men7.
C.jejuni is responsible for diarrhoea worldwide. Most cases
of Campylobacter diarrhoea are sporadic but large outbreaks
due to this predominantly invasive organism do occur.
Asymptomatic carriage is uncommon in developed nations.
However, in South India upto 14.8% of healthy individuals
excrete this organisms in faeces and have no evidence of
disease8.
Undercooked or raw poultry is thought to be a major source
of infection and contaminated water supplies have served as
a source for several community outbreaks of Campylobacter
dysentery9. Person to person transmission has been de
scribed but is probably rare.
Clinical features
The incubation period is variable (24 hours to 10 days). The
spectrum of clinical illness is wide and varies from severe
dysentery on the one hand to mild watery diarrhoea on
the other10. Diarrhoea and fever occur in some 90% of all
20
Entero haemorrhagic E.coli (EHEC)
E.Coli 0157:H7 produces the haemorrhagic colitis syndrome.
It is a relatively recently recognized cause of dysentery in
humans. In North America it has rapidly emerged as an
important enteric pathogen and has been responsible for
several community outbreaks of dysentery14. These strain
produce two toxins, one of which is identical to the potent
cytotoxin-neurotoxin-enterotoxin produced by Shigella dysenteriae type I (Shiga toxin)15.
The incubation period of this self-limited dysenteric illness is
3-4 days and the average duration of illness is about 8 days.
Typically, severe crampy abdominal pain, and copious
bloody diarrhoea are present. Fecal leukocytes and fever are
uncommon. Hemolytic uremic syndrome and thrombotic,
thrombocytopenic purpura are two potentially life
VOL in No. 1 —
St. John's Medical College Journal
or Medicine
threatening but rare complications. Detection of EH EC in
faecal specimen is difficult.
Non typhoidal Salmonellosis :
Disease caused by any serotype of the genus salmonella
other than S.typhi is referred to as non-typhoidal
Salmonellosis. Salmonellae are flagellated, non spore
forming aerobic or facultatively anaerobic gram negative
bacilli.
Salmonella species are one of the most common causes of
food-borne infections. Contaminated food, fingers, flies and
fomites constitue the major routes by which infection
occurs. These organisms can cause large common-source
outbreaks of dysentery. Contaminated poultry, meats, eggs
and dairy products are most often responsible for these
outbreaks.
Person-to-person transmission is common
especially where crowding occurs, as in nurseries and
mental institutions. The main portal of entry is via the mouth.
Typically these organisams attack the ileum intially with
colonic involvement becoming progressively more severe as
the disease progresses. Following mucosal penetration, a
locally elaborated cytotoxin inhibits cell protein synthesis and
this leads to cell necrosis16 followed by mucosal ulceration,
invasion of the lamina propria, the lymphatics and the blood
stream. Of all the organisms responsible for bloody di
arrhoea, salmonellae are the most invasive and therefore
most commonly produce septicemia. Most infections,
however, will not spread beyond the intestinal mucosa or
regional lymph nodes.
Clinical features
The majority of patients with Salmonella gastroenteritis
present with mild disease. The short incubation period is
followed by nausea, vomiting and abdominal pain for 1 2 days. Watery diarrhoea which can sometimes mimic
cholera occurs in a small percentage of patients. Colonic
involvement characterized by bloody stools dominates the
clinical picture. The colitic illness can be particularly severe
in individuals in whom there is decreased gastric acid
secretion (as after vagotomy or during antacid therapy), in
the extremes of age and in individuals with lymphoprolifera
tive disorders. Proctoscopic findings include hyperemia,
granularity, friability and ulcerations. The duration of Salmo
nella colitis is variable. It generality lasts fora few days but can
continue for 2-3 months. Definitive diagnosis is by stool
culture.
Clostridium Difficile
C.difficile is a gram positive anaerobic, sporulating organism
generally producing disease in individuals in whom the
normal intestinal flora has been altered as after or during
antimicrobial therapy and chemotherapy. Clindamycin
and ampicillin are antibiotics most often associated with
the development of disease. C .difficile toxin can be recovered
MARCH
1990
in the stools of 2-3% of healthy individuals. However, in
patients with antibiotic associated diarrhoea or colitis the
C.difficile toxin is detectable in 90-100% of patients while
in hospitalised patients without diarrhoea it is present in 1015%.
C.difficile produces two toxins (A & B) which contribute to
colitis17. Toxin A not only causes fluid secretion and mucosal
damage in both the large and small bowel but also has
a cytopathic effect in cell cultures. Toxin B is a much more
potent cytotoxin and is cytopathic to virtually all cell lines
tested. There is some evidence that the B toxin alters
intestinal motility.
Clinical features
Most patients initially present with diarrhoea and abdominal
pain. Symptoms may develop at any time during the course
of antimicrobial therapy and less commonly upto 6-8 weeks
following discontinuation of the offending drug. As with all
enteric infections the severity of disease may vary from
mild, nonspecific watery diarrhoea to severe bloody di
arrhoea with the passage of 20 or more bloody stools per day.
The illness may last several weeks. Rarely, patients may
present with toxic megacolon or colonic perforation instead
of diarrhoea. On sigmoidoscopy the mucosa may show only
erythema on the one hand or marked granularity, erythema,
ulceration and Pseudomembrane formation on the other.
Detection of toxin in the stool is presumptive evidence that
C.difficile is the cause of the illness. Culture of these
organisms from faeces requires special media and is there
fore not performed routinely.
Yersinae enterocolitica
Yersinae enterocolitica is a non-lactose fermenting, urease
positive, gram negative rod. Human yersinia infection is
usually acquired by the oral route. The incubation period is
2-11 days, with an average of 5 days. These organisms
invade itestinal epithelial cells and also elaborate a heat
stable enterotoxin18.
Yersinia gastroenteritis has been reported primarily from
Scandinavian and European countries and is uncommon in
India. Several epidemics have been related to contaminated
milk and ice cream. It is generally believed that animals (pets
or food sources) are involved in the transmission of the
disease.
Clinical features
Several clinical syndromes have been described with
Yersinia and they tend to vary with the age of patient.
Enterocolitis is the most common clinical mode of presen
tation. The illness occurs most frequently in children less
than five years of age. Thepresentation is non specific, with
fever abdominal cramps, vomiting and diarrhoea which
usually lasts one to three weeks. Bloody
diarrhoea,
2 i —
St. John’s Medical College Journal of Medicine
however, occurs in only 25% of all infections19. In adults,
diarrhoea or dysentery is often associated with colicky right
iliac fossa abdominal pain which may be mistaken for acute
appendicitis20. Profuse watery diarrhoea possibly related to
the enterotoxin can also occur.
Diagnosis is established by culture of stools or body fluid
including blood, peritoneal fluid and mesenteric lymph nodes.
The value of serological tests such as agglutinating antibod
ies are still being evaluated.
Diagnostic approach :
In infective colitis a presumptive aetiological diagnosis can
often be made on the basis of the history (including that of
travel) symptomatology, and a knowledge of the common
causes of colitis within one’s own community. Two features
distinguish dysentery from an acute attack of idiopathic
ulcerative colitis: a positive culture for a pathogen and a self
limited course without relapse. However, positive culture is
present in only 40-60% of reported cases of bacterial colitis.
In these cases histopathologic examination of colonic
mucosa obtained within 4 days of onset of symptoms may be
helpful21.
A particularly useful technique in the diagnosis of an infectious
diarrhoea is microscopic examination of stool22 (Figure 1).
Invasive organisms such as Shigella and Campylobacter
produce sheets of polymorphonuclear leukocytes and red
blood cells whereas Salmonella and Clostridium difficile
produce variable numbers of faecal leucocytes and red
blood cells. An acute exacerbation of idiopathic ulcerative
colitis can also lead to discharge of leukocytes and erythro
cytes in faeces.
Dehydration and electrolyte imbalances do not usually occur
in patients with acute bacterial colitis. Nevertheless, careful
attention to hydration should be given and where necessary
oral hydration therapy instituted with a glucose-electrolyte
solution23. The nutritional consequences of acute diarrhoea
can be devastating particularly in children whose nutritional
status is poor. Nutrients should therefore not be withheld. In
fact, the patient should be encouraged to eat as much as
possible during the episode of illness.
Therapy
Absorbent drugs (kaolin, pectin), antimotility drugs
(diphenoxylate, loperamide, codeine) and antisecretory
drugs (chlorpromazine) have little if any role in the treatment
of blood and mucus diarrhoea because of limited efficacy.
In fact, diphenoxylate has been shown to prolong shigella
excretion. There is also the danger of precipitating a toxic
megacolon and inducing bacteremia because of increased
contact time between the pathogenic bacteria and colonic
mucosa.
Fig 1 : Alogrithm for the diagnosis of infectious diarrhoea"
High fever > 103°F, systemic illness, tenesmus
Bloody diarrhoea, prolonged course > 2 weeks,
Dehydration
Yes
No
I
Symptomatic therapy
ORS if necessary
No stool culture or
antimicrobial drugs
I
Direct fecal smear
__________ I
No leukocytes Parasites
Leukocytes
Culture
Culture
Shigella
Salmonella
Campylobacter
Yersinea
EIEC, EHEC
ETEC, EPEC
C.difficile
1
Specific treatment ’ ------------- J
rare-Salmonella,
—
* Treatment usually indicated only when illness is severe.
•• Modified from : Infectious diarrhoea. Gorbach SL: in
Slesinger & Fordtran Textbook of
Gastrointestinal diseases IV Edition, W.B.
Saunders 1989.
22
VOL 111 No- 1-----
St. John's
Medical
College Journal
of Medicine
Antimicrobial drugs continue to be extensively used in clinical
practice despite the fact that, in general, they do not alter the
course of the disease. On the contrary, their use may be
detrimental because there is the risk of propagating
antimicrobial resistance and prolonging faecal excretion of
the bacteria. Antibiotics themselves may cause diarrhoea
and are expensive.
Antimicrobials have been found useful only in the following
situations: (i) moderate to severe shigellosis, (ii) in
Campylobacter colitis provided treatment is given in the first
2-3 days of illness, (iii) in Clostridium difficile colitis and, (iv)
in Salmonella infections when associated conditions as
outlined in Table 3 are present.
Table 3 : Indications for therapy in Salmonella gastro
enteritis.
Lymphoproliferative disorders
Leukemia, Lymphoma
Malignancies
Immunosuppression
AIDS, corticosteroids, transplant patients
Abnormal cardiovascular system
Prosthetic heart valves
Vascular grafts
Valvular heart disease
Hemolytic anemia
Extremes of age
Severe sepsis.
When deciding upon an antimicrobial drug, the choice must
be governed by a knowledge of local sensitivity patterns
particularly when treating Shigella dysentery. This is be
cause shigellae are notorious in developing both plasmid
and non-plasmid mediated resistance to antimicrobials.
Probably the drug of choice for treating shigellosis is nalidixic
acid (4g/day for 5 to 7 days in adults and 55 mg/kg/day in
children). Ampicillin 500 mg orally four times daily or 1 gm
intravenously every six hours is preferred for drug sensitive
strains. Children should receive 50-100 mg/kg of body
weight per day for five days. When isolates in a community
are known to be resistant to ampicillin, trimethoprim (TMP) sulfamethoxazole (SM) can be given in a dose of 10 mg TMP/
Kg body weight per day and 50 mg SM/Kg body weight per
day for 5 days24. Encouraging results have recently been
reported with the quinolone derivatives norfloxacin 400 mg
twice daily and ciprofloxacin 500 mg twice daily25,26. A single
oral dose of 2.4 gm of tetracycline is reportedly effective
in treating shigellosis in adults27. Carriers are treated with a
combination of trimethoprim (5 mg/kg/body weight) and
sulfamethoxazole (25 mg/kg/body weight/day) for a period of
28 days with 90% success.
Erythromycin is the drug of choice for treatment of Campylo
bacter colitis. It is useful only if given within 3 days of the onset
of symptoms26,29. Faecal excretion of the organism is,
however, reduced by erythromycin (250-500mg four times a
MARCH
1990
day for 7 days). The value of the quinolones (ciprofloxacin,
norfloxacin) in Campylobacter colitis is being evaluated30.
Therapy for C.difficile colitis includes discontinuation of any
implicated antimicrobial agent, and institution of vancomycin
which is active against C.difficile if the disease is severe or
persists. Metronidazole or bacitracin are also useful if the
disease is severe or persists. The response rate to vancomy
cin is 95%.
Antibiotic treatment of acute bacterial diarrhoea in general
and acute bacterial colitis in particular is disappointing
because despite the profusion of drugs available, in only
limited instances have they been shown to beneficially alter
the course of the colitis.
References :
1. Moriarty KJ, O'Grady J, RolstonDDK, Clark ML, Dawson AM. Effect of
prostacyclin on water and solute transport in the human jejunum. Gut
1986;27:158
2. Dupont HL, Hornick RB, Synder MJ et al. Protection induced by oral live
vaccine or primary infection. J Infect Dis 1972:125:12
3. Labrec E, Schneider H, Magnani T et al. Epithelial cell penetration as an
essential step in the pathogenesis of bacillary dysentery. J Bacteriol
1964:88:1503.
4. Dupont HL, Hornick RB, Dawkins AJ, Synder MJ, Formal SB. The response
of man to virulent shigella flexneri 2a. J Infect Dis 1969; 119:296
5. Bareett-Connor E, Conner JD. Extraintestinal manifestation of shigellosis.
Am J Gastroenterol 1970:53:234
6. Butler T, Islam M, Azad AKetal. Causes of death in diarrhoeal diseases
after rehydration therapy. An Autopsy study of 140 patients in Bangladesh.
Bull WHO 1987,65:317.
7. Fennell CA, ToltenPA, Quinn TCet al. Characterization of Campylobacter
like organism isolated from homosexual men. J Infect Dis 1984:149:58
8. Rajan DP, Mathan VI. Prevalence of Campylobacter fetus sub sp jejuni in
healthy populations in Southern India. J Clin Microbiol 1982:15:749
9. Mentzing LO. Waterbourne outbreaks of Campylobacter enteritis in central
Sweden. Lancet 1981:2:352.
10.
Blaser MJ, Reller LB. Campylobacter enteritis. N.Engl J
1981:305:1444.
Med
11.
Hodge DS, Prescolt JF, Shewen PE. Direct Immunofluroescence
microscopy for rapid screening of Campylobacter enteritis. J din Microbiol
1986,24:863.
12. Dupont HL, FounalSB, HormickMJ. Pathogenesis of E.coli diarrhoea
N Engl J Med 1971:285:1
13.
Mannier R, Wells JG, Swanson RC et al. An outbreak of
enteropathogenic E.Coli Food borne disease traced to imported french
cheese. Lancet 1973:2:1376.
14. Riley LW, Remis RS, Helgerson SD etal. Haemorrhagic colitis assodated
with a rare E.coli serotype. N Engl J Med 1982:308:681.
15. O’Brien AD, Lively TA, Chang TW et al. Purification of shigella
dysenterie I (shiga) like toxin from E.coli 0157:H7 strain assodated with
haemorrhagjp colitis. Lancet 1983:2:573.
23 —
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of Medicine
16. Koo FCW, Peterson JW, Houston CW et al. Pathogenesis of
experimental salmonellosis. Inhibition of protein synthesis bycytotoxin Infect
Immun 1984;43:93.
17. Sullivan NM, Pettett S & Wilkin TD. Purification and characterization
of toxin A & B of Clostridium difficile. Infect Immun 1982:35:1032
18. Boyce JM, Evans EJ, Dupont HL: Production of heat stable enterotoxin
by yersinia enterocolitca. Infect Immunol 1979:25:532.
19. Marks Ml, Pai CH, LafleurL, etal: Y. Enterocolitica gastroenteritis. A
prospective study of clinical, bacteriologic & epitdemiologic features. J Pediatr
1980;96:26
20. Vantrappen G, Agg HO, Penette E et al : Yersinia enteritis and
enterocolitis. Gastroenterology 1977;78:220
21. Nostrant TT, Kumar NB, Appleman HD. Histopathology differentiates
acute self limited colitis from
ulcerative colitis. Gastroenterology
1987;92:318
22. Harris JC, DuPont HI, Hornick RB. Fecal leukocytes in diarrhoeal
diseases. Ann Intern Med 1972;72:697
23.
Rolston DDK. Treatment of Tropical diarrhoea In: Gastrointestinal
2 4
Infections in the Tropics. Ed.Rustgi VK, Basel, Karger (in press}.
24. Nelson JD, Kusrriiesz H, Jackson LH and Woodman E. Timethroprim Sulfamethoxasole therapy for shigellosis. JAMA 1976:235:1239.
25. Ruiz-Palacios GM. Norfloxacin in the treatment of bacterial enteric
infections. Scand J Infect Dis 1986,48:55
26. Ericsson LD, Johnson PC, Dupont HL etal. Ciprofloxacin or trimethoprim/
sulphamethoxazole as initial therapy for traveller’s diarrhoea. A placebo
controlled, randomised trial. Ann Intern Med 1987:106:216.
27. Pickering LK, Dupont HL, Olaste J. Single dose tetracycline therapy for
shigellosis in adults. JAMA 1978:239:853
28. Anders BJ, Paisky JW, Laner BA et al. Double blind placebo controlled
trial of erythromycin for treatment of Campylobacter enteritis. Lancer
1982:1:131.
29. Salazar-Lindo E, Sack B, Cheawoo E et al. Early treatment With
erythromycin of Campylobacter jejuni associated dysentery in children. J
Pediatr 1986:109:355
30. Ruiz-Palacios GM. Norfloxacin in the treatment of bacterial enteric
infection. Scand J Infect Dis (supplement) 1986:48:55.
WE III No. 1-----
GE - SYMPOSIUM
St. John's 'Medical College Journal of Medicine
INTESTINAL AMOEBIASIS - PERSISTING PROBLEMS
CHALLENGES
AND
N. MADANAGOPALAN, R. MANJULA
INTRODUCTION :
Colonic inflammation manifests as bloody diarrhoea with
tenesmus. The list of conditions which can produce this
clinical picture of inflammatory bowel disease is vast.
Symptomatic intestinal amoebiasis is a common cause of
specific inflammatory bowel disease in our country. Indeed
this is becoming more frequently recognized even in temper
ate countries.
DEFINITION :
Amoebiasis as defined by the World Health Organisation in
1968 is a condition where humans harbour erythrophagocytic pathogenic Entamoeba histolytica (trophozoites or
cysts). There is great need to reclassify the condition based
not only on clinical presentation but also on immunological
responses in the host. It is also not clear what role other
amoebae such as Acanthamoeba, Naeglaria an even Dien
tamoeba fragilis play.
PATHOGENESIS:
While the prevalence of infestation with Entamoeba histolyt
ica may range from 2% to even 50% depending upon the
population surveyed, it should be realised that the presence
of infestation is not synonymous with physical illness. At a
given time only a small percentage of those infected have
manifest illness attributable to the parasite. The higher
prevalence of symptomatic amoebasis in tropical countries
is linked to poor sanitation.
The factors that induce virulence to the parasite, be they viral,
bacterial, nutritional or hormonal still remain to be sorted out.
Yet another puzzle is the patient with positive parasitological
evidence of infestation as well as invasion, but with negative
serology. So is the occasional asymptomatic patient who
has positive serology in significantly high titres.
There is often lack of correlation between the clinical features,
detection of the trophozoite or cysts of Entamoeba histolytica
N. MADANAGOPALAN
DR. R. MANJULA
DEPARTMENTOF DIGESTIVE HEALTH AND
DISEASES
GOVERNMENT PERIPHERAL HOSPITAL
ANNA NAGAR, MADRAS.
MARCH 1990
in faeces and the serological response of such individuals.
This is responsible for the constant apprehension amongst
clinicians to ascribe a causal relationship between the
detection of the organism in faeces and the many vague
gastrointestinal disturbances, so frequent in this part of the
world.
The cystic stage is a natural phenomenon for survival of the
species and tissue invasiveness is detrimental not only to the
host but also to the parasite. The excystment of the ingested
infectic cyst, taking place in the small intestine is influenced
by gastric acidity, digestive enzymes, food ingested and
intestinal transit. The almost selected localisation of the
amoebae in the colon is probably determined by
a) slow intestinal-movement and stasis providing greater
opportunity for colonisation particularly in the caecum.
b) The very low oxygen tension and the low oxidation
reduction potential prevalent in the colon.
c) Bacterial flora favouring propagation of the amoebae.
However the specific microflora involved have not been
established.
d) Zymodemes have been linked to possible pathogenic
states of the parasite. There is belief there are many
pathogenic zymodemes of the amoeba of which II and XI are
the most common pathologic associates.
The factors contributing to gangereuous/destructive lesions
of the colon have been the subject of frequent study.
Corticosteroids, immunosuppressive drugs and coex
istent malignancy may all be contributory factors. Yet
another factor frequently mentioned in literature but luckily
not so frequently encountered in clinical practice, atleast in
this part of the country, is the reported higher incidence of
fatal amoebic colitis in pregnancy/puerperium. Raised
steroid levels in pregnancy and late puerperium, and the
allied nutritional and circulatory factors are reported to be
contributing factors.
The role of viruses, nutrition, immunological status as also
the diet of the host may determine localisation and tissue
invasion of the organism. A previous infection or sensitization
by the organism instead of offering protection to the host may
favour invasiveness upon reinfection. This may apply not
only for the colonic but also for the hepatic lesions.
CLINICAL FEATURES :
Amoebiasis is usually classified as Symptomatic and
Asymptomatic. Symptomatic intestinal amoebiasis presents
2 5—
St. John’s Medical
College Journal
of Medicine
c) Amoeboma : An amoeboma can be a very important
development in the course of colonic amoebiasis and may
closely mimic malignancy. It is an inflammatory granuloma
a) Dysentery
with or without a fibroblastic reaction evoked by E.histolytica.
b) Non-dysenteric colitis
Amoebomas may be multiple. An amoeboma may occur in
c) Amoeboma
the colon at any site from the caecum to the anal orifice. It may
d) Amoebic appendicitis
e) Complications and sequelae of intestinal amoebiasis such be palpable per abdomen or per rectum or be visible at
endoscopy, or demonstrated as a filling defect on contrast
as
studies. Amoebomas may also cause intestinal obstruction,
1. Perforation and peritonitis
intussusception or volvulus and have been observed both
2. Haemorrhage
during the course Of florid amoebic dysentery and after an
3. Intussusception
apparent cure of dysentery. A condyloma is another manifes
4. Post dysenteric colitis
tation usually around the anus. In both amoeboma and
5. Stricture
condyloma it is essential that apart from a smear examination
of the surface a core tissue biopsy is obtained to ensure
Some forms of intestinal amoebiasis need mention
that a coexisting neoplastic lesion is not missed. It is not
uncommon to find a benign or malignant lesion with a
a) Fulminant amoebic colitis
is estimated to occur in
superficial amoebic ulceration.
about 0.5% of patients with amoebic dysentery. If pyrexia,
prostration, toxaemia and marked distension of the abdomen
d) Other presentations: A few cases of intraperitoneal
with or without pedal oedema are present in a patient with
abscesses secondary to colonic perforation may simulate
dysentery in whom a faecal a rectal swab reveals plently of
a liver abscess as aspiration of such lesions which may
entamoeba histolytica trophozoites, “Fulminant Amoebic
present as a mass around the right hypochondrium reveals
Colitis” should be suspected. There is almost complete
chocolate/brownish, (but usually foul smelling) material.
incontinence of the anal sphincter and highly alkaline
unformed faeces with blood and mucus is passed continu Apart from free perforation it is possible for the infective
ously. the discharge is usually very offensive, typical of that
material with or without gas forming organisms and the
condition. The invariably attracts a lot of house flies. Renal
amoeba to seep through the wall of grossly oedematous
failure sets in rapidly in such cases and quite frequently is
inflammed colon and rectum. Peritoneal reaction in the form
fatal. Though heroic surgery has occasionally been reported
of tenderness and guarding is never so arresting as in other
as a life saving procedure it is usually not readily
causes of bowel perforation. Colonic lesions of amoebic
undertaken.
aetiology may even perforate into the gall bladder and biliary
as
Surgery may be of value in localised perforation with or
without intraperitoneal abscess formation before the general
condition of the patient becomes too poor to offer surgical
relief. It is possible that the perforation may be at multiple
sites. Perforation is more frequently in the caecum, ascend
ing colon and rectosigmoid and more often retroperitoneal
than intraperitoneal. Perforation is more frequent in children
and the mortality very high in such a situation.
b) Destroyed colon picture : Segmental destruction of the
colon by necrotising and/or gangerenous lesions simulating
a neoplastic or inflammatory mass is yet another presenta
tion not uncommonly encountered. The erythrophagocytic
amoebae may be found in abundance in all planes of the
colon invading blood vessels and lymphatics. Barium con
trast studies may reveal pooling of the contrast material in a
portion of the -“destroyed colon" still communicating on
either end with apparently normal tubes of intestine. Slough
lying free within that cavity may be responsible for intriguing
radiological pictures. Surgery may help in establishing a
definitive diagnosis and ensures good relief if patients
survive the procedure. The success rate of surgery in such
destroyed colons not reponding to medical therapy is better
than in those with clinical features of fulminant amoebic
colitis.
26
tree.
Amoebic typhlitis and pericaecal/periappendicular abscess
of amoebic aetiology pose frequent diagnostic and
therapeutic problems. Demonstration of Entamoeba histolyt
ica in the luminal contents of the appendix does not
neccessarily mean tissue invasion of the appendix by the
organism. Amoebae may even be present in the wall of the
terminal ileum apart from the wall of appendix in patients who
undergo emergency resection for such gangerenous/
destructive lesions.
TREATMENT
Though the list of drugs in vast, metronidazole still takes the
pride of place. Tinidazole has no special benefits over
metronidazole in ensuring prompt relief of symptomatic
amoebiasis, colonic or extracolonic. No currently available
drug can claim to universally induce total parasite clearance
as well as clinical cure. It is unfortunate that in spite of all
development in treatment, death due to fulminant and
perforative colitis still occurs.
SUMMARY
Symptomatic Intestinal Amoebiasis is still a great arch simuVOL in No. i
St. John's Medical College Journal of Medicine
latorof disease though asymptomatic cyst passers with or
without coexisting unrelated causal diseases are far greater
than patients with symptomatic amoebiasis. While one be
comes more and more aware that he or she is overdiagnos
ing amoebiasis, missing the diagnosis is still not an unknown
event. Confessions are good for the soul but not for one's
reputation. Amoebiasis can really tilt the scale either to bring
repute from a spectacular diagnosis made or land one in an
awkward situation for having mistaken some other causal
disease as of mere amoebic aetiology.
FORTHCOMING SYMPOSIA
JUNE
- 1990
CARDIOLOGY & CARDIOTHORACIC SURGERY SYMPOSIUM
RHEUMATIC HEART DISEASE
OCTOBER
1990
MEDICINE SYMPOSIUM
CURRENT ASPECTS ON DIABETES MELLITUS
DECEMBER - 1990
DERMATOLOGY SYMPOSIUM
ALLERGY
MARCH 1990
2 7—
St. John’s Medical
CASE REPORT
College Journal of Medicine
ENDOSCOPIC CORD LATERALISATION FOR BILATERAL
VOCAL CORD PALSY
RC.NAYAR, K.M.NALINESHA, J.J.ALAPATT, D.PRASAD
KEY WORDS :
ENDOSCOPIC
PALSY.
LATERILISATION/BILATERAL
CORD
ABSTRACT
Endoscopic vocal cord lateralisation is an established tech
nique used in the treatment of bilateral vocal cord palsy.
The Authors modification of Kirchners original procedure4
is presented herewith. The cords are lateralised by a
permanent suture, placed around the vocal cord. The
sutures are placed after exposure of the larynx, by the use
of an external skin incision.
The least invasive of all lateralising procedures are those
performed endoscopically. The first such procedure was
described by Thornell in 19493, wherein the arytenoid carti
lage was removed endoscopically. However as this proce
dure is technically very difficult and was often associated
with excessive bleeding, it fell into disrepute.1
Kirchner in 1979, described a simple and elegant technique,
of lateralising the vocal cords by using a temporary external
suture4, which rekindled interest in endoscopic cord
lateralisation procedures.
We used this procedure with some modifications, on a patient
of bilateral vocal cord palsy, the results of which are
presented herewith.
An anecdotal case is presented and its results analysed.
CASE REPORT
INTRODUCTION
A.U., A female aged 70 years presented to the ENT
Outpatient Department of the St.John’s Medical college
Hospital, on the 18th of October 1988 with complaints of a
sudden onset of respiratory difficulty of one weeks duration.
Bilateral vocal cord palsy presents most often with life
threatening airway obstruction. The management initially
consists of a tracheostomy to secure an airway1. As the vocal
cords are fixed in a paramedian position and the glottic chink
is narrow, the patient’s voice is apparently normal.
Further surgical management is directed towards lateralising
the vocal cords to regain an adequate airway. However, this
is invariably at the expense of a good voice, and carries with
it an appreciable risk of aspiration. These sequeale need to be
weighed carefully in each individual case against the
benefits of decannulation.2
R.C.NAYAR
K.M.NALINESHA
J.J.ALAPATT
D.PRASAD
DEPARTMENT OF ENT,
ST.JOHN’S MEDICAL COLLEGE HOSPITAL
BANGALORE 560 034
ADDRESS FOR CORRESPONDENCE
DR. RAVI.C.NAYAR
ASSISTANT PROFESSOR, DEPARTMENT OF ENT
ST.JOHN’S MEDICAL COLLEGE HOSPITAL
BANGALORE 560 034.
2 8
Examination revealed a bilateral vocal cord palsy, with an
inadequate glottic chink, for which an emergency tracheo
stomy was performed. Detailed endoscopic evaluation failed
to reveal any causative factor of the cord palsy.
She was diagnosed as a case of idiopathic bilateral vocal
cord palsy. After a follow up period of one year failed to reveal
any evidence of spontaneous recovery, she was readmitted
for a definitive cord lateralisation procedure.
The procedure was performed under general anaesthesia.
A horizontal skin incision at the level of the thyroid cartilage
was used, the larynx was exposed in the midline, by
retracting the strap muscles laterally. Two needles of 21G
were inserted through the thyroid cartilage above and below
the level of the vocal cords. These were then visualised
endoscopically.1 Prolene sutures were threaded into one
needle and out through the other, under endoscopic guid
ance. The ends of the sutures were tied on the outer aspect
of the thyroid cartilage, after interposing a portion of the strap
muscle under the knot. Similarly a second suture was passed
over the vocal process to support the first. The knots were
tightened until a satisfactory glottic chink was obtained.(Fig1)
On the 2nd post operative day, a fiberoptic endoscopy was
performed. The airway was assessed to be adequate, only
then was decannulation attemped.
VOL III No. i
—
St. John’s Medical College Journal of Medicine
CORD LATERALISATION
PRE & POST OP SPIROMETRY
I
| EXPECTED VALUE
PRE-OPERATIVE VALUE
IWBM POST•OPERATIVE VALUE
Fig 1 : Diagramatic representation of the authors modfication of kirchners
procedure
Fig 2 : Graph showing improvement in lung functions after the procedure
The pulmonary function test, performed before and after the
cord lateralisation procedure revealed, a marked improve
ment in all respiratory airway flow parameters. These values
post operative approached the expected values,i.e. near
normal.(Fig.2 Table 1)
the vocal cords. These have been classified as static
procedures and dynamic procedures (Table II & Table III).1*2
Static procedures, attempt to increase the glottic chink,
without an attempt to restore cord movements, by nerve,
muscle or nerve muscle transplants. As usual, the plethora
of procedures underlines the lack of unanimity on the “ideal
procedure”.
The patient was discharged after successful decannulation,
Though her voice was weaker, as assessed subjectively, it
was acceptable to her.
DISCUSSION
Among the static procedures, surgery performed endoscopi
cally is least traumatic to the larynx, but bleeding when it
occurs is difficult to control. Laser surgery is believed to
overcome this drawback6.
There are many surgical procedures described to lateralise
The procedure described by Kirchner, in 1946, is elegant
She is on a close follow up and is asymptomatic to date.
TABLE 1
SPIROMETRY
PRE AND POST CORD LATERALISATION
Predicted valve
1,45 Its
1.06 Its
85.7%
2.33 Its
2.09 Its
2.79 Its
3.78
FVC
FEV1
FEV1%
FEF25
FEF50
PEFR
RAW
Pre-operative
0.33 Its
0.33 Its
100%
.73 Its %
.67 Its
0.43 Its
18.93
Post-operative
1.05 Its
1.01 Its
96.19%
2.25 Its
1.06 Its
2.25 Its
5.23
TABLE II
CORD LATERALISATION PROCEDURES
STATIC
KELLEY (1941)
WOODMAN (1946)
THORNELL (1949)
MONTGOMERY (1961)
DAWNEY (1968)
MARCH 1990
ARYTENOIDECTOMY
ARYTENOIDECTOMY
ARYTENOIDECTOMY
ARYTENOIDOPEXY
ARYTENOIDECTOMY
LATERAL APPROACH
TRANSLARYNGEAL
LARYNGOFISSURE
2 9—
St. John’s Medical College Journal of Medicine
TABLE III
SURGERY FOR CORD LATERALISATION
DYNAMIC
HORSELEY (1909)
-
RECURRENTS LARYNGEAL NERVE DECOMPRESSION
FRASER (1924)
-
ANSA CERVICAL TO RLN ANASTAMOSIS
BARNES (1927)
-
PHRENIC NERVE TO RLN ANASTAMOSIS
MORELEDGE (1971)
-
PHRENIC NERVE TO POST CRICOARY MUSCLE
TUCKER (1971)
-
ANSA WITH NERVE MUSCLE PED TO CRICOARY
MIEHLKE (1974)
- VAGUS NERVE TO RLN ANASTAMOSIS
MIGLETS (1974)
- RECURRENT LN TO POST CRICOARY MUSCLE
and effective and can be recommended as the endoscopic
procedure of choice in centres lacking laser facilities. Briefly,
he described a procedure of placing external sutures, to
retract one vocal cord laterally. A segment of vocalis muscle
was excised endoscopically, at the level of the suture. The
suture retracted the vocal cord laterally, and once fibrosis
developed, the external sutures were removed.(Ag 3).
This obviates the need to remove a portion of the vocalis
muscle which was done to ensure that the glottic chink
remains patent in the post-operative period. Hence, bleed
ing is minimised. However, as a consequence, strict atten
tion to asepsis, use of intra and post operative antibiotics,
and close follow up are mandatory.
The procedure as described is effective, and is now the
method of choice in our centre.
The need for documenting and reporting pulmonary flow
volume characteristics before and after any decannulation
procedure has been emphasised keeping in mind the
plethora of procedures and dogmatic assertions of their
respective proponents.1
CONCLUSION
A modification of Kirchners procedure, of endoscopically
lateralising the vocal cords is presented.
Fig 3 : Diagramatic representation of Kirchners original procedure
The major drawback of this procedure, is the bleeding which
occurs during the excision of the vocalis muscle segment.
The procedure we used differs from Kirchners original proce
dure as follows:
i) An external incision is used. This permits more careful
localisation of the needle puncture sites, and reduces the likely
hood of accidental trauma as with the blind approach. It also
permits the surgeon to extend the procedure to a formal
artenoidectomy in case the airway obtained after lateralisation
is unsatisfactory.5 The larynx is not opened or entered, and the
morbidity of such a step is avoided.
ii) The sutures are placed permanently.
3 0
The procedure is simple, and supplements the endoscopic
procedure with an external exposure of the larynx. This adds
to the safety of the procedure and enables the surgeon to
extend the procedure to a formal arytenoidectomy if
required. The sutures used tolateralise the vocal cords,
are placed permanently, thereby obviating the necessity to
remove a section of the vocal cords.
REFERENCES
1) Bailey B.Y. Biller H.F: Surgery of the larynx (ed 1) W.B Saunders and
Co, Philadelphia, 1985:117-134.
2) C.W.Cummings, J.M. Fredickson J.M. Harker LA et al.Otolaryngology
Head & Neck Surgery (ed 1) The CV Mosby Co, Toronto, 1986:2181-2190.
3) Thornell W.C. “New Intralaryngeal approach for bilateral abductor paraly
sis of Vocal Cords" Trans Am Acad Ophithal Otol 1949:53:631-635.
4) Kirchner F. “Endoscopic Lateralisation of the vocal cord in abductor
paralysis of the larynx." Laryngoscope 1979:89:1179-1182.
5) Woodman D.G. “A modification of the extralaryngeal approach to arytenoi
dectomy for bilateral abductor paralysis. Arch Otol 1946:43:63-67.
6) Stell P.M. Scott-Brown's Otolaryngology vol IV (5th edition)
Butterworths, London. 1987:169-185.
VOL III No. 1
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