THE EFFECT OF LIGATING THE TAIL
OF THE PANCREAS IN
JUVENILE
DIABETES
G.
DeTAKATS, M.D., M.S., F.A.C.S., CHICAGO, 1930
Surg
Gynecol obst 53:45-53, 1931
In
previous animal experiments, carried out following the original suggestion of
Mansfield, it was found that when the tail of the pancreas was tied off or
completely isolated in the dog, a series of important changes resulted.The isolated tail ceased to function as an organ of external secretion,
as the acini degenerated and a marked sclerosis and atrophy of the tail took
place (5). The islands seemed to survive this sclerotic process and showed
hyperplasia and hypertrophy,Moreover,
this hyper-regeneration was encountered in the unlighted head and body of the
pancreas (7).My co-workers and I
could also demonstrate an increase in carbohydrate utilization in the normal
dog, following a ligation of the tail of the pancreas (9).The increase in sugar tolerance was noticeable between the
third and fourth months after the operation but did not persist to any extent,
over a period of a year. Causes for the return of'the sugar tolerance to
normal in the normal dog 'are now being investigated.
Whether such suggestive
experimental findings could be applied in human diabetes was doubtful.In a preliminary report on the first diabetic child operated on, Wilder
and I pointed out (8) that hypertrophy of the islets might not take place in
human diabetes, and, even if it did, the new islets might succumb to the same
delctary influence that inhibited the efficient function of the original
cells. Yet the following clinical facts seemed to make a clinical trial
promising.
First,
the great regenerative power of the human islet cells is seen following
destruction of pancreatic tissue in acute pancreas necrosis or carcinoma of
the pancreas.While temporary glycosuria may occur in these diseases, the
loss of tissue is readily compensated for and true diabetes mellitus dose not
frequently result. Such examples from the Literature and our own observations
have bean recorded elsewhere (6). Second, the pancreas of the diabetic also
shows signs of regeneration. Particularly Weichselbaum and Cecil (3) pointed
out the occurrence of hypertrophic islets in diabetes. Other observations are
cited in a previous article (6) and an excellent summary together with a
number of new observations on islet regeneration is given by Shields Warren.
As
we had experimental evidence which suggested a possible increase in islet
function and as numerous postmortem observations are on record regarding the
regenerative power of the diabetic pancreas, we felt that it was worth while
to try to determine the effect of ligature of the tail of the pancreas in
patients suffering with diabetes.
INDICATIONS
Juvenile
diabetes seemed theoretically the type of diabetes in which an attempt to Increase
sugar tolerance would be most promising.The regenerative power of the islets in children is obviously greater
than in adults; for secondary changes in the vascular system, particularly in
the blood supply of the islets, have not yet taken place.In children, the islets themselves do not show morphological changes,
although, as emphasized by Warren, in many adult patients with diabetes, the
islets are singularly free of degenerative processes.
Furthermore,
the juvenile type of diabetes is usually severe and difficult to manage.While it is true, that the advent of insulin has reduced the mortality
in juvenile diabetes from 90 per cent to around 10 percent , and while
according to recent figures of Wilder and Allen the mortality in the year 1929
at the Mayo Clinic was only 1.2 percent, it must be remembered that there
still remains many cases of juvenile diabetes in which the diabetes is
inadequately controlled and the children affected die of diabetic coma. When
the operation of ligating the pancreas is suggested, it must be postulated
that the operative risk is not greater than the mortality percentage of the
diabetic child per se, and that the diabetes itself will not be aggravated.Both these postulates can be easily fulfilled by this
surgical attempt.
Naturally
not all diabetic children are suitable for such a trial.In mild cases, when the child’s tolerance is fairly stable and the
caloric intake is high enough for normal development without too much insulin,
the patients are doing well under medical management.Joslin feels that this new generation of juvenile diabetics, who grew
up under continuous dietary and insulin control, are offering the best example
for the vast importance of insulin.It
would not seem justifiable, with our present knowledge of the effects of this
operation, to advise surgery to this group.
It
is then in the severe type of juvenile diabetes with unstable tolerance, with
frequent occurrence of acidosis and coma at the slightest infection, with
unexpected insulin reactions, that this operation might be tried.But here again the time of operation must be carefully selected.It has been stated by Wilder (8) that juvenile diabetes usually starts
with unusual severity and that under adequate dietary and insulin control, the
tolerance gradually improves and becomes stable.If one is to evaluate the result of this operation, the child
must have been diabetic for at least 2 years and must have been practically
sugar free for at least 6 months, with a stable or slightly improving
tolerance.On the other hand,
patients whose diabetes dates back 8 or 10 years, much of which time they have
not been properly controlled, may show too many secondary changes to permit
great improvement form operation.
PREPARATION OF PATIENT
As in any other operation on diabetics, the patient must be sugar free
and should have no diacetic acid in the urine.It has also seemed advisable to administer for the last 3 days from120
to 150 grams of carbohydrate in the diet, so that sufficent glycogen is stored
in the liver.An enema is
given only if the patient has not had a bowel movement on the day before the
operation.A light sedative, one
or two tablets of allonal, is prescribed for the night before the operation,
and the dose repeated 2 hours before the operation. The morning dose of
insulin is omitted, and a glass of orange juiuce is given at least 2 hours
before operation.Half an hour
before the operation ( 1/3 grain to ¼ grain) and atropine 1/120 grainare injected under the skin.
RESULTS
OF SURGERY
Case
1.Detailed history of this case
was given in a previous communication (8).The diabetes had been present previous to operation for 8 years.Patient had been under dietary and later insulin management, supervised
by Dr. Russell M. Wilder at the Mayo Clinic for 6 years.At first his tolerance grew worse steadily.For the last 2 years before operation the patient had been taking 40
units of insulin.The dextrose
value of the diet being 190 carbohydrates, protein 50 and fat 150.
The
operation was performed on January 21, 1929.The small, definitely hypoplastic tall was divided with a high
frequency cautery.The patient had a stormy convalescence during which time
drainage of the omental bursa had to be instituted twice.He was discharged from the hospital on March 16, 1929, on the
original diet, with 45 units of insulin, 5 units more than before the
operation.For the next 3 months,
the insulin requirement remained steadily between 40 and 38 units.From April 26 on, insulin reactions began to occur after the morning
dose, which prompted a gradual reduction.On May 9, 1929 110 days after the operation the lowest level of 25
units was reached.From then on
the insulin had to be increased to 35 to 39 units, a stitch abscess of the
abdominal incision having developed.On June 3, the boy’s dietwas increased, as he still weighed 8 pounds less than before the
operation.The diet consisted of
carbohydrates 102 grams, protein 75 grams, and fat 161 grams, the dextrose
value of 166.On June 18, 1929,
the insulin dose was 39 units., on August 2, 29uunitus.On May 31, 1930, 17 months after the operation the patient weighed 5
pounds more than before the operation, had grown an inch and a half, took 63
grams more dextrose, with 8 units of insulin.In September, 1930,20
months after the operation the patient was on a diet of carbohydrates 134,
protein 88, fat 162, dextrose value of 200 and 37 units of insulin, a gain of
80 grams of tolerance since the operation (1)
A severe diabetic
child whose previous diabetic history is well known, and who was stabilized
for 3 years before operation, is at the present writing, growing and is
gaining weight normally, with a slightly diminished dose of insulin, but
utilizing an additional 80 grams of dextrose.This definite increase in tolerance occurred in a patient who for 6
years had gradually lost tolerance and who for the last 2 years previous to
operation had not shown any change at all.
Case 2:Detailed history was given elsewhere (6).He had been in a tuberculosis sanitarium with tuberculosis cervical
lymph glands for over 3 years, being discharged as well at the age of 10.At the age of 14, 3 years previous to operation, it was first noticed
by the parents that he passed a great deal of urine and had lost weight.He wa admitted a few days later to the Billings Hospital in coma.In November 1927, he was discharged on a diet of carbohydrates 90,
protein 65, fat 216, calories 2,600, without insulin.Between this date and the date of operation, October 15, 1929, he had a
further admissions to the Billings Hospital.More and more insulin had to be given, but control was very difficult.He had several respiratory infections, an emergency appendectomy, all
of which affected his tolerance.He
had also been very careless about his diet and ignored it several times.Finally on his tenth admission, as he had done poorly on a low
carbohydrate, high fat diet, and continued to pass sugar on a diet of
carbohydrates 130, protein 85, fats 200, with 80 units of insulin, it was
considered advisable to try him on a high carbohydrate, low fat intake.This resulted, at least temporarily in a marked decrease in the insulin
requirement.On his discharge
August 30, 1929, his diet consisted of carbohydrates 300, protein 75, fat 100,
dextrose value of 354 with 45 units of insulin.
On
October 1, 1929, the patient was admitted to the Wesley Memorial Hospital
under the diabetic management of Dr. William H. Holmes (Case No. 147.279
W.M.H.)He was operated upon on
October 18, 1929, during the Clinical Congress of the American College of
Surgeons.The pre-operative diet
was carbohydrates 300, protein 75, fat 100, and insulin 35-35-35.The operation was performed as described in this paper.The patient made an uneventful recovery with primary union of the
incision.He left the hospital on
the fourteenth day.A month later
on the same diet and 60 units of insulin he weighed 42 kilograms (+ 3
kilograms, since the operation).Two
months after the operation, the patient had gained another 4 kilograms.Four months after the operation he was getting severe insulin
reactions, so that the dosage had to be reduced to 40 units a day.On February 25, 1930, he was readmitted to Billings Hospital because of
an upper respiratory infection.Temperature
rose to 101.1 degrees F.He
required now 70 units of insulin but could soon be reduced to 45-50 units.
On
March 9, 1930, he was taken off the high carbohydrate diet and given
carbohydrates 59, protein 50, fat225, a glucose value of 120.the insulin requirement fell to 18 units.The next week the insulin had to be raised and on March 23, a
chickenpox developed with high temperature and extensive eruption.The insulin requirement rose to 50 units and his tolerance was upset
for several months.On June 20,
1930, Miss Florence Smith, chief dietitian of the Billings Hospital, reported
the following data.Diet
carbohydrates 139, protein 75, fat 200, a dextrose value of 203, with 55 units
of insulin.This was 3 months
after the chickenpox infection started, but the tolerance seemed to increase
slowly.
On
October 25, 1930, a year after the operation, patient ws still taking the same
diet and insulin, although occasionally, when under rigid control in the
hospital, it was possible to reduce the insulin to 35 units.This patient’s tolerance is not stable, and during the school year is
always lower then in the diabetic camp.
A diabetic child,
whose disease is known to have been present for at least 2 years, and whose
tolerance was rapidly growing worse, was operated on.The child made a rapid recovery.Four
months after the operation, a reduction of insulin could take place.Five months after the operation, the high carbohydrate low
fat diet was changed to a low carbohydrate, high fat diet with a large
reduction of insulin.A little
later, a chickenpox infection upset the sugar tolerance, from which this
patient, 3 months after this infection and 11 months after the operation, is
gradually recovering.
In a disease of
life’s duration, with spontaneous fluctuations, with such sensitive response
to infections and emotional influences, we can not be too cautious in
interpreting results.It is true
that the result in either of the two cases operated upon is not a fair example
of what can be accomplished with the method.In the first patient, the presence of a small, hypoplastic tail of the
pancreas prevented the isolation of a large enough portion of the gland.In the second patient, as pointed out by Wilder, the high carbohydrate
diet, which has been given according to Porges and others to stimulate
insulin-production, might have been injurious and that better results could
have been expected if the pancreas had been allowed to rest rather than being
stimulated in the period when the islets were undergoing hypertrophy.Insufficient time has elapsed in both cases to predict the ultimate
result.
Nevertheless, the
animal experiments and the observations in the two clinical cases show
striking parallelism.The
increase in tolerance is gradual, occurs around the fourth month, and does not
persist at its highest level but gradually diminishes.The assumption that an islet hypertrophy takes place in the diabetic
child could not be verified up to date histologically, but seems very
probable.
This regeneration or
even super-regeneration of islets does not strike at the real cause of
diabetes.Unless we will be able to protect these islets from injurious
effects of nervous or hormonal origin, the new islets will become exhausted
like the original ones.If
Epstein’s theory of tryptic action on the islets were true, the exclusion of
external secretion from the tail would be particularly significant.If some other insulin-inactivating agent were at work, then a surgical
attempt of islet regeneration alone would not lead to permanent
results.
So long as the cause
of diabetes is unknown, a surgical attempt to improve diabetes can only have
the following aims:
1.A stabilization of tolerance, whereby the children are more
easily controlled, loss subject to acidosis and coma.In other words, to transform the unstable juvenile diabetes into a
stable type of the older patient.Both
cases seem to show this effect very definitely.
2.A reduction or possible abolition of insulin, on a
liberal diet.If better
utilization of sugar would take place on the same or less amount of insulin,
the better development of these children might be brought about.This second requirement has not yet been entirely fulfilled. There
is enough suggestion, however, in the first cases toward further trial
A
report on other cases, with a further report on the first two children will be
made at a later date.
SUMMARY
In
two carefully selected cases of juvenile diabetes the tail of the pancreas has
been isolated on the basis of animal experiments, which show hypertrophy and
hyperplasia of the islets and increased carbohydrate tolerance after such an
operation.Longer period of
observation, and further trial on other cases promise a better evaluation of
such attempts.
BIBLIOGRAPHY
1.Rier, A, Braun, H., and Kusmmell, H. Chinurg;eche, Operationglelure.Leipsig: Joh. Ambroalus Berth 1924.
2.Cusi, R. L. A study of the pathological anatomy of the pancreas in
diabetes mellitus.J. Exper.
Med., 1909, xi, 266-290.
3.Iderm. On hypertrophy and regeneration of the islands of Langerhaus.1911, siv, 500-537.
5.Idem. The histologic changes in the isolated tall of the pancreas.Arch. Surg., 1929, xi, 775-589.
6.Idem.Ligation of the tail
of the pancreas in juuuvenile diabetes.Endocrinology,
1930, xiv, 255-264
7.Idem.Unpublished
experiments.
8.Detakas, Geza, and Wilder, Russell, M. Isolation of the tail of the
pancreas in a diabetic child.J.
Am. M. Assoc, 1929 xciii, 605-610.
9.Detakas, Geza, Hannett, Frances, Henderson, Dorotry, and Seitz, Ira J.The effect of ligating the tail of the pancreas on carbohydrate
metaboism.Arch. Surg., 1930, xx,
866-884.
10.Hendon, G. A. Experiences with venoclysis, Ann. Surg, 1930, xci,
753-760.
11.Joslen, E. P. Treatment of Diabetes Mellitus.4th Ed. Philadelphia; Leis and Febiger, 1928.
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13.McKittrick, Leland S., and Root, R. W. Diabetic Surgery.Philadelphia: Les and Febiger, 1930.
14.McNealy, r. W., and Lichtenstein, M.E. Studyu of arterial occlusiuon by
means of autogenous fascial strips.Surg.,
Gynec. & Obst., 1928 xlvii, 99-101.
15.Ssosen – Jarorevitch, A. J. Zur chirurgischan.Anatomis des Milchilus Zischr. F. Anal. U. Entw., 1927, lxxxiv, 218-237
16.Warren, Shields.The
pathology of diabetes mellitus.Philadelphia:Lea & Febigar, 1930..
17.Weichselbaum, A. and Kyrle.Ueber
das Verhelten des Langerhaus Insela im fostalen und postfoetalen Leban.Arch. F. mikr. Anst., 1930 lxxiv, 223.
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treatment of diabetes of children.J. Am. M. Assoc., 1930, xciv, 147-151.
19.Wilder, Russell, M. Personal communicuation.
Other
Related Articles:
1.de Takats G, Cuthbert FP. Surgical attempts at increasing
sugar tolerance. Arch.Surg:750-764,1933
2. de Takats G, Wilder RM. Isolation of tail of pancreas in a
diabetic child. JAMA 93:606-610, 1929.
3.Takats G. Ligation of the tail of the pancreas in juvenile
diabetes. Endocrinology 14:255-264, 1930
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