J.Jpn. Surg. Soc.. 55(7): 766-794, 1954
宿題報告
Pancreatectomy
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Surgical Department, Tokyo Metropolitan Police Hospital Hazime YOSHIOKA |
Table 1.
Diseases number of cases
Cancer of stomach 29
Cancer of the head of the pancreas 5
Cancer of the body of the pancreas 1
Cancer of the common bile duct 6
Table 2.
Resection of Number of cases. Mortality
the head 30 (the first half 54%, the latter half 32%)
the body 1 0
the tail 11 0
the total 2/44 cases 50%
Since the pancreas is a very important gland of internal and external secretion, fundamental studies are urgently required in order to carry out successful pancreatectomy. In this paper I will present a summary of our experimental works, which have been conducted in our laboratory since 1949.
1. Carbohydrate metabolism.
A. Interrelation between the pancreatic remnat and development of diabetes.
Yoshioka and his coworkers found that diabetes did not occur when the pancreatic remnant was more than 1/5 of its original weight, but the carbohydrate metabolism was suddenly disturbed if the remnant was reduced more. From this experimental data we may suppose that pancreatectomy may never result in diabetes, when more than 1/5 of the pancreas parenchyma remained.
B. General Survey of the metabolism of the diabetes of pancreatectomized animals.
The overproduction theory and the non-utilization theory have been hitherto the two opposing explanations for the diabetic syndrome. We measured the rate of utilization of sugar in the perpheral tissues and also the rate of sugar output by the liver.
a. The rate of utilization of sugar in the peripheral tissues
We have deviced a method of measuring the rate of withdrawal of sugar from the blood by the peripheral tissues. Using this method we have measured the rate of utilization of sugar by the peripheral tissues at various blood sugar level of liverless dogs, which were given constant intravenous infusion of known amounts of dextrose. The net results we have obtained are as follows. The rate of utilization of sugar varies directly with the height of the blood-sugar level in depancreatized dogs as in the normal dog. The diabetic dog utilizes less sugar than does the normal dog at every particular glycemic level. In order to utilize the same amounts of sugar the blood sugar level of the depancreatized dog must be about 200 mg/dl higher than that of the normal dog. At the same blood-sugar level the depancreatized dog can utilize remarkably less sugar than the normal dog.
b. The rate of supply of sugar to the blood from the liver.
Using the liver catheterization technic and the bromsulphthalein method for the estimation of hepatic blood flow, we calculated the absolute amounts of sugar entering and leaving the liver per unit time. The difference between them is the net rate of output of sugar from the liver. The rate of the output of sugar from 100 g of liver per minute was 14.5 mg in normal dog, 30.1 mg in alloxan-diabetic dog, 25.7 mg in partially pancreatectomized dog (the remnant was 1/5) and 34.5 mg in total depancreatized dog.
From the above stated we may say that in depancreatized diabetic dogs the output of sugar from the liver is increased and the utilization of sugar iin the peripheral tissues is decreased.
c. The homeostatic regulated blood sugar level.
The average of the normal dogs was 78 mg%, that of the all oxandiabetic dogs 164 mg% and of the depancreatized dogs 148 mg%.
d. The disturbance of the homeostatic regulating mechanism of the liver for the control of blood-sugar level.
The hepatic regulating mechanism as the response to the change of the blood-sugar level is not so rapid and smooth in depancreatized dogs as in normal dogs.
e. The manners of protein and fat.
In depancreatized dogs the breakdown of protein and the formation of ketone bodies are remarkably accelerated. The RQ is 0.7.
C. The basal insulin reqiurement of depancreatized dogs.
The average of 10 totally depancreatized dogs was 0.019 units per Kilo per hour. This value if applied on a man weighing 60 Kgm for 24 hours, would give a figure of 27 units, which coincides with the hitherto reported insulin requirement, i.e.. 20-30 units in totally depancreatized man.
It is noteworthy that the basal insulin requirement of partially depancreatized dogs (0.02 units) is less than that of alloxan-diabetic dogs (0.042 units) and that of the totally depancreatized dogs (0.019 units) is still smaller than the partially depancretized.
It may be due to the existence of the Hyperglycemic Factor in the pancreas.
D. The characteristics of pancreatic diabetes
There are three characteristics in pancreatic diabetes.
1) Insulin requirement is remarkably small as compared with severe spontaneous diabetes mellitus.
2) Loss of weight, which cannot be controlled by insulin
3) Development of fatty liver
E. The Hyperglycemic Glycogenolytic Factor HGF "Glucagon"
a. Extraction and purification, Glucagon is said to be protein or polypeptide, therefore it may be digested by trypsin. In order to prevent the breakdown of the hormon by the action of panereatic juice during extraction, first we ligated the pancreatic ducts of dogs. Three months later, we administered alloxan to the dogs, in order to destroy the β cells of Langerhans's islets. From so pretreated pancreas we successfully extracted the Hyperglycemic Factor-"Glucagon".
b. Physiological function
1) The effects on liver glycogen
Using the liver catheterization and the bromsulphthalein method, we have ascertained remarkable increase of output of sugar from the liver soon after intravenous injection of glucagon and consequently a steep rising of blood-sugar level, resulting in the decrease of glycogen content of the liver was seen.
2) The effects on utilization of sugar in the peripheral tissue
In the eviscerated dog the injection of glucagon did not cause any fluctuation of the blood sugar level.
All the above-stated effects of glucagon are similar to the actions of epinephrine.
3) Diffenences from epinephrine actions
Glucagon has no epinephrine-like actions on the cardiovascular system. It lowers the arterial blood pressure after a slight rise.
In alloxan-diabetic dogs, whose β cells of the pancreas are completely destroyed, the blood-sugar level is raised by vagus stimulation, so that glucagon is presumably secreted by vagus-stimulation simultaneously with insulin.
4) The role of glucagon
As above mentioned glncagon increases the supply of glucose for the blood from the liver, which is utililzed in the peripheral tissues in turn by insulin.
2. Water and Electroltyes Metabolism.
A. Disturbances of water balance
On the first day of pancreatectomy the urine volume per day decreases according to the temporary increase of ADS as a response to operation. Thereafter the urine volume gradually increases and the water balance becomes negative. The volume of the extracellular fluid decreases, but the total body water decreases more rapidly, so that the intracellular fluid decreases progressively. Therefore, the animals lose body weight.
B. Disturbance of Electrolyte Metabolism
The osmolar concentration of the blood becomes elevated. The osmolar concentration of the urine does not decrease despite the remarkably increased excretion of the urine. Consequently the loss of electrolytes may be large. The patterns of all electrolytes are as follows. Serum sodium decreases markedly, but serum chloride does not decrease so remarkably as sodium, because sodium has transferred its allegiance to the ketone acids and has shifted into cells in turn of potassium. Serum potassium becomes gradually elevated.
C. Development of acidosis
D. Renal function
Despite the progressive reduction of RPF, GFR increases, so that FF becomes elevated. The rate of reabsorption in the tubules decreases as the solute concentration of serum rises. Consequently the polyuria may presumably be caused by the elevation of GFR and reduction of the rate of reabsorption in tubules. In the kidney the Kimmelstiel-Wilson's syndrome is frequently seen.
E. Effect of insulin therapy
All the above-mentioned disturbances of water, electrolytes aud acid-base equibria can be completely restored by insulin administration, being explained by "Osmotic Diuresis."
When the plasma sugar rises above a certain concentration the quantity of glucose presented to the tubules by the glomerular filtrate exceeds thir reabsorption capacity. The sugar that thereby escapes reabsorption limits reabsorption of water in the terminal tubules. In addition, the glucose which accumulates in the extracellular fluid, being unable to penetrate cells freely, increases the effective osmotic pressure of this fluid. This draws water from the tissue cells, inhibits the reabsorption of sodium chloride from the tubules. The net result is polyuria, dehydration and salt depletion.
3. The Influence on Endocrine Glands
A. Pituitary
The postoperative temporary elevation of ADS is the same as the usual response to surgery. It is interesting that ADS does not appear after this period despite the grave water depletion.
B. Thyroid
PBI decreases immediately after pancreatectomy as in the usual operation, out it rises progressively so much as to 10 γ/dl, exceeding the preoperative value. Histologically the thyroid gland presents the feature of hyperfunction.
C. Adrenal cortex
The excretion of 17 K-S increases, corticoid remarkably elevates, eosinophiles decreases and 17 hydroxycorticoid increases so much as to 20 γ/dl, which is about twice as high as normal.
Histologically features of hyperactivity is seen 10 days after the operation in both glomerulosa and fasciculata, 3 weeks after operation in the glomerulosa and 40 days after operation in the fasciculata. In general surgery the elevetion of corticoid limits PBI (corticogenic hypothyroidism). But in pancreatectomy it is characteristic that both the adrenal cortex and the thyroid become hyperactive.
D. Parotid gland
Atrophy of the striated tubules and lymphocytic infiltration in the interstitium can be seen.
E. Ovary.
Follicular atresia and increase of the interstitium can be seen. Estrogen decreases.
4. Central Nervous System
For the purpose of studying the changes occured in the central nervous system, which may be caused by the severe pancreatic diabetes, a series of sections stained by Nissle methode was followed rostrally from the medulla oblongata in 2 depancreatized and 1 alloxan-diabetic dogs, which survived 3 weeks. But no changes were discovered anywhere. The Nucleus dorsalis n. vgi presented no retrograde degeneration as Burgsch, Dresel ＆ Lewy claimed. But in the pituitary we encountered the change so worthy of special note.
5. The Appearance of Special Cells in the pituitary after Pancreatectomy―"Pancreatectomy Cells".
After pancreatectomy Special cells appear in the anterior and posterior lobe, intermedia, pars tuberalis and eminentia medialis. The cells are most distinctive when stained by Nissle methode. The cells do not appear in the brain substance. The form of the cells is irregular, being round, oval or slender. The outline is not smooth, but rugged. The nucleus has gross chromatin grannles and a dense nuclear membrane and is darkly stained. The cytoplasma is thick or thin and is stained metachromatically deep yellowbrown so that the cells can be identified easily even by weak magnification.
From the contour of the cells processus or network are frequently seen. By simple staining with hematoxylin the cytoplasma stains slightly and the identification of the cell is difficult. By hematoxylin-eosin staining the cell takes an eosine tone. By periodic acid Schiff reaction the cell stains positive. By staining with Gomori's method the identification of the cell is difficult. The genesis and the physiological significations of the cells are not yet known. However as the existence of ''pancreatotrophic hormon" is not yet ascertained today, the appearance of the "pancreatectomy cells" in the pituitary may have some suggestion.
6. Digestion and Absorption
A. Changes in amounts of ferments in feces
a. Diastase in the feces always decreases in 1-2 weeks by pancreas resection, but it returns rapidly to normal in 4-5 weeks when the pancreatic remnant is more than 1/5 of its orginal weight. When the remnat is less than 1/5, the restoration of the ferment in amounts is not sufficient. In the cases of ligation of the pancreatic ducts and total pancreatectomy the amount of diastase shows no trend of recovery.
b. Trypsin in the feces undergoes a remarkable reduction by pancreatic resection and shows insufficient recovery, even if the remnant is 1/5 of its original weight. In the case of ligation of the ducts and total pancreatectomy this ferment remains dropped.
c. Lipase in the feces. It is noteworthy that this ferment never undergoes the diminution by any pancreas operation.
I have experienced one human case of total pancreatectomy where the diastase and trypsin were almost zero, while lipase remained within normal limits.
B. Digestibility=((Intake-Output)/Intake) × 100
a. Carbohydrate
The average of normal dogs was 98% of the totally pancreatectomized being 82%. The rate of the reduction is 16%.
b. Fat
The average of normal dogs was 87% and of totally pancreatectomized 40%. The rate of the reduction is 53%.
c. Protein
The average of normal dogs 75% of totally pancreatectomized being 31%. The rate of the reduetion 58%.
7. Technic of Pancreatoduodenal Resection
I will present some advice before I state the technic.
1) The problem whether necrosis should result in some parts of the pancreas and duodenum when one of the three main arteries of pancreas, i.e.a. pancreaticoduodenalis sup. et. inf. and a lienalis, was ligated, was not solved. In order to answer this question, we injected "Teichmann'sche Masse" into each one of these arteries, using 40 cadavers and took arteriograph of each. And we obtained the following conclusions. "Teichmann'sche Masse" injected into each of these arteries extends to every part of the pancreas and duodenum. Therefore, it is enough to warrant the blood supply of the pancreas and duodenum by leaving only one artery. When the three arteries are all ligated and the "Teichmann'sche Masse" is injected into a. gastroepiploica sin., the contrast substance extends to the tail and the body of the pancreas, but does not reach the head of it. But in the case of resection of the head of the pancreas and duodenum, the blood supply of the pancreatic remnant should be warranted by the route of the hilum of the spleen, even if the main arteries were all ligated,
2) During operation we should not damage the following vessels, which are apt to be carelessly ligated ; A. hepatica, A. mesenterica sup., V. portae and V. mesenterica sup. et inf.
3) Through duodenal resection secretin and cholecystochinin do not disappear. Their existence can be proved to the extent of 2 meters below the Treitz' s band.
4) Effective drainage is always necessary against unevitable leakage of bile and pancreatic juice.
The steps of my procedure will be listed in order. This order of operation is chosen because it permits establishment of the diagnosis and determination of operability without committing the surgeon to the radical procedure. It enables the surgeon to establish the contrainidications to operation and also permits to give up the operation.
Steps of procedure
1) Division of the stomach
2) Exposure of the Bursa omentalis and inspection
3) Incision of peritoneum at the superior and inferior border of the pancreas
4) Elevation of the body of pancreas and division (closure of the stump except the duct)
5) Freeing of the head of the pancreas from the portal vein
6) Ligation and division of the gastroduodenal artery and the common bile duct
7) Division of the jejunum (freeing of the proximal jejunal mesenterium)
8) Delivery of the proximal jejunum and the fourth portion of the duodenum to the superior mesenteric vessels
9) Elevation of the duodenum and the head of the pancreas
10) Freeing and division of the uncinate process from the superior mesenteric artery
11) The removal en bloc of the resected specimen
Steps in the reconstruction
1) Choledochojejunostomy
2) Pancreatojejunostomy
3) Gastrojejunostomy
4) Insertion of drain and closure of wound
Addition : Appraisal of the division of Plexus pancreaticus capitlis for the purpose of the relieving of severe pain of chronic pancreatitis.
Autonomic nerve fibers from Ganglion solare enters into the uncinate process as a grosscollected bundle, which we call "Plexus pancreaticus capitalis".
By division of this nervous plexus we could deliver 8 patients of chronic pancreatitis from severe pains.
(author's abstract)
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