[CANCER RESEARCH 37, 2387-2394, July 1977]
Effects on Nutrition of Surgery of the Liver, Pancreas, and
Genitourinary Tract1
Maurice E. Shils
MemorialSloan-KetteringCancerCenter,Cornell universityMedicalCollege,New York,New York 10021
Summary
Carcinoma of the pancreas is increasing in the United
States and has a grave prognosis. Surgical treatment has
moved from subtotal pancreatectomy to total pancreatec
tomy and now to en bloc resection and vascular replace
ment. Pancreatic exocrine and endocrine insufficiency fol
lowing resection add to the nutritional problems presented
by this major surgery and its high complication rate. Recog
nition of these problems and adequate treatment decrease
morbidity and mortality. Major hepatic resection imposes
metabolic problems in the immediate postoperative period
that are minimized by improving preoperative nutritional
status and by providing adequate postoperative support
with albumin and carbohydrate. Urinary tract diversion for
pelvic cancer involving the ureters and/or bladder has pro
gressed from ureterosigmoidostomy with its high incidence
of disturbances of electrolyte and acid-base balance to ure
teroileostomy with its appreciably lower rate of complica
tions.
alfold that when the tumor is in the head of the pancreas
[Ref. 47; K. W. Warren, in published discussion following
presentation by J. C. Fish (20)], with the rates in the other
2 categories being intermediate. In addition, the 5-year
survival following surgery when carcinoma is in the head of
the pancreas ranges from 13 to 18% [Ref. 47; K. W. Warren,
in published discussion following presentation by J. C. Fish
(20)] and that with tumor in the ampulla and duodenum is
2 (47) to 3 (65) times greater.
Weight loss is a very common feature in carcinoma of the
pancreas no matter where the lesion is located (10). It is
often associated with jaundice and pain. Warren et al. (65)
recorded preoperative weight losses, averaging 12 to 16
pounds@,depending on the site, in 253 patients with periam
pullary cancer. Weight loss in patients with ductal carci
noma of the pancreas commonly occurred in 39%, anorexia
and asthenia in 15 and 14%, respectively, and steatorrhea in
9% (5). Resectability in the latter group is only 19%, and 5year survival after total pancreatectomy is very low (5, 56).
Pancreatoduodenectomy
Carcinomaof the Pancreas
This operative procedure was described by Whipple et a!.
(66) in 1935 for the surgical treatment of carcinoma of the
Carcinoma of the pancreas is increasing and now ranks
ampulla of Vater. During the early years of its application,
4th as the most common cause of death by cancer in males,
operative mortality was extremely high (10) but has appreci
exceeded only by lung, large bowel, and prostate cancer.
ably decreased with experience and improved support tech
The American Cancer Society estimated that in 1976 cancer
niques and antibiotics. Other carcinomas of the periampul
of the pancreas would cause 20,000 deaths in the United
lary region that are amenable to treatment by this operation
States with an estimated 23,000 new cases that would be include those of the distal common bile duct and duo
diagnosed (1).
denum. Some surgeons utilize it for carcinoma of the head
of the pancreas. In the usual operative procedure the distal
portion of the stomach is removed; the pancreas is tran
Site of Carcinoma,Incidence,and Prognosis
sected (usually at its neck but varying amounts may be
removed or even the entire organ), and the duodenum and a
The common bile duct lies behind the head of the pan
few
inches of jejunum distal to the ligament of Treitz are
creas, which it grooves, and frequently joins the main pan
resected.
The entire specimen is removed by division of the
creatic duct (duct of Wirsung) at the ampulla of Vater in the
duodenum. Hence, this area has been termed “periampul common bile duct. A cholecystectomy is usually performed,
lary.―The manifestations of carcinoma of the head of the and some surgeons perform a vagotomy. Various methods
of reconstruction are possible. The extent of resection is
pancreas and other malignant tumors of the periampullary
indicated in Chart 1A; 1 type of reconstitution (retrocolic
areas are so frequently undistinguishable that most writings
on the subject consider these neoplasms together. The method) is shown in Chart lB.
Three options are available to the surgeon in dealing with
relative frequency of periampullary neoplasms in 4 series is
the
pancreatic stump: (a) inversion of the transected end of
given in Table 1. There are 2 important aspects to this
the
pancreas
into the jejunal lumen; (b) suturing the cut end
distribution; the resectability rate by pancreatoduodenec
of the duct of Wirsung to the jejunal mucosa; and (C) liga
tomy for carcinoma of the ampulla of Vater is at least sever
tion of the pancreatic duct with oversewing of the tran
sected pancreas (Chart 2). There appear to be major differ
bar 29 to December 1, 1976, Key Biscayne, Fla.
ences of opinion among surgeons on the value of perform
I
Present
at
the
Conference
on
Nutrition
and
Cancer
Therapy,
Novam
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2387
M. E. Shils
Table 1
of Periampullary
Frequency
patientsRef.
Cancers
of
Site%
35Ref.
37Ref.
47Ref.
65Pancreas83505038Ampulla10273237Duodenum471015Bileduct316810No.
of patients15944239253
plications2 (10). Brunschwig (6) opposed anastomosis on
the grounds that ligation of the pancreatic duct was simpler
and that continued patency was highly unlikely with anasto
mosis. In a retrospective comparison, Goldsmith et a!. (28)
found no difference in postoperative morbidity and mortal
ity or in histological appearance of the remnant at postmor
tem examination in patients who had the pancreatic duct
reimplanted at pancreatoduodenectomy and those who had
the duct ligated and the cut end of the pancreas closed
(Table 2). The decision as to the treatment of the pancreatic
stump has nutritional implications, since ligation of the
pancreatic duct with oversewing of the transected end of
the pancreas will lead to complete pancreatic insufficiency
in all instances.
The postoperative complication rate in this procedure is
high, reaching 50% or more in various published series. The
result is prolonged hospitalization with a number of the
problems interfering with normal food intake. Table 2 lists
the incidence in 4 series of those complications which
could be expected to affectnutritional
status.Gastrointes
tinal hemorrhage was often secondary to erosion caused by
pancreatic fistulas.
A
B
Chart 1. A, pancreatoduodenectomy. Lines of section of stomach, pan
creas, duodenum, and common bile duct are shown; a vagotomy and chole
cystectomy are indicated . B , anastomoses after resection and reconstruction
using an antecolic loop of jejunum. The head of the pancreas has been
removed, and its stump and duct have been closed [taken from Powis and
Young (53)].
A
B
PancreaticInsufficiency
The problem of exocrine enzyme insufficiency following
pancreatoduodenectomy has been examined. Wollaeger et
al. (69) studied 10 patients who had a number of variants in
their surgical reanastomosis. In 8 patients with pancreatic
duct reanastomosis observed 3 weeks to 1 year after sur
gery, fat and nitrogen losses varied from normal to high.
Fish et a!. (20) studied the absorption of 6 patients surviving
20 to 84 months postpancreatoduodenectomy in whom the
pancreatic stump was invaginated into the end of the je
junum. When no pancreatic extract was ingested, 3 patients
had marked fat malabsorption (17 to 30%); this improved
completely in 2 patients with pancreatic extract and partially
in 1. Fecal nitrogen was increased in 3 patients and im
Table 2
Postoperativecomplications of paricreatoduodenectomyfor
malignantdisease%of
patientsRef.Ref.Ref.Ref.Ref.Ref.Complications473156°56b28C28dHemorrhage823281599Pan
fistula9142227Biliary
Chart 2. Pancreatoduodenectomy. Diagrammatic representation of 4
methods used in the management of the pancreas. A, anastomosis of the
pancreatic duct to the mucosa of the jejunum; B, inversion of the cut end of
the pancreas into the jejunum; C, ligation of the pancreatic duct with over
sewing of the transected end of the pancreas; D , total pancreatectomy [taken
from Aston and Longmire (3)].
ing pancreatic duct anastomosis. The basis for the contro
versy is related to the high incidence of postoperative pan
creatic fistula, particularly in earlier experience, with its
high morbidity and mortality (47, 59). Some have empha
sized the importance of anastomosing the pancreatic duct
to the intestinal tract to decrease this and associated com
2388
fistula784Peritonitis
519111318scessWound
and/or ab
infection914331149Ileus
obstruction353773Intestinal
or
fistula0.4364No.
patients2396836274534No.
of
with122362700total
of patients
pancreatec
tomy
a From
1942
to
1968.
b From
1969
to
1972.
C Pancreatic
duct
ligated.
d Pancreatic
duct
anastomosed.
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Surgery of Liver, Pancreas, and Genitourinary Tract
proved with enzyme therapy. Two of 4 patients with periam
pullary carcinoma had marked steatorrhea following pan
creatoduodenectomy, with the pancreatic remnant anasto
mosed to the stomach (12). Even for those undergoing
resection for cancer of the ampulla, pancreatic exocrine
insufficiency occurred in 27.7% (47). Following implanta
tion of a portion of distal pancreas into the duodenum of
dogs, the pancreatic remnant at sacrifice was found to be
atrophied with dilation of the pancreatic duct and obstruc
tion of the orifice in the duodenum (20). Others have also
found atrophy and fibrosis of exocrine tissue after auto
transplantation of the canine pancreas to the neck with an
external fistula (16). Warren2 has emphasized that anasto
mosis of the duct to jejunal mucosa had a much greater
likelihood of maintaining a patent duct. Nevertheless, with
this technique he has reported that 22% of his patients
developed evidence of pancreatic exocrine insufficiency
(65). Aston and Longmire (3) found that 7 of 28 patients had
pancreatic insufficiency and 2 of these had had duct to
mucosa anastomosis.
The probability of pancreatic enzyme deficiency should
be considered and checked in any patient with pancreato
duodenectomy even with ductal reanastomosis. Pancreatic
exocrine insufficiency leads to the loss of calories in the
stool and to a deficiency of absorption of important nutri
ents such as amino acids, calcium, magnesium, and fat
soluble vitamins. Effective replacement necessitates the
choice of an effective pancreatic extract and its use in
adequate amounts. Although there are a number of prod
ucts marketed for use as enzyme replacement therapy,
there is relatively little quantitative information on their ac
tual enzyme activities and comparisons of clinical effective
ness. There have been a number of clinical reports of in
creased fat absorption with commercial pancreatic extracts
in patients following pancreatectomy (38, 53). Commercial
extracts showed considerable differences in lipase activity
when tested in vitro, with best results being obtained with
Cotazym, Lipan, Panteric granules, and Viokase. It has
been estimated that complete replacement of the pan
creatic lipase secreted in 1 day by a normal man would
require approximately 34 g of a high-potency preparation
(27). Giulian et a!. (26) and Pairent et al. (53) have tested
various commercial pancreatic supplements for their effec
tiveness in improving fat absorption in dogs with the pan
creatic duct ligated. Again, there was a considerable differ
ence in effectiveness among such preparations with varia
tions also depending on the method of measuring fat ab
sorption. When fat absorption from regular test meals was
measured, Progestive, Convertin, Viokase, Cotazym, and
Panteric were among the better preparations. However, in
the doses administered (6 tablets or capsules per day), none
were capable of returning fat absorption to normal (53).
We have found some patients to be intolerant of certain
preparations and tolerant of others. In a few instances it has
been necessary to use enteric coated preparations to avoid
nausea and abdominal distress.
The amounts of pancreatic extract recommended for
treatment of such patients has varied from a minimum of 1.2
g2 up to 2.5 to 5.0 g (20, 38) per meal. Others have recom
mended administration of 8 g divided into 12 hourly doses
(36). Others have found no benefit of hourly dosage when
the amounts given with meals were adequate (38). It has
been suggested that, if a fully satisfactory result is not
achieved with Viokase or Cotazym in doses of 2 to 3 g with
each meal, the same daily dose should be given on an
hourly basis. Where gastric secretion is normal, concomi
tant administration of sodium bicarbonate may improve
digestion. Since the surgical procedures for pancreatic car
cinoma usually involve major gastric resection, bicarbonate
administration does not appear indicated.
Diabetes
Another aspect of this procedure concerns the endocrine
function of the remnant of pancreas. Decreased glucose
tolerance has been noted in 10 pancreatoduodenectomized
patients (5 to 39 months, post operative) in whom fasting
blood sugar levels were within normal limits (12, 20). Miyata
et a!. (45) have investigated
this matter
in more detail
in
pancreatoduodenectomized patients in whom at least the
caudal half of the pancreas was preserved; the control
group was composed of 12 gastrectomized patients with a
Billroth II anastomosis. Fasting levels of glucose, nonesteri
fied fatty acids, and immunoreactive insulin were within'
normal limits; however, following glucose ingestion the
blood sugar levels were appreciably higher than those of
gastrectomized and normal individuals. The immunoreac
tive insulin levels in the pancreatoduodenectomized
pa
tients were appreciably less than those of gastrectomized
patients and only slightly higher than those of normal mdi
viduals at 30 and 60 mm. Hence, insufficient insulin re
sponse from the remnant of the pancreas appears to be a
major cause of glucose intolerance in these cancer pa
tients. This problem is complicated by the fact that approxi
mately 10 to 12% of patients presenting with carcinoma of
the pancreas are overtly diabetic (5, 28, 31) and 10 to 35%
(depending on the site of the tumor) have asymptomatic
glycosuria or hyperglycemia (65).
The effect of pancreatic duct ligation in dogs on endo
crine function was studied for approximately 7 months. One
of the 16 dogs became continuously diabetic, although the
others maintained normal blood sugars; but 9 had latent
diabetes with intermittent hyperglycemic levels and abnor
mal glucose tolerance curves (34). Four of 5 dogs with
ligation with subsequent acinar tissue atrophy were found
by Pairent et a!. (53) to have diabetic glucose tolerance
curves. Others have found the ligated pancreas in dogs to
retain adequate endocrine function for prolonged periods
(40). Canine pancreas autotransplanted to the neck and
with free flow of secretion became atrophic and fibrotic
(16).
The question has been raised as to the role of preexisting
pancreatic pathology in the remnant of pancreas in contrib
uting to pancreatic insufficiency (exocrine and endocrine)
following pancreatoduodenectomy in patients with carci
noma or pancreatitis. This has been studied in patients in
whom such surgery had been performed following acute
trauma and in whom residual pancreas was normal. Eight
een to 24 months after the pancreatic remnant was sutured
to the intestine, there was only mild elevation of fecal fat
above normal, and jejunal lipase concentration following a
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2389
M. E. Shils
test meal was normal; there was no clinical diabetes or need
for insulin (57). In the 1 patient tested, serum insulin with
and without glucose load was within normal limits. It was
suggested that pancreatic insufficiency in patients with car
cinoma or pancreatitis following partial resection is related
to pathology in the remnant.
Total Pancreatectomy and Regional Pancreatectomy
stomach, duodenum, spleen, gallbladder, and common bile
duct with skeletonizing of portal vein and hepatic artery. In
type 2 there is the additional resection of the celiac axis and
hepatic and/or superior mesenteric arteries. In individual
patients gastrectomy may be total or subtotal, and varying
amounts of colon and jejunum are removed as indicated
(23, 24). Of 18 patients undergoing 1 of the procedures, 16
had been explored and deemed unresectable elsewhere.
There were 3 postoperative deaths; 6 patients were alive at 1
year (24).
The low 5-year survival rate of patients with carcinoma of
the head of the pancreas (approximately 15%) has resulted
in increasing advocacy of total pancreatectomy. This has
been recommended because it eliminates the danger of
pancreatic fistula without significantly increasing the surgi
cal risk and because it eliminates the possibility of failure to
remove carcinoma existing more distally either because of
spread or multifocal tumor (5, 9, 15, 56).
Total pancreatectomy poses a difficult metabolic situa
tion with its resultant exocrine and endocrine insufficiency.
Even with the optimum use of pancreatic extract, there
tends to be increased loss of fat and nitrogen in stool. The
usual diabetic-type diet with its increased protein and fat
tends to exacerbate malabsorption and diarrhea. Replacing
dietary fat with glucose to decrease steatorrhea increases
the requirement for insulin. In a series of 48 totally pancrea
tectomized patients followed with respect to their control of
diabetes, Pliam et a!. (54) found that 50% were easily man
aged, 8% were managed with difficulty only when there was
concomitant illness, 18% had occasional hypoglycemic re
actions managed with carbohydrate p.o. , 4% did poorly
with persistent glycosuria, and 20% were found to be very
difficult with ketoacidosis or hyperglycemic episodes re
quiring hospitalization.
Following pancreatectomy in dogs, plasma glucagon i@
present and may increase when insulin is not given (42).
Following total pancreatectomy in a man, plasma (pan
creatic) glucagon disappeared within 30 mm after resection
but was present again after 18 hr and disappeared after 9
days. After an initial decrease, plasma glucagon-like immu
noreactive substance(s) (measured by an antiserum that
cross-reacts with glucagon-like products from small bowel
mucosa) rose abruptly on the 2nd postoperative day and
remained elevated thereafter (46).
Because pancreatic tumors often extend beyond the pan
creas at the time of exploration, resectability rate is low and
survival is much lower despite total pancreatectomy. This is
emphasized in the recent review of 101 cases of ductal
carcinoma of the pancreas by Brooks and Culebras (5) who
reported that 21 .8% were deemed inoperable because of
metastases or poor condition of the patient, 24.8% had only
a biopsy of the tumor at laparotomy, and 34.6% had some
sort of palliative bypass, leaving only 18.8% who had sur
gery performed with intention of cure. Survival of the latter
group was poor. More radical surgery termed regional pan
createctomy has been developed by Fortner (21) in an effort
to remove en bloc the pancreas, adjacent tissue, and nodes
along the primary lymph drainage. In the type 1 procedure
there is total removal of the pancreas, pancreatic segment
of portal vein, transverse mesocolon with middle colic yes
sels, surrounding soft tissues, regional lymph nodes, distal
2390
In this complex and radical surgery a number of postoper
ative complications with nutritional significance have oc
curred. There were 6 patients with either gastrojejunal or
colonic fistulas; 8 patients had significant infections, and
many had prolonged postoperative recovery. Adequate nu
tritional support has played a major role in permitting recov
ery of many of these individuals. Because of infection,
fistulas, anorexia, diarrhea, and malabsorption, usually in
combination, prolonged total parenteral nutrition was used
in maintaining a number of these patients and proved to be
lifesaving. Because Intralipid has not been readily available,
we have relied upon high-glucose infusions as the major
source of calories, with insulin added to the total parenteral
nutrition solutions initially at 1 unit of regular insulin for
every 100 carbohydrate calories. Fractional coverage with
regular insulin is given for glycosuria. The i.v insulin is then
adjusted upward or downward as indicated.
A xylose tolerance test has been performed preopera
tively and postoperatively in a number of patients, in some
cases with serial follow-up. Almost all of these patients have
had depressed xylose absorption postoperatively; absorp
tion returned to normal after a period of 4 to 9 months.
Weight loss associated with depressed appetite and malab
sorption has been significant; surviving patients are ap
proximately 30% below their preoperative weight. Watery
diarrhea has been frequent and has been associated with
magnesium depletion and acidosis in some patients. The
reason for this diarrhea and malabsorption of xylose is not
clear but may be related variably to a number of factors
including gastrectomy and duodenectomy, denervation and
severance of lymphatics, small bowel resection in some
instances, and bacterial overgrowth of small bowel. Five of
6 bowel fistulas closed spontaneously with total parenteral
nutrition. Home total parenteral nutrition (58) permitted sur
vival in 1 patient during a prolonged critical period of mal
absorption. With cessation of parenteral support, anorexia,
diabetes mellitus, pancreatic insufficiency, and other types
of malabsorption continue to present serious nutritional
problems to the radically pancreatectomized patient. There
must be administration of adequate amounts of pancreatic
extracts with all meals and snacks. Good control of the
diabetes maximizes carbohydrate utilization and minimizes
fluid and sodium losses secondary to osmotic diuresis
caused by glycosuria. Medium-chain triglycerides are neu
tral fats the fatty acids of which are primarily of the C8 and
C,0type; these are more efficiently absorbed in the absence
of pancreatic enzymes than are the usual long-chain fats.
They are also absorbed more efficiently when there is an
insufficiency of conjugated bile salts or when there are
impaired absorptive mechanisms (32). Glucose oligosac
charides may also be helpful in increasing the caloric intake
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Surgery of Liver, Pancreas, and Genitourinary Tract
and absorption in pancreatically insufficient patients, since
these relatively short-chain glucose polymers can be hydro
lyzed to glucose by the brush-border enzyme Sucrase-a
dextrinase (30). This white powdery material is not sweet
and may be used in a variety of ways to supplement intake.
There may be reduction in vitamin B,2 absorption in ap
proximately 40 to 50% of patients with chronic pancreatic
insufficiency (64). Malabsorption of this vitamin has been
observed in patients with total pancreatectomy (48). In
these subjects the B12absorption is improved by administra
tion of pancreatic extract.
Liver Resection
Until the early 1950's removal of liver tissue was usually
limited to wedge or guillotine type of resection with rela
tively minor losses in terms of function. With a description
of a controlled technique for resection of the right lobe of
the liver (39), major hepatic resection became frequent. It is
not surprising that some of the earliest efforts thereafter
involved resection of cancer (49-52). Advances in anesthe
sia and operative techniques, blood replacement, antibiot
ics, and understanding of metabolic derangements caused
by massive liver resection have appreciably decreased mor
bidity and mortality. The surgeon is now greatly aided by
preoperative information for more precise localization of
the tumor provided by computerized transaxial tomography
and selective hepatic arteriography. Arteriography also pro
vides valuable information on the pattern of hepatic artery
branches to aid in their dissection.
Recurrence of cancer after transplantation has been high.
Starzl (62) recommended that patients with primary hepa
toma should not be treated by transplantation. Williams et
a!. (68) reported 1 patient of 6 with primary hepatomas living
3 years; 2 patients who had transplantation for metastatic
disease and 4 of 5 patients having transplantation for carci
noma of the hepatic duct were found to have tumor at
autopsy.
PreoperativeNutritionalCare
Many patients with primary or secondary liver involve
ment are undernourished; there may also be a history of
alcoholism and the oombination may result in extensive
fatty infiltration. This state imposes increased surgical risk
in terms of normal metabolic response to surgical stress
and increases mortality. McDermott and Ackroyd (43) have
stressed the importance of delaying surgery if possible until
some degree of nutritional repletion can be accomplished
in malnourished patients. The mode of nutritional rehabili
tation may involve p.o. , tube, or parenteral feedings, with
the route and the nutrient composition depending upon the
clinical situation.
PostoperativeCare
Normal liver tissue is endowed with a tremendous capac
ity for regeneration. Nevertheless, after major hepatic re
section the early biochemical and metabolic changes that
Major resectionfor cancers has been performed forthe can occur can be serious and life-threatening. Appropriate
most part in 5 situations: primary malignant liver tumors in steps are necessary to manage these changes to permit
recovery and rapid regeneration . McDermott et al. (44) have
adults; primary malignant liver tumors in infants and chil
dren; cancer metastatic to liver from other sites; to permit reported a significant drop in blood sugar following resec
en bloc excision of cancer of adjacent organs in stomach tions of 70% or more, and severe hypoglycemia has been
noted in patients following total hepatectomy and liver
and colon; and to palliate the malignant carcinoid syn
drome. Up to 90% of the liver may be resected with survival transplantation. Other groups have not observed such
of the patient. Total hepatectomy and orthotopic liver trans
marked blood sugar changes following resection, perhaps
plantation is possible in those patients who have extensive because of routine use of glucose postoperatively (2, 52). In
primary cancer of the liver, gallbladder, and bile ducts or any case, it seems wise to obviate this danger by monitoring
metastatic colon cancer confined to the liver. In addition,
blood sugar and infusing 10% glucose solution i.v. continu
resections are done for nonmalignant tumors such as be ously for at least the 1st several days or until adequate p.o.
nign hepatomas, cholangiomas, hamartomas, angiomas,
intake of carbohydrates is assured. Often following p.o.
teratomas,and cysts.
carbohydrate, blood sugar may be elevated for several
The natural history of primary malignant liver tumors in weeks. Since the liver is the site of albumin synthesis, it is
adults is such that almost all die with 3 to 7 months follow
not surprising that hypoalbuminemia will occur to a sign ifi
ing onset of symptoms. It is rare that a patient survives more cant degree unless replaced by parenteral administration.
than 1 year. Foster's review (25) indicates that following
Failure to do so can lead to progressive fall in osmotic
resection there is a survival rate of 36% in non-Asian adults pressure in the vascular compartment and accumulation of
with hepatoma; this excludes operative death in 22%. Pre marked interstitial fluid with increased vascular load and
sumably, this survival rate should increase with more effec
the danger of pulmonary edema. The need for supplemen
tive chemotherapy. Hepatoma in infants and children is less tary albumin persists for approximately 1 week. The
likely to metastasize early than is the adult variety (25). amounts of albumin given have usually averaged 25 g/day
Operative death rate in this age group is 23% with a survival for the 1st 5 days or so (22, 44, 52). By the end of the 3rd
of other patients for more than 5 years of 33.3%; a sign ifi
postoperative week, nearly normal albumin levels are usu
cant number of other patients were alive and free of disease ally found.
at less than 5 years. Resection of metastases remains a
Preoperatively, some patients [20% in the series of Pack
controversial subject, but the data reviewed by Foster give and Molander (52)] may have elevated serum prothrombin
encouragement for removal of localized and solitary meta
time, which is corrected by preoperative administration of
staticdisease of the liver.
vitamin K, oxide i.m. Fibrinogen, prothrombin, and other
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2391
M. E. Shils
coagulation factors (V, VII, IX, X) that are synthesized by the
liver will fall following major resection (22, 44, 52). Despite
the postoperative administration of vitamin K, prothrombin
levels remained depressed in the postoperative phase; such
depression is not reflected in any clinical disorder. These
factors gradually return to normal as hepatic regeneration
HepaticRegeneration
Massive hepatic resection in man brings into focus the
question of rate of regeneration and the factors affecting
that rate. The remarkable ability of the liver in experimental
animals to replace lost tissues rapidly and completely by
progresses.
compensatory cellular hypertrophy and hyperplasia has
After subtotal hepatectomy there is a rapid fall in serum long been recognized and also occurs in man. The morpho
triglycerides. This is expected since the liver is the major logical and biochemical sequence of events during regener
source of serum triglycerides and since peripheral tissues ation in laboratory animals (primarily the rat) have been
are continuously removing circulating fat. As serum triglyc
reviewed together with consideration of regulatory mecha
erides fall there is a rapid rise in levels of nonesterified fatty nisms (7, 33). Almost immediately after extirpation of ap
acids,thatreflects
an increasedmobilizationof fattyacids proximately two-thirds of the liver, a series of morphologi
from adipose tissue (44). As hepatic regeneration proceeds cal changes appear; by as early as 6 hr postoperatively,
there is progressive rise of the triglycerides and a fall in there is increased capacity to synthesize protein. These
nonesterified fatty acids over the 1st several weeks. De changes culminate in an outburst of mitotic division in
creased total serum calcium reflects a fall in serum albumin.
parenchymal cells at 24 to 30 hr. The rat liver returns
Transient low serum sodium and potassium have been re roughly on an exponential course to approximately normal
ported in some patients after liver resection (2), while others size in 10 to 20 days. In his review Harkness (33) has pointed
have reported low levels of serum inorganic phosphates out that considerable variations in diet have little effect on
following clinical hepatic resection and hepatic transplanta
the initial process of regeneration that may take place even
tion (22, 23). Hypophosphatemia in dogs following partial on a protein-free
dietinthe rat.The increasein number of
hepatectomy is associated with increased hepatic uptake parenchymal cell nuclei is practically the same in starved as
and diminished urinary excretion of phosphate (22).
in fed animals, although the increase in weight of the liver is
Evidence of liver decompensation has been observed in markedly less.
cases of extended right hepatic lobectomy (52). In such
Observations in man are relatively limited. Packetal. (50,
instances reduction of protein intake and initiation of a 51) had opportunitiesfor direct visualizationof liver of
medical regimen for hepatic precoma are indicated. These patients after major hepatic resection. In 1 patient there was
disturbances disappear in a short period. At this time it is an estimated 50% increase in liver size in 1 week following
important to provide sufficient intake of protein and other resection; another patient had complete regeneration in 5
nutrients to permit optimum liver regeneration. When he months. McDermott et a!. (44) have followed liver regenera
patic dysfunction persists following resection or liver trans
tion by ‘31-Iabeled
rose bengal following major hepatic re
plantation, and especially when this is associated with por
section, and their data also indicate that there is restoration
tal vein shunting, the i.v. amino acid regimen developed by of normal liver mass within 6 months.
Fischer et a!. (19) may be useful. The rationale for this
The question of the specificity and nature of “regenera
therapy has been reviewed by Soeters and Fischer (60). tive stimulus― or the hepatotrophic substance or sub
They postulate that, in catabolic states such as liver failure stances has been of continuing interest and appears to be
and associated conditions such as sepsis, catecholamine gaining momentum. One stimulus to this subject has been
discharge is associated with marked increases in glucagon the observation that Eck-fistula dogs develop not only he
secretion and a decreased insulin:glucagon ratio. The re patic encephalopathy but also liver atrophy. Recent interest
suit is a release of large amounts of amino acids from has centered on the probability that such a factor or factors
protein sources; the aromatic amino acids cannot be catab derive from pancreas or other viscera and enter the liver via
olized by the failing liver and accumulate in the circulation.
the portal blood and on the role of pancreatic hormones.
Decreased plasma branch-chain amino acids together with Rats made alloxan diabetic had a marked proliferative re
the increased aromatic amino acids allow toxic aromatic sponse of their livers to insulin administration, although
amino acids to penetrate the blood-brain barrier in in there was some regeneration after hepatic resection even if
insulin treatment was withheld, suggesting that more than
creased amounts and encephalopathy develops. The nutri
ent formulation is designed to reverse the catabolic state by insulin was involved (70). Bucher and Swaffield (8) reported
providing sufficient calories and other nutrients and to re that insulin and glucagon together stimulated hepatic re
verse encephalopathy by increasing branch-chain amino generation in rats. Further support for the concept that
acid concentration while decreasing aromatic amino acid glucagon and insulin are needed to produce maximal re
concentration in order to restore the normal plasma molar sponse to partial hepatectomy in rats has been advanced
ratio of branch-chain amino acids to aromatic amino acids (67). Starzl et a!. (63) found that infusion of insulin, but not
and to reverse the amino acid losses from muscle and liver. of glucagon or of insulin and glucagon mixtures infused
The administration of the keto analogs of 5 essential amino into the left portal vein of dogs following portal cava shunt,
acids (valine, leucine, isoleucine, methionine, and phenyl reduced atrophy, preserved hepatocyte structure, and tre
bled cell renewal. Since the insulin protection in this study
alanine) and 5 amino acids (histidine, threonine, trypto
phan, lysine, and arginine) i.v. or p.o. has been reported to was not quite complete, there may be missing ancillary
improve portal-systemic encephalopathy in 8 of 11 patients substances. Contradictory data have been advanced in sug
gesting that insulin is not a critical factor in regeneration in
(41).
2392
CANCER
RESEARCH
VOL. 37
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Surgery of Liver, Pancreas, and Genitourinary Tract
rabbits (11) or dogs (17). Regardless ofthe origin or nature
of the hepatotrophic factor(s), it would appear that optimal
regeneration rates of the liver require adequate nutritional
support during the hypertrophic stage.
Urinary Diversion for Pelvic Cancer
Urinary diversion is required for pelvic malignant tumors
that necessitate cystectomy. The simplest methods of un
nary diversion are nephrostomy, which involves simply in
serting a tube through the skin into the pelvis of the kidney,
or a cutaneous ureterostomy,inwhich 1 or both uretensare
brought to the skin. Serious problems of infection and
patient comfort led Coffey in 1911 (14) to publish a descnip
tion of an implantation of ureters into the sigmoid colon
(ureterosigmoidostomy). A high incidence of obstruction of
the ureters following implantation with resultant hydrone
phrosis led to a variety of modifications for ureteral implan
tation. In addition, there was frequent pyelonephnitis
caused by ascending infection from continual fecal contam
ination. Metabolic problems also occurred. In a large series
Ferris and Odel (18) found that 79% of their patients had
some degree of hyperchloremia and 80% were acidotic at
varying intervals following ureterosigmoidostomy. A clinical
syndrome was associated with the acidosis consisting of
thirst, anorexia, vomiting, fatigue, and malaise, and in chil
dren a failure to grow and vitamin-resistant rickets were
noted. In addition to the hyperchloremic acidosis, hypo
phosphatemia and hypokalemia developed. Prior to discov
ery of the relation of this syndrome to potassium homeosta
sis, the accepted treatment for this syndrome was a low-salt
diet with added sodium bicarbonate (18). A number of urol
ogists felt initially that the primary problem related to the
development of pyelonephnitis with renal dysfunction. How
ever, it became increasingly apparent that the metabolic
basis for the syndrome was the result of absorption in the
colon of significant amounts of sodium and chloride from
the urine with resultant osmotic diuresis and potassium loss
(61). Local secretion of potassium by the colon was another
source of ionic loss. Metabolic acidosis markedly increases
aldosterone secretion, and this plays a role in potassium
wastage. Potassium depletion intensifies acidosis because
of decreased urinary bicarbonate reabsorption. Because of
the inherent metabolic problems of ureterosigmoidostomy,
this procedure has essentially been abandoned. However,
there are still patients who had this procedure done some
years ago who continue to have the metabolic problems.
Ureterosigmoidostomy was replaced by a cutaneous ure
teroileostomy (ileal conduit) (4). In this surgical procedure a
segment of ileum approximately 20 cm long is resected with
its blood supply; the continuity of the ileum is restored, the
uretens are sutured to the ileal mucosa, the proximal end of
the segment is closed, and the distal end is brought to the
abdominal opening. When the resection has healed, the
urine is collected in the bag. There is some reabsorption of
urea and other urine constituents by the ileum. However,
the relatively short segment of ileum with runoff into the
bag minimizes metabolic problems as compared to the
ureterosigmoidostomy. In addition, this procedure has the
advantage of separating the urine contents from intestinal
contents with resultant decreased retrograde kidney infec
tion. It has been found that in approximately 2 years the
villi of the mucosa of the segment are lost (29).
Approximately 10 years ago there was a short-lived inter
est in using a jejunal segment instead of an ileal segment for
bladder formation. However, clinical experience soon dem
onstrated that metabolic problems occurred with this ap
proach. These changes were the opposite of those occur
ring with ureterosigmoidostomy. Hyponatremia, hypochlo
remia, and hyperkalemia occurred because of loss of so
dium and chloride in excess of water into the jejunal blad
den and reabsorption of potassium; azotemia developed
secondarily to hypovolemia and impaired glomerular filtra
tion (13). Clinically, the patients developed anorexia, nau
sea, vomiting, abdominal cnamping, personality and neuro
logical changes, and weakness. As a result of these findings
the use of jejunal loop was abandoned and is used only for
patients in whom no other bowel loop is available.
Since treatment of bladder cancer with resultant total
cystectomy also includes pelvic radiation therapy, some
patients may have significant bowel damage and delayed
postoperative recovery. Weight loss is not uncommon. As a
result of these complications and poor food intake, nutni
tional support in the presence of these complications is
often beneficial in maintaining the patient during a critical
period.
References
1. American Cancer Society. Cancer Facts and Figures ‘76,
pp. 10-11 . New
York: American Cancer Society, 1975.
2. Aronsen, K. F., Ericsson, B., and Pihi, B. Metabolic Changes following
Major Hepatic Resection. Ann. Surg., 169: 102-110, 1969.
3. Aston, S. J., and Longmire, W. P., Jr. Management of the Pancreas after
Pancreatoduodenectomy. Ann. Surg., 179: 322-327, 1974.
4. Bricker, E. M. Bladder Substitution After Pelvic Evisceration Surg. Clin.
North Am. 30: 1511-1521, 1950.
5. Brooks, J. R., and Culebras, J. M. Cancer of the Pancreas: Palliative
Operation, Whipple Procedure or Total Pancreatectomy? Am. J. Surg.,
131: 516-520, 1976.
6. Brunschwig, A. A Report Upon a Technique for Pancreatoduodenec
tomy. Surg. Gynecol. Obstet., 118: 263-264, 1964.
7. Bucher, N. L. R. Regeneration of Mammalian Liver. Intern. Rev. Cytol.,
15: 245-300, 1963.
8. Bucher, N. L. R., and Swaffield, M. N. Regulation of Hepatic Regenera
tion in Rats by Synergistic Action of Insulin and Glucagon. Proc. NatI.
Acad. Sci. U.S., 72: 1157-1160, 1975.
9. Castellanos, J. , Manifacio, G., Lillehei, R. C. , and Shatney, C. H. Total
Pancreatectomy for Ductal Carcinoma of the Head of the Pancreas:
Current Status. Am. J. Surg., 131: 595-598, 1976.
10. Cattell, R. B., and Warren, K. W. Surgery of the Pancreas, pp. 267-268,
327-328. Philadelphia: W. B. Saunders Co., 1953.
11 . Chandler, J. G. Hepatotrophic Activity in NonPancreatic
Nonduodenal
Portal Blood. Surg. Forum, 27: 360-363, 1976.
12. Christiansen, J. , Olsen, J. H., and Worming, H. The Pancreatic Function
following Subtotal Pancreatectomy for Cancer. Scand. J. Gastroenterol.
Suppl., 9: 189-193, 1971.
13. Clark, 5. 5. Electrolyte Disturbances Associated With Jejunal Conduit. J.
Urol.,112: 42-47, 1974.
14. Coffey, A. C. Physiologic Implantation of the Severed Ureter or Common
Bile-Duct into the Intestine. J. Am. Med. Assoc., 56: 397-403, 1911.
15. Collins, J. J., Craighead, J. E., and Brooks, J. R. Rationale for Total
Pancreatectomy for Carcinoma of the Pancreatic Head. New EngI. J.
Med.,274:599-602,1966.
16. Dreiling, D. A. , and Ashikari, H. Physiologic Studies of the Heterotopic
Autotransplanted
Pancreas. Surg. Forum, 17: 203-205,
1966.
17. Duguay, L. R., and Orloff, M. J. Regulation of Liver Regeneration by the
Pancreas in Dogs. Surg. Forum, 27: 355-360, 1976.
18. Ferris, D. 0., and Odd, H. M. Electrolyte Pattern of the Blood after
Bilateral Ureterosigmoidostomy.
1950.
J. Am. Med. Assoc., 142: 634-641,
JULY 1977
Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1977 American Association for Cancer Research.
2393
M. E. Shils
19. Fischer,J. E., Rosen, H. M., Ebeid,A. M.,James,J. H.,Keane,J. M.,and
Soeters, P. B. The Eftect of Normalization of Plasma Amino Acids on
Hepatic Encephalopathy in Man. Surgery, 80, 77-91 , 1976.
20. Fish, J. C. , Smith, L. B. , and Williams, A. D. Digestive Function after
Radical Pancreatoduodenectomy. Am. J. Surg., 117: 40—45,
1969.
21. Fortner, J. G. Regional Resection of Cancer of the Pancreas: A New
Surgical Approach. Surgery, 73: 307-320, 1973.
22. Fortner, J. G., Beattie, E. J., Jr., Shiu, M., Howland, W. S., Watson, R.
C., Gaston, J. P., and Benua, R. S. Surgery in Liver Tumors. In: M. M.
Ravitch, 0. C. Julian, H. W. Scott, Jr., A. P. ThaI, 0. H. Wangensteen,
and F. M. Steichen (ads.), Current Problems in Surgery. Chicago: Year
Book Medical Publishers, 1972.
23. Fortner, J. G., Beattie, E. J., Jr., Shiu, M. H., Kawano, N., and Howland,
W. S. Orthotopic and Heterotopic Liver Homografts in Man. Ann. Surg.,
172: 23—32,
1970.
24. Fortner, J. G., Kim, P. K., Cubilla, A. , Turnbull, A. , Pahnke, L. D., and
Shils, M. E. Regional Pancreatectomy (En Bloc Pancreatic, Portal Vein,
and Lymph Node Resection). Ann. Surg., in press.
25. Foster, J. H. Survival after Liver Resection for Cancer. Cancer, 26: 493—
502, 1970.
26. Giulian, B. B., Mitsuoka, J., Mansfield, A. 0., Trapnell, J. E., Seddon, J.
A. , and Howard, J. M. Treatment of Pancreatic Exocrine Insufficiency. II.
Effects on Fat Absorption of Pancreatic Lipase and Fifteen Commercial
Pancreatic Supplements as Measured by l's' Tagged Triolein in the Dog.
Ann. Surg., 165: 571-579, 1967.
27. Giulian, B. B., Single, L. M., Mansfield, A. 0., Pairent, F. W., and
Howard, J. M. Treatment of Pancreatic Exocrine Insufficiency. I. In Vitro
Lipolytic Activities of Pancreatic Lipase and Fifteen Commercial Pan
creatic Supplements. Ann. Surg., 165: 564-570, 1967.
28. Goldsmith, H. 5. , Ghosh, B. C. , and Huvos, A. G. Ligation versus Implan
tation of the Pancreatic Duct after Pancreaticoduodenectomy. Surg.
Gynecol. Obstet., 132: 87-92, 1971.
29. Goldstein, M. J., Melamed, M. R., Grabstald, H., and Sherlock, P. Pro
gressive Villous Atrophy of the Ileum Used as a Urinary Conduit. Gastro
enterology, 52: 859-864, 1967.
30. Gray, G. M. Carbohydrate Digestion and Absorption. New Engl. J. Med.,
292: 1225-1230, 1975.
31. Gray, L. W., Jr., Crook, J. N., and Cohn, J., Jr. Carcinoma of the
Pancreas. In: Seventh National Cancer Conference, pp. 503-510. Phila
delphia: J. B. Lippincott Co., 1973.
32. Greenberger. N. J., and Skillman, T. G. Medium-Chain Triglycerides:
Physiologic Considerations and Clinical Implications. New EngI. J. Med.,
280: 1045-1058, 1969.
33. Harkness, R. D. Regeneration of Liver. Brit. Med. Bull., 13: 87-93, 1957.
34. Idezuki, Y. , Goatz, F. C., and Lillehei, R. C. Late Effect of Pancreatic
Duct Ligation on Beta Cell Function. Am. J. Surg., 117: 33-39, 1969.
35. Jordan, G. L. , Jr. Benign and Malignant Tumors of the Pancreas in the
Periampullary Region, pp. 449-532. In: J. M. Howard and G. L. Jordan,
Jr. (ads), Surgical Disease of the Pancreas. Philadelphia: J. B. Lippincott
Co.,1960.
36. Jordon, P. H., Jr. , and Grossman, M. I. Effect of Dosage Schedule on the
Efficacy of Substitution Therapy in Pancreatic Insufficiency. Gastroen
terology, 36: 447-451 , 1959.
37. Lansing, P. B. , Blalock, J. B. , and Ochsner, J. L. Pancreatoduodenec
tomy: A Retrospective Review, 1949-1969. Am. Surgeon, 38: 79-86,
1972.
38. Littman, A., and Hanscom, D. H. Pancreatic Extracts. New EngI. J. Med.,
281: 201-204, 1969.
39. Lortat-Jacobs, J. L., and Robert, H. G. Hepatectomie Droite Reglée.
Presse Med., 60: 549, 1952.
40. Mack, E. A., Hiebert, J. M., Goodman, M. L., and Egdahl, A. H. Insulin
Secretion in Dogs with Long-term Pancreatic Duct Ligation. Surg.
Forum, 19: 364-366, 1968.
41. Maddrey, W. C., Weber, F. C., Jr., Coulter, A. W., Chura, C. M., Cha
panis, N. P., And Walser, M. Effects of Keto Analogues of Essential
Amino Acids in Portal-Systemic Encephalopathy. Gastroenterology, 71:
190-195, 1976.
42. Matsuyama, T., and FoA, P. P. Plasma Glucose, Insulin, Pancreatic, and
Enteroglucagon Levels in Normal and Depancreatactomized Dogs. Proc.
Soc. Exptl. Biol. Med. , 147: 97-102, 1974.
43. McDermott, W. V., Jr., and Ackroyd, F. W. Nutrient Demands Imposed by
Surgery of the Liver. Am. J. Clin. Nutr., 23: 652-656, 1970.
44. McDermott, W. V., Jr., Greenberger, N. J. , Isselbacher, K. J., and Weber,
2394
A. L. Major Hepatic Resection: Diagnostic Techniques and Metabolic
Problems. Surgery, 54: 56-64, 1963.
45. Miyata, M., Takao, T., Uozumi, T., Okamoto, E., and Manaba, H. Insulin
Secretion after Pancreatoduodenactomy. Ann. Surg., 179: 494—498,
1974.
46. Miyata, M., Yamamoya, T., Yamaguchi, M., Nakao, K., and Yoshida, T.
Plasma Glucagon After Total Resection of the Pancreas in Man. Proc.
Soc.Exptl.Biol.Med.,152:540-543,1976.
47. Mongé,J. J., Judd, E. S., and Gage, R. P. Radical Pancreatoduodenec
tomy: A 22-Year Experience with the Complications, Mortality Rate, and
Survival Rate. Ann. Surg., 160: 711-719, 1964.
48. Morishita, R., Fujii, M., Yamamoto, T., Wakisaka, G.. Matsumoto, Y.,
and Ono, H. Effect of Pancreatin on Vitamin B,2 Malabsorption in Pa
tients with Total Pancreatectomy. Digestion, 11: 240—248,
1974.
49. Pack, G. T., and Baker, H. W. Total Right Hepatic Lobectomy. Ann.
Surg., 138: 253-258, 1953.
50. Pack, G. T., lslami, A. H., Hubbard, J. D., and Brasfield, R. D. Regenera
tion of Human Liver After Major Hepatectomy. Surgery, 52: 617-623,
1962.
51. Pack, G. T., Miller, T. R., and Brasfield, A. D. Total Right Hepatic
Lobectomy for Cancerofthe Gallbladder. Ann. Surg., 142: 6-16, 1955.
52. Pack, G. T., and Molander, D. W. Metabolism before and after Hepatic
Lobectomy for Cancer. Arch. Surg., 80: 685—692,
1960.
53. Pairent, F. W., Trapnell, J. E., and Howard, J. M. The Treatment of
Pancreatic Exocrine Insufficiency. Ill. The Effects of Pancreatic Ductal
Ligation and Oral Pancreatic Enzyme Supplements on Fecal Lipid Excre
tion in the Dog. Ann. Surg., 170: 737-746, 1969.
54. PIlam, M. B., and ReMine, W. H. Further Evaluation of Total Pancreatec
tomy. Arch. Surg., 110: 506—511,
1975.
55. Powis, S. J. A. , and Young, H. B. A Modified Pancreaticoduodenectomy.
Surg. Gynecol. Obstet., 137: 259-262, 1973.
56. ReMine, W. H., Priestley, J. T., Judd, E. S., and King, J. N. Total
Pancreatectomy. Ann. Surg., 172: 595-604, 1970.
57. Salam, A., Warren, W. D., KaIser, M., and Laguna, V. Pancreatoduode
nectomy for Trauma: Clinical and Metabolic Studies. Ann. Surg., 175:
663-669,
1972.
58. Shils, M. E. A Program for Total Parenteral Nutrition at Home. Am. J.
Clin. Nutr. 28: 1429-1435, 1975.
59. Silen, W. Pancreas. In: S. Schwartz (ad.), Principles of Surgery, Ed. 2,
pp. 1255-1280. New York: McGraw-Hill Book Co., 1974.
60. Soaters, P. B., and Fischer, J. E. Insulin, Glucagon, Amino Acid Imbal
ance, and Hepatic Encaphalopathy. Lancet, 2: 880-882, 1976.
61. Stamey, T. A. The Pathogenesis and Implications of the Electrolyte
Imbalance in Ureterosigmoidostomy. Surg. Gynecol. Obstet., 103: 736-
758,1956.
62. Starzl. T. E. Experience in Hepatic Transplantation, pp. 348-391 . Phila
delphia: W. B. Saunders Co., 1969.
63. Starzl, T. E., Porter, K. A., Watanabe, K., and Putnam, C. W. Effects of
Insulin, Glucagon, and lnsulin/Glucagon Infusions on Liver Morphology
and Cell Division after Complete Portacaval Shunt in Dogs. Lancet, 1:
821-825,
1976.
64. Toskes, P. P., Hansell, J., Carda, J., and Deren, J. J. Vitamin B,, Malab
sorption in Chronic Pancreatic Insufficiency. New EngI. J. Med., 284:
627-632,
1971.
65. Warren, K. W., Veidenheimar, M. C. , and Pratt, H. 5. Pancreatoduode
nectomy for Periampullary Cancer. Surg. CIin. North Am., 47: 639-645,
1967.
66. Whipple, A. 0.. Parsons, W. B., and Mullins, C. R. Treatment of Carci
noma of the Ampulla of Vater. Ann. Surg., 102: 763-779, 1935.
67. Whittemore, A. D., Vorhees, A. B., Jr., and Price, J. B., Jr. Hepatic Blood
Flow and Pancreatic Hormones as Modifiers of Hepatic Regeneration.
Surg. Forum., 27: 363-365, 1976.
68. Williams, R., Smith, M., Shilkin, K. B., Herbartson, B., Joysey, V., and
CaIne, A. V. Liver Transplantation in Man: The Frequency of Rejection,
Biliary Tract Complications, and Recurrence of Malignancy Based On An
Analysis of 26 Cases. Gastroenterology, 64: 1026-1048, 1973.
69.Wollaeger,
E.E.,Comfort,
M. W.,Clagett,
0.T.,andOsterberg,
A.E.
Efficiency of Gastrointestinal Tract after Resection of Head of Pancreas.
J. Am. Med. Assoc., 137: 838-848, 1948.
70. Younger, L. R., King, J. , and Steiner, D. F. Hepatic Proliferative Re
sponse to Insulin in Severe Alloxan Diabetes. Cancer Res., 26: 14081414, 1966.
CANCER RESEARCHVOL. 37
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Effects on Nutrition of Surgery of the Liver, Pancreas, and
Genitourinary Tract
Maurice E. Shils
Cancer Res 1977;37:2387-2394.
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