722929

review-article2017
NCPXXX10.1177/0884533617722929Nutrition in Clinical PracticePetzel and Hoffman

Invited Review
Nutrition in Clinical Practice
Volume 32 Number 5
Nutrition Implications for Long-Term Survivors October 2017 588–598
© 2017 American Society
of Pancreatic Cancer Surgery for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533617722929
https://doi.org/10.1177/0884533617722929
journals.sagepub.com/home/ncp

Maria Q. B. Petzel, BS, RD, CSO, LD, CNSC, FAND1; and

Leah Hoffman, PhD, RD/LD2

Abstract
With slowly increasing survival rates in pancreatic cancer and international consensus guidelines recommending surgical resection
of premalignant lesions, survival post–pancreatic resection is increasing. With longer survival time, the significant comorbidities of
such major surgery have far-reaching effects on the nutrition status of the survivor of pancreatic cancer. This review describes the
many nutrition-related side effects of pancreatic surgery, including the development of pancreatic enzyme insufficiency, micronutrient
deficiencies, diabetes, fatty liver, and metabolic bone disease. Beyond causing additional medical problems, each of these can have
significant effects on quality of life and functional status. The potential mechanisms, diagnosis criteria, and potential treatments of these
conditions are described. Overall, little literature exists to fully describe the effects of these comorbidities, and even less is able to guide
effective treatments for this population. Clinicians caring for these patients should begin incorporating goals for promotion of long-term
health and reduction of these known and reported comorbidities in patients who have undergone pancreatic surgery. Treatment plans in
this population remain understudied, and clinicians may need to consider recommendations for similar disease states when developing
interventions for these patients. (Nutr Clin Pract. 2017;32:588-598)

Keywords
pancreatic cancer; pancreaticoduodenectomy; pancreatectomy; nutrition assessment; survival; vitamins; trace elements

Pancreatic cancer is generally known for its dismal long-term sur-
vival rate; however, nearly 16,000 long-term survivors (>5 years
postdiagnosis) of pancreatic cancer are currently living in the
United States according to data from the National Cancer
Institute’s Surveillance, Epidemiology, and End Results program.1
Due to the anatomic location of pancreatic cancer and treatment
for the disease, patients living long-term after pancreatic cancer
are at risk for nutrition issues related to alterations in exocrine,
endocrine, and biliary function.2 Long-term sequelae are expected
due to major alterations in intestinal anatomy, including malab-
sorption (vitamin and mineral deficiencies or osteoporosis), and
metabolic derangements, including hepatic dysfunction and dia-
betes.3 Additionally, there may be metabolic consequences of che-
motherapy leading to electrolyte amnormalities.4,5
This year, approximately 53,670 people in the United States
will be diagnosed with pancreatic cancer, and 43,090 will die of
it.6 Most cases (94%) are exocrine cancers, the most common
being pancreatic ductal adenocarcinoma (PDAC).6 About 15%–
20% of patients with PDAC present with resectable tumors.7
Surgery is the only chance for a cure for PDAC,8 and even then
about 80% of patients will have disease recurrence.9 The 5-year
survival rate for pancreatic adenocarcinoma is 8.5%; however,
among those for whom it is caught in early stage, the 5-year
survival rate is about 29%.6,10 More rare, neuroendocrine
tumors and islet cell tumors make up about 3%–5% of all pan-
creatic cancer cases.11 These have a 5-year survival rate of 42%
and, in those found with a resected localized tumor, 55%.12
Although the purpose of this narrative review is to look at nutri-
tion concerns for long-term survivors of pancreatic cancer, the
surgical treatment is often the same (due to anatomic location)
for other forms of cancers and benign or precancerous growths.
Therefore, much of the long-term survivorship considerations
discussed here are the same for those with resected cancers of
the ampulla, distal common bile duct, or duodenum and benign
or precancerous growths, such as serous cystic neoplasms,
mucinous cystic neoplasms, intraductal papillary mucinous
neoplasms, and solid pseudopapillary neoplasms.8
From the 1Department of Clinical Nutrition and Department of Surgical
Oncology, The University of Texas MD Anderson Cancer Center,
Houston, Texas, USA; and 2Department of Nutritional Sciences, The
University of Oklahoma Health Sciences Center, Oklahoma City,
Oklahoma, USA
Financial disclosure: None declared.
Conflicts of interest: Maria Q. B. Petzel—AbbVie, Inc, onetime
honorarium in 2016.
This article originally appeared online on August 17, 2017.
Corresponding Author:
Maria Q. B. Petzel, BS, RD, CSO, LD, CNSC, FAND, Department of
Clinical Nutrition, The University of Texas MD Anderson Cancer Center,
1515 Holcombe Blvd, Unit 322, Houston, TX 77030, USA.
Email mpetzel@mdanderson.org
Petzel and Hoffman
Figure 1. Normal anatomy. © 2017 The University of Texas
MD Anderson Cancer Center.
For this review, we assume that, since surgery is the only
definitive of cure for pancreatic cancer, all long-term survivors
will have undergone surgery. Long-term survival of cancer is
generally considered to be >5 years after diagnosis. We also
focused on those articles that addressed survivors of cancer
exclusively or in part. We limited the use of references that
reported solely on patients with chronic pancreatitis or cystic
fibrosis, as these may be associated with other complicating
disease or psychosocial factors.13 Because the data are lacking,
we sometimes do include literature based on patients with
chronic pancreatitis and cystic fibrosis but note when doing so.
Anatomic Influences
The pancreas is located in the abdomen and sits behind the
stomach; it is made up of the head, body, and tail (Figure 1).
The anatomic location of the tumor influences the type of sur-
gery performed.14-19 The most commonly performed surgery for
PDAC is a pancreaticoduodenectomy (PD), also called a
Whipple procedure.7 The head of the pancreas, gallbladder,
duodenum, and part of the stomach are removed (Figure 2) in a
standard PD. In a pylorus-preserving PD (PPPD), the stomach
is left intact.7,14 Table 1 outlines the general anatomic changes
with each surgical procedure. Figures 3 and 4 depict the typical
reconstruction of anatomy following PD and PPPD, respec-
tively. Many of the nutrition consequences for long-term survi-
vors of pancreatic cancer are due to the removal of the duodenum
and/or stomach.13,20,21 Not only are these required for nutrient
breakdown and absorption, but these structures also secrete gas-
trointestinal hormones influencing gut motility, so disruption in
their hormone production can cause gastrointestinal asyn-
chrony.3,20,22 Much of the absorption of vitamins and minerals
(most notably iron and calcium) is in this first part of the small
intestine.21,23 Though rarely seen, partial gastrectomy as part of
a standard PD increases the risk of vitamin B12 deficiency due
589
Figure 2. Resected anatomy (classic pancreaticoduodenectomy).
© 2017 The University of Texas MD Anderson Cancer Center.
to reduction in intrinsic factor production.13,21 While early
delayed gastric emptying poses a significant—and often
serious—nutrition complication in the recovery period immedi-
ately after surgery, this generally resolves in the weeks follow-
ing surgery, and other anatomic alterations are more likely to
effect the long-term survivor.24,25 More rapid intestinal motility,
dumping syndrome, or pancreatic exocrine insufficiency (PEI)
may lead to steatorrhea, which can cause loss of calcium and
magnesium through precipitation with fatty acids, forming
poorly absorbable soap complexes that pass in the stool; very
severe steatorrhea may also lead to loss of sodium and potas-
sium.21 Because of the complex nature of PD and its effect on
multiple organs, patients post-PD are at higher risk for nutrition
complications when compared with the second-most common
surgery for pancreatic cancer, distal pancreatectomy (DP),
which removes the tail of the pancreas and may or may not
include a splenectomy (Figures 5 and 6).17 With the large num-
ber of potential nutrition comorbidities related to this surgery
and the potential for patients to live longer after PD than ever
before, the purpose of this review is to identify long-term com-
plications of PD and discuss potential solutions found in the
literature to treat nutrition-related side effects.
Major Findings
Pancreatic Exocrine Insufficiency
Patients may experience onset of PEI before diagnosis, during
nonsurgical treatment, and/or following surgery.2 Causes of or
influences on degree of PEI include underlying pancreatic dis-
ease, extent of tissue loss, changes in postprandial stimulation,
and asynchrony of the gastrointestinal tract.3,26 Although tests
exist to diagnose PEI, they can be cumbersome and difficult
for use in clinical practice. Those tests that are simpler to per-
form, such as fecal elastase (FE) and 13C-labeled mixed
590 Nutrition in Clinical Practice 32(5)

Table 1. Surgical Procedure and Anatomic Changes.7,15-19

Surgical Procedure Anatomy Resected Reconstruction

Pancreaticoduodenectomy
(PD), also known as
Whipple procedure
Pylorus-preserving PD,
also known as pylorus-
preserving Whipple
Total pancreatectomy
Distal pancreatectomy
Central pancreatectomy
Head of pancreas, duodenum, gallbladder, Hepaticojejunostomy, pancreaticojejunostomy or
distal stomach, and part of common bile duct pancreaticogastrostomy, and gastrojejunostomy.
Rare variations of surgery or reconstruction may
include leaving the gallbladder and connecting the
jejunum to the gallbladder (cholecystojejunostomy)
or the common bile duct (choledochojejunostomy).
Head of pancreas, duodenum, gallbladder, and Hepaticojejunostomy, pancreaticojejunostomy or
part of common bile duct are removed. (The pancreaticogastrostomy, and duodenojejunostomy.
stomach and pylorus are kept intact.) Rare variations of surgery or reconstruction may
include leaving the gallbladder and connecting the
jejunum to the gallbladder (cholecystojejunostomy)
or the common bile duct (choledochojejunostomy).
Removes the entire pancreas and sometimes the Same as PD reconstruction but no remnant pancreas
spleen in addition to that removed with a PD and, therefore, no pancreaticojejunostomy or
pancreaticogastrostomy.
Removes only the tail of the pancreas or the
tail and a portion of the body of the pancreas.
The spleen may be removed as well.
Neck/body of the pancreas removed (head and Pancreaticojejunostomy with tail of pancreas.
tail preserved).

Figure 3. Reconstruction of pancreaticoduodenectomy. © 2017

The University of Texas MD Anderson Cancer Center.
triglyceride breath test, are of limited accuracy postoperatively
as compared with fecal fat excretion or coefficient of fat
absorption.26 Detailed descriptions of pancreatic function tests
are elsewhere in the literature,26-28 and these tests are listed in
Table 2. Because testing is cumbersome, PEI is often recog-
nized clinically (see Table 3 for signs and symptoms of PEI)
and treated empirically.28 However, clinical diagnosis of PEI is
generally less sensitive than functional testing and may lead to
Figure 4. Reconstruction of pylorus preserving
pancreaticoduodenectomy. Illustration by Scott A. Weldon, MA,
CMI, and printed with permission from The Elkins Pancreas
Center at Baylor College of Medicine, Houston, Texas.
underdiagnosis and undertreatment of PEI.3,26,28,32 It is sug-
gested that if patients have clinical symptoms of PEI, treatment
should be initiated, but in the absence of symptoms, functional
testing should be performed, as PEI cannot be excluded simply
because of a lack of symptoms.26
Petzel and Hoffman
Figure 5. Normal anatomy with mass in tail of pancreas.
Illustration by Scott A. Weldon, MA, CMI, and printed with
permission from The Elkins Pancreas Center at Baylor College of
Medicine, Houston, Texas.
Figure 6. Distal pancreatectomy. Illustration by Scott A.
Weldon, MA, CMI, and printed with permission from The Elkins
Pancreas Center at Baylor College of Medicine, Houston, Texas.
Incidence of PEI following surgery for cancer is reported in
50%–100% of patients post-PD26,32-35 and 0%–42% in DP.26,32,36
Variations in reports may occur because several diagnostic tests
are used, time since surgery varies, and studies are of small
sample size and heterogeneous populations, often including
those with malignant and benign disease as well as with and
591
Table 2. Diagnostic Tests for Pancreatic Exocrine
Insufficiency.26-28
Coefficient of fat absorption
Fecal fat excretion
13C-labeled mixed triglyceride breath test
Urinary PABA excretion rate
Fecal elastase (fecal elastase 1)
Fecal chymotrypsin level
PABA, para-aminobenzoic acid.
Table 3. Signs and Symptoms of Pancreatic Exocrine
Insufficiency.2,27-31
Abdominal bloating
Cramping after meals
Excessive gas (burping or flatulence)
Fatty or oily stools
Frequent stools
Foul-smelling stools or gas
Floating stools
Stools that are light tan or yellow
Indigestion
Loose stools
Unexplained weight loss
without pancreatitis.26 Matsumoto and Taverso evaluated FE in
patients before and after PD for a heterogeneity of diseases at
preoperative and routine postoperative visits.33 They found that
patients with moderate or severe PEI (low FE) before PD did
not have improvement after surgery.33 Assessment of those with
normal FE, preoperatively, showed reduction from baseline in
73% and 50% of patients at 12 and 24 months, respectively.33
Similar results were found for individuals post-DP. Speicher
and Traverso’s36 evaluation of patients with normal FE before
surgery found that FE was low in 12% and 8% of patients at
follow-up of 3 and 12 months, respectively, but normal in all by
24 months following extended DP (resection to right of the por-
tal vein). Normal FE was found for all patients who underwent
a less extensive DP (resection to the left of the portal vein) at all
time points.36 Overall, it is reasonable to conclude and educate
patients that if they have PEI before surgery, it will endure long-
term. If they have normal pancreatic function before DP, they
can expect normal function within 2 years of surgery; however,
those undergoing PD should be counseled about a 50% chance
of reduction in pancreatic function long-term. Anecdotally,
patients often believe that PEI will resolve with surgery, and
failure to provide good patient education early during enzyme
replacement may lead to discontinuation of the medication,
which can subsequently lead to multiple nutrition issues.
Note also that patients may still have adequate enzyme pro-
duction (as evidenced by normal FE) after surgery but that sur-
gery may lead to asynchrony within the gastrointestinal tract
592
and, therefore, symptoms of malabsorption because enzymes
are not meeting food at the appropriate point in the digestive
system.26,27 Some surgeons prefer to attach the pancreatic rem-
nant to the stomach (pancreaticogastrostomy) instead of small
intestine as a proposed method for reduced pancreatic fistula or
for technical reasons during minimally invasive surgery12,37,38;
however, this may lead to need for higher doses of pancreatic
enzyme replacement therapy (PERT) since exposure of pancre-
atic secretions directly to gastric acid will inactivate endoge-
nous pancreatic enzymes.39,40
The primary strategy for management of PEI is PERT.
Enzyme doses should be started low and then titrated up every
few days as needed based on the fat content of the diet, charac-
teristics of stools, and symptoms of each patient.3,30 Dosing
suggestions vary but generally start at 20,000–75,000 lipase
units per meal and 5000–50,000 lipase units per snack.2,3,26,27,30-
32,41,42
PERT dosages should not exceed 10,000 lipase units per
kilogram of body weight per day or 2500 lipase units per kilo-
gram per meal up to 4 times a day.30 This wide range of dosages
reflects that some patients are self-restricting meal sizes and fat
content and need lower amounts of PERT vs other patients who
are eating normal-size meals with large amounts of fat. The
individual’s current eating pattern should be taken into account
when deciding a starting dose of enzymes. Those who are self-
restricting for symptom management may be able to titrate the
dose and liberalize the diet with good success.
For optimal replacement, the enzyme dose should be
divided and administered throughout the meal. Starting
enzymes with the first bite of food and consuming them
throughout the meal and at the end will ensure that they are
mixed with the food in the gut.30,41 Ideally, with adequate
enzyme supplementation, patients may not need to restrict the
fat content of their diets.2,27,43 However, fat restriction may
benefit some patients with severe steatorrhea. Sarner suggests
consuming <75 g/d of fat.41 However, it should be kept in mind
that this may not represent an actual restriction on fat intake, as
a “healthy diet” that meets the acceptable macronutrient distri-
bution range is likely to provide <75 g/d of fat (an adult con-
suming 2000 kcal/d with 30% of total energy intake from fat
would consume only 67 g/d of fat). For patients having trouble
consuming adequate energy due to limited tolerance of fat,
medium-chain triglyceride oil may be substituted for other fats
because medium-chain triglycerides do not require enzymatic
action or bile salts for digestion or absorption.41,44 Adequate
dosing of PERT is critical for full digestion and absorption of
nutrients in patients who experience PEI, but it is also plays a
role in improving or maintaining quality of life, likely related
to improving bowel function and reducing diarrhea and
steatorrhea.26
Micronutrient Deficiency
Information about micronutrient deficiencies in the long-term
postresection pancreatic cancer survivor is limited. Much of
Nutrition in Clinical Practice 32(5)
what we know is from case reports and small retrospective
evaluations of a heterogeneous group of subjects after PD or
total pancreatectomy for varying types of cancer or benign dis-
ease, such as pancreatitis. Methodology also varies, as some
studies evaluate dietary intake, serum levels, and presence of
deficiency symptoms; others do not take into account dietary
intake, which may be deficient itself. Because of the sparse-
ness of high-grade literature on this subject, the incidence of
deficiencies remains unknown in this population, and compre-
hensive recommendations for monitoring deficiencies in the
long-term survivor of pancreatic surgery are not feasible.
Instead, it is recommended that clinicians caring for these
patients be aware of micronutrient deficiencies that have been
reported in the literature (albeit in small studies) and observe
their patients for signs or symptoms of these deficiencies. Our
current practice for micronutrient evaluation is reflected in
Table 4. Dietary intake of micronutrients—especially those
presented here—should be evaluated, with adequacy of PERT,
when completing long-term follow-up with these patients. In
addition to inadequate dietary intake, micronutrient deficiency
is likely multifactorial due to loss of the primary absorptive site
from the duodenectomy, altered physiology and synchrony of
the gastrointestinal tract, as well as altered chemistry, such as
changes in the production of intrinsic factor and changes in the
pH of chyme.45,46 Historically, the recommendation was to
consider replacement or supplementation of fat-soluble vita-
mins with water-miscible forms; however, the studies pre-
sented suggest that additional supplementation may be
unnecessary if high-enough doses are given orally and PERT is
adequate.
Fat-Soluble Vitamins
Vitamin A
The best-documented symptom of vitamin A deficiency in this
population is night blindness, or prolonged dark adaptation.
One patient in a case report complained of inability to see in
dimly lit areas but adequate vision in good lighting.47 A case
report of a patient 10 years post–total pancreatectomy who
developed night blindness and dry skin was found to have
serum vitamin A deficiency, among other nutrient deficiencies,
related to his self-withdrawal from PERT.48 Deficiency may be
unknown by the patient; of 7 patients with pancreatic insuffi-
ciency with low serum retinol, only 3 had night blindness, and
none showed other physical signs or symptoms of deficiency,
such as xerosis, hyperkeratinized skin lesions, bone pain, or
anemia.49 Dressler et al reported low serum vitamin A in 4 of
49 patients >6 months (mean, 39 months) following total pan-
createctomy despite being on PERT, but patients were not
evaluated for night blindness in this study.50 Because factors
that affect fat absorption also affect vitamin A digestion and
absorption, an apparently adequate dietary intake of vitamin A
may not be sufficient to maintain serum retinol levels.
Petzel and Hoffman 593

Table 4. Practice-Based Recommendations for Micronutrient Evaluation.

Examination Baseline Evaluation Follow-Up

Bone mineral density After completion of surgical recovery Normal: every 5 y
and any adjuvant treatment, within Abnormal: annually—refer to primary care
2 y postoperatively or bone health clinic for management
Serum evaluation: copper, zinc, selenium, folate, Within 1 y after surgical resection Normal: annually
vitamin B12, methylmalonic acid, retinol or sooner if patient has signs/ Abnormal: attempt repletion and recheck
binding protein (vitamin A), α tocopherol symptoms of malabsorption in 3 mo
(vitamin E), 25-OH vitamin D, hemoglobin
A1C, complete blood count, magnesium

Armstrong et al found that, after a Whipple procedure, patients
consumed adequate vitamin A in the diet but had low serum
levels of retinol.46 If a deficiency is suspected, serum retinol is
the most appropriate laboratory test for assessment. It is a con-
stant marker of vitamin A status as long as there is no inflam-
mation or infection present.51
For patients with pancreatic insufficiency, Dutta et al were
able to normalize low serum retinol with 30,000 IU of retinol
palmitate daily for 4 weeks; 1 patient failed to normalize with
oral therapy and required treatment with 100,000 IU of paren-
teral vitamin A.49 The recommended daily allowance (RDA) is
700 mcg for women and 900 mcg/d for men.52 As suggested by
the data from Armstrong et al,46 this amount may not be ade-
quate for patients after a Whipple procedure, and higher doses
may be needed. In a case report by Tiang and Warne, normal-
ization also required resumption of PERT.48
Vitamin D
In 2 studies analyzing the diets of patients 4 months after pan-
createctomy or a Whipple procedure, dietary intake of vitamin
D was insufficient in all participants.46,53 In addition to inade-
quate intake, a patient with fat malabsorption is unlikely to
absorb adequate vitamin D. Insufficient serum levels of 25-OH
vitamin D have been reported in pancreatic insufficiency54,55
and post–pancreatic resection.45,50,56 To treat a vitamin D defi-
ciency in patients who are obese or who have malabsorption,
the Endocrinology Society clinical guidelines recommend a
higher dose of either vitamin D2 (ergocalciferol) or vitamin D3
(cholecalciferol) of at least 6000–10,000 IU daily until 25-OH
vitamin D levels are >30 ng/mL, followed by a maintenance
dose of 3000–6000 IU daily.57 These guidelines are signifi-
cantly higher than the Institute of Medicine’s recommended
600 IU for adults and 800 IU daily for older adults, but the
RDA is directed at healthy adults.58 In the setting of pancreatic
insufficiency, the required dose to treat a deficiency may be
even higher. If serum 25-OH vitamin D levels fail to normalize
in an individual patient following the endocrinology guide-
lines, 1 of the following may be more appropriate. Dutta et al
treated participants with chronic alcoholic pancreatitis and
vitamin D deficiency with 50,000 IU 3 times per week for 4
weeks and normalized 25-OH vitamin D levels in 7 of 10
participants.49 Klapdor et al found doses up to 20,000 IU daily
were required to normalize 25-OH vitamin D levels in patients
with chronic pancreatitis and pancreatic cancer, all of whom
were taking adequate doses of pancreatic enzymes.56 No side
effects were reported or detected by serum calcium.56 Oral
administration is the preferred route, and high doses have been
shown to increase serum 25-OH vitamin D without injec-
tions.56 Vitamin D supplements may be taken on an empty
stomach and without fat at the meal.
Vitamin E
Although intake has been reported to be adequate after pancre-
atectomy,53 low serum vitamin E has been documented in
patients with pancreatic insufficiency49 and following pancre-
atic surgery for malignancy in patients compliant and noncom-
pliant with PERT,48,50 although in very few patients. This may
be due to inadequate absorption. To correct vitamin E defi-
ciency in patients with pancreatic insufficiency, Dutta et al
were able to normalize serum vitamin E using 400 IU orally
once daily for 2 weeks and then reevaluating.49
Other Vitamins and Minerals
Iron
Given that the first part of the small intestine is the primary site
for iron absorption,21,23 deficiency may occur following
removal of the duodenum during PD and PPPD. However,
there is limited literature reporting iron deficiency or related
anemia. Low iron has been reported in several instances; how-
ever, these have not been accompanied by results of low serum
ferritin or anemia.45,46 Other studies have found serum iron
within normal limits,34,59,60 as well as total iron-binding capac-
ity,59,60 transferrin, and iron saturation.59 Limitations of these
studies are that neither hemoglobin nor serum ferritin (largely
accepted as the best measure of total body iron stores) is
reported. Armstrong et al suggested that long-term survivors
may have subclinical iron deficiency causing symptoms of
fatigue and anxiety.45
These authors personally cared for a small number of
patients with low serum ferritin, low hemoglobin, and no
594
known source of blood loss (negative fecal occult blood, nega-
tive endoscopy). These patients presented ≥2 years post-PD
and without recurrent disease. Patients were treated with oral
or intravenous (IV) iron replacement, resulting in normaliza-
tion of hemoglobin and serum ferritin. For this reason, although
the evidence is lacking, these authors recommend monitoring
appropriate parameters for evidence of iron deficiency
anemia.
Vitamin B12
Although dietary intake may meet the RDA, after a Whipple
procedure, the patient may be unable to properly absorb ade-
quate vitamin B12. Pancreatic proteases are required to release
vitamin B12 from food protein so that it can be bound to intrin-
sic factor for absorption.61-63 In addition, intrinsic factor is pro-
duced and secreted by the parietal cells in the stomach.
Reduced intrinsic factor production is seen after partial gas-
trectomy61 (potentially affecting patients who have undergone
the standard Whipple procedure with distal gastrectomy).
Further compromising absorption, patients may be receiving
long-term acid suppression therapy following surgery, which
may contribute to inadequate cleaving of B12 from food.61
Two studies examined vitamin B12 status in a small number of
patients (10 and 7 subjects) and documented malassimilation
of vitamin B12 in those with pancreatic insufficiency62 and
post-PD.63 More recently, Armstrong et al reported on a group
of 10 patients following PD for malignancy at 6–46 months
postoperatively and found no incidence of vitamin B12 defi-
ciency.46 Recent studies of patients following partial gastrec-
tomy for gastric cancer at 4 and 5 years postresection reported
on a collective 778 subjects, finding vitamin B12 deficiency in
1.6%–15.7% of patients.64,65 Because of the lacking literature
specific to pancreatic cancer and resection, studies addressing
the anatomic change implicated in the cause of vitamin B12
deficiency should be considered. Therefore, patients who have
undergone classic PD should be considered at risk for vitamin
B12 deficiency and monitored accordingly.
Because there are significant bodily stores of vitamin B12,
clinical manifestations of deficiency may take several years to
develop. Serum cobalamin levels are diagnostic of vitamin
B12 deficiency. In a deficiency state, 1000 µg of cyanocobala-
min can be given intramuscularly monthly. Reticulocyte count
should return to normal 1 week after injection; iron deficiency
should be considered if there is no improvement.66
Zinc
There are no reliable indicators for diagnosing deficiency.
Normal plasma levels of zinc are not well established, because
the body keeps a very narrow range for zinc homeostasis.
Serum zinc can be measured but should be interpreted with cau-
tion, as inflammation and hypoalbuminemia, infection, and fed/
fasting state affect serum measurement. Diagnosis may be best
Nutrition in Clinical Practice 32(5)
made by evaluating dietary intake, bioavailability of intake, and
clinical signs suggestive of deficiency. Confirmation of diagno-
sis may be made by measuring response to supplemental zinc.67
Zinc deficiency has been reported following surgery for pancre-
atic cancer in case reports and small retrospective evalua-
tions.46,50,68-70 Deficiency is thought to be related to disturbance
of zinc absorption in the jejunum as well as poor protein absorp-
tion and, therefore, poor zinc transport, as well as inadequate
dosing of or adherence to PERT.70 Yazbeck et al68 described a
single case of a young female patient presenting with symp-
toms, including alopecia, total body hair loss, dry scaly skin,
glossitis, and maculopathy with vision loss. She was found to
have, after overnight fast, low serum zinc as well as low biotin.
She was treated with supplemental biotin and zinc IV for 1
week and then transitioned to oral replacement with PERT; after
3 months, she had improvement/resolution of presenting symp-
toms. She was then maintained on a regular diet, pancreatic
enzymes, and a multivitamin/mineral supplement. Other simi-
lar cases have been described with similar treatment and main-
tenance utilizing adequate PERT.69-71
Other
Other miscellaneous mineral deficiencies have been reported
in single-case reports or other very small cohorts, including
selenium, biotin, copper, and vitamin B6. Selenium was
reported to be low among 4 patients in a study by Armstrong et
al of 9 patients following PD. It is unclear how the deficiency
was treated, but it is notable that not all patients were taking
PERT at the time of the evaluation.46 A single case of biotin
deficiency was reported by Yazbeck et al68 in a patient 3 years
post-PD with zinc and vitamin D deficiency linked to no use of
PERT. Studies by Dresler et al evaluated serum copper in
patients post–total pancreatectomy, and no deficiencies were
noted.50 However, Yasuda et al presented a case study of 1
patient being followed after PD with distal gastrectomy in
which the patient had low serum copper—this was corrected
with methaphyllin (3 g/d) and initiation and continuation of
pancreatic enzyme replacement.69 In that case as well as one
other presented by Yasuda et al, the patients were reported to
have deficiency in vitamin B6, which was treated with oral
pyridoxal phosphate hydrate and continued or initiated use of
PERT.69 In summary, other micronutrient deficiencies may
exist that have not been consistently reported in the literature,
but these seem to generally resolve with adequate PERT
therapy.
Magnesium
Deficiency of magnesium may be multifactorial in the long-
term survivor of pancreatic cancer, as it could be related to a
history of chemotherapy or anatomic changes following sur-
gery. As previously described, patients with ongoing steator-
rhea are at higher risk for magnesium losses due losses of
Petzel and Hoffman
magnesium in the stool. In an observational study, Dresler et al
reported on 49 patients who had undergone total pancreatec-
tomy (42 of these for malignancy). These patients were evalu-
ated a mean of 39 months postoperatively and found to have
low serum magnesium—among other deficiencies—despite
being on PERT.50 The study does not include information about
chemotherapy received, but it is important to note that 1 class
of chemotherapeutic agents that is used against pancreatic
cancer—the platinum-based agents, especially cisplatin—car-
ries a risk of hypomagnesemia as an acute or chronic side
effect related to nephrotoxicity.5,72-76
Diabetes
Pancreatogenic or type 3 diabetes (as classified by the
American Diabetes Association and the Centers for Disease
Control and Prevention) develops due to the loss of pancreatic
parenchyma.77 It differs from type 2 diabetes in that patients
continue to have normal or enhanced peripheral insulin sensi-
tivity.78,79 It is reported to occur in 8%–23% of patients shortly
after surgery and increase to 18%–50% of patients during long-
term follow up77,78 (median 27 months postoperatively, per 1
study).79 In studies that included patients who had surgical
resection for cancer, postoperative development of diabetes is
reported to occur in 5%–9% of patients following DP at a
median of 21 months postoperatively.79 For post-PD patients, 1
study analyzed patients with pancreatic cancer separately from
those with pancreatitis and found that 39% of patients with
cancer developed diabetes.79 For those with diabetes before
surgery, diabetes worsens (requiring more medication or a
transition to insulin) in about half following PD and a quarter
following DP.77 Although there are no specific guidelines for
treatment of diabetes in the long-term survivor of pancreatic
cancer, it is appropriate for glycemic management strategies to
include exercise, carbohydrate-controlled diet, weight loss (if
overweight), and pharmacologic treatment including insu-
lin.78,79 The goal of therapy should be a hemoglobin A1c <7%
or fasting glucose between 70 and 130 mg/dL.78 Metformin is
often the noninsulin therapy of choice, but because of potential
gastrointestinal side effects (including diarrhea), the dose
should be escalated slowly and consideration given to an
extended-release preparation.78
Fatty Liver
The occurrence of nonalcoholic fatty liver disease (NAFLD) or
hepatic steatosis is reported among 7%–40% of patients fol-
lowing pancreatectomy.80-93 Risk factors identified via multi-
variate analysis include female sex,80-82,85,90 pancreatic
cancer,81,83-85 pancreatic remnant characteristics,81,84 low post-
operative serum albumin,80,85,90,92 pancreaticoduodencec-
tomy,85 PEI,92 and postoperative weight loss.89,92 Attention to
treatment of NAFLD is important in the long-term pancreatic
cancer survivor because, without treatment, it may progress to
steatohepatitis, fibrosis, or cirrhosis.50,80,89,92
595
The etiology of NAFLD in this population is not fully
understood; theories include malabsorption of amino acids
or fat-soluble nutrients leading to deposition or accumula-
tion of triglycerides in the liver92,93 and fatty acid deficiency
due to malabsorption leading to increased conversion of car-
bohydrates into fat and, therefore, increased deposition in
the liver.90 PERT has been suggested for treatment of post-
PD NAFLD. The potential mechanism for benefit of PERT is
reversal or prevention of fat malabsorption. The use of PERT
has been investigated in small studies, including retrospec-
tive reviews. Kishi et al85 completed a retrospective chart
review evaluating 473 patients who were or were not pre-
scribed digestive enzymes for PEI, and they examined
whether the groups differed in diagnosis or severity of
hepatic steatosis. In a comparison of those who received
pancrelipase (900 mg/d [60,000–96,000 lipase units/day] or
1800 mg/d [120,000–192,000 lipase units/day]) vs pancre-
atin (an older, less potent form of PERT)94 vs no enzymes,
those patients who received pancrelipase had significantly
more rapid and more complete improvement of hepatic ste-
atosis than those on pancreatin or no enzymes (92% improve-
ment in 12 months vs 51% and 56%, respectively).85 Nagai
et al identified patients who developed NAFLD after PD for
a trial of pancrelipase for treatment of fatty liver. Patients
were prescribed 1800 mg (120,000–192,000 lipase units/
day) of pancrelipase (LipaCreon, Eisai, Japan) and were
evaluated at 1, 3, and 6 months posttreatment. These patients
demonstrated significant improvement in liver appearance
on computed tomography. Although some did not have reso-
lution of NAFLD, there were no significant adverse effects
observed.95 Satoi and colleagues completed a small random-
ized controlled trial of pancrelipase vs standard pancreatin-
containing products and found no statistically significant
difference in NAFLD after treatment. However, in the con-
trol group that received standard enzyme products, crossover
to pancrelipase resulted in improvement in—but not resolu-
tion of—NAFLD in 5 of 10 patients.96 Yamazaki and col-
leagues propose use of an elemental formula enriched with
branched-chain amino acids, taken per feeding tube or by
mouth, for 60 days postoperatively plus high-dose pancre-
atic enzymes as a means to prevent NAFLD. Their results
demonstrated significantly fewer cases of NAFLD in the
treatment group vs historical controls, but the follow-up
interval was only 3 months after surgery.97 The use of PERT
and other strategies to aid with prevention of malnutrition
and, therefore, prevention of or treatment for NAFLD are
compelling. Although studies have suggested that PERT may
benefit hepatic steatosis, it has not been evaluated for long-
term effect. Therefore, for those patients starting PERT for
NAFLD, it is unknown if stopping the enzymes will lead to
refractory occurrence of fatty liver.82 Although there is no
current recommendation regarding monitoring, it is our cur-
rent practice to work with patients before or after medical
diagnosis of NAFLD to ensure an adequate PERT regimen
and a diet limited in fat and excess carbohydrate.
596
Bone Density
Because the duodenum is the primary and most efficient site of
calcium absorption and because most patients post-PD is
receive acid-suppressive therapy, which can impair the solubil-
ity of calcium salts (calcium carbonate and calcium phos-
phate),23 there is concern that long-term survivors of pancreatic
cancer may be at higher risk for bone density loss. However,
there is very little reported about bone mineral content or bone
mineral density (BMD) in this population. In each of the fol-
lowing studies discussed, BMD was measured by dual-energy
x-ray absorptiometry. Dressler et al evaluated bone density in
13 individuals who were part of a larger study of 49 patients
post–total pancreatectomy (42 for malignancy and 7 for pan-
creatitis). These 13 individuals were compared with age-
matched and sex-matched controls. There were no significant
differences in bone mineral content between the patients and
the controls at 2 years after surgery, but when 8 of those 13
subjects were reevaluated at variable times 3 to >5 years post-
operatively, subjects showed lower bone mineral content than
their controls, and those at >5 years postoperatively (n = 3) had
a mean reduction of 17.6% vs the controls.50 Haaber et al54
evaluated BMD in 58 patients with chronic pancreatitis and
pancreatic insufficiency. Results showed osteopenia in 62% of
patients and osteoporosis in 22%. When groups were stratified
into those with and without PEI, there were no significant dif-
ferences between them.54 Because literature on this subject is
sparse but the theoretical concern is high, we looked beyond
the pancreatic cancer and PEI literature to that of Roux-en-Y
gastric bypass, as the anatomic changes are similar to those
after PD and PPPD.20 A small longitudinal study of women
having undergone Roux-en-Y gastric bypass evaluated bone
density. Twenty-four patients were examined with dual-energy
x-ray absorptiometry at each of 3 visits—preoperative and 2
and 5 years postoperative. The study showed 1 subject with
osteopenia at presentation and another at 2 years; at 5 years
postoperatively, 8 patients had osteopenia and 1 had osteopo-
rosis. At the 5-year follow-up visit, 1 of the original 2 cases of
osteopenia had corrected after supplementation with calcium
and vitamin D, but the other did not. These changes in BMD
were not reflective of natural disease in women of the same
age. Although the subjects had reductions in BMD, they did
not show significant changes in serum vitamin D, except they
did have correlation with increasing parathyroid hormone, sup-
porting a process of bone remodeling.98 Although robust stud-
ies are lacking, the available literature suggests that it is
important to monitor BMD in the population of long-term sur-
vivors of pancreatic cancer and that strategies to prevent osteo-
porosis are important to implement early in this group.
Conclusion
With slowly increasing 5-year survival rates of pancreatic can-
cer and constantly improving diagnostic imaging, the potential
exists for more long-term survival after pancreatic resection.
Nutrition in Clinical Practice 32(5)
With this increase in survival time, the long-term nutrition-
related side effects of pancreatic resection are likely to become
more prevalent, but little research currently exists that examines
these comorbidities in this patient population. Until this research
gap is addressed, clinicians have few options other than to con-
sider research focused on nutrition-related problems in similar
populations. After pancreatic resection, patients may experi-
ence similar issues as those with chronic pancreatitis or cystic
fibrosis, who also experience pancreatic enzyme insufficiency
and its sequelae. After pancreatic resection, patients may expe-
rience nutrition consequences similar to those of patients who
have undergone bariatric surgery, specifically Roux-en-Y gas-
tric bypass.20 In the absence of appropriate research to support
recommendations for the long-term survivor of pancreatic can-
cer after surgery, clinicians may consider borrowing from the
literature for these other conditions to inform their interven-
tions, with careful follow-up for safety and response to therapy.
Given the lack of literature available, our current practice is
outlined in Table 4.
In conclusion, patients who have undergone pancreatic
resection are at risk for many nutrition-related comorbidities,
including effects on gastrointestinal and hepatic function, glu-
cose control, bone health, and the status of many micronutri-
ents. Patients—especially those with benign disease—are
living longer after surgery, and the standard of care for these
patients should include monitoring and evaluating these nutri-
tion problems with the goal of promoting long-term disease-
free survival.
Statement of Authorship
Both authors equally contributed to the conception and design of
the work; contributed to the acquisition, analysis, and interpretation
of the data; drafted the manuscript; critically revised the manu-
script; agree to be fully accountable for ensuring the integrity and
accuracy of the work; and read and approved the final manuscript.
References
1. Howlader N, Noone A, Krapcho M, et al, eds. Table 22.21 Cancer of the
Pancreas (Invasive) Estimated United States Cancer Prevalence Counts
on January 1, 2014. Bethesda, MD: National Cancer Institute; 2017.
2. Ottery F. Supportive nutritional management of the patient with pancre-
atic cancer. Oncology (Williston Park). 1996;10(9)(suppl):26-32.
3. Phillips ME. Pancreatic exocrine insufficiency following pancreatic resec-
tion. Pancreatology. 2015;15(5):449-455.
4. Davis PF, Douglas T, Gilbert CD, et al. Side effects of cancer therapy.
In: Polovich M, Olsen MM, LeFebvre KB, Oncology Nursing Society,
eds. Chemotherapy and Biotherapy Guidelines and Recommendations for
Practice. 4th ed. Pittsburgh, PA: Oncology Nursing Society; 2014:171-436.
5. Muehlbauer PM, Shelburne N, Shields S. Principles of antineoplastic ther-
apy. In: Polovich M, Olsen MM, LeFebvre KB, Oncology Nursing Society,
eds. Chemotherapy and Biotherapy Guidelines and Recommendations for
Practice. 4th ed. Pittsburgh, PA: Oncology Nursing Society; 2014:25-50.
6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin.
2017;67(1):7-30.
7. Pancreatic Cancer Action Network. Surgery. https://www.pancan.org/
facing-pancreatic-cancer/treatment/surgery/. Published 2017. Accessed
April 24, 2017.
Petzel and Hoffman
8. American Cancer Society. Surgery. https://www.cancer.org/cancer/pancre-
atic-cancer/treating/surgery.html. Published 2017. Accessed April 24, 2017.
9. Pancreatic Cancer Action Network. Pancreatic cancer facts 2016. https://
www.pancan.org/wp-content/uploads/2016/02/2016-GAA-PC-Facts.pdf.
Published 2016.
10. SEER. Cancer stat facts: pancreas cancer. https://seer.cancer.gov/stat-
facts/html/pancreas.html. Published 2017. Accessed March 27, 2017.
11. American Cancer Society. Pancreatic cancer. https://www.cancer.org/can-
cer/pancreatic-cancer.html. Published 2017. Accessed March 27, 2017.
12. National Cancer Institute. Pancreatic neuroendocrine tumors (islet cell
tumors) treatment (PDQ)—health professional version. https://www.
cancer.gov/types/pancreatic/hp/pnet-treatment-pdq. Published 2017.
Accessed April 3, 2017.
13. Keim V, Klar E, Poll M, Schoenberg MH. Postoperative care follow-
ing pancreatic surgery: surveillance and treatment. Dtsch Arztebl Int.
2009;106(48):789-794.
14. Pappas S, Krzywda E, McDowell N. Nutrition and pancreaticoduodenec-
tomy. Nutr Clin Pract. 2010;25(3):234-243.
15. Christein JD, Smoot RL, Farnell MB. Central pancreatectomy: a technique
for the resection of pancreatic neck lesions. Arch Surg. 2006;141(3):293-299.
16. Christein JD, Farnell MB. The role of total pancreatectomy in the treat-
ment of pancreatic cancer. In: Von Hoff DD, Evans DB, Hruban RH, eds.
Pancreatic Cancer. Sudbury, MA: Jones & Bartlett; 2005:287-298.
17. Gallagher SF, Zervos EE, Murr MM. Distal pancreatectomy. In: Von Hoff
DD, Evans DB, Hruban RH, eds. Pancreatic Cancer. Sudbury, MA: Jones
& Bartlett; 2005:299-311.
18. Riall TS, Yeo CJ. Pylorus preservation versus standard pancreaticoduo-
denecctomy. In: Von Hoff DD, Evans DB, Hruban RH, eds. Pancreatic
Cancer. Sudbury, MA: Jones & Bartlett; 2005:313-320.
19. Yen TWF, Abdalla EK, Pisters PWT, Evans DB. Pancreaticoduodenectomy.
In: Von Hoff DD, Evans DB, Hruban RH eds. Pancreatic Cancer.
Sudbury, MA: Jones & Bartlett; 2005:265-285.
20. Kang CM, Lee JH. Pathophysiology after pancreaticoduodenectomy.
World J Gastroenterol. 2015;21(19):5794-5804.
21. Wastell C. Malabsorptive states after gastrointestinal surgery. Br Med J.
1968;3(5619):661-664.
22. Sullivan S, Alpers D, Klein S. Nutritional physiology of the alimentary
tract. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR,
eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD:
Lippincott Williams & Wilkins; 2014:540-573.
23. Weaver CM, Heaney RP. Calcium. In: Ross AC, Caballero B, Cousins
RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease.
11th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &
Wilkins; 2014:133-149.
24. Mohammed S, Van Buren Ii G, McElhany A, Silberfein EJ, Fisher WE.
Delayed gastric emptying following pancreaticoduodenectomy: inci-
dence, risk factors, and healthcare utilization. World J Gastrointest Surg.
2017;9(3):73-81.
25. Beane JD, House MG, Miller A, et al. Optimal management of delayed
gastric emptying after pancreatectomy: an analysis of 1,089 patients.
Surgery. 2014;156(4):939-946.
26. Sabater L, Ausania F, Bakker OJ, et al. Evidence-based guidelines for the
management of exocrine pancreatic insufficiency after pancreatic surgery.
Ann Surg. 2016;264(6):949-958.
27. Dominguez-Munoz JE. Pancreatic exocrine insufficiency: diagnosis and
treatment. J Gastroenterol Hepatol. 2011;26(suppl 2):12-16.
28. Lindkvist B, Phillips ME, Dominguez-Munoz JE. Clinical, anthropomet-
ric and laboratory nutritional markers of pancreatic exocrine insufficiency:
Prevalence and diagnostic use. Pancreatology. 2015;15(6):589-597.
29. Dominguez-Munoz JE. Pancreatic enzyme therapy for pancreatic exo-
crine insufficiency. Gastroenterol Hepatol. 2011;7(6):401-403.
30. Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pan-
creatic insufficiency: present and future. Clin Exp Gastroenterol. 2011;4:
55-73.
31. Layer P, Keller J, Lankisch PG. Pancreatic enzyme replacement therapy.
Curr Gastroenterol Rep. 2001;3(2):101-108.
597
32. Bartel MJ, Asbun H, Stauffer J, Raimondo M. Pancreatic exocrine insuf-
ficiency in pancreatic cancer: a review of the literature. Dig Liver Dis.
2015;47(12):1013-1020.
33. Matsumoto J, Traverso LW. Exocrine function following the whipple
operation as assessed by stool elastase. J Gastrointest Surg. 2006;10(9):
1225-1229.
34. Muniz CK, dos Santos JS, Pfrimer K, et al. Nutritional status, fecal elas-
tase-1, and 13C-labeled mixed triglyceride breath test in the long-term
after pancreaticoduodenectomy. Pancreas. 2014;43(3):445-450.
35. Nordback I, Parviainen M, Piironen A, Raty S, Sand J. Obstructed pancre-
aticojejunostomy partly explains exocrine insufficiency after pancreatic
head resection. Scand J Gastroenterol. 2007;42(2):263-270.
36. Speicher JE, Traverso LW. Pancreatic exocrine function is preserved after
distal pancreatectomy. J Gastrointest Surg. 2010;14(6):1006-1011.
37. Wray CJ, Ahmad SA, Matthews JB, Lowy AM. Surgery for pancreatic
cancer: recent controversies and current practice. Gastroenterology.
2005;128(6):1626-1641.
38. Morera-Ocon FJ, Sabater-Orti L, Munoz-Forner E, Perez-Griera J, Ortega-
Serrano J. Considerations on pancreatic exocrine function after pancreati-
coduodenectomy. World J Gastrointest Oncol. 2014;6(9):325-329.
39. Ma JP, Peng L, Qin T, et al. Meta-analysis of pancreaticoduodenectomy
prospective controlled trials: pancreaticogastrostomy versus pancreatico-
jejunostomy reconstruction. Chin Med J (Engl). 2012;125(21):3891-3897.
40. Makni A, Bedioui H, Jouini M, et al. Pancreaticojejunostomy vs pancreat-
icogastrostomy following pancreaticoduodenectomy: results of compara-
tive study. Minerva Chir. 2011;66(4):295-302.
41. Sarner M. Treatment of pancreatic exocrine deficiency. World J Surg.
2003;27(11):1192-1195.
42. Ellison NM, Chevlen E, Still CD, Dubagunta S. Supportive care for
patients with pancreatic adenocarcinoma: symptom control and nutrition.
Hematol Oncol Clin North Am. 2002;16(1):105-121.
43. DiMagno EP, Reber HA, Tempero MA; American Gastroenterological
Association. AGA technical review on the epidemiology, diagnosis,
and treatment of pancreatic ductal adenocarcinoma. Gastroenterology.
1999;117(6):1464-1484.
44. Babayan VK. Medium chain triglycerides and structured lipids. Lipids.
1987;22(6):417-420.
45. Armstrong T, Strommer L, Ruiz-Jasbon F, et al. Pancreaticoduodenectomy
for peri-ampullary neoplasia leads to specific micronutrient deficiencies.
Pancreatology. 2007;7(1):37-44.
46. Armstrong T, Walters E, Varshney S, Johnson CD. Deficiencies of micronutri-
ents, altered bowel function, and quality of life during late follow-up after pan-
creaticoduodenectomy for malignancy. Pancreatology. 2002;2(6):528-534.
47. Appaswamy S, De Silva D, Tyagi A, Grocott LE, Heath PD, Gillow T.
Reversible night blindness in a patient with neuroendocrine tumour of
pancreas. Eye (Lond). 2005;19(6):720-722.
48. Tiang S, Warne R. Nyctalopia: the sequelae of hypovitaminosis A. BMJ
Case Rep. 2010;2010:bcr0520102965.
49. Dutta SK, Bustin MP, Russell RM, Costa BS. Deficiency of fat-soluble
vitamins in treated patients with pancreatic insufficiency. Ann Intern Med.
1982;97(4):549-552.
50. Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic conse-
quences of (regional) total pancreatectomy. Ann Surg. 1991;214(2):131-140.
51. Parrish CR, Baumgartner MR, Goodin BJ. Small intestine malabsorptive
disorders. In: Maltarese LE, Mullin GE, Raymond JL, eds. The Health
Professional’s Guide to Gastrointestinal Nutrition. Chicago, IL: Academy
of Nutrition and Dietetics; 2015:47-62.
52. Office of Dietary Supplements. Vitamin A fact sheet for health profes-
sionals. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/.
Published 2016. Accessed April 30, 2017.
53. Maskell C, Daniels P, Johnson CD. Dietary intake after pancreatectomy.
Br J Surg. 1999;86(3):323-326.
54. Haaber AB, Rosenfalck AM, Hansen B, Hilsted J, Larsen S. Bone min-
eral metabolism, bone mineral density, and body composition in patients
with chronic pancreatitis and pancreatic exocrine insufficiency. Int J
Pancreatol. 2000;27(1):21-27.
598
55. Christensen AT, Ostergard T, Andersen V. Severe impaired deambulation
in a patient with vitamin D and mineral deficiency due to exocrine pancre-
atic insufficiency. JOP. 2011;12(5):482-484.
56. Klapdor S, Richter E, Klapdor R. Vitamin D status and per-oral vitamin D
supplementation in patients suffering from chronic pancreatitis and pan-
creatic cancer disease. Anticancer Res. 2012;32(5):1991-1998.
57. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treat-
ment, and prevention of vitamin D deficiency: an Endocrine Society clini-
cal practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
58. Office of Dietary Supplements. Vitamin D fact sheet for health profes-
sionals. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/.
Published 2016. Accessed April 30, 2017.
59. Ong HS, Ng EH, Heng G, Soo KC. Pancreaticoduodenectomy with pancre-
aticogastrostomy: assessment of patients’ nutritional status, quality of life
and pancreatic exocrine function. Aust N Z J Surg. 2000;70(3):199-203.
60. Fink AS, DeSouza LR, Mayer EA, Hawkins R, Longmire WP Jr. Long-
term evaluation of pylorus preservation during pancreaticoduodenectomy.
World J Surg. 1988;12(5):663-670.
61. Carmel R. Cobalamin (vitamin B12). In: Ross AC, Caballero B, Cousins
RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease.
11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:369-389.
62. Bang Jorgensen B, Thorsgaard Pedersen N, Worning H. Short report:
lipid and vitamin B12 malassimilation in pancreatic insufficiency. Aliment
Pharmacol Ther. 1991;5(2):207-210.
63. Shamberger RC, Hendren WH, Leichtner AM. Long-term nutritional
and metabolic consequences of pancreaticoduodenectomy in children.
Surgery. 1994;115(3):382-388.
64. Kim JH, Bae YJ, Jun KH, Chin HM. Long-term trends in hematological
and nutritional status after gastrectomy for gastric cancer. J Gastrointest
Surg. 2017;21(8):1212-1219.
65. Jun JH, Yoo JE, Lee JA, et al. Anemia after gastrectomy in long-term sur-
vivors of gastric cancer: a retrospective cohort study. Int J Surg. 2016;28:
162-168.
66. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood.
2008;112(6):2214-2221.
67. King JC, Cousins RJ. Zinc. In: Ross AC, Caballero B, Cousins RJ, Tucker
KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed.
Baltimore MD: Lippincott Williams & Wilkins; 2014:189-205.
68. Yazbeck N, Muwakkit S, Abboud M, Saab R. Zinc and biotin defi-
ciencies after pancreaticoduodenectomy. Acta Gastroenterol Belg.
2010;73(2):283-286.
69. Yasuda H, Fujiwara N, Ishizaki Y, Komatsu N. Anemia attributed
to vitamin B6 deficiency in post-pancreaticoduodenectomy patients.
Pancreatology. 2015;15(1):81-83.
70. Yu HH, Yang TM, Shan YS, Lin PW. Zinc deficiency in patients undergo-
ing pancreatoduodenectomy for periampullary tumors is associated with
pancreatic exocrine insufficiency. World J Surg. 2011;35(9):2110-2117.
71. Yu HH, Shan YS, Lin PW. Zinc deficiency with acrodermatitis entero-
pathica-like eruption after pancreaticoduodenectomy. J Formos Med
Assoc. 2007;106(10):864-868.
72. Lam M, Adelstein DJ. Hypomagnesemia and renal magnesium wasting in
patients treated with cisplatin. Am J Kidney Dis. 1986;8(3):164-169.
73. Saif MW. Management of hypomagnesemia in cancer patients receiving
chemotherapy. J Support Oncol. 2008;6(5):243-248.
74. Schilsky RL, Anderson T. Hypomagnesemia and renal magnesium wast-
ing in patients receiving cisplatin. Ann Intern Med. 1979;90(6):929-931.
75. Sutton RA, Walker VR, Halabe A, Swenerton K, Coppin CM. Chronic
hypomagnesemia caused by cisplatin: effect of calcitriol. J Lab Clin Med.
1991;117(1):40-43.
76. Olsen M, Davis PF, Douglas TT, et al. Side effects of cancer therapy. In:
Polovich M, Olsen MM, LeFebvre KB, Oncology Nursing Society, eds.
Chemotherapy and Biotherapy Guidelines and Recommendations for
Practice. 4th ed. Pittsburgh, PA: Oncology Nursing Society; 2014:171-390.
77. Burkhart RA, Gerber SM, Tholey RM, et al. Incidence and severity of
pancreatogenic diabetes after pancreatic resection. J Gastrointest Surg.
2015;19(2):217-225.
Nutrition in Clinical Practice 32(5)
78. Cui Y, Andersen DK. Pancreatogenic diabetes: special considerations for
management. Pancreatology. 2011;11(3):279-294.
79. Maeda H, Hanazaki K. Pancreatogenic diabetes after pancreatic resection.
Pancreatology. 2011;11(2):268-276.
80. Hata T, Ishida M, Motoi F, et al. Clinical characteristics and risk factors
for the development of postoperative hepatic steatosis after total pancre-
atectomy. Pancreas. 2016;45(3):362-369.
81. Ohgi K, Okamura Y, Yamamoto Y, et al. Perioperative computed tomog-
raphy assessments of the pancreas predict nonalcoholic fatty liver disease
after pancreaticoduodenectomy. Medicine (Baltimore). 2016;95(6):e2535.
82. Takemura N, Saiura A, Koga R, Yamamoto J, Yamaguchi T. Risk factors
for and management of postpancreatectomy hepatic steatosis [published
online September 20, 2016]. Scand J Surg.
83. Ito Y, Kenmochi T, Shibutani S, et al. Evaluation of predictive factors in
patients with nonalcoholic fatty liver disease after pancreaticoduodenec-
tomy. Am Surg. 2014;80(5):500-504.
84. Kato H, Isaji S, Azumi Y, et al. Development of nonalcoholic fatty liver
disease (NAFLD) and nonalcoholic steatohepatitis (NASH) after pancre-
aticoduodenectomy: proposal of a postoperative NAFLD scoring system.
J Hepatobiliary Pancreat Sci. 2010;17(3):296-304.
85. Kishi Y, Shimada K, Nara S, Esaki M, Kosuge T. Administration of pan-
crelipase as effective treatment for hepatic steatosis after pancreatectomy.
Pancreas. 2015;44(6):983-987.
86. Nagaya T, Tanaka N, Kimura T, et al. Mechanism of the development
of nonalcoholic steatohepatitis after pancreaticoduodenectomy. BBA Clin.
2015;3:168-174.
87. Nakagawa N, Murakami Y, Uemura K, et al. Nonalcoholic fatty liver dis-
ease after pancreatoduodenectomy is closely associated with postoperative
pancreatic exocrine insufficiency. J Surg Oncol. 2014;110(6):720-726.
88. Nomura R, Ishizaki Y, Suzuki K, Kawasaki S. Development of
hepatic steatosis after pancreatoduodenectomy. AJR Am J Roentgenol.
2007;189(6):1484-1488.
89. Okamura Y, Sugimoto H, Yamada S, et al. Risk factors for hepatic
steatosis after pancreatectomy: a retrospective observational cohort
study of the importance of nutritional management. Pancreas.
2012;41(7):1067-1072.
90. Sato R, Kishiwada M, Kuriyama N, et al. Paradoxical impact of the rem-
nant pancreatic volume and infectious complications on the development
of nonalcoholic fatty liver disease after pancreaticoduodenectomy. J
Hepatobiliary Pancreat Sci. 2014;21(8):562-572.
91. Song SC, Choi SH, Choi DW, Heo JS, Kim WS, Kim MJ. Potential risk fac-
tors for nonalcoholic steatohepatitis related to pancreatic secretions following
pancreaticoduodenectomy. World J Gastroenterol. 2011;17(32):3716-3723.
92. Tanaka N, Horiuchi A, Yokoyama T, et al. Clinical characteristics of de
novo nonalcoholic fatty liver disease following pancreaticoduodenec-
tomy. J Gastroenterol. 2011;46(6):758-768.
93. Yoo DG, Jung BH, Hwang S, et al. Prevalence analysis of de novo hepatic
steatosis following pylorus-preserving pancreaticoduodenectomy. Dig
Surg. 2014;31(4-5):359-365.
94. Terrie YC. Understanding pancreatic enzyme products. Pharmacy Times.
http://www.pharmacytimes.com/publications/issue/2008/2008-12/
p2ppeps-1208. Published 2008. Accessed April 30, 17.
95. Nagai M, Sho M, Satoi S, et al. Effects of pancrelipase on nonalcoholic
fatty liver disease after pancreaticoduodenectomy. J Hepatobiliary
Pancreat Sci. 2014;21(3):186-192.
96. Satoi S, Sho M, Yanagimoto H, et al. Do pancrelipase delayed-release
capsules have a protective role against nonalcoholic fatty liver disease
after pancreatoduodenectomy in patients with pancreatic cancer? A ran-
domized controlled trial. J Hepatobiliary Pancreat Sci. 2016;23(3):167-
173.
97. Yamazaki S, Takayama T, Higaki T, et al. Pancrelipase with branched-
chain amino acids for preventing nonalcoholic fatty liver disease after
pancreaticoduodenectomy. J Gastroenterol. 2016;51(1):55-62.
98. Raoof M, Naslund I, Rask E, Szabo E. Effect of gastric bypass on bone
mineral density, parathyroid hormone and vitamin D: 5 years follow-up.
Obes Surg. 2016;26(5):1141-1145.