DOI:10.2214/AJR.07.2809
AJR 2007; 189:1484-1488
© American Roentgen Ray Society
Development of Hepatic Steatosis After Pancreatoduodenectomy
Ryohei Nomura1,
Yoichi Ishizaki1,
Kazuhiro Suzuki2 and
Seiji Kawasaki1
1 Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of
Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
2 Department of Radiology, Juntendo University School of Medicine, Tokyo,
Japan.
Received December 19, 2006;
accepted after revision July 6, 2007.
Address correspondence to Y. Ishizaki
(ishizaki{at}med.juntendo.ac.jp).
Abstract
OBJECTIVE. To determine the effects of pancreatoduodenectomy on
hepatic fat content, hepatic CT attenuation was evaluated after
pancreatoduodenectomy.
CONCLUSION. Pancreatoduodenectomy had a significant influence on
hepatic fat content and was associated with frequent occurrence of hepatic
steatosis, which was easily recognized with CT.
Keywords: CT • hepatic steatosis • pancreatoduodenectomy
Introduction
Pancreatoduodenectomy (Whipple procedure) has been used increasingly to
resect a variety of malignant tumors of the pancreatic head and periampullary
area. At many tertiary referral centers, pancreatoduodenectomy is performed
with a complication rate of less than 40% and a death rate of 5% or lower
[1,
2]. Because approximately one
half of the exocrine and endocrine tissue is left intact after
pancreatoduodenectomy, the postoperative morbidity and mortality associated
with this operation are principally due to leakage from the
pancreatojejunostomy or to other perioperative events. As experience with
pancreatoduodenectomy grows, however, an increasing number of patients recover
from the procedure and live with the resulting alteration of the anatomic
configuration of the upper gastrointestinal tract. The long-term metabolic
consequences of pancreatoduodenectomy are difficult to predict and range from
minimal to major metabolic derangements
[3,
4]. Although a small number of
reports [5,
6] have suggested that fatty
liver occurs in patients who have undergone pancreatoduodenectomy,
quantitative analyses of the development of hepatic steatosis after
pancreatoduodenectomy by use of CT attenuation values have been scant. In this
study, we retrospectively examined the unenhanced follow-up CT records of
patients who had undergone pancreatoduodenectomy to obtain their hepatic CT
attenuation values and to evaluate changes in hepatic fat content and the
development of hepatic steatosis.
Materials and Methods
The prospective database of our university surgical department for the
period between October 2001 and October 2005 was reviewed retrospectively.
Between October 2001 and October 2005, 69 patients underwent
pancreatoduodenectomy at our institution. In all 69 patients, the surgical
reconstructions were performed according to the Child method
[7]. On the basis of the
findings at preoperative evaluation, patients with fatty liver, excessive
alcohol consumption (> 150 g weekly), severe obesity (body mass index
[weight in kilograms divided by height squared in meters] > 30), diabetes
mellitus, chronic hepatitis type B or type C, or steroid therapy were excluded
from this study. Nineteen patients who did not undergo postoperative
unenhanced abdominal CT also were excluded. The records of the other 42
patients who underwent postoperative unenhanced CT approximately 6 months
after pancreatoduodenectomy (mean, 6.0 months; range, 5.2–6.9) were
analyzed. There were 25 men and 17 women with a mean age of 65 years (range,
35–83 years). Pancreatoduodenectomy was performed for cancer of the
pancreatic head in 20 patients, cancer of the lower bile duct in 10, ampullary
cancer in seven, duodenal cancer in one patient, and benign disease in four
patients (intraductal papillary mucinous neoplasm in three patients, benign
bile duct stricture in one patient). Nine patients received adjuvant
chemotherapy (three cycles of gemcitabine 1,000 mg/m2 as a
30-minute infusion weekly on days 1, 8, and 15 followed by a 1-week rest).
Body weight, body mass index, fasting lipid levels, fasting blood glucose
level, and levels of liver-associated enzymes (aspartate aminotransferase,
alanine aminotransferase, alkaline phosphatase, and 
-glutamyl
transpeptidase) were determined before pancreatoduodenectomy and at the time
of postoperative unenhanced CT. In 25 of 42 patients, unenhanced CT scans were
available approximately 12 months after pancreatoduodenectomy (average, 12.1
months; range, 11.1–13.0 months), and hepatic steatosis on CT images was
evaluated. Unenhanced CT scans were available for nine of 14 patients in whom
hepatic steatosis developed 6 months after pancreatoduodenectomy and for 16 of
28 patients in whom hepatic steatosis did not develop.
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Fig. 1 —56-year-old man with pancreatic cancer. CT scan shows areas
used to calculate liver-to-spleen CT attenuation value ratios. Hepatic and
splenic attenuation values were measured on unenhanced CT scans by use of four
regions of interest in liver and one in spleen.
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CT images were obtained with a 4-MDCT scanner (Aquilion, Toshiba) without
IV contrast material during a single breath-hold. Scanning parameters for
unenhanced CT were as follows: beam collimation, 3 mm; table speed, 10.5
mm/rotation; gantry rotation time, 0.5 second; 120–135 kVp; 60–225
mAs. The raw data set was reconstructed at 5-mm thickness. CT images were
reviewed on a PACS workstation (TWS-5100L1, Toshiba Medical Systems) by a
radiologist blinded to the clinical course. One patient with liver metastasis
was included in the study because the decrease in liver attenuation was due to
fat infiltration rather than to liver metastasis.
For each patient, the average CT attenuation values in four sectors of the
liver and in one region of the spleen were monitored for evaluation of the
effect of pancreatoduodenectomy on hepatic fat content. Each region of
interest was a circular area with a diameter of 1.5 cm
(Fig. 1). To detect the
development of hepatic steatosis and to monitor its severity, we calculated
the liver-to-spleen attenuation ratio on CT and the difference between hepatic
and splenic attenuation on CT. Hepatic steatosis was defined as a
liver-to-spleen attenuation ratio less than 0.9 or a hepatic attenuation value
at least 10 H lower than the splenic attenuation value
[8,
9].
Continuous variables were expressed as mean ± SD. Statistical
analysis of laboratory data was conducted with a paired-samples Student's
t test. Categoric variables were compared by use of the chi-square
test. Calculations were made with the StatView computer program (SAS
Institute). Differences at p < 0.05 were considered statistically
significant.
Results
Effect of Pancreatoduodenectomy on Hepatic Attenuation and Fat Content
Although the mean splenic attenuation values of all patients remained
unchanged after pancreatoduodenectomy (p = 0.231, paired Student's
t test), the mean hepatic attenuation values of all patients had a
statistically significant decrease (p < 0.001, paired Student's
t test), and the mean liver-to-spleen attenuation ratio and
difference between hepatic and splenic attenuation of all patients decreased
significantly (p < 0.001, p < 0.001, respectively,
paired Student's t test) (Table
1).
Time Course of Imaging Findings
In nine patients in whom hepatic steatosis developed 6 months after
pancreatoduodenectomy, steatosis had progressively resolved 12 months after
pancreatoduodenectomy in three patients, whereas it was still evident in the
other six. Among 16 patients in whom hepatic steatosis did not develop 6
months after pancreatoduodenectomy, 14 had stable imaging findings 12 months
after pancreatoduodenectomy, and the other two had progression of steatosis.
Hepatic steatosis had developed in eight (32%) of 25 patients 12 months after
pancreatoduodenectomy.
Frequency and Clinical Evaluation of Hepatic Steatosis
Twenty-eight (67%) of the patients had decreased hepatic attenuation but
not enough to be labeled on CT criteria for hepatic steatosis. Six months
after pancreatoduodenectomy, 14 (33%) of the patients had decreased hepatic
attenuation, meeting the criteria for hepatic steatosis defined in this study
(Fig. 2). The decrease in
hepatic attenuation was diffuse throughout the liver rather than focal in all
14 subjects. Figures 3A and
3B shows a representative case
in which CT attenuation of the liver decreased dramatically after
pancreatoduodenectomy. None of the preoperative variables listed in
Table 2 in the patients who met
the criteria for hepatic steatosis after pancreatoduodenectomy was
significantly different from that in patients who did not meet the criteria.
Among 28 patients who did not meet the criteria, postoperative
liver-associated enzyme levels, body weight, body mass index, total
cholesterol level, and triglyceride level were normal 6 months after
pancreatoduodenectomy. In 14 patients who met the criteria for hepatic
steatosis, postoperative fasting blood glucose level and aspartate
aminotransferase level were significantly increased after
pancreatoduodenectomy. Presence of pancreatic cancer and postoperative
adjuvant chemotherapy did not affect the development of hepatic steatosis
(Table 3).
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Fig. 3A —83-year-old woman with representative CT findings of hepatic
steatosis after pancreatoduodenectomy. Unenhanced abdominal CT image obtained
before pancreatoduodenectomy shows normal homogeneous hepatic CT attenuation,
which is slightly higher than spleen attenuation (liver-to-spleen attenuation
ratio, 1.257; difference between liver and spleen attenuation, 12.16).
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Fig. 3B —83-year-old woman with representative CT findings of hepatic
steatosis after pancreatoduodenectomy. Unenhanced abdominal CT image obtained
6 months after pancreatoduodenectomy shows marked decrease in hepatic
attenuation (liver-to-spleen attenuation ratio, –0.0901; difference
between liver and spleen attenuation, –55.78).
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Discussion
In this study, the mean hepatic attenuation value, and thus the hepatic fat
content, of all patients was significantly influenced by
pancreatoduodenectomy. Fourteen (33%) of 42 patients had a decrease in hepatic
attenuation, thus meeting the criteria for liver steatosis, and the fasting
blood glucose level was significantly elevated. Although liver biopsy is used
as the standard method for quantitative assessment of the degree of hepatic
steatosis, it is an invasive procedure that can cause morbidity
[8]. Instead of histologic
evaluation of hepatic fat content, unenhanced CT can be performed for
diagnosis of hepatic steatosis with well-established accuracy
[9–13].
There is a good inverse relation between the attenuation value and the
triglyceride content of the liver. For the diagnosis of hepatic steatosis, a
cutoff value of the liver-to-spleen attenuation ratio of less than 0.9 or a
hepatic CT attenuation value 10 H less than that of the spleen have been used
frequently [8,
9]. These two indexes have been
suggested to have high diagnostic performance and no significant difference in
the evaluation of hepatic steatosis
[14].
The mechanism responsible for the effects of pancreatoduodenectomy on
hepatic fat content has not been elucidated. Pancreatic resection results in
hormonal abnormalities that are dependent on the extent and location (proximal
vs distal) of the resected portion of the gland. The form of glucose
intolerance that results from pancreatic resection is termed pancreatogenic
diabetes [15]. It is
associated with features distinct from both type 1 and type 2 diabetes. In
addition to insulin deficiency, the endocrine abnormalities that accompany
pancreatic resection can include glucagon deficiency and pancreatic
polypeptide deficiency. The regulation of glucose metabolism is largely
dependent on these three circulating glucoregulatory hormones secreted by the
pancreas [16,
17].
Hepatic steatosis is relatively uncommon in patients with type 1 diabetes
but is very common in those with type 2 diabetes, occurring in approximately
one half of all cases [18].
The cause of fatty infiltration of the liver in type 1 diabetes is increased
release of fatty acids from adipose tissue secondary to hyperglycemia and an
inadequate insulin level. In type 2 diabetes, fatty infiltration is caused by
increased dietary fat and carbohydrate intake and increased metabolism of
fatty acids. Although the cause of the hepatic lesions complicating
pancreatoduodenectomy is unknown, pancreatogenic diabetes may be related to
hepatic steatosis.
The rapid weight loss after pancreatoduodenectomy that results in
protein-calorie malnutrition and a decrease in essential amino acids may be
another factor in the pathogenesis of hepatic steatosis
[19]. In this study, the
average body weight 8 weeks after the operation had decreased significantly
from 56.3 ± 10.0 kg to 49.7 ± 8.1 kg (p < 0.001).
The most likely mechanism of fatty infiltration is decreased synthesis of
lipoproteins, which results in decreased export of lipid from the liver.
Bacterial overgrowth with production of endotoxin followed by mitochondrial
damage due to lipid peroxidation also has been postulated as a mechanism of
fatty liver in protein-calorie malnutrition
[20].
A number of case reports and study findings have suggested that
chemotherapy can be associated with steatosis
[21]. Several chemotherapeutic
drugs (for example, 5-fluorouracil, platinum derivatives, and taxanes) induce
oxidative stress in both cancer cells and normal cells exposed to
chemotherapy. This chemotherapy-induced oxidative stress can lead to hepatic
steatosis. Although in this study hepatic steatosis tended to be more common
in patients receiving adjuvant chemotherapy (p = 0.082), the
difference did not reach statistical significance.
Pancreatoduodenectomy had a significant influence on hepatic fat content
and was associated with frequent occurrence of hepatic steatosis. Periodic
unenhanced CT studies are useful for detecting and monitoring the clinical
course of hepatic steatosis after pancreatoduodenectomy. The frequent
occurrence of hepatic steatosis after pancreatoduodenectomy may result in
secondary hepatic dysfunction.
Acknowledgments
We extend special thanks to Shozaburou Shibata for work related to the
management of the CT data and CT image analysis.
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Abstract
Introduction
