Islet Isolation and Transplantation

Tatsuya Kin, James Shapiro, Edmond A Ryan, Jonathan RT Lakey
Clinical Islet Transplant Program, University of Alberta and Capital Health Authority.
Edmonton, Alberta, Canada
ABSTRACT
Context Annular pancreas is an uncommon
congenital anomaly formed by a thin band of
normal pancreatic tissue encircling the
duodenum.
Case report We report the first case of an
islet isolation and transplantation from an
annular pancreas. The pancreas together with
duodenum was procured from a 32-year-old
previously healthy man after diagnosis of
brain death. The pancreas including the
annular portion was distended well after
intraductal collagenase perfusion. A total of
276,064 islet equivalent was recovered and
transplanted into a type 1 diabetic patient.
Conclusions Bearing in mind the shortage of
donors, patients with this anomalous
condition should not be excluded as potential
organ donors.
INTRODUCTION
Annular pancreas is a rare congenital anomaly
formed by a thin band of normal pancreatic
tissue that completely or partially encircles
the second portion of the duodenum. During
embryonic development, the ventral
pancreatic primordium moves to the right and
rotates posteriorly until it comes to lie to the
left of the duodenum, subsequently fusing to
the dorsal primordium. Annular pancreas is
believed to be due to a defect in the normal
rotation of the ventral primordium [1].
Although the genetic and molecular basis for
this anomaly remains obscure, Indian
hedgehog or sonic hedgehog inactivation in
mice has been shown to cause overgrowth of
ventral pancreatic tissue, a phenotype
strikingly similar to annular pancreas [2].
Since 1986, our Clinical Islet Transplant
Program at the University of Alberta has
obtained more than 900 human pancreata
from cadaveric donors for islet isolation. We
report our first case of islet isolation and
transplantation from an annular pancreas.
CASE REPORT
A 32-year-old male who did not have notable
medical history was admitted for head trauma
secondary to a vehicle accident. The
laboratory tests including serum amylase
levels were within normal range. After
diagnosis of brain death and obtaining
consent, his pancreas was procured at a
distant hospital and sent to our laboratory.
The pancreas was preserved by the two-layer
method for 11.5 hours prior to islet isolation.

Page 2
JOP. J Pancreas (Online) 2005; 6(3):7001-7xxx.
JOP. Journal of the Pancreas – http://www.joplink.net – Vol. 6, No. 3 – May 2005. [ISSN 1590-8577]
275
Upon arrival, the organ was visually inspected
as usual and diagnosis of annular pancreas
was easily made based on its anatomical
structure (Figure 1). Any other abnormal
findings were not observed. Two catheters (16
G) were inserted into the main duct and
directed towards the head and tail of the
pancreas following dissection of the main
duct in the mid-body of the pancreas. Then
the pancreas was distended with collagenase
solution through the catheters. During the 10
min of intraductal delivery of enzyme,
uniform distension of the gland, including the
ring of pancreatic tissue was observed.
Leakage of the solution was observed only
from the orifice of Wirsung’s duct. The
orifice of Santorini duct was not detected. The
pancreas was transferred to a digestion
chamber device for mechanical and enzymatic
digestion. There was 13.7 g of undigested
tissue remaining in the chamber after
digestion, while initial weight of the pancreas
was 110.2 g. Islet yield after digestion was
388,365 islet equivalent (IE). Islets were
purified by continuous gradients of Ficoll
using a refrigerated cell processor. After
culture for 18 hours and subsequent re-
purification of less pure preparation, a total of
276,064 IE were recovered in 4.0 mL of
pelletted volume. The viability of the islet
tissue was 92% as measured using a
membrane integrity test (SYTO-13/ethidium
bromide) [3]. The islets were transplanted into
a type 1 diabetic patient. Islet infusion was
clinically uneventful and did not significantly
affect portal pressure. Immediate islet
function was demonstrated by the rapid
elevation of serum C peptide, and confirmed
by the significant decrease in the daily dose of
exogenous insulin (Table 1).
DISCUSSION
Annular pancreas is an extremely rare
anomaly, with an incidence of three in 20,000
autopsies [4]. During the past 19 years, we
obtained more than 900 pancreata from brain-
dead donors for islet isolation, and this is the
first case of annular pancreas we encountered.
The coexistence of annular pancreas with
pancreas divisum is well documented [1].
Previous studies have demonstrated a higher
frequency of pancreas divisum in individuals
with annular pancreata than in the general
population [5]. In our case, the donor did not
have pancreas divisum, as the orifice of
Santorini duct was obliterated.
To our knowledge, this is the first reported
case of an islet isolation and transplantation
from an annular pancreas, although whole
organ transplantation of an annular pancreas
has been reported previously [6, 7].
Intraductal collagenase perfusion and uniform
distention of the gland are crucial to
pancreatic digestion during clinical islet
isolation. Therefore, pancreata with
parenchymal damage are not ideal for islet
isolation. In cases of annular pancreas, special
care must be taken to avoid parenchymal
injury when dissecting the duodenum.
Regarding cannulation methods, some centers
employ a single catheter insertion from the
head of pancreas. Our method of cannulation
Figure 1. Photograph of the annular pancreas during
intraductal collagenase perfusion.
Table 1. Graft function after transplantation.
Pre-
transplant
Post-
transplant
Fasting serum C-peptide
Reference range:
0.17-0.66 nmol/L
<0.10
0.25
Fasting blood glucose
Reference range:
3.6-6.1 mmol/L
15.1
7.2
Insulin requirement
(units/kg/day)
0.50
0.29

Page 3
JOP. J Pancreas (Online) 2005; 6(3):7001-7xxx.
JOP. Journal of the Pancreas – http://www.joplink.net – Vol. 6, No. 3 – May 2005. [ISSN 1590-8577]
276
following exposure of the duct in the mid-
pancreas seemed to enable to get adequate
distention of the ring portion of the pancreas.
In conclusion, we have reported a successful
case of islet isolation and transplantation from
an annular pancreas. Bearing in mind the
shortage of donors, patients with this
anomalous condition should not be excluded
as potential organ donors.
Received February 18th, 2005 - Accepted
March 17th, 2005
Keywords Abnormalities; Diabetes Mellitus;
Islets of Langerhans
Abbreviations IE: islet equivalent
Correspondence
Jonathan RT Lakey
1074 Dentistry/Pharmacy Building
University of Alberta
Edmonton, Alberta
Canada T6G 2N8
Phone: +1-780.492.3077
Fax: +1-780.492.6335
E-mail: jlakey@ualberta.ca
References
1. Ladd AP, Madura JA. Congenital duodenal
anomalies in the adult. Arch Surg 2001; 136:576-84.
[PMID 11343551]
2. Hebrok M, Kim SK, St Jacques B, McMahon AP,
Melton DA. Regulation of pancreas development by
hedgehog signaling. Development 2000; 127:4905-13.
[PMID 11044404]
3. Barnett MJ, McGhee-Wilson D, Shapiro AMJ,
Lakey JRT. Variation in human islet viability based on
different membrane integrity stains. Cell Transplant
2004; 13:481-8. [PMID 15565860]
4. Ravitch MM, Woods AC Jr. Annular pancreas.
Ann Surg 1950; 132:1116-27. [PMID 14790583]
5. Baggott BB, Long WB. Annular pancreas as a
cause of extrahepatic biliary obstruction. Am J
Gastroenterol 1991; 86:224-6 [PMID 1992639]
6. Barone GW, Henry ML, Elkhammas EA, Tesi RJ,
Ferguson RM. Whole-organ transplant of an annular
pancreas. Transplantation 1992; 53:492-3. [PMID
1738944]
7. Romagnoli J, Papalois VE, Hakim NS.
Transplantation of an annular pancreas with enteric
drainage. Int Surg 1998; 83:36-7. [PMID 970651

There are no products listed under this category.