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Chapter 3 / Chronic Pancreatitis 31
Longitudinal Pancreaticojejunostomy
Operative pancreatic drainage for pancreatitis was described in a small
series of patients by Puestow and Gillesby in 1957. A modication of this
original drainage procedure that more closely resembles modern day
technique was reported by Partington and Rochelle in 1960. e clas-
sic operation for pancreatic drainage, the lateral pancreaticojejunostomy
(LPJ), entails opening the pancreatic duct anteriorly along its length within
a brotic gland, medially to the level of the gastroduodenal artery. e
opened pancreatic duct is then anastomosed to a Roux-en-Y jejunal limb
(Fig. 3.1).
Potential signicant procedure-specic complications include intra-
operative hemorrhage due to splenic vein or gastroduodenal artery injury,
postoperative hemorrhage typically from the gastroduodenal artery, and
anastomotic leak seen in 10% of cases.
Multiple retrospective case series have been reported evaluating out-
comes with LPJ, with pain relief rates of 48% to 91%. Morbidity rates are low
(20% on average) and endocrine and exocrine function is often preserved.
LPJ is an eective and safe procedure for pain relief in many patients with
dilated duct pancreatitis. A secondary failure rate does exist with LPJ,
often attributed to disease burden in the head of the pancreas. Intraductal
stone disease in the head of the pancreas can be cleared with intraopera-
tive pancreatoscopy and lithotripsy, which has been shown to improve
outcomes (reduced readmissions, increased pain relief rates). Patients with
signicant burden of inammatory brosis in the head of the pancreas may
be better served with a localized pancreatic head resection along with a
pancreaticojejunostomy.
Local Resection of the Pancreatic Head with Longitudinal
Pancreaticojejunostomy
In the mid-1980s, Frey and colleagues described adding a localized resec-
tion of the head of the pancreas along with an LR-LPJ. is procedure
addresses the inammatory disease burden often found in the head of the
pancreas in patients with dilated duct pancreatitis. In addition, LR-LPJ has
the advantage of duodenal preservation. In modern series, pain relief rates
of 62% to 88% are reported, with morbidity of 20% to 30% (Fig. 3.2).
Pancreatoduodenectomy
In 1946, Dr. Whipple described pancreatoduodenectomy (PD) for CP.
Patients with an inammatory mass in the head of the pancreas and those
with diuse small duct disease with the head as the suspected pacemaker
of disease may benet from PD. Pain relief rates of 70% to 89%, morbid-
ity of 16% to 53%, and mortality of less than 5% are reported. Procedure-
specic signicant complications include intraoperative hemorrhage from
portal vein injury, postoperative biliary leak, postoperative pancreatic s-
tula (POPF), postoperative hemorrhage from the ligated gastroduodenal
artery, and delayed gastric emptying, the latter two often associated with
postoperative pancreatic leak. Grading of POPF is according to clinical sig-
nicance (Table 3.4).
e pylorus-preserving pancreatoduodenectomy (PPPD) was popular-
ized in the 1970s by Traverso and Longmire and has been embraced by many
pancreatic surgeons. Pylorus preservation i s intended to improve nutritional
outcomes, although studies have not conrmed this proposed advantage.
Pain relief rates and endocrine outcomes are similar between the classic PD
(with antrectomy) and PPPD, although improved professional rehabilitation
and improved quality of life after PPPD have been touted. Technical conduct
of PD (and distal pancreatectomy [DP]) is detailed in Chapter 7.
Section I / Pancreas32
FIGURE 3.1 A. After exposure of the full length of the pancreas, the pancreatic duct is identi-
ed by aspiration using a 21-gauge needle on a 5-mL syringe. B. The Roux-en-Y limb is brought
alongside the pancreas in an isoperistaltic fashion. The longitudinal pancreatic ductotomy is vis-
ible. Two corner stitches are placed between the jejunum and the apices of the ductotomy. An
enterotomy is then made lengthwise along the jejunum, in parallel to the pancreatic ductotomy.
Aspiration of dilated
pancreatic duct
A
B
(Continued)
Chapter 3 / Chronic Pancreatitis 33
Duodenum-Preserving Pancreatic Head Resection
In the 1970s, Beger described the technique of duodenum-preserving pan-
creatic head resection. In this procedure, the inamed and brotic pancre-
atic head tissue is resected, leaving the duodenum and terminal bile duct
intact. e intent is to minimize surgical morbidity, including the long-term
morbidity of duodenal resection. Pain relief after this procedure has been
reported in 77% to 88% of patients with professional rehabilitation in 63% to
69% and morbidity of 29%. Several variations of duodenum-preserving pan-
creatic head resection have evolved at various centers, primarily in Europe
(Fig. 3.3).
Multiple randomized controlled trials comparing the dierent
approaches to pancreatic head resection have been undertaken and are
summarized in Table 3.5. While the advantage of any single procedure has
not been demonstrated, this eort in outcome research has been important
in moving the eld of pancreatic surgery forward.
Pancreas
Stomach
Roux-en-Y
jejunal loop
Duodenum
Pancreas
Duct
Stomach
Duodenum
Roux-en-Y
jejunal loop
Omentum
Transverse
mesocolon
Transverse
colon
C
FIGURE 3.1 (Continued) C. A completed Roux-en-Y lateral pancreatojejunostomy. (From
Lillemoe K, Jarnigan W, eds. Master techniques in surgery: hepatobiliary and pancreatic
surgery. Philadelphia, PA: Lippincott Williams & Wilkins, 2013.)
Section I / Pancreas34
FIGURE 3.2 Frey procedure. A. The Frey procedure combines a circumscript excision
in the pancreatic head with longitudinal opening of the pancreatic duct toward the tail.
B. Reconstruction is performed with an anastomosis with a Roux-en-Y jejunal loop.
Compared to the Beger procedure, the extent of resection of the pancreatic head is smaller;
however, reconstruction is easier as it only requires one anastomosis to the pancreas. (From
Lillemoe K, Jarnigan W, eds. Master techniques in surgery: hepatobiliary and pancreatic
surgery. Philadelphia, PA: Lippincott Williams & Wilkins, 2013.)
A
B
Chapter 3 / Chronic Pancreatitis 35
Distal Pancreatectomy
In CP patients with a midpancreatic body ductal stricture or those with dis-
ease localized to the body and tail of the pancreas, a DP can be benecial.
Pain relief rates of 57% to 84% are reported with return to work in 29% to
73% and morbidity rates of 15% to 32%. POPF is the most important poten-
tial procedure-specic complication and occurs in up to 30% of cases.
Grade A B C
Clinical condition Well Often well Ill appearing/bad
Specic treatment No Yes/no Yes
US/CT (if obtained) Negative Negative/positive Positive
Persistent drainage
(after 3 wk)
No Usually yes Ye s
Reoperation No No Yes
Death related to POPF No No Possibly yes
Signs of infection No Yes/no Yes
Sepsis No No Yes
Readmission No Yes/no Yes/no
US, ultrasound; CT, computed tomography; POPF, postoperative pancreatic stula.
From Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic stula: an international study
group (ISGPF) denition. Surgery 2005;138:8–13.
Grading System for Postoperative Pancreatic Fistula
TABLE
3.4
A
FIGURE 3.3 Beger procedure. A. The pancreas is dissected on the level of the portal vein.
The pancreatic head is excavated and the duodenum is preserved with a thin layer of pan-
creatic tissue. If the bile duct is obstructed, it can be opened and an internal anastomosis
with the excavated pancreatic head can be performed as shown.
(Continued)
Section I / Pancreas36
Total Pancreatectomy with Islet Autotransplantation
An early description of TP for CP comes from Dr. Clagett in 1944. Tellingly,
his patient died 10 weeks postoperatively from a hypoglycemic event. In
some patients with debilitating pain from CP, TP can be an eective means
of pain relief. Candidates for TP include patients with diuse small duct
pancreatitis, those that have failed lesser procedures, and those with hered-
itary pancreatitis.
Parenchymal preserving procedures are always considered preferen-
tially to TP when possible to minimize morbidity. e obligatory incipient
pancreatogenic diabetes that results from TP can be prohibitively morbid,
even with current diabetes management tools including the insulin pump.
e largest recent series of patients undergoing TP is from the Mayo Clinic
in 2005. In that series, 26% of long-term survivors were rehospitalized for
glycemic control, and diabetes-related quality of life was poor.
In the 1970s, IAT was developed at the University of Minnesota, where
islets are harvested from the resected pancreas immediately after resection
and returned to the patient through the portal vein into the liver. e rst
successful procedure was described by Dr. Sutherland in 1978. Over the
B
FIGURE 3.3 (Continued) B. The reconstruction is performed with two anastomoses, of
the pancreatic tail remnant and of the excavated pancreatic head with a Roux-en-Y jejunal
loop. (From Lillemoe K, Jarnigan W, eds. Master techniques in surgery: hepatobiliary and
pancreatic surgery. Philadelphia, PA: Lippincott Williams & Wilkins, 2013.)
Chapter 3 / Chronic Pancreatitis 37
past decade, interest in this technique has grown, with now several centers
oering TP–IAT for CP.
Morbidity rates of 48% to 56% and 0% to 2% mortality are reported
in TP–IAT. Pain relief is described in 80% to 85% patients after TP–IAT.
Statistically signicant improvements in both physical and mental
health–related quality of life are noted as early as 6 months postopera-
tively and appear durable in 3-year follow-up. Insulin independence is
described in 25% to 40% patients in short-term follow-up up to 3 years.
Longer-term follow-up demonstrates decline in islet function over time;
however, C-peptide production has been documented up to 13 years post-
operatively. Longer-term follow-up is needed for this relatively radical
procedure.
Minimally Invasive Pancreatic Surgery
Laparoscopic pancreatic resection originated in the 1990s with the explo-
sion of laparoscopy and the associated development of laparoscopic tools
including the endoscopic stapler. Laparoscopic distal pancreatectomy
(LDP) is the most commonly performed laparoscopic pancreas resection. A
large multi-institutional study evaluated 667 DPs, 159 (24%) of which were
laparoscopic. Of these, only 14 (9%) of these LDPs were for CP. While LDP
is most commonly performed for benign or low-grade neoplasms, it is also
applied to patients with CP. e inammatory distortion of anatomy, loss
of normal tissue planes, and frequent coexistence of sinistral (left-sided)
portal hypertension in CP make these cases extremely challenging.
Laparoscopic PD is being performed at many centers now through-
out the world. e largest single-center series is from India by Palanivelu
with 75 patients, with mean operative time of 357 minutes, blood loss
74mL, hospital stay 8.2 days, morbidity 26.7%, and mortality 1.3%. At the
Mayo Clinic, Kendrick has reported on 65 patients, with outcomes similarly
comparable to open resection, and has additionally reported on 11 patients
safely undergoing major venous reconstruction via a totally laparoscopic
route. e limitations of laparoscopic PD in the CP patient are similar to
those encountered for DP.
Study Comparison N Morbidity Mortality Pain Relief, %
Klempa et al. 1995 PD 21 51 0 70
DPPHR 22 54 5 82
Buchler et al. 1995 PPPD 20 20 0 67
DPPHR 20 15 0 94
Farkas et al. 2006 PPPD 20 40 0 90
DPPHR 20
0 0 85
Izbicki et al. 1995 DPPHR 20 20 0 95
LR-LPJ 22 9 0 89
Izbicki et al. 1998 LR-LPJ 31 19 3 90
PPPD 30 53 0 71
Strate et al. 2005 DPPHR 38 NR NR 82
LR-LPJ 36 NR NR 81
PD, pancreatoduodenectomy; DPPHR, duodenum-preserving pancreatic head resection; PPPD,
pylorus-preserving pancreatic head resection; LR-LPJ, local resection pancreatic head with
longitudinal pancreaticojejunostomy.
Comparative Randomized Controlled Trials of Pancreatic
Head Resection
TABLE
3.5
Section I / Pancreas38
CONCLUSIONS
CP remains a challenging disorder in the current era. In basic science, progress
is occurring in the understanding of underlying genetic and cellular mecha-
nisms of disease, with hopes for smart pharmacologic interventions includ-
ing enzyme pathway inhibition. On the surgical front, sophisticated therapies
are evolving including minimally invasive techniques and TP with IAT. In
addition, in neuroscience, the recognition of neuroplasticity and maladaptive
central pain pathways as an important factor in CP pain management holds
promise for continued progress in the management of this dicult disease.
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head of the pancreas in severe chronic pancreatitis. Surger y 1985;97:465–475.
Buchler MW, Friess H, Muller MW, et al. Randomized trial of duodenum preserving
pancreatic head resection versus pylorus preserving whipple in chronic pancre-
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surgical drainage of the pancreatic duct in patients with chronic pancreatitis.
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39
EPIDEMIOLOGY
Cancer of the exocrine pancreas, commonly referred to as pancreatic ductal
adenocarcinoma (PDAC), aects over 44,000 people a year and is the fourth
leading cause of cancer-related deaths in the United States with approxi-
mately 37,000 annual mortalities. Approximately 11 new cases of PDAC
are diagnosed per 100,000 of the population annually. At diagnosis, most
patients are advanced (metastatic), with only 15% to 20% of patients being
candidates for a potentially curative surgical resection. Resection oers the
best possibility for cure (particularly when margin negative and node nega-
tive), with 5-year survival rates around 20% when performed at specialized
high-volume centers. Nevertheless, median survival after resection is only
about 2 years and, for all stages, 5-year survival is an abysmal 3%.
PATHOLOGY
Solid Epithelial Neoplasms of the Exocrine Pancreas
e most common solid exocrine pancreatic tumors are pancreatic ductal
adenocarcinoma and its variants, acinar cell carcinoma and pancreatoblas-
toma. PDAC accounts for greater than 90% of all exocrine tumors of the
pancreas and represents the vast majority of cases referred for surgical con-
sultation. us, the rest of the discussion in this chapter will focus on the
management of PDAC. Histologically, the neoplastic cells in PDAC show
ductal dierentiation, induce an intense and characteristic desmoplastic
stromal reaction, and display an inltrative growth pattern. PDAC is thought
to develop from benign proliferative precursor lesions, termed pancreatic
intraepithelial neoplasia (PanIN), as a result of the progressive accumulation
of tumorigenic mutations. Variants of PDAC include giant cell, adenosqua-
mous, mucinous (noncystic), and anaplastic carcinomas. Acinar cell carci-
nomas tend to form larger tumors than PDAC, form acini which display an
eosinophilic and granular cytoplasm, and have a slightly better prognosis
than PDAC. Pancreatoblastomas occur in children 1 to 15 years old, con-
tain both epithelial and mesenchymal components, are usually larger than
10cm, and have a more favorable prognosis than PDAC.
ETIOLOGY
Risk Factors for Pancreatic Ductal Adenocarcinoma
e risk of developing PDAC is related to demographic, acquired, and host
factors. Overall, any given person has a 0.5% risk of developing PDAC by
age 70.
(a) Demographic Factors: e peak incidence of PDAC is in the seventh to
eighth decades, with more than 80% of cases occurring between 60 and
80 years. PDAC is more common in men compared to females, with a rela-
tive risk of 1.35. Compared with Whites, both the incidence and mortality
Pancreatic Adenocarcinoma
Jashodeep Datta, Jeffrey A. Drebin,
and Charles M. Vollmer Jr
4
Section I / Pancreas40
rates for PDAC are higher in African Americans of both genders. Other
demographic characteristics associated with PDAC include lower socio-
economic status, migrant status, and Ashkenazi Jewish heritage.
(b) Acquired or Environmental Factors: Tobacco smoke exposure is the most
consistently observed environmental risk factor for the development of
PDAC, while the contributory role of alcohol or various dietary substances
is more equivocal. PDAC risk increases in obese patients—a large cohort
study showed a 1.72 relative risk of PDAC in patients with body mass
index (BMI) ≥
30 kg/m
2
compared to individuals with BMI≤23 kg/m
2
.
Moreover, moderate physical activity was associated with decreased
PDAC rates. An association between diabetes mellitus (DM) and PDAC
has also been posited due to the observation that approximately 80%of
PDAC patients have impaired glucose metabolism, impaired glucose
tolerance, or DM. Type 2 DM of at least 5 years’ duration has been
demonstrated to increase the risk of PDAC twofold. However, among
newly diagnosed diabetics, only 0.85% developed PDAC within 3 years.
Additionally, chronic pancreatitis, cystic brosis, benign endocrine
tumors, and pernicious anemia have also been implicated in elevating
PDAC risk.
(c) Host Factors: Only around 2% of PDAC can be considered “inherited.”
is consists of two distinct cohorts: (i) familial lineage of PDAC (genet-
ics as yet undetermined) and (ii) genetic syndromes caused by recog-
nized germ line mutations. ese are as follows: (i) hereditary pancreatitis
(50-fold risk): autosomal dominant, PRSSI mutation on gene locus 7q35,
and recurrent pancreatitis from a young age; (ii) hereditary nonpolyposis
colorectal cancer (HNPCC type II) (eightfold risk): autosomal dominant,
MSH2/MLH1 mutation, and colonic, endometrial, and gastric cancers;
(iii) Peutz-Jeghers syndrome (32-fold risk): autosomal dominant, STK11/
LKB1 mutation on 19p13, and gastrointestinal hamartomatous polyps
and mucocutaneous pigmentation; (iv) familial atypical multiple mole
melanoma (FAMMM) syndrome (12- to 20-fold risk): autosomal domi-
nant, p16 mutation on 9p21, and multiple atypical nevi and melanoma;
(v) hereditary breast and ovarian cancer (5- to 10-fold risk): autosomal
dominant, BRCA2 mutation on 13q12–13, and breast and ovarian can-
cers; and (vi) ataxia–telangiectasia: autosomal recessive, ATM mutation
on 11q22–23, and ataxia, telangiectasia, and hematologic malignan-
cies. In addition, analysis of kindreds enrolled in the National Familial
Pancreas Tumor Registry revealed an 18-fold increased risk of PDAC in
familial PDAC kindreds compared to sporadic PDAC groups. e germ
line mutation(s) responsible for the familial predisposition to PDAC is/
are yet to be elaborated. Elevated risk begins with at least two aected
rst-degree relatives and escalates signicantly with each additional
family member. ere is no known established relationship between a
family history of pancreatic cancer and the development of pancreatic
cystic neoplasms that devolve into PDAC.
Molecular Genetics
Signicant advances have been made in understanding the molecular
genetics associated with PDAC in recent years. e pathogenesis of PDAC
involves alterations in the following: (i) tumor suppressor genes: p16, p53,
MADH4/DPC4, and BRCA2 are found to be inactivated in up to 90%, 75%,
55%, and 7% of sporadic PDAC cases, respectively; (ii) oncogenes: activating
point mutations in K-ras—a guanine nucleotide–binding protein involved
in growth factor signal transduction—are seen in between 80% and 100%
of PDAC cases. In spite of being widely investigated as a potential diagnos-
tic or prognosticative marker in PDAC, K-ras cannot be recommended for