PANCREATIC UPDATE
| INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS (IPMN)—Waddah B. Al-Refaie, MD,
Assistant Professor of Surgery, Division of Surgical Oncology, University of Minnesota, and Minneapolis Veterans Affairs
Medical Center
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| Introduction: IPMNs represent ≈5% of pancreatic exocrine tumors; characteristics—mucin-producing with cystic dilatations
and papillary growth projection; wide histologic spectrum
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| Demographics: mean age at diagnosis, 6th to 7th decade; in more contemporary series, no sex or racial predilection; no
classic set of signs and symptoms (usually found incidentally); of those with symptoms, 50% present with abdominal
pain and 20% with pancreatitis; often diagnosed as pseudocyst (detailed history and physical examination for history of
pancreatitis essential to avoid this mistake); majority of tumors occur in head of pancreas, up to 35% diffuse, and <10%
in tail, uncinate process, or body of pancreas
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| Histopathologic features: wide spectrum; benign, borderline, or invasive; macroscopic features important to know in preoperative
period, including cross-sectional imaging; must have pathologist document type of IPMN (main duct, branch duct,
or mixed type; prognostic features); World Health Organization classification includes adenoma, borderline, or invasive; preoperative
work-up similar to that with any pancreatic mass; patients present with cystic mass throughout pancreas; detailed
history and physical examination, with attention to history of pancreatitis; serum tumor markers of no proven value; computed
tomography (CT) of abdomen and pelvis important (high volume of information), whereas endoscopic ultrasonography and
fine needle aspiration not as helpful; in upper gastrointestinal endoscopy, classic feature of mucin exuding from papilla of
pancreas helpful in distinguishing IPMN; magnetic resonance cholangiopancreatography (MRCP) provides excellent cross-
sectional imaging (probably will substitute for endoscopic retrograde cholangiopancreatography [ERCP] to avoid intubating
pancreas and related complications); thin-cut dual-phase CT recommended (≥2.5 mm); determine whether mass cystic or
solid; important to recognize nature of pancreatic pass and to follow one pattern of diagnosis; thin-cut CT helps in determining
tumor-vessel relationship (whether tumor resectable); regardless of histology, if tumor involves celiac or superior mesenteric
artery (SMA) or superior mesenteric vein–portal vein confluence, not resectable; up to 20% aberrant right hepatic artery
encountered; presence of extrapancreatic disease precludes resection; CT criteria for resectability—absence of tumor or
disease at celiac and SMA vessels; patent portal vein–superior mesenteric vein confluence; absence of metastasis
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| Distinguishing IPMNs from other pancreatic lesions: serous cystic neoplasms—classically have multiple
cysts; honeycomb appearance with central calcification; traditionally found in head of pancreas (similar to IPMN); benign in
majority of cases; surgery performed for symptoms only; IPMN tends to communicate with duct of pancreas, compared to mucinous
cystic neoplasm (MCN; mucin exuding from duct found in IPMN); chronic pancreatitis—pancreatic ductal dilatation
present in both; calcification absent in IPMN; ≤15% of patients with IPMN have intraductal mass; multi-institutional
studies showed majority had main-duct IPMN; main-duct IPMN most common and with highest rate of malignancy (almost
42%, according to one study); IPMN vs MCN—traditionally, IPMN found in head of pancreas, while MCN found in distal
portion; equal sex distribution in IPMN, while MCN more common in women; IPMN ubiquitous in pancreas, whereas MCN
isolated; ovarian-like stroma distinguishes MCN from IPMN; ductal dilatation unlikely in MCN, but more likely in main- or
mixed-type IPMN; all features identifiable in preoperative period, except ovarian-like stroma
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| Surgical management of IPMN: pancreatectomy; R0 resection desired, and partial pancreatectomy (pancreaticoduodenectomy
vs distal pancreatectomy) advocated; total pancreatectomy in diffuse-type IPMN sometimes performed (possible
postoperative diabetes); up to 15% of patients require conversion from partial to total pancreatectomy; reason for high
conversion rate better understanding of IPMN; international consensus guidelines advocate partial pancreatectomy; pancreatectomy
offered for main-type and mixed-type IPMNs because of high likelihood of invasive component; nonoperative approach
recommended for branch-type IPMN, especially when small-duct, asymptomatic, and no nodules; more common in older patients;
decision about treatment in branch-type IPMN—base treatment decisions on features (whether more likely to be
malignant), comorbidities of patient, and patient preference; no data to support branch-type IPMN with mixed component
(large or asymptomatic duct); intraoperative margin assessment important; no evidence to support extended lymphadenectomy
in IPMN (even in invasive IPMN, low rate of lymph node metastasis); pancreatectomy-related mortality <5%; complication
profile similar to that for pancreatic ductal adenocarcinoma for resection; surgical margins after resection of IPMN important;
however, caution necessary; performing R0 resection does not mean there is no disease in remnant of pancreas (only confirms
no disease in resection margin); artifact and loss of epithelium described; each case individualized based on resection; distant
recurrence more common than local, especially for invasive component; branch-type more likely indolent disease than main-
duct or invasive component in invasive IPMN; study—addition of chemotherapy for invasive IPMN favorably affected survival,
especially for patient with node-positive disease
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| Predictors of malignancy: nodularity on duct of pancreas and increased ducts of main duct prognostic features of malignancy;
main-duct IPMN and obstructive jaundice prognostic of high risk for invasive IPMN (compared to absence of nodularity
or branch-type IPMN); study—patients with branch-type IPMN less likely to have invasive type (except Johns Hopkins
group); multifocality location in head associated with low risk for invasive IPMN; no correlation between size of lesion and invasion
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| Survival outcome: Japanese study—patients with branch-type IPMN had more favorable prognosis; patients with noninvasive
type had more favorable outcomes than those with invasive type
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| Methods of follow-up: limited data; consider risk factors in preoperative setting, type (branch, duct, or mixed), and presence
of nodularity; watchful waiting reasonable in low-risk patients; necessary to utilize high-resolution cross-sectional imaging
in follow-up; recommended algorithm—consensus from international group for branch-type IPMN; if mass >3 cm,
perform resection; if branch-type and <1 cm, follow patient and determine risks for malignancy; after pancreatectomy,
cross-sectional imaging (high-resolution CT or magnetic reesonance imaging [MRI]) recommended for surveillance for
IPMN; length of follow-up unclear; serum tumor markers of no value; possible development of synchronous or other
metachronous malignancy at same time
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| PANCREAS—James A. Schulak, MD, Professor of Surgery, Case Western Reserve University School of Medicine, and
Director, Division of Transplant and Hepatobiliary Surgery, University Hospitals of Cleveland, OH
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| Anatomy: surgery to pancreas requires good understanding of possible vascular anomalies, particularly those related to arterial
supply of foregut; liver and stomach can receive arterial supply from SMA in different ways; pancreas dual organ (98%
exocrine; 2% endocrine [islet cells]); neuroendocrine tumors—frequently cause pancreatitis; usually small, but often strategically
located around pancreatic duct, blocking it and causing chronic pancreatitis; 3 major reasons for surgery—
acute pancreatitis (to reverse severe inflammatory response syndrome [SIRS]); chronic pancreatitis (due to development of
pseudocyst or intractable pain); neoplastic disease (solid or cystic, malignant or benign)
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| Acute pancreatitis: major causes alcohol or gallstones; also various drugs and hyperlipidemia; not surgical disease;
most patients have edematous pancreas, fever, and chills; usually resolves with conservative measures
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| When surgical intervention necessary: patients who develop necrosis in pancreas (demonstrated by contrast-enhanced
CT) may need intervention; intervene only when patients fail medical management (includes support and use of antibiotics [imipenem-cilastatin
and fluconazole]); if patient has clear-cut fluid collection and appears ill, pancreas should be aspirated; if no
bacteria or fungi present, surgery not necessary (exception deteriorating patient; need to operate to remove infected fluid and reduce
inflammatory syndrome); most patients resolve with good medical support as long as they have no infection; previously,
infection trigger for surgery (to drain pancreas); today, not always the case; culturing fluid collection in acute
pancreatitis—Candida second-most common organism cultured; fluid collection, even when infected, can be managed
with percutaneous drainage (less invasive); if no improvement, surgery necessary; patients with sterile necrosis—if fail to
resolve, have ongoing inflammation, or have life-threatening hemorrhage, consider angiography first; surgical technique
straightforward; should not pull, grab, or use any force to remove tissue (can cause bleeding); adequate drainage; results similar
with packing or drains; fistulas—patients who undergo drainage or resection may develop fistula; most fistulas heal without
surgery; if drainage <50 mL/day, manage at home; no evidence that octreotide works; if drainage 50 to 100 mL/day and high in
amylase, patient may need total parenteral nutrition (TPN) to promote healing or stoppage of leakage
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| Chronic pancreatitis: usually have pseudocyst or serious unrelenting pain; etiology often alcohol but could be persistent
pancreatitis due to any reason; medical management—if patient can tolerate discomfort long enough, often resolves
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| Surgical intervention: indications—severe pain requiring narcotic use and causing major alteration in lifestyle; failure
to thrive; pancreatic mass; obstructive jaundice; chronic symptomatic pseudocyst; patient with sinistral portal hypertension;
acute pancreatitis, chronic pancreatitis, and thrombosis of splenic vein can lead to gastroparesis (patients often
need spleen removed or stomach devascularized)
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| Pseudocysts: speaker believes surgery necessary only if pseudocyst bothersome; obtain new CT before performing surgery
on pseudocyst (may have already resolved); even larger cysts can resolve; Mayo Clinic experience showed that 50%
of cysts >10 cm resolved; pancreatic cyst not pseudocyst if patient never had pancreatitis (instead, cystic neoplasm); obtain
ERCP to determine whether pseudocyst communicates with pancreatic duct; if communication present, percutaneous
drainage ineffective; have endoscopist place stent across papilla (reduces resistance to flow of pancreatic fluids from pancreas);
can also perform endoscopic transgastric drainage; necessary to wait until cyst wall mature, then biopsy (ensure
fibrotic tissue present and not epithelial cells [indicative of neoplasm])
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| Other surgical considerations: dilated duct pancreatitis—also perform surgery; longitudinal
pancreaticojejunostomy—easy operation; not necessary to sew bowel to mucosa; if chronically obstructed pancreatic
duct from pancreatitis present, distal pancreatectomy often better than Whipple procedure; spleen-preserving technique; tedious
but leaves patient in better condition afterwards; if mass present in head of pancreas and patient has obstructive jaundice,
perform Whipple procedure; needle biopsies only helpful if positive; patients almost always good candidates for
pylorus-sparing pancreaticoduodenostomy
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| Pancreatic neoplasms: when resections performed in high-volume centers, mortality rate usually <3% (in patients <65
or 70 yr of age, <1%); obtain adequate imaging and determine whether superior mesenteric vein, SMA, and celiac artery
involved with tumor (if involved, unable to perform resection [only consider surgery if performing palliative bypass]);
needle biopsy before surgery not important; percutaneous biopsy important only if no surgical intervention and patient
desires nonsurgical therapy (diagnosis necessary); Whipple procedure—2 techniques (standard and pylorus-sparing);
no difference in outcomes for cure of cancer and complications (exception, delayed gastric emptying less frequent with
standard operation); survival—if tumor <2 cm, no positive lymph nodes, and clear margins, 40% chance of cure; if tumor
>2 cm with positive nodes, 5-yr survival 20% to 25%; if unable to perform operation with low morbidity and mortality,
omit surgery; however, patients who have had Whipple procedure and recurrent cancer often live 2 to 4 yr; tumors in
body and tail of pancreas—by time of presentation, often too late; perform distal pancreatectomy with good margin
and splenectomy
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| Cystic neoplasms of pancreas: cystic lesion is neoplasm until proven otherwise; types include serous, mucinous, and
intraductal papillar mucinous (now seen with greater frequency); IPMNs ductal disease (communicate with main [more
likely malignant] and branch ducts); mucinous cystic neoplasms—rarely communicate with duct; 30% to 50% chance
of becoming malignant, and need resection; serous neoplasms—almost never become malignant; if classic appearance
on CT with no mucin on aspiration, observation adequate; any cyst >3 cm or causing symptoms worrisome; classical serous
pancreatic neoplasm in tail of pancreas large; patient probably has symptoms; speaker would resect unless patient
old, feeble, and not good candidate; important to aspirate cysts if need to observe them, unless <2 cm; if mucin present
or have high carcinoembryonic antigen (CEA) content, clearly neoplasm with high risk for malignancy; treatment resection;
not necessary to perform cancer operation if certain that serous cyst; if cyst part of IPMN or mucinous cyst adenoma,
should perform cancer operation (good margins); cystic neoplasms have fairly high rates of becoming cancerous;
algorithm for managing cysts—if tumor <2 cm, and patient old and fragile, observation; if >2 cm, further evaluation;
if mucin or CEA present in cyst, surgery
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| PANCREATIC NECROSECTOMY—Michael G. Sarr, MD, JC Masson Professor of Surgery, Mayo Clinic College of
Medicine, Rochester, MN
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| Approaches: CT road map for necrosectomy; marsupialization—old technique; create peritoneostomy; pancreatic debridement;
pack lesser sac open; problem that incision closes by second intention; mortality similar but fluids lost; problems include
packing changes often require anesthesia, loss of tissue fluids, loss of abdominal domain, trauma of packing changes, and
persistent necrosis; one-stop approach—pancreatic necrosectomy; place wide sump drainages in pancreatic bed; mortality
same; problem 40% of patients require another approach due to persistent undrained necrosis or persistent abscess;
pancreatic necrosectomy (leaving irrigation catheters in pancreatic bed and perfusing pancreatic wound
postoperatively)—popularized in Germany; postoperative irrigation used 2 L/hr for ≥10 days; mortality same; useful in selective
cases; staged debridement—performed if necessary to operate early; repeated necrosectomy (mean of 2 times);
eventual wound closure over drains; mortality same; initial operative approach—midline incision (preserves lateral
abdominal wall for drains); full exposure of pancreas; perform extensive necrosectomy, looking at paracolic retroperitoneal
gutters on right and left sides, using CT as guide; also look above pancreas in supraretroperitoneal space and base of
small bowel mesentery; speaker prefers using Waterpik irrigator; if returning, loose wet gauzes placed into bed of pancreas
with drains on top; cover vessels with silastic sheet; fascial reapproximation; perform necrosectomy 2 days later
and irrigate; once satisfied with control, speaker places gastrostomy tube, needle catheter jejunostomy if primarily middle
and left part of gland; if head of gland that goes through right mesocolon and affects duodenum, formal jejunostomy;
multiple soft closed-suction drains; fascial closure; minimal-access approach—new and difficult; endoscopic
necrosectomy—not always effective; must reendoscope patients multiple times
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Suggested Reading
Adsay NV et al: Chronic pancreatitis or pancreatic ductal adenocarcinoma? Semin Diagn Pathol 21:268, 2004; Baril
NB et al: Does an infected peripancreatic fluid collection or abscess mandate operation? Ann Surg 231:361, 2000; Connor
S et al: Early and late complications after pancreatic necrosectomy. Surgery 137:499, 2005; D'Angelica M et al:
Intraductal papillary mucinous neoplasms of the pancreas: an analysis of clinicopathologic features and outcome. Ann Surg
239:400, 2004; Heinrich S et al: Evidence-based treatment of acute pancreatitis: a look at established paradigms. Ann
Surg 243:154, 2006; Hruban RH et al: An illustrated consensus on the classification of pancreatic intraepithelial neoplasia
and intraductal papillary mucinous neoplasms. Am J Surg Pathol 28:977, 2004; Levi E et al: MUC1 and MUC2
in pancreatic neoplasia. J Clin Pathol 57:456, 2004; Lim JE et al: Prognostic factors following curative resection for
pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg 237:74, 2003; Nealon
WH et al: Main pancreatic ductal anatomy can direct choice of modality for treating pancreatic pseudocysts (surgery versus
percutaneous drainage). Ann Surg 235:751, 2002; Pawlik TM et al: Feasibility of a randomized trial of extended
lymphadenectomy for pancreatic cancer. Arch Surg 140:584, 2005; Sohn TA et al: Intraductal papillary mucinous neoplasms
of the pancreas: an updated experience. Ann Surg 239:788, 2004; Sugiyama M et al: Predictive factors for malignancy
in intraductal papillary-mucinous tumours of the pancreas. Br J Surg 90:1244, 2003; Tanaka M et al:
International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms
of the pancreas. Pancreatology 6:17, 2006; Wada K et al: Outcomes following resection of invasive and noninvasive
intraductal papillary mucinous neoplasms of the pancreas. Am J Surg 189:632, 2005; Warshaw AL: Pancreatic
necrosis: to debride or not to debride-that is the question. Ann Surg 232:627, 2000; Windsor JA: Minimally invasive
pancreatic necrosectomy. Br J Surg 94:132, 2007
Educational Objectives
| The goal of this program is to improve the management of pancreatic lesions. After hearing and assimilating this program,
the clinician will be better able to:
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 | 1. Differentiate intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic lesions.
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| 2. Recognize the predictors of malignancy for IPMNs.
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| 3. Determine when surgery is indicated in acute or chronic pancreatitis.
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| 4. Utilize the algorithm for managing cystic neoplasms of the pancreas.
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| 5. Describe the various approaches for pancreatic necrosectomy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts
were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial
interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Al-Refaie was recorded at the 30th Annual San Diego Postgraduate Assembly in Surgery, held February 26
through March 2, 2007, in San Diego, CA, and sponsored by the University of California, San Diego, School of Medicine,
Department of Surgery. Dr. Schulak was recorded at the 2nd Annual Surgery Update Course, held November 10-11,
2006, in Cleveland, OH, and sponsored by the Case Western Reserve University School of Medicine, Department of Surgery.
Dr. Sarr was recorded at the 36th Annual Postgraduate Course in Surgery, held April 12-14, 2007, in Charleston,
SC, and sponsored by the Medical University of South Carolina, Department of Surgery. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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