INSULINOMA
Vermie Garcia, MD; Michael H. Alay-ay, MD; Hernandez, MD; Leo Angelo Doble, MD
Fontano MJ, Francisco TP, Gabuat H, Gaffud PB, Gagtan M, Gallardo ELH, Garan EA, Garcia
CB, Garcia KFL, Garcia MJ, Garzon MMP, Tolentino MK
Department of Surgery – Clinical Division
University of Santo Tomas Hospital
INTRODUCTION
β-celltumors (insulinomas) are the most common pancreatic endocrine neoplasm and
maybe responsible for the elaboration of sufficient insulin to induce significant hypoglycaemia.
There is a characteristic clinical triad known as Whipple’s triad, resulting from these pancreatic
lesion; 1) attacks of hypoglycaemia occur with blood glucose levels below 50mg/dl of serum; 2)
the attack consist principally of such central nervous system manifestations as confusion,
stupor, and loss of consciousness; and, 3) attacks are precipitated by fasting or exercise and
are probably relieved by feeding or parenteral administration of glucose.
CASE PRESENTATION
Our patient is a 50 year old female, married, Filipino, Born Again Christian, born in
Surigao del Sur and currently residing at B7 L4, Silvertown 3, MalagasangRd., Imus, Cavite.
She was admitted at our institution last April 14, 2010 with a chief complaint of generalized
weakness.
History started ten years prior to admission, when patient occasionally experienced
dizziness, altered sensorium with generalized weakness, palpitations, blurring of vision, and
sweating. Symptoms noted to occur early in the morning after waking up. There were no
sensory deficits, heat and cold intolerance, polyuria, polyphagia, polydipsia. She sought consult
at a local hospital and was advised to have mental check-up due to altered sensorium but did
not comply.
Five years prior to admission, persistence of symptoms prompted consult at a local
hospital in Rizal where her blood glucose was incidentally noted to be low (unrecalled result).
Assessment then was hypoglycemia. No medication was given instead was advised to increase
glucose intake and have her blood glucose monitored regularly.
Six months prior to admission, symptoms occurred more frequently accompanied by
easy fatigability and nausea which noted to be relieved by eating. There were no episodes of
vomiting and abdominal pain noted. She sought consult at a local hospital in Cavite where she
was advised to monitor her blood glucose levels, and increase glucose intake.
Three months prior to admission, she sought
consult at USTH-OPD due to persistence of
symptoms and was admitted under the service of
Medicine. She then underwent serial fasting glucose
determination. However, her first blood glucose
level was already 40.5 mg/dL which is below 50
mg/dL (NV: 70.9-110mg/dL), blood insulin level was
Figure 1. CT Scan of abdomen
66.83 (NV: 0.275 units of insulin/lb of ideal wt.), C-peptide at 8.1 ng/mL (NV: 0.4-21ng/ml), and
HbA1c at 4.9 (NV: 4.5-6%). CT scan was then requested which revealed a well defined
enhancing pancreatic body nodule measuring 1.5x1.7x1.6 cms abutting the pancreatic duct
(Figure 1). She was advised to undergo surgery prior to discharge but lost to follow up and was
seen only on the day of the next admission under the service of Surgery.
Review of systems was fairly unremarkable except for weight gain which was
approximately 50% after two years. There were no noted abdominal pain, anxiety, black tarry
stools, bloatedness, headache, amenorrhea, infertility, anorexia, loss of coordination, mental
changes or confusion, muscle pain, nausea and vomiting, sensitivity to the cold and vision
problems.
Patient’s personal and social history was unremarkable. With regards to her past
medical history, she was diagnosed with acute renal failure s/p hemodialysis (3 sessions) in
2005. She also had CAP in 2005 where she was given unrecalled medications. Patient is nondiabetic, no history of PTB, asthma, and allergies. Her family is positive for hypertension, stroke,
asthma and liver disease.
On admission, the patient was conscious,
coherent,
ambulatory, not in cardio respiratory
distress with stable vital signs. Her weight and
height were 88.5 kg and 156cm respectively with
a BMI of 36.4 which is considered as obese. She
had warm moist skin, no active dermatoses, no
jaundice, pink palpebral conjunctiva, anicteric
Figure 2. CBG monitoring (mg/dL) on admission (04/15/2010)
sclera. There was no tragal tenderness, midline
nasal septum and no nasal discharge. Supple neck, no palpable cervical lymphadenopathy and
thyroid not enlarged.
She had symmetrical chest expansion, no crackles or retractions
appreciated, equal and clear breath sounds. Adynamic precordium, AB at 6th LICS AAL, S1>S2
apex, S2>S1 base, no murmurs appreciated. Globular abdomen, NABS, soft, liver span 8 cm R
MCL, no palpable mass, no tenderness, (-) Murphy’s sign, (-) CVA tenderness. Pulses full and
equal, no cyanosis, no edema. Neurologic examination was unremarkable.
On admission, laboratory work-ups from previous admission were correlated with the
present complaint. Assessment then was hypoglycemia secondary to hyperinsulinemia to
consider insulinoma. Diet consisted of 35 kcal/kg/day (65% CHO, 15% CHON, 25% fat) to
address her hypoglycemic episodes. Serial CBG monitoring was continued (Figure 2). Patient
was then scheduled for spleen sparing-distal pancreatectomy. Prior to operation, cbc showed
normal results while urinalysis revealed pyuria. Blood chemistry showed hypokalemia, 3.22
mmol/L (N:3.8-5mmol/L) and patient was given Kalium durule. ECG showed sinus rhythm with
normal tracing however, chest x-ray revealed cardiomegaly. Patient then was given the
assessment by CV-Med of minimal to moderate risk of developing perioperative cardiac
complications due to cardiomegaly and hypertension stage II. While the patient is on NPO, she
was maintained on D5NR 1L to avoid the development of symptomatic hypoglycemia. Two units
of packed RBC were prepared and she was given Class 1 ASA risk stratification by the
anesthesiology prior to surgery.
Patient underwent distal pancreatectomy-spleen sparing procedure last April 20, 2010
(Figures 3, 4 and 5). Intra-operatively a solitary 2.5x2cm mass was palpated at the body of the
pancreas (Figure 5). Surgery proceeded first by opening the retroperitoneum at the inferior
margin of the pancreas. The splenocolic ligament was then divided and ligated. After which the
Figure 3. Head and Body of the Pancreas
Figure 4. Spleen
Figure 5. A 2.5x2cm mass at the body of pancreas
superior mesenteric vein was then followed proximally through the avascular plane as it joins
the splenic vein to form the portal vein. The splenic artery was also identified and isolated
together with the splenic vein. The pancreas is then divided just to the left of the portal vein and
the pancreatic duct was identified and ligated followed by overlapping vertical mattress sutures
at the neck of the pancreas. The banches and tributaries of the splenic artery and vein to the
pancreas were serially ligated untl the tail of the pancreas was reached and the spleen was
preserved (Figure 4).
Post-operatively, patient was stable,
conscious and not in cardio respiratory
distress. Patient’s vital signs, urine output,
CBG and the JP drain were carefully
monitored.
Levemir
and
Actrapid
supplementaion were given as post operative
medications to control her blood glucose and
insulin levels and was progressed form a diet
Figure 6.CBG monitoring post-operatively.
of clear liquids to diet as tolerated. Patient had several episodes of hypertension and fever but
they were managed cautiously and CBG monitoring continued (Figure 6). She was also reffered
to DM Center for instructions on insulin injections.
DISCUSSION
The pancreas consists of the head, uncinate process, neck, body and tail. The head lies
within, and closely attached to, the ‘C’ of the duodenum. The main pancreatic duct (Wirsung)
runs the length of the gland. It usually joins the common bile duct at the ampulla of Vater to
enter the second part of the duodenum at the duodenal papilla. The accessory duct (Santorini)
opens into the duodenum proximal to the main duct. The gland is lobulated and produces the
exocrine secretion of digestive hormones from serous-secreting cells, arranged in alveoli.
Between these lie the islets of Langerhans, containing A cells (glucagons), B cells (insulin) and
D cells (gastrin and somatostatin). It lies in contact with the spleen and runs in the lienorenal
ligament. The spleen, in healthy adult humans, is approximately 11 centimetres (4.3 in) in length
and usually weighs 150 grams (5.3 oz) and lies beneath the 9th to the 12th thoracic ribs.
One of the major function of the pancreas is to secret insulin. The major function of
insulin is to counter the concerted action of a number of hyperglycemia-generating hormones
and to maintain low blood glucose levels. Because there are numerous hyperglycemic
hormones, untreated disorders associated with insulin generally lead to severe hyperglycemia
and shortened life span.In addition to its role in regulating glucose metabolism, insulin
stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells.
Insulinoma is an endocrine tumor of the pancreas derived from beta cells that ectopically
secretes insulin, which results in hypoglycemia. The average age of occurrence is 40–50 years.
Insulinomas are generally small (>90% are < 2 cm), usually not multiple (90%), and only 5–15%
are malignant; they almost invariably occur only in the pancreas, distributed equally in the
pancreatic head, body, and tail.
The most common clinical symptoms are due to the effect of the hypoglycemia on the
central nervous system (neuroglycemic symptoms) and include confusion, headache,
disorientation, visual difficulties, irrational behavior, or even coma. Also, most patients have
symptoms due to excess catecholamine release secondary to the hypoglycemia including
sweating, tremor, and palpitations. Characteristically these attacks are associated with fasting.
Insulinomas should be suspected in all patients with hypoglycemia, especially with a history
suggesting attacks provoked by fasting or with a family history of MEN-1.
The diagnosis of insulinoma requires the demonstration of an elevated plasma insulin
level at the time of hypoglycemia. The most reliable test to diagnose insulinoma is a fast up to
72 h with serum glucose, C-peptide, and insulin measurements every 4–8 h. If at any point the
patient becomes symptomatic or glucose levels are persistently <2.2 mmol/L (40 mg/dL), the
test should be terminated and repeat samples for the above studies obtained before glucose is
given. Some 70–80% of patients will develop hypoglycemia during the first 24 h and 98% by 48
h. In addition to having an insulin level >6 µU/mL when blood glucose is <40 mg/dL, some
investigators also require an elevated C-peptide and serum proinsulin level, an insulin/glucose
ratio >0.3, and a decreased plasma B-hydroxybutyrate level for the diagnosis of insulinomas.
Surreptitious use of insulin or hypoglycemic agents may be difficult to distinguish from
insulinomas. The combination of proinsulin levels (normal in exogenous insulin/hypoglycemic
agent users), C-peptide levels (low in exogenous insulin users), antibodies to insulin (positive in
exogenous insulin users), and measurement of sulfonylurea levels in serum or plasma will allow
the correct diagnosis to be made.
Insulinomas are usually localized with CT scanning and endoscopic ultrasound (EUS).
Technical advances in EUS have led to preoperative identification of more than 90% of
insulinomas. Arteriography with catheterization of small arterial branches of the celiac system
combined with calcium injections (which stimulate insulin release from neoplastic tissue but not
from normal islets), and simultaneous measurements of hepatic vein insulin during each
selective calcium injection localizes tumors in 47% of patients.Intraoperative transabdominal
high-resolution ultrasonography with the transducer wrapped in a sterile rubber glove and
passed over the exposed pancreatic surface detects more than 90% of insulinomas.Helical or
multislice CT scan has 82-94% sensitivity. In one study, dual-phase helical CT proved more
sensitive than single-phase for detection of insulinoma.
In patients presenting with signs and symptoms compatible with hypoglycemia with
hyperinsulinemia includes reactive hypoglycaemia, functional hypoglycaemia with gastrectomy,
adrenal Insufficiency, hypopituitarism, hepatic insufficiency, manchausen syndrome (insulin selfinjections), nonislet cell tumor causing hypoglycaemia, surreptitious administration of insulin or
OHAs. In our patient, she presented with signs and symptoms compatible with that of
Insulinoma like sympathetic nervous system symptoms resulting from hypoglycemia namely,
palpitations, irritability and weakness. The Whipple’s triad were also satisfied with hypoglycemic
symptoms produced during fasting, blood glucose levels <50mg/dL during symptomatic attack,
and these symptoms were relieved by administration of glucose.
MANAGEMENT
Conservative management
Due to persistently elevated insulin levels, patients will often become hypoglycemic with
fasting. To prevent hypoglycemia in these patients, it is advisable to recommend small frequent
meals that are rich in carbohydrates. Furthermore, patients should be advised to have a supply
of glucose-rich snacks or candies on hand, in case they become symptomatic. It is desirable for
these patients to have a meal shortly before sleep and again when waking in the morning. In
addition to symptoms from fasting, Whipple's triad includes symptoms during exercise.
Therefore, strenuous exercise should be avoided as much as possible. If prolonged physical
activity must be undertaken, the patient should have glucose-rich drinks or glucose-rich snacks
on hand.
The role of drug therapy is primarily in the management of patients with metastatic or
unresectable disease or in patients who are not surgical candidates or refuse surgery. For
patients in whom a surgical cure has been achieved, there should be no need for further
therapy. Medical treatment is indicated when symptoms are not controlled by diet alone. Firstline therapy often consists of diazoxide, a nondiureticbenzothiadiazine. Diazoxide is recognized
to stimulate b-cell adrenergic receptors, thus decreasing insulin release, and was used in the
medical management of insulinoma since 1963.Chemotherapy is not primarily recommended as
a first-line treatment for malignant disease. Despite the sense of urgency that this diagnosis
brings, treatment is initially conservative and includes a 3- to 6-month follow-up with ultrasound
or CT scan in patients who are medically stable. Further treatment is considered for patients
who develop pain, have direct serious effects from the tumor, intractable symptomatology
related to excess insulin, or progression of disease. Diazoxide should be used in all patients
symptomatic from insulinoma. This group often includes patients awaiting surgery or in whom
surgery was unable to localize the primary tumor. Diazoxide plays a substantial role in the
palliation of patients with metastatic disease. The standard dose ranges from 150 to 450 mg
daily, often divided into doses every 8 hours, but may be increased to as high as 800 mg per
day. The drug may be started at low doses and titrated up, depending on the severity of
hypoglycemia. Side effects include sodium and water retention and occasionally hirsutism. The
concomitant use of a thiazide diuretic is often helpful in managing these effects. Diazoxide can
be effective in the symptom management of patients with stable disease.
Because most insulinomas are benign, there is often no need for chemotherapy.
Furthermore, there may be no need for the use of adjuvant or neoadjuvant therapy for treating
patients with insulinomas with no evidence of metastatic disease.
Surgical Management
Most insulinomas are benign and the treatment of choice is surgical resection. The
choice of procedure depends on the location of the tumor. The combination of intraoperative
ultrasound and palpation can detect the most tumors. Ultrasound can determine the proximity
of the tumor to the pancreatic duct. Enucleation of the insulinoma may be performed in patients
who have a solitary tumor that is not encroaching on the pancreatic duct hence, it is not done to
the patient. Even when preoperative localization is performed, it remains important that the
entire pancreas be assessed at the time of surgery. Laparotomy is performed through an upper
midline incision or an extended subcostal incision. Access to the pancreas is gained by opening
the gastrocolic omentum and entering the lesser sac. The duodenum is widely kocherized and
the transverse mesocolon is separated from the inferior border of the pancreas. This separation
allows for examination and bimanual palpation of the entire pancreas. If necessary, the spleen
may be mobilized from its lateral attachments to allow complete delivery of the pancreatic body
and tail for inspection and palpation. Insulinomas are often small, round, and reddish-brown
nodules and solitary. If it is determined with the aid of intraoperative ultrasound that tumor
enucleation can be performed safely, this is the procedure of choice for tumors to the right of the
superior mesenteric vein. A Whipple procedure (pancreaticoduodenectomy) is rarely necessary,
but it may be required if the tumor is in close proximity to major ductal structures.
In general, distal pancreatectomy is performed en-bloc along with resection of the
spleen. Most of the time, the en-bloc pancreatic-spleen resection is performed for technical
reasons, it makes the operation short and easy but does not offer any special advantage for the
patient (Cruz, et al).
There is no real consensus on the need to perform spleen preservation in the setting of
a malignant neoplasm. In the large series of 235 distal pancreatectomies reported by
Lillemoe et al., only 49 patients (21%) underwent resection for adenocarcinoma of the pancreas.
They always recommend an en-bloc distal pancreatectomy with splenectomy. AndrénSandberg et al., also believe that splenectomy should be routinely performed because splenic
artery preservation is hazardous for oncologic radicality when distal pancreatectomy is
performed for cancer. However, this argument should not be used against preservation of the
spleen. Involvement of the splenic vein, and the splenic artery distant from the coeliac axis, is
frequently found, and does not preclude distal pancreatic resection for malignant tumours in the
body-tail of the pancreas. Mobilization of the caudal surface of the body of the pancreas from
the retroperitoneum is performed after division of the splenic artery close the coeliac trunk,
followed by division of the splenic vein close to the junction to the mesenteric vein. It allows an
extensive retroperitoneal lymph node dissection. The spleen may be preserved by maintaining
the integrity of the short gastric vessels and the left gastro-epiploic vessels (Warshaw's
technique). According to Balcom et al., spleen-sparing distal pancreatectomy may also be
preferable in the setting of a malignant neoplasm not directly involving the spleen because it is a
putative mechanism for maintenance of immune surveillance. Also, for Sasson et al., whenever
possible, splenic conservation should be attempted in patients undergoing total or distal
pancreatectomy for adenocarcinoma of the pancreas. Schwarz et al. have studied the impact of
splenectomy on hospital stay and survival after resection of pancreatic adenocarcinoma. In this
analysis, splenectomy has no significant measurable impact on postoperative recovery, but has
a negative influence on long-term survival independent of disease-related factors. The authors
concluded that splenectomy should be avoided in the operative treatment of exocrine pancreatic
cancer at any localization.
The French surgeon Mallet-Guy first described, in the 1940s, the technique of spleenpreserving pancreatic left resection for patients with chronic pancreatitis. Since that time, the
reasons why spleen-preserving distal pancreatectomy was performed or not performed, are not
clear in the literature. In some reports, the incidence of splenic preservation was rather low at
20%, as reported by Rattner et al., and 24% as reported by Sakorafas et al. In some other
reports, including our series, the spleen was salvaged successfully in 31–57.9% of cases . The
main reason for performing pancreatic left resection with splenectomy is the finding of
pancreatic tissue firmly and densely adherent to the splenic vessels. The en-bloc distal
pancreatic-spleen resection is mostly performed for technical reasons, to make the operation
short and easy, as compared with spleen-preserving distal pancreatectomy, a technically
demanding and more time-consuming procedure. We believe that—even in cases of severe
chronic pancreatitis followed by gross pancreatic calcification, marked oedema and fibrosis that
also encase the splenic vessels—spleen-sparing distal pancreatectomy should be encouraged,
applying the Warshaw's technique with preservation of the short gastric vessels. In other cases,
the oedema resulting from chronic inflammation surrounding the splenic vessels may facilitate
splenic vessel preservation and splenic conservation.
In the Johns Hopkins's series the incidence of pancreatic fistula after enucleation was
reported to be 50%. Recently, Kiely et al. have introduced some major operative modifications,
the introduction of intraoperative ultrasound imaging to identify the pancreatic duct and closure
of the pancreatic defect after enucleation. In this series, despite these refinements in the
technique, the pancreatic fistula rate was 27%, and the hospital stay was 12.6 days. Tumour
enucleation does not address the malignant potential of these tumours and should be used (in
selected cases) with caution to avoid inadequate tumour margins. In the literature, when the
tumour was located in the body or tail of the pancreas, the technique most frequently used was
distal pancreatectomy. In some series, it was not stated whether there was conservation of the
spleen at the time of distal pancreatectomy.
Insulinomas in the neck, body, and tail of the gland not amenable to enucleation are
treated with spleen-preserving distal pancreatectomy . Solitary tumors in the neck or body of the
pancreas that are not amenable to enucleation may also be treated by median pancreatectomy.
In this procedure, the pancreas is exposed. The superior mesenteric and portal veins are
dissected from the posterior pancreas and the splenic vessels are preserved. The tumor is
resected with a 1-cm margin on either side. The proximal stump of the pancreas is closed with
interrupted sutures or a stapler, whereas the distal stump is anastamosed to a Roux-en-Y loop
similar to the distal pancreas in a pancreaticoduodenectomy. This procedure prevents the
morbidity of a duodenal and common bile duct resection, thus still preserving the distal
pancreas.
The spleen plays a crucial role in the body's ability to fight off bacteria, living without the
organ makes a person more likely to develop infections, especially dangerous ones such as
Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. These
bacteria cause severe pneumonia, meningitis, and other serious infections. Vaccinations to
cover these bacteria should be given in patients without a spleen. Infections after spleen
removal usually develop quickly and make the person severely ill. They are referred to as
overwhelming post-splenectomy infections, or OPSI. Such infections cause death in almost 50%
of cases. Children under age 5 and people who have had their spleen removed in the last two
years have the greatest chance for developing these life-threatening infections. Other
complications related to splenectomy include blood clot in the vein that carries blood to the liver,
hernia at the incision site, infection at the incision site, pancreatitis, lung collapse and injury to
the pancreas, stomach, and colon.
The major morbidities of these operations include pancreatic fistula and persistent
hyperinsulinism
for
all
procedures,
bile
leak
and
prolonged
gastric
ileus
for
pancreaticoduodenectomy, and injury to the spleen necessitating splenectomy. Mortality from
the largest of operations can be kept to below 4%. If the tumor cannot be found or if high
insulin/low glucose levels persist after tumor removal, the patient needs to be sent to a center of
excellence for further imaging and reoperation. Blind distal resection is not indicated.
In patients with multiple tumors (MEN-1), a modified approach should be taken. The
pancreas should be exposed and fully evaluated. Multiple tumors are often present in the tail
and body of the pancreas, necessitating a distal pancreatectomy. Any remaining tumors in the
head of the pancreas can be managed with enucleation. This approach does increase the risk
of postoperative diabetes, but it is the only true chance for a surgical cure. Additionally, one
group has described inserting a catheter into the portal vein through the umbilical vein. They
injected 0.025 mEq/kg of calcium gluconate and sampled portal venous blood at 0, 30, 60, 90,
and 120 seconds after injection. When no rise in serum insulin levels were found, they were
satisfied that no insulinoma tissue remained.The patient with malignant disease poses a more
complex management problem. Patients with a curative resection for malignancy have roughly
a 50% chance of disease-free survival at 3 years and an absolute survival advantage over
patients with a palliative resection. In patients without diffuse disease, there is more than a 60%
5-year survival rate and an approximately 30% 5-year survival rate in patients with diffuse
disease.Therefore, the recommendation would be to resect the primary tumor if possible, along
with any other resectable metastatic disease and involved lymph nodes. In the later stages of
disease, debulking surgery has a definite role to play in palliation of symptoms. Other
techniques, such as cryoablation, or resection of hepatic metastases can offer substantial
palliation. Laparoscopic pancreatic surgery may find increasing use in the management of
patients with insulinoma. Laparoscopic resection was described in 1996 and is a viable method
of therapy.
REFERENCES
Distal pancreatectomy: en-bloc splenectomy vs spleen-preserving pancreatectomy
Laureano Fernández-Cruz, David Orduña, Gleydson Cesar-Borges, and Miguel Angel López-Boado. Department
of Surgery, Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
Lillemoe KD, Kaushal S, Cameron JL, Sohn TA, Pitt HA, Yeo CJ. Distal pancreatectomy: indications and
outcomes in 235 patients. Ann Surg. 1999;229:693–8.
Andren-Sandberg A, Wagner M, Tihanyi T, Lofgren P, Fries H. Technical aspects of left-sided pancreatic
resection for cancer. Dig Surg. 1999;16:305–12.
Balcom JH, 4th, Rattner DW, Warshaw AL, Chang Y, Fernández-del Castillo C. Ten-years experience with 733
pancreatic
resections:
changing
indications,
older
patients,
and
decreasing
length
of
hospitalization. Arch Surg. 2001;136:391–8.
Sasson AR, Hoffman JP, Ross EA, Kagan SA, Pingpank JF, Eisenberg BL. En bloc resection for locally advanced
cancer of the pancreas: is it worthwhile? J Gastrointest Surg. 2002;6:147–57.
Schwarz RE, Harrison LE, Conlon KC, Klimstra DS, Brennan MF. The impact of splenectomy on outcomes after
resection of pancreatic adenocarcinoma. J Am Coll Surg. 1999;188:516–21.
Sarr MG, Carpenter HA, Prabhakar LP, Orchard TF, Hughes S, van Heerden JA, et al. Clinical and pathologic
correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from
malignant (or premalignant) neoplasms? Ann Surg. 2000;231:205–12
Thompson LDR, Becker RC, Prygodzki RM, Adair CF, Heffess CS. Mucinous cystic neoplasm (mucinous
cystadeno-carcinoma of low grade malignant potential) of the pancreas. Am J Surg Pathol. 1999;23:1–6.
Zamboni G, Scarpa A, Bogina G, Iacona C, Bassi C, Talamini G, et al. Mucinous cystic tumors of the
pancreas. Am J Surg Pathol. 1999;23:410–22.
Pyke CM, van Heerden JA, Colby TV, Sarr MG, Weaver AL. The spectrum of serous cystadenoma of the
pancreas. Clinical, pathologic, and surgical aspects. Ann Surg. 1992;215:132–9.
Talamini MA, Moesinger R, Yeo CJ, Poulose B, Hruban RH, Cameron JL, et al. Cystadenomas of the pancreas: is
enucleation an adequate operation? Ann Surg. 1998;227:896–903.
Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. Cystic pancreatic neoplasms: enucleate or resect? J
Gastrointest Surg. 2003;7:890–7.
Meyer
W,
Kohler
J,
Gebhardt
C.
Cystic
neoplasms
of
the
pancreas
–
cystadenomas
and
cystadenocarcinomas. Langen-becks Arch Surg. 1999;384:44–9.
Le Borgne J, de Calan L, Partensky C. Cystadenomas and cystadenocarcinomas of the pancreas: a
multiinstitutional retrospective study of 398 cases. French Surgical Association. Ann Surg. 1999;230:152–
61.
Shima Y, Mori M, Takakura N, Kimura T, Yagi T, Tanaka N. Diagnosis and management of cystic pancreatic
tumours with mucin production. Br J Surg. 2000;87:1041–7.
Mallet-Guy P, Vachon A. Masson; Paris: 1943. Pancreatites chroniques gauches.
Rattner DW, Fernandez-del Castillo C, Warshaw AL. Pitfalls of distal pancreatectomy for relief of pain in chronic
pancreatitis. Am J Surg. 1996;171:142–5.
Evans JD, Morton DG, Neoptolemos JP. Chronic pancreatitis and pancreatic carcinoma. Postgrad Med
J. 1997;73:543–8.
Schoenberg MH, Schlosser W, Ruck W, Beger HG. Distal pancreatectomy in chronic pancreatitis.Dig
Surg. 1999;16:130–6.
Govil S, Imrie CW. Value of splenic preservation during distal pancreatectomy for chronic pancreatitis. Br J
Surg. 1999;86:895–8.
Sakorafas GH, Sarr MG, Rowland CM, Farnell MB. Post-obstructive chronic pancreatitis: results with distal
resection. Arch Surg. 2001;136:643–8.
Bauer A, Uhl W, Tcholakov O, Wagner M, Friess H, Böchler MW. Böchler MW, Friess H, Uhl W, Malfertheiner P.
Blackwell; UK: 2002. Pancreatic left resection in chronic pancreatitis – indications and limitations,
Chronic pancreatitis – novel concepts in biology and therapy; pp. 529–39.
Fernandez-Cruz L, Saenz A, Astudillo E, Pantoja JP, Uzcategui E, Navarro S. Laparoscopic pancreatic surgery in
patients with chronic pancreatitis. Surg Endosc. 2002;16:996–03.
Hutchins RR, Hart RS, Pacifico M, Bradley NJ, Williamson RC. Long-term results of distal pancreatectomy for
chronic pancreatitis in 90 patients. Ann Surg. 2002;236:612–18.
University of Santo Tomas
Faculty of Medicine and Surgery
A Case of Insulinoma
Group 5
Fontano, Michael Jeff B.
Francisco, Therese Pauline D.
Gabuat, Harry M.
Gaffud, Prima Bianca N.
Gagtan, Majelle L.
Gallardo, Estee Laurence Heart C.
Garan, Elizabeth Aileen L.
Garcia, Cholson Banjo E.
Garcia, Kristina Fatima Louise P.
Garcia, Mark Jesreel O.
Garzon, Maria Monica Pamela N.
Tolentino, Maria Kariza L.