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Islet cell tumors.Gastroenterologist.
1997 Sep;5(3):213-32.
Although quite
rare, the islet cell tumors present an important challenge to the
clinician because of their protean manifestations and potential
lethality. Early diagnosis is essential and depends on recognition of
the classic and variant clinical syndromes followed by confirmation of
elevated peptide levels by radioimmunoassay. Medical control of the
hormonal syndrome with agents such as diazoxide for insulinoma,
omeprazole for gastrinoma, and octreotide for vipoma and glucagonoma
allows an orderly and thorough investigation for associated
endocrinopathies and comorbid medical conditions. Localization and
staging of the tumors are important because they may be small and
occult, widely metastatic, or multifocal in the context of multiple
endocrine neoplasia type I (MEN I) syndrome. Computed tomography,
visceral angiography, endoscopic ultrasonography, and indium-labeled
octreotide scanning are the most useful preoperative imaging
techniques. Surgical exploration that includes intraoperative
ultrasonography remains an essential localization technique for occult
tumors, particularly insulinomas and gastrinomas. For all patients
other than some with advanced metastatic disease or MEN I syndrome, an
aggressive surgical approach with the intent of complete and curative
tumor excision is indicated. Surgical cure is possible in most
insulinomas, a substantial proportion of gastrinomas, and some
patients with the other more rare and malignant islet cell tumors. At
present, adjuvant medical therapies for unresectable malignant disease
have limited efficacy. However, a variety of newer and innovative
tumor localization techniques, operative strategies, and nonoperative
treatment modalities hold considerable promise for the attainment of
higher cure rates and improved palliation.
Islet cell
tumors of the pancreas: clinical, radiologic, and pathologic
correlation in diagnosis and localization.Radiographics.
1997 Mar-Apr;17(2):453-72;
Islet cell
tumors are rare pancreatic or peripancreatic neoplasms that produce
and secrete hormones to a variable degree. These tumors are best
divided on clinical grounds into those that produce a recognizable,
clinically evident endocrine syndrome (ie, functioning) and those that
exhibit no clinical evidence of hormone production (ie, clinically
silent). Clinically silent tumors produce symptoms due to mass effect
because of their large size. They are often partially cystic or
necrotic. Functioning islet cell tumors usually manifest earlier in
the course of the disease because of the distinctive signs and
symptoms of the associated endocrine syndrome. Clinically silent and
functioning tumors cannot be histologically distinguished reliably
even with the use of immunohistochemical stains. Insulinoma and
gastrinoma, the two most common functioning lesions, are typically
small homogeneous masses. Other functioning islet cell tumors include
glucagonoma, somatostatinoma, vipoma, and adrenocorticotropic
hormone-producing tumor. Larger tumors are associated with
calcification, cystic degeneration and necrosis, and a more aggressive
behavior (local and vascular invasion as well as distant metastases).
There are many different techniques for detection and characterization
of these lesions that are usually chosen according to the
radiologist's experience and preference. Treatment and prognosis of
these lesions depend on the hormone produced, their size, and their
behavior.
Nonfunctioning
islet cell tumors of the pancreas: a difficult diagnosis but one worth
the effort.Am
Surg. 1997 Jul;63(7):573-7;
Islet cell
tumors of the pancreas usually secrete gastroenteropancreatic peptides
causing well-recognized clinical syndromes. Description of these
syndromes and the identification of the responsible hormones by
radioimmunoassay has led to a better understanding of neuroendocrine
regulatory function. More recently, similar tumors have been seen that
contain various peptides on immunohistochemical stain but do not
secrete these substances sufficiently to cause clinical symptoms.
Nonetheless, they have the same malignancy and metastatic rate as most
of the functional tumors. Between 1972 and 1996, 44 patients with
islet cell tumors have been treated at the Indiana University Medical
Center Hospital, and of these 14 have been nonfunctional. Preoperative
imaging studies, such as CT scan and endoscopic ultrasound, were able
to visualize a lesion but not to make the specific diagnosis, even
with fine-needle aspiration. Pancreatic ductal preservation on
endoscopic retrograde cholangiopancreatography with CT evidence of a
mass should arouse suspicion of an islet cell tumor. Once discovered,
all but 1 of the 14 patients has under gone resective therapy, with
only 1 postoperative death. Treatment has been aggressive, with 11 of
the 13 resected patients undergoing pancreaticoduodenectomy, and 2
others distal pancreatectomy. Four of the seven patients with positive
lymph node metastases are dead, while all patients with negative nodes
are still alive. Thus far, 10 of the original 14 patients are alive,
surviving an average of 32.7 months, with a median survival of 31.1
months. Because these tumors have a better overall prognosis, vigorous
attempts at total or subtotal resection should be carried out, since
the long-term survival is enhanced by tumor bulk reduction or curative
resection when possible.
Islet cell
tumors of the pancreas.:
Surg Clin North
Am. 1995;75(5):1025-40.
Pancreatic
endocrine neoplasms are a heterogeneous group of tumors that produce
active hormones and result in distinct clinical syndromes. For the
most part, they are malignant and require sophisticated diagnostic and
localization techniques in order to identify their presence. Delays in
diagnosis are the rule rather than the exception. Improvements in the
diagnosis of gastrinomas and insulinomas appear to result in an
increase in resectability rates. The widespread availability of
intraoperative ultrasonography, as well as improved knowledge of the
location of these tumors, has also had an impact on improved cure
rates. With heightened awareness of these syndromes, increasing
numbers of patients can be identified and more effective treatments
developed for the refractory and recurrent tumors.
Imaging and
localization of islet-cell tumours of the pancreas on CT and MRI.Best
Pract Res Clin Endocrinol Metab. 2005 Jun;19(2):195-211.
Islet-cell
tumours are neuroendocrine tumours that arise from the endocrine
pancreas. They may be associated with a variety of syndromes and are
subclassified into functioning and non-functioning tumours. They range
from benign to malignant. They demonstrate characteristic features
when imaged with both computed tomography (CT) and magnetic resonance
imaging (MRI). Sensitivity and specificity, as well as detection of
extrapancreatic extension, are generally superior with MRI. However,
CT is currently still more readily available to patients. Multiphase,
post-contrast series are commended for the evaluation of islet-cell
tumours with either modality.
Surgical
experience with functioning pancreatic neuroendocrine tumors.
Am Surg. 2002
Aug;68(8):660-5.
Pancreatic
islet-cell tumors (ICTs) are rare malignancies usually recognized by
specific clinical endocrinopathies. The purpose of this study is to
evaluate our surgical experience with functioning pancreatic ICT in an
academic referral center. Twenty patients (male:female 12:8) with a
mean age of 53 years (range 26-82) underwent surgery for a functioning
pancreatic ICT [gastrinoma (eight), multiple endocrine neoplasia
(three), insulinoma (seven), glucagonoma (four), and VI-Poma (vasoactive
intestinal peptide; one)] between June 1975 and March 2001. Signs and
symptoms of hormonal excess were present in 95 per cent (19 of 20).
One patient (glucagonoma) presented with obstructive jaundice and mild
glucose intolerance. Elevated peptide levels were detected
preoperatively in 65 per cent, including all patients with an
insulinoma. Curative resections were attempted in 80 per cent
including three procedures for insulinoma. Palliative procedures were
performed in 20 per cent--all gastrinomas. One patient with an
insulinoma had diffuse nesidioblastosis. Three patients (with
gastrinoma, insulinoma, and glucagonoma) had lymph node-positive
disease and three patients with gastrinoma had liver metastasis. The
overall 30-day morbidity rate was 30 per cent and mortality rate 0 per
cent. Symptomatic improvement was achieved in 90 per cent at a mean
follow-up of 44 months. Two patients developed diabetes after a
subtotal and a total pancreatectomy, respectively. Sixty-three per
cent of patients who underwent an attempted curative resection are
alive at a mean follow-up of 47 months (range 3-231) and all patients
who underwent a palliative procedure are alive at a mean follow-up of
31 months (range 27-36). Functioning pancreatic ICTs are fascinating
tumors that produce distinct clinical syndromes. Symptomatic
improvement is accomplished in the majority of patients after surgery
and short-term palliation is achieved in patients with nonresectable
disease.
Islet cell
tumors of the pancreas: the medical oncologist's perspective.
Surg Clin North Am. 2001
Jun;81(3):527-42.
Islet cell
tumors of the pancreas are rare, indolent, neuroendocrine tumors.
Approximately 50% of the patients diagnosed with these tumors present
with symptoms related to various biologically active hormones that are
secreted by these neoplasms. Currently, the only curative treatment
for islet cell tumors is complete surgical resection. Management of
metastatic disease is conservative. Initial treatment of these tumors
includes expectant observation and medical management of symptoms with
clinical monitoring and serial CT scans to assess tumor growth.
Patients with rapidly progressive disease, with local symptoms caused
by tumor bulk, or with uncontrolled symptoms related to hormone
secretion require more aggressive medical or surgical intervention.
The somatostatin analogue octreotide may help control hormone
secretion and stabilize tumor growth. Patients refractory to
octreotide with tumor predominantly in the liver are potential
candidates for mechanical ablative techniques, such as hepatic
arterial embolization. Radiofrequency ablation and cryosurgical
techniques may also be useful, although specific data are limited.
Surgical resection of metastatic disease may offer palliative relief
of symptoms related to hormone secretion in carefully selected
patients. Chemotherapy may be used for palliation when ablative
techniques have failed or when significant extrahepatic disease is
present. Streptozicin-based combinations remain the first line
standard, but major objective responses are less common than had been
previously thought. Because of the overall modest success of current
chemotherapeutic regimens, patients with advanced disease in need of
treatment should be encouraged to enroll in clinical trials testing
newer antineoplastic agents or newer treatment strategies.
Functional
pancreatic islet cell tumors with liver metastasis: the role of
cytoreductive surgery and transcatheter arterial chemoembolization: a
report of five cases.
Zhonghua Yi Xue Za Zhi (Taipei).
1998 ;61(12):748-54.
Malignant
pancreatic islet tumors are slow-growing tumors. Their relatively
benign behavior makes aggressive treatment worthwhile. From January,
1987, to January, 1998, five cases of malignant pancreatic islet
tumors with liver metastasis were diagnosed at the Veterans General
Hospital-Taipei. Of these, three were gastrinomas and the others were
vasoactive intestinal peptide (VIPoma, 1 case) and insulinoma (1
case). Four patients (3 with gastrinomas and 1 with insulinoma) had
undergone cytoreductive surgery when the diagnosis of metastasis was
made. All five patients underwent transcatheter arterial
chemoembolization (TACE). All patients had improved symptoms after
cytoreductive surgery and TACE. The survival of patients who underwent
combined surgery and TACE was 38 and 17 months in the two gastrinoma
cases, more than eight months in one gastrinoma case and more than 20
months in the insulinoma case (these 2 patients are still alive). One
VIPoma patient who underwent TACE survived for 12 months. In
conclusion, treatment for metastatic pancreatic islet cell tumors
require a multidisciplinary approach. Metastasis of the tumor is not a
contraindication for aggressive therapy. Combined cytoreductive
surgery and TACE can relieve symptoms and are of benefit for patients
with pancreatic islet cell tumors with liver metastases.
Functioning
oncocytic islet-cell carcinoma: Report of a case with
electron-microscopic and immunohistochemical confirmation. Am J Surg
Pathol 1985;9:517–524.
A case of a
58-year-old woman with an unusual variant of malignant islet-cell
tumor showing oncocytic features is described. Using the light
microscopy technique, the tumor appeared comprised of solid nests of
uniform cells with abundant, eosinophilic cytoplasm and round nuclei
with granular chromatin. Ultrastructurally, the cells contained
numerous abnormal mitochondria, dilated rough endoplasmic reticulum,
and scattered dense-core neurosecretory granules, often associated
with cytoplasmic filaments. Tumor cells were focally immunoreactive
for insulin, glucagon, and somatostatin and diffusely immunoreactive
for alpha 1-antitrypsin as assayed by the avidin--biotin technique.
The tumor was immunonegative for human chorionic gonadotropin, gastrin,
adrenocorticotropic hormone, and serotonin. The patient exhibited some
of the clinical features associated with glucagonoma syndrome,
including diabetes mellitus and chronic diarrhea. The tumor behaved in
a malignant fashion, with widespread lymphatic involvement and bony
metastases at the time of presentation. This report of an oncocytic
islet-cell carcinoma supports the concept of oncocytic differentiation
in islet-cell tumors in a fashion analagous to oncocytic carcinoids.
Clear cell islet
cell tumor. Am J Clin Pathol 1983;79:512–517.
A patient with
an islet cell tumor presented initially with a supra-renal mass that
histologically had an extensive clear cell component. Electron
microscopic and immunocytochemical findings were essential to prove
that the extrapancreatic mass with clear cells was an unusual
metastatic manifestation of an islet cell tumor. Both the pancreatic
and extrapancreatic tumor cells contained neurosecretory granules and
produced vasoactive intestinal polypeptide and substance P. The clear
cell morphology was due to the accumulation of lipid and glycogen and
cytoplasmic swelling.
Nonislet origin of
pancreatic islet cell tumors. J Clin Endocrinol Metab
2004;89:1934–1938.
The histogenesis
of pancreatic islet cell tumors was investigated by morphological
identification of putative precursor lesions in pancreatic tissue from
patients with multiple endocrine neoplasia type 1 (MEN1), tissue
microdissection, and genetic analysis. MEN1 mutation and absence of
the MEN1 wild-type allele in different precursor lesions strongly
suggest that pancreatic islet cell tumors are derived from the ductal/acinar
system but not from pancreatic islet tissue. Pluripotent cells within
the exocrine pancreas appear capable of formation into small atypical
accumulations of MEN1-deficient cells with both exocrine and endocrine
phenotype. The findings suggest presence of multiple developmental
aberrations in MEN1 pancreas that potentially serve as precursor
material for neuroendocrine tumors.
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