Surgical therapy for endocrine tumors of abdominal origin

Surgery continues to be the primary treatment of endocrine neoplasia. Only occasionally are other therapies appropriate and, in those cases, usually only for palliation. In this review, we address the surgical management of endocrine tumors of the pancreas, the adrenal glands, and the gastrointestinal tract (specifically carcinoid tumors). Endocrine tumors, although rare, often present in quite dramatic fashion but are generally associated with excellent survival rates when treated with appropriate surgical resection.     

Nonductal tumors of the pancreas. The importance of laparotomy

OBJECTIVES: To delineate the incidence of nonductal pancreatic neoplasms and determine whether distinguishing clinical or radiologic characteristics exist. METHODS: From 1977 through 1990, we examined 353 patients with a pancreatic mass as demonstrated on abdominal computed tomography or ultrasonography. Patients with chronic pancreatitis or functioning neuroendocrine tumors were excluded. All patients underwent operative exploration for histopathologic diagnosis and resection when possible. RESULTS: Adenocarcinoma of the pancreas was seen in 322 patients. The remaining 31 patients (8.8%) were found to have nonductal tumors of the pancreas, including nonfunctioning islet cell tumors (15), cystadenoma (nine), lymphoma (five), lipoma (one), and mesothelioma (one). These neoplasms were evenly distributed between the head and tail of the pancreas, while most of the ductal pancreatic carcinomas were located in the pancreatic head. While abdominal computed tomography and ultrasonography accurately identified most cystic neoplasms, the remaining nonductal lesions were indistinguishable from ductal pancreatic tumors. Preoperative biochemical studies and liver function tests failed to separate ductal and nonductal pancreatic masses. Average survival for patients with nonductal lesions was significantly longer compared with ductal tumors of the pancreas. CONCLUSIONS: Because increasing reliance on advanced radiologic and invasive nonoperative diagnostic testing may deny proper surgical therapy to patients with nonductal neoplasms of the pancreas, laparotomy and histopathologic diagnosis are advisable in most patients with an isolated pancreatic mass.     

Solid and papillary epithelial neoplasm of the pancreas, diagnosis by cytology

In this paper, I report a rare, low-grade malignant tumor, solid and papillary epithelial neoplasm of the pancreas (SPENP). I also discuss and review 157 previously reported cases. Unlike other malignant tumors of the pancreas, this neoplasm is typically found in young women, does not have metastases, and is amenable to cure after complete surgical resection. I discuss clinical features, diagnostic procedures, and differential diagnosis. Fine-needle aspiration can be effective in obtaining a preoperative diagnosis of SPENP, since the tumor has characteristic cytologic features. Also, use of clinical data, ultrasonography studies, computed tomography, magnetic resonance imaging, arteriography, and cytologic findings in the preoperative workup are important in obtaining an accurate diagnosis. Although potentially curable, late metastases and current inability to predict aggressive behavior by some tumors require lengthy follow-up.     

Lack of survival benefit of extended lymph node dissection for ductal adenocarcinoma of the head of the pancreas: retrospective multi-institutional analysis in Japan

It has not been established that extended lymph node resection is necessary for ductal adenocarcinoma of the head of the pancreas. According to the general rules for the study of pancreatic cancer, a multiinstitutional, retrospective clinical study was undertaken to investigate the efficiency of extended lymph node dissection for this malignancy. Altogether 501 patients underwent resection of the pancreas between 1991 and 1994 at 77 medical facilities; the surgical procedures, staging, lymph node dissection, curability, and survival rate were analyzed retrospectively. Eighteen of the patients died within 30 postoperative days, leaving 483 patients to be studied. The resection was curative microscopically in 94 patients, resulting in a 3-year survival of 29%. Macroscopically curative resection resulted in a 3-year survival of 14%; noncurative resection produced a 3-year survival of 6%. Although extended lymph node dissection was performed on 38 patients in stage I, 42 patients in stage II, 206 patients in stage III, and 1 patient in stage IV, there was no improvement in survival when the results were compared to those seen after standard or palliative lymph node dissection. The extent of lymph node dissection has not affected the prognosis for ductal adenocarcinoma of the head of the pancreas at any stage of the course of the disease. Excessive lymph node dissection in advanced cases does not necessarily lead to a favorable prognosis. The patients who undergo a radical operation with an adequate lymph node dissection have longer survivals.     

Longitudinal analysis of multiple indicators of health decline among spousal caregivers

CONCLUSION: In view of the frequent absence of symptoms related to pancreatic lesions, screening tests for VHL should always include assessment of the pancreas and, considering the frequency of polycystic manifestations, VHL should always be borne in mind in the differential diagnosis of multiple pancreatic cysts, especially when occurring in young patients and in the absence of a positive history of pancreatic disease. BACKGROUND: Von Hippel-Lindau disease (VHL) is a hereditary disease transmitted with an autosomal dominant character and characterized by hemangioblastomas of the central nervous system and retina, renal tumors and cysts, and pheochromocytoma. Pancreatic manifestations of VHL are reported in the literature with incidences ranging from 16 to 29% of cases and consist mainly in cystadenomas of the serous type and in multiple cystic lesions, often with complete replacement of the gland. METHODS AND RESULTS: We report five cases of VHL with a polycystic pancreas as the main or only manifestation, all devoid of symptoms related to involvement of the pancreas, who were referred to our Pancreatic Surgery center with diagnoses of multiple pancreatic pseudocysts of undefined origin.     

Perceived motivational climate and cognitive and affective correlates among Norwegian athletes

CONCLUSION: The diagnosis of a pancreatic carcinoid should be based on the measurement of serotonin in serum or its demonstration in the tumor and/or by the measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a rare but definite entity; usually having metastasized by the time of diagnosis. The term "serotonin-producing tumor of the pancreas" has been suggested as an alternative designation for "pancreatic carcinoid." BACKGROUND: The literature on carcinoid tumors of the pancreas is confusing because much of it preceded the development of the more specific immunological, chemical and staining techniques currently available. METHODS: 43 case reports were collected from the world's literature, based on a demonstrable pancreatic neuroendocrine tumor plus a positive finding of at least one of the following without another dominant hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin) in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific assays, information was collected on the silver-staining properties of the tumor; properties which have traditionally been associated with carcinoid tumors. Positive silver staining in tumor cells (argyrophilic and/or argentaffin reaction) is strongly indicative of the carcinoid tumor but the findings are less specific than the hormone assays and immunohistologic stains. RESULTS: In this review of 43 cases, including two current ones, the pancreatic carcinoid tumor has the following important features: 1. It is a rare tumor that is usually diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%) have been malignant. They are, therefore, associated with a high incidence of the "carcinoid syndrome." 2. To date, prognosis in therapy is poor, based on delayed diagnosis, a resultant low incidence of resectability, and an uncertain duration of survival after resection. 3. Pancreatic carcinoid tumors remain difficult to differentiate from other endocrine tumors. The measurement of urinary 5-HIAA excretion or the demonstration of elevated serotonin level in the tumor or in serum is essential to its distinction. Silver staining of the tumor, although of historic importance, has been superceded by the hormone-specific studies. 4. To distinguish it from other endocrine tumors of the pancreas, the terms "pancreatic serotoninoma" or "serotonin-producing tumor of the pancreas" have been suggested as possible alternatives. Its growth characteristics may be related more to its cell of origin than to its extent of hormone secretion. Not all of the tumors result in recognizable hyperserotoninemia.     

Pancreatic cancer screening. Analysis of the problem and the role of radionuclide imaging

The clinical, surgical, and pathologic findings in a five year prospective study of 192 patients referred with a high probability of pancreatic cancer are reported. We have defined the requirements of any pancreatic imaging procedure as its ability to distinguish a normal pancreas from pancreatic cancer or chronic pancreatitis and the capability of detecting tumors less than 5 cm in diameter. There was a 47 percent incidence of pancreatic disease (27 percent pancreatic cancer and 20 percent chronic pancreatitis). Prospective radionuclide imaging as routinely performed was found to be of little clinical value in this patient population; it was neither specific nor sensitive to pancreatic cancer or chronic pancreatitis. Preliminary data with longitudinal multiplane emission tomography show an improved diagnostic accuracy and the ability to detect resectable tumors, but its efficacy needs to be prospectively compared with other screening tests on a carefully defined patient population.     

Perforation during nasogastric and orogastric tube insertion

We herein report a rare case of peripelvic extravasation due to peritoneal dissemination of pancreatic carcinoma. A 75-year-old female with left flank pain was admitted. Computed tomographic scan demonstrated a huge urinoma medial and posterior to the left kidney, and an irregular mass around the left lower ureter. Retrograde pyelography showed complete ureteral obstruction. The probable diagnosis was spontaneous peripelvic extravasation due to left ureteral tumor or ovarian tumor. Laparotomy revealed a tumor involving the body and tail of the pancreas and some disseminated tumors in the retroperitoneum. Pathological diagnosis was metastatic carcinoma of the pancreas. Malignant tumors in the digestive organs should be taken into consideration in the differential diagnosis of peripelvic extravasation.     

Management of patients and subjects at risk for multiple endocrine neoplasia type 1: MEN 1. GENEM 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases according to the French Registry of GENEM 1), tumors of the endocrine pancreas (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%) and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the fourth decade of life, but familial screening (using genetic tools whose diagnostic accuracy approaches 100%) has lowered the age of diagnosis. Screening for MEN 1 in a patient harboring an apparently sporadic tumor will depend on the endocrine gland involved. Extensive screening for MEN 1 in the presence of HPT will be conducted only when the familial history is suggestive, when parathyroid glands are hyperplastic or when multiple parathyroid adenomas have been found at surgery. All patients with an endocrine pancreas tumor need to be investigated for the presence of other endocrine lesions of MEN 1. Extensive screening for MEN 1 is only recommended when a patient with a pituitary tumor or an adrenal tumor has a familial history suggestive of MEN 1. Otherwise regular measurement of blood calcium and PTH levels seem sufficient. Extensive screening for endocrine lesions when MEN 1 is suspected involves hormone measurements and imaging procedures. For the diagnosis of HPT, calcemia and PTH 1-84 must be measured. In the absence of clinical symptoms, basal measurement of serum gastrin, glucose, insulin, glucagon, VIP, somatostatin and pancreatic polypeptide levels are combined with abdominal ultrasonography. When symptoms suggest the Zollinger-Ellison syndrome, the secretin stimulation test is recommended. The diagnosis of a pituitary tumor is made by pituitary imaging and selected hormone assays (mainly PRL). To detect an adrenal tumor, CT scan is recommended, combined with serum potassium, urinary free cortisol and androgen measurement. When the diagnosis of MEN 1 is made, clinical and hormonal follow-up (once a year) and imaging surveillance (every 3-5 years) may be sufficient to detect new other endocrinopathies (unless suggestive clinical symptoms arise). Surgical management of each endocrine lesion must be done by skilled surgeons according to therapeutic protocols which have been discussed in detail. Genetic screening is an integral part of familial screening which may be conducted in collateral and in the offspring of MEN 1 patients. Obviously ethical principles (informed consent, etc.) must be respected. As it is now possible to detect presymptomatic gene carriers with a high degree of accuracy, follow-up is needed to make appropriate management decisions. The marked anxiety provoked by screening in an overtly asymptomatic healthy subject must not be underestimated. Conversely, a negative genetic diagnosis helps to reassure the subject and avoid repetitive and costly follow-up.     

Secreting retroperitoneal paraganglioma. Apropos of a case

A case of secreting, asymptomatic retroperitoneal paraganglioma is presented. Paragangliomas are rare neuroendocrine tumors and the malignant behaviour, higher than pheochromocytomas, is based on metastases or local recurrence. The treatment is complete surgical excision. Radiotherapy and chemotherapy may be used for palliation of symptoms.     

Dermoid cyst of the pancreas: a rare cystic neoplasm

Dermoid cysts of the pancreas, also called cystic teratomas, are a rare entity and are included in the group of neoplasms with a germ cell origin. Only twelve cases have been described in the world literature. The symptomatology is due to tumor compression of the neighboring tissues. Ultrasonography and computed tomography may be helpful, but there are no pathognomonic data for their preoperative recognition. The differential diagnosis should include all other cystic tumors of the pancreas. Complete surgical removal is mandatory. We describe the diagnostic and surgical procedures in a 74 year-old man with a pre-operatively unsuspected dermoid cyst. We review the previously published cases and emphasize the appropriate therapeutical management.     

K-ras oncogene mutations in osteoclast-like giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium

Osteoclast-like giant cell tumors (OCGTs) of the pancreas and liver are enigmatic tumors. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may, in fact, arise from epithelial precursors. It is also unclear whether the osteoclast-like giant cells in OCGTs are neoplastic or nonneoplastic. We identified OCGTs of the pancreas and liver that were associated with atypical intraductal epithelial proliferations or mucinous cystic neoplasms. To determine the relationship between the noninvasive epithelial proliferations and the infiltrating OCGTs, each individual component was analyzed for mutations at codon 12 of the K-ras oncogene. Four of the five-duct epithelial lesions harbored activating mutations of the K-ras oncogene. In each case, the same K-ras mutation was also present in the mononuclear cells from the paired OCGT. Moreover, these same mutations were detected when the osteoclast-like giant cells were individually microdissected and analyzed. A panel of immunohistochemical stains was performed, and the osteoclast-like giant cells demonstrated macrophage differentiation. These cells were consistently reactive for the monocyte/macrophage marker KP1, but showed absent staining for a panel of epithelial markers. The infiltrating mononuclear cells lacked strong staining for epithelial markers and monocyte/macrophage markers. These findings suggest that OCGTs of the pancreas and liver are undifferentiated carcinomas that arise directly from intraductal epithelial precursors. The finding of K-ras mutations in the osteoclast-like giant cells may reflect their propensity to phagocytize tumor cells.     

Adenocarcinoma of the pancreas. Diagnosis and evaluation

SYMPTOMS: Pain, jaundice, or weight loss are the presenting features of 90% of the cases. Patients with tumors of the body or the tail of the pancreas do not rapidly develop jaundice. Therefore, their diagnosis is delayed and metastasis are more frequently detected at diagnosis. RADIOLOGIC DIAGNOSIS: The diagnosis may be established by ultrasonography, endoscopic ultrasonography and most importantly by CT scan with helicoidal continuous acquisition and contrast injection. However, these methods do not efficiently detect tumors smaller than 2 cm or with only superficial peritoneal involvement. Laparoscopy and angiography are used less and less frequently to evaluate resectability. The diagnostic work-up with CT scanning is able to anticipate resectability in 50 to 90% of the cases. PATHOLOGY: Histopathology must be obtained since 10% of the pancreatic carcinoma are not of the ductal type and not all pancreatic tumors are malignant. When a pathological specimen cannot be obtained during surgery, a cytology specimen may be obtained with a fine needle guided by CT scan. PROGNOSIS: Survival depends on the possibility of a complete resection of the tumor. If complete resection is obtained, the prognostic factors are in decreasing importance: tumor size, lymphatic and vascular involvement, and invasion of peri-pancreatic tissues.     

Papillary cystic and solid tumor of the pancreas

The papillary cystic and solid tumor of the pancrease (PCSTP) is a primary pancreatic neoplasm of unknown etiology occurring most commonly in young women and regularly containing hemorrhagic areas. Clinical symptoms are non-specific. Although these tumors reach an average diameter of 10 cm, they are often discovered by accident. Because patients with surgically resected PCSTP have very good prognoses, it is important to distinguish these tumors from other growths in the pancreas, for example mucinous cystadenoma. Whereas, due to the variable proportion of fluid components, these tumors offer non-characteristic structure at ultrasonography, computed tomography (CT) possesses high specificity for PCSTP, particularly when calcifications are present. Angiography distinguishes these tumors from hypervascular neoplasms, such as the endocrinologically inactive islet cell tumor. Magnetic resonance tomography (MRT) is especially suited for imaging the hemorrhagic areas in solid tumor formations, as well as hemorrhagic debris in the fluid portions and layer phenomena are frequently observed.     

Intraoperative gastrin measurements during surgical management of patients with gastrinomas: experience with 20 cases

Despite recent advances in imaging techniques for endocrine tumors of the duodenum and the pancreas, preoperative localization of gastrinomas is inconsistent. Successful surgical management of patients with Zollinger-Ellison syndrome (ZES) and removal of all gastrin-secreting tumors remains a difficult task. The aim of the study was to evaluate the predictive value of intraoperative gastrin measurements for successful surgical treatment in patients with gastrinomas. Intraoperative gastrin measurements were performed in 20 patients with ZES who underwent resection of gastrin-secreting tumors. Gastrin was measured with a radioimmunologic assay in blood samples obtained from a peripheral vein and from the portal vein at the beginning of the operation (T0) and 20 minutes after removal of the lesion(s) (T1). In 16 patients gastrin was also measured 4 minutes after injection of secretin 3 U/kg (T2). Thirteen patients (65%) were cured by surgery. In two of them, peripheral and portal gastrin levels were normal at T0, precluding any further interpretation of the test. Completeness of surgery was confirmed by normalization of gastrin levels at T1 or the absence of stimulation at T2 (or both) in 10 patients. In only one case did the gastrin levels remain elevated at T1 despite a favorable outcome after surgery. In each of the seven patients (35%) who had persisting disease at 1 year, failure of the surgical procedure was predicted by persistence of high levels of gastrin at T1. In patients with hypergastrinemia, the positive predictive value of intraoperative gastrin measurement for completeness of surgery and the specificity were 100%. The negative predictive value was 88% and the sensitivity 91%. The overall accuracy of the test was 94%. In patients with ZES the normalization of systemic hypergastrinemia during surgery affirms the successful removal of all gastrin-secreting tumors. We conclude that intraoperative gastrin measurement is a valuable addendum for optimizing the surgical management of gastrinoma.     

FNAC guided by computed tomography in the diagnosis of primary pancreatic adenosquamous carcinoma. A report of three cases

BACKGROUND: Pancreatic adenosquamous carcinoma (ASqC) is an unusual histologic subtype of nonendocrine neoplasia of the pancreas. Although fine needle aspiration cytology (FNAC) is now accepted as a reliable procedure for the diagnosis of pancreatic malignancies, many of these unusual tumors are still diagnosed after surgery or at necropsy. CASES: Between January 1995 and July 1996, 3 of 35 primary pancreatic malignant tumors were diagnosed as ASqC based on computed tomography-guided FNAC. After cytologic diagnosis, all three patients were treated with neoadjuvant chemotherapy and radiotherapy. Two patients completed the treatment and underwent a surgical pancreatic-duodenectomy with antrectomy. The remaining patient is currently under treatment. That patient had a highly infiltrative pancreatic mass that affected the muscular small bowel wall. An endoscopic biopsy was performed. The cytologic diagnosis was confirmed by histology in all cases. Immunohistochemically both components, squamous and glandular, showed reactivity for several keratins, while only the glandular pattern was reactive with carcinoembryonic antigen (CEA). CONCLUSION: FNAC is an accurate, rapid and sensitive tool in the diagnosis of ASqC of the pancreas. We recommend a careful search for both malignant components. Immunoreactivity for CEA can be of help in the detection of the glandular component of this tumor.     

A primary solitary tumor of the lesser omentum with immunohistochemical features of gastrointestinal stromal tumors

We here present a primary solitary tumor of the lesser omentum that was found in a 71-yr-old woman. Differential diagnosis could not be made preoperatively; therefore, histopathological examination including immunohistochemical studies were performed to determine the nature of the tumor. The resected specimen, measuring 17 cm at the largest point, consisted of the outer solid part and the inner multiloculated cysts. Microscopically, the tumor was characterized by interlacing bundles of elongated spindle cells, with the nuclei focally showing a palisading pattern. However, skeinoid fibers were not observed anywhere. One to three mitoses per 50 high power fields were observed. Immunohistochemically, the tumor was negative for S-100 protein and smooth muscle-specific actin, but stained positive for CD34. The microscopic features were consistent with those of potentially malignant gastrointestinal stromal tumors. Stromal tumors that represent the differentiation toward neither typical leiomyomas or schwannomas rarely occur in the lesser omentum with only one such instance having been reported to date. Due to this rarity, it is difficult to make the differential diagnosis preoperatively, even with existing imaging techniques, and predicting the clinical behavior of such omental tumors is also often difficult. Therefore, complete resection should be performed when such tumors are encountered in daily practice.     

Immature teratoma of the ovary with a neural component ("solid" teratoma). A clinicopathologic study of 20 cases

Twenty cases of immature teratoma of the ovary with a neural component are analyzed. A plea is made for use of the nomenclature adopted from the new World Health Organization classification of ovarian tumors, the past confusion over terminology and histogenesis of this rare tumor is discussed. All the primary tumors in the present series contained at least some immature tissues (predominantly of neural origin) and were thus graded from 1 to 3 according to the criteria of Thurlbeck and Scully. No grade 0 tumors ("benign solid teratomas") were identified. We believe that thorough sectioning almost always insures the identification of immature elements. The prognosis was closely related to the histologic grade, but correlated poorly withthe clinical stage, the latter being influenced by the common finding (25 per cent of the cases in this series) of peritoneal implants composed exclusively of mature glial tissue, which is associated with a benign clinical evolution. This phenomenon of maturation or differentiation appears to be the rule rather than the exception in this tumor, since implants are usually of better or equal differentiation when compared with their primary tumors and older patients tend to have lower grade tumors than younger patients. Since the majority of patients with this tumor are young, primary surgical therapy should be conservative, unilateral salpingooophorectomy often being sufficient. Spontaneous or operative rupture of the tumor capsule carries an increased risk of subsequent dissemination. We have noted impressive clinical responses in patients with disseminated tumors of a high histologic grade after treatment with triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide) but do not recommend adjuvant therapy in patients with only grade 0 implants.     

A modification of split-skin graft

Although acine cell neoplasms have for a long time been regarded as benign tumors, they are presently considered to represent the carcinomas. These rare tumors mainly affect the parotid glands, and only exceptionally involve other salivary glands. Clinically, acic cell carcinoma present as isolated tumors simulating a pleomorphic adenoma. The diagnosis is histopathological, and complete surgical removal of the tumor is the treatment of choice, with cervical lymphatic voiding and/or postoperative radiotherapy in selected cases. A prolonged patient follow-up is required, for the tumor may recur many years after surgery. We report a case of acinic cell carcinoma in submaxillary gland.     

Topological characteristics of chromatin in a cell-free system from Drosophila embryos

BACKGROUND: Vasoactive intestinal polypeptide (VIP)-secreting tumors of the pancreas represent a rare subtype of pancreatic islet cell tumors with an estimated incidence of 0.2 to 0.5 per million per year. We provide data on a relatively large series of patients with VIP-secreting tumors and review current literature regarding this specific entity. METHODS: A retrospective review was performed of all patients with VIP-secreting tumors of the pancreas treated from 1977 to 1992 at our institution. Presenting signs, symptoms, mode of diagnosis, extent of disease, surgical resectability, tumor size, treatments, hormone levels, and survival were assessed. RESULTS: Eighteen patients were identified, 9 male and 9 female. Ages ranged from 23 to 74 years (mean 51 years). Secretory diarrhea was the most common symptom, occurring in 16 of 18 patients (89%). The most common tumor location was the tail of the pancreas (9 patients). Fourteen patients (78%) had liver metastasis at diagnosis. Curative resections were attempted in only 5 patients (28%). The mean survival was 3.6 years with the longest disease-free survival being 15 years and longest overall survival 15 years. CONCLUSIONS: VIP-secreting tumors are extremely rare entities and usually metastatic at the time of diagnosis. Despite advanced disease, these patients can have extended survival.