Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred thirty-nine surgically treated patients with medullary carcinoma of the thyroid gland (MTC) were seen in our institution between January, 1926 and December, 1973. The incidence of this tumor among all thyroid cancers was 8%. Twenty-nine patients had the familial form of MTC; they were subclassified, on the basis of the phenotype, into a group of 15 patients with Sipple syndrome (or multiple endocrine neoplasia (MEN) Type 2A) and a group of 14 patients with mucosal-neuroma phenotype (or MEN type 2B). Better survivorship was seen in the younger patients, in those with bilateral tumors, in familial MTC, and in patients whose tumor was confined to the thyroid gland at the initial surgery. The incidence of tumor recurrence was 34%. However, in those with adequate surgical treatment, the recurrence was only 23%. The 5- and 10-year survivorships were 80% and 67%, respectively. The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.
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PMID:Medullary carcinoma of the thyroid gland. 111 37

Endocrine pancreatic tumors are slowly growing neuroendocrine neoplasms with a malignant potential which may cause symptoms such as hypoglycemia, multiple ulcers, diarrhea, flush, hyperglycemia and skin rash. A prospective study was performed on 84 patients with endocrine pancreatic tumors. In 59 patients (70%) the tumors were malignant. Of the 84 patients, 23 had insulinomas, 25 gastrinomas, 20 nonfunctioning tumors, 14 the WDHA syndrome, 1 somatostatinoma and 1 glucagonoma. The median age at diagnosis was 53 years and the median delay from first symptom to diagnosis was 2 years. The most common site of the pancreatic primary tumor was the tail (41%), and metastases were most frequently located in the liver (60%) and lymph nodes (44%). Plasma chromogranin A + B was elevated in 94%, serum pancreatic polypeptide (PP) in 74%, plasma neurotensin in 67% and serum gastrin in 62%. Serum HCG-alpha and -beta subunits were elevated in 41 and 30% respectively, all except 3 having a verified malignant tumor. The median survival from first symptom and diagnosis was 14.2 and 8.7 years respectively. Patients with MEN-1 had a significantly better survival from diagnosis than sporadic cases (median 15.1 versus 5.8 years). Patients who received interferon after failing chemotherapy had a significantly better survival than those given chemotherapy alone (5-year survival 65 and 50% respectively).
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PMID:Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. 247 25

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.
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PMID:Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia. 809 74

During a period of 13.5 years 17 patients with a gastrinoma and an associated Zollinger-Ellison syndrome were treated. In three patients (18%) the gastrinoma was part of a multiple endocrine neoplasia type I (MEN I). The median interval from the initial symptoms to the definite diagnosis was 5.0 years. During this interval seven patients (41%) underwent gastric surgery up to four times. The preoperative imaging studies localized the primary tumor in only seven patients (41%). In five of six diagnostic laparotomies the primary site of the tumor was identified and proved by pathologic work-up. The surgical procedures (n = 13) included five resections of the pancreas (3 x pancreatic head, 2 x left pancreatic resection), two duodenal resections, three enucleations of the tumor and three palliative operations (hospital mortality: 0%). Following laparotomy the gastrinoma could be histologically proved in eleven of 17 patients (6 x pancreas, 4 x duodenum, 1 x in the hepatoduodenal ligament). The rate of metastatic spread as characteristic feature of malignancy was 59%. After complete resection of the primary tumor (n = 8) none of these patients died because of the gastrinoma during the follow-up (median: 7.3 years). In the remaining patients three deaths were caused by the metastatic spread of the gastrinoma. Considering the high rate of preceding operations, the high malignancy rate and the excellent prognosis after RO-resection the diagnostic interval in patients with ZES is too long. Despite the modern radiographic imaging the exploratory laparotomy is of high value in patients with ZES.
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PMID:[Surgical therapy of gastrinoma with associated Zollinger-Ellison syndrome]. 896 20

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.
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PMID:Calcitonin-secreting tumors of the pancreas: about six cases. 959 18

Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions </= 1 cm in diameter on palpation, intraoperative ultrasonography, and microscopy. It occurred in 37% and 50% of the patients with and without radiologic tumor localization, respectively. The number of positive tumor markers was similar for patients with limited and major disease (2.3 vs. 2.7), whereas four or more such markers were found in all those with malignancies. The mean marker level was higher in patients with radiologically demonstrable tumors and lower in those with limited disease, but with a substantial overlap. OctreoScan testing was negative in all cases with limited disease and was the single most sensitive method (75%) in the others. Limited pancreatic disease could not be identified preoperatively, and the present means of biochemical pancreatic tumor identification invariably involved the presence of at least one lesion >/= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.
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PMID:Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration: can it be predicted by preoperative tumor localization? 960 80

Multiple endocrine neoplasia type 1 (MEN1) gene mutations are reported in some gastrinomas occurring in patients without MEN1 as well as in some other pancreatic endocrine tumors (PETs). In some inherited syndromes phenotype-genotype correlations exist for disease severity, location, or other manifestations. The purpose of the present study was to correlate mutations of the MEN1 gene in a large cohort of patients with sporadic gastrinomas to disease activity, tumor location, extent, and growth pattern. DNA was extracted from frozen gastrinomas from 51 patients and screened by dideoxyfinger-printing (ddF) for abnormalities in the 9 coding exons and adjacent splice junctions of the MEN1 gene. Tumor DNA exhibiting abnormal ddF patterns was sequenced for mutations. The findings were correlated with clinical manifestations of the disease, primary tumor site, disease extent, and tumor growth postoperatively. Tumor growth was determined by serial imaging studies. Sixteen different MEN1 gene mutations in the 51 sporadic gastrinomas (31%) were identified (11 truncating, 4 missense, and 1 in-frame deletion). Nine of the 16 mutations were located in exon 2 compared to 7 of 16 in the remaining 8 coding exons (P = 0.005 on a per nucleotide basis). Primary pancreatic or lymph node gastrinomas with a mutation had only exon 2 mutations, whereas duodenal tumors uncommonly harbored exon 2 mutations (P = 0.011). Similarly, small primary tumors (<1 cm) more frequently contained a nonexon 2 mutation (P = 0.02). There was no difference between patients with or without a mutation with respect to clinical characteristics, primary tumor site, disease extent, or proportion of patients disease free after surgery. Postoperative tumor growth tended to be more aggressive in patients with a mutation (P = 0.09). No correlation in the rate of disease-free status or postoperative tumor growth in patients with active disease to the location of the mutation was seen. These results demonstrate that the MEN1 gene is mutated in 31% of sporadic gastrinomas, and mutations are clustered between amino acids 66-166, which differs from patients with familial MEN1, in whom mutations occur throughout the gene. The presence of an MEN1 gene mutation does not correlate with clinical characteristics of patients with gastrinomas, gastrinoma extent, or growth pattern; however, the location of the mutation differed with gastrinoma location. These data suggest that mutations in the MEN1 gene are important in a proportion of sporadic gastrinomas, but the presence or absence of these mutations will not identify the clinically important subgroups with different growth patterns.
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PMID:Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas. 1063 74

Neuroendocrine tumors of the lung consist of a spectrum of neoplasms, including typical carcinoids, atypical carcinoids, large-cell neuroendocrine carcinomas (LCNEC), and small-cell lung carcinomas (SCLC). We previously reported frequent inactivation of the gene responsible for multiple endocrine neoplasia type 1 (MEN1) in both typical and atypical carcinoid tumors. In the present study, we extend the analysis of human NE lung tumors to include 9 primary SCLCs, 36 SCLC cell lines, and 13 primary LCNECs for MEN1 gene inactivation. In SCLC, loss of heterozygosity (LOH) at the MEN1 gene on chromosome band 11q13 was detected in one primary tumor and two cell lines. The coding sequence and splice junctions of the MEN1 gene were screened for mutations in all 44 tumors and cell lines, and no mutations were detected. Northern blot analysis of 13 SCLC cell lines showed the MEN1 transcript to be present and of normal size. In LCNECs, a somatic frameshift in the MEN1 gene (1226delC) was found in one of 13 tumors, representing the first mutation observed outside the spectrum of neoplasms associated with MEN1. Interestingly, neither a deletion nor a mutation was detected in the other allele, and wild-type mRNA sequence was expressed in the tumor, suggesting that the MEN1 gene was not inactivated by a conventional two-hit mechanism. The data support the hypothesis that SCLC and lung carcinoids develop via distinct molecular pathways; however, further investigation is necessary to determine the significance of the MEN1 gene mutation observed in a single case of LCNEC. Published 2000 Wiley-Liss, Inc.
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PMID:MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. 1073 3

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diarrhea (7%). Other less common misdiagnosis were Crohn disease (2%) and various diarrhea diseases (celiac sprue [3%], irritable bowel syndrome [3%], infectious diarrhea [2%], and lactose intolerance [1%]). Other medical disorders were present in 55% of all patients; patients with sporadic disease had fewer other medical disorders than patients with MEN-1 (45% versus 90%, p < 0.00001). Hyperparathyroidism and a previous history of kidney stones were significantly more frequent in patients with MEN-1 than in those with sporadic ZES. Pulmonary disorders and other malignancies were also more common in patients with MEN-1. These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. The presence of prominent gastric body folds, a clinical sign that has not been appreciated, is another important clue to the diagnosis of ZES. Patients with MEN-1 presented at an earlier age; however, in general, the initial symptoms were similar to patients without MEN-1. Gastrinoma extent and location have minimal effects on the clinical presentation. Overall, neither the introduction of successful antisecretory therapy nor widespread publication about ZES, attempting to increase awareness, has shortened the delay in diagnosis or reduced the incidence of patients presenting with peptic complications. The introduction of successful antisecretory therapy, however, has dramatically decreased the rate of surgery in controlling the acid secretion and likely led to patients presenting with less severe symptoms and fewer complications. (ABSTRACT TRUNCATED)
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PMID:Zollinger-Ellison syndrome. Clinical presentation in 261 patients. 1114 36

Familial thyroid cancer can arise from parafollicular cells (familial medullary thyroid cancer) or from follicular cells (familial nonmedullary thyroid cancer). Familial medullary thyroid cancer may occur in isolation or as part of multiple endocrine neoplasia (MEN) type II syndromes. Genetic testing for a RET mutation on chromosome 10 is used to identify new family members who are gene carriers. Total thyroidectomy should be used in gene carriers without clinical disease before age 6 in medullary thyroid cancer and MEN type IIA, and as soon as the diagnosis is made in MEN type IIB after the first year of life. Those with clinical disease should have at least a bilateral central neck dissection. Modified radical neck dissection is recommended for patients when the primary tumor is 1.5 cm. A normal postoperative serum calcitonin level suggests that the operation has been curative. Physicians need to be aware of ethical and lifestyle issues related to patients with familial disease and their family members. Familial nonmedullary thyroid cancer occurs as a discrete entity or as part of other family cancer syndromes such as Gardner syndrome, Cowden disease, and other rare syndromes. Familial nonmedullary thyroid cancer almost exclusively includes patients with papillary or Hurthle cell cancers. These families appear to have more benign thyroid conditions. The gene (or genes) for familial papillary thyroid cancer is yet to be identified, whereas that for some Hurthle cells (TCO) has been mapped to chromosome 19p13.2. Familial nonmedullary thyroid cancer is somewhat more aggressive than its sporadic counterpart, but is less aggressive than medullary thyroid cancer. Total thyroidectomy and central neck dissection followed by radioactive iodine ablation and thyroid hormone suppression appear to be the most effective therapy.
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PMID:Familial thyroid cancer. 1114 85


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