In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas. We describe eight patients with MEN-1 and hypergastrinemia (seven with the Zollinger-Ellison syndrome) in whom we searched for neuroendocrine tumors in the pancreas and duodenum. Tumors were found in the proximal duodenum in all eight patients: solitary tumors (diameter, 6 to 20 mm) in three patients and multiple microtumors (diameter, 2 to 6 mm) in the other five. Paraduodenal lymph-node metastases were detected in four patients. Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases. In contrast, no immunoreactivity for gastrin was present in the endocrine tumors found in the seven pancreatic specimens available for study, except for one tumor with scattered gastrin-positive cells. In four of the six patients whose duodenal gastrinomas were removed, serum gastrin levels returned to normal; in the other two patients gastrin concentrations decreased toward normal. We conclude that in patients with MEN-1 and the Zollinger-Ellison syndrome, gastrinomas occur in the duodenum, but the tumors may be so small that they escape detection.

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Pancreatic specimens of nine patients suffering from multiple endocrine neoplasia type I (MEN I) were investigated with regard to tumor frequency and growth pattern, islet hyperplasia and endocrine cell neoformation, immunocytochemical hormone profile of the tumors, and correlation to clinical symptoms.The majority of the 201 tumors were microadenomas (diameter < 0.5 cm), which frequently displayed a trabecular growth pattern. Microadenomatosis was considered the most distinct feature of the M E N I pancreas. Additional larger tumors (diameter > 1.0 cm) were found in five patients. Whereas islet hyperplasia appears not to belong to the spectrum of the pancreatic lesions in M E N I, nesidioblastosis was occasionally observed. Immunocytochemical screening revealed that among hormone-positive tumors (approximately 80% of the tumors), pancreatic polypeptide tumors (PPomas), glucagonomas, and insulinomas were the most frequent. The high incidence of PPomas in these pancreases probably accounts for the elevated serum PP levels found in many MEN I patients. Somatostatinomas, gastrinomas, vasoactive intestinal polypeptide tumors (VIPomas), and neurotensinomas were rare. Clinically overt hyperinsulinism, observed in two patients and associated with a large insulinoma, was cured by tumor resection. Eight of nine patients presented a Zollinger-Ellison's syndrome (ZES), but only in two patients were gastrinproducing tumors found. The source of gastrin in MEN I patients with a ZES, in whom no gastrinoma could be detected, remains unclear.

Specimens from the pancreas and duodenum of 26 patients with sporadic Zollinger‐Ellison syndrome (ZES) and 18 patients with multiple endocrine neoplasia type 1 (MEN‐1) and hypergastrinemia (17 with ZES) were screened immunocytochemically for gastrinomas. Location, size, multicentricity, and malignancy of the gastrinomas were evaluated. The MEN‐1 patients had gastrinomas in the duodenum (nine of 18), pancreas (one of 18), and periduodenal lymph nodes (two of 18). No gastrinoma was identified in six patients. Most duodenal gastrinomas were multiple (five of nine) and smaller than 0.6 cm (six of nine). Lymph node metastases were present in eight of 12 patients. All 26 patients with sporadic ZES had a solitary gastrinoma; 14 were found in the pancreas and had a diameter greater than 2 cm. Ten patients had a duodenal gastrinoma, two with a diameter less than 0.6 cm. In two patients, only periduodenal “lymph node gastrinomas” were detected. Eighteen of the sporadic gastrinomas were malignant. These results suggest that duodenal location and multicentricity of gastrinomas are associated with the MEN‐1 syndrome, and solitary gastrinomas, either in the pancreas or the duodenum, are predominantly seen in sporadic ZES.

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We report the autopsy fi ndings for a 45-year-old man with polyradiculoneuropathy and fatal acute disseminated encephalomyelitis after having Mycoplasma pneumoniae pneumonia. M. pneumoniae antigens were demonstrated by immunohistochemical analysis of brain tissue, indicating neuroinvasion as an additional pathogenetic mechanism in central neurologic complications of M. pneumoniae infection.A 45-year-old, previously healthy man had fever, pain in the extremities, nasal discharge, and cough with nonpurulent sputum. He sought clinical care 1 week after onset of illness because of his deteriorating general state, including a headache and paresthesias in both hands. Bilateral basal pneumonia was diagnosed and treated with clarithromycin. During the ensuing 4 days, a rapidly ascending polyradiculoneuropathy resulted in tetraparesis, followed by facial palsy, ophthalmoplegia, and then paralysis of all cranial nerves. The initially fully alert patient became comatose, and assisted respiration was necessary.On day 9 of the patient's illness, an ELISA (Genzyme Diagnostics Virotech, Rüsselsheim, Germany) was performed on serum samples and showed a Mycoplasma pneumoniae immunoglobulin (Ig) G antibody titer of 28.2 Virotech-units/mL (VE) (cut-off 9.0-11.0) and an IgM antibody titer of 20.9 VE (cut-off 9.0-11.0). A PCR for M. pneumoniae was positive in tracheobronchial secretions on day 12, and complement fi xation test (antigen purchased from Virion CH-8803 Rüschlikon, Zürich, Switzerland) showed M. pneumoniae antibody titers of 1,280 (serum) and 4 (cerebrospinal fl uid) on day 16.Serologic tests for cytomegalovirus, Epstein-Barr virus, HIV, measles virus, mumps virus, spring-summer encephalitis virus, Borrelia burgdorferi, Brucella spp., Legionella spp., Treponema pallidum, and Toxoplasma gondii were negative. No herpes simplex virus 1 or 2 was detected by PCR in cerebrospinal fl uid, and PCR results were also negative for Chlamydia pneumoniae in tracheobronchial secretions.On day 8, cerebrospinal fl uid examinations showed a total cell count of 43/mm 3 (89% granulocytes and 11% mononuclear cells), total protein 1.3 g/L, and glucose 4.3 mmol/L. On day 15, when the patient was comatose, a total cell count of 794/mm 3 (84% granulocytes and 16% mononuclear cells), total protein 4.6 g/L, and glucose 1.5 mmol/L. Blood values showed leucocytosis with neutrophilia and mild thrombocytosis of 480 g/L.A computed tomographic scan on day 15 showed brain edema and multiple infl ammatory/demyelination lesions in the subcortical white matter of both hemispheres and within the brain thalami, capsulae internae, midbrain, and pons. Electroneurographic and myographic results showed a severe form of a peripheral axonal neuropathy. No antigangliosid (GM) 1 or anti-GM2 antibodies were found in the patient's serum on day 12. We did not look for GQ1b antibodies.The clinical diagnosis was polyradiculoneuropathy (atypical Guillain-Barré syndrome) and acute encephalitis as complications of bilateral pneumonia caused by M. pneumoniae. In addition to c...

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inactivation of p53 by the virally encoded protein HBX. 7 We analyzed the 3 exons of the p16 INK4 (MTS1) gene by single-strand conformation polymorphism (SSCP) and DNA Hepatocellular carcinoma (HCC) is one of the most fre-sequencing in 26 patients with HCC with different etiologiquent human malignancies worldwide. Its incidence shows cal/pathological backgrounds. In addition, we determined the a striking geographic variability, with a high prevalence in methylation status and allele-loss frequency of the populations exposed to aflatoxin B1. Other major etiologic p16 INK4 (MTS1) gene in HCC. Our results suggest that (1) a factors for HCC development are hepatitis B or C virus infec-subset of noncirrhotic HCC cases could be familial, as sugtion and cirrhosis. Recently, the existence of familial inheri-gested by germ-line mutations of p16 INK4 (MTS1); and (2) sotance of HCC in an Alaskan population has been suggested. 1 matic inactivation of the p16 INK4 (MTS1) gene by methylation The molecular mechanisms involved in hepatocarcinogen-or deletion is frequently observed in human hepatocarcinoesis remain poorly understood. The most widely known can-genesis. cer-associated gene in HCC is p53. Somatic mutations in codon 249 have been identified at a high frequency in HCC PATIENTS AND METHODSfrom African and Chinese populations exposed to aflatoxin Patients. Twenty-six patients who underwent partial hepatec-B1. 2,3 However, transfection of a murine p53 gene mutated tomy for HCC in the Departments of Surgery of the University Hospiat the position corresponding to human codon 249 into hepa-tals of Bern or Lausanne (Switzerland) were studied. Tumor and tocytes is insufficient to transform hepatocytes. 4 In Western nontumor liver tissue samples were available for histological examiand other low-aflatoxin B1-exposed countries, somatic p53 nation and DNA extraction. In all cases, the tumor-free liver parenchyma surrounding the tumor was carefully examined histopathologgene alterations are infrequently associated with HCC. 5,6 ically. Alcohol abuse-related HCC with cirrhosis is the most common Also, hepatitis B-and C-related HCC display a low incitype observed in Switzerland. Because it is rarely treated with surdence of p53 mutations, possibly because of the functional gery, our HCC samples lacking cirrhosis are overrepresented relative to actual incidence. The relevant clinicopathological characteristics are summarized in Table 1. All patients were white Swiss citizens except patient 11, who was a Bengali refugee. A control group of From the