A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Chromogranins A, B, and C, proteins that are co-stored and co-released with peptides and amines, have been identified in a variety of neuroendocrine tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumours in patients with endocrine pancreatic tumours, carcinoid tumours, pheochromocytomas, and small cell lung cancer. The radioimmunoassay determining the plasma concentrations of chromogranin A + B showed a greater sensitivity than that determining chromogranin A alone. All patients with endocrine pancreatic tumours, carcinoids, and pheochromocytomas had increased levels of chromograin A + B, whereas a small number of the patients (5/18 with endocrine pancreatic tumours and ⅓ with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. We have demonstrated that a polyclonal antiserum against a mixture of chromogranin A and B might be a more sensitive marker than chromogranin A alone for diagnosing neuroendocrine tumours. This is not surprising, since both chromogranins are widely distributed in neuroendocrine cells.

During a study on the modulatory effect of inhaled nitric oxide (NO) on the airway, we observed an increased bleeding tendency. Therefore, we studied bleeding time and blood rheology in rabbits during inhalation of 3, 30 and 300 parts per million (ppm) NO. The rabbits were intubated during neurolept anaesthesia and were ventilated mechanically. The bleeding time was significantly increased after 15 min of inhalation of 30 ppm NO, from 51 +/- 5 to 72 +/- 7 s (mean +/- SEM, P < 0.001, n = 7). However, there were no changes in haematocrit, whole blood or plasma viscosity, erythrocyte aggregation tendency, or erythrocyte deformability. Inhalation of 3 ppm NO increased bleeding time from 46 +/- 11 to 59 +/- 8 s (n.s., n = 4) and 300 ppm NO from 48 +/- 12 to 78 +/- 17 s (P < 0.05, n = 4). In another group of rabbits mean arterial pressure (MAP) was monitored using NO inhalation. A non-significant decrease was seen with 3 ppm and 30 ppm NO, from 63 +/- 2 to 59 +/- 3 mmHg (n = 6) and from 65 +/- 2 to 61 +/- 1 mmHg (n = 6) respectively. Inhalation with 300 ppm NO decreased MAP from 62 +/- 3 to 55 +/- 2 mmHg (P < 0.05, n = 6). We conclude from these data that inhalation of NO, 30 ppm or more exerts systemic effects.

Chromogranins A, B and C, proteins that are costored and coreleased with peptides and amines, have been identified in a variety of endocrine and nervous tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumors in patients with endocrine pancreatic tumors (EPT), carcinoid tumors, pheochromocytomas and small cell lung cancer (SCLC). Radioimmunoassay (RIA) of the plasmdserum concentrations of chromogranin A + B showed a greater sensitivity than RIA of chromogranin A alone. All patients with EPT, carcinoids and pheochromocytomas had increased levels of chromogranin A + B, whereas a small number of the patients (5/18 with EPT and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C.

Somatostatin-receptor scintigraphy using the 111In-labelled somatostatin-analogue octreotide ([111In-DTPA-D-Phe1]-octreotide) was performed in 40 patients with carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18 previously unidentified lesions were detected with this scintigraphy. Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide has a future role in the staging of patients with carcinoid disease.