摘要:

Despite certain advances, the overall prognosis for pancreatic carcinoma has remained extremely dismal. Even now, not more than 5% of all patients diagnosed as having pancreatic carcinoma survive 5 years. With this background, the standards and new developments for this entity are discussed.

ISSN:0012-2823    

DOI:10.1159/000201390

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Teprenone (geranylgeranylacetone) is a gastric mucosal protective drug used clinically in Japan for treatment of gastric ulcers and gastritis. Its effect on portal hypertensive (PHT) gastric mucosa which has impaired defensive mechanisms is not known. In 20 PHT and 20 sham-operated rats, we studied the effects of teprenone or placebo on: (1) portal pressure; (2) gastric pH; (3) gastric mucosal blood flow using laser Doppler flowmetry, and (4) hexosamine content in gastric mucosa. The gastric mucosal blood flow was significantly higher in the PHT + teprenone group than in the PHT + placebo group (463 ± 75 and 381 ± 82 perfusion units, respectively; p < 0.05). The hexosamine content was significantly lower in PHT rats than in sham-operated controls (12.6 ± 2.3 vs. 14.3 ± 2.2 μg/mg, respectively). Teprenone treatment significantly increased the gastric mucosal hexosamine concentration in both sham-operated and PHT rats (17.2 ± 3.1 and 15.6 ± 3.6 μg/mg, respectively). These effects of teprenone, combined with its known prostaglandin-stimulat-ing action, suggest a potential role for this agent in the treatment of PHT gastric mucosal abnorm

ISSN:0012-2823    

DOI:10.1159/000201310

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

8 patients with papillary cancer (4 with metastases, 4 in remission), 7 follicular cancer patients (6 with metastases), 2 patients with anaplastic thyroid cancer, and 4 other non-medullary thyroid cancer patients all received an intravenous bolus injection of 220 MBq [111In-DTPA-D-Phe1]octreotide. Planar anterior and posterior n camera images of head-neck, chest and abdomen were obtained 24 and 48 h after injection. All primary cancers showed [111ln-DTPA-D-Phe1]octreotide uptake; none occurred in patients in remission. The results were compared with conventional radio-iodine scintigraphy in patients with metastasised, differentiated thyroid cancer.

ISSN:0012-2823    

DOI:10.1159/000201391

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Paediatric oncology continues to search for improved methods for the early detection and effective treatment of solid tumours, especially those of the nervous system, which constitute 50% of all solid tumours in children and adolescents. These tumours, including neuroblastoma, meningioma, low-grade astrocytoma and medulloblastoma express somatostatin receptors and can be imaged effectively using 111In-octreotide. In addition to improved imaging techniques, somatostatin analogues are being developed for use in radiorecep-tor-guided surgery, as a component of adjuvant chemotherapy and for supportive treatment. Radioreceptor-guided surgery utilises 125I-Tyr3-octreotide or 125I-lanreotide to detect tumour foci within minutes of injection. It allows the detection of 0.1-1.0 mg tumour (1 × 105 to 1 × 106 tumour cells). This technique has successfully located foci of occult tumour in children with neuroblastoma. Somatostatin analogues are also currently being studied as tumour growth inhibitors between regular chemotherapy cycles and for the treatment of chemotherapy-induced pancreatitis in children with leukaemia. Research on somatostatin receptor subtype expression in paediatric tumours suggests that further investigation of analogue effects on growth inhibition and induction of differentiation will contribute to improved therapy for children with solid tumour

ISSN:0012-2823    

DOI:10.1159/000201392

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Prostaglandins reduce damage by noxious agents to isolated gastric cells. The mechanism remains unexplained. This study was done to examine involvement of microtubules with prostaglandin-mediated cell protection. Cultured mucus-producing cells of rat gastric mucosa were used. Cultured cells were incubated with 16,16-dimethyl-prostaglandin E2 (dmPGE2), colchicine, or vehicle alone in calcium-containing (1.3 mM) and calcium-free medium. The cells were then exposed to 8% ehtanol. Cell integrity and damage were assessed by 51Cr release and in part by transmission electron microscopy (TEM). Specific 51Cr release was closely related to percentage change of necrotic cells assessed by TEM. Cell damage caused by 8% ethanol was greater in medium-containing calcium than in calcium-free medium. dmPGE2 at 10-5M inhibited cell damage in calcium-containing medium. Colchicine itself at concentrations up to 10-5M did not affect cell integrity, but at 10-5M concentration potentiated damage caused by 8% ethanol in calcium-containing medium. Pretreatment with 10-5M colchicine abolished the protective effect of dmPGE2. Microtubules may mediate protection by dmPGE2 of cultured gastric cells against ethanol damage.

ISSN:0012-2823    

DOI:10.1159/000201311

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Carcinoid tumours may develop from enterochromaffin cells in the gastrointestinal tract. Benign insulin-producing tumours may develop from islet cells, whereas other islet cell tumours might derive from multipotent stem cells in the pancreatic ducts. The idea that multiple endocrine neoplasia type 1 (MEN-1) tumours in the pancreas originate from multipotent stem cells is supported by our demonstration that CD44 is expressed in exocrine cells, in gastrin-producing endocrine cells only and in some non-functioning islet cell tumours; there are no gastrin-producing cells in the adult pancreas. We have identified phospholipase Cβ3 (PLCβ3) as the gene implicated in MEN-1. It appears to be a tumour supressor gene since it is expressed in endocrine pancreatic tumours, some lung carcinoids, and medullary thyroid carcinomas. So, neuroendocrine tumours might have a dual growth-regulating system, involving both traditional growth factors through the tyrosine kinase system and also G-protein-mediated growth signals. Deletion of PLCβ3, which is an important enzyme in the signal transduction pathway of G-protein-mediated signals, might be important in the growth regulation of neuroendocrine tumours. It is proposed that its deletion causes dysregulation of growth control in neuroendocrine cells, with possible distortion of the apoptotic process. In the last stage of the disease, tumour biology is altered and becomes more aggressive. Further, chromogranin A may be both a tumour marker for neuroendocrine tumours and a growth-promoting agent for neuroendocrine tumour cells; it is a very good marker of tumour mass but is also related to poor prognosis of survival. Mutation analyses of PLCβ3 and studies of the growth-promoting effect of chromogranin are ongoing and should lead to more effective therap

ISSN:0012-2823    

DOI:10.1159/000201393

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Due to the increased costs of medical care, a cost-benefit analysis is needed when trying for the ‘ultimate’ biochemical diagnosis of gastro-enteropancreatic (GEP) tumours. The glycoprotein chromogranin family has proved useful in screening for neuroendocrine tumours. In patients with midgut carcinoid tumours, chromogranin A is more sensitive than urinary 5-hydroxyindoleacetic acid but by combining these two biochemical markers most GEP tumours can be diagnosed. Chromogranin A is also a prognostic marker for survival in patients with midgut carcinoid tumours. Pancreastatin constitutes a part of the chromogranin A molecule and is a less sensitive general screening marker for neuroendocrine gut and pancreatic tumours, but levels, in combination with chromogranin A, might give some insight into tumour biology. Specific markers such as gastrin, glucagon, vasoactive intestinal peptide, insulin, neuropeptide K and substance P should be used to further characterise hormone production in neuroendocrine tumours. However, in some patients, confirmation of diagnosis requires provocation tests, such as the secretin or meal provocation tests. Staging information can be obtained by new investigations such as intra-operative or endoscopic ultrasound, octreoscan, and positron emission tomography. We combine the biochemical characterisation of neuroendocrine tumours with studies of growth factors/receptors, adhesion molecules, proliferation markers, somatostatin receptor content, induction of the enzymes p68 kinase and 2’5’-A-synthetase, and apoptosis, to establish a sound rationale for therapeutic decisions, enabling every patient to receive individualised tr

ISSN:0012-2823    

DOI:10.1159/000201394

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied the effects of a mild irritant, 10% ethanol, and sofalcone on the gastric mucosal defense mechanisms in newborn rats, comparing the effects to those seen in adult rats. The results indicated (1) that both mucosal prostaglandin E2 (PGE2) content and mucus gel layer thickness increased with age, (2) that sofalcone, but not 10% ethanol, increased mucosal PGE2 content and mucus gel thickness in 1- and 8-week-old rats, (3) that both sofalcone and 10% ethanol decreased mucosal damage induced by 50 or 75% ethanol in both age groups, and (4) that 10% ethanol, but not sofalcone, decreased ethanol-induced mucosal damage in rats pretreated with indomethacin. We concluded that 10% ethanol and sofalcone increase gastric mucosal defense mechanisms in newborn rats as in older rats.

ISSN:0012-2823    

DOI:10.1159/000201312

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This paper considers the confirmation of diagnosis, made initially from histological analysis of tumour tissue, of neuroendocrine tumour disease, using elevated secretory products in the blood. These include hormones, peptides, neurotransmitters and packaging proteins of secretory vesicles such as chromogranin A.

ISSN:0012-2823    

DOI:10.1159/000201395

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Compared with other imaging modalities and clinical investigation, the 111ln-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean ( ± SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% ( ± 6%). 8 patients had 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discusse

ISSN:0012-2823    

DOI:10.1159/000201396

出版商:S. Karger AG    

年代:1996

数据来源: Karger