A splice variant of the transcript for guanylyl cyclase C is expressed in human colon and colorectal cancer cells.

Guanylyl cyclase C is a sensitive and specific biomarker for metastatic colorectal cancer. A variant of the guanylyl cyclase C transcript was identified that possesses a 142-bp deletion at the 3' end of exon 1 reflecting alternative splicing of mRNA, introducing a shift in the open reading frame that prevents translation of a guanylyl cyclase C-related product. This variant was identified in human intestine and colon carcinomas, but not in extraintestinal tissues or tumors. These studies demonstrate that GCC and the splice variant contribute to the pool of GCC transcripts detected by RT-PCR in human tissues. They indicate that primers for RT-PCR that amplify regions downstream from the deletion are required to assess the full complement of GCC transcripts (GCC + GCC(var)) in human tissues and body fluids for staging and postoperative surveillance of patients with colorectal cancer.

Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma.

Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma.

Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues.

Guanylyl cyclase C (GCC) has been detected only in intestinal mucosa and colon carcinoma cells of placental mammals. However, this receptor has been identified in several tissues in marsupials, and its expression has been suggested in tissues other than intestine in placental mammals. Selective expression of GCC by colorectal tumor cells in extraintestinal tissues would permit this receptor to be employed as a selective marker for metastatic disease. Thus, expression of GCC was examined in human tissues and tumors, correlating receptor function with detection by PCR. GCC was detected by ligand binding and catalytic activation in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues or tumors. Similarly, PCR yielded GCC-specific amplification products with specimens from normal intestine and primary and metastatic colorectal tumors, but not from extraintestinal tissues or tumors. Northern blot analysis employing GCC-specific probes revealed an approximately 4-kb transcript, corresponding to recombinant GCC, in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues. Thus, GCC is selectively expressed in intestine and colorectal tumors in humans and appears to be a relatively specific marker for metastatic cancer cells in normal tissues. Indeed, PCR of GCC detected tumor cells in blood from some patients with Dukes B colorectal cancer and all patients examined with Dukes C and D colorectal cancer, but not in that from normal subjects or patients with Dukes A colon carcinoma or other nonmalignant intestinal pathologies.

[The determination of tissue CEA in colorectal adenocarcinomas: an immunohistochemical study]. / Determinación del CEA tisular en adenocarcinomas colorrectales: un estudio inmunohistoquímico.

We carried out a CEA immunohistochemical study on 80 colorectal carcinomas, using the PAP methodology. Also we studied peritumoral "normal" mucosa on 69 cases. All tumoral (80/80) and the major part of normal colonic mucosa (68/69) cases stained positively. We present our experience with this immunohistochemical staining using a qualitative semi-quantitative evaluation, as an easy and reliable procedure. This permits to obtain, by immunostaining, a better homogeneous group of tumours (Apical, Mixed and Cytoplasmic, or Weak and Strong), necessary to further correlation with various tumoral parameters. On the basis of this evaluation, we found: A staining of weak intensity (65/68) of Apical type (55/68) in the vast majority of the normal, peritumoral mucosa. In tumors we found a prevalence of strong intensity (67/80), in relation to its major content of CEA. With respect to the type of immunostaining, although Apical staining (32/80) exists the Cytoplasmic (34/80) is predominant together with the Mixed type (14/80). This is expression of the alterations in secretion and distribution of the tissue CEA. We analyze the difficulties of such classification caused by the tumoral heterogeneity and we include other data whose significance is not always clear.

[A correlation between serum levels of preoperative CEA and CEA immunohistochemical staining in colorectal carcinoma]. / Correlación entre niveles séricos de CEA preoperatorios y tinción inmunohistoquímica del CEA en el carcinoma colorrectal.

We analyzed the distribution of tissue CEA in 80 colorectal adenocarcinomas with the PAP immunohistochemical technique. We used a qualitative method with a double grading criterion--topography and intensity of staining--as well as a semiquantitative method in the immunostaining interpretation. We applied a pattern of immunostaining: apical, cytoplasmic or mixed, to each tumor. Likewise, we obtained the pre-operatory serum levels of CEA. The normal value in our laboratory is less than 10 ng/ml. We correlated the immunostaining pattern with the serum levels of CEA, obtaining a global statistical significant correlation (p < 0.01), as well as apical versus cytoplasmic correlation (p = 0,0,3). The apical staining pattern agreed with this CEA levels < 10 ng/ml, whereas the cytoplasmic staining was associated with high frequency with CEA levels > 10 ng/ml. In conclusion the immunohistochemical staining for tissular CEA permits to improve the prognostic efficiency of serum CEA levels.

[Rupture of splenic artery aneurysm as a cause of acute abdomen]. / Ruptura de aneurisma de arteria esplénica como causa de abdomen agudo.

A male, 52 years old, presenting acute abdominal pain and hypovolemic shock, was diagnosed by ultrasound and CAT of fissured aneurysm of the splenic artery. Emergency laparotomy confirmed that the aneurysm had ruptured into the peritoneal cavity.

The effect of cyclosporin and lipopolysaccharide on fibroblasts: implications for cyclosporin-induced gingival overgrowth.

Drug-induced gingival overgrowth is an adverse side effect associated principally with 3 different types of drugs; specifically the antiepileptic phenytoin, the calcium channel antagonist nifedipine, and the immunosuppressant cyclosporin. The present study has analyzed the effect of cyclosporin and lipopolysaccharide on fibroblasts from 3 different sources: 1) normal healthy human gingiva (NHGF); 2) overgrown gingiva from 2 patients taking cyclosporin (CHGF); and 3) human fetal lung (WI-38). Fibroblasts isolated from cyclosporin-associated gingival overgrowth were significantly less responsive to cyclosporin in terms of DNA, total protein, and proteoglycan synthesis. This finding supports the in vivo response where few fibroblasts are seen but marked overgrowth of fibrous tissue occurs. Lipopolysaccharide derived from Fusobacterium nucleatum and Escherichia coli was capable of inhibiting DNA synthesis significantly in all 3 fibroblast types. Total protein synthesis by CHGF cells was inhibited differentially by Fusobacterium nucleatum LPS and addition of cyclosporin to this system resulted in reversal of the inhibition. A synergistic effect was noted when the proteoglycan output of NHGF cells was assessed in response to co-incubation with cyclosporin and Escherichia coli LPS. The study shows that bacterial LPS may be an important co-factor in the pathogenesis of cyclosporin-induced gingival overgrowth.

[Brown bowel syndrome: diagnostic and therapeutic problems]. / Síndrome del intestino marrón: problemas diagnósticos y terapéuticos.

A new case of a brown bowel syndrome is presented in a 27 year-old man, clinically with severe esteatorrhea of many years of duration, with moderate pancreatic exocrine insufficiency and intestinal motility disorders suggesting a functional change secondary to a deposit of lipofucsin. We comment the pathogenic, diagnostic and therapeutic implications related to this circumstance.

[Surgical treatment of Zenker's diverticulum. Apropos of 14 cases]. / Tratamiento quirúrgico del divertículo de Zenker. A propósito de 14 casos.

We present our experience in the surgical treatment of 14 cases of Zenker's diverticulum, diagnosed from January, 1969 to December, 1988. In 11 cases we performed one stage diverticulectomy; in 4 cases, manometric findings required cricopharyngeal myotomy. In 3 cases surgical treatment was not indicated; 2 patients had liver cirrhosis and high surgical risk and the third patient declined the treatment. Current treatment is discussed.

[Presentation of 6 cases of cystadenocarcinoma of the pancreas]. / Aportación de seis casos de cistoadenocarcinomas de páncreas.

Cystadenocarcinomas represent approximately 1% of the pancreatic tumors and are difficult to diagnose clinically and by pathology. Due to their rarity, published series are small. We present 6 cases of pancreatic cystadenocarcinoma collected over a period of 15 years at the Visceral Surgery Service of the Valencia University Hospital. The better evolution and prognosis of these tumors in comparison with pancreatic adenocarcinomas is noteworthy.

[Peptic stenoses of the esophagus]. / Estenosis pépticas del esófago.

The authors present a series of 32 cases of reflux peptic strictures of the esophagus. The mean age of the patients is 54 years, with a 3/1 predominance of males. The etiologic antecedent was hiatal hernia in every case, with a clinical time of evolution of 29 months, dysphagia being the most frequent symptom (100%). Complementary diagnosis was based fundamentally on endoscopy and barium transit, explorations that also allow exclusion of other pathologies. All the patients underwent medical treatment, this being the only treatment in 4 cases. The other 28 cases were treated surgically. The technique used was, in the cases in which the esophagus could be dilated, dilatation associated with an antireflux technique, and when not dilatable, resection with reconstruction using stomach (Sweet) or colonoplasty. The global mortality was two patients (5.2%). Patients were followed-up for a minimum of 2 years and the global results have been good, with recurrence in 3 cases (7.7%). Postoperative dysphagia appeared in 17 cases (44.7%), in all of the transitory.

Pigmentary changes in rat oral mucosa following antimalarial therapy.

Pharmacogenic pigmentation of the oral mucosa has been reported following the use of a number of anti-malarial drugs. The nature and distribution of the pigment is inconclusive in the literature. The aim of the present study was to document pigment deposition within the oral mucosa of DA rats following prolonged chloroquine and pyrimethamine administration. The drugs were given as a combined dosage and separately to different groups via stomach gavage tube. After 12 weekly administrations the palatal mucosa was examined histochemically and ultrastructurally for changes in numbers and size of active melanocytes using the dopa-oxidase technique. The serum was analysed for changes in ACTH and testosterone levels. Morphometric analysis of cells incubated for dopa-oxidase showed a significant increase in the size of dopa positive cells with both drugs but an increase in the number of active melanocytes with chloroquine only. Serum levels of ACTH remained unchanged with both drugs but pyrimethamine caused an elevation in testosterone.