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Biomedical subjects

F Pimentel

Publications and source records attributed to F Pimentel.

At least 19 recordsLinked to original sources

Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma.

Although gallbladder carcinoma (GBC) is a highly malignant neoplasm, there is very limited information about the molecular changes involved in its pathogenesis. To identify the chromosomal locations of putative tumor suppressor gene loci involved in the pathogenesis of GBC, we conducted a genome-wide allelotyping or loss of heterozygosity (LOH) analysis of GBCS: Microdissected tissue from 24 archival GBCs and their matched control DNAs were analyzed for PCR-based LOH using 169 microsatellite markers spanning all nonacrocentric autosomal arms and the X chromosome. The chromosomal arms with the greatest frequencies of LOH (> or = 60%) were 3p, 6q, 7q, 8p, 9p, 9q, 11q, 12q, 17p, 18q, 19p, 22q, and XQ: The average fractional allele loss index in GBC cases was high (0.43) and frequent breakpoints were detected in gallbladder tumors. Of interest, 21 different regions of frequent LOH (hot spots) defined as > or = 50% for individual GBC samples were detected in this neoplasm, nearly half of them confined to one microsatellite marker. We conclude that in GBC at least 21 chromosomal regions with frequent allele losses are involved, suggesting that several putative tumor suppressor genes are inactivated in its pathogenesis. Overall, these data provide global estimates of the extent of genetic changes leading to GBC and will be useful for the identification of new tumor suppressor genes and for multiple new markers for translational research.

Adenocarcinoma↗

Increased activity in the biliary Con A-binding fraction accounts for the difference in crystallization behavior in bile from Chilean gallstone patients compared with Dutch gallstone patients.

Chile has one of the highest prevalences of cholesterol gallstone disease in the world. Recent data indicate that this is partly caused by genetic (Indian) factors. However, the causal factors inducing increased gallstone formation have not been elucidated. The aim of this study was to compare biliary composition and cholesterol crystallization in bile from patients of high and moderate risk areas (Chile and The Netherlands) for gallstone disease. Bile was sampled at cholecystectomy from 30 Chilean and 26 Dutch gallstone patients. The Con A-binding fraction (CABF) was extracted from fresh native bile samples by incubation with Con A-sepharose. Reconstitution of the CABF to the Con A-extracted native bile induced almost full recovery of crystallization confirming the validity of this technique. There was no difference between the two groups regarding sex and age. Chilean bile nucleated significantly faster (3.5 +/- 0.6 vs. 7.9 +/- 1.5 days) despite the fact that Dutch bile had a significantly higher cholesterol saturation index (CSI) (1.6 vs. 1.2, P = .01). The total lipid content was not different. Chilean bile contained more total protein (5 vs. 2.9 mg/mL, P = .008). IgG, IgM, Haptoglobin and alpha-1-acid glycoprotein were not different between the two groups. IgA, though, was significantly higher in the Chilean samples (0.44 vs. 0.19 mg/mL, P < .001). Extraction of CABF increased crystal observation time (COT) and decreased crystal growth in both groups. However, the effects were much more pronounced in the Chilean samples. Compared with Dutch bile, Chilean bile crystallizes much faster despite a lower CSI. Chilean bile contains an increased content of Con A-binding nucleation promoting activity.

Bile↗

Results of surgical treatment of gastric cancer.

BACKGROUND/AIM: The extent of gastric resection and the role of lymphadenectomy in the treatment of gastric cancer are controversial. METHODS: This study evaluates the results of radical gastric resection (D2 lymphadenectomy) in 375 patients with a gastric carcinoma operated according to a prospective protocol. RESULTS: Total gastrectomy was performed in 196 and a subtotal gastrectomy in 179 patients, with an operative mortality of 3.5 and 2.8%. The presence of lymph node metastasis was related to the depth of the tumor in the gastric wall. The cumulative 5-year survival was dependent on the depth of tumoral invasion in the gastric wall and also on the presence of lymphatic metastasis. Curative resection had a significantly better 5-year survival (72%) than noncurative resection (26%). CONCLUSION: Although it is difficult to prove the benefits of extended lymphadenectomy in the surgical treatment of gastric carcinoma, the results of these series seem to support its usefulness.

Female↗

[Subclinical apoplexy in pituitary tumors].

Acute pituitary apoplexy is a rare event, even in patients with pituitary macroadenomas. On the other hand, the presence of necrotic/hemorrhagic areas, especially in macroadenomas, seems to be more common than earlier reported in the CT period. After the introduction of MR in the presurgical workup of these patients, these apopleptic areas have been more easily diagnosed preoperatively. Forty consecutive patients with pituitary macroadenomas were studied with high-resolution 1.5 T T1 coronal, sagittal and axial slices over the sellar region. Special attention was paid in the detection of necrotic, cystic and hemorrhagic areas within these tumors. Ten patients had hemorrhagic/necrotic areas within their tumors, without any sign or symptom of acute apoplexy. These areas varied from small (2 mm) to very large (30 mm) ones. Seven patients had non-secreting tumors, 2 GH and 1 prolactin secreting tumors, which is the same profile of secretory pattern for the whole series (40 patients). The clinical picture included (other than that caused by endocrine secretion) slowly progressive (but not acute) visual loss (n = 8) and headache (n = 3). After surgical decompression of the surrounding structures and visual apparatus, which was facilitated by the presence of the necrotic areas, there was visual improvement in 6 patients and headache resolution in 2. The presence of asymptomatic apopletic areas in these macroadenomas and their absence in microadenomas as can be seen in the literature suggest that they are related more to the size of the tumor than to its endocrine secretion pattern. This is in agreement with a vascular insufficiency hypothesis in the pathogenesis of these lesions.

Adenoma↗

Cavernous sinus invasion by pituitary macroadenomas. Neuroradiological, clinical and surgical correlation.

The classical imaging gold-standard for this diagnosis is the presence of tumor lateral to the carotid artery. Seventeen patients with pituitary macroadenomas with intraoperative confirmation of cavernous sinus invasion were studied with MRI. Only 8 patients had tumor lateral to the carotid artery; 13 had tumor within the carotid syphon and all lacked the ring enhancement of the medial wall of the cavernous sinus. In 10 patients, widening of the posterior double leaflets of the cavernous sinus could be. All patients were operated by the transesphenoidal route. Only one patient was cured by surgery alone. Only 3 patients disclosing the above mentioned MRI features were identified in a series of 250 patients and did not have cavernous sinus invasion. The present criteria proved to be useful in the pre-operative diagnosis of cavernous sinus invasion and patients' counselling. Pre-operative diagnosis of cavernous sinus invasion of pituitary tumors has a great impact in the management of such patients.

Acromegaly↗

Malignant obstructive jaundice. Evaluation and management.

A large number of laboratory tests, radiologic studies, and endoscopic techniques are available for the evaluation of the jaundiced patient. Similarly, the therapeutic options have increased with the development and improvement of endoscopic, percutaneous, and laparoscopic procedures, and the morbidity and mortality rates associated with open surgery have decreased. The challenge is to select, on an individual basis, the most efficient and cost-effective evaluation as well as the management with the lowest morbidity and mortality rates and the best short- and long-term goals.

Cholestasis↗

Biliary aminopeptidase-N and the cholesterol crystallisation defect in cholelithiasis.

Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gall stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients. This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation.

Adult↗

[Gastrointestinal bleeding of unknown origin. Experience in 31 cases].

Thirty one patients with GI bleeding of obscure origin, defined as those with normal upper endoscopy and colonoscopy, were studied to know the yield of different diagnostic procedures. Seventeen patients consulted for hematochezia and bleeding less than 10 days of evolution in 71%. Small bowel X ray examination was performed in 14 cases with a diagnostic effectiveness (number of diagnosis/number or examination) of 14%, angiography was performed in 12 cases with an effectiveness 33%, radiolabeled erythrocyte scanning in 12 cases with an effectiveness of 75%, scintigraphy with pertechnetate in 6 cases with an effectiveness of 17% and intraoperatory endoscopy in 2 cases with an effectiveness of 50%. A definitive diagnosis was reached in 8 patients during the first admission and in 6 during the second admission. The principal etiologies were small bowel tumors in 3 cases, cecal ulcers in 2 and ileal diverticula in 2. Ten subjects were subjected to surgical and 2 to endoscopic treatment. Five patients with recurrent bleeding remain without diagnosis. It is concluded that radiolabeled erythrocyte scanning and angiography are effective examinations that should follow upper and lower endoscopies in the diagnosis of a concealed GI bleeding. When a diagnosis is not reached in the first admission, patients should be following with repeated diagnostic procedures.

Adolescent↗

[Colorectal cancer. Study of survival and surgical results].

The aim of this study was to assess the progress in the surgical treatment of colorectal carcinoma in a 15 years period at the Catholic University Clinical Hospital. The medical records of 397 patients were retrospectively analyzed. Two hundred eighty four patients (164 male) aged 24 to 90 years old, subjected to elective and curative interventions, were selected for the study and separated in two groups: 132 subjects operated between 1975 and 1984 (group A) and 152 operated between 1985 and 1989 (group B). Group B patients were older (66.7 vs 61.3 years old), had a higher proportion of Dukes A tumors (11 vs 18%) and a lower proportion of lesions localized in the rectum (37 vs 49%). Rectal operations had higher morbidity than colonic interventions (35 vs 17.5%). Operative mortality was 0.7% in group A and 0.6% in group B. Ninety one percent of patients had a mean follow up of 38 months. Five years actuarial survival was 52% in group A and 69% in group B and 58, 74 and 46% for tumors Dukes A, B and C respectively.

Actuarial Analysis↗

[The common channel syndrome in adults].

Congenital abnormalities of the distal bile and pancreatic duct occur predominantly as a long common channel. A common channel of more than 15 mm is considered abnormal, since the length allows a reflux of pancreatic secretion into the bile duct and vice versa. The very rare occurrence of a long common channel syndrome in adults has been observed in two female patients (24 and 58 years old). Both presented cholangitis and/or pancreatitis. Diagnosis was established by ERCP. The definitive therapy in both cases was hepatico-jejunal anastomosis which improved symptoms in both patients. Endoscopic sphincterotomy is unsatisfactory since it does not cut the entire common channel. The rare etiology of a long common channel in patients with cholangitis and pancreatitis is safely verified by ERCP and safely cured by surgical intervention.

Acute Disease↗

Extracorporeal shock-wave lithotripsy and endoscopy: combined therapy for problematic bile duct stones.

Endoscopic treatment of bile duct stones is currently successful in 86% of patients. We prospectively studied the efficacy and complication rate of extracorporeal shock-wave lithotripsy (ESWL) of problematic bile duct stones combined with endoscopy. When stone removal was not possible, patients were subjected to ESWL. Fragmented stones were removed endoscopically. During 1 year, 220 patients presenting with choledocholithiasis were diagnosed and 188 were successfully treated endoscopically. In all, 3 subjects received alternative treatment and the remaining 29 (13%) constituted our study group; 19 (65%) were women and the mean age was 76.7 years. Overall, 22 (76%) were high-risk patients; 23 (79%) were jaundiced and 9 (31%) had cholangitis at admission. The most frequent indication for ESWL was stone size. Stone fragmentation was achieved in 80% of cases. Complications were mild and were managed conservatively. No patient died. Complete stone clearance was possible in 23 (80%) cases. The association of ESWL and endoscopy enhanced the success rate of endoscopic stone clearance from 86% to 96%. During the same period, open surgery was performed in 4 cases for residual common bile duct (CBD) stones and in 32 cases in association with simultaneous cholecystectomy.

Aged↗

Catabolism of chylomicron remnants in patients with previous acute pancreatitis.

A recent study reports that patients with previous acute pancreatitis commonly have an abnormal clearance of serum triglycerides after an oral fat load. This observation supports the hypothesis that patients with previous acute pancreatitis and normal fasting serum triglyceride levels may have a preexistent abnormality in the metabolism of chylomicrons. To test this hypothesis, the catabolism of chylomicrons and their remnants was studied in a series of 7 patients who had sustained an attack of pancreatitis (2, gallstone related; 2, alcohol ingestion; 1, hydatid cyst; and 3, no associated pathological condition) at least 18 mo earlier. All the patients had previously had abnormal oral-fat tolerance test results. These patients were compared with a series of 6 healthy volunteers. Chylomicrons were endogenously labeled with an oral dose of retinyl palmitate, and their plasma elimination half-life was calculated. The retinyl palmitate absorption rate constants were similar in control and pancreatitis patients. The chylomicron t1/2 were 2.3 +/- 0.8 (SD) h and 3.9 +/- 1.8 h in the control and pancreatitis groups, respectively (p = 0.07). The chylomicron remnant t1/2 was 2.7 +/- 1.1 h in the control group and 5.2 +/- 2.4 h in the pancreatitis group (p less than 0.05). This study supports the hypothesis that subjects with previous acute pancreatitis may have an abnormality in the catabolism of chylomicron particles. This abnormality may represent a preexistent genetic condition expressed in either the apoprotein composition of chylomicrons or in the hepatic apolipoprotein E-receptor activity.

Acute Disease↗

[Gastric cancer: surgical results and survival].

From 1975 to 1984, 292 patients with gastric cancer were treated according to a prospective and standardized surgical protocol. This series included 195 men and 97 women, with an average age of 62.5 +/- 11 years (SD). In 20 patients (6.8%) surgery was not performed and 99 were considered unresectable at laparotomy. Gastric resection was performed in 173 (63.3%) (distal subtotal gastrectomy in 94 and total gastrectomy in 79). Operative mortality for subtotal gastrectomy was 3.1% and 6.3% for total gastrectomy. Early gastric cancer was found in 21 patients (none presented lymph node metastases). The cancer invaded the muscular layer in 18 (31% with lymph node metastases) and reached beyond the muscular layer in 134 patients (60.8% with lymph node metastases). The five year actuarial survival was 0% in patients who did not undergo gastric resection, 35.5% for those patients with tumor invading the serosal layer or beyond who were resected, 56.5% for those with invasion up to the muscular layer and 91.8% for patients with early gastric cancer. For those patients who underwent a curative resection, actuarial five year survival was 81%.

Actuarial Analysis↗