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Biomedical subjects

A Castells

Publications and source records attributed to A Castells.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis.

OBJECTIVES: The prevalence of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) is not well established, as some reports suggest a low risk, whereas others indicate that HCC may be no less frequent than in other types of cirrhosis. METHODS: We compared the incidence of HCC in a series of 140 patients with PBC (five men, 135 women, mean age 54 +/- 1.6 yr) followed-up for a mean of period of 5.6 +/- 0.4 yr with a group of patients with cirrhosis related to hepatitis C virus (HCV) who were matched for age, sex, and follow-up period. In all patients, HCC was prospectively screened by clinical, laboratory, and ultrasound procedures. RESULTS: Five patients with PBC (3.6%) developed HCC. All were in stage IV of the disease. The incidence of HCC in the 45 patients with late stages of the disease (III or IV) was 11.1%, similar to that found in patients with HCV-related cirrhosis, which was 15.0%. The relative risk for HCC in late stages of PBC was of 0.812 (95% CI, 0.229-2.883) with respect to HCV-related cirrhosis. The probability for developing HCC was significantly higher in patients with HCV-related cirrhosis than in PBC patients overall (p = 0.001), but was similar in patients with HCV-related cirrhosis and in patients with PBC in stages III and IV (p = ns). CONCLUSION: The risk for HCC in patients with late stages of PBC is similar to that in patients with HCV-related cirrhosis.

Carcinoma, Hepatocellular↗
PubMed2000

A region of deletion on chromosome 22q13 is common to human breast and colorectal cancers.

Chromosomal allelic losses have varying frequency in breast cancer, with key regions including chromosomes 1, 3p, 7q, 9p, 16q, 17, and 22q. Recently, we have been able to map a new target region of allelic loss on chromosome 22q involved in colorectal cancer. The aim of the current investigation was to determine whether this target region may also be involved in human breast carcinogenesis. Thirty-six pairs of matched normal and tumor specimens from breast cancer patients, as well as eight breast cancer-derived cell lines, were genotyped using 17 microsatellite markers spanning chromosome 22q. Allelic deletion was found in 19 of 36 tumors (53%), and the pattern observed in those cases with partial losses was consistent with a region flanked by D22S1171 and D22S928. This interval overlaps that identified in colorectal cancer and comprises nearly 1.1 Mb. This study provides evidence of a common region of deletion on chromosome 22q13 involved in both breast and colorectal cancers and underscores the existence of putative tumor suppressor gene(s) at this location.

Alleles↗
PubMed2000

Prevalence and prognostic value of hepatocellular carcinoma in cirrhotic patients presenting with spontaneous bacterial peritonitis.

BACKGROUND/AIMS: This study examined the prognostic power of hepatocellular carcinoma in patients presenting an episode of spontaneous bacterial peritonitis treated with 3rd generation cephalosporins or quinolones, and subsequent prophylaxis with norfloxacin until death or transplantation. METHODS: The study comprises the prospective evaluation of 168 consecutive cirrhosis patients presenting an episode of spontaneous bacterial peritonitis. RESULTS: Hepatocellular carcinoma was diagnosed in 35 out of the 168 (20%) patients included in the study (10 single; 25 advanced tumors). Renal impairment developed in 82 patients. Resolution of infection was achieved in 90% of the cases, the hospital survival being 70%. Renal impairment, advanced tumor stage, albumin, and GGT showed independent prognostic value for hospital mortality. At the end of follow-up 101 patients had died, the 1- and 2-year survival being 36% and 31%, respectively. Four variables independently predicted survival: advanced tumor (OR: 3.9; p=0.00001), renal impairment (OR: 2.1; p=0.00001), bilirubin (OR: 1.6; p=0.02) and creatinine (OR: 1.3; p=0.03). Advanced tumor retained independent predictability in patients surviving hospitalization (OR: 7.5; p=0.0001), the 6-month survival being significantly lower in patients with advanced tumor (12% vs 57%, p<0.00001). CONCLUSION: The prevalence of hepatocellular carcinoma in cirrhotic patients with spontaneous bacterial peritonitis is high, and its presence should be actively sought. Advanced tumor impairs both hospital and long-term survival, and should be considered in the design of future trials.

Aged↗
PubMed2000

Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts.

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non-specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.

This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (</=5 cm in 16) and multinodular/massive in 76. After a median follow-up of 17 months, 79 patients died, the 1-, 2-, and 3-year survival being 54%, 40%, and 28%. The multivariate study identified PST (P =.01), constitutional syndrome (P =.04), vascular invasion (P =.001), and extrahepatic spread (P =.04) as independent predictors for mortality. The 1-, 2-, and 3-year survival for the 48 patients without adverse factors (Stage 0) was 80%, 65%, and 50%, respectively, and 29%, 16%, and 8% in the 54 patients with at least one adverse parameter (Stage I). Therefore, Stage 0 would correspond to an intermediate stage, while Stage I would represent an advanced status, before reaching an end-stage phase. In conclusion, the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern. Therapeutic trials should be designed and evaluated considering these characteristics.

Adult↗
PubMed1999

Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer.

BACKGROUND & AIMS: Chromosomal allelic losses have a varying frequency in colorectal cancer. The aim of this study was to define the target region of allelic loss on chromosome 22q in human colorectal carcinogenesis. METHODS: Fifty-seven pairs of matched normal colonic mucosa and tumor specimens from patients with colorectal cancer, as well as 15 colon cancer-derived cell lines, were genotyped using 15 microsatellite markers spanning chromosome 22q. A potential candidate gene was analyzed by a single-strand conformation polymorphism (SSCP)/direct DNA sequencing approach. RESULTS: After excluding 7 tumors with evidence of microsatellite instability, allelic loss was observed in 11 of the informative tumors (22%), 5 of which exhibited losses in all informative loci. The remaining 6 tumors showed variable patterns of partial allelic loss on chromosome 22q, thereby localizing a minimal region of allelic deletion between markers D22S1171 and D22S928. Physical mapping showed that this interval was 0.57 cM consisting of approximately 425 kilobases. Database searches identified the NBK/BIK gene, a proapoptotic BCL-2 family member, as a candidate gene in that region. However, SSCP/sequencing analysis excluded mutations of this gene. CONCLUSIONS: This study provides evidence for the involvement of putative tumor-suppressor gene(s) on chromosome 22q in human colorectal carcinogenesis. The identification of a 0.5-cM interval serves as the basis for the isolation of such a gene by positional cloning.

Alleles↗
PubMed1999

Prognostic factors in nonresectable pancreatic adenocarcinoma: a rationale to design therapeutic trials.

OBJECTIVE: Most patients with pancreatic cancer show an advanced tumor at the time of diagnosis. In recent years, new therapies have been developed in such patients, thus forcing the analysis of factors that influence their survival. The present study was aimed at determining the prognostic factors in a series of 134 consecutive patients with pancreatic carcinoma not suitable for surgical resection, due to either locally advanced tumors or metastatic spread. METHODS: First, 34 epidemiological, clinical, analytical, and tumor-related parameters recruited at admission were included in a univariate analysis of survival by using the Kaplan-Meier method. Those significant variables in the previous step were thereafter introduced in a Cox regression procedure. A prognostic index for calculating the relative risk of death of each patient was also proposed. RESULTS: The median survival time in the whole series was 3.11 months, the 3, 6, and 12 months probability of survival being 51%, 28%, and 8%, respectively. Eight of 34 variables (jaundice and toxic syndrome at admission, serum cholesterol, iron and alanine aminotransferase concentrations, leukocyte count, baseline performance status, and the presence of distant metastases) were selected in the univariate analysis. Of these eight parameters, the Cox regression analysis identified a preserved baseline performance status (OR = 2.14, 95% CI = 1.49-3.04) and the absence of metastases (OR = 1.34, 95% CI = 1.03-1.73) as the only variables independently associated with a longer survival. Therefore, a prognostic index was constructed allowing the division of patients in three different groups according to their relative risk of death (RRD) = exp (performance status x 0.7589 + presence of metastases x 0.2891). CONCLUSIONS: The results of the present investigation suggest that baseline performance status and distant metastases should be considered in designing and evaluating any therapeutic trial in patients with nonresectable pancreatic carcinoma.

Adenocarcinoma↗
PubMed1999

K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance.

PURPOSE: Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed. PATIENTS AND METHODS: Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. RESULTS: The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P<.005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). CONCLUSION: Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.

Adenocarcinoma↗
PubMed1998

[Usefulness of ultrasonography and computerized tomography in predicting resectability of pancreatic carcinoma].

BACKGROUND: Surgical resection is the only curative treatment of pancreatic carcinoma (PC). An accurate assessment of the extension of PC is mandatory to select appropriate patients to this therapeutic option. This study was aimed at assessing the usefulness of abdominal ultrasonography (US) and computed tomography (CT) to establish tumoral staging and to predict tumor resectability. PATIENTS AND METHODS: Between January 1990 and December 1995, 84 PC patients were submitted to surgical procedures (potentially curative resection in 30%, biliodigestive anastomosis in 51% and exploratory laparotomy in 13%). Preoperative staging was carried out by means of abdominal US and/or CT. Definitive staging was established according to surgical findings, using the TNM classification. RESULTS: Accuracy of preoperative evaluation with regard to tumoral staging was 65%, being underestimated in 29 (35%) patients. This underestimation was mainly due to lesions in stage I. In addition, preoperative staging predicted tumor unresectability with a 50% sensitivity and a 83% specificity. CONCLUSIONS: US and CT have a good specificity in the staging and unresectability prediction of pancreatic cancer. However, their usefulness is limited by their low sensitivity.

Aged↗
PubMed1998

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power.

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.

Adult↗
PubMed1998

Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.

This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty-two percent of the patients presented a self-limited postembolization syndrome, without treatment-related mortality. Fifty-five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a median follow-up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child-Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.

Aged↗
PubMed1998

Value of postoperative surveillance after radical surgery for colorectal cancer: results of a cohort study.

PURPOSE: Early detection of recurrence after curative resection for primary colorectal cancer should improve patients' prognosis. However, the usefulness of postoperative surveillance programs has not been clarified yet. The present cohort study was aimed at assessing the effectiveness of systematic follow-up in patients with colorectal cancer who were operated on for cure, regarding both rate of tumor recurrence amenable to curative-intent surgery and rate of survival. METHODS: One hundred ninety-nine colorectal cancer patients who underwent radical primary surgery were followed according a well-defined postoperative surveillance program, which consisted of laboratory studies (including serum carcinoembryonic antigen assay) every three months, physical examination and abdominal ultrasound or computed tomography every six months, and chest radiograph and total colonoscopy once per year. Cohorts were defined according to patients' compliance with the proposed follow-up program. A multivariate regression model was constructed to predict survival. RESULTS: One hundred forty patients were considered to be compliant with the surveillance program, whereas the remaining 59 patients occasionally attended follow-up investigations or did not comply at all. Although there were no differences in the overall recurrence rate (38 vs. 41 percent; P = 0.52), curative-intent reoperation was possible in 18 patients (34 percent) of those with tumor recurrence in the compliant cohort but in only 3 patients (12 percent) in the noncompliant cohort (P = 0.05). Similarly, the probability of survival was higher in the compliant cohort, both regarding overall (63 vs. 37 percent at 5 years; P < 0.001) and cancer-related (69 vs. 49 percent at 5 years; P < 0.02) rates. Cox regression analysis disclosed that only a more advanced TNM stage (odds ratio, 8.17; 95 percent confidence interval, 1.13-59.29) and noncompliance with the postoperative surveillance program (odds ratio, 2.32; 95 percent confidence interval, 1.50-3.60) had an independent negative impact on survival. CONCLUSION: Systematic postoperative surveillance in patients with colorectal cancer who were operated on for cure increases both the rate of tumor recurrence amenable to curative-intent surgery and rate of survival.

Aged↗
PubMed1998

Port site metastases and recurrence after laparoscopic colectomy. A randomized trial.

BACKGROUND: This study was performed to prospectively assess the impact of the laparoscopic approach to the patterns of port site metastases (PSM) and recurrence rate (RR) of resected colon carcinomas as compared with conventional colectomies. METHODS: All patients were included in a prospective randomized trial comparing laparoscopic-assisted colectomy (LAC) versus open colectomy (OC) for colon cancer. The randomization was stratified for localization of the lesion. Patients with metastasic disease at time of the surgery were excluded. Follow-up in the outpatient clinic was done every 3 months for a minimum of 12 months. Endpoints for the study were metastasis at port site and laparotomy incision as well as recurrence rate. RESULTS: Of 91 segmental colectomies performed from November 1993 to January 1996, there were 44 LAC and 47 OC. Patient data were similar in both groups (age, sex, Dukes stage, type of operation). Mean follow-up was 21.4 months, with a range of 13 to 41 months. There were no wounds or PSM in those series. RR was similar for both groups. For LAC, it was five of 31 (16.1%); for OC, it was six of 40 (15%). CONCLUSIONS: The laparoscopic approach has a recurrence rate similar to that for open procedures for colon cancer. However, additional follow-up of these patients is needed before we can determine whether or not the laparoscopic approach influences overall survival.

Aged↗
PubMed1998

Detection of colonic cells in peripheral blood of colorectal cancer patients by means of reverse transcriptase and polymerase chain reaction.

Circulating tumour cells play a central role in the metastatic process, but little is known about the relationship between this cellular subpopulation and the development of secondary disease. This study was aimed at assessing the presence of colonic cells in peripheral blood of patients with colorectal cancer in different evolutionary stages, by means of reverse transcriptase polymerase chain reaction (RT-PCR) targeted to carcinoembryonic antigen (CEA) mRNA. In vitro sensitivity was established in a recovery experiment by preparing serial colorectal cancer cell dilutions. Thereafter, 95 colorectal cancer patients and a control group including healthy subjects (n=11), patients with other gastrointestinal neoplasms (n=11) or inflammatory bowel disease (n=9) were analysed. Specific cDNA primers for CEA transcripts were used to apply RT-PCR to peripheral blood samples. Tumour cells were detected down to five cells per 10 ml blood, thus indicating a sensitivity limit of approximately one tumour cell per 10(7) white blood cells. CEA mRNA expression was detected in 39 out of 95 colorectal cancer patients (41.1%), there being a significant correlation with the presence of distant metastases at inclusion. None of the healthy volunteers and only 1 of 11 patients (9.1%) with other gastrointestinal neoplasms had detectable CEA mRNA in peripheral blood. By contrast, CEA mRNA was detected in five of the nine patients (55.6%) with inflammatory bowel disease. These results confirm that it is feasible to amplify CEA mRNA in the peripheral blood, its presence being almost certainly derived from circulating malignant cells in colorectal cancer patients. However, CEA mRNA detectable in blood of patients with inflammatory bowel disease suggests the presence of circulating non-neoplastic colonic epithelial cells.

Adult↗
PubMed1998

[Endoscopic ultrasonography in the staging of esophageal cancer. Therapeutic implications].

Endoscopic ultrasonography (EUS) provides accurate visualization of the different layers of the gastrointestinal wall and surrounding structures, allowing TN staging of tumors prior surgery. The aim of this study was to evaluate the sensitivity, specificity and accuracy of EUS in the staging of esophageal carcinoma as well as its applicability and usefulness in tumors with nontraversable stenoses. EUS was performed in 43 patients with esophageal carcinoma. The technique was carried out with a radial echoendoscope under sedation with i.v. midazolam. Both, the infiltration of the tumor through the layers of the esophageal wall (T staging) and the presence of lymph nodes in different areas (N and M staging) were determined. In cases with nontraversable stenoses, only the proximal tumor margin was assessed by means of EUS. EUS showed T1 stage in only one case and more advanced stages in the remaining patients: T2 (n = 12), T3 (n = 22) and T4 (n = 4). We know the outcome of 28 patients, 14 of whom underwent surgery. In these patients, the sensitivity for T and N staging was 86% and 92% respectively, and the accuracy 86% in both. Both, T and N, were overstaged in one case (7%) and understaged in another (7%). The tumor caused nontraversable stenoses in 59% of patients (n = 26). In 4 patients the staging could not be assessed with sufficient reliability. In the subgroup of patients with nontraversable stenoses who underwent surgery, the accuracy of EUS when comparing with histopathology was 80%. Endoscopic ultrasonography has a high sensitivity and accuracy in the staging of esophageal tumors even in cases with nontraversable stenoses.

Aged↗