PubMed Health⌕ Search

Biomedical subjects

A Castells

Publications and source records attributed to A Castells.

At least 19 recordsLinked to original sources
PubMed2006

SMAD4 mutations found in unselected HHT patients.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (ENG) or activin receptor-like kinase 1 (ALK1, ACVRL1) genes; both members of the transforming growth factor (TGF)-beta pathway. Mutations in SMAD4, another TGF-beta pathway member, are seen in patients with the combined syndrome of juvenile polyposis (JP) and HHT (JP-HHT). METHODS: We sought to determine if HHT patients without any apparent history of JP, who were undergoing routine diagnostic testing, would have mutations in SMAD4. We tested 30 unrelated HHT patients, all of whom had been referred for DNA based testing for HHT and were found to be negative for mutations in ENG and ALK1. RESULTS: Three of these people harboured mutations in SMAD4, a rate of 10% (3/30). The SMAD4 mutations were similar to those found in other patients with the JP-HHT syndrome. CONCLUSIONS: The identification of SMAD4 mutations in HHT patients without prior diagnosis of JP has significant and immediate clinical implications, as these people are likely to be at risk of having JP-HHT with the associated increased risk of gastrointestinal cancer. We propose that routine DNA based testing for HHT should include SMAD4 for samples in which mutations in neither ENG nor ALK1 are identified. HHT patients with SMAD4 mutations should be screened for colonic and gastric polyps associated with JP.

Activin Receptors, Type II↗
PubMed2005

Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.

AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. METHODS: We included 754 patients with a median follow up of 728.5 days (range 1-1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.

Aged↗
PubMed2005

The European panel on the appropriateness of gastrointestinal endoscopy guidelines colonoscopy in an open-access endoscopy unit: a prospective study.

BACKGROUND: The demand for gastrointestinal endoscopy is increasing in most developed countries, resulting in an important rise in overall costs and waiting lists for endoscopic procedures. Therefore, adherence to appropriate indications for these procedures is essential for the rational use of finite resources in an open-access system. AIM: To assess indications and appropriateness of colonoscopy according to the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria. METHODS: From May to June 2004, all consecutive patients referred to our Unit for open-access colonoscopy were considered for inclusion in this prospective study. Appropriateness of each colonoscopy was established according to the EPAGE criteria. In order to evaluate whether appropriateness of use correlated with the diagnostic yield of colonoscopy, relevant endoscopic findings were also recorded. RESULTS: A total of 350 consecutive patients were included in the study. In 38 of them, the colonoscopy indication was not listed in the EPAGE guidelines and, consequently, they were not evaluated. In the remaining 312 patients, the indication for the procedure was considered inappropriate in 73 (23%) patients. Both referring doctor characteristics (specialty and health care setting) and patient data (age) correlated with appropriateness of endoscopy. The diagnostic yield was significantly higher for appropriate colonoscopies (42%) than in those judged inappropriate (21%) (P = 0.001). CONCLUSIONS: A noteworthy proportion of patients referred for colonoscopy to an open-access endoscopy unit are considered inappropriate because of their indication, with significant differences among specialties. These results suggest that implementation of validated guidelines for its appropriate use could improve this situation and, considering the correlation between appropriateness and diagnostic yield, even contribute to improve the prognosis of patients with colorectal diseases.

Adult↗
PubMed2005

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

BACKGROUND: Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. OBJECTIVES: To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. METHODS: Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. RESULTS: In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. CONCLUSIONS: Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.

Abscess↗
PubMed2005

Mechanisms of colon cancer prevention with and beyond COX-2 inhibition.

Colorectal cancer is the most common cancer in Western countries and the second leading cause of cancer-related death. Sporadic lesions represent 75-80% of all colorectal cancer, whereas 20-25% are in younger individuals or in patients with a family history of cancer, suggesting a heritable susceptibility. Persons with germline alterations in cancer-promoting genes, such as those with familial adenomatous polyposis and hereditary non-polyposis colorectal cancer, stand to benefit significantly from chemopreventive interventions, along with those who had already developed any colorectal neoplasia (either adenoma or carcinoma). Among the most promising approaches to chemoprevention is the use of non-steroidal anti-inflammatory drugs, including both selective and non-selective cyclooxigenase-2 inhibitors. Although the present article is mainly focused on these drugs and their mechanisms of action, other strategies with potential involvement in colorectal cancer chemoprevention such as peroxisome proliferator activated receptor ligands, epithelial growth factor receptor blockers, calcium, vitamin D, folate, and DNA methyltransferase inhibitors are also reviewed.

Animals↗
PubMed2004

Laparoscopic-assisted approach in rectal cancer patients: lessons learned from >200 patients.

BACKGROUND: The applicability of laparoscopic surgery in the treatment of colorectal diseases is still controversial. Early reports on laparoscopic-assisted colectomy in patients with colon cancer suggested that it minimizes surgical trauma, decreases perioperative complications, and leads to a more rapid recovery. To our knowledge, no previous studies have compared the laparoscopic vs the open approach in rectal cancer. The aim of this paper was to assess the results of laparoscopic techniques in patients with rectal cancer. METHODS: From March 1998 to February 2003, all patients admitted to our unit with adenocarcinoma of the rectum were evaluated for surgery by the laparoscopic approach. RESULTS: A total of 220 patients with a mean age of 67.3 years were included in the study. One hundred thirty patients (59%) were treated with neoadjuvant chemoradiotherapy. In >75% of the patients, a surgical procedure with sphincter preservation was performed. The rate of conversion to the open approach was 20%. Ten patients had intraoperative complications. Fifty-eight patients (26.3%) developed postoperative complications. The length of hospital stay was 6.8 days. The distribution of tumor stages was as follows: stage I, 16.81%; stage II, 33.6%; stage III, 26.36%; stage IV, 19.09%. The mean number of lymph nodes was 13.8. The incidence of local relapse was 5.3%, with a follow-up of 18 months. CONCLUSION: Laparoscopic surgery can be safely performed in patients with adenocarcinoma of the rectum with good short-term results. Randomized controlled trials are needed to confirm these results.

Adenocarcinoma↗
PubMed2004

Laparoscopic-assisted colectomy in patients with liver cirrhosis.

BACKGROUND: Nonhepatic abdominal surgery, and especially colorectal surgery, is associated with high rates of morbidity and mortality among cirrhotic patients. With proper patient selection and preoperative optimization of the patient's condition, laparoscopic-assisted colectomy could become effective and safe for patients with compensated liver cirrhosis. The aim of this study was to evaluate the safety and feasibility of minimal-access surgery in these patients. METHODS: Between September 1993 and March 2003, 820 patients underwent laparoscopic-assisted colectomy at our hospital. We studied all patients with liver cirrhosis who underwent this operation. RESULTS: Seventeen patients with cirrhosis were included in the study. Twelve were Child's A and five were Child's B. The mean operative time was 150 min (ranges 75-280), mean estimated blood loss was 245 ml (ranges 100-250). The conversion rate to open surgery was 29% (five patients). Median length of hospital stay was 5 days. The morbidity rate was 29% (five patients). There were no anastomotic leaks or operative-related deaths. The median follow-up was 21 months. CONCLUSIONS: Laparoscopic-assisted colorectal surgery can be performed in compensated cirrhotic patients with low morbidity and mortality. Adequate patient selection and expertise in advanced minimal-access surgery are essential to obtain such good results.

Adenocarcinoma↗
PubMed2004

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

Adult↗
PubMed2004

[Hospital registry of pancreatic tumors. Experience of the Hospital Clínic in Barcelona (Spain)].

OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.

Adult↗
PubMed2003

Clinical usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by means of endosonography-guided fine-needle aspiration biopsy.

AIM: To establish the usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by comparing this technique with conventional cytology in aspirates obtained by endosonography-guided fine-needle aspiration. METHODS: All consecutive patients with pancreatic focal lesions undergoing endosonography-guided fine-needle aspiration were included. Samples were obtained with the concurrence of an attendant cytopathologist. Detection of codon-12 KRAS mutations was performed by the restriction fragment length polymorphism-polymerase chain reaction method. The effectiveness of conventional cytology, KRAS mutational analysis and their combination was established with respect to the definitive diagnosis. A cost-effectiveness analysis was also performed. RESULTS: Thirty-three patients had pancreatic adenocarcinoma and 24 patients had other lesions. A total of 136 samples was obtained. In patients in whom specimens were adequate (93% for cytology; 100% for mutational analysis), the specificity of both techniques was 100%, whereas the sensitivity favoured cytology (97% vs. 73%). When inadequate samples were considered as misdiagnosed, a combination of both techniques reached the highest overall accuracy (cytology, 91%; mutational analysis, 84%; combination of both, 98%). CONCLUSIONS: Cytology from aspirates obtained by endosonography-guided fine-needle aspiration is the most precise single technique for the diagnosis of pancreatic adenocarcinoma. However, when adequate specimens are not available to reach a cytological diagnosis, the addition of KRAS mutational analysis represents the best strategy.

Adenocarcinoma↗
PubMed2002

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer].

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Aged↗
PubMed2001

The management of leaking rectal anastomoses by minimally invasive techniques.

BACKGROUND: The salvage of a leaking rectal anastomosis has been reported in selected cases. Herein we present our experience in the management of rectal anastomotic dehiscence by minimally invasive techniques. METHODS: A total of 94 patients underwent anterior rectal resection for rectal cancer in an 18-month period. The operation was laparoscopic-assisted in 76 cases (81%). RESULTS: Clinical anastomotic dehiscences occurred in 10 cases (10.6%). Conservative therapy, including the percutaneous drainage of pelvic abscesses, was successful in three cases. Among the seven patients who required reoperation, the anastomosis was taken down in only one case. In four of these cases, the reoperation was performed laparoscopically, including peritoneal lavage and the creation of a diverting stoma. There were no complications resulting from the use of laparoscopy in the early postoperative period. Closure of the stoma was possible in eight patients. CONCLUSIONS: The salvage of a leaking rectal anastomosis is feasible in the vast majority of these cases (80%). The combination of laparoscopy and interventional radiology is a good alternative to laparotomy in patients who have had previous laparoscopic rectal excision.

Abscess↗
PubMed2001

Acute phase response in laparoscopic and open colectomy in colon cancer: randomized study.

PURPOSE: All types of trauma to the organism produce a systemic response that is proportional to the severity of the lesion caused. The more rapid clinical recovery during the postoperative period of patients undergoing laparoscopic-assisted colectomy vs. patients receiving conventional surgery suggests that laparoscopic surgery produces less surgical trauma. The aim of this randomized, prospective study was to compare acute phase postoperative response in patients diagnosed with colon neoplasm undergoing open segmentary colectomy vs. laparoscopic-assisted colectomy. METHODS: From June 1994 to July 1997 the results of 97 patients (58 submitted to open colectomy and 39 undergoing laparoscopic-assisted colectomy) were analyzed. Blood determinations of cortisol, prolactin, C-reactive protein and interleukin-6 were performed before surgery and at 4, 12, 24, and 72 hours after surgery. RESULTS: The plasma levels of cortisol and prolactin were higher in the postoperative period with both surgical techniques with no significant differences being observed. The levels of interleukin-6 achieved a maximum peak at 4 hours after surgery, later showing a decrease and practically achieving basal levels at 72 hours in both groups. The levels of interleukin-6 were higher with significant differences at 4, 12, and 24 hours in the patients undergoing open colectomy. The plasma levels of C-reactive protein were significantly lower at 72 hours in patients receiving laparoscopic-assisted colectomy. CONCLUSIONS: The results obtained in this randomized, prospective study suggest that acute phase systemic response is attenuated in patients undergoing laparoscopic-assisted colectomy in comparison with patients receiving open colectomy.

Acute-Phase Reaction↗