Use of fully covered self-expanding metal stents for the management of benign biliary conditions.

BACKGROUND AND AIM: biliary self-expanding metal stents (SEMS) have the advantage of being inserted undeployed with very small sizes and provide, when fully opened, large diameters for biliary drainage. However, their use in benign conditions has been very limited, mainly because of difficulty in their extraction. We present our initial experience with a fully covered SEMS (Wallflex) for the management of benign problems of the bile duct. PATIENTS AND METHODS: in a prospective study, stents of 8 mm in diameter and 4, 6 or 8 cm long were inserted by means of ERCP. These SEMS were chosen when according to medical judgement it was thought that diameters greater than 10 French (3.3 mm) were needed for proper biliary drainage. Stents were extracted also endoscopically, several months later when deemed clinically appropriate. RESULTS: twenty biliary SEMS were inserted. Reasons for insertion were: large intrahepatic biliary fistula after hydatid cyst surgery (1), perforation of the papillary area following endoscopic sphincterotomy (2), coaxial insertion to achieve patency in obstructed uncovered stents inserted in benign conditions (3), benign strictures (7), multiple and large common bile duct stones that could not be extracted because of tapering and stricturing of the distal common bile duct (7). In all cases, successful biliary drainage was achieved and there were no complications from insertion. Stents were easily extracted after a mean time of 132 days (36-270) in place. Complete resolution of biliary problems was obtained in 14 patients (70%). CONCLUSIONS: in our initial experience, the fully covered Wallflex biliary stent was removed without any complication after being in place in the common bile duct for a mean time of over four months. Therefore, it could be used in the management of benign biliary conditions.

Long-term follow-up of patients with small-bowel angiodysplasia on capsule endoscopy. Determinants of a higher clinical impact and rebleeding rate.

BACKGROUND: the clinical impact of small-bowel angiodysplasia has not been defined. We present a prospective study to determine the features of individuals with a higher risk of rebleeding or a worse clinical outcome. PATIENTS AND METHODS: thirty patients with angiodysplasia found on CE were included and followed for 12 months. Angiodysplasia were classified by their size as small ( 10 mm). We also studied angiodysplasia lesion numbers in each patient. Rebleeding was defined as a hemoglobin drop of more than 2 g/dl in the absence of melena or hematochezia in the case of occult GI bleeding, or with any or both manifestations. RESULTS: a therapeutic procedure was carried out in 13 patients (43.4%). Individuals with large angiodysplasia had higher transfusion requirements, a higher proportion of therapeutic procedure performed after CE, lower hemoglobin concentration, and a lower rebleeding rate. Patients with ten or more angiodysplasia lesions had also higher transfusion requirements and lower hemoglobin levels, but we found no differences in the number of therapeutic procedures or rebleeding rate between both groups. On follow up rebleeding was detected in 5 patients (16.7%), all of them with small angiodysplasias. Rebleeding was more frequent in patients who did not receive further interventions (23.53 vs. 7.69%; p = 0.037). CONCLUSIONS: angiodysplasia size >or= 10 mm determines a worse clinical impact and more possibilities of receiving a therapeutic procedure. Our findings support that patients with large lesions would benefit from therapeutic interventions with a reduction in rebleeding rate.

[Palliative management of malignant gastric outlet obstruction with endoscopically inserted self-expanding metal stents].

AIM AND BACKGROUND: the insertion of self-expanding metal stents to palliate malignant gastric outlet obstruction is a minimally invasive procedure that is being increasingly used. We discuss experience with this technique in a level-II hospital in the Spanish National Health System. PATIENTS AND METHODS: a retrospective five-year study (2003-2007) was conducted in 23 patients who underwent 27 procedures aimed at resolving malignant gastric outlet obstruction (mean, 0.45 procedures per month) using endoscopically inserted noncovered stents (Wallstent and Wallflex). RESULTS: insertion was technically feasible in all 27 (100%) attempts, with satisfactory clinical results in 25 cases (92.5%). Endoscopy alone was used 10 times (37%), and both endoscopy and fluoroscopy on 17 (63%) occasions. After stent insertion, one patient was intervened for treatment, and a patient with an unsuccessful prosthesis received a palliative surgical bypass. Four stents became obstructed by tumoral ingrowth, and patency was reestablished by inserting a new stent. Obstructive jaundice caused by stents covering the papilla of Vater occurred in three cases. There were no other complications or mortality due to the procedure. Mean survival was 104 days (range 28-400, SD +/- 94). CONCLUSIONS: in our experience endoscopic insertion of self-expanding metal stents appears to be a safe and efficient palliative method for malignant gastric outlet obstruction, and can be performed successfully in a center with our characteristics.

Outcomes of bile duct drainage by means of ERCP in geriatric patients / Resultados del drenaje de la vía biliar por CPRE en pacientes con edad geriátrica.

BACKGROUND AND OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is usually the procedure of choice for relieving bile duct obstruction. a large number of patients undergoing this intervention are geriatric population (aged 75 years of age and older). Our aim was to assess the efficacy of ERCP in this group of patients as compared to younger ones. PATIENTS AND METHODS: A retrospective study. All patients in whom a therapeutic biliary endoscopy had been performed over a four-year period of time (2002-2005) were included. RESULTS: 178 geriatric patients and 159 younger ones underwent ERCP. No differences were found in successful biliary drainage (97.7 vs. 98.7%), complication number (11.8 vs. 14.4%), or mortality rate (1.1 vs. 0.6%). On the other hand, more common bile duct stones were found in geriatric patients (57.3 vs. 39.6%, p = 0.004), and also more self-expanding metal stents were employed to drain malignant obstructive jaundice (47 vs. 8%, p = 0.0035). In the youngest group, more ERCPs were repeated in the same patients (4 vs. 10%, p = 0.001). CONCLUSIONS: The geriatric population showed similar success and morbidity and mortality rates when compared to younger patients in draining their bile duct by means of ERCP. Common bile duct stones were more frequently found in geriatric patients. No patients needing an ERCP should be excluded only because of their age.

Cytochrome P450 expression in rat gastric epithelium with intestinal metaplasia induced by high dietary NaCl levels.

Drug metabolizing enzymes like cytochrome P450 (CYP) play an important role in determining the susceptibility of organs or tissue to the toxic effects of drugs or other xenobiotics. There is some evidence indicating that individual isoforms of CYPs are over-expressed in different types of malignant tumors including that of oesophagus, pancreas, breast, lung, colon and stomach. Nevertheless, it is not clear if this change in expression is previous or after the appearance of malignancy. This is important in order to clarify the possible role of xenobiotics in the development of gastric cancer. On the other hand, it has been reported that a high salt ingestion leads to histological changes in rat stomach mucosa including enhanced cell proliferation, lipid peroxidation and intestinal metaplasia. The aim of this study is to explore the expression and activity of CYP families involved in the metabolism of carcinogens in normal rat stomach mucosa and intestinal metaplasia induced by high NaCl ingestion. Male Wistar rats were exposed to diets containing different NaCl concentrations (0.6% control group, 6%, 12%, 18% and 24%) for 12 weeks and histological changes as well as CYP modulation were monitored in gastric mucosa. Chronic gastritis, regenerative hyperplasia and focal metaplasia were noted in animals receiving the 12%, 18% and 24% NaCl diets. In the same groups, induction of CYP1A1 and CYP3A2 was produced, mainly in areas of metaplasia. The expression of xenobiotic metabolizing enzymes in the gastric mucosa might contribute to chemical activation in the stomach, metabolizing both exogenous and endogenous compounds implicated in the development of gastric cancer.

[Small size choledochocele as a cause of chronic epigastric pain: diagnosis and treatment by means of ERCP]. / Coledococele de pequeño tamaño como causa de dolor epigástrico crónico: diagnóstico y tratamiento mediante CPRE.

Choledochocele belongs to type III Alonso-Lej's classification of biliary cysts and they are considered the less frequent of such cysts. The definition most often given of choledochocele is a cystic dilation of the distal intramural portion of the bile duct, protruding into the duodenal lumen. ERCP is one of the diagnostic and therapeutic procedures of choice, specially when they are small and the cystic cavity is usually collapsed. The ballooning of the papilla during contrast injection in ERCP is thought to be a diagnostic sign. We present a patient suffering from chronic epigastric pain due to a small choledochocele. Magnetic Resonance Cholangiopancreatography failed to diagnose it. ERCP offered both diagnosis and treatment by means of biliary sphincterotomy.

Thrombin is present in the lungs of patients with primary extremity osteosarcoma and pulmonary metastases.

Osteosarcoma is a rare cancer, which metastasizes to the lung in up to 80% of cases. Thrombin is involved in metastasis and is present in the lungs of patients with pulmonary metastases (PM). To identify its role in PM and osteosarcoma, we measured thrombin levels in the bronchoalveolar lavage fluid (BALF) of 15 patients. BALF was collected at different stages of the disease and correlated with the diagnosis of PM. We also assessed fibrinogen overexpression in the tumors. We found that 11/15 (73%) patients with high thrombin levels in the lungs developed PM within the first 12 months from primary surgery. The median thrombin concentration in the BALF of these patients increased up to 8x10(-9) M (range, 3x10(-9)M-15x10(-9)M), which represents a more than 100-fold increase compared to patients without PM (p<0.0001). Eight of 15 (53%) primary and 11/15 (73%) metastatic samples showed fibrinogen overexpression. A significant difference between high thrombin levels, fibrinogen overexpression and PM was found compared to patients without PM (p=0.00073 and p=0.025). These results show that thrombin levels are increased in the lungs of patients with primary osteosarcoma and a high risk of developing PM. They suggest that thrombin may be involved in the development of PM.

Prenatal and postnatal blood lead level and head circumference in children to three years: preliminary results from the Mexico City Prospective Lead Study.

Multiple regression modeling was used to explore the relationship between prenatal and postnatal blood lead levels and child head circumference in the first three years of life. Maternal blood lead at 36 weeks of pregnancy and cord blood lead were found to be inversely related to 6 month and 18 month head circumference, respectively. Child 12 month blood lead was inversely related to 36 month head circumference. Limitations of the data set and the statistical techniques were discussed, as were the interpretations of the findings.

Tumor angiogenesis as a prognostic factor in oral cavity carcinomas.

Currently, lymph node metastasis and thickness of the tumor are the gold standard as a predictor of survival in patients with oral cavity squamous cell carcinoma (OSCC). However, there is a significant correlation between microvessel density and the development of cervical metastases or recurrence. Previous studies have demonstrated that head and neck cancers are able to induce an angiogenic response in experimental models. This factor shows a strong correlation with regional recurrence. In this study we propose to use angiogenesis as an independent prognostic indicator of recurrence. We evaluated the expression of tumor angiogenesis in OSCC and determinated its possible usefulness as a prognostic factor. Thirty-three cases with diagnosis of OSCC were identified from January 1985 to January 1997 in the Head and Neck Department of the Instituto Nacional de Cancerología in Mexico City. These cases were analyzed retrospectively for a minimum period of six months. All of them received a conventional complete treatment to the primary tumor and lymph node metastasis. Paraffin-embedded tumor specimens were available in all patients. The tumors were scanned and the areas of highest microvessel density (MVD) were immunostained for CD-34 using QBEnd/10 antibody. Statistical analysis included descriptive statistics, Wilcoxon test curves, and Cox's proportional hazards model for multivariate analysis. We identified 33 patients with OSCC, 16 were men and 17 women. The mean age among all patients was 58.9 years old. Based on tumor size 33.3% were T1, 27.3% T2, 12.1% T3, and 27.3% T4. The median microvessel count was 32.5. The mean percentage of MVD was 37 in patients with regional recurrence and in those patients without regional metastasis was 29 (p<0.05). 57.9% of the patients who presented recurrence had vessel counts over the median (p<0.01). In fact, 6 patients (46%) who showed more than 20% of angiogenesis expression and higher MVD presented with recurrence. Only 3 patients (23%) who had less than 20% of angiogenesis expression and lower MVD developed recurrence (p<0.01). Higher MVD was seen with increasing T and N stages; however, it did not show correlation with survival. In this study, angiogenesis expression demonstrated to be an independent factor of recurrence in patients with OSCC. It is suggested that it should be used as an independent prognostic indicator. In concordance with previous reports, we observed a significant correlation between MVD determination and recurrence of the tumor, followed by lymph node metastases and tumor size.

[Prognostic factors in breast cancer with contralateral supraclavicular or axillary lymphatic metastases]. / Factores pronósticos en cáncer de mama con metástasis a ganglios supraclaviculares o axila contralateral.

OBJECTIVE: To evaluate prognostic factor differences between surviving and decreased breast cancer patients in clinical stage IV with supraclavicular or contralateral axilla metastasis when first seen. METHODS: From the clinical records of 13 years (1975-88) two groups of ten patients each were obtained. Group 1 were women alive and free of disease for more than five years. Group 2 had similar characteristics but had died of the disease. In both groups clinical data were evaluated (age, menstrual status and survival); from slides the histologic factors like tumor size, nodal status, fibrosis percentage, inflammatory infiltrate, nuclear grade and necrosis were evaluated; immunohistochemistry of CD34 for angiogenesis, cathepsin D, p53 antioncogen, c-erb-B2 oncogen, epidermic growth factor, estrogen and progesterone receptors and cellular kinetics were performed; Kaplan Meier survival curves were constructed for the factors showing intergroup differences. RESULTS: The factors associated to the living patients were: low inflammatory infiltrate (p = 0.001), low fibrosis (p = 0.007), lower p53 expression (p = 0.03) and positive estrogen receptor (p = 0.03); other factors were marginally associated: positive progesterone receptor (p = 0.07) and having less than 6 positive lymph nodes (p = 0.07).

[Treatment of malignant colorectal obstruction by means of endoscopic insertion of self-expandable metallic stents]. / Tratamiento de la obstrucción neoplástica del colon meciante la inserción endoscópica de prótesis metálicas autoexpandibles.

BACKGROUND AND AIM: Self-expandable metallic stents are being used increasingly to treat the obstruction of different segments of the digestive tract and biliary tree. We present our centre experience on the initial resolution of malignant colorectal obstruction by means of this type of stents. PATIENTS AND METHODS: During a 18-month period, 13 patients patients suffering from malignant obstruction at the level of rectum, sigmoid or descending colon tried to be initially treated by means of endoscopic insertion of stents (non covered enteral Wallstents). Ten procedures were performed with both endoscopy and fluroscopy and three with only endoscopy. RESULTS: In 12 of the 13 patients (92,3%) the obstruction was solved by means of correct stent insertion. All the exclusively endoscopic procedures (without fluoroscopy) were successful. Six (50 %) patients with tumours at the rectosigmoid underwent later scheduled surgery. In the remaining six ones (a patient with an ovarian carcinoma and five with colonic adenocarcinoma) the stents were considered to be a palliative definitive treatment. Stent migration was observed in two of these patients and both were extracted endoscopically. Only one patient needed to have another stent inserted. A tumoural colo-vesical fistula developed in another patient in the palliative group, inside the previous inserted stent, and was treated by coaxial insertion of an esophageal Ultraflex. There were no other complications or mortality related to the endoscopic procedures. CONCLUSIONS: Self-expandable metallic stents might be considered, in general, as the initial treatment for the malignant obstruction at the level of rectum, sigmoid and descending colon

Ki-67: a proliferative marker that may predict pulmonary metastases and mortality of primary osteosarcoma.

Alterations in Ki-67 activity have been associated with tumor progression and poor outcome in cancer patients. This study was undertaken to identify the potential of this proliferative marker as a predictor of pulmonary metastases (PM) and mortality in osteosarcoma patients. In 38 patients with tissue available for immunohistochemical analysis, overexpression of Ki-67 was assessed. Chi-square and log rank tests were used to determine differences between proportions of the marker with PM and mortality and survival distributions respectively. P values equal or less than .05 were considered statistically significant. The median follow up of this case series was 28 months. Eighteen (47.4%) of 38 patients developed PM, and 17 (44%) overexpressed Ki-67. We found a high frequency of PM (15 of 17) among those cases that overexpressed Ki-67. This relationship was significant (P = .000006) when compared to the rest of the group. We also found a statistically significant correlation between patients with positive and negative Ki-67 scores and higher and lower mortality (P = .000962). These findings suggest that Ki-67 overexpression could be used as a prognostic molecular marker for the development of PM in osteosarcoma patients.

Knigth's Move in the Periodic Table, From Copper to Platinum, Novel Antitumor Mixed Chelate Copper Compounds, Casiopeinas, Evaluated by an in Vitro Human and Murine Cancer Cell Line Panel.

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas((R)) has of general formula [Cu(N-N)(N-O)H(2)O]NO(3) (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H(2)O]NO(3) (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeina's 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials.