LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival.

PURPOSE: Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes in protein expression in colon cancer-associated fibroblasts compared with normal fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II patients. EXPERIMENTAL DESIGN: CAFs and NFs isolated from colon cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training, then quantitative PCR and IHC for validation in different cohorts of patients. Combined datasets were used for prediction of risk assessment at stages II and III. RESULTS: A desmoplastic signature composed of 32 proteins, highly specific for stromal components in colon cancer, was identified. These proteins were enriched for extracellular matrix organization components, TGFß signaling pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques. LOXL2 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of patients. High expression of LOXL2 was associated with higher recurrence P = 0.001 HR, 5.38 [95% confidence interval (CI), 1.70-17.01] and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90-38.29). IHC analysis revealed a prognostic value for LOXL2 in stage II patients. CONCLUSIONS: We identified LOXL2 to be associated with the outcome of colon cancer patients. Furthermore, it can be used to stratify patients at stages II and III for further therapeutic decisions.

[Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients]. / Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes.

OBJECTIVE: To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. MATERIAL AND METHODS: A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000. RESULTS: A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(-). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(-) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(-) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%. CONCLUSION: Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(-), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.

[Significance of free perigastric fluid detected by echoendoscopy in patients with gastric cancer]. / Significado del líquido libre perigástrico identificado por ecoendoscopia en pacientes con cáncer gástrico.

OBJECTIVES: To determine the diagnostic value of free perigastric fluid identified by echoendoscopy in patients with gastric cancer and to establish the factors related to the presence of peritoneal carcinomatosis in these patients. MATERIAL AND METHODS: We retrospectively included 100 patients with a histological diagnosis of gastric adenocarcinoma referred for echoendoscopy. A positive result was defined as the echoendoscopic identification of free perigastric fluid. This result was compared with the final study based on exploratory laparoscopy-laparotomy. The histological and endoscopic characteristics were compared with the final result. RESULTS: Free perigastric fluid was found in 21 patients (21%). Among these, 15 (71%) showed peritoneal carcinomatosis, confirmed by laparoscopy (12 patients) or echoendoscopy-guided fine-needle-aspiration biopsy (three patients). In seven of the 79 patients (8%) not showing the presence of ascites, peritoneal implants were identified by exploratory laparoscopy-laparotomy. The sensitivity, specificity, positive predictive value and diagnostic accuracy of free fluid in the diagnosis of carcinomatosis was 68%, 92%, 71%, 91% and 87%, respectively. No histologic or endoscopic factors related to the malignancy of echoendoscopically-detected fluid were identified. CONCLUSION: In patients with gastric cancer, free perigastric fluid identified by echoendoscopy is an important predictive factor of peritoneal carcinomatosis and may have significant implications in the management of these patients.

Amyloidosis and Crohn´s disease.

Secondary amyloidosis is a rare but serious complication of inflammatory bowel disease that may influence the prognosis even more than the underlying disease. Due to a better knowledge of the association of secondary amyloidosis to inflammatory bowel disease, early diagnosis of this complication is becoming more frequent, but its treatment continues to pose a challenge. We report 4 cases of patients with Crohn´s disease and amyloidosis diagnosed in the inflammatory bowel disease Units of Toledo and Ciudad Real, which represent 0.68% of the patients with Crohn´s disease of our health areas. There have been not cases of amyloidosis in patients with ulcerative colitis. In our 4 patients the secondary amyloidosis was clearly related to Crohn´s disease,which was often of fistulising type. The predominant clinical picture of amyloidosis was nephrotic syndrome. The patients responded to medical and surgical treatment of Crohn´s disease and colchicine, which improved renal function in all cases except in one who required kidney transplantation.

[Metastatic Crohn's disease]. / Enfermedad de Crohn metastásica.

Metastatic Crohn's disease is a granulomatous cutaneous lesion that appears in patients with Crohn's disease and is located in any skin area, separated from the lesions in the gastrointestinal tract. This entity is characterized by its heterogeneous behavior, both in its localization and clinical expression and in its effect on patients' quality of life. Histology is essential for diagnosis and shows non-caseating granulomas. There are no treatment guidelines and various therapeutic strategies have been employed, with variable response. In most patients, treatment with biological agents is highly effective. We describe three cases of metastatic Crohn's disease with the aim of analyzing the characteristics of this entity, which should always be included in the differential diagnosis of skin lesions in patients with Crohn's disease. A literature review is also provided.

[Serological diagnosis of atrophic gastritis with a combination of pepsinogen I and II, gastrin-17 and anti-Helicobacter pylori antibodies]. / Diagnóstico serológico de gastritis atrófica con una combinación de pepsinógeno I y II, gastrina-17 y anticuerpos anti-Helicobacter pylori.

OBJECTIVE: Noninvasive diagnosis of atrophic gastritis would help to identify individuals at increased risk of gastric carcinoma. In the present study, we evaluated the utility of a serological panel combining pepsinogen I and II, gastrin-17, and anti-Helicobacter pylori antibodies (Gastropanel) as a screening method for atrophic gastritis. PATIENTS AND METHODS: The serological panel was evaluated in 56 patients divided in two groups: group 1 consisted of 47 patients with uninvestigated dyspepsia and group 2 was composed of nine consecutive patients with gastric carcinoma. In all patients, we performed endoscopy with biopsies of the gastric antrum and body. Levels of pepsinogen I and II, gastrin-17, and anti-H. pylori antibodies were determined through a specific EIA test (Biohit plc, Helsinki, Finland) in fasting serum samples. RESULTS: Atrophic gastritis was significantly more frequent in patients with gastric carcinoma than in those with dyspepsia (56 vs 6%; p = 0.0015). Agreement between the Gastropanel and gastric histology was good (kappa = 0.68). The sensitivity and specificity of the Gastropanel in the diagnosis of atrophic gastritis was 87.5% and 100%, respectively. However, the Gastropanel would not have detected four of the nine cases of gastric carcinoma, since these tumors arose in stomachs with nonatrophic mucosa. CONCLUSIONS: Gastropanel is a useful noninvasive method for the diagnosis of atrophic gastritis. However, its utility as a screening method is limited by cases of gastric carcinoma that arise in stomachs without atrophic mucosa.

[Contribution of endoscopic ultrasound to the diagnosis of pancreatic metastases from renal carcinoma. Apropos of two cases]. / Aportación de la ecoendoscopia al diagnóstico de las metástasis pancreáticas del carcinoma renal: a propósito de dos casos.

Pancreatic metastases represent 2% of pancreatic tumors. The neoplasms most frequently metastasizing to the pancreas are breast, lung, melanoma and kidney tumors. We present the cases of two patients with pancreatic metastases from renal carcinoma diagnosed 4 and 8 years after the diagnosis and surgical treatment of the primary renal tumor. In both patients, endoscopic ultrasound was useful in the detection and characterization of these pancreatic lesions and allowed fine-needle aspiration for cytological study to be performed.

[Clinicopathological characteristics of uninvestigated dyspepsia in Spain]. / Características clinicopatológicas de la dispepsia no investigada en España.

INTRODUCTION: Most patients with uninvestigated dyspepsia are diagnosed with functional dyspepsia. Various types of Helicobacter pylori gastritis have been described, each of which is associated with a distinct natural history of the infection (i.e. a different risk of ulcer or gastric cancer). OBJECTIVE: To determine the clinical and pathological characteristics of patients with uninvestigated dyspepsia in our area and the prevalence of the distinct types of H. pylori gastritis among patients with functional dyspepsia. MATERIAL AND METHODS: Ninety-eight patients (47 men and 51 women, mean age 35.8+/-13 years) with uninvestigated dyspepsia were included in this study. All the patients completed the Dyspepsia-Related Health Scale and all patients underwent gastroscopy with biopsy and the C13-urea breath test. RESULTS: Fourteen patients had organic causes of dyspepsia and 78 had functional dyspepsia. Fifty-one patients with functional dyspepsia (65%) had H. pylori infection; of these, 27 had pangastritis, 21 had antrum-predominant gastritis, 2 had multifocal atrophic gastritis and 1 had normal gastric mucosa. Among uninfected patients, 2 had multifocal atrophic gastritis. CONCLUSIONS: The prevalence of functional dyspepsia in this series was 85%. Twenty-seven percent of patients with functional dyspepsia had a combination of H. pylori infection and antrum-predominant gastritis, the type of gastritis predisposing to duodenal ulcer. Only 5% of the patients had multifocal atrophic gastritis, which is associated with a high risk of gastric cancer.

Nasolacrimal stenting: toward improving outcomes with a simple modification of the song stent.

The purpose of this study was to evaluate, in a prospective, single-center study, the effectiveness of Song's polyurethane stents, modified "in-house," in the percutaneous management of epiphora. Patients (n = 170; age range 18-83, mean = 64; 50 male, 120 female) with severe epiphora had the modified stents inserted (183 eyes/195 stents) to treat unilateral/bilateral and complete/partial obstruction of the nasolacrimal system. The etiology of the obstruction was idiopathic in 119 cases (61%) and chronic dacryocystitis in 76 (39%). The set designed by Song was used in all patients but modified by us such that the extreme end is cone-shaped. The original technique was slightly modified by us and the procedure was conducted on an outpatient basis. The initial technical success rate of stent placement was 97%. Resolution of epiphora was complete in 180 eyes and partial in 3. On follow-up (mean = 18 months; range: 2 days to 24 months), 165 of 195 stents (85%) remained patent. Primary patency rates at follow-up were 86%, 84%, 84%, and 79% in the first 6 months, second and third 6 months, and the present (24 months), respectively. Stents became obstructed in 30 patients, but all but 2 were easily withdrawn and 20 of these patients remained asymptomatic for a mean of 14 months (secondary patency of 67%). Following stent removal, the withdrawn stent was replaced with a new stent in the same intervention on 14 occasions. In another six cases, patency was re-established without the need of a second stent. The procedure is simple and safe, both in stent insertion as well as in mechanical de-blocking and withdrawal when occluded. Success was >80 % in the short term (1-year follow-up). Stenting failure does not preclude other treatment because with the modification that we had introduced, the extreme end of the stent becomes more accessible to mechanical de-blocking, withdrawal, and relocation. The levels of primary and secondary patencies are promising and warrant more extensive investigation.

Resolution of epiphora with nasolacrimal stents: results of long-term follow-up in a multicenter prospective study.

PURPOSE: To evaluate in a prospective, multicenter setting the long-term effectiveness of polyurethane stents in the percutaneous management of epiphora. MATERIALS AND METHODS: Patients (n = 426; age range, 19-88 years, mean, 48; 91 men, 335 women) with severe epiphora had stents (470 eyes/496 stents) inserted to treat unilateral or bilateral and complete or partial obstruction of the nasolacrimal system. The etiology of the obstruction was idiopathic in 280 cases (59.5%) and chronic dacryocystitis in 190 (40.4%). The stent set designed by Song was used in all patients, and the original technique was slightly modified by us and conducted on an outpatient basis. RESULTS: The initial technical success rate of stent placement was 95%. The average time of the procedure was 6 minutes (range, 3-70). Resolution of epiphora was complete in 452 eyes and partial in 18. On follow-up (mean, 24 months; range, 1 week to 67 months), 340 of 496 stents remained patent (68.5%). Segregating primary patency by year of follow-up, the rates were 75.6%, 68.4%, 64.8%, 60.1%, and 59.2% in the first, second, third, fourth, and the current (67 months) years, respectively. Minor complications such as moderate pain (21 cases), epistaxis (75 cases), palpebral edema and hematoma (31 cases), and headache (four cases) and two acute dacryocystitis events were recorded. Of the 156 obstructed stents, 114 were withdrawn, and 49 of these patients remained asymptomatic for a mean of 27 months (secondary patency, 31.4%). After stent removal, the sac configuration was unchanged in 93 (81.5%), contracted in 11 (9.6%), and widened in 10 (8.8%) cases. CONCLUSIONS: The procedure is simple and safe, both in stent insertion and in withdrawal when occluded. The success rate was >75% in the short term and >55% in the long term. Although not totally without concerns, the technique is attractive for most patients who prefer not to undergo surgery or are unsuitable surgical candidates. Stent failure does not preclude subsequent treatment options and is an excellent first-line treatment of epiphora.