High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening. PATIENTS AND METHODS: A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages. Secondary endpoint was the ability of the test to detect advanced precancerous lesions (advanced adenoma or advanced serrated lesion). RESULTS: A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection according to TNM stages was 84% for stage I, 94% for stage II and 96% for stage III (70/73) (P< 0.024). Sensitivity to detect advanced precancerous lesions was 23% with a refined version of the test (including protein and updating bioinformatic thresholding). CONCLUSION: A blood-based multimodal ctDNA assay detected CRC with high accuracy. This minimally invasive, accessible and convenient assay may help to increase the effectiveness of CRC screening.

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer.

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.

Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study.

INTRODUCTION: Serrated polyposis syndrome (SPS) is accompanied by a substantially increased colorectal cancer (CRC) risk. To prevent or treat CRC in patients with a very high polyp burden, (sub)total colectomy with ileorectal or ileosigmoidal anastomosis is regularly performed. The CRC risk after (sub)total colectomy might be decreased, but evidence is lacking. We aimed to assess the yield of endoscopic surveillance in patients with SPS who underwent (sub)total colectomy. METHODS: For this post hoc analysis, we used prospectively collected data from a large international prospective cohort study. We included patients diagnosed with SPS (World Health Organization type I and/or III) who underwent (sub)total colectomy. Primary endpoint was the cumulative 5-year incidence of CRC and advanced neoplasia (AN). RESULTS: Forty-eight patients (mean age 61 [±7.8]; 52% men) were included and followed up for a median of 4.7 years (interquartile range 4.7-5.1). None of the patients developed CRC during follow-up. Five patients developed AN, corresponding to a cumulative 5-year AN incidence of 13% (95% confidence interval 1.2-23). In 4 patients, AN was diagnosed at the first surveillance endoscopy after study inclusion, and in 1 patient, AN was detected during subsequent rounds of surveillance. The risk of AN was similar for patients with ileorectal and ileosigmoidal anastomosis (logrank P = 0.83). DISCUSSION: (Sub)total colectomy mitigates much of the excess risk of CRC in patients with SPS. Advanced neoplasms are mainly detected at the first endoscopy after (sub)total colectomy. Based on these results, after the first surveillance, intervals might be extended beyond the currently recommended 1-2 years.

Candidate predisposing germline copy number variants in early onset colorectal cancer patients

Purpose. A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called ‘missing heritability’. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. Methods/patients. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. Results. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. Conclusions. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC (AU)

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Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview.

OBJECTIVE: The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. METHODS: Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. RESULTS: Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. CONCLUSIONS: The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.

Candidate predisposing germline copy number variants in early onset colorectal cancer patients.

PURPOSE: A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. METHODS/PATIENTS: We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. RESULTS: We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. CONCLUSIONS: These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

Effect of oral anticoagulants on the outcome of faecal immunochemical test.

BACKGROUND: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. METHODS: Individuals aged 50-69 years were invited to receive one FIT sample (cutoff 75 ng ml(-1)) between November 2008 and June 2011. RESULTS: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3-1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4-10.8; P=0.4). CONCLUSIONS: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets.

A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer.

Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility.

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale.

A two-phase case-control study for colorectal cancer genetic susceptibility: candidate genes from chromosomal regions 9q22 and 3q22.

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24. METHODS: CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24. RESULTS: None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk. CONCLUSIONS: TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts.

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.

Applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding.

BACKGROUND: The Rockall score is used to assess the prognosis of patients with upper gastrointestinal bleeding. AIM: To assess the applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding. METHODS: Retrospective evaluation of the Rockall score in the period 1995-2001. To evaluate the applicability of the Rockall system, two groups were created: group I (Rockallor=6 points). RESULTS: Two hundred and twenty-two patients were included. The median age of patients was 65 +/ -17 years. Hypotension and associated diseases were present in 20 and 50% of patients, respectively. Re-bleeding occurred in 50 patients (23%) whose median score was 7, whereas the median score of patients without re-bleeding was 6 (p=0.14). There were 20 deaths (9%) with a median score of 8, whilst the median score of surviving patients was 6 (p<0.001). Sixteen patients in group I (18.4%) and 34 in group II (25.2%) re-bled (p=0.25). All the patients who died belong to group II with a Rockall score>or=6 (15% versus 0% in groups II and I, respectively, p<0.001). CONCLUSION: The Rockall score can be used in patients who undergo therapeutic endoscopy for upper gastrointestinal bleeding to identify those with high risk for mortality.

Papel del Helicobacter pylori en el cáncer gástrico tras gastrectomía parcial por úlcera benigna / Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease

Objetivo: determinar la prevalencia de la infección por Helicobacter pylori en pacientes gastrectomizados por enfermedad no neoplásica, y que han desarrollado posteriormente cáncer gástrico. Material y métodos: estudio retrospectivo con reclutamiento de todos los pacientes con gastrectomía parcial por enfermedad péptica benigna que han sido sometidos a una exploración endoscópica entre 1995-2001. Se ha realizado una comparación de las principales características clínicas e histológicas y de la presencia de Helicobacter pylori en los pacientes con y sin cáncer del remanente gástrico. Resultados: se han estudiado un total de 73 pacientes en este periodo. Se han encontrado 15 pacientes (20,5%) con cáncer en el remanente gástrico, 14 adenocarcinomas (71% tipo intestinal y 29% tipo difuso) y un linfoma. El tiempo transcurrido entre el diagnóstico de cáncer gástrico y la gastrectomía previa ha sido de 32 (14-48) años. Se ha detectado un alto porcentaje de infecciónpor Helicobacter pylori (100% en los pacientes con cáncervs. 81,5% en los pacientes sin cáncer, p < 0,07). No se ha observado relación entre el tipo de reconstrucción gástrica (Billroth I o II) y el porcentaje de infección por Helicobacter pylori. Conclusiones: la infección por Helicobacter pylori es frecuente en pacientes gastrectomizados por patología benigna. Los resultados de este estudio sugieren que la infección por Helicobacter pylori podría jugar un papel en el cáncer gástrico

Objective: to determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for nonneoplastic disease who later developed gastric stump cancer. Material and methods: retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. Results: a total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p <0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. Conclusions: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer

[Helicobacter pylori and gastric cancer: relationship with histological subtype and tumor location]. / Helicobacter pylori y cáncer gástrico: relación entre el subtipo histológico y la localización del tumor.

INTRODUCTION: Helicobacter pylori (HP) has been implicated in the pathogenesis of gastric adenocarcinoma. Published data on HP infection and its association with both histological subtype and tumor localization are contradictory and few data are available on this topic in Spain. The aim of the present study was to evaluate the association of HP infection with histological subtype and tumor localization in a series of patients with gastric adenocarcinoma. MATERIAL AND METHOD: We retrospectively reviewed all the patients diagnosed with gastric neoplasms in Hospital del Mar in Barcelona between 1995 and 2001. The histological subtype was established using Lauren's classification. Tissue samples were obtained from the surgical specimen or from endoscopic biopsies. HP infection was histologically determined through hematoxylin-eosin, Masson's trichromic, and Giemsa staining. RESULTS: During the study period, 304 gastric neoplasms, 275 (90.4%) adenocarcinomas, 22 (7.2%) lymphomas, 3 (1.0%) leiomyosarcomas, 2 (0.7%) degenerated gastrointestinal stromal tumors (GIST) and 2 (0.7%) Kaposi's sarcomas were diagnosed. In patients with adenocarcinoma, the mean age at diagnosis was 69 years and most patients were male (62%). A total of 48.1% of the neoplasms were located in the gastric antrum, 23.7% in the body and 19.1% in the fundus (13.6% in the period 1994-1997 and 25.4% in the period 1998-2001, p = 0.018). Intestinal-type gastric carcinoma was observed in 56% of the patients, diffuse-type in 28% and indeterminate-type in 16%. HP infection was confirmed in 69% of the patients (68% in intestinal subtype, 69% in diffuse subtype, and 69% in indeterminate subtype, p = 0.84), and was significantly associated with distal adenocarcinomas vs. proximal adenocarcinomas (73.6% vs 48.6%, p < 0.05). CONCLUSIONS: No differences were observed between the histological type of adenocarcinoma and HP infection. In the last few years, the incidence of fundic adenocarcinomas has increased. These tumors show a lower association with HP infection.

Helicobacter pylori y cáncer gástrico: relación entre el subtipo histológico y la localización del tumor / Helicobacter pylori and gastric cancer: relationship with histological subtype and tumor location

INTRODUCCIÓN: La infección por Helicobacter pylori (HP) seha implicado en la patogenia del adenocarcinoma gástrico. Se han publicado resultados contradictorios respecto a la infección por HP y su relación tanto con el subtipo histológico como con la localización del tumor; hay pocos datos al respecto en nuestro medio. El objetivo del estudio ha sido la evaluación de estos aspectos en nuestra serie de pacientes con adenocarcinoma gástrico. MATERIAL Y MÉTODO: Evaluación retrospectiva de todos los pacientes diagnosticados de neoplasia gástrica en el Hospital del Mar de Barcelona en el período comprendido entre 1995y 2001. El subtipo histológico se ha establecido basándonos en la clasificación de Lauren. Las muestras de tejido se obtuvieron a partir de la pieza de resección o de las biopsias realizadas con endoscopia. La infección por HP se determinó histológicamente mediante tinciones con hematoxilina eosina, tricrómico de Masson y Giemsa. RESULTADOS: En el período del estudio se diagnosticaron 304neoplasias gástricas: 275 (90,4%) adenocarcinomas, 22(7,2%) linfomas, 3 (1,0%) leiomiosarcomas, 2 (0,7%) tumores del estroma gastrointestinal (GIST) degenerados y 2(0,7%) sarcomas de Kaposi. En relación con los pacientes con adenocarcinoma, la edad media en el momento del diagnóstico fue de 69 años y el sexo predominante varón (62%).En antro se localizó el 48,1% de las neoplasias; en cuerpo, el23,7%, y en el fundus, el 19,1% (el 13,6% en el período1994-1997 y el 25,4% en el período 1998-2001; p = 0,018). Se ha observado un patrón intestinal en el 56% de los casos, difuso en el 28% e indeterminado en el 16%. En el 69% de los casos se confirmó la infección por HP (el 68% en el subtipointestinal, el 69% en el difuso y el 69% en el indeterminado; p = 0,84), y de manera significativa en la mayoría de los adenocarcinomas distales respecto a los proximales (el 73,6frente al 48,6%; p < 0,05).CONCLUSIONES: No se han observado diferencias entre el tipo histológico de adenocarcinoma y la infección por HP. En los últimos años se ha constatado un incremento en los adenocarcinomas de localización fúndica; en estos tumores hay una menor asociación con la infección por HP

INTRODUCTION: Helicobacter pylori (HP) has been implicated in the pathogenesis of gastric adenocarcinoma. Published data on HP infection and its association with both histological sub-type and tumor localization are contradictory and few data are available on this topic in Spain. The aim of the present study was to evaluate the association of HP infection with histological subtype and tumor localization in a series of patients with gastric adenocarcinoma. MATERIAL AND METHOD: We retrospectively reviewed all the patients diagnosed with gastric neoplasms in Hospital del Mar in Barcelona between 1995 and 2001. The histological subtype was established using Lauren’s classification. Tissue samples were obtained from the surgical specimen or from endoscopic biopsies. HP infection was histologically determined through hematoxylin-eosin, Masson’s trichromic, and Giemsa staining. RESULTS: During the study period, 304 gastric neoplasms,275 (90.4%) adenocarcinomas, 22 (7.2%) lymphomas, 3(1.0%) leiomyo sarcomas, 2 (0.7%) degenerated gastrointestinal stromal tumors (GIST) and 2 (0.7%) Kaposi’s sarcomas were diagnosed. In patients with adenocarcinoma, theme an age at diagnosis was 69 years and most patients were male (62%). A total of 48.1% of the neoplasms were located in the gastric antrum, 23.7% in the body and 19.1% in the fundus (13.6% in the period 1994-1997 and 25.4% in the period1998-2001, p = 0.018). Intestinal-type gastric carcinoma was observed in 56% of the patients, diffuse-type in 28% and indeterminate-type in 16%. HP infection was confirmed in 69% of the patients (68% in intestinal subtype, 69% indiffuse subtype, and 69% in indeterminate subtype, p =0.84), and was significantly associated with distal adenocarcinomasvs. proximal adenocarcinomas (73.6% vs 48.6%,p < 0.05).CONCLUSIONS: No differences were observed between the histological type of adenocarcinoma and HP infection. In the last few years, the incidence of fundic adenocarcinomas has increased. These tumors show a lower association with HP infection

Role of Helicobacter pylori in stomach cancer after partial gastrectomy for benign ulcer disease.

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.

Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis.

To assess the incidence, clinical course, predictive factors, and prognosis of renal failure in patients with cirrhosis and gastrointestinal bleeding, 175 consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed. Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and nontransient in 12. Renal failure was more common in patients with cirrhosis than in a control population of bleeding patients without cirrhosis matched by age and severity of the bleeding episode. Among 39 clinical and laboratory variables obtained at admission or during hospitalization related with the bleeding episode or with liver and renal function, the presence of hypovolemic shock, number of packed red blood cells transfused, Child-Pugh class at admission, and baseline platelet count were independent predictors of renal failure. The development of renal failure and hypovolemic shock was the only independent predictors of in-hospital mortality. Mortality rate among the 20 episodes with renal failure was 55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without renal failure (P <.01). The development of nontransient renal failure entailed a much greater mortality as compared with transient renal failure (10 of 12 [83%] vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is mainly related to the severity of bleeding and baseline liver function. Renal failure is a strong predictor of mortality in patients with cirrhosis and gastrointestinal bleeding.

Laparoscopic-assisted vs. open colectomy for colorectal cancer: influence on neoplastic cell mobilization.

Laparoscopic surgery for treatment of colorectal cancer has been suggested to enhance tumor dissemination. Recently, molecular techniques have been developed to detect micrometastatic disease in patients with solid tumors, with a higher accuracy than cytologic or immunohistochemical approaches. This study was undertaken to investigate the potential harmful effects of laparoscopic-assisted colectomy on neoplastic cell mobilization in patients with resectable colorectal cancer. Fifty patients with nonmetastatic colorectal cancer were randomly assigned to laparoscopic-assisted (LAC, n = 26) or open (OC, n = 24) colectomy. Peripheral venous blood samples were obtained preoperatively, immediately after tumor removal, and 24 hours later. In 10 patients from each treatment group, portal blood and peritoneal fluid samples were also obtained before and after resection. Neoplastic cells were detected by means of reverse transcriptase-polymerase chain reaction targeted to carcinoembryonic antigen (CEA) transcription. CEA mRNA was detected in peripheral venous blood samples from 35 of 50 colorectal cancer patients preoperatively. Among those 15 baseline-negative patients, four experienced conversion 24 hours after tumor resection (2 [33%] of 6 in the LAC group vs. 2 [22%] of 9 in the OC group; NS). At that time point, clearance of CEA mRNA expression was observed in 14 of the 35 baseline-positive patients (9 [45%] of 20 in the LAC group vs. 5 [33%] of 15 in the OC group; NS). In addition, only one patient in the LAC group with baseline-negative CEA mRNA expression experienced portal blood conversion after tumor removal, although his peripheral blood level remained negative. Finally, baseline peritoneal fluid CEA mRNA expression was never detected, but one patient in each group became positive postoperatively. These results confirm that preoperative and perioperative mobilization of neoplastic cells is a frequent occurrence in patients with colorectal cancer, but the surgical approach (LAC vs. OC) does not seem to be a determining factor.