Efficiency of Colorectal Cancer Surveillance in Patients with Ulcerative Colitis: 38 Years' Experience in a Patient Cohort from a Defined Population Area.

BACKGROUND AND AIMS: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program. MATERIAL AND METHODS: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10 years. RESULTS: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10 years, 2.0% at 20 years, 3.0% at 30 years, and 9.4% at 40 years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42-5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients. CONCLUSION: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).

BACKGROUND: The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent. PATIENTS AND METHODS: A nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured. RESULTS: IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63). CONCLUSION: This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.

Surgery for neoplastic changes in ulcerative colitis--can limited resection be justified? Outcome for patients who underwent limited surgery.

BACKGROUND: Patients with ulcerative colitis (UC) are at an increased risk of developing colorectal cancer (CRC). The aim of this study was to investigate the outcome for the patients who underwent limited resection of the colon and/or rectum instead of panproctocolectomy (PPC), with special attention to those with neoplastic changes. METHODS: Since 1977, all known patients with UC from our catchment area have been included in our surveillance programme. A total of 210 patients with UC have been followed up with regular colonoscopies and biopsies. Indications for surgery were severe therapy-resistant disease (TRD), high-grade dysplasia (HGD), CRC or repeated findings of low-grade dysplasia (LGD). Patient compliance was excellent. RESULTS: Fifty-one patients were operated on. In 29 of these patients, PPC was performed initially. At the end-point of the study, additionally seven patients had been radically operated on and three more patients planned to undergo such an operation. Accordingly, 22 patients had their first operation performed as a resection of either a part of or the whole colon or rectum. In this group, there were four patients diagnosed with CRC and three with dysplasia-associated lesion or mass (DALM). One of them died 6 months after surgery because of disseminated CRC, whereas the other patients were alive at the end-point of the study. One of these seven patients with CRC or DALM had at end-point been radically operated on and two patients were awaiting such a procedure (in two patients because of LGD and in one patient because of TRD). Six of the patients who had a colorectal resection performed on the indication of TRD were radically operated later on, five of them because of relapsed TRD and one patient because of LGD in the remaining rectal mucosa. Twenty-one patients gained a mean of 9.4 years with presumably better bowel function, from undergoing a limited resection instead of PPC. None of the patients who underwent a colonic and/or rectal resection died because of CRC or metachronous cancer in their remaining colon or rectum. CONCLUSION: The results of this study indicate that a limited resection of the colon and/or rectum in patients with UC, which requires surgical intervention increases the time with presumably better bowel function and may therefore be an alternative to PPC without increased risk of dying from CRC. This is dependent on the flexibility of the medical service and patient compliance.

Low folate levels may protect against colorectal cancer.

BACKGROUND AND AIMS: Dietary folate is believed to protect against colorectal cancer (CRC). However, few studies have addressed the role of circulating levels of folate. The aim of this study was to relate prediagnostic plasma folate and homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms to the risk of developing CRC. SUBJECTS: Subjects were 226 cases and 437 matched referents from the population based Northern Sweden Health and Disease Cohort. RESULTS: We observed a bell-shaped association between plasma folate concentrations and CRC risk; multivariate odds ratio for middle versus lowest quintile 2.00 (95% confidence interval (CI) 1.13-3.56). In subjects with follow up times greater than the median of 4.2 years however, plasma folate concentrations were strongly positively related to CRC risk; multivariate odds ratio for highest versus lowest quintile 3.87 (95% CI 1.52-9.87; p trend = 0.007). Homocysteine was not associated with CRC risk. Multivariate odds ratios for the MTHFR polymorphisms were, for 677 TT versus CC, 0.41 (95% CI 0.19-0.85; p trend = 0.062), and for 1298 CC versus AA, 1.62 (95% CI 0.94-2.81; p trend = 0.028). Interaction analysis suggested that the result for 1298A>C may have been largely due to linkage disequilibrium with 677C>T. The reduced CRC risk in 677 TT homozygotes was independent of plasma folate status. CONCLUSIONS: Our findings suggest a decreased CRC risk in subjects with low folate status. This possibility of a detrimental component to the role of folate in carcinogenesis could have implications in the ongoing debate in Europe concerning mandatory folate fortification of foods.

Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors.

BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction. MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification). RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68. CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) has antiapoptotic and mitogenic effects on various cell types, and raised IGF-1 levels are increasingly being implicated as potential risk factors for cancer. AIMS: To examine the relationship between IGF-1 and its major plasma binding protein, IGF binding protein 3 (IGFBP-3), and the risk of colorectal cancer. METHODS: We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort. IGF-1 and IGFBP-3 were measured in prediagnostic plasma samples from 168 men and women who developed cancers of the colon (n=110) or rectum (n=58), and from 336 matched controls. RESULTS: Conditional logistic regression analyses showed an increase in colon cancer risk with increasing levels of IGF-1 (odds ratios (ORs) 1.00, 1.89, 2.30, 2.66; p(trend)=0.03) and IGFBP-3 (ORs 1.00, 0.91, 1.80, 1.93; p(trend)=0.02). Rectal cancer risk was inversely related to levels of IGF-1 (ORs 1.00, 0.45, 0.33, 0.33; p(trend)=0.09) and IGFBP-3 (ORs 1.00, 0.75, 0.66, 0.49; p(trend)=0.21). Mutual adjustments between IGF-1 and IGFBP-3 did not materially alter these relationships. CONCLUSIONS: These results support earlier findings of increased risk of colon cancer in subjects with elevated plasma IGF-1. Our results however do not support the hypothesis that the risk of rectal cancer could also be directly related to IGF-1 levels.

COL11A1 in FAP polyps and in sporadic colorectal tumors.

BACKGROUND: We previously reported that the alpha-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of beta-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/beta-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/beta-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer.

A postfundoplication study on Z-line appearance and intestinal metaplasia in the gastroesophageal junction.

The purpose of this study was investigate the Z-line appearance by using a previously proposed classification, the ZAP classification, and to investigate the prevalence of intestinal metaplasia in the Z-line, among fundoplicated patients. Sixty patients, who had undergone fundoplication 2 to 17 years earlier, were included in the study. The prevalence of intestinal metaplasia was 20%. Intestinal metaplasia was found to be associated with age, more than 10 years of symptoms of gastroesophageal reflux disease preoperatively, tongues of columnar epithelium in the distal esophagus, carditis, and ZAP grade. ZAP grade, furthermore, was associated with male gender and more than 10 years of symptoms of gastroesophageal reflux disease preoperatively. Among patients with intestinal metaplasia, different ZAP grades can indicate different etiologic factors. Even among patients undergoing fundoplication (i.e., patients with an anatomically altered gastroesophageal junction), the ZAP classification is a feasible tool to characterize the Z-line appearance. The ZAP classification could prove valuable in selecting patients for follow-up treatment.

Immunohistochemical markers for Barrett's esophagus and associations to esophageal Z-line appearance.

BACKGROUND: Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barrett's esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barrett's esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. METHODS: Thirty-nine specimens with intestinal metaplasia were compared--9 from Barrett's esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. RESULTS: No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barrett's esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barrett's esophagus and cardia. CK7/20 showed a rising frequency of Barrett's esophagus staining pattern with rising ZAP grade. CONCLUSION: CK7/20 is a feasible marker for Barrett's esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.

The Z-line appearance and prevalence of intestinal metaplasia among patients without symptoms or endoscopical signs indicating gastroesophageal reflux.

BACKGROUND: A four-graded classification of the Z-line appearance (ZAP) has been proposed, which was shown to correlate with the prevalence of intestinal metaplasia (IM) among patients with gastroesophageal reflux disease (GERD). The aim of this study was to determine the ZAP grade and the prevalence of IM among patients without GERD. METHODS: In this study, 53 consecutive patients without signs or symptoms of GERD were included. RESULTS: A normal Z-line (ZAP grade 0) was found in 26 patients (51%), and this group had a lower prevalence of Helicobacter pylori infection and atrophy in the cardia than ZAP grade patients. The non-GERD patients in this study had less ZAP pathology than the GERD patients in our previous study. Intestinal metaplasia at the Z-line, observed in 17% of the patients, was found to associate with peptic ulcer and carditis. CONCLUSION: The normal Z-line is feasibly defined as ZAP grade 0.

Rearrangements of minisatellites in the human telomerase reverse transcriptase gene are not correlated with its expression in colon carcinomas.

Telomerase activation is crucial in human carcinogenesis. The limiting component of telomerase, the catalytic subunit (hTERT), is undetectable in normal somatic cells but present in most tumor cells, including the earliest stages of colon carcinoma. The mechanisms involved in the differential expression in normal and tumor cells are not understood. In normal cells hTERT expression is shut down by a repressor, and upregulation could be a consequence of cis-acting changes in the hTERT gene, making it resistant to repression. We have identified a polymorphic and a monomorphic minisatellite in the second intron of the hTERT gene, and polymorphic one in intron 6. The polymorphic minisatellite in intron 2 contains binding sites for c-Myc, which has been shown to upregulate hTERT transcription. Screening colon carcinoma DNAs for rearrangements of hTERT minisatellites we detected no changes in 33 samples from tumors, most of which express hTERT. This indicates that size rearrangements of the hTERT minisatellites are not required for telomerase expression in colon carcinomas. Minor changes and one LOH were seen in five tumors.

Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2.

Collagen is the major component of the interstitial extracellular matrix (ECM). ECM is known to play an active role in numerous biological processes such as cell shape, proliferation, migration, differentiation, apoptosis as well as carcinogenesis. We used mRNA differential display RT-PCR to study differentially expressed genes in tissue samples from 24 colorectal cancers and four normal colon epithelia. Twenty of the 24 tumours showed expression of a gene COL11A1, not expressed in the normal samples. This gene is not normally expressed in adult colon tissue, but was here found to be expressed in 27 out of a total of 34 (79%) colorectal carcinomas. An analysis of other collagens showed that COL5A2 was not expressed in normal colon but was co-expressed with COL11A1 in the tumours. Our results suggest that stromal expression of COL11A1 and COL5A2 is associated with malignancy in colorectal cancer.

A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) status, age at diagnosis and cancer risk.

Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described.

Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors.

BACKGROUND: The gene expression pattern in tumor cells differs from that in corresponding normal cells. In order to identify differentially expressed genes in colorectal tumors and normal colorectal epithelium, a differential display experiment was used to compare RNA expression in normal and tumor tissue samples. RESULTS: One gene fragment was expressed only in normal tissue and not, or to a much lesser extent, in the adenomas, carcinomas and cancer cell lines. The isolated gene fragment was identical to Aquaporin 8 (AQP8), a water channel protein. In situ hybridization demonstrated that AQP8 was expressed in the cells facing the lumen in the normal colonic epithelium. CONCLUSION: Our result suggests that the expression of AQP8 is a marker of normal proliferating colonic epithelial cells and suggest these cells to be involved in fluid transport in the colon.

Human colorectal cancers with an intact p16/cyclin D1/pRb pathway have up-regulated p16 expression and decreased proliferation in small invasive tumor clusters.

A systematic spatial heterogeneity with high proliferative activity at the luminal border and low activity at the invasive margin is an unexpected behavior that has been observed in colorectal cancer (CRC). To clarify this phenomenon and possible underlying regulatory mechanisms, we have by immunohistochemistry elucidated the proliferative activity and the expression of G1/S regulatory proteins in small and large tumor cell clusters at the invasive margin in 97 CRCs. By identifying small tumor clusters at the tumor front, actually invading cancer cells could be characterized and analyzed separately. These cells could then be compared with the main tumor mass represented by the larger tumor clusters. The proliferation was significantly lower in small tumor clusters compared with larger clusters (P < 0.001) and the decrease in proliferation was correlated with a p16 up-regulation (r(s) = -0.41, P < 0.001). Interestingly, CRCs lacking p16 expression (18%) or tumors with other aberrations in the p16/cyclin D1/pRb pathway had a less pronounced decrease in proliferation between large and small clusters (P < 0.001), further strengthening the association between p16 and ceased proliferation at the invasive margin. This contrasts to tumors with low p27 or abnormal p53 levels showing sustained proliferation in small tumor clusters. Our findings imply that invading CRC cells generally have low proliferative activity, and this phenomenon seems to be mediated through p16 and the p16/cyclin D1/pRb pathway.

Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma.

In hepatocellular carcinoma (HCC) iron has been implicated as a risk factor primarily in patients with hereditary haemochromatosis (HH) and cirrhosis. The wild-type HH (HFE) protein complexes with the transferrin receptor (TFR), and two HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of the TFR for transferrin resulting in an increased cellular uptake of iron. In previous studies we found an interaction between HFE and TFR genotypes in multiple myeloma and breast and colorectal carcinomas. In the present investigation we have studied HFE and TFR genotypes in 54 Swedish patients with HCC, using DNA from archival samples of paraffin wax blocks. The same HFE-TFR interaction as in the previously studied neoplastic disorders was found. Individuals carrying the HFE282Tyr allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser allele showed an increased risk for HCC (OR = 3.5; 95% confidence interval, CI = 1.3-9.3), which was further increased in HFE Tyr homozygotes and compound (Tyr/Asp) heterozygotes in combination with TFR 142Ser homozygosity (OR = 17.2; 95% CI = 1.8-168.9). The presence of liver cirrhosis could only be assessed in part of the patient material. In patients with verified liver cirrhosis the risk figures were substantially increased: for HFE 282 Tyr carriers in combination with TFR 142 Ser/Ser OR = 7.2; 95% CI = 2.0-25.5 and for HFE 282Tyr homozygotes and compound heterozygotes in combination with TFR 142Ser homozygosity, OR = 62.8; 95% CI = 6.1-642.5.

Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer.

PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer. METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68). RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05). CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.

Eighteen-year surveillance of dysplasia-associated lesion in ulcerative colitis.

The case of a 65 year old patient with ulcerative colitis is reported, who had a dysplasia-associated lesion or mass (DALM) in her rectum. Refusing surgery after detection of the lesion and on follow-up, she underwent surgery only 18 years later when frank carcinoma (Dukes C) was detected. Even if DALM may take a variable course, surgical excision is still highly recommended.

The esophageal Z-line appearance correlates to the prevalence of intestinal metaplasia.

BACKGROUND: Intestinal metaplasia at the gastroesophageal junction is associated with Barrett esophagus, gastric cardiac cancer, and gastritis. The aim of this study was to determine the prevalence of intestinal metaplasia among patients with symptoms suggestive of gastroesophageal reflux disease (GERD) and to study clinical, endoscopic, and histologic associations with intestinal metaplasia at the squamocolumnar junction. METHODS: One hundred and eighty-six patients with symptoms indicating gastroesophageal reflux were included in the study. A new classification of the Z-line appearance was used. RESULTS: The Z-line appearance was found to correlate with the prevalence of intestinal metaplasia at the squamocolumnar junction (P = 0.0001). Intestinal metaplasia at the squamocolumnar junction was found in 15.0% of the patients. There was a statistically significant association between intestinal metaplasia at the squamocolumnar junction and tongues of columnar epithelium at the Z-line (P = 0.020), intestinal metaplasia in the cardia (P = 0.020), positive CLO test (P = 0.026), smoking (P = 0.041), and age (P = 0.050). There was no association with endoscopic or histologic signs of esophagitis or with the severity or duration of GERD symptoms. CONCLUSION: Intestinal metaplasia at the squamocolumnar junction correlates with the Z-line appearance, which would justify a new classification.