Angiosarcoma involving colon and bone successfully responded to paclitaxel and zoledronate: case report.

Angiosarcoma involving the gastrointestinal tract is extremely rare. We present a case of multifocal angiosarcoma involving the colon and bone. A 73-year-old male presented with anemia and pain in the left supra-iliac lesion. Colonoscopy revealed multiple hemorrhagic-appearance tumors. Computed tomography scan showed masses in the sigmoid colon and bone. A left-sided colectomy was performed to prevent bleeding from the tumor. The histopathological diagnosis was angiosarcoma of multiple sites of the colon. We chose a combination of paclitaxel and zoledronate as the chemotherapy regimen. After surgery, bone lesions were diminished by chemotherapy and showed no uptake on (18)F-fluorodeoxyglucose-positron emission tomography. The patient survived for 38 months after surgery.

Elevated risk of colorectal adenoma with Helicobacter pylori-related chronic gastritis: a population-based case-control study.

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.

Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels.

A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population.

Cancer high-risk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males.

BACKGROUND: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study. METHODS: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on "atrophy-positive" and "atrophy-negative" criteria used for cancer screening was investigated. RESULTS: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, < or =70 ng/mL; pepsinogen I/II ratio, < or =3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive value. Cancer incidence rate was 276 per 100,000 person-years for the atrophy-positive group and 70 per 100,000 person-years for the atrophy-negative group. Incidence rate was higher in groups fulfilling stricter positive criteria detecting more extensive atrophy, reaching 424 per 100,000 person-years. In addition, 9.2% of atrophy-negative subjects with pepsinogen I of >70 ng/mL and pepsinogen I/II ratio of < or =3.0 (reflecting putative inflammation-based high pepsinogen II level) are at high risk for cancer, particularly diffuse-type cancer, with a cancer incidence rate comparable with atrophy-positive subjects (216 per 100,000 person-years). CONCLUSION: Atrophy-positive subjects by pepsinogen filter test, particularly those fulfilling stricter criteria, and atrophy-negative subjects with low pepsinogen I/II ratio reflecting putative extensive active inflammation constitute populations at high risk for gastric cancer, requiring thorough endoscopic examination.

Potent induction therapy with interferon and ribavirin combination therapy does not achieve a higher sustained virological response rate in chronic hepatitis C with genotype 1b and high hepatitis C virus RNA level.

AIMS: To compare twice-daily interferon (IFN)-beta administration and once-daily IFN-alpha-2b administration as induction therapy in ribavirin combination therapy in chronic hepatitis C with a high viral load of genotype-1b hepatitis C virus (HCV). METHODS: Sixty-one chronic hepatitis patients with a high viral load of genotype-1b HCV were randomly divided into three groups: group A was given IFN-beta 6 MU induction therapy twice daily for 2 weeks; group B was given IFN-alpha-2b 6 MU induction therapy once daily for 2 weeks; and group C was given no induction therapy. All three groups were then given IFN-alpha-2b 6 MU 3 days/week for the rest of the 24-week study period. Ribavirin was given for the entire 24-week study period. RESULTS: Although the cumulative HCV-RNA negative rates tended to be higher in group A than in group B, the differencewas not significant. The HCV-RNA negative rate at week 2 was significantly higher in groups A and B than in group C (P < 0.05). The sustained virological response (SVR) rate was 16% overall, 21% for groups A and B, and 5% for group C; the SVR rate of groups A plus B tended to be higher than that of group C (P = 0.093). CONCLUSIONS: There was no difference between the effects of the two induction therapies; potent induction therapy does achieve higher early viral clearance but not a higher SVR rate.

Serum pepsinogen and gastric cancer screening.

Since the 1990's, the test for serum pepsinogen as a marker for chronic atrophic gastritis has been incorporated into gastric cancer screening programs, on a trial basis, to identify people at high risk for gastric cancer. The addition of the serum test to the cancer screening program has been shown to improve the detection rate of cancer and pepsinogen testing is useful in detecting early-stage gastric cancers arising from atrophic gastric mucosa, which macroscopically tend to be elevated and histologically differentiated. Furthermore, the cost for the detection of a single cancer case is much less than that for conventional screening. Thus, with the introduction of pepsinogen testing, complimenting barium X-ray, a more efficient screening system is available.

Nonparasitic solitary giant hepatic cyst causing obstructive jaundice was successfully treated with monoethanolamine oleate.

A 77-year-old man hospitalized for epigastric pain showed jaundice of the skin and conjunctivae. Laboratory tests revealed elevated hepatobiliary enzymes and inflammatory markers, and imaging studies demonstrated a 12 cm hepatic cyst compressing the common bile duct. The diagnosis was a giant hepatic cyst causing obstructive jaundice. Cyst drainage and sclerotherapy with 5% monoethanolamine oleate was performed twice, resulting in almost complete disappearance of the cyst. Obstructive jaundice due to a hepatic cyst, as seen in this case, is relatively rare and this report includes a review of other similar cases in Japan.

High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk.

INTRODUCTION: Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk. EXPERIMENTAL DESIGN: Gastric mucosae were collected from 154 healthy volunteers (56 H. pylori negative and 98 H. pylori positive) and 72 cases with differentiated-type gastric cancers (29 H. pylori negative and 43 H. pylori positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated. RESULTS: Among healthy volunteers, methylation levels of all the eight regions were 5.4- to 303-fold higher in H. pylori positives than in H. pylori negatives (P < 0.0001). Methylation levels of the LOX, HAND1, and THBD promoter CGIs and p41ARC exonic CGI were as high as 7.4% or more in H. pylori-positive individuals. Among H. pylori-negative individuals, methylation levels of all the eight regions were 2.2- to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (P < or = 0.01). Among H. pylori-positive individuals, methylation levels were highly variable, and that of only HAND1 was significantly increased in gastric cancer cases (1.4-fold, P = 0.02). CONCLUSIONS: It was indicated that H. pylori infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in H. pylori-negative individuals.

Contrast-enhanced ultrasonography in the diagnosis of solid renal tumors.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasonography (CEUS) in the diagnosis of solid renal tumors. METHODS: Twenty-nine patients with solid tumors detected on gray scale ultrasonography underwent resection for suspected renal malignancy. Findings of arterial phase contrast computed tomography (CT) and CEUS were compared for each diagnosis. RESULTS: Histopathologic examination of resected lesions showed malignancy in 26 patients (clear cell carcinoma, n = 18; papillary renal cell carcinoma, n = 6; collecting duct carcinoma, n = 1; and infiltrative urothelial carcinoma, n = 1) and benign tumors in 3 patients (oncocytoma, n = 2; and angiomyolipoma, n = 1). Contrast CT failed to show tumor blood flow in 5 of 29 patients, whereas CEUS showed this in all patients. Positive predictive values of CEUS and contrast CT in the diagnosis of renal malignancy were 100% and 82.8%, respectively. Among clear cell carcinomas, hypervascularity was observed on contrast CT in 16 of 18 patients and on CEUS in 17 of 18 patients. On the basis of hypervascularity, diagnostic sensitivity values for clear cell carcinoma were 94.4% for CEUS and 88.9% for contrast CT, whereas specificity values were 45.5% for CEUS and 72.7% for contrast CT. Among papillary cell carcinomas, contrast CT showed avascular lesions in 4 of 6 patients. However, CEUS showed blood flow in these lesions, leading to diagnosis of hypovascular renal tumors. CONCLUSIONS: Contrast-enhanced ultrasonography was more sensitive for detecting slight tumor blood flow than contrast CT and was useful in preoperatively diagnosing malignant hypovascular renal tumors but was less so for hypervascular renal tumors.

Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography.

With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle-aged male subjects underwent workplace screening over a 7-year period using a combination of PG testing and DR. This program's effectiveness, as well as other characteristics of the program, was analyzed. Forty-nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer.

Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils.

The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer.

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.