Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients.

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.     

The oncologic benefit of high ligation of the inferior mesenteric artery in the surgical treatment of rectal or sigmoid colon cancer

PURPOSE: It remains controversial as to whether high ligation of the inferior mesenteric artery (IMA) should be performed during surgical treatment for sigmoid colon or rectal cancer. The purpose of this study is to attempt to clarify the extent of the oncologic benefit of high ligation of the IMA. MATERIALS AND METHODS: From January 1995 to July 2001, a total of 1,389 patients underwent high ligation of the IMA; 387 patients featured non-disseminated sigmoid colon cancer and 1,002 patients had rectal cancer. Pathology of the primary tumors, IMA nodes, and clinical outcome were reviewed. RESULTS: Forty-three patients (3.1%) revealed IMA node metastasis. Of these 43 patients, 29 (67.4%) featured tumor recurrences/metastases. After a minimum 5-year follow-up, 11 of these 43 patients (25.6%) were alive and disease free. Of these 43 patients, the 5-year disease-free survival rate for patients featuring sigmoid cancer was 50% and for patients with rectal cancer 13.8%. The beneficial rate of high ligation of the IMA for non-disseminated sigmoid colon cancer and rectal cancer was 0.8%, for non-disseminated sigmoid colon cancer 1.8%, and for non-disseminated rectal cancer, the rate was only 0.4%. The rates of IMA metastasis in patients with T stage tumors were 0% (pT1), 1.0% (pT2), 2.6% (pT3), and 4.3% (pT4). CONCLUSIONS: Although patients afflicted with IMA node metastasis revealed a rather high incidence of tumor recurrence/metastasis, 25.6% of these patients remained disease free following IMA node dissection after a minimum 5-year follow-up. We consider that IMA node dissection is more beneficial in patients with non-disseminated sigmoid pT4 tumor.     

Foley® catheter-assisted endoscopic treatment of severe anastomotic stenosis following anterior resection of the rectum

Rectal stenosis following low anterior resection is common. Several methods of treatment have been described. We introduce a simple method for the treatment of anastomotic stenosis using a conventional proctoscope and an electric knife with a Foley® catheter as an anvil. Under direct vision, this technique can afford accurate and safe incision of stenosis.     

Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with hepatocellular carcinoma

BACKGROUND/AIMS: Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families. METHODS: From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children. RESULTS: The study included a total of 13676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status. CONCLUSIONS: Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.     

Pathogenesis of infantile hemangiomas

1.Review the key features of the life cycle of infantile hemangiomas.2.Highlight cellular and molecular pathways involved in hemangioma-genesis.3.Discuss theories that may account for hemangioma-genesis.In the past, it was believed that a mother's visual impressions or behavior during pregnancy caused the growth of infantile hemangioma in her unborn child. She might have had an excessive craving for strawberries, witnessed the slaughter of an animal, directly contacted human or animal blood, or mocked a child with a similar birthmark.1 This folklore began to slowly fade once hemangiomas were examined through the light microscope. In 1863, Virchow2 suggested that hemangiomas are composed of proliferating new blood vessels resulting from progressive irritation of tissue. In 1933, Laidlow and Murray3 proposed a phylogenetic origin for hemangiomas and hypothesized that hemangiomas are remnants of vascular tufts functioning as accessory lungs for primitive amphibia. Pack and Miller4 (1950) hypothesized that hemangiomas develop from embryonic islands of angioblastic cells that were isolated from the systemic vasculature during fetal development.     

Antiviral treatment responses in patients with chronic hepatitis C virus infection evaluated by a third generation anti-hepatitis C virus assay

summary . Antibodies to hepatitis C virus (HCV) may decrease or disappear after viral clearance in treated or spontaneously resolved infection. We evaluated the usefulness of serial antibody assays in predicting the antiviral treatment responses. One hundred and four chronic hepatitis C patients who received 24 weeks of interferon and ribavirin combination therapy were assayed with a third generation enzyme immunoassay anti-HCV. The mean titre of anti-HCV decreased by more than 50% (from 89.5 ± 10.8 to 43.6 ± 17.5) at 48 weeks post-treatment in patients with a sustained virological response, while in nonsustained virological responders and nonresponders, the titres remained over 85% of the pretreatment level at 48 weeks post-treatment. There was a divergence of anti-HCV titres between sustained and nonsustained virological responders during 6–9 months. By using the ratio of 9-month to 6-month titres as an index and receiver operator characteristic curve analysis with the cut-off point set at 90%, we could differentiate sustained virological responders from nonsustained virological responders with a sensitivity and specificity of 91.7% and 90.9%, respectively, 3 months after treatment. The titre of this third generation anti-HCV decreased progressively in sustained virological responders and this assay may be used to monitor and predict antiviral treatment responses.     

Combining systemic chemotherapy with chemoembolization in the treatment of unresectable hepatic metastases from colorectal cancer

Treatment of liver metastases from colorectal cancer include surgical resection, radiation, hepatic chemoembolization, immunotherapy and intravenous chemotherapy. Complete surgical resection of liver metastases is feasible only for solitary or unilobar metastasis. Unresectable hepatic metastases of colorectal origin are resistant to radiation and immunotherapy, and the unsatisfactory results of systemic chemotherapy and chemoembolization have led to more aggressive treatment. A new method that combines systemic chemotherapy and chemoembolization is proposed. In this study, data from a total of 40 patients with unresectable hepatic metastasis from colorectal cancer were collected. All of these patients received combined chemoembolization and systemic chemotherapy. Embolization was performed by the selective cannulation of right and left hepatic artery. Equal amounts of a mixture of 10 ml lipiodol, 1,500 mg 5-fluorouracil (5-FU) and 15 mg leucovorin was deployed selectively in equal parts into the main right and left hepatic artery. Two weeks following chemoembolization, patients underwent systemic chemotherapy with 2,600 mg/m² 5-FU continuous infusion for 24 h and received 150 mg leucovorin intravenous bolus. The course of chemotherapy was repeated weekly for 24 weeks. The median follow-up period was 27 months (range 10–36 months). Following the intention-to-treat principle, the objective tumor response rate was 47.5%. The median disease-free interval was 12 months and the median survival time was 16 months. Most of the patients (73%) died of hepatic failure, while the second largest group died of abdominal carcinomatosis. In conclusion, the results of this study are of sufficient interest to justify future randomized trials.     

Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwanese

AIM:To elucidate the prognostic role and relationship ofthree molecular markers such as tumor suppressor genep53,proliferating cell nuclear antigen(PCNA)and Ki-67in gastric stromal tumor.METHODS:A total of 108 surgically resected gastricsmooth muscle tumor specimens were collected fromJanuary 1987 to December 1999.Immunohistochemicalstudies were performed on the paraffin sections of 99of 108 CD117-positive tumors with antibodies of p53,PCNA,and Ki-67.Immunoreactivity of three molecularmarkers was recorded by labeling index(LI,%)and wasanalyzed for clinicopathologic and survival correlation.RESULTS:Of the 99 cases,immunostaining revealedthat 52 patients(52.5%)had p53,and 37 patients(37.3%)had Ki-67 immunoreactivity(defined as>10%of LI).All patients(100%)had PCNA immunoreactivityranging from 12% to 93% of LI,divided into high orlow by median.Statistics revealed that LI of threemarkers positively correlate to each other(P<0.01)and to microscopic tumor mitotic counts(P<0.001).By combination,patients with≥2 markers(positiveor high)in tumors had early tumor recurrence(P<0.001)and unfavorable outcome(P<0.001).Univariate analysis indicated that patients with tumorsize>5 cm(P=0.003),tumor mitosis>5/50 HPF(P<0.001),p53 immunoreacUvity(P=0.001),Ki-67 immunoreactivity(P=0.026),high PCNA LI(P=0.015)and male gender(P=0.036)were six predictors for earlydisease recurrence.Subsequent multivariate analysisrevealed that mitotic counts,tumor size,and p53immunoreactivity were three independent prognosticfactors for both disease free and overall survival ofpatients.By combination of three independent prognosticfactors for grouping,we found higher tumor recurrencerate(P<0.001)and shorter survival(P<0.001)existed ingroups with increasing factors.CONCLUSION:We first provide the prognostic valueand linkage of three molecular markers in GISTs.Thecombination of three factors(p53,tumor size,andtumor mitosis)provides a more powerful prediction ofprognosis than any single factor does.     

Liver stiffness measurement in the risk assessment of hepatocellular carcinoma for patients with chronic hepatitis

Backgroud/aims  

The risk of hepatocellular carcinoma (HCC) increased with progression of hepatic fibrosis as assessed by liver stiffness measurement (LSM). This study used LSM to assess the risk of HCC presence in patients with chronic hepatitis.