Sheth, Ankur MD, MPH; Train, Polly MD; Kochhar, Ruby MD; Arbour, G Thomas Jr MD; Khurana, Vikas MD, FACP, FACG Author Information

1006 Background: Statins (HMG CoA reductase inhibitors) are commonly used cholesterol-lowering agents that are noted to suppress tumor growth in several animal models, however clinical data for a chemoprotective role of statins in lung cancer is lacking. We investigated the effect of statins on the development of lung cancer in the US veteran population. Methods: The VISN 16 database, which contains clinical and demographic information about all veterans (>1.4 million patients) cared for in the South Central VA Health Care Network, was queried from Oct 1998 to June 2004. Retrospective case control design was used. Patients were included in the statin users group if they were using statins prior to the diagnosis of lung cancer but the dose, duration and type of statin used was not factored into the analysis. Statistical analysis was performed using SAS software version 9.0 (Chicago, IL). Multiple logistic regression analysis was used with calculation of odds ratios and 95% confidence intervals. The data was adjusted for age, gender, smoking and alcohol use. Results: A total of 484,226 patients were studied. The mean age was 61.2 (SD+/−15.1) years and 91.7% were men, 164,645 (34%) were using statins. Lung cancer (ICD code of 162) was seen in 7280 (1.5%); 1994 (1.2%) statin users and 5286 (1.7%) statin non-users. Statin users were less likely to develop lung cancer (Odds ratio 0.52: 95% CI 0.49–0.55). The data was controlled for age (OR 1.038, 95% CI for OR 1.036–1.039, p=<0.0001), gender (OR 0.42, 95% CI for OR 0.36–0.49, p=<0.0001), smoking (OR 1.80, 95% CI for OR 1.66–1.95, p=<0.0001), and alcohol use (OR 1.13, 95% CI for OR 1.08–1.19, p=<0.001). All these were highly significant covariates. Conclusions: Statins are associated with a 48% risk reduction of lung cancer after controlling for age, gender, smoking and alcohol use. An internal consistency of the database is reflected by an increased risk associated with documented risk factors. Our data should be evaluated with caution, given the limitations of the population, the database and the fact that this is a case control study. Some factors known to increase the risk of lung cancer like asbestos exposure were not incorporated into the study. No significant financial relationships to disclose.

Purpose: E-cadherin expression is diverse, and differences in patient characteristics may produce variability in expression. Whereas some studies have indicated that downregulation of e-cadherin, associated with loss of cellular adhesiveness, was correlative with poor prognosis and metastasis, other studies have failed to confirm this. The present study uses a highly homogenous population of patients at high-risk for breast cancer, on the basis of ethnic and socio-economic status, to examine the relationship between e-cadherin and other prognostic markers in breast cancer. Methods: Immunohistochemical staining was undertaken for estrogen (ER) and progesterone (PR) receptors, epidermal growth factor receptor 2 (Her-2), p53, vascular endothelial factor (VEGF), and hypoxia inducible factor 1alpha (HIF-1alpha) and the levels of these markers was compared to e-cadherin expression in a high-risk African-American patient population. Results: E-cadherin expression persisted into the later stagers of the disease, and was strongly associated with Her-2 and HIF-1alpha expression, but not p53, ER/PR or VEGF. Conclusions: In contrast to other studies on heterogeneous populations, e-cadherin is preserved in aggressive tumors in this high-risk population. The ethnic and socio-economic risk stratification needs to be accounted for in studies correlating markers and prognosis.

3546 Background: Malignancies that co segregate provide important markers for high risk patients. Colorectal and prostate cancers share some common risk factors including age, family history and a diet high in fat. Several studies have been done to evaluate the association between them, however the results have been conflicting and inconclusive. We studied the association between colorectal and prostate cancers and evaluated the effect of colon cancer diagnosis on the risk for prostate cancer. Methods: VISN 16 data warehouse, which contains clinical and demographic information about all veterans (>1.4 million patients) cared for at the 10 VA Medical Centers in 4 states comprising the South Central VA Health Care Network in the mid-south region of the US, was queried from Oct 1998 to June 2004. Retrospective case control design was used. Multiple logistic regression analysis was used with calculation of odds ratios and 95% confidence intervals were used universally. Statistical analysis was performed using SAS software version 9.0 (Chicago, IL). Results: We analyzed 443,774 male patients from our database. The mean age of the selected group was 62.5 (S.D. +/- 14.5). There were 26,087 (5.88%) prostate cancer (ICD-9 185) and 5423 (1.22%) colorectal cancer (ICD-9 153 & 154) patients. There was a significant increase in the incidence of prostate cancer in patients diagnosed with colorectal cancer compared to patients without colorectal cancer (Odds Ratio 1.75, 95% CI 1.61 to 1.89, p-value < 0.0001). The data was controlled for age (OR 1.077, 95% CI for OR 1.076–1.078, p=<0.0001), smoking (OR 1.80, 95% CI for OR 1.66–1.95, p=<0.0001), and alcohol use (OR 1.13, 95% CI for OR 1.08–1.19, p=<0.001). All these were highly significant covariates. Conclusions: Our data suggest that colorectal cancer is a significant risk factor for prostate cancer. Patients with colorectal cancer may be considered for more aggressive screening for prostate cancer. The data should be evaluated with caution given the limitations of the population, the database and the design of the study. Some factors known to increase the risk of prostate cancers like family history, diet and race were not incorporated into the study. No significant financial relationships to disclose.

A 53 years old man with hepatitis C presented 5 years ago, with right upper quadrant pain and a liver lesions (Right lobe:10×10 cm and a smaller left lobe lesion). Alpha-fetoprotein (AFP) level was 900 ng/ml (normal 0 -9 ng/ml), biopsy revealed hepatocellular carcinoma (HCC). He did not receive any therapy and 8 months later his AFP levels went down to 230 ng/ml and CT scan showed complete clearing of left lobe lesion and right lobe lesion had 50% shrinkage. He reports taking a variety of herbal agents since the diagnosis of HCC and the list included, Black Walnut, Barley Green, Ellagic Acid, Cell Forte, Coral Calcium, Chlorophyll water, Milk Thistle, Activin OPC 50 and Gene flora. Liver lesion remained stable and AFP levels dropped to two digits and remained between 25 and 75 ng/ml for around three years. Patient quit taking herbal medications on his physician's advice and due to the cost of herbal medications ($1000/month). His AFP levels started rising and tumor size increased. He was started on chemotherapy, AFP rose to 42000 ng/ml with progression of liver lesions. He refused further chemotherapy and was referred to hospice. He is alive at the time of writing this report, 5 years after the diagnosis of HCC. Discussion: HCC has a median survival of 6 to 20 months. Given the variety of agents he was taking it is difficult to identify any single agent. Several of the herbal medicines he was taking are suspected to have anticancer activity. Studies have shown that Ellagic acid inhibits the growth of cancer cells and promotes apoptosis. Cell forte (IP6inositol + regular inositol) inhibit cell adhesion, migration and invasion in human breast cancer cells. Conclusion: We report a case of advanced HCC that showed significant response to herbal supplements. Further research on the anti-tumor effects of these herbal agents can result in better understanding of HCC and may lead to the development of newer therapeutic agents.

Background: Prostate and colorectal cancers share some common risk factors including age, family history and a diet high in fat. For both cancers the screening for general population starts at age 50. Several studies were done to evaluate the association between them, however the results have been conflicting and inconclusive. Aim: To study the association between prostate and colorectal cancers and to evaluate the effect of prostate cancer diagnosis on the risk for colorectal cancer. Design: VISN 16 data warehouse, which contains clinical and demographic information about all veterans (>1.4 million patients) cared for at the 10 VA Medical Centers in 4 states comprising the South Central VA health Care Network in the mid-south region of the US, was queried from Oct 1998 to June 2004. Patients with prostate cancer were identified using ICD-9 (185) codes and patients with colorectal cancers were identified using ICD-9 (153 & 154) codes. Retrospective case control design was used. Multiple logistic regression analysis was used with calculation of odds ratios and 95% confidence intervals were used universally. Statistical analysis was performed using SAS software version 9.0 (Chicago, IL). Results: We analyzed 443,774 male patients from our database. The mean age of the selected group was 62.5(S.D. ± 14.5). There were 26,087 (5.88%) prostate cancer and 5423 (1.22%) colorectal cancer patients in the study group. There was a significant increase in the incidence of colon cancer in patients diagnosed with prostate cancer compared to patients without prostate cancer (Odds Ratio 1.79, 95% CI 1.65 to 1.93 p-value < 0.0001) after the data was controlled for the above covariates. Discussion: The increased incidence of colon cancer in patients with prostate cancers may be due to several risk factors that are common to both prostate and colon cancers. The data should be evaluated with caution given the limitations of the population, the database and the design of the study. Some factors known to increase the risk of colorectal cancers like family history, diet and inflammatory bowel disease were not incorporated into the study. Conclusion: Our data suggest that prostate cancer is a significant risk factor for colorectal cancer. Patients with prostate cancer may be considered for more aggressive screening for colorectal cancer.

Interferon is a group of glycoproteins with a diverse spectrum of biological activities including antiviral, antiproliferative and antineoplastic properties. We report a case illustrating the curative effect of Interferon on perianal squamous cell cancer. Case Report: 45-year-old caucasian man was referred to the hepatology clinic for management of chronic Hepatitis C infection. He was started on Pegylated Interferon Alfa 2a at 180mcg sq. q weekly and Ribavirin 1000 mg PO q day. Patient gave history of perirectal pain for the past several months. Physical examination revealed an erythematous sessile lesion measuring 1.2cm × 5cm on the left side, 2 cm from anus at 7 o clock position. The remainder of his exam was unremarkable. Patient was evaluated by dermatology and underwent a biopsy after 2 weeks of interferon therapy. Microscopic evaluation revealed squamous cell cancer extending to deep and lateral margins of excision. Subsequently he underwent surgical excisions of the remainder of the lesion, 6 weeks after the initiation of the interferon therapy, which failed to show any evidence of tumor. Considering erroneous localization repeat excisional biopsy was performed at 14 weeks, which was also normal. We postulate that regression of perianal squamous cell cancer was caused by interferon. Discussion: Squamous cell cancers of skin have been treated by various modalities including surgical excision, cryotherapy, radiation therapy and topical 5-florouracil. In various experimental studies interferons by intralesional injection therapy have been used as a form of treatment for cutaneous squamous and basal cell cancers. Our patient was seen with a 6-month history of perianal squamous cell cancer of the skin and was incidentally started on pegylated Interferon Alfa-2a for the treatment of hepatitis C. His initial biopsy was positive for involvement of lateral and deep margins. Subsequent surgical excisions at the local site failed to show any tumor, suggesting regression of remaining tumor. Our case is unique as most of the experimental studies are being done with local injection of Interferon Alfa-2b instead of systemic therapy with pegylated Interferon Alfa-2a. Conclusion: Systemic therapy with pegylated Interferon Alfa-2a has a role in treating squamous cell cancers. Further studies need to be done to define its role in the management of cutaneous squamous cell cancers.

Many genetic traits common to aggressive breast carcinoma have been identified; yet little is known about the interrelationships of such traits during tumor development, especially in women prone to aggressive cancer. This study examined the expression of four biological markers associated with poor prognosis at each stage of breast cancer progression in primary tumors from women of lower economic status and assessed the relationship between these markers.

Paraneoplastic systemic sclerosis (SSc) occurs in about 3%–7% of individuals with SSc. There are reports of accelerated SSc syndromes associated in particular with breast cancer. Further exacerbations of the rheumatic condition may be induced by treatment of the cancer. We report a 30-year-old African-American woman with a contiguous diagnosis of breast cancer and paraneoplastic SSc. She was treated with neoadjuvant chemotherapy and developed an accelerated SSc syndrome with pericarditis and cardiac tamponade, with lethal results. This case report stresses the need for control of the rheumatic condition prior to the initiation of antineoplastic therapy.