Kentucky hepatoma: epidemiologic variant or same problem in a different region?

BACKGROUND: Hepatitis and cirrhosis are common etiologic factors in hepatocellular carcinoma (HCC) in the United States. However, noncirrhotic, nonfibrotic HCC has been recognized more frequently in Kentucky. The aim of this study was to evaluate the epidemiologic features of this variant of HCC. HYPOTHESIS: Kentucky hepatoma, defined as a noncirrhotic, nonfibrotic, hepatitis-negative HCC, occurs in an older population with more favorable preoperative factors when compared with other patients with HCC. DESIGN: A prospective review of our 1002 hepatopancreaticobiliary patients, the Kentucky Cancer Registry, and the Surveillance, Epidemiology, and End Results database. SETTING: An academic referral center. PATIENTS: All patients with HCC treated from January 1, 1999, through September 30, 2005, were reviewed for clinicopathologic factors, recurrence, and outcome. RESULTS: In a review of the region's 703 patients with HCC, we have seen a 4-fold increase in age-specific HCC diagnosis, with the most rapid increase seen in the 60- to 69-year-old age group. In our institution's 103 patients with HCC, 62 (60.2%) were without hepatitis or cirrhosis. These noncirrhotic, hepatitis-free patients were found to be significantly older (70 vs 55 years; P = .001), to be more often female (40.3% vs 24.4%; P = .01), to have a larger tumor size (6.5 vs 3.9 cm; P = .004), to have fewer liver lesions (1 vs 3; P = .22), and to more frequently undergo surgical therapy (75.6% vs 53.8%; P = .01) than the patients with cirrhosis or hepatitis (n = 41). CONCLUSIONS: A larger percentage of the patients with HCC seen in our region are significantly different from those in other reports throughout the United States in preoperative clinical and pathologic presentation. The reason for this change is as yet unknown, but the incidence continues to rise annually.     

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

A profile of the online dissemination of national influenza surveillance data

Background  

Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.     

The use of radiation therapy after breast-conserving surgery in hormonally treated breast cancer patients is dependent on patient age, geographic region, and surgeon specialty

BACKGROUND: The use of radiation therapy (RT) after breast-conserving surgery (BCS) is inconsistent in patients treated with hormonal therapy (HT). We sought to identify factors influencing the decision to use RT in this setting. METHODS: Patients in the North American Fareston vs. Tamoxifen Adjuvant (NAFTA) trial who had BCS were evaluated for factors influencing the use of RT using univariate and multivariate analyses. RESULTS: Of the 1,811 patients enrolled in the NAFTA trial, 1,222 (67.4%) had BCS. Of these, 241 (19.7%) did not have RT. There were no significant differences in tumor grade, lymphovascular invasion, estrogen receptor status, or nodal status between those who received RT and those who did not. On univariate analyses, patients who did not receive RT were more likely to be older (median 72 versus 66 years, P < .001), have larger tumors (median 1.35 versus 1.10 cm, P = .009), and be progesterone negative (18.3% versus 13.1%, P = .048). Surgeons in the West were most likely to omit RT, whereas those in the Midwest were least likely to omit it (26.7% versus 7.2%, P < .001). Surgical oncologists were more likely to omit RT after BCS than general surgeons (21.8% versus 13.7%, P < .001). Academic affiliation (P < .001), number of breast procedures performed per year (P = .017), and the percentage of breast practice (P = .019) also correlated with whether or not RT was used. On multivariate analysis, patient age (P < .001), geographic region (P = .006), and surgeon specialty (P = .027) remained significant. CONCLUSION: Patient age, geographic region, and surgeon training influence the decision to use RT after BCS in patients receiving HT.     

A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients

Background

Little is known about the long-term prognosis of small bowel carcinoids because currently no staging system exists.

Methods

A search of the Surveillance, Epidemiology and End Results (SEER) database identified 6,380 patients with small bowel carcinoid tumors from 1977 to 2004. Patients were analyzed according to various clinicopathologic factors and a tumor (T1, T2, T3), lymph node (N0, N1), and metastasis (M0, M1) staging system was created according to these parameters.

Results

Among the 6,380 patients, 2,985 women and 3,395 men, with a median age of 66 years (range 14-98), the median tumor size was 1.9 cm (range .1-30 cm). Multivariate analysis demonstrated that age, size of the primary tumor, and depth of invasion were significant factors. Four stages were created according to statistically significant prognostic factors: 13% of patients were classified into stage I, 31% into stage II, 16% into stage III, and 40% into stage IV. Five-year survival rates were 96%, 87%, 74%, and 43% for stages I through IV, respectively.

Conclusions

The newly developed TNM staging system accurately discriminates prognosis for small bowel carcinoid tumors.     

Factors determining adequacy of axillary node dissection in breast cancer patients

With increased focus on quality assurance, a complete axillary lymph node dissection (ALND) has been defined as the removal of 10 or more lymph nodes (LN). The objective of this study was to determine which patient, physician, and geographic factors predict the adequacy of ALND in breast cancer patients. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multicenter, prospective study of 4,131 patients, all of whom had a sentinel node biopsy and completion ALND. Univariate and multivariate analyses were performed to determine which factors were independently associated with the removal of 10 or more LN. Of the 4,131 patients in this study, the median number of LN removed was 11 (range; 3-45). Ten or more LN were removed in 3,213 (77.8%) patients. The median patient age in this study was 60 (range; 27-100), with a median tumor size of 1.5 cm (range; 0.1-11.0 cm). On univariate analysis, patient age, tumor size, and palpability were correlated with adequacy of ALND. Academic affiliation and percentage of breast practice were significant physician factors predictive of adequacy of ALND. Both geographic region and community size were significantly correlated with adequacy of ALND. On multivariate analysis, patient age (p = 0.024), surgeon academic affiliation (p < 0.001), percentage breast practice (p < 0.001), and community size (p = 0.003) were significant determinants of adequacy of ALND. Younger patients were more likely to have an adequate ALND. Surgeons in academic practice had a higher rate of adequate ALND, as did those practicing in larger communities. Surgeons with a more breast experience had a lower rate of adequate ALND. Patient age, surgeon academic affiliation, and breast experience, as well as community size are all significant factors predictive of adequacy of ALND.     

Caspase activation and changes in Bcl-2 family member protein expression associated with E2F-1-mediated apoptosis in human esophageal cancer cells.

The prognosis for patients with esophageal cancer remains poor, prompting the search for new treatment strategies. Overexpression of E2F-1 has been shown to induce apoptosis in several cancer cell types. In the present study, the effect of adenovirus-mediated E2F-1 overexpression on human esophageal cancer cell lines Yes-4 and Yes-6 was evaluated. Cells were treated by mock infection, infection with an adenoviral vector expressing beta-galactosidase (Ad5CMV-LacZ), or E2F-1 (Ad5CMVE2F-1). Western blot analysis confirmed marked overexpression of E2F-1 in Ad5CMVE2F-1-infected cells. Overexpression of E2F-1 resulted in marked growth inhibition and rapid loss of cell viability due to apoptosis, although Yes-6 cells were somewhat more resistant to E2F-1-mediated growth inhibition than Yes-4 cells. Cell cycle analysis revealed that overexpression of E2F-1 led to G2 arrest, followed by apoptotic cell death. p53 expression remained undetectable in both cell lines after E2F-1 overexpression. The apoptosis inhibitor proteins of the Bcl-2 gene family, Bcl-2, Mcl-1, and BcI-XL, decreased at 48 h after infection in Yes-4 cells, but remained unchanged in Yes-6 cells. Levels of retinoblastoma gene product (pRb) declined at 48 h after E2F-1 infection in Yes-4 cells, at which apoptosis predominated, whereas pRb expression remained constant in Yes-6 cells. Expression of p14ARF did not change after E2F-1 infection in either cell line. Involvement of caspase 3 and caspase 6 in E2F-1-mediated apoptosis was demonstrated by cleavage of caspase 3/CPP32 and poly-ADP-ribose polymerase, as well as fragmentation of the caspase 6 substrate, lamin B. These results indicate that the sensitivity of esophageal cancer cells to E2F-1-mediated apoptosis may be related to differential expression of Bcl-2 family member proteins and suggest that the adenovirus-mediated E2F-1 gene therapy may be a promising treatment strategy for the treatment of this disease.