bluuebunny/crossref_metadata_2025 huggingface dataset:
Interval Laparoscopic Cholecystectomyin the Management of Acute Biliary Pancreatitis
Authors: Schachter M. D. Pinhas , Peleg M. D. Timor , Cohen M. D. Oded
Published: September 2007

The timing of laparoscopic cholecystectomy following
an attack of acute biliary pancreatitis is controversial.
The traditional approach of interval
cholecystectomy has been challenged recently. The
present study was designed to evaluate the benefits
of interval laparoscopic cholecystectomy for patients
with mild acute pancreatitis (Ranson less than 3).
Nineteen patients with mild pancreatitis underwent
ultrasonographic evaluation to confirm the biliary
etiology. ERCP was performed in all patients on the
first available endoscopy list, and endoscopic sphincterotomy
was performed in two patients with calculi
or dilated common bile duct on ultrasonographic
examination. Medical treatment was administered
and laparoscopic cholecystectomy was scheduled
after 8–12 weeks to allow the inflammatory process
to settle. There were no recurrent attacks of pancreatitis
during this period. The degree of difficulty of
the laparoscopic procedure was assessed by the presence
of adhesions to the gallbladder area, difficulty
of dissection in the Calot′s triangle, intraoperative
bleeding and the need for a drain. Six patients
(31.5%) had severe adhesions, difficult dissection of
the cystic duct and artery, bleeding and prolonged
operating time. In two of these patients (10.5%) the
procedure was converted to open cholecystectomy.
In conclusion, our results suggest that postponing
laparoscopic cholecystectomy in acute pancreatitis
patients is not advantageous surgically and does
not justify the risk of further morbidity caused by
the gallbladder disease.
Pancreatic Pseudocysts Transpapillaryand Transmural Drainage
Authors: Libera E. Della , Siqueira E. S. , Morais M. , Rohr M. R. S. , Brant C. Q. , Ardengh J. C. , Ferrari A. P.
Published: September 2007

Background: Pancreatic pseudocyst endoscopic drainage
has been described as a good treatment option,
with morbidity and mortality rates that are lower
than surgery. The aim of our study is to describe the
efficacy of different forms of endoscopic drainage
and estimate pseudocyst recurrence rate after short
follow up period.

Patients and Methods: We studied 30 patients with
pancreatic pseudocyst that presented some indication
for treatment: persistent abdominal pain, infection
or cholestasis. Clinical evaluation was performed
with a pain scale, 0 meaning absence of pain
and 4 meaning continuous pain. Pseudocysts were
first evaluated by abdominal CT scan, and after
endoscopic retrograde pancreatography the patients
were treated by transpapillary or transmural (cystduodenostomy
or cystgastrostomy) drainage. Pseudocyst
resolution was documented by serial CT
scans.

Results: 25/30 patients could be treated. Drainage
was successful in 21 (70% in an ‘intention to treat’
basis). After a mean follow‐up of 42±35.82 weeks,
there was only 1 (4.2%) recurrence. A total of 6 complications
occurred in 37 procedures (16.2%), and all
but 2 were managed clinically and/or endoscopically:
there was no mortality related to the procedure.
Patients submitted to combined drainage
needed more procedures than the other groups.
There was no difference in the efficacy when we
compared the three different drainage methods.

Conclusions: We concluded that pancreatic pseudocyst
endoscopic drainage is possible in most
patients, with high success rate and low morbidity.
Mucobilia in Association With a BiliaryCystadenocarcinoma of the Caudate Duct:A Rare Cause of Malignant Biliary Obstruction
Authors: Chamberlain Ronald S. , Blumgart Leslie H.
Published: September 2007

Mucobilia is a rare condition characterized by the
accumulation of abundant mucus within the intra‐ or
extrahepatic biliary tree. A variety of hepatobiliary
and pancreatic neoplasms are mucin producing
and have been associated with the development of
mucobilia including biliary mucinosis, biliary papillomatosis,
mucin‐producing cholangiocarcinoma
(MPCC), or cystic neoplasms of the pancreas or
biliary tree (cystadenoma or cystadenocarcinoma).
We report the case of 46 year‐old male with a biliary
cystadenocarcinoma of the caudate lobe which resulted
in chronic biliary obstruction and relapsing
cholangitis. A review of the literature for both mucobilia
and biliary cystadenocarcinoma is provided
along with a discussion addressing the clinical presentation,
diagnosis, treatment, and prognosis for
this rare entity.
Cholecystectomy, Conversion and Complications
Authors: Thompson M. H. , Benger J. R.
Published: September 2007

Background Faced with a difficult laparoscopic
cholecystectomy the surgeon may feel that conversion
to open operation would risk greater complications
because of the laparotomy. Information on the
effect of conversion is lacking. The purpose of this
study is to measure the complications of laparoscopic
cholecystectomy and observe the effect of the
conversion rate.

Methods A total of 957 patients were studied.
There were three consecutive series of patients; the
first undergoing open cholecystectomy (384 patients),
the second laparoscopic cholecystectomy with a 5.8%
conversion rate (412 patients) and the third laparoscopic
cholecystectomy with a 1.3% conversion rate
(161 patients). Data was collected prospectively using
a continuous audit, and the complication rate
compared on an intention to treat basis. In addition a
panel of experienced surgeons was asked to score the
complications depending on their severity and a
composite complication score calculated. Comparison
between the 3 groups was then undertaken.
Results Open cholecystectomy produced a postoperative
complication rate of 6%. Initially this
appeared to fall to 3.1% with the introduction of
laparoscopic cholecystectomy, but when the complications
occurring in the converted patients were
included (i.e., on an intention to treat basis) the rate
increased to 5.6% in the first group of laparoscopically‐
treated patients and 3.1% in the second. These
differences were not statistically significant. A similar
pattern emerged when scoring the severity of the
complications as judged by the expert panel. The
inclusion of intra‐operative complications appears
to remove any small advantage for laparoscopic
cholecystectomy. The reduction in the conversion
rate between the two laparoscopic groups from 5.8%
to 1.2% was statistically significant.

Conclusion When considered on an intention to
treat basis laparoscopic cholecystectomy offers no
advantage over open operation in terms of the frequency
or severity of complications. Reducing the
frequency of conversion from a laparoscopic to an
open procedure also has no significant effect on the
complications encountered. We conclude, therefore,
that the complication rate is independent of the conversion
rate and that the surgeon, when faced with
difficulty at laparoscopic cholecystectomy, should
not be deterred from converting to open operation
for fear of the post‐operative consequences.
Synchronous Hepatic Cryotherapy and Resection of Colonic Primary is a High Risk Procedure
Authors: Cheung D. , Morris D. L.
Published: September 2007

Thirteen patients underwent hepatic cryotherapy
and synchronous colonic resection. Two of the nine
patients developed hepatic abscess – this is a rare
complication of cryotherapy alone.
Cholangiographic Features in the Diagnosisand Management of Obstructive IctericType Hepatocellular Carcinoma
Authors: Lau W. Y. , Leow C. K. , Leung K. L. , Leung Thomas W. T. , Chan Michael , Yu Simon C. H.
Published: September 2007

In 11 years and 3 months, 2037 patients with HCC
were seen and 48 patients (2.4%) were diagnosed to
have obstructive icteric type HCC. Five patients
were terminally ill and were not investigated further.
Forty three patients were initially investigated
by endoscopic retrograde cholangiography (ERC) or
percutaneous transhepatic cholangiogram (PTC) and
classified as having obstructive icteric type 1, 2, or 3
HCC based on the cholangiographic findings. The
obstruction in type 1 HCC was due to intraluminal
tumour casts and/or tumour fragments obstructing
the hepatic ductal confluence or common bile duct,
while intraluminal blood clots, from haemobilia,
filling the biliary tree was the cause in type 2 HCC.
The pathology in type 3 HCC was extraluminal
obstruction by extensive tumour encasement of the
intra–hepatic biliary ductal system and/or extrinsic
compression of the hepatic and common bile ducts
by tumour(s) and/or malignant lymph nodes. At
the initial ERC/PTC, 10 patients (5 resected, 50%)
had obstructive icteric type 1 and 23 patients (0 resected)
had obstructive icteric type 3 HCC. Of the 10
patients initially classified according to cholangiography
to have obstructive icteric type 2 HCC,
subsequent investigations revealed that 6 patients
had type 1 HCC (4 resectable, 67%) and 4 patients
had type 3 HCC (0 resectable). The classification of
the obstructive icteric type HCC into types 1, 2, and
3, based on the initial cholangiographic appearances
has simplified and rationalized our management
strategy for this condition.
Adenoma of the Papillae of Vater.Report of Eleven Cases
Authors: Kiviniemi Heikki , Mäkelä Jyrki , Palm Jukka , Saarela Arto
Published: September 2007

Eleven patients with a preoperative diagnosis of
adenoma of the papillae of Vater were followed up
during the fifteen‐year period from 1984 till 1998 in
the Oulu University Hospital. Seven patients were
treated primarily by transduodenal excision without
any recurrences so far. One of these seven patients
was found to have adenocarcinoma in a histological
examination.

Active surgery for adenoma of the papillae of
Vater is recommended because of the precancerous
nature of the lesion, and because malignancy cannot
always be detected by endoscopic biopsies. Transduodenal
excision could be recommend for patients
at high operative risk, especially in cases with small
adenomas and low‐grade dysplasia, where histologically
free resection margins can be achieved, but
pancreaticoduodenectomy should still be performed
on patients at low operative risk.
Peliosis Hepatis With IntrahepaticHemorrhage: Successful Embolizationof the Hepatic Artery
Authors: O′Riordan K. , Blei A. , Vogelzang R. , Nemcek A. , Abecassis M.
Published: September 2007

Peliosis hepatis is defined as the appearance of
blood filled lakes in the hepatic parenchyma. It has
been associated with various pharmacological
agents and infections. Treatment has been primarily
symptomatic and includes discontinuation of offending
medications, partial hepatectomy or occasionally
liver transplantation. We report a 58 year
old white female on hormone replacement therapy
who developed symptomatic peliosis hepatis and
underwent successful superselective hepatic artery
embolization with control of bleeding.
Standardization of Steroid Hormone Assays: Why, How, and When?
Authors: Stanczyk Frank Z. , Lee Jennifer S. , Santen Richard J.
Published: September 2007

Lack of standardization of high-quality steroid hormone assays is a major deficiency in epidemiologic studies. In postmenopausal women, reported levels of serum 17β-estradiol (E2) are highly variable and median normal values differ by approximately a 6-fold factor. A particular problem is the use of E2 assays for prediction of breast cancer risk and osteoporotic fractures, where assay sensitivity may be the most important factor. Identification of women in the lowest categories of E2 levels will likely provide prognostic information that would not be available in a large group of women in whom E2 levels are undetectable by less sensitive assays. Detailed and costly methods involving extraction and chromatography in conjunction with RIA provide generally acceptable E2 results in postmenopausal serum, whereas less tedious, direct immunoassays suffer from inadequate specificity and sensitivity. Studies comparing the two types of methods generally report higher E2 values with the direct methods as a result of cross-reactivity with other steroids and reduced correlation with biological variables such as body mass index. Similar problems exist with measurements of E2 and estrone in men, and estrone and testosterone in women. Interest in mass spectrometry–based assays is increasing as potential gold standard methods with enhanced sensitivity and specificity; however, these assays require costly instrumentation and highly trained personnel. Taking all of these issues into consideration, we propose establishment of standard pools of premenopausal, postmenopausal, and male serum, and utilization of these for cross-comparison of various methods on an international basis. An oversight group could then establish standards based on these comparisons and set agreed upon confidence limits of various hormones in the pools. These criteria would allow validation of sensitivity, specificity, precision, and accuracy of current steroid hormone assay methodology and provide surrogates until a true gold standard can be developed. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1713–9)
Weight Gain Prior to Diagnosis and Survival from Breast Cancer
Authors: Cleveland Rebecca J. , Eng Sybil M. , Abrahamson Page E. , Britton Julie A. , Teitelbaum Susan L. , Neugut Alfred I. , Gammon Marilie D.
Published: September 2007

Background: To examine the effects of prediagnostic obesity and weight gain throughout the life course on survival after a breast cancer diagnosis, we conducted a follow-up study among a population-based sample of women diagnosed with first, primary invasive, and in situ breast cancer between 1996 and 1997 (n = 1,508).

Methods: In-person interviews were conducted shortly after diagnosis to obtain information on height and weight at each decade of life from age 20 years until 1 year before diagnosis. Patients were followed to determine all-cause (n = 196) and breast cancer–specific (n = 127) mortality through December 31, 2002.

Results: In multivariate Cox proportional hazards models, obese women had increased mortality due to breast cancer compared with ideal weight women among those who were premenopausal at diagnosis [hazard ratio (HR), 2.85; 95% confidence interval (95% CI), 1.30-6.23] and postmenopausal at diagnosis (HR, 1.91; 95% CI, 1.06-3.46). Among women diagnosed with premenopausal breast cancer, those who gained >16 kg between age 20 years and 1 year before diagnosis, compared with those whose weight remained stable (±3 kg), had more than a 2-fold elevation in all-cause (HR, 2.45; 95% CI, 0.96-6.27) and breast cancer–specific mortality (HR, 2.09; 95% CI, 0.80-5.48). Women diagnosed with postmenopausal breast cancer who gained more than 12.7 kg after age of 50 years up to the year before diagnosis had a 2- to 3-fold increased risk of death due to all-causes (HR, 2.69; 95% CI, 1.63-4.43) and breast cancer (HR, 2.95; 95% CI, 1.36-6.43).

Conclusions: These results indicate that high levels of prediagnostic weight and substantial weight gain throughout life can decrease survival in premenopausal and postmenopausal breast cancer patients. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1803–11)
Excess Body Weight and Colorectal Cancer Risk in Canada: Associations in Subgroups of Clinically Defined Familial Risk of Cancer
Authors: Campbell Peter T. , Cotterchio Michelle , Dicks Elizabeth , Parfrey Patrick , Gallinger Steven , McLaughlin John R.
Published: September 2007

Overweight and obesity are linked with several chronic diseases, including colorectal cancer, among men, but results among women are equivocal. Previous evidence suggests that menopausal status, postmenopausal hormone use, and family history of cancer may modify the link between adiposity and colorectal cancer. In data from two population-based case-control studies (cases: 1,292 males and 1,404 females; controls: 1,465 males and 1,203 females) in Ontario and Newfoundland, Canada, we examined the link between colorectal cancer and body mass index (BMI) at two reference periods (BMI 2 years prior and BMI at age 20 years), weight gain since age 20 years, and height. Based on recent BMI indices among men, obesity (BMI ≥30 kg/m2) was associated with an 80% [95% confidence interval (95% CI), 1.43-2.27] increased risk of colorectal cancer relative to a normal BMI (18.5-24.9 kg/m2). The same comparison for BMI at age 20 years suggested a 94% increased risk of colorectal cancer (95% CI, 1.19-3.16). Odds ratios were similar among subgroups of men with and without a clinically defined familial risk of cancer (according to the Amsterdam or revised Bethesda criteria for Lynch syndrome). Associations were moderately stronger for cancer of the colon than cancer of the rectum. Among women, BMI and weight gain were not linked with colorectal cancer; the null associations were persistent in subgroups of familial risk of cancer, menopausal status, estrogenic status, and subsite. Tall height (>1.75 m), however, was linked with increased risk of colorectal cancer among women (odds ratio, 2.27; 95% CI, 1.46-3.59) but not among men. This study suggests that obesity is associated with increased risk of sporadic and Lynch syndrome–related colon and rectal cancers among men but not among women, whereas height is directly linked with all such cancers among women but not among men. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1735–44)
Associations between Androgen and Vitamin D Receptor Microsatellites and Postmenopausal Breast Cancer
Authors: Wedrén Sara , Magnusson Cecilia , Humphreys Keith , Melhus Håkan , Kindmark Andreas , Stiger Fredrik , Branting Maria , Persson Ingemar , Baron John , Weiderpass Elisabete
Published: September 2007

We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAGn and VDR An genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (≤21 or ≥22 repeats for AR and ≤18 or ≥19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAGn repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with ≥20 repeats. Women carrying two VDR alleles with <21 An were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1775–83)
Dose-Response Modeling of Occupational Exposure to Polycyclic Aromatic Hydrocarbons with Biomarkers of Exposure and Effect
Authors: Pesch Beate , Kappler Martin , Straif Kurt , Marczynski Boleslaw , Preuss Ralf , Roβbach Bernd , Rihs Hans-Peter , Weiss Tobias , Rabstein Sylvia , Pierl Christiane , Scherenberg Michael , Adams Ansgar , Käfferlein Heiko Udo , Angerer Jürgen , Wilhelm Michael , Seidel Albrecht , Brüning Thomas
Published: September 2007

In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1−, 2+9−, 3−, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2′-deoxyguanosine/106 dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman rs = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (rs = 0.01, P < 0.0001 for PAHs; rs = −0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2′-deoxyguanosine/106 dGuo were weakly negative (rs = −0.22, P = 0.004 for PAHs) or flat (rs = −0.08, P = 0.31 for hydroxyphenanthrenes). Linear splines were applied to assess the relationships between the log-transformed variables. All regression models were adjusted for smoking and type of industry. For hydroxyphenanthrenes, 51.7% of the variance could be explained by phenanthrene and other predictors. Up to 0.77 μg/m3 phenanthrene, no association could be found with hydroxyphenanthrenes. Above that point, hydroxyphenanthrenes increased by a factor of 1.47 under a doubling of phenanthrene exposure (slope, 0.56; 95% confidence interval, 0.47-0.64). Hydroxyphenanthrenes may be recommended as biomarker of occupational PAH exposure, whereas biomarkers of DNA damage in blood did not show a dose-response relation to PAH exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1863–73)
Exploring the Underlying Hormonal Mechanisms of Prenatal Risk Factors for Breast Cancer: A Review and Commentary
Authors: Troisi Rebecca , Potischman Nancy , Hoover Robert N.
Published: September 2007

Prenatal factors have been hypothesized to influence subsequent breast cancer development. Directly evaluating the associations of in utero exposures with risk, however, presents several methodologic and theoretical challenges, including the long induction period between exposure and disease and the lack of certainty regarding the critical timing of exposure. Indirect evaluation of these associations has been achieved by use of proxies such as gestational and neonatal characteristics. Evidence suggests that preeclampsia is associated with a reduced breast cancer risk, whereas high birth weight and dizygotic twinning seem associated with an increased risk. Asians born in Asia have substantially lower breast cancer risks than women born in the West. Although data thus far are few, what exists is not consistent with a unifying hypothesis for a particular biological exposure (such as estrogens or androgens) during pregnancy as mediating the observed associations between pregnancy factors and breast cancer risk. This suggests that additional studies of prenatal factors should seek to broaden the range of hormones, growth, and other endocrine factors that are evaluated in utero. Once candidate biomarkers are identified, assessing them with respect to breast cancer and with intermediate end points in carcinogenesis should be a priority. In addition, investigations should explore the possibility that in utero exposures may not act directly on the breast, but may alter other physiologic pathways such as hormone metabolism that have their effect on risk later in life. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1700–12)
GLIOGENE—an International Consortium to Understand Familial Glioma
Authors: Malmer Beatrice , Adatto Phyllis , Armstrong Georgina , Barnholtz-Sloan Jill , Bernstein Jonine L. , Claus Elizabeth , Davis Faith , Houlston Richard , Il'yasova Dora , Jenkins Robert , Johansen Christoffer , Lai Rose , Lau Ching , McCarthy Bridget , Nielsen Hanne , Olson Sara H. , Sadetzki Siegal , Shete Sanjay , Wiklund Fredrik , Wrensch Margaret , Yang Ping , Bondy Melissa
Published: September 2007

Evidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in ∼5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for “glioma gene” and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1730–4)
Validation of Self-Reported Smoking Status Using Saliva Cotinine: A Rapid Semiquantitative Dipstick Method
Authors: Montalto Norman J. , Wells Wayne O.
Published: September 2007

Purpose: This study evaluated the performance characteristics of a novel rapid method for verifying smoking status in individuals by measurement of cotinine, the primary metabolite of nicotine, in saliva samples using an immunochromatographic strip in a “dipstick” format compared with liquid chromatography/mass spectrometry (LC/MS).

Materials and Methods: A prospective comparison was made of smoking status as determined by measurement of cotinine in urine by LC/MS (the gold standard) and in saliva using a semiquantitative dipstick assay that uses cotinine-specific monoclonal antibodies attached to gold particles and a series of avidity traps to measure cotinine levels (saliva NicAlert®). One hundred seventy-two individuals from a family practice/general medical setting agreed to participate after informed consent and institutional review board approval. Saliva NicAlert® tests were done by untrained operators who followed written directions.

Results: Comparison of smoking status as determined by urine cotinine measurement by LC/MS (50 ng/mL cutoff) with the saliva strip test results, averaged over the two operators, indicated that the saliva test strip results had a sensitivity of 99% and a specificity of 96%. Saliva NicAlert® also identified four smokers who reported being nonsmokers but were confirmed to be smokers by LC/MS.

Conclusions: The saliva NicAlert® assay seems to be a valid, highly sensitive, and specific method for validating self-reported smoking status and may have clinical applications in selected medical settings. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1858–62)
Detection of Cotinine in Newborn Dried Blood Spots
Authors: Spector Logan G. , Hecht Stephen S. , Ognjanovic Simona , Carmella Steven G. , Ross Julie A.
Published: September 2007

Maternal smoking while pregnant is a plausible risk factor for childhood cancers because many seem to initiate in utero and tobacco-specific carcinogens cross the placenta. Social desirability bias may affect maternal report of smoking in case-control studies and could explain inconsistently observed associations with offspring cancer. Detection of tobacco smoke biomarkers in dried blood spots (DBS), which are increasingly stored by newborn screening programs, may improve retrospective assessment of fetal tobacco exposure. As proof-of-principle, we examined cotinine in DBS of 20 infants enrolled in a pilot study of pregnancy among low-income women. We recruited 107 pregnant women (<30 weeks of gestation) from six Women, Infants, and Children clinics in Minneapolis and St. Paul in 1999. Blood samples obtained at enrollment were tested for total cotinine using gas chromatography/mass spectrometry. Women were then interviewed at 7 months of gestation to determine current smoking habits. DBS were obtained from the Minnesota Department of Health. We tested DBS from 10 infants whose mothers had detectable serum cotinine at baseline and 10 control infants whose mothers had none. One quarter of each DBS was assayed for cotinine using gas chromatography/mass spectrometry; levels were estimated assuming 50 μL blood per sample. Mean cotinine was 29 ng/mL (SD, 7.5), 45 ng/mL (SD, 9.7), and 9 ng/mL (SD, 7.4), respectively, among infants of all smokers, infants of four women who acknowledged smoking at 7 months of gestation, and infants of nonsmokers. These results suggest that DBS analysis may identify infants of women who smoke throughout pregnancy. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1902–5)
Effect of a 12-Month Exercise Intervention on the Apoptotic Regulating Proteins Bax and Bcl-2 in Colon Crypts: A Randomized Controlled Trial
Authors: Campbell Kristin L. , McTiernan Anne , Li Shuying S. , Sorensen Bess E. , Yasui Yutaka , Lampe Johanna W. , King Irena B. , Ulrich Cornelia M. , Rudolph Rebecca E. , Irwin Melinda L. , Surawicz Christina , Ayub Kamran , Potter John D. , Lampe Paul D.
Published: September 2007

Background: Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts.

Methods: Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt samples were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry.

Results: Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus −0.18; P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO2max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (−0.36 versus +0.69; P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus −0.85; P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03).

Conclusions: A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1767–74)
Plasma Volume Expansion in Pregnancy: Implications for Biomarkers in Population Studies
Authors: Faupel-Badger Jessica M. , Hsieh Chung-Cheng , Troisi Rebecca , Lagiou Pagona , Potischman Nancy
Published: September 2007

There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of preeclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1720–3)
Adiposity and Sex Hormones in Girls
Authors: Baer Heather J. , Colditz Graham A. , Willett Walter C. , Dorgan Joanne F.
Published: September 2007

Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone–binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 μg/dL compared with 78.8 μg/dL for the highest quartile, and each kg/m2 increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (Ptrend = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m2 increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (Ptrend < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1880–8)
A Prospective Study of Body Size and Breast Cancer in Black Women
Authors: Palmer Julie R. , Adams-Campbell Lucile L. , Boggs Deborah A. , Wise Lauren A. , Rosenberg Lynn
Published: September 2007

The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of ≥25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never-users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1795–802)
Early Onset Pancreatic Cancer: Evidence of a Major Role for Smoking and Genetic Factors
Authors: Raimondi Sara , Maisonneuve Patrick , Löhr J-Matthias , Lowenfels Albert B.
Published: September 2007

Pancreatic cancer ranks 4th as a cause of cancer mortality and in ∼5% to 10% of patients, this lethal tumor develops before age 50. We used age-, sex-, and country-specific cancer incidence and mortality data to describe the burden of early onset pancreatic cancer (EOPC) worldwide. We also reviewed the current published evidence on smoking and genetic factors associated with EOPC. We found an excess of EOPC resulting in a substantial number of years-of-life-lost in countries from Central and Eastern Europe. Worldwide, the proportion of EOPC is strongly correlated with lung cancer mortality (R2 = 0.53), suggesting that approximately half of the variation in the proportion of EOPC could be explained by smoking. The unusual pattern of the incidence of pancreatic cancer by gender and race supports the primary role of smoking in the etiology of EOPC: the excess male-to-female rate ratio, attributable mainly to smoking, gradually approaches unity with increasing age. Moreover, male-to-female rate ratios are greater in blacks than in whites only in younger patients. Published studies also identified genetic alterations involved either alone or in association with smoking in the development of EOPC. In conclusion, EOPC constitutes only 1% to 5% of the total deaths from pancreatic cancer worldwide, but is responsible for 20% to 30% of the total number of years-of-life-lost caused by the disease. Smoking and genetic mutations are the major identified risk factors and seem to be even more important for EOPC than for PC in older age groups. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1894–7)
Serologic Response to Oncogenic Human Papillomavirus Types in Male and Female University Students in Busan, South Korea
Authors: Clifford Gary M. , Shin Hai-Rim , Oh Jin-Kyoung , Waterboer Tim , Ju Young-Hee , Vaccarella Salvatore , Quint Wim , Pawlita Michael , Franceschi Silvia
Published: September 2007

In the absence of genital samples, human papillomavirus (HPV) serology may be useful to assess HPV infection in young men and women. HPV seroprevalence and determinants of seropositivity were assessed in 817 female and 518 male university students in Busan, South Korea, of whom 74% and 44%, respectively, reported never having had penetrative sexual intercourse. Type-specific HPV DNA status, assessed by a short PCR fragment primer set, was available from genital samples. Seropositivity to L1 proteins of HPV types 16, 18, 31, 33, 45, 52, and 58 were assessed using multiplex HPV serology. Among women, HPV seroprevalence was significantly higher among sexually active (26.1%) than nonsexually active students [11.1%, odds ratio (OR) = 2.9; 95% confidence interval (95% CI), 1.8-4.7], although the association was weaker than that for HPV DNA prevalence (OR, 14; 95% CI, 4.7-42). Furthermore, HPV seroprevalence was higher among HPV DNA-positive (24%) than HPV DNA-negative women (13%), and there was a positive correlation of type-specific seroprevalence with the presence of HPV DNA of the same type. In contrast, HPV seropositivity among men was not associated with sexual behavior or the presence of HPV DNA. Seroprevalence correlates with genital HPV exposure in young women, but its meaning in young men is unclear. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1874–9)
The Impact of Autoimmune Diseases on the Incidence and Prognosis of Cutaneous Malignant Melanoma
Authors: Kaae Jeanette , Wohlfahrt Jan , Boyd Heather A. , Wulf Hans Christian , Biggar Robert J. , Melbye Mads
Published: September 2007

Background: Persons being treated with IFNα-2b for advanced cutaneous malignant melanoma (CMM) have been reported to have a greatly improved prognosis if they develop autoantibodies or clinical signs of autoimmunity during therapy. Consequently, we examined whether autoimmune diseases might also be associated with lower CMM incidence and better prognosis.

Methods: We established a study cohort based on the entire Danish population, obtaining information on CMM and autoimmune diseases from the Danish national registers. Using log-linear regression models adjusting for age, period, and sex, we compared CMM incidence and CMM-specific mortality rates in persons with and without a history of autoimmune disease.

Results: Between 1977 and 2003, 20,482 cases of CMM were registered in the Danish Cancer Register. Previously diagnosed autoimmune diseases did not affect the incidence of CMM (incidence rate ratio, 1.0; 95% confidence interval, 0.9-1.1). In the first 5 years after CMM diagnosis, we observed 8,957 deaths in individuals with CMM (5,181 expected). CMM-specific mortality rates 1 to 5 years after diagnosis were similar in CMM patients with and without autoimmune diseases (mortality rate ratio, 0.9; 95% confidence interval, 0.7-1.2).

Conclusions: Autoimmune conditions were not associated with CMM incidence or prognosis. The better CMM prognosis previously observed when autoantibodies or clinical signs of autoimmunity developed during IFNα-2b therapy may have been related to variation in individual responses to this therapy, with individuals sensitive to treatment exhibiting more signs of autoimmunity but also (independently) experiencing greater antitumor responses as a result of treatment. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1840–4)
Serum 25(OH)-Vitamin D Concentration and Risk of Esophageal Squamous Dysplasia
Authors: Abnet Christian C. , Chen Wen , Dawsey Sanford M. , Wei Wen-Qiang , Roth Mark J. , Liu Bing , Lu Ning , Taylor Philip R. , Qiao You-Lin
Published: September 2007

Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer.

Methods: We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing esophageal squamous cell carcinoma. All subjects underwent endoscopy and biopsy and were categorized by the presence or absence of histologic squamous dysplasia. We used crude and multivariate-adjusted generalized linear models to estimate the relative risks (RR) and 95% confidence intervals (95% CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration.

Results: Two-hundred and thirty of 720 subjects (32%) had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations than subjects without dysplasia, 36.5 and 31.5 nmol/L, respectively (Wilcoxon two-sample test, P = 0.0004). In multivariate-adjusted models, subjects in the highest compared with the lowest quartiles were at a significantly increased risk of squamous dysplasia (RR, 1.86; 95% CI, 1.35-2.62). Increased risks were similar when examined in men and women separately: men (RR, 1.74; 95% CI, 1.08-2.93); women (RR, 1.96; 95% CI, 1.28-3.18).

Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1889–93)
Increased Expression of Corepressors in Aggressive Androgen-Independent Prostate Cancer Cells Results in Loss of 1α,25-Dihydroxyvitamin D3 Responsiveness
Authors: Ting Huei-Ju , Bao Bo-Ying , Reeder Jay E. , Messing Edward M. , Lee Yi-Fen
Published: September 2007

Vitamin D has antiproliferative activity in prostate cancer; however, resistance to vitamin D–mediated growth inhibition occurs. To investigate the mechanisms of vitamin D resistance, we screened two prostate cancer sublines of CWR22rv1, CWR22R-1, and CWR22R-2, with differential sensitivity to vitamin D. CWR22R-2 showed less response to the antiproliferative effect of vitamin D than CWR22R-1. The vitamin D receptor (VDR)–mediated transcriptional activity was also decreased in CWR22R-2. We further showed that the DNA-binding ability of VDR was decreased and the amount of NCoR in VDR response element was increased in CWR22R-2. Analysis of VDR-associated protein profiles found higher expression of the corepressors, NCoR1 and SMRT, in CWR22R-2 cells. Treatment with the histone deacetylase inhibitor, trichostatin A, increased vitamin D/VDR transcriptional activity and promoted the antiproliferative effect of vitamin D in CWR22R-2 cells. Targeted down-regulation of NCoR1 and SMRT by small interference RNA was able to restore CWR22R-2 response to vitamin D. Together, we showed that increased NCoR1 and SMRT expression in CWR22R-2 cells resulted in reduced VDR-mediated transcriptional activity and attenuated antiproliferative response to vitamin D. Our data suggest that the integrity of the vitamin D/VDR–mediated signaling pathway is crucial in predicting vitamin D responsiveness and thus provide a rational design to improve vitamin D–based treatment efficacy based on molecular profiles of patients. (Mol Cancer Res 2007;5(9):967–80)