Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer.

The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases.

ContextData regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease.ObjectiveTo assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism.Data Sources and Study SelectionThe databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched.Data ExtractionIndividual data on 55 287 participants with 542 494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25 977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations.ResultsAmong 55 287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51 837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease.ConclusionsSubclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.

We conducted a systematic meta‐analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case‐control studies, 75 cohorts and 2 nested case‐control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for ‘current’ and/or ‘former’ smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73–12.11), laryngeal (RR = 6.98; 95% CI: 3.14–15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86–15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63–4.84) and oral (RR = 3.43; 95% CI: 2.37–4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.

Background: Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. Purpose: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. Methods: To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (⩽30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. Results: The mean age (± standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 ± 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age ± SD at diagnosis of pancreatic cancer: 56.9 ± 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23–105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3–1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. Conclusions: Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.