Interval breast cancer risk associations with breast density,family history and breast tissue aging

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case–control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69–0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts—an increased risk of developing an interval breast cancer.     

Cholecystectomy reduces subsequent cholangiocarcinoma risk in choledocholithiasis patients undergoing endoscopic intervention

BACKGROUNDCholangiocarcinoma is a disease with a high mortality rate. Our previous study revealed that cholelithiasis patients who undergo endoscopic sphincterotomy (ES)/endoscopic papillary balloon dilatation are at a higher risk for subsequent cholangiocarcinoma than cholelithiasis patients who undergo cholecystectomy.AIMTo clarify the relationship between recurrent biliary events and subsequent cholangiocarcinoma risk in choledocholithiasis patients.METHODSFrom one million random cases in the Taiwan National Health Insurance Research Database 2004–2011, we selected symptomatic choledocholithiasis patients older than 18 years who were admitted from January 2005 to December 2009 (study group). Cases for a control group were defined as individuals who had never been diagnosed with cholelithiasis, matched by sex and age in a 1:3 ratio. The study group was further divided into ES/endoscopic papillary balloon dilatation, both ES/endoscopic papillary balloon dilatation and cholecystectomy, and no intervention groups.RESULTSWe included 2096 choledocholithiasis patients without previous intervention or cholangiocarcinoma. A total of 12 (2.35%), 11 (0.74%), and 1 (1.00%) subsequent cholangiocarcinoma cases were diagnosed among 511 ES/endoscopic papillary balloon dilatation patients, 1485 patients with no intervention, and 100 ES/endoscopic papillary balloon dilatation and cholecystectomy patients, respectively. The incidence rates of recurrent biliary event were 527.79/1000 person-years and 286.69/1000 person-years in the subsequent cholangiocarcinoma and no cholangiocarcinoma group, showing a high correlation between subsequent cholangiocarcinoma risk and recurrent biliary events.CONCLUSIONCholedocholithiasis patients who undergo further cholecystectomy after ES/endoscopic papillary balloon dilatation have decreased subsequent cholangiocarcinoma risk due to reduced recurrent biliary events.     

Clinical outcome of elderly patients with Epstein–Barr virus positive diffuse large B‐cell lymphoma treated with a combination of rituximab and CHOP chemotherapy

Several studies have suggested the possibility of a prognostic relationship between Epstein–Barr virus (EBV) and diffuse large B‐cell lymphoma (DLBCL). The clinical outcome of EBV‐associated DLBCL is not clear, especially since the introduction of rituximab. We retrospectively analyzed 222 elderly patients (≥50 years) with DLBCL who received R‐CHOP chemotherapy and evaluated the state of EBV‐encoded RNA‐1 (EBER). Eighteen cases (8.1%) were EBER‐positive (+). After a median of six cycles of R‐CHOP chemotherapy, the response rate (≥partial response) was 72.2% (13/18) in the EBV (+) patients and 90.2% (184/204) in the EBV (?) DLBCL patients (P = 0.021). Four of 18 (22.2%) EBV (+) DLBCL patients received two or fewer cycles of R‐CHOP chemotherapy. R‐CHOP chemotherapy was also interrupted early more frequently compared with the EBV (?) group (2.5%) (P = 0.00). At a median follow‐up of 32.8 months, there was no significant difference in the overall survival between the groups (P = 0.627). The EBV (+) DLBCL patients with early interruption of R‐CHOP chemotherapy showed a trend toward a high EBV‐DNA titer (≥1,000 copies/mL) (P = 0.091). The results suggest that the EBV (+) tumoral status of elderly DLBCL patients who undergo R‐CHOP chemotherapy does not predict their survival but that their EBV status may contribute to the early interruption of R‐CHOP chemotherapy. Am. J. Hematol. 88:774–779, 2013. © 2013 Wiley Periodicals, Inc.     

Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

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Double umbilical cord blood transplantation for children and adolescents

Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.