Three-dimensional prediction of free-flap volume in autologous breast reconstruction by CT angiography imaging

Purpose

   The diagnostic use of computer tomography angiography (CTA) to identify perforating blood vessels for abdominal free-flap breast reconstruction was extended to estimate the three-dimensional (3D) preoperative flap volume and to compare it with the real intraoperative flap weights in order to (1) evaluate the accuracy of CTA-based 3D flap volume prediction, and (2) to analyze abdominal tissue estimation for required breast volume reconstruction.

Methods

   Preoperative CTA was performed in 54 patients undergoing unilateral breast reconstruction with a free, deep, inferior epigastric artery perforator flap. 3D flap volumes ( \(\hbox {cm}^{3}\) ) based on CTA data were calculated and compared with the actual intraoperative flap weight (g). In addition, a breast volume to flap volume ratio was calculated to analyze whether the estimated 3D abdominal flap volume would match that of the breast to be removed.

Results

   40 CTA data sets (74.1 %) fulfilled the technical requirements for a reliable determination of flap volume. 3D CTA flap volume prediction showed no relevant differences to the actual flap weight (p = 0.44) and high correlations (r = 0.998, \(p < 0.001\) ), allowing a prediction accuracy within 0.29 \(\pm \) 3.0 % (range: from \(-\) 8.77 to 5.67 %) of the real flap weight. Significantly larger flap volumes were harvested compared with the actually required breast volumes ( \(p < 0.001\) ), leading to an average of 21 % of the remnant flap tissue potentially being discarded.

Conclusions

   CTA-based 3D flap volume prediction provides accurate preoperative guidelines concerning the needed amount of abdominal tissue that can be harvested to achieve acceptable symmetry.     

ADH1B*2 allele is protective against alcoholism but not chronic liver disease in the Hungarian population

Background Standardized death rates from chronic liver diseases (CLDs) in Hungary are much higher than the European Union average. Carrying the alcohol dehydrogenase 1B 48His allele (rs1229984 or ADH1B*2) could decrease the risk of alcoholism, but with persistent drinking may confer a greater risk of CLDs. The aim of this study was to assess the prevalence of this polymorphism in the Hungarian population and its association with alcohol consumption and with CLDs. Methods and results A total of 278 cases with diagnosed CLDs and 752 controls without any alterations in liver function, all males aged 45–64, were screened for ADH1B Arg48His polymorphism. ADH1B*2 allele frequencies in controls and cases were 8.31% and 4.50%, respectively (χ² = 9.2; P = 0.01). Carrying the ADH1B*2 allele was associated with significantly lower odds ratio (OR) for drinking frequency (OR = 0.63; P = 0.003), the number of positive answers on CAGE (Cut‐down, Annoyed, Guilt, Eye‐opener) assessment (OR = 0.58; P = 0.005) and a positive CAGE status (OR = 0.55; P = 0.007). There was a significant association between ADH1B*2 and CLDs (OR = 0.50; P = 0.003), but it disappeared after adjusting for CAGE status and scores (OR = 0.67 P = 0.134; OR = 0.67 P = 0.148, respectively) and weakened after adjusting for drinking frequency (OR = 0.61; P = 0.045). Among heavy drinkers the presence of ADH1B*2 did not increase the risk of cirrhosis but there was a significant interaction between genotype and CAGE status (P = 0.003, P = 0.042), with ADH1B*2 conferring reduced risk of CLDs in CAGE negatives. Conclusion In Hungarians, the ADH1B 48His allele reduces the risk of alcoholism, but not the risk of chronic liver disease among heavy drinkers.     

Preliminary evidence of a noncausal association between the X-chromosome inactivation pattern and thyroid autoimmunity: a twin study

An increased frequency of skewed X-chromosome inactivation (XCI) is found in clinically overt autoimmune thyroid disease (AITD) compared with controls. Whether skewed XCI is involved in the pathogenesis of autoantibodies to thyroid peroxidase (TPOAb) in euthyroid subjects is unknown. To examine the impact of XCI on the serum concentration of TPOAb, we studied whether within-cohort and within-twin-pair differences in XCI are associated with differences in serum concentrations of TPOAb. A total of 318 euthyroid female twin individuals distributed in 159 pairs were investigated. XCI was determined by PCR analysis of a polymorphic CAG repeat in the first exon of the androgen receptor gene. TPOAb concentrations were measured using a solid-phase time-resolved fluoroimmunometric assay. Overall (within cohort), there was a significant association between XCI and serum concentrations of TPOAb; regression coefficient (β)=1.45 (95% confidence interval, 0.52–2.38), P=0.003. The association remained significant in the within-pair analysis; β=1.74 (0.79–2.69), P<0.001. The relationship was nonsignificant within the 82 monozygotic pairs (β=0.57 (−0.78–1.92), P=0.405), whereas the association was significant in the 77 dizygotic pairs (β=2.17 (0.81–3.53), P=0.002). This preliminary finding of a significant association between TPOAb concentrations and XCI within cohort and within dizygotic but not within monozygotic twin pairs may indicate that XCI per se does not have a major role in the pathogenesis of TPOAb. More likely, XCI and TPOAb are influenced by shared genetic determinants.     

Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breast

BACKGROUND:

Through this study, the authors sought to investigate the biologic and immunologic effects of preoperative trastuzumab in patients with ductal carcinoma in situ (DCIS) of the breast.

METHODS:

Patients with DCIS were enrolled in this open‐label phase 2 trial and tested for HER2. Trastuzumab was given by intravenous infusion (8 mg/kg). The patients then had surgery 14 to 28 days after treatment. Tissue and peripheral blood samples were obtained before therapy and at the time of surgery to examine residual disease and immunologic response.

RESULTS:

Median age of the 69 enrolled patients was 53 years, mean mammographic size of the DCIS lesions was 5.2 ± 1.2 cm, and 24 patients (35%) were found to have HER2 overexpression/amplification (12 received trastuzumab and 12 untreated patients provided tissue for blinded, controlled biomarker analyses). No overt histologic evidence of response was noted. No significant change in mean pretherapy staining for Ki‐67 (44.3 ± 3.4%) and cleaved caspase‐3 (2.6 ± 0.8%) was noted when surgical specimens from drug‐treated patient samples were compared with those not treated. Trastuzumab significantly augmented antibody‐dependent cell mediated cytotoxicity (ADCC) in 100% of patients; this was demonstrated to be mediated through CD56+ degranulating natural killer cells (P < .01). One patient developed a significant anti‐HER2 humoral CD4 T‐cell response.

CONCLUSIONS:

Single‐dose monotherapy with trastuzumab for patients with HER2‐positive DCIS does not result in significant, clinically overt, histologic, antiproliferative, or apoptotic changes, but does result in the ability to mount ADCC mediated through natural killer cells and may also induce T‐cell dependent humoral immunity. Further studies of trastuzumab for DCIS appear warranted. Cancer 2011. © 2010 American Cancer Society.