Clinical Usefulness of AJCC Response Criteria for Neoadjuvant Chemotherapy in Breast Cancer

Purpose

Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria.

Methods

A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)—absence of invasive carcinoma in the breast and node; (2) partial response (PR)—decrease in either or both T or N stage; (3) no response (NR)—no change or increase in either or both T or N stage.

Results

Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS.

Conclusions

AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.     

Neo‐adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource‐poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo‐adjuvant therapy for breast cancer have been conducted in resource‐rich countries. We chose Nigeria, a resource‐poor country, as the major site for a phase II feasibility open‐label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo‐adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m² twice daily (2,000 mg/m² total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo‐adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.     

Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells

Park J‐C, Kim J.C, Kim B‐K, Cho K‐S, Im G‐I, Kim B‐S, Kim C‐S. Dose‐ and time‐dependent effects of recombinant human bone morphogenetic protein‐2 on the osteogenic and adipogenic potentials of alveolar bone‐derived stromal cells. J Periodont Res 2012; 47: 645–654. © 2012 John Wiley & Sons A/S Background and Objective: Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a well‐known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP‐2‐induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose‐ and time‐dependent effects of rhBMP‐2 on the osteogenic and adipogenic differentiation of human alveolar bone‐derived stromal cells (hABCs) in vivo and in vitro. Material and Methods: hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP‐2 (100 μg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8‐wk healing period. To further understand the dose‐dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time‐dependent (0, 3, 5, 7 and 14 d) effects of rhBMP‐2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome‐proliferator‐activated receptor gamma‐2 and lipoprotein lipase, were assessed using quantitative RT‐PCR. Results: rhBMP‐2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose‐ and time‐dependent manner with minimal deviation in vitro. The expression of osteogenesis‐ and adipogenesis‐associated mRNAs were concomitantly up‐regulated by rhBMP‐2. Conclusion: The findings of the present study showed that rhBMP‐2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose‐ and time‐dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP‐2.     

Factors Influencing Improvement of Trauma-Related Symptoms Among Somali Refugee Youth in Urban Kenya

Somali refugee youth present with a heightened risk for common mental disorders (CMDs), and yet few studies have discussed factors influencing mental health outcomes after psychosocial interventions. This study aimed to identify key factors that contribute to the improvement of CMD symptoms among Somali youth displaced in urban Kenya. Logistic regression analyses revealed that trauma exposure and emotional coping predict overall symptom improvement, pointing to a differential intervention effect on those with differing levels of religious belief and attitudes toward violence. This study provides insights into how psychosocial factors likely contribute to positive intervention outcomes in Somali refugee youth.

     

Submucosal Hemangioma of the Trachea in an Infant: Diagnosis and Follow-Up with 3D-CT/Bronchoscopy

Introduction:

Infantile hemangiomas of the airway are diagnosed at bronchoscopy as part of the investigation of stridor or other respiratory symptoms. Here, we present three-dimensional computed tomography (3D-CT)/bronchoscopy findings of submucosal subglottic hemangioma missed at bronchoscopy.

Case Presentation:

We report on the clinical usefulness of 3D-CT/bronchoscopy as the primary diagnostic tool and follow-up method in the evaluation of suspected airway infantile hemangiomas, especially when the hemangioma is the submucosal type.

Conclusions:

3D-CT/bronchoscopy will reduce the need for invasive laryngoscopic studies and help to diagnose submucosal hemangiomas undetected on laryngoscope. Additionally, 3D-CT/bronchoscopy will help evaluating the extent of the lesion, degree of airway narrowing, and treatment response.     

Individual Pulmonary Veins Outgrow Somatic Growth After Primary Sutureless Repair for Total Anomalous Pulmonary Venous Drainage

Indications of sutureless repair (SR) for pulmonary vein anomalies have evolved from re-operational SR for pulmonary vein stenosis after the repair of total anomalous pulmonary venous drainage (TAPVD) to primary SR for TAPVD associated with right atrial isomerism or isolated TAPVD with small individual pulmonary veins (IPVs) and an unfavorable pulmonary vein anatomy. We sought to determine whether small IPVs outgrow somatic growth after primary SR. Between 2004 and 2013, 21 children underwent primary SR for TAPVD: 13 with a functionally single ventricle, 11 with right atrial isomerism, six with isolated TAPVD, and 13 with a pulmonary venous obstruction. TAPVD types were supracardiac in nine, infracardiac in 10, and mixed in two. Utilizing cardiac computed tomography (CT), the maximal diameter of each IPV was measured, and pulmonary vein index (PVI, summation of cross-sectional areas of all four IPVs divided by body surface area) was calculated. There were five early deaths after SR. Among survivors, 10 had both preoperative and postoperative cardiac CT at a 3.6-month median interval. On postoperative cardiac CT, IPVs were patent in all patients except one who developed a left lower pulmonary vein obstruction. There was a 71 ± 48 % postoperative increase in the actual diameter of all four IPVs, and PVI increased significantly from 215 ± 55 to 402 ± 117 mm²/m² (P value = 0.005). IPVs outgrew somatic growth after primary SR of TAPVD. Primary SR may be a useful measure in TAPVD patients whose IPVs are small.     

Impairment of p38 MAPK-mediated cytosolic phospholipase A2 activation in the kidneys is associated with pathogenicity of Candida albicans

In studying the mechanisms underlying the susceptibility of the kidney to candidal infection, we previously reported that the reduced production of cytokines [i.e. tumour necrosis factor-alpha (TNF-alpha)] via platelet-activating factor (PAF)-induced activation of nuclear factor-kappaB (NF-kappaB) renders the organ susceptible to the fungal burden. In this study, we investigated the possibility that pathogenic Candida albicans may evade clearance and perhaps even multiply by inhibiting elements in the signalling pathway that lead to the production of TNF-alpha. The fungal burden of pathogenic C. albicans in the kidneys was 10(4)-10(5)-fold higher than that of a non-pathogenic strain. PAF-induced early activation of NF-kappaB and TNF-alpha mRNA expression were both observed in the kidneys of mice infected with non-pathogenic strains of C. albicans, but not in mice infected with pathogenic strains. Impairment of PAF-mediated early NF-kappaB activation following infection with pathogenic C. albicans was associated with the prevention of activation of the enzyme cytosolic phospholipase A(2) (cPLA(2)) as well as the upstream pathway of cPLA(2), p38 mitogen-activated protein kinase. Collectively, these findings indicate that C. albicans exerts its pathogenicity through impairing the production of anticandidal cytokines by preventing cPLA(2) activity. This novel mechanism provides insight into understanding pathogenic C. albicans and perhaps identifies a target for its treatment.