Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

The need for a standard national immunization record

Perhaps the most significant link in achieving the nation's immunization objectives is the extent of parental knowledge. Admittedly, this is a weak link. The 1990 federal objectives calling for an official format using common guidelines for completion of immunizations, though well-conceived, has not been used exclusively by health care givers. The lack of accord has permitted the proliferation of many different immunization records that are not only confusing to parents, but also to health care providers at times. A standard national immunization record could be an essential element in strengthening the weak link of parental knowledge of immunizations and stressing the importance of preserving such a record for a lifetime.     

p27(Kip1) expression and grading of breast cancer diagnosed on cytological samples

The progressive reduction in p27(Kip1) (p27) protein immunohistochemical staining with increasing histological grading is a well-established finding occurring in breast cancer, and its role as diagnostic complement and prognostic marker has been thoroughly evaluated. To clarify whether this test may be applied to breast cytopathology, we performed p27 immunostaining on fresh fine-needle cytology (FNC) samples from 10 benign and 40 malignant breast lesions. On average, p27 immunostaining was significantly lower in carcinomas than in benign lesions (P < 0.005). In particular, among carcinomas, p27 immunostaining progressively reduced from well-to poorly differentiated lesions (G1 vs. G2, P < 0.05; G1 vs. G3, P < 0.001; G2 vs. G3; P < 0.001). A similar trend was noted in a subgroup of 20 matched FNCs and histological samples of breast carcinomas, when p27 immunostaining on FNCs was stratified according to the histological grading (G1 vs. G2, P = 0.18; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05). In addition, p27 immunostaining on FNCs showed a good positive correlation with that on histology (Spearman R = 0.58; P < 0.01), with a diagnostic concordance between samples of 85%, by using the standard 50% positive cell cutoff. Taken in concert, our data suggest that p27 immunostaining is a reliable marker of tumor cell differentiation in breast cytopathology as well as in histopathology. Accordingly, staining FNCs for p27 may be an useful complement in addition to cytological grading in the preoperative assessment of breast cancer.     

Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy

ObjectivesTo compare the occurrence of depression, anxiety, self body image perception, sleep disturbances, and diminished quality of life in prostate cancer patients undergoing adjuvant androgen-deprivation therapy (ADT) as opposed to patients in follow-up alone.Methods and materialsHospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Restless Legs Syndrome Study Group essential diagnostic criteria, Body Image Scale and Functional Assessment of Cancer Therapy Prostate were administered to consecutive prostate cancer patients who underwent radical prostatectomy or radiation therapy and are presently either under adjuvant ADT or included in a follow-up program.ResultsOf the 103 patients enrolled, 49 (47.6%) were receiving adjuvant ADT and 54 (52.4%) were not. Compared with the controls, the patients undergoing ADT showed higher levels of depression (P = 0.002), worse self body image perception (P = 0.001), worse quality of life (P = 0.0001) and worse sleep quality (P = 0.04). ADT was significantly associated with depression at multivariate analysis after adjustment for age, stage, Gleason score, as well as demographic and social variables (P = 0.001). Depression scores showed a strong inverse correlation with quality of life scores (P < 0.01).ConclusionsAdjuvant ADT is associated with depression, worse quality of life, and altered self body image in prostate cancer patients.     

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer

Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.

Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.

Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.     

The Addition of Radiation to Chemotherapy does not Improve Outcome When Compared to Chemotherapy in the Treatment of Resected Pancreas Cancer: The Results of a Single-Institution Experience

Background

Pancreas cancer is highly lethal even at early stages. Adjuvant therapy with chemotherapy (CT) or chemoradiation (CRT) is standard following surgery to delay recurrence and improve survival. There is no consensus on the added value of radiotherapy (RT). We conducted a retrospective analysis of clinical outcomes in pancreas cancer patients treated with CT or CRT following surgery.

Methods

Patients with resected pancreas adenocarcinoma were identified in our institutional database. Relevant clinicopathologic and demographic data were collected. Patients were grouped according to adjuvant treatment: group A: no treatment; group B: CT; group C: CRT. The primary endpoint of overall survival was compared between groups B vs. C. Univariate and multivariate analyses of potential prognostic factors were conducted including all patients.

Results

A total of 146 evaluable patients were included (group A: n = 33; group B: n = 45; group C: n = 68). Demographics and pathologic characteristics were comparable. There was no significant survival benefit for CRT compared with CT (mOS 16.8 months vs. 21.5 months, respectively, p = 0.76). Local recurrence rates were similar in all three groups. Univariate analyses identified absence of lymph node involvement (hazards ratio [HR] 1.43, p = 0.0082) and administration of adjuvant therapy (HR 0.496, p = 0.0008) as significant predictors for improved survival. Multivariate analyses suggested that patients without nodal involvement derived the most benefit from adjuvant treatment.

Conclusions

The addition of RT to CT did not improve survival over CT. Lymph node involvement predicts inferior clinical outcome.     

Gastrectomy in Advanced Gastric Cancer Effectively Palliates Symptoms and May Improve Survival in Select Patients

Background

The role of gastrectomy in the face of incurable gastric cancer is evolving. We sought to evaluate our experience with incomplete (i.e., R2) gastrectomy in advanced gastric cancer.

Methods

We reviewed 210 locally advanced or metastatic gastric cancers (1992–2008). Patient characteristics and outcomes were compared between three groups: gastrectomy (N?=?99), exploration without resection (N?=?66), and no surgery (N?=?45).

Results

Clinicopathologic characteristics were similar between groups. Symptoms successfully resolved after gastrectomy in 48 % with a complication rate of 32 % and mortality of 6 %. Overall median survival for all patients was 6.2 months: 10.0 months after gastrectomy, 4.1 months after exploration without resection, and 5.3 months for no surgery (p?<?0.001). Perioperative complications were the only predictor of symptom resolution following resection (OR?=?0.175). Resolution of symptoms (p?<?0.001, Hazards Ratio (HR)?=?0.09) and preoperative nausea/vomiting (p?=?0.017, HR?=?0.55) improved survival, while linitis plastica (p?=?0.035, HR?=?4.05) and spindle cell morphology (p?=?0.011, HR?=?1.98) were predictors of poor survival in patients undergoing resection.

Conclusions

Gastrectomy in the setting of advanced gastric cancer may be useful in up to half of patients with an acceptable perioperative mortality rate. Symptom resolution offers a potential survival advantage but is dependent upon a complication-free course, so should only be considered selectively.