Genomic characterisation of breast fibroepithelial lesions in an international cohort

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy

Breast Cancer Research and Treatment - Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast...     

Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer

Background

Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may predispose patients to cognitive impairment. This study aimed to evaluate the effect of BDNF gene polymorphism on chemotherapy-associated cognitive impairment.

Methods

Overall, 145 patients receiving chemotherapy for early-stage breast cancer (mean age: 50.8 ± 8.8 y; 82.1% Chinese) were recruited. Patients'' cognitive functions were assessed longitudinally using the validated Functional Assessment of Cancer Therapy–Cognitive Function (v.3) and an objective computerized tool, Headminder. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition after adjusting for ethnicity and clinically important covariates.

Results

Of the 145 patients, 54 (37%) reported cognitive impairment postchemotherapy. The Met/Met genotype was associated with statistically significant lower odds of developing cognitive impairment (odds ratio [OR] = 0.26; 95% CI: 0.08–0.92; P = .036). The Met carriers were less likely to experience impairment in the domains of verbal fluency (OR = 0.34; 95% CI: 0.12–0.90; P = .031) and multitasking ability (OR = 0.37; 95% CI: 0.15–0.91; P = .030) compared with the Val/Val homozygote. No associations were observed between Headminder and the BDNF Val66Met polymorphism.

Conclusions

This is the first study to provide evidence that carriers of the BDNF Met allele are protected against chemotherapy-associated cognitive impairment. Further studies are required to validate the findings.     

Surgical management of endoscopic retrograde cholangiopancreatography-related perforations

Background: A retrospective review was carried out of consecutive cases of endoscopic retrograde cholangiopancreatography (ERCP)‐related perforation to identify risk factors and technique affecting surgical outcome. Methods: Eighteen patients (0.45%) out of 4030 ERCP performed were operated on for ERCP‐related perforation at Singapore General Hospital. Results: The group's median age was 72.5 years and 14 patients had ductal stone disease. Five perforations were discovered at ERCP while 10 required computed tomography for diagnosis. Eight patients were operated on within 24 h whereas 10 patients had surgery after 24 h. Five of six with type I (lateral duodenal) perforations had early surgery versus one of seven with type II (peri‐Vaterian; P = 0.03). There were four type III (bile duct) perforations and one type IV (retroperitoneal air). Five of six patients with type I perforation had simple repair compared with five of seven type II requiring the complex duodenal diversion procedure (P = 0.10). Three patients (16.7%) succumbed after surgery due to sepsis and myocardial infarction. Advanced age>70 years resulted in higher mortality of 30% versus none in patients <70 years (P = 0.22). Conclusions: Early diagnosis is important but difficult especially for the type II perforations. Duodenal diversion is used more frequently in patients with type II perforations and those operated on late. Advanced age contributes to poorer outcome in surgical treatment of ERCP perforations.     

Intrahepatic biliary cystadenoma presenting with obstructive jaundice

Biliary cystadenoma (BCA) is a rare neoplasm of the bile duct with malignant potential. We report a case of intrahepatic BCA with an unusual presentation of obstructive jaundice. Computed tomography scan of the abdomen revealed a dilated common bile duct and intrahepatic ducts with internal septa. Endoscopic retrograde cholangiography showed an oval filling defect in the bile duct causing the obstruction. At laparotomy, this proved to be a multiloculated mucinous polyp in the common bile duct, with its origin in the left intrahepatic duct, detected using intraoperative choledochoscopy. A left hemihepatectomy was performed, and histology confirmed intrahepatic mucinous BCA with mesenchymal stroma. The imaging process and surgical options for BCA are discussed.     

Low incidence of penetrating trauma in a high-volume tertiary center: 10-year mortality review

Background

Trauma morbidity and mortality outcome is better in high-volume trauma centers. However, there are few publications investigating the experience of high-volume centers with high non-trauma emergency load but seeing a relatively low incidence of trauma. The objective of this study is to review the presentation and outcomes for the low volume of patients presenting with penetrating injuries in a high-volume hospital.

Methods

Data were extracted from the Singapore General Hospital database between 1998 and 2007. There were 1,233 patients who sustained penetrating injuries and were brought to the hospital during the 10-year period. Of these, only 78 patients had injury severity score (ISS) values of 16 or more. In the same period, there were 1,270 patients with ISS > 15 who were admitted with blunt injury. SPSS 10.1 was used to conduct univariate and multivariate analyses to elucidate risk factors for mortality.

Results

Age, ISS, and trauma injury severity score (TRISS) were significant predictors of mortality. Gender and type of injury were not predictive of mortality. Mortality outcomes were independently predicted by age, TRISS, and ISS. The most common site of injury was the chest, followed closely by the head and neck. The abdomen/pelvis was the third most common site of injury. There was no significant difference in anatomical site injury pattern between the survivors and non-survivors. For both groups, chest injuries and head and neck injuries dominated, with maximal abdominal/pelvic injuries a distant third.

Conclusion

With a trauma system in place, high-volume centers with a low volume of penetrating injury patients can still manage uncommon injuries without jeopardizing patient care.     

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR)?=?1.43, 95?% confidence interval (CI)?=?1.26?C1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR?=?1.39, 95?% CI?=?1.20?C1.61) and ER-negative (per-allele OR?=?1.55, 95?% CI?=?1.28?C1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14?C1.68), 1.48 (1.25?C1.74), and 1.58 (1.28?C1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95?% CI) of 1.26 (1.12?C1.43) at rs1219648, 1.22 (1.07?C1.38) at rs2981582, 1.21 (1.07?C1.36) at rs2981579, and 1.18 (1.04?C1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95?% CI) of 1.16 (1.00?C1.34), 1.15 (1.02?C1.29), and 1.15 (1.01?C1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90?% for those with a combination of 6 or more risk alleles, compared to patients with ??3 risk alleles.     

Unconventional techniques of fundus imaging: A review

The methods of fundus examination include direct and indirect ophthalmoscopy and imaging with a fundus camera are an essential part of ophthalmic practice. The usage of unconventional equipment such as a hand-held video camera, smartphone, and a nasal endoscope allows one to image the fundus with advantages and some disadvantages. The advantages of these instruments are the cost-effectiveness, ultra portability and ability to obtain images in a remote setting and share the same electronically. These instruments, however, are unlikely to replace the fundus camera but then would always be an additional arsenal in an ophthalmologist''s armamentarium.