Microglandular adenosis: a prime suspect in triple‐negative breast cancer development

Microglandular adenosis (MGA) and atypical MGA (AMGA) are unusual lesions of the breast. They were once regarded as benign proliferative lesions and innocent bystanders. Several lines of evidence suggested that they could be neoplastic, clonal lesions and a non‐obligate precursor for triple‐negative breast cancers (TNBC). Recent work published in The Journal of Pathology by Guerini‐Rocco and colleagues provided further evidence regarding the precursor–product relationship between MGA/AMGA and TNBC. Using a massively parallel sequencing approach, they demonstrated that MGA/AMGA, particularly those associated with TNBC, could be clonal neoplastic lesions showing clonal non‐synonymous mutations, but none in pure MGA. Importantly, those alterations were observed in the associated TNBC. They were also able to identify recurrent alterations in TP53 in those MGA/AMGA cases as well as their associated TNBC. The findings, in conjunction with others, underscore the significance for MGA in clinical diagnosis. The potential of a benign lesion to progress into an aggressive malignant tumour implies that modification of the current management approach may be necessary. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The main trends in a complex program of rehabilitation of children with oncological diseases

The present-day therapeutical programmes allow physicians to cure as many as 70% of children with malignant neoplasms, in some tumor forms, the proportion of recovered children is much higher, which shows it urgent to elaborate comprehensive rehabilitation programmes required for the effective integration of prior patients of children's cancer clinics into a group. The paper presents a complex rehabilitation programme worked out at the Research Institute of Pediatric Oncology and Hematology, Russian Cancer Research Center, Russian Academy of Medical Sciences. The basic directions of the programme are medical, psychological, pedagogical, and social rehabilitation. For medical rehabilitation, phytotherapy, medical laser, climate therapy, and therapeutical exercises are widely used. Of particular value are physical and recreational activities, which include the use of therapeutical exercises, active recreational activities, participation in sporting events, and conditioning swimming. Psychological and pedagogical rehabilitation is aimed at solving personality and familial problems, at developing intellectual abilities, and at eliminating steady-state bad habits and behavioral deviations. A psychological and pedagogical programme is based on the work of art-therapeutical shops where a child realizes his/her strivings, which promotes the recovery of his/her mental and social status. The work of psychologists and psychotherapeutists with children's parents occupies a highly important place since correction of child-parent relations serves as a necessary basis for mental recovery in a child. The most important factor of social rehabilitation is an educational programme aimed at acquiring knowledge and at stimulating cognitive activities. To implement the comprehensive programme increases life quality in children who have sustained cancer diseases, improves their social adaptation and thus facilitates integration of these children in society.     

AngleNav: MEMS Tracker to Facilitate CT-Guided Puncture

As a low-cost needle navigation system, AngleNav may be used to improve the accuracy, speed, and ease of CT-guided needle punctures. The AngleNav hardware includes a wireless device with a microelectromechanical (MEMS) tracker that can be attached to any standard needle. The physician defines the target, desired needle path and skin entry point on a CT slice image. The accuracy of AngleNav was first tested in a 3D-printed calibration platform in a benchtop setting. An abdominal phantom study was then performed in a CT scanner to validate the accuracy of the device’s angular measurement. Finally, an in vivo swine study was performed to guide the needle towards liver targets (n = 8). CT scans of the targets were used to quantify the angular errors and needle tip-to-targeting distance errors between the planned needle path and the final needle position. The MEMS tracker showed a mean angular error of 0.01° with a standard deviation (SD) of 0.62° in the benchtop setting. The abdominal phantom test showed a mean angular error of 0.87° with an SD of 1.19° and a mean tip-to-target distance error of 4.89 mm with an SD of 1.57 mm. The animal experiment resulted in a mean angular error of 6.6° with an SD of 1.9° and a mean tip-to-target distance error of 8.7 mm with an SD of 3.1 mm. These results demonstrated the feasibility of AngleNav for CT-guided interventional workflow. The angular and distance errors were reduced by 64.4 and 54.8% respectively if using AngleNav instead of freehand insertion, with a limited number of operators. AngleNav assisted the physicians to deliver accurate needle insertion during CT-guided intervention. The device could potentially reduce the learning curve for physicians to perform CT-guided needle targeting.     

颅脑有限元模型演化规律及其生物力学研究进展

交通事故中头颈部损伤因其较高的致命性,已成为最严重的损伤类型。有限元模型在创伤性脑损伤生物力学机理研究中得到日益广泛应用。回顾头颈部有限元模型的生物力学研究历史和现状,并阐述车辆碰撞交通事故中人体颅脑典型交通伤演化规律和生物力学研究进展,探索头颈部损伤安全防护的方法,以期为车辆碰撞事故中人体颅脑损伤生物力学研究和相应的汽车安全防护装置研制提供理论依据。     

Clonal evolution of high‐grade serous ovarian carcinoma from primary to recurrent disease

High‐grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum‐ and taxane‐based chemotherapy, the majority of patients experience recurrence of treatment‐resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.     

Climacteric symptoms and knowledge about hormone replacement therapy among Hong Kong Chinese women aged 40-60 years

OBJECTIVES: To evaluate the use of hormone replacement therapy (HRT), the prevalence of climacteric symptoms, and the knowledge about HRT. METHODS: A prospective study was conducted by telephone interview among a randomly selected population-based sample of 978 Hong Kong Chinese women aged 40-60 years. RESULTS: Of 414 women with a history of either natural or surgical menopause, 22 (5.3%) and 17 (4.1%), respectively, were either past or current users of HRT. The climacteric symptom scores of premenopausal women were significantly lower than those of perimenopausal women, but were comparable with those of postmenopausal women. The commonest climacteric symptom was 'muscle and joint pains' which was reported in 553 (56.6%) women, while only 228 (23.3%) and 151 (15.4%) women reported hot flushes and night sweating, respectively. Moreover, only 230 (23.5%) women realized that HRT could relieve menopausal symptoms and only 33 (3.4%) women were aware that HRT was protective against osteoporosis. In general, women with more climacteric symptoms, who had ever used HRT, and those with higher education level and higher family income, had better knowledge about HRT. CONCLUSIONS: Postmenopausal Hong Kong Chinese women have a low HRT usage rate and the majority of them are lacking of the knowledge about HRT.     

Multilocus Sequence Types of Carbapenem-Resistant Pseudomonas aeruginosa in Singapore Carrying Metallo-β-Lactamase Genes,Including the Novel blaIMP-26 Gene

Nine imipenem-resistant Pseudomonas aeruginosa isolates were found to contain a variety of metallo-β-lactamase genes, including bla_IMP-1, bla_IMP-7, bla_VIM-2, bla_VIM-6, and the novel bla_IMP-26. Multilocus sequence typing showed a diversity of sequence types. Comparison with isolates from an earlier study showed that the epidemic clones from 2000 have not become established.Carbapenem-resistant Pseudomonas aeruginosa is an increasing problem worldwide. While many underlying mechanisms may account for carbapenem resistance in this species, the possession of metallo-β-lactamase (MBL) genes is of particular concern because these enzymes are able to hydrolyze all β-lactam antimicrobials with the exception of aztreonam. In addition, these genes may be mobilized and transferred between different species of bacteria. We conducted a study in 2008 to investigate if there were any changes in the epidemiology of P. aeruginosa isolates containing MBL genes in our hospital compared to results from an earlier survey carried out in 2000 (3).Of 2,552 nonduplicate P. aeruginosa organisms isolated in 2008, 123 isolates were imipenem resistant. Of these, 11 were positive for MBL production by imipenem-EDTA disk diffusion (5). Nine of these yielded a product by multiplex PCR for MBL genes (2). The individual MBL genes were then amplified and sequenced. The clonal relationship between isolates with MBL genes was determined by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA restricted with SpeI (3). The PFGE band patterns were analyzed with Bionumerics (Applied Maths NV, Sint-Martens-Latem, Belgium), and all strains with more than 85% similarity were considered to belong to the same clone. All strains were further subjected to multilocus sequence typing (MLST) (1). Because it is a nucleic acid sequence-based method, MLST is able to characterize bacterial types in an unambiguous fashion and establish evolutionary relationships between strains better than band-based methods like PFGE. Representative MBL-producing P. aeruginosa isolates from the 2000 survey were also subjected to PFGE and MLST. MLST profiles were submitted to eBURST V3 (http://eburst.mlst.net/) on 10 March 2010. Isolates sharing six out of seven alleles were assigned to the same BURST group and can be considered to belong to the same clonal complex descended from a common founder genotype. The PFGE, MBL gene sequence, and MLST results are summarized in Fig. ​Fig.11.Open in a separate windowFIG. 1.Dendrogram of PFGE patterns of P. aeruginosa isolates with metallo-β-lactamase genes, showing the year of isolation, MLST sequence type, and BURST group.In our previous study, 21 of 2,094 (1.0%) of all nonduplicate P. aeruginosa isolates in our hospital had MBL genes (3). With the exception of one isolate with bla_IMP-7, all other isolates had bla_IMP-1 and belonged to one of two PFGE clones. Isolates belonging to clone A had sequences identical to that of the original bla_IMP-1 first reported in Japan. Four representatives of clone A isolated from our hospital in 2000 had sequence type 964 (ST964) by MLST. Isolates belonging to clone B isolated in 2000 had sequences for variant bla_IMP-1 (bla_IMP-1v) with four silent mutations. Three representatives of this clone from 2000 had ST233 and one had ST742 based on MLST. All four representatives of clone B belong to the same BURST group, which was different from that of clone A.In contrast, in the 2008 survey, 9 of 2,552 (0.35%) nonduplicate P. aeruginosa isolates had MBL genes. Unlike the earlier study, there were no large clonal outbreaks. Two isolates with bla_IMP-1v had similar PFGE patterns and belonged to the same BURST group as representative isolates from clone B in 2000.Two isolates from 2008 with bla_IMP-7 had similar PFGE patterns and shared the same BURST group. The rest of the isolates from 2008 had distinct PFGE patterns.There was a greater diversity of MBL genes compared to the 2000 survey results. In particular, this is the first time that bla_VIM-2 and bla_VIM-6 have been found in P. aeruginosa in Singapore. bla_IMP-26 is a novel MBL gene that differs from bla_IMP-4 at position 145 (G-to-T change). The translated amino acid sequence differs from IMP-4 at residue 49 (phenylalanine for valine). This sequence has been previously deposited in the GenBank database as IMP-4 from an Acinetobacter calcoaceticus isolate from Malaysia (accession number {"type":"entrez-protein","attrs":{"text":"ABC24668.1","term_id":"83583501"}}ABC24668.1).Three of the isolates in this study (separately containing bla_VIM-2, bla_IMP-1, and bla_IMP-7) belonged to ST235. This sequence type has been described in a VIM-producing P. aeruginosa isolate in Belgrade and is the founder of an international clonal complex of isolates bearing MBL genes found in several countries in Europe (6). Recently, an increasing prevalence of IMP-1-producing P. aeruginosa has been found in Hiroshima, Japan. This was due entirely to the clonal expansion of only two lineages, ST235 (BURST group 3) and ST357 (BURST group 108) (4). This is similar to the situation that existed in Singapore in 2000, where only two lineages (BURST groups 29 and 44) accounted for the majority of MBL-producing P. aeruginosa (3).It is noteworthy that the original fear that a clone of MBL-producing P. aeruginosa would become established in Singapore has not been realized. The BURST group 29 and 44 lineages from 2000 were represented by only one to two isolates in 2008. The two P. aeruginosa isolates with bla_IMP-7 in 2008 are unrelated to the solitary isolate with bla_IMP-7 from 2000. It has been suggested that P. aeruginosa displays an epidemic population structure, with a limited number of clones emerging from a large number of unrelated genotypes (7). Although we did not correlate our study with hospital infection control measures, the Japanese data and our own seem to suggest that controlling the prevalence of MBL-producing P. aeruginosa may be achieved by preventing the transmission of specific epidemic clones.While it is reassuring to note that the prevalence of MBL producers in carbapenem-resistant P. aeruginosa has not increased, the increased diversity of MBL genes represents a new cause for concern. We were unable to characterize the gene responsible for the MBL phenotype in two isolates in this study, and these may represent novel resistance determinants. Although clones of MBL-producing P. aeruginosa have not become established, it seems likely, given the variation of MBL genes and MLST types in this study, that MBL-producing P. aeruginosa continues to be introduced to our hospital from diverse sources.     

Clinical and molecular epidemiology of erythromycin-resistant beta-hemolytic lancefield group G streptococci causing bacteremia

Among 100 patients with group G beta-hemolytic streptococcal bacteremia in a 6-year period (1997 to 2002), seven had bacteremia caused by erythromycin-resistant strains. Five of the seven patients had cellulitis and/or abscesses. The two isolates resistant to erythromycin and clindamycin possessed erm genes, one ermTR and the other ermB. The five isolates resistant to erythromycin but sensitive to clindamycin and one of those resistant to both erythromycin and clindamycin possessed mef genes.