Epithelial-mesenchymal transition profiles in triple negative breast carcinoma may explain its aggressive nature.

Epithelial-mesenchymal transition (EMT) is increasingly explored in cancer progression. Considering that triple negative (TN) breast cancer has the poorest survival among molecular subtypes, we investigated 49 TN, 45 luminal and 25 HER2-enriched female breast carcinomas for EMT expression (using E-cadherin and vimentin immunohistochemistry) against lymphovascular and/or lymph node invasion. E-cadherin and vimentin expressions were semi-quantitated for positive- cancer cells (0=0-<1%, 1=1-10%, 2 =11-50%, 3=>50%) and staining intensity (0=negative, 1=weak, 2=moderate, 3=strong), with final score (low=0-4 and high=6-9) derived by multiplying percentage and intensity scores for each marker. Low E-cadherin and/or high vimentin scores defined EMT positivity. Low E-cadherin co-existing with high vimentin defined "complete" (EMT-CV), while low E-cadherin (EMT-C) or high vimentin (EMT-V) occurring independently defined "partial" subsets. 38 (31.9%) cancers expressed EMT, while 59.2 % TN, 13.3% luminal and 12% HER2-enriched cancers expressed EMT (p<0.05). Among the cancers with lymphovascular and/or lymph node invasion, EMT positivity by molecular types were 66.7% TN, 7.4% luminal and 11.8% HER2-enriched (p<0.05). Although EMT-V, associated with stem-cell properties was the dominant TN EMT profile, EMT-CV, a profile linked to vascular metastases, was encountered only in TN. EMT appears important in TN cancer and different EMT profiles may be associated with its aggressive nature.

Failure of sterilization in a dental outpatient facility: Investigation, risk assessment, and management.

In 2017, an incident of failed sterilization of dental instruments occurred at a large dental outpatient facility in Singapore. We aim to describe findings of the investigation of the sterilization breach incident, factors related to risk of viral transmission to the potentially affected patients, and the contact tracing process, patient management, and blood test results at a 6-month follow-up. A full assessment of the incident was immediately carried out. The factors related to risk of viral transmission due to affected instruments were analyzed using 3 keys points: breached step(s) and scale of the incident, prevalence of underlying bloodborne diseases and immunity in the Singapore population, health status of potential source patients, and type of dental procedure performed, and health status of affected patients and type of dental procedure received. Up to 72 affected instrument sets were used in 714 potentially affected patients who underwent noninvasive dental procedures. The investigation revealed that there was a lapse in the final step of steam sterilization, resulting in the use of incompletely sterilized items. The assessment determined that there was an extremely low risk of bloodborne virus transmission of diseases to the patients. At the 6-month follow-up, there were no infected/colonized cases found related to the incident. Lapses in the sterilization process for medical and dental instruments can happen, but a risk assessment approach is useful to manage similar incidents. Quick response and proper documentation of the sterilization process can prevent similar incidents.

FISHing for 1p19q codel in oligodendroglioma.

Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting.

Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing.

Effect of staining beverages on color and translucency of CAD/CAM composites.

This study investigated the color (ΔE) and translucency changes (ΔTP) of CAD/CAM composites after exposure to staining solutions using both spectrophotometer and shade-matching device. Direct (Filtek Z350XT [ZT]), indirect (Shofu Ceramage [CE]) and CAD/CAM (Shofu HC Block [HC], Lava Ultimate [LU], Vita Enamic [EN]) composite specimens measuring 12 × 14 × 1.5 mm were fabricated, divided into five groups (n = 8), and immersed in cola, tea, coffee, red wine, distilled water (control) at 37°C for 7 days. Color parameters were determined with both spectrophotometer and shade-taking device at baseline and 1 week. Delta E (ΔE) with white and black backgrounds, and Delta TP (ΔTP) were computed. Statistical testing was performed with ANOVA and Tukey post hoc test (P < .05). Mean ΔE (white) values ranged from 0.20 ± 0.06 to 12.26 ± 1.95 while mean ΔE (black) varied from 0.22 ± 0.11 to 14.21 ± 2.37. Mean ΔTP values ranged from 0.13 ± 0.17 to -3.87 ± 2.16. CAD/CAM composites fared better in red wine than direct and indirect materials. Clinically perceptible color changes (ΔE > 3.3) were observed for almost all materials when exposed to wine, coffee and tea. Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine caused the most discoloration and translucency changes. Limitations of these materials must be considered when placing an aesthetic restoration. CLINICAL SIGNIFICANCE: Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine generally caused the most discoloration and translucency changes. Although CAD/CAM composites were more color stable than direct and indirect materials when exposed to red wine, color changes were still clinically perceptible.

Intrapancreatic accessory spleen: An eluding diagnosis.

Intrapancreatic accessory spleen (IPAS) is a benign anomaly of splenic embryology and a rare cause of pancreatic pseudotumour. Here, we report a case of a 70-year-old Malay lady whose IPAS was discovered incidentally during her surveillance computed tomography for her underlying left lower lung fibrosis. Radiologically, the lesion mimicked a neuroendocrine pancreatic tumour and was only diagnosed pathologically as IPAS after surgery. In conclusion, recognising IPAS as a differential for enhancing pancreatic mass allows us to exhaust all non-invasive diagnostic means to diagnose this benign lesion. It will allow the patient to avoid unnecessary surgery and its accompanying complications.

Three-Dimensional Accuracy of Digital Implant Impressions: Effects of Different Scanners and Implant Level.

PURPOSE: To compare the three-dimensional (3D) accuracy of conventional direct implant impressions with digital implant impressions from three intraoral scanners, as well as different implant levels-bone level (BL) and tissue level (TL). MATERIALS AND METHODS: Two-implant master models were used to simulate a threeunit implant-supported fixed dental prosthesis. Conventional test models were made with direct impression copings and polyether impressions. Scan bodies were hand-tightened onto master models and scanned with the three scanners. This was done for the TL and BL test groups, for a total of eight test groups (n = 5 each). A coordinate measuring machine measured linear distortions (dx, dy, dz), global linear distortion (dR), angular distortions (dθy, dθx), and absolute angular distortions (Absdθy, Absdθx) between the master models, test models, and .stl files of the digital scans. RESULTS: The mean dR ranged from 35 to 66 µm; mean dθy angular distortions ranged from -0.186 to 0.315 degrees; and mean dθx angular distortions ranged from -0.206 to 0.164 degrees. Two-way analysis of variance showed that the impression type had a significant effect on dx, dz, and Absdθy, and the implant level had a significant effect on dx and Absdθx (P < .05). Among the BL groups, the mean dR of the conventional group was lower than and significantly different from the digital test groups (P = .010), while among the TL groups, there was no statistically significant difference (P = .572). CONCLUSION: The 3D accuracy of implant impressions varied according to the impression technique and implant level. For BL test groups, the conventional impression group had significantly lower distortion than the digital impression groups. Among the digital test groups, the TR system had comparable mean linear and absolute angular distortions to the other two systems but exhibited the smallest standard deviations.

Metallosis following implantation of magnetically controlled growing rods in the treatment of scoliosis: a case series.

AIMS: We present a case series of five patients who had revision surgery following magnetic controlled growing rods (MGCR) for early onset scoliosis. Metallosis was found during revision in four out of five patients and we postulated a mechanism for rod failure based on retrieval analysis. PATIENTS AND METHODS: Retrieval analysis was performed on the seven explanted rods. The mean duration of MCGR from implantation to revision was 35 months (17 to 46). The mean age at revision was 12 years (7 to 15; four boys, one girl). RESULTS: A total of six out of seven rods had tissue metallosis and pseudo-capsule surrounding the actuator. A total of four out of seven rods were pistoning. There were two rods which were broken. All rods had abrasive circumferential markings. A significant amount of metal debris was found when the actuators were carefully cut open. Analytical electron microscopy demonstrated metal fragments of predominantly titanium with a mean particle size of 3.36 microns (1.31 to 6.61). CONCLUSION: This study highlights concerns with tissue metallosis in MCGR. We recommend careful follow-up of patients who have received this implant. Cite this article: Bone Joint J 2016;98-B:1662-7.

ERRATUM: Phyllodes tumours of the breast: retrospective analysis of a University Hospital's experience.

No abstract available.

Phyllodes tumours of the breast: retrospective analysis of a University Hospital's experience.

Taking cognizance of the purported variation of phyllodes tumours in Asians compared with Western populations, this study looked at phyllodes tumours of the breast diagnosed at the Department of Pathology, University of Malaya Medical Centre over an 8-year period with regards to patient profiles, tumour parameters, treatment offered and outcome. Sixty-four new cases of phyllodes tumour were diagnosed during the period, however only 30 (21 benign, 4 borderline and 5 malignant) finally qualified for entry into the study. These were followed-up for 4-102 months (average = 41.7 months). Thirteen cases (8 benign, 3 borderline, 2 malignant) were Chinese, 9 (all benign) Malay, 7 (4 benign, 1 borderline, 2 malignant) Indian and 1 (malignant) Indonesian. Prevalence of benign versus combined borderline and malignant phyllodes showed a marginally significant difference (p=0.049) between the Malays and Chinese. Patients' ages ranged from 21-70 years with a mean of 44.9 years with no significant difference in age between benign, borderline or malignant phyllodes tumours. Except for benign phyllodes tumours (mean size = 5.8 cm) being significantly smaller at presentation compared with borderline (mean size = 12.5 cm) and malignant (mean size = 15.8 cm) (p<0.05) tumours, history of previous pregnancy, breast feeding, hormonal contraception and tumour laterality did not differ between the three categories. Family history of breast cancer was noted in 2 cases of benign phyllodes. Local excision was performed in 17 benign, 2 borderline and 3 malignant tumours and mastectomy in 4 benign, 2 borderline and 2 malignant tumours. Surgical clearance was not properly recorded in 10 benign phyllodes tumours. Six benign and all 4 borderline and 5 malignant tumours had clearances of <10 mm. Two benign tumours recurred locally at 15 and 49 months after local excision, however information regarding surgical clearance was not available in both cases. One patient with a malignant tumour developed a radiologically-diagnosed lung nodule 26 months after mastectomy, was given a course of radiotherapy and remained well 8-months following identification of the lung nodule.

Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia.

Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

Orbital implant placement using a computer-aided design and manufacturing (CAD/CAM) stereolithographic surgical template protocol.

Surgical implant placement in the orbital region for the support of a prosthesis is challenging due to the thin orbital rim and proximity to vital structures. This article reports the use of a computer-aided design and manufacturing (CAD/CAM) stereolithographic surgical template protocol for orbital implant placement in four patients, who were followed-up for about 7 years. A total of 11 orbital implants were inserted, eight of these in irradiated bone. No intraoperative complications were noted in any of the patients and the implants were all inserted in the planned positions. The survival rate of implants placed in irradiated bone that received hyperbaric oxygen therapy was 62.5% (5/8). One implant failed in a burns injury patient at 74 months after functional loading. The overall survival of implants in the orbital region and the cumulative survival at 7 years was 63.6%. With regard to skin reactions around the abutments, 85% were grade 0, 13% were grade 1, and 2% were grade 2 according to the Holgers classification. The mean survival time of the first prosthesis was 49 months. High patient satisfaction was achieved with the implant-retained orbital prostheses.

Three-dimensional accuracy of a digitally coded healing abutment implant impression system.

PURPOSE: This study examined the three-dimensional (3D) accuracy of the Encode Impression System (EN) in transferring the locations of two implants from master models to test models and compared this to the direct impression (DI) technique. The effect of interimplant angulation on the 3D accuracy of both impression techniques was also evaluated. MATERIALS AND METHODS: Seven sectional polymethyl methacrylate mandibular arch master models were fabricated with implants in the first premolar and first molar positions. The implants were placed parallel to each other or angulated mesiodistally or buccolingually with total divergent angles of 10, 20, or 30 degrees. Each master model was secured onto an aluminum block containing a gauge block, which defined the local coordinate references. Encode healing abutments were attached to the implants before impressions were made for the EN test models; pickup impression copings were attached for the DI test models. For the seven test groups of each impression technique, a total of 70 test models were fabricated (n = 5). The EN test models were sent to Biomet 3i for implant analog placement. The centroid of each implant or implant analog and the angular orientation of the long axis relative to the x- and y-axes were measured with a coordinate measuring machine. Statistical analyses were performed. RESULTS: Impression technique had a significant effect on y distortion, global linear distortion, and absolute xz and yz angular distortions. Interimplant angulation had significant effects on x and y distortions. However, neither impression technique nor interimplant angulation had a significant effect on z distortion. CONCLUSIONS: Distortions were observed with both impression techniques. However, the results suggest that EN was less accurate than DI.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Perception of quality of life amongst end stage renal failure patients undergoing haemodialysis.

AIMS: The objective of the study was to examine the quality of life amongst the end stage renal disease (ESRD) haemodialysis patients in Malaysia. MATERIALS AND METHODS: A cross sectional descriptive study was conducted on 72 ESRD patients at a Dialysis Centre in Malaysia. The modified KDQOL-SF™ subscales, kidney disease-targeted scale and 36 item health survey scale questionnaires were used. RESULTS: The overall health rating was 66.73 ± 11.670 indicating good quality of life. There was no significant difference between quality of life for the different domains according to gender (p >0.05). However, there were significant differences between quality of life in the domain of burden of kidney disease. Physical functioning deteriorated significantly with age (p=0.012) while social functioning was lowest in the 50-65 years age group (p=0.037). Those who had no morbidities had significantly better scores on the effects of kidney (p=0.036), burden of kidney disease (p=0.011) and physical functioning (p=0.025). CONCLUSIONS: Patients undergoing haemodialysis have been found to have good quality of life despite having ESRD. It is therefore of paramount importance to constantly monitor the standard of care for these patients to enable them to live their life to the fullest.

Retention of forearm plates: risks and benefits in a paediatric population.

Most surgeons favour removing forearm plates in children. There is, however, no long-term data regarding the complications of retaining a plate. We present a prospective case series of 82 paediatric patients who underwent plating of their forearm fracture over an eight-year period with a minimum follow-up of two years. The study institution does not routinely remove forearm plates. A total of 116 plates were used: 79 one-third tubular plates and 37 dynamic compression plates (DCP). There were 12 complications: six plates (7.3%) were removed for pain or stiffness and there were six (7.3%) implant-related fractures. Overall, survival of the plates was 85% at 10 years. Cox regression analysis identified radial plates (odds ratio (OR) 4.4, p = 0.03) and DCP fixation (OR 3.2, p = 0.02) to be independent risk factors of an implant-related fracture. In contrast ulnar plates were more likely to cause pain or irritation necessitating removal (OR 5.6, p = 0.04). The complications associated with retaining a plate are different, but do not occur more frequently than the complications following removal of a plate in children.

Total hip replacement in morbidly obese patients with osteoarthritis: results of a prospectively matched study.

We compared 55 consecutive total hip replacements performed on 53 morbidly obese patients with osteoarthritis with a matched group of 55 total hip replacements in 53 non-obese patients. The groups were matched for age, gender, prosthesis type, laterality and preoperative Harris Hip Score. They were followed prospectively for five years and the outcomes were assessed using the Harris Hip Score, the Short-form 36 score and radiological findings. Survival at five years using revision surgery as an endpoint, was 90.9% (95% confidence interval 82.9 to 98.9) for the morbidly obese and 100% for the non-obese patients. The Harris Hip and the Short-form 36 scores were significantly better in the non-obese group (p < 0.001). The morbidly obese patients had a higher rate of complications (22% vs 5%, p = 0.012), which included dislocation and both superficial and deep infection. In light of these inferior results, morbidly obese patients should be advised to lose weight before undergoing a total hip replacement, and counselled regarding the complications. Despite these poorer results, however, the patients have improved function and quality of life.

Malignant peripheral nerve sheath tumour in the ischio-rectal fossa.

Primary sarcomas in the ischiorectal fossa are occasionally reported and represent a significant challenge due to the proximity of rectum, levator muscles and pudendal neurovascular structures. We report a case in which the diagnosis changed between biopsy (desmoid tumour) and resection (malignant peripheral nerve sheath tumour), requiring a multidisciplinary surgical approach involving different sub-specialties. It also illustrates the importance of undertaking sarcoma surgery in a recognized sarcoma centre with sarcoma expertise available across a range of disciplines.

Continuing professional development for surgeons.

With the introduction of revalidation, continuing professional development (CPD) is becoming an increasingly important part of a surgeon's professional life. There is minimal existing information describing the CPD practices and attitudes of surgeons to CPD. This review describes the current CPD expectations of the General Medical Council and the current CPD activities and attitudes of surgeons, based around the results of an on-line study performed by the Royal College of Surgeons of Edinburgh.