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1.
Anaesthesia ; 78(5): 561-570, 2023 05.
Article in English | MEDLINE | ID: mdl-36723442

ABSTRACT

Pre-operative risk stratification is a key part of the care pathway for emergency bowel surgery, as it facilitates the identification of high-risk patients. Several novel risk scores have recently been published that are designed to identify patients who are frail or significantly unwell. They can also be calculated pre-operatively from routinely collected clinical data. This study aimed to investigate the ability of these scores to predict 30-day mortality after emergency bowel surgery. A single centre cohort study was performed using our local data from the National Emergency Laparotomy Audit database. Further data were extracted from electronic hospital records (n = 1508). The National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score were then calculated. The most abnormal National or Laboratory Decision Tree Early Warning Score in the 24 or 72 h before surgery was used in analysis. Individual scores were reasonable predictors of mortality (c-statistic 0.699-0.740) but all were poorly calibrated. A National Early Warning Score ≥ 4 was associated with a high overall mortality rate (> 10%). A logistic regression model was developed using age, National Early Warning Score, Laboratory Decision Tree Early Warning Score and Hospital Frailty Risk Score as predictor variables, and its performance compared with other established risk models. The model demonstrated good discrimination and calibration (c-statistic 0.827) but was marginally outperformed by the National Emergency Laparotomy Audit score (c-statistic 0.861). All other models compared performed less well (c-statistics 0.734-0.808). Pre-operative patient vital signs, blood tests and markers of frailty can be used to accurately predict the risk of 30-day mortality after emergency bowel surgery.


Subject(s)
Frailty , Humans , Cohort Studies , Retrospective Studies , Risk Assessment , Hospital Mortality
2.
J Laryngol Otol ; 136(1): 91-93, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34823613

ABSTRACT

BACKGROUND: Migrated ingested foreign bodies in the aerodigestive tract can lodge within vital organs and vessels, causing potentially devastating complications. It is often difficult to localise these foreign bodies, with extrication resulting in the requirement for open approaches which may cause significant morbidity. CASE REPORT: This paper presents the case of an ingested migrated stingray bone lodged adjacent to the vertebral artery in the upper cervical spine. This was managed via an endoscopic transoral approach, with the assistance of an image-guidance system. RESULTS: Successful extraction of the foreign body was achieved, with minimal residual morbidity. CONCLUSION: Our study showed that image-guided endoscopic surgery is a safe, precise and feasible option for the localisation and removal of migrated foreign bodies in the aerodigestive tract involving critical neurovascular structures.


Subject(s)
Cervical Vertebrae , Foreign-Body Migration/surgery , Natural Orifice Endoscopic Surgery , Humans , Male , Middle Aged , Mouth
3.
Med J Malaysia ; 76(3): 414-416, 2021 05.
Article in English | MEDLINE | ID: mdl-34031342

ABSTRACT

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.


Subject(s)
Fusion Proteins, bcr-abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Fusion Proteins, bcr-abl/genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Neoplasm Recurrence, Local , Protein Kinase Inhibitors/therapeutic use , Treatment Outcome
4.
Ann R Coll Surg Engl ; 103(3): 180-185, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33645274

ABSTRACT

INTRODUCTION: The UK has an ageing population with an increased prevalence of frailty in the over 70s. Emergency laparotomy for acute intra-abdominal pathology is increasingly offered to this population. This can challenge decision making and information given to patients should not only be based on mortality outcomes but on relative expected quality of life and change to frailty syndromes. MATERIALS AND METHODS: This was a single site National Emergency Laparotomy Audit (NELA)-based retrospective cohort audit for consecutive cases in the septuagenarian population assessing mortality, length of stay outcome and subjective postoperative functioning. Follow-up was conducted between one and two years postoperatively to determine this. RESULTS: Some 153 patients were identified throughout the single site NELA database. Median age was 79 years with a ratio of 1.7 men to women. Median rate of all-cause mortality was 35.3% at the median follow-up of 19 months. Median time from admission to death was 120 days. Of those who had died by the time of follow-up, significant preoperative indicators included clinical frailty scale (p < 0.0001), preoperative P-POSSUM (mortality). At follow-up, 35% responded to a quality of life follow-up. This revealed a decline in mid-term physical functioning, lower energy, higher fatigue and reduction in social functioning. There was also an increase in pre- and postoperative clinical frailty scale score. CONCLUSION: In the septuagenarian-plus population it is important to consider not only risk stratification with mortality scoring (P-POSSUM or NELA-adjusted risk), but to take into account frailty. Postoperative rehabilitation and careful recovery is paramount. Where possible, during the counselling and consent for emergency laparotomy, significant postoperative long-term deterioration in physical, emotional and social function should be considered.


Subject(s)
Emergencies , Frailty/epidemiology , Functional Status , Hospital Mortality , Laparoscopy , Laparotomy , Length of Stay , Quality of Life , Aged , Aged, 80 and over , Cohort Studies , Fatigue , Female , Follow-Up Studies , Frail Elderly , Humans , Male , Retrospective Studies , Social Interaction , United Kingdom/epidemiology
5.
Ann R Coll Surg Engl ; 102(8): 611-615, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32735121

ABSTRACT

INTRODUCTION: Laparoscopic anti-reflux surgery is the standard surgical treatment for gastro-oesophageal reflux disease in patients for who long-term pharmacotherapy is intolerable or ineffective. Advances in anaesthesia and minimally invasive surgery have led to day case treatment being adopted by some centres. The objective of this study is to describe our day case pathway and peri- and postoperative outcomes. MATERIALS AND METHODS: This is a single centre, retrospective case series review of a prospectively collected database from October 2014 to August 2019 performed in a tertiary centre for upper gastrointestinal surgery. Data collected included demographics, comorbidities, indications, complications, length of stay and readmission. RESULTS: A total of 362 patients underwent laparoscopic anti-reflux surgery with or without hiatus hernia repair of up to 10cm, with day case rates of 59%. Unplanned admission following day surgery was 5.1% (13/225) and 30-day readmission was 2.2% (8/362); 90.6% of patients remained in hospital for less than 24 hours. There was one intraoperative complication and one patient required revisional surgery within 30 days. The rate of all postoperative complications was 1.38% (5/362) with one postoperative mortality. DISCUSSION: The inclusion of larger hernias is unusual, as most studies limit size to 5cm or less. Our results show the safety and feasibility of the procedure even when applied to hiatus hernias up to 10cm. Success was multifactorial and based on standardisation of procedures and support from dedicated specialist nursing staff. CONCLUSION: Laparoscopic anti-reflux surgery can be performed safely as a day case procedure even in larger hiatus hernias, with a dedicated care pathway and specialist nurse practitioners to support it.


Subject(s)
Hernia, Hiatal/epidemiology , Hernia, Hiatal/surgery , Herniorrhaphy , Adult , Aged , Aged, 80 and over , Cost Savings/statistics & numerical data , Gastroesophageal Reflux/etiology , Hernia, Hiatal/complications , Herniorrhaphy/adverse effects , Herniorrhaphy/economics , Herniorrhaphy/methods , Herniorrhaphy/statistics & numerical data , Humans , Middle Aged , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome , United Kingdom , Young Adult
6.
Head Neck ; 42(10): 2779-2781, 2020 10.
Article in English | MEDLINE | ID: mdl-32621399

ABSTRACT

Respiratory particle generation and dispersal during nasoendoscopy and swab testing is studied with high-speed video and laser light illumination. Video analysis reveals droplet formation in three manoeuvres during nasoendoscopy - sneezing, vocalization, and nasal decongestion spray. A capillary bridge of mucus can be seen when a nasoendoscope exits wet nares. No droplet formation is seen during oral and nasopharyngeal swab testing. We outline the following recommendations: pull the face mask down partially and keep the mouth covered, only allowing nasal access during nasoendoscopy; avoid nasal sprays if possible; if nasal sprays are used, procedurists should be in full personal protective equipment prior to using the spray; withdrawal of swabs and scopes should be performed in a slow and controlled fashion to reduce potential dispersion of droplets when the capillary bridge of mucus breaks up.


Subject(s)
COVID-19 Testing , Endoscopy , Mucus , Nasal Cavity , Phonation/physiology , Sneezing/physiology , Administration, Intranasal , Humans , Infection Control , Infectious Disease Transmission, Patient-to-Professional , Nasal Sprays , Personal Protective Equipment
8.
Ann R Coll Surg Engl ; 101(5): 313-317, 2019 May.
Article in English | MEDLINE | ID: mdl-30855162

ABSTRACT

INTRODUCTION: The high rate of recurrence following ileocaecal resection for Crohn's disease may lead to repeat surgery in 20-30% of patients at five years after surgery. Recurrence usually occurs at the anastomosis and the neoterminal ileum and the association of a strictureplasty to widen the bowel lumen in the regions immediately proximal ('anastomotic inlet') and distal ('anastomotic outlet') to the anastomosis may delay or reduce the risk of surgical recurrence. MATERIALS AND METHODS: A side to side isoperistaltic anastomosis, with an associated V-modified strictureplasty on the anti-mesenteric border at the level of the anastomosis inlet and outlet has been designed. We produced a wet lab ex vivo model of the anastomosis and, to evaluate the different calibre of the anastomotic segments, we compared it with ex vivo models of three anastomotic configurations currently used in surgery for Crohn's disease: i) side to side isoperistaltic anastomosis; ii) modified side-to-side isoperistaltic anastomosis with double Heineke-Mikulicz procedure (Sasaki anastomosis); iii) anti-mesenteric functional end-to-end handsewn anastomosis (Kono-S anastomosis). RESULTS: Differences were recorded at the level of the anastomosis inlet and outlet, with a larger volume estimated in the Sasaki anastomosis and in the V-modified anastomosis. The V-modified anastomosis had a larger volume compared with the Sasaki anastomosis for a longer segment of small bowel. CONCLUSIONS: We have developed an experimental animal model for a new anastomotic technique which could be applied in surgery for Crohn's disease following small-bowel or ileocolic resection.


Subject(s)
Colon/surgery , Crohn Disease/surgery , Ileum/surgery , Secondary Prevention/methods , Anastomosis, Surgical/methods , Animals , In Vitro Techniques , Recurrence
9.
Trop Biomed ; 36(1): 310-314, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-33597452

ABSTRACT

We report the presence of Zika virus RNA in naturally infected field captured Aedes aegypti and Ae. albopictus mosquito larvae in Malaysia from May 2016 to April 2017. Zika virus RNA was detected (n = 30) in the larvae of both Aedes mosquito species. Phylogenetic analysis of the NS5 partial sequence of all positive samples shows that the circulating Zika virus in the field collected larvae are of the Asian lineage.

10.
Ann R Coll Surg Engl ; 100(1): 47-51, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29046077

ABSTRACT

Introduction The misdiagnosis of appendicitis and consequent removal of a normal appendix occurs in one in five patients in the UK. On the contrary, in healthcare systems with routine cross-sectional imaging of suspected appendicitis, the negative appendicectomy rate is around 5%. If we could reduce the rate in the UK to similar numbers, would this be cost effective? This study aimed to calculate the financial impact of negative appendicectomy at the Queen Alexandra Hospital and to explore whether a policy of routine imaging of such patients could reduce hospital costs. Materials and methods We performed a retrospective analysis of all appendicectomies over a 1-year period at our institution. Data were extracted on outcomes including appendix histology, operative time and length of stay to calculate the negative appendicectomy rate and to analyse costs. Results A total of 531 patients over 5 years of age had an appendicectomy. The negative appendicectomy rate was 22% (115/531). The additional financial costs of negative appendicectomy to the hospital during this period were £270,861. Universal imaging of all patients with right iliac fossa pain that could result in a 5% negative appendicectomy rate would cost between £67,200 and £165,600 per year but could save £33,896 (magnetic resonance imaging), £105,896 (computed tomography) or £132,296 (ultrasound) depending on imaging modality used. Conclusions Negative appendicectomy is still too frequent and results in additional financial burden to the health service. Routine imaging of patients with suspected appendicitis would not only reduce the negative appendicectomy rate but could lead to cost savings and a better service for our patients.


Subject(s)
Appendicitis/diagnostic imaging , Appendicitis/economics , Adolescent , Adult , Appendectomy , Appendicitis/epidemiology , Appendicitis/surgery , Child , Cost-Benefit Analysis , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Young Adult
11.
Eur J Vasc Endovasc Surg ; 53(6): 880-885, 2017 06.
Article in English | MEDLINE | ID: mdl-28396238

ABSTRACT

BACKGROUND: The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying graduated compression stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million per year in England alone. OBJECTIVE: The aim was to determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE. METHODS: The randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial (ISRCTN 13911492) will randomise adult elective surgical patients identified as being at moderate and high risk of VTE to receive either the current "standard" combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH related complications (including bleeding). Recruitment commenced in April 2016 with the seven UK centres coming "on-line" in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK (14/140/61).


Subject(s)
Fibrinolytic Agents/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Stockings, Compression , Surgical Procedures, Operative/adverse effects , Venous Thromboembolism/prevention & control , Clinical Protocols , Combined Modality Therapy , Drug Administration Schedule , Fibrinolytic Agents/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , Research Design , Risk Factors , Time Factors , Treatment Outcome , United Kingdom , Venous Thromboembolism/diagnostic imaging , Venous Thromboembolism/etiology
12.
Int J Microbiol ; 2016: 2164761, 2016.
Article in English | MEDLINE | ID: mdl-27746817

ABSTRACT

The administration of antimicrobials in aquaculture provides a selective pressure creating a reservoir of multiple resistant bacteria in the cultured fish and shrimps as well as the aquaculture environment. The objective of this study was to determine the extent of antibiotic resistance in aquaculture products and aquaculture's surrounding environment in Sarawak, Malaysian Borneo. Ninety-four identified bacterial isolates constituted of 17 genera were isolated from sediment, water, and cultured organisms (fish and shrimp) in selected aquaculture farms. These isolates were tested for their antibiotic resistance against 22 antibiotics from several groups using the disk diffusion method. The results show that the highest resistance was observed towards streptomycin (85%, n = 20), while the lowest resistance was towards gentamicin (1.1%, n = 90). The multiple antibiotic resistant (MAR) index of the isolates tested ranged between 0 and 0.63. It was suggested that isolates with MAR index > 0.2 were recovered from sources with high risk of antibiotic resistant contamination. This study revealed low level of antibiotic resistance in the aquaculture bacterial isolates except for streptomycin and ampicillin (>50% resistance, n = 94) which have been used in the aquaculture industry for several decades. Antibiotic resistant patterns should be continuously monitored to predict the emergence and widespread of MAR. Effective action is needed to keep the new resistance from further developing and spreading.

13.
Clin Pharmacol Ther ; 100(5): 558-564, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27416001

ABSTRACT

The US Food and Drug Administration's Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol-driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81-3.27) comparing angioedema in patients initiating angiotensin-converting enzyme (ACE) inhibitors vs. beta-blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta-blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86-3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol-driven assessment.


Subject(s)
Adrenergic beta-Antagonists/adverse effects , Angioedema/chemically induced , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Drug-Related Side Effects and Adverse Reactions , Product Surveillance, Postmarketing/statistics & numerical data , Databases, Factual , Humans , Models, Statistical , United States , United States Food and Drug Administration
14.
Acta Chir Belg ; 115(2): 131-5, 2015.
Article in English | MEDLINE | ID: mdl-26021946

ABSTRACT

BACKGROUND: The increasing subspecialisation of general surgeons in their elective work may result in problems for the provision of expert care for emergency cases. There is very little evidence of the impact of subspecialism on outcomes following emergency major upper gastrointestinal surgery. This prospective study investigated whether elective subspecialism of general surgeon is associated with a difference in outcome following major emergency gastric surgery. METHODS: Between February 1994 and June 2010, the data from all emergency major gastric procedures (defined as patients who underwent laparotomy within 12 hours of referral to the surgical service for bleeding gastroduodenal ulcer and/or undergoing major gastric resection) was prospectively recorded. The sub-specialty interest of operating surgeon was noted and related to post-operative outcomes. RESULTS: Over the study period, a total of 63 major gastric procedures were performed of which 23 (37%) were performed by specialist upper gastrointestinal (UGI) consultants. Surgery performed by a specialist UGI surgeon was associated with a significantly lower surgical complication (4% vs. 28% of cases; p=0.04) and in-patient mortality rate (22% vs. 50%; p=0.03). CONCLUSIONS: Major emergency gastric surgery has significantly better clinical outcomes when performed by a specialist UGI surgeon. These results have important implications for provision of an emergency general surgical service.


Subject(s)
Clinical Competence , Digestive System Diseases/surgery , Digestive System Surgical Procedures/adverse effects , Laparotomy/adverse effects , Specialties, Surgical , Aged , Aged, 80 and over , Digestive System Diseases/complications , Digestive System Diseases/pathology , Emergencies , Female , Humans , Length of Stay , Male , Middle Aged , Outcome and Process Assessment, Health Care , Prospective Studies
15.
J Laryngol Otol ; 129 Suppl 2: S83-5, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25706169

ABSTRACT

PURPOSE: The management of extrapulmonary small cell carcinoma has not been standardised to date. This study reviewed the clinical course, management and survival outcomes of patients with extrapulmonary small cell carcinoma in the head and neck region. METHODS: Nine patients with extrapulmonary small cell carcinoma in the head and neck were included in this study. RESULTS: Five patients received radical surgery followed by adjuvant chemotherapy or radiotherapy or both. Two other patients were treated with chemotherapy consisting of CPT11 plus cisplatin or CPT11 plus cisplatin plus VP-16 three times. Two other patients received chemoradiotherapy consisting of S-1 or CPT11 plus cisplatin. The median overall survival was 14.5 months, with a three-year survival rate of 23.7 per cent. CONCLUSIONS: The prognosis of extrapulmonary small cell carcinoma is generally poor. Further prospective multicentre studies are required for better understanding of disease entities and response to treatment modalities.


Subject(s)
Carcinoma, Small Cell/mortality , Carcinoma, Small Cell/therapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Chemoradiotherapy , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease Progression , Drug Combinations , Etoposide/administration & dosage , Female , Humans , Irinotecan , Male , Middle Aged , Neoplasm Staging , Oxonic Acid/administration & dosage , Radiotherapy, Adjuvant , Survival Rate , Tegafur/administration & dosage
16.
J Laryngol Otol ; 129 Suppl 2: S95-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25706172

ABSTRACT

BACKGROUND: Hyalinizing clear cell carcinoma is a rare minor salivary gland neoplasm. The treatment of choice is surgical resection with or without post-operative radiotherapy. This tumour often demonstrates a good prognosis. CASE REPORT: We report a case of hyalinizing clear cell carcinoma arising in the nasopharynx. A 27-year-old female presented with progressive hearing disturbance and tinnitus. On examination, an expansile mass was observed in her nasopharynx. Biopsy was performed and the pathology results returned as clear cell carcinoma. RESULTS AND CONCLUSION: Surgical resection was performed trans-orally accompanied by trans-palatal approach. She has no recurrence during more than two years of follow up.


Subject(s)
Adenocarcinoma, Clear Cell/surgery , Nasopharyngeal Neoplasms/surgery , Oral Surgical Procedures , Palate/surgery , Adult , Female , Humans , Hyalin
17.
J Laryngol Otol ; 129 Suppl 2: S98-101, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25706173

ABSTRACT

OBJECTIVE: To determine the clinical effect of post-operative radiotheraphy and systemic chemotherapy for the treatment of salivary duct carcinoma. STUDY DESIGN: Retrospective review. DESIGN: The medical records of 26 patients treated by surgery with or without radiotheraphy and/or systemic chemotherapy for salivary duct carcinoma were retrospectively reviewed to investigate the role of post-operative adjuvant treatment for the patients' prognosis. RESULTS: The overall three-year and five-year survival rates were 54 and 48.1 per cent, respectively. There was no correlation with the clinical stage and the patients' prognosis. The overall three-year survival of the patients with or without post-operative radiotheraphy was 64 and 33 per cent, respectively (p = 0.29). The overall three-year survival of the patients with or without post-operative chemotherapy was 53 and 56 per cent, respectively (p = 0.78). CONCLUSION: Post-operative adjuvant therapy did not improve the patients' overall prognosis with salivary duct carcinoma. Developing novel treatment modalities may be necessary to improve the prognosis of this aggressive disease.


Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy, Adjuvant/mortality , Head and Neck Neoplasms/therapy , Salivary Ducts , Salivary Gland Neoplasms/therapy , Humans , Neoplasm Staging , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival Rate
19.
Oncogene ; 33(31): 4039-49, 2014 Jul 31.
Article in English | MEDLINE | ID: mdl-24141769

ABSTRACT

High-risk human papillomaviruses are causative agents of cervical cancer. Viral protein E7 is required to establish and maintain the pro-oncogenic phenotype in infected cells, but the molecular mechanisms by which E7 promotes carcinogenesis are only partially understood. Our transcriptome analyses in primary human fibroblasts transduced with the viral protein revealed that E7 activates a group of mitotic genes via the activator B-Myb-MuvB complex. We show that E7 interacts with the B-Myb, FoxM1 and LIN9 components of this activator complex, leading to cooperative transcriptional activation of mitotic genes in primary cells and E7 recruitment to the corresponding promoters. E7 interaction with LIN9 and FoxM1 depended on the LXCXE motif, which is also required for pocket protein interaction and degradation. Using E7 mutants for the degradation of pocket proteins but intact for the LXCXE motif, we demonstrate that E7 functional interaction with the B-Myb-MuvB complex and pocket protein degradation are two discrete functions of the viral protein that cooperate to promote acute transcriptional activation of mitotic genes. Transcriptional level of E7 in patient's cervical lesions at different stages of progression was shown to correlate with those of B-Myb and FoxM1 as well as other mitotic gene transcripts, thereby linking E7 with cellular proliferation and progression in cervical cancer in vivo. E7 thus can directly activate the transcriptional levels of cell cycle genes independently of pocket protein stability.


Subject(s)
Cell Cycle Proteins/metabolism , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Human papillomavirus 16/metabolism , Nuclear Proteins/metabolism , Papillomavirus E7 Proteins/metabolism , Trans-Activators/metabolism , Tumor Suppressor Proteins/metabolism , Uterine Cervical Neoplasms/virology , Cell Line, Tumor , Cells, Cultured , Female , Forkhead Box Protein M1 , Gene Expression Profiling , HEK293 Cells , HeLa Cells , Humans , Keratinocytes/metabolism , Mitosis , Mutation , Papillomavirus E7 Proteins/genetics , S Phase , Transcriptional Activation , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
20.
J Laryngol Otol ; 127(10): 1034-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24125062

ABSTRACT

OBJECTIVE: We present a case of large, symptomatic lingual thyroid which was successfully and safely removed via a transoral approach, using the da Vinci robotic system, in an academic medical centre in Singapore. CASE REPORT: A 17-year-old female adolescent presented with a large lingual thyroid causing upper airway obstruction. She underwent robotic, minimally invasive, transoral resection using the da Vinci system. Post-operative recovery was uneventful; she was able to commence oral feeding almost immediately, and was discharged from hospital on the fourth post-operative day. CONCLUSION: It is surgically feasible and safe to undertake transoral robotic resection of a large lingual thyroid. This approach may allow faster recovery and shorter hospitalisation for patients. Surgical safety requires a full understanding of the intralingual neurovascular anatomy.


Subject(s)
Lingual Thyroid/surgery , Minimally Invasive Surgical Procedures/methods , Robotics/methods , Thyroidectomy/methods , Adolescent , Anatomy/education , Female , Humans , Length of Stay , Mouth/surgery , Singapore , Treatment Outcome
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