ABSTRACT
BACKGROUND: Intra-tumour genetic heterogeneity has been reported in both leukaemias and solid tumours and is implicated in the development of drug resistance in CML and AML. The role of genetic heterogeneity in drug response in solid tumours is unknown. METHODS: To investigate intra-tumour genetic heterogeneity and chemoradiation response in advanced cervical cancer, we analysed 10 cases treated on the CTCR-CE01 clinical study. Core biopsies for molecular profiling were taken from four quadrants of the cervix pre-treatment, and weeks 2 and 5 of treatment. Biopsies were scored for cellularity and profiled using Agilent 180k human whole genome CGH arrays. We compared genomic profiles from 69 cores from 10 patients to test for genetic heterogeneity and treatment effects at weeks 0, 2 and 5 of treatment. RESULTS: Three patients had two or more distinct genetic subpopulations pre-treatment. Subpopulations within each tumour showed differential responses to chemoradiotherapy. In two cases, there was selection for a single intrinsically resistant subpopulation that persisted at detectable levels after 5 weeks of chemoradiotherapy. Phylogenetic analysis reconstructed the order in which genomic rearrangements occurred in the carcinogenesis of these tumours and confirmed gain of 3q and loss of 11q as early events in cervical cancer progression. CONCLUSION: Selection effects from chemoradiotherapy cause dynamic changes in genetic subpopulations in advanced cervical cancers, which may explain disease persistence and subsequent relapse. Significant genetic heterogeneity in advanced cervical cancers may therefore be predictive of poor outcome.
Subject(s)
Antineoplastic Agents/therapeutic use , Genetic Heterogeneity , Uterine Cervical Neoplasms/genetics , Adult , Aged , Combined Modality Therapy , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapyABSTRACT
Laparoscopic surgical techniques are increasingly being used to treat gynaecological malignancies as studies confirm long-term results similar to open procedures. Within the UK National Health Service, there is a drive towards day of surgery admission and reducing inpatient stay. We audited the length of inpatient stay, acceptability to patients of day of surgery admission and timing of discharge and accessibility to early community follow-up, among women undergoing laparoscopic assisted vaginal hysterectomy and bilateral salpingo-oophorectomy in our unit over a 6-month period. We show that women find short inpatient stays acceptable and that many can be safely discharged, with no postoperative hospital follow-up, within 24 h. Adequate pre-admission procedures and easy access to advice, post-discharge must be ensured.
Subject(s)
Ambulatory Surgical Procedures/standards , Hysteroscopy/standards , Laparoscopy/standards , Outcome Assessment, Health Care , Ovariectomy/standards , Adult , Aged , Aged, 80 and over , Continuity of Patient Care/standards , Databases, Factual , Female , Follow-Up Studies , Humans , Length of Stay , Medical Audit , Middle Aged , Patient Discharge , United KingdomABSTRACT
Effective communication across the primary/secondary interface is vital for the planning and delivery of appropriate patient care throughout the cancer patient journey. This study describes GPs' views of the communication issues across the primary/secondary interface in relation to ovarian cancer patients using qualitative interviews with purposively sampled general practitioners (GPs) and an audit of hospital medical records of 30 deceased ovarian cancer patients. Issues raised by the GPs related to the content and format of communications, but of most concern was the tardiness. The time lag between dictation and typing letters ranged from 0 to 27 days, with a delay of up to 8 days for signing before transit through various mail systems to the GP. Three stages in the patient journey were characterized by particular issues: (1) in the pre-diagnostic and diagnostic stage was a need for prompt information regarding the results of tests and diagnoses, and clearer guidance on the use of tests and fast-track referrals; (2) in the active treatment phase, when GPs could lose touch with their patients, they needed effective communication in order to provide moral support and crisis management; and (3) when oncology withdrew and the focus of care switched back to the community for the terminal phase, GPs needed information to enable them to pick up the baton of care. There is a need to develop and evaluate interventions aimed at improving the content and speed of communications between secondary and primary care. Such interventions are likely to be complex and might include the greater use of telephone or fax for more selected communications, a review of secretarial support, the use of email, the development of GP designed proformas, the feasibility of patient/carer letter delivery options, nurse-led communication, universal electronic patient records, or a revisiting of the patient-held record.
Subject(s)
Communication Barriers , Family Practice , Ovarian Neoplasms/therapy , Correspondence as Topic , Female , Hospitalization , Humans , Interprofessional Relations , Interviews as Topic , Male , Oncology Service, Hospital/organization & administration , Patient Discharge , Physician-Patient Relations , Referral and Consultation , Refusal to Treat , Time FactorsABSTRACT
Transvaginal ultrasound is commonly used in the investigation of postmenopausal bleeding. In this article, we report the use of transrectal ultrasound in the assessment of postmenopausal bleeding and detection of an endometrial carcinoma, where other methods of assessment were unsuccessful.
