Insertion rates and complications of central lines in the UK population: A pilot study.

BACKGROUND: Central venous catheters are inserted ubiquitously in critical care and have roles in drug administration, fluid management and renal replacement therapy. They are also associated with numerous complications. The true number of central venous catheters inserted per year and the proportion of them associated with complications are unknown in the UK. METHODS: We performed a prospective audit at five hospitals, as a feasibility pilot for a larger, nationwide audit. Using a novel secure online data collection platform, developed earlier and adapted for this project, all central venous catheters inserted for patients admitted to the Intensive Care Units were documented at five pilot sites across the UK. RESULTS: A total of 117 data collection forms were submitted. Users found the electronic data collection system easy to use. All data fields were ready for analysis immediately after data input. Out of the 117 central venous catheters, 17 were haemodialysis catheters and five pulmonary artery introducers. Experienced practitioners (at least three years' experience) inserted 85% of the central venous catheters. The site of insertion was the internal jugular vein for 80%, femoral for 12% and subclavian for 8% of central venous catheters. Most central venous catheters were inserted in ICU (49%) or theatres (42%). Ultrasound was used for 109 (93%) of central venous catheter insertions and its use was not associated with fewer complications. In 15 cases venopuncture was attempted more than once (all with ultrasound) and this was associated with significantly increased risk of complications. There were eight immediate complications (6.8%): five related to venopuncture and inability to pass a guidewire, two carotid artery punctures and one associated with significant arrhythmia. CONCLUSION: This study demonstrates the ease and feasibility of collecting detailed descriptive data on central line insertion and its immediate complications in the UK over two weeks. In our proposed nationwide audit, organisation-level data on local policies and standard operating procedures is required to complete the picture on this important aspect of intensive care practice.

A Cost-Effectiveness Analysis of Contact X-ray Brachytherapy for the Treatment of Patients with Rectal Cancer Following a Partial Response to Chemoradiotherapy.

AIMS: Following chemoradiotherapy in patients with rectal cancer, the addition of contact X-ray brachytherapy (CXB) in partial responders might increase the proportion of patients with a clinical complete response (cCR) and who are thus suitable for watch and wait management. However, the long-term cost-effectiveness of this approach has not been evaluated. MATERIALS AND METHODS: Decision analytical modelling and a Markov simulation were used to compare long-term costs, quality-adjusted life years (QALYs) and cost-effectiveness from a third-party payer (National Health Service) perspective for treatment strategies after chemoradiotherapy; watch and wait with CXB when a cCR was not initially achieved after external beam radiotherapy (EBRT) (WWCXB), watch and wait with EBRT alone (WWEBRT) and radical surgery for all patients. The effect of uncertainty in model parameters and patient demographics was investigated. RESULTS: WWCXB had a higher QALY payoff than both radical surgery and WWEBRT and was less costly in most scenarios and demographic cohorts. In all plausible scenarios, WWCXB was the most cost-effective, at a threshold of £20 000/QALY. This finding was insensitive to uncertainty associated with model parameters. CONCLUSIONS: WWCXB is likely to be cost-effective compared with both WWEBRT alone and radical surgery. These findings support the use of CXB boost as an adjunct to a watch and wait strategy.

Organ Preservation Using Contact Radiotherapy for Early Rectal Cancer: Outcomes of Patients Treated at a Single Centre in the UK.

AIMS: Contact radiotherapy for early rectal cancer uses 50 kV X-rays to treat rectal cancers under direct vision. We present data of a series of patients treated at a single centre with prospective follow-up and functional assessment. MATERIALS AND METHODS: All patients were treated at the Queen's Centre for Oncology, Hull, UK between September 2011 and October 2015. Patients received a biopsy, magnetic resonance imaging (MRI) of the liver/pelvis, computed tomography of the chest and endorectal ultrasound. Patients were deemed to be either unfit for radical surgery or refused it due to the need for a permanent stoma. Follow-up consisted of 3 monthly flexible sigmoidoscopy and MRI of the liver/pelvis and 12 monthly computed tomography of the chest. RESULTS: In total, 42 patients were treated with contact radiotherapy ± external beam chemo/radiotherapy without any primary surgical excision. The median age was 78 years (range 50-94 years). Local recurrence-free survival was 88%, disease-free survival was 86% and overall survival was 88% with a median follow-up of 24 months (range 5-54 months). The median time to recurrence was 12 months (range 4-14 months). The estimated 30 day surgical mortality for this cohort with radical surgery was 12%. Mortality from the contact radiotherapy procedure was 0%. Functional outcomes as investigated by the Low Anterior Resection Syndrome (LARS) score were good, with 65% having no LARS. CONCLUSIONS: Contact radiotherapy for early rectal cancer is a safe, well-tolerated outpatient procedure, allowing organ preservation, with excellent oncological and functional outcomes. For elderly co-morbid patients with suitable rectal cancers this should be considered as a standard of care.

Developing a digital data collection platform to measure the prevalence of sepsis in Wales.

OBJECTIVE: To develop a secure, efficient, and easy-to-use data collection platform to measure the prevalence of sepsis in Wales over 24 hours. MATERIALS AND METHODS: Open Data Kit was used on Android devices with Google App Engine and a digital data collection form. RESULTS: A total of 184 students participated in the study using 59 devices across 16 hospitals, 1198 datasets were submitted, and 97% of participants found the Open Data Kit form easy to use. DISCUSSION: We successfully demonstrated that by combining a reliable Android device, a free open-source data collection framework, a scalable cloud-based server, and a team of 184 medical students, we can deliver a low-cost, highly reliable platform that requires little training or maintenance, providing results immediately on completion of data collection. CONCLUSION: Our platform allowed us to measure, for the first time, the prevalence of sepsis in Wales over 24 hours.

Fatal herpes simplex virus hepatitis following neoadjuvant chemoradiotherapy and anterior resection for rectal cancer.

We describe the case of a young patient who contracted fatal herpes simplex virus hepatitis following neoadjuvant chemoradiotherapy and anterior resection for rectal cancer. The rarity and non-specific presentation of this treatable disease, which masqueraded as the sequelae of postoperative sepsis, resulted in a diagnosis following death. Features that should prompt inclusion of herpes simplex virus hepatitis in the differential diagnoses are suggested and the case is a reminder of how neoadjuvant therapy may subtly alter a patient's immunocompetency.

Mandard tumour regression grade, perineural invasion, circumferential resection margin and post-chemoradiation nodal status strongly predict outcome in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

AIMS: The pathology of tumours after chemo/radiotherapy for locally advanced rectal cancer can be difficult to interpret. The ypTNM staging does not accurately predict outcomes. Therefore, we developed a new prognostic index for this purpose. MATERIALS AND METHODS: The Nottingham Rectal Cancer Prognostic Index (NRPI) is based on a study of 158 patients with locally advanced rectal cancer treated with preoperative chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with/without concurrent capecitabine chemotherapy. Surgery was carried out after an interval of 6-10 weeks. Factors found to be significant on univariate analysis to predict for disease-free (DFS) and overall survival were further explored in multivariate analysis. The significant factors (Mandard tumour regression grade, perineural invasion, circumferential resection margin status and nodal status) were weighted to establish a score for the index. The median follow-up was 40 months (range 3-90 months). RESULTS: On survival analysis, four distinct prognostic groups were found: Score 0 = excellent prognosis, 1-3 = good prognosis, 4-8 = moderate prognosis, 9-14 = poor prognosis. The NRPI significantly predicted both DFS and overall survival (P < 0.0001). DFS at 5 years was 95, 63, 25 and 0% for the four groups. On multivariate analysis the NRPI was found to be the strongest predictor of DFS including nodal and circumferential resection margin status (P < 0.0001). It was a stronger predictor of overall survival than the American Joint Committee on Cancer/Dukes staging (P < 0.0001). CONCLUSIONS: The NRPI allocates patients into distinct prognostic categories. This seems to be a much stronger predictive factor than the American Joint Committee on Cancer/Dukes staging. This requires further validation, but seems to be a useful clinical index for future studies.

Prognostic importance of Mandard tumour regression grade following pre-operative chemo/radiotherapy for locally advanced rectal cancer.

PURPOSE: To assess the prognostic value of the Mandard tumour regression score (TRG) following pre-operative chemo/radiotherapy in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The study involved 158 patients with locally advanced rectal cancer treated with pre-operative long course chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with or without concurrent capecitabine chemotherapy at a dose of 1650 mg/m(2)/day. Surgery was normally performed after an interval of 6-10 weeks. The response to pre-operative treatment was carefully graded by a single pathologist using the five point Mandard score. The median follow-up was 40 months (range 3-90 months). RESULTS: Of the 158 patients 14% were TRG1, 41% were TRG2, 31% were TRG3, 13% were TRG4 and 1% were TRG5. The groups were combined into TRG1, TRG2 and TRG3-5 to simplify further analysis. The Mandard score was clearly related to both disease-free (p < 0.001) and overall survival (p = 0.012). On multivariate analysis perineural invasion, nodal status, TRG and circumferential resection margin status were the most powerful predictors of disease-free survival. CONCLUSIONS: The Mandard tumour regression score is an independent prognostic factor and predicts for long-term outcome following pre-operative chemo/radiotherapy in rectal cancer.

Regression of rectal cancer with radiotherapy with or without concurrent capecitabine--optimising the timing of surgical resection.

AIMS: To determine tumour regression (volume-halving time) obtained after chemo/radiotherapy, and thereby the ideal interval between the start of treatment and surgery in order to obtain a high rate of complete response. MATERIALS AND METHODS: In total, 106 patients with cT3,4 rectal cancer who received preoperative radiotherapy alone or concurrently with capecitabine chemotherapy at Nottingham City Hospital, UK were studied. The rectal tumour volume visible on the computed tomography planning scan was compared with the residual pathological volume and the tumour volume-halving time calculated. The radiotherapy response was graded according to the Mandard system. RESULTS: Fifty-three patients had radiotherapy alone, with 53 patients having concurrent chemoradiotherapy. The median tumour volume-halving time was found to be 14 days and not influenced by the addition of chemotherapy. The Mandard score, the interval from the start of treatment to surgery and the tumour volume-halving time were statistically associated with tumour regression. The median tumour volume in our series of 54 cm(3) would require an interval of 20 weeks after the start of treatment to surgery to regress to <0.1 cm(3) (10 volume-halving times; 140 days). CONCLUSIONS: The initial tumour volume and median volume-halving time provide the best estimates for determining the optimum length of interval between the completion of preoperative chemo/radiotherapy and surgery in locally advanced rectal cancer.

Impact of neutropenia on delivering planned chemotherapy for solid tumours.

The ability to deliver the planned dose and intensity of chemotherapy (the amount of drug administered/unit of time) is important for tumour control and survival. In clinical practice, neutropenic events are the main limiting factors towards achieving this aim. We assessed the impact of neutropenic events [defined as either hospital admission due to febrile neutropenia (FN), dose delay > or =7 days due to neutropenia or dose reduction of > or =15% due to neutropenia] on dose intensity (DI) in a random sample of 50 patients with various solid tumours. Fifty patients who received systemic chemotherapy for solid tumours were assessed as part of this study. Using a pre-programmed data collection tool via computer, retrospective data were collected. The neutropenic events were defined before data collection. The patient characteristics are as follows: breast 26 patients (stage I-6; II-3; III-17), colorectal 16 patients (stage I-6; II-3; III-7) and others 8 patients [small cell lung cancer (SCLC), ovarian, peritoneal and oesophageal cancers]. The chemotherapy regimens used are Flourouracil, Epirubicin, cyclophosphamide (FEC) 14 patients (28%); 5 Flourouracil/folinic acid (5FU/FA) 12 patients (24%); Adriamycin, cyclophosphamide (AC) 11 patients (22%); other 13 patients (26%). Neutropenic events occurred in a significant proportion of patients (overall 40%; breast 26%; colorectal 56%; others 25% of patients) and in a significant number (21%) of chemotherapy cycles. Overall, dose delay was the most common neutropenic event, occurring in 30% of patients (breast 32%; colorectal 31%; others 25%% of patients). Dose reduction due to neutropenia was noted in 20% of patients (breast 12% colorectal 38% others 13%% of patients). Hospitalizations due to FN affected 8% of patients. Only two patients had granulocyte colony-stimulating factor (GCSF) as treatment for two cycles. Relative dose intensity (RDI) in patients with neutropenic events was 81% compared with 92% in patients without an event and the results were consistent for different cancers. In total, 65% of patients who experienced one neutropenic event were likely to experience subsequent events. In conclusion neutropenic events have a significant impact on the ability to deliver planned DI. Hence, proactive use of GCSF has the potential to improve adherence to the planned schedule of chemotherapy.

Lapatinib: a tyrosine kinase inhibitor with a clinical role in breast cancer.

Lapatinib is a dual (ErbB-1 and ErB-2) receptor tyrosine kinase inhibitor (TKI) that was recently approved by the FDA for the treatment of advanced breast cancer. It shows synergy with trastuzumab, and has demonstrated clinical activity in trastuzumab-resistant tumour. This paper reviews the drug development of lapatinib from preclinical studies to the pivotal Phase III trial and ongoing clinical studies. Areas of interest include the advantages of small molecule TKIs versus antibodies in targeting HER receptors and the efficacy of lapatinib in the treatment of cerebral metastases. The surprisingly high response rate in inflammatory breast cancer raises the possibility of other novel predictive biomarkers. The potential for combination and sequencing with other biological and cytotoxic agents is both exciting and challenging.

Single fraction radiotherapy for small superficial carcinoma of the skin.

AIMS: To define the optimal dose and maximum tumour size of basal and squamous cell carcinoma of skin that can be treated by single fraction radiotherapy. MATERIALS AND METHODS: A review was undertaken of 1005 lesions of basal/squamous cell carcinoma of the skin involving 806 patients treated at a single centre with 10 years of follow-up. Doses of 18, 20 and 22.5 Gy were used. The recurrence and necrosis free survival rates for different anatomical sites and radiation doses were calculated. RESULTS: The overall disease-free and necrosis-free rates at 5 years were 90% and 84%, respectively. The crude 10-year recurrence rate was 4% (95% CI 3.4-5.4%), with late skin necrosis at 6% (95% CI 4.8-7.2%). There was no difference in tumour recurrence rates between 20 and 22.5 Gy (P=0.3), but there was a significantly higher skin necrosis rate at the treated site in the patients who had received 22.5 Gy (P=0.003). Most skin necrosis healed spontaneously, with only 16% requiring surgical intervention. Tumours involving the inner canthus had a significantly higher recurrence rate than those involving other areas of the head and neck. CONCLUSIONS: Single fraction radiotherapy is an acceptable treatment for small superficial BCC and SCC of the head and neck region in patients who have difficulty attending multiple hospital visits as long as the field size required for treatment is no larger than 3 cm in diameter. The optimal applied dose for such a lesion on a flat surface is 20 Gy.