Outcomes after intensity-modulated compared with 3-dimensional conformal radiotherapy with chemotherapy for squamous cell carcinoma of the anal canal.

Purpose: We report our institution's treatment techniques, disease outcomes, and complication rates after radiotherapy for the management of anal canal carcinoma with intensity-modulated radiotherapy (imrt) and concurrent chemotherapy relative to prior cases managed with 3-dimensional conformal radiotherapy (3D-crt). Methods: In a retrospective review of the medical records of 21 patients diagnosed with biopsy-proven stage i (23%), stage ii (27%), or stage iii (50%) squamous-cell carcinoma of the anal canal treated with curative chemotherapy and imrt between July 2009 and December 2014, patient outcomes were determined. Results for patients treated with 3D-crt by the same group were previously reported. The median initial radiation dose to the pelvic and inguinal nodes at risk was 45 Gy (range: 36-50.4 Gy), and the median total dose, including local anal canal primary tumour boost, was 59.4 Gy (range: 41.4-61.2 Gy). Patients received those doses over a median of 32 fractions (range: 23-34 fractions). Chemotherapy consisted of 2 cycles of concurrent fluorouracil-cisplatin (45%) or fluorouracil-mitomycin C (55%). Results: Median follow-up was 3.1 years (range: 0.38-6.4 years). The mean includes a patient who died of septic shock at 38 days. The 3-year rates of overall survival, metastasis-free survival, locoregional control, and colostomy-free survival were 95%, 100%, 100%, and 100% respectively. No patients underwent abdominoperitoneal resection after chemoradiotherapy or required diverting colostomy during or after treatment. Those outcomes compare favourably with the previously published series that used 3D-crt with or without brachytherapy in treating anal canal cancers. Of the 21 patients in the present series, 10 (48%) experienced acute grade 3, 4, or 5 toxicities related to treatment. Conclusions: The recommended use of imrt with concurrent chemotherapy as an improvement over 3D-crt for management of anal canal carcinoma achieves a high probability of local control and colostomy-free survival without excessive risk for acute or late treatment-related toxicities.

Analysis of pathological complete response rates with paclitaxel-based regimens in trimodality therapy for esophageal cancer.

The study aimed to examine whether omission of 5-fluorouracil (5-FU)-containing chemotherapy alters pathological complete response rates in patients receiving trimodality therapy for locally advanced esophageal cancer. A total of 159 patients were identified. One hundred twenty-nine patients received platinum/5-FU concurrently with radiotherapy, and 30 received taxane/platinum-containing chemoradiotherapy prior to esophagectomy. Patients were staged using the 2002 American Joint Committee on Cancer staging system. Patients were matched between chemotherapeutic groups, with no significant demographic or clinical differences other than T stage (14% T2 in the 5-FU group; no T2 in the platinum/taxane group) and radiotherapy technique (8.5% received intensity-modulated radiotherapy in the 5-FU group; 60% in the platinum/taxane group). Pathological complete response rates for 5-FU and platinum/taxane-based groups were not significantly different (45% and 30%, respectively; P = 0.1548). Five-year overall survival and progression-free survival were not statistically different between the two groups. Significant predictors of pathological complete response included N stage (56% N0 and 33% N1; P = 0.0083), histology (37% adenocarcinoma and 59% squamous cell; P = 0.0123), tumor location (39% distal and 59% proximal/mid; P = 0.048), gastroesophageal junction involvement (33% involved and 55% uninvolved; P = 0.005), and radiotherapy end-to-surgery interval (50% < 55 days and 34% ≥ 55 days; P = 0.04). Grades 3-4 hematological toxicity was higher in the 5-FU group (36%) than in the paclitaxel-containing therapy group (17%; P = 0.0484). Use of paclitaxel-containing chemoradiotherapy did not result in inferior pathological complete response, overall survival, or progression-free survival rates, and resulted in less hematological toxicity than 5-FU treatment.

Organisation and planning of anaesthesia for emergency surgery.

Patients presenting for emergency surgery represent a category at high risk of complications, with substantial morbidity and mortality, whose management may be extremely challenging. In this first of two articles we consider the identification and evaluation of high risk emergency patients, the provision of critical care support, the management of sepsis, common postoperative complications and in-theatre death.

Clinical review: Spinal imaging for the adult obtunded blunt trauma patient: update from 2004.

PURPOSE: Controversy exists over how to 'clear' (we mean enable the clinician to safely remove spinal precautions based on imaging and/or clinical examination) the spine of significant unstable injury among clinically unevaluable obtunded blunt trauma patients (OBTPs). This review provides a clinically relevant update of the available evidence since our last review and practice recommendations in 2004. METHODS: Medline, Embase. Google Scholar, BestBETs, the trip database, BMJ clinical evidence and the Cochrane library were searched. Bibliographies of relevant studies were reviewed. RESULTS: Plain radiography has low sensitivity for detecting unstable spinal injuries in OBTPs whereas multidetector-row computerised tomography (MDCT) approaches 100%. Magnetic resonance imaging (MRI) is inferior to MDCT for detecting bony injury but superior for detecting soft tissue injury with a sensitivity approaching 100%, although 40% of such injuries may be stable and 'false positive'. For studies comparing MDCT with MRI for OBTPs; MRI following 'normal' CT may detect up to 7.5% missed injuries with an operative fixation in 0.29% and prolonged collar application in 4.3%. Increasing data is available on the complications associated with prolonged spinal immobilisation among a population where a minority have an actual injury. CONCLUSIONS: Given the variability of screening performance it remains acceptable for clinicians to clear the spine of OBTPs using MDCT alone or MDCT followed by MRI, with implications to either approach. Ongoing research is needed and suggestions are made regarding this. It is essential clinicians and institutions audit their data to determine their likely screening performances in practice.

Metabolic acidosis in the critically ill: part 2. Causes and treatment.

The correct identification of the cause, and ideally the individual acid, responsible for metabolic acidosis in the critically ill ensures rational management. In Part 2 of this review, we examine the elevated (corrected) anion gap acidoses (lactic, ketones, uraemic and toxin ingestion) and contrast them with nonelevated conditions (bicarbonate wasting, renal tubular acidoses and iatrogenic hyperchloraemia) using readily available base excess and anion gap techniques. The potentially erroneous interpretation of elevated lactate signifying cell ischaemia is highlighted. We provide diagnostic and therapeutic guidance when faced with a high anion gap acidosis, for example pyroglutamate, in the common clinical scenario 'I can't identify the acid--but I know it's there'. The evidence that metabolic acidosis affects outcomes and thus warrants correction is considered and we provide management guidance including extracorporeal removal and fomepizole therapy.

Metabolic acidosis in the critically ill: part 1. Classification and pathophysiology.

Metabolic acidaemia (pH < 7.35 not primarily related to hypoventilation) is common amongst the critically ill and it is essential that clinicians caring for such patients have an understanding of the common causes. The exclusive elimination routes of volatile (carbon dioxide), organic (lactic and ketone) and inorganic (phosphate and sulphate) acids mean compensation for a defect in any one is limited and requires separate provision during critical illness. We discuss the models available to diagnose metabolic acidosis including CO2/HCO3(-) and physical chemistry-derived (Stewart or Fencl-Stewart) approaches, but we propose that the base excess and anion gap, corrected for hypoalbuminaemia and iatrogenic hyperchloraemia, remain most appropriate for clinical usage. Finally we provide some tips for interpreting respiratory responses to metabolic acidosis and how to reach a working diagnosis, the consequences of which are considered in Part 2 of this review.

Clearing the cervical spine after polytrauma: implementing unified management for unconscious victims in the intensive care unit.

Determining the best method for excluding cervical spine injury while a polytrauma victim is unconscious remains a controversial topic despite a number of published guidelines. A structured questionnaire demonstrated major differences between intensivists, neurosurgeons, orthopaedic surgeons and spinal surgeons with regard to the imaging modalities requested, the perception of their performance, the relative risks of missed injuries and the complications of immobilisation. Unconscious victims of polytrauma often come under the care of several subspecialties, with the direct consequence that management can be contradictory and lack standardisation. Advanced Trauma Life Support and Eastern Association for the Surgery of Trauma guidelines can reinforce and even contribute to non-standardised care. Having performed this clinician survey, we have now developed a multidisciplinary management protocol appropriate for Northern Ireland.

Clearing the cervical spine in unconscious polytrauma victims, balancing risks and effective screening.

Cervical spine injury occurs in 5-10% of cases of blunt polytrauma. A missed or delayed diagnosis of cervical spine injury may be associated with permanent neurological sequelae. However, there is no consensus about the ideal evaluation and management of the potentially injured cervical spine and, despite the publication of numerous clinical guidelines, this issue remains controversial. In addition, many studies are limited in their application to the obtunded or unconscious trauma victim. This review will provide the clinician managing unconscious trauma victims with an assessment of the actual performance of clinical examination and imaging modalities in detecting cervical spine and isolated ligamentous injury, a review of existing guidelines in light of the available evidence, relative risk estimates and a proposed management scheme.

Anticipation and planning for anaesthesia provision within MR units in the UK.

We surveyed 33 UK MR units that have been developed by New Opportunity Funding (NOF) with reference to planning for and provision of anaesthetic services. The likely clinical and resource implications were documented. Units were developed predominantly in acute general hospitals with paediatric, critically ill and neuroscience patients represented. It may be predicted that up to 50% of newly built units will require anaesthetic provision and this should be anticipated at the planning stage. A senior anaesthetist should be involved in the planning process.

T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy.

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure. PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for >or= 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up. RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications. CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.

Local excision and postoperative radiation therapy for rectal adenocarcinoma.

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival.