Return to Activities of Daily Living after Breast Cancer Surgery: An Observational Prospective Questionnaire-Based Study of Patients Undergoing Mastectomy with or without Immediate Reconstruction.

Background: Patients often ask about the time taken to return to activities of daily living (ADLs) after breast surgery, but there is a lack of data to give accurate guidance. We aimed to assess the feasibility of a study to determine the time taken to return to ADLs after mastectomy with or without breast reconstruction. Materials and Methods: A prospective multicentre, self-reported questionnaire-based feasibility study of women who had undergone mastectomy ± reconstruction was performed, between Jan 2017 and Dec 2019. Women were asked to self-report when they returned to 15 ADLs with a 5-option time scale for "return to activity." Results: The questionnaire was returned by 42 patients (median [range] age: 64 [31-84]). Of these, 22 had simple mastectomy, seven mastectomy and implant reconstruction, seven mastectomy and autologous reconstruction (DIEP), and six did not specify. Overall, over 90% could manage stairs and brush hair by two weeks and 84% could get in and out of the bath by four weeks. By 1-2 months, 92% could do their own shopping and 86% could drive. 68% of women employed returned to work within four months. Compared to simple mastectomy, patients undergoing reconstruction took a longer time to return to getting in/out of bath (<2 vs. 2-4 weeks), vacuuming (2-4 weeks vs. 1-2 months), and fitness (1-2 vs. 3-4 months). There was a slower return to shopping (1-2 months vs. 2-4 weeks), driving and work (both 3-4 vs. 1-2 months), and sports (3-4 vs. 1-2 months) in autologous reconstruction compared to implant reconstruction. Conclusion: This study is feasible. It highlights slower return to specific activities (particularly strength-based) in reconstruction patients, slower in autologous compared with implant reconstruction. The impact on return to ADLs should be discussed as part of the preoperative counselling as it will inform patients and help guide their decision making. A larger study is required to confirm these results.

Treatment with afobazole at delayed time points following ischemic stroke improves long-term functional and histological outcomes.

There is currently a significant lack of therapeutic options for acute ischemic stroke, and no drug has been approved for treating patients at delayed time points (≥6h post-stroke). Afobazole, an anxiolytic currently used clinically in Russia, has been shown to reduce neuronal and glial cell injury in vitro following ischemia. Experiments using the permanent middle cerebral artery occlusion (MCAO) rat model were carried out to determine if afobazole can reduce ischemic stroke damage in vivo and expand the therapeutic window for stroke treatment. Post-stroke (24h) application of afobazole (0.3-3mg/kg) significantly decreased infarct volume at 96h post-surgery, as determined by Fluoro-Jade and NeuN staining of brain sections. Moreover, afobazole helped preserve both the levels and normal histological distribution of myelin basic protein, indicating a reduction in white matter injury. A time-dependence study showed that either pre-treatment or treatment started 6 to 48h post-stroke with the drug yields improved outcomes at 96h. The decrease in infarct volume produced by afobazole was blocked by the application of either a σ-1 (BD 1063, 30mg/kg) or a σ-2 (SM-21, 1mg/kg) antagonist, indicating that both receptor subtypes are involved in the effects of afobazole. Treatment with afobazole starting at 24h post-stroke resulted in enhanced survival one month following surgery. Behavioral testing of animals 28-32days post-surgery using the elevated body swing and forelimb grip-strength tests revealed that treatment with afobazole starting 24h post-stroke significantly reduces behavioral deficits caused by ischemic stroke. The increase in survival and improved functional outcomes are accompanied by a reduction in infarct volume, as determined by thionin staining of brain sections. Taken together, our data support the use of afobazole as a post-stroke pharmacological agent to expand the current therapeutic window.

A Qualitative Assessment of Radiotherapy Training at a UK Regional Cancer Centre.

AIMS: Specialty trainees in clinical oncology must be competent in the coordination of both radiotherapy and systemic therapy at the completion of their training. Radiotherapy technology and postgraduate medical education have evolved significantly over the last two decades, but little is known of the educational impact of those changes within the dual training of the clinical oncology programme. A qualitative assessment of the radiotherapy component of training was undertaken at a single regional cancer centre in order to identify potential areas for improvement. MATERIALS AND METHODS: Consultants and trainees (n = 10) at a regional cancer centre underwent semi-structured interviews regarding their lived experience of learning radiotherapy skills and knowledge. As consultants and trainees can be considered equal co-investors in the process of radiotherapy learning, the same question stems were used for both groups. An interpretative phenomenological analysis was undertaken by the investigators to elicit the perception of both groups. RESULTS: Consultant and trainee assessments of current radiotherapy learning standards differ for several aspects of training, as do their expectations of the other in learning processes. A lack of time is a major barrier in modern practice, and both groups can propose novel measures to improve learning locally. CONCLUSIONS: Arrangements for learning radiotherapy have not kept pace with the rate of change in the clinical oncology discipline. Trainees and consultants have contrasting views on the state of training, its strengths and weaknesses, and pathways to improvement, which should be reconciled by programme coordinators charged with upgrading the training system.

The introduction of single best answer questions as a test of knowledge in the final examination for the fellowship of the Royal College of Radiologists in Clinical Oncology.

AIMS: The single best answer (SBA) format of multiple choice questions (MCQ) is recognised to be better suited to the assessment of the higher levels of knowledge essential for clinical practice, such as data interpretation, problem solving and decision making, than traditional true/false MCQ. In autumn 2006, the Royal College of Radiologists (RCR) introduced SBA questions as its sole written test of knowledge for the Final Fellowship Examination in Clinical Oncology (Final FRCR Examination). This article reviews the application of SBA questions to clinical oncology and analyses the first year's experience of the new examination format. METHODS: The results of the last two true/false MCQ examinations (autumn 2005 and spring 2006) and the first two SBA examinations (autumn 2006 and spring 2007) were analysed. The predictive values of the different components of the Final FRCR Examination (SBA, true/false MCQ, case orientated questions COQ, clinical and oral examinations) were compared. RESULTS: In autumn 2005, 86% of candidates passed the true/false MCQ paper but only 48% passed the examination overall. In spring 2006, 91% of candidates passed the true/false MCQ paper but the overall pass rate was only 36%. In contrast, the pass rate for the SBA papers was 66% for both autumn 2006 and spring 2007, which was comparable to the overall pass rate of 53% and 52% respectively. All the components of the examination (SBA, true/false MCQ, COQ, clinical and oral examinations) had similar negative predictive values of between 80% and 90% (p = 0.3, chi-square test). However, the positive predictive value of true/false MCQ was inferior to the other sections of the examination (46% compared to 74%, 80%, 74% and 72% for SBA, COQ, clinicals and orals respectively, p < 0.001, chi-square test). CONCLUSION: The new format SBA questions are more reliable than the previous true/false MCQ in discriminating between knowledgeable and unknowledgeable candidates in the Final FRCR Examination in Clinical Oncology.

Measuring competence in endoscopic sinus surgery.

BACKGROUND: Competence based education is currently being introduced into higher surgical training in the UK. Valid and reliable performance assessment tools are essential to ensure competencies are achieved. No such tools have yet been reported in the UK literature. OBJECTIVE: We sought to develop and pilot test an Endoscopic Sinus Surgery Competence Assessment Tool (ESSCAT). The ESSCAT was designed for in-theatre assessment of higher surgical trainees in the UK. METHODS: The ESSCAT rating matrix was developed through task analysis of ESS procedures. All otolaryngology consultants and specialist registrars in Scotland were given the opportunity to contribute to its refinement. Two cycles of in-theatre testing were used to ensure utility and gather quantitative data on validity and reliability. Videos of trainees performing surgery were used in establishing inter-rater reliability. RESULTS: National consultation, the consensus derived minimum standard of performance, Cronbach's alpha = 0.89 and demonstration of trainee learning (p = 0.027) during the in vivo application of the ESSCAT suggest a high level of validity. Inter-rater reliability was moderate for competence decisions (Cohen's Kappa = 0.5) and good for total scores (Intra-Class Correlation Co-efficient = 0.63). Intra-rater reliability was good for both competence decisions (Kappa = 0.67) and total scores (Kendall's Tau-b = 0.73). CONCLUSION: The ESSCAT generates a valid and reliable assessment of trainees' in-theatre performance of endoscopic sinus surgery. In conjunction with ongoing evaluation of the instrument we recommend the use of the ESSCAT in higher specialist training in otolaryngology in the UK.

Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours?

The prognostic significance of extragonadal rather than gonadal presentation of germ-cell tumour in 51 patients presenting between 1979 and 1988 with abdominal tumours was compared with that of 51 control patients with testicular primary tumours matched for bulk fo disease, serum tumour marker concentration, age and year of treatment. Very large volume tumour was found at initial staging in 24 extra-gonadal cases (47%) and high tumour markers in 29 (57%). Actuarial survival at 2 and 5 years was 82% and 70% for cases and 78% and 63%, respectively, for controls. These outcomes were not significantly different and the relative hazard of death for cases compared with controls was 0.7 (95% confidence intervals 0.3-1.5). Thus the presentation of germ-cell tumours with a retroperitoneal mass does not itself adversely influence prognosis compared with testicular presentation with equivalent disease extent. However it is rare for extragonadal presentation to be associated with small volume disease.

Hypobaric hypoxia: a method for testing bioreductive drugs in vivo.

Hypobaric hypoxia has been used to induce tumor hypoxia for in vivo comparison of the anti-tumor effects of the bioreductive agents SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide), RSU 1069 (1(2-nitro-1-imidazolyl)-3-aziridino-2-propanol), and Nitromin (methylbis(2-chloroethyl)amine N-oxide). BDF mice bearing the T50/80 mammary carcinoma were treated with these agents over a range of doses under normobaric (oxic) and hypobaric (hypoxic) conditions. The time taken for the tumor to double treatment volume (volume doubling time) was used as a measure of anti-tumor effect. Volume doubling time was plotted against log dose and dose response curves were fitted. A dose enhancement ratio (the ratio of drug doses required to give an equivalent anti-tumor effect under oxic and hypoxic conditions) was determined. The dose enhancement ratios for SR 4233 and RSU 1069 were 8.8 and 8.5, respectively, showing that these agents had an equivalent and substantial enhancement of their cytotoxicity when combined with hypobaric hypoxia. For Nitromin, no significant dose response effect was obtained under oxic conditions precluding the calculation of the dose enhancement ratio. SR 4233 was found to have increased systemic toxicity when combined with hypobaric hypoxia, suggesting that it is more readily activated than the other drugs tested. This in vivo test system will allow determination of the dose enhancement ratio for novel bioreductive agents and facilitate their comparison.

Effect of digital rectal examination (and ejaculation) on serum prostate-specific antigen after twenty-four hours. A randomized, prospective study.

The purpose of this randomized, controlled, clinical trial was to determine the effect of the digital rectal examination (DRE) on the prostate-specific antigen (PSA) serum levels in view of conflicting literature reports and screening methods and misconceptions by physicians. We showed that the DRE had no clinically important effect on PSA values twenty-four hours later. The mean PSA rose from 1.57 to 1.62 ng/mL, similar to the controls. Ejaculation had no meaningful effect on the serum PSA values.

Histone deacetylase inhibitors and cell proliferation in pea root meristems.

The histone deacetylase (HDA) inhibitors, trichostatin A (TSA) and HC toxin halt mitosis in cultured root meristems of Pisnum sativum, while the anti-protozoan HDA inhibitor apicidin is ineffective. Two-dimensional PAGE of proteins from root meristems exposed to TSA and HC toxin did not show significant differences compared to controls, although a previously tested HDA inhibitor, butyrate, exhibited dramatic variations in its protein profile. Northern analysis of butyrate- and TSA-treated root meristems indicated that non-proliferating cells are expressing significant amounts of transcripts of the known cell proliferation associated genes: histone H2A, MAP kinase, cycA2:1 and cdc2. Western analysis reveals the presence of hyperacetylated nuclear proteins in HDA-inhibitor treated cells. These results suggest that the HDA inhibitors, butyrate and TSA, halt mitosis without down-regulating genes that typically have low or nonexistent expression levels in non-dividing cells.

Radiation recall dermatitis in a patient treated with dacarbazine.

Radiation recall describes an inflammatory reaction at a previously irradiated site associated with the use of chemotherapeutic agents. Dacarbazine, a tetrazine cytotoxic drug, has not been noted to cause this phenomenon. We report the case history of a 44-year-old female patient who developed a recall dermatitis due to dacarbazine in a site previously irradiated for the treatment of malignant melanoma. The skin erythema responded quickly to oral corticosteroid treatment. Further cycles of dacarbazine were facilitated with oral corticosteroid premedication. We conclude that dacarbazine should be considered as a potential cause of radiation recall dermatitis and that this can be managed and prevented with oral corticosteroids.

Radical radiotherapy for inoperable non-small cell lung cancer: what factors predict prognosis?

We set out to determine the factors that predict the outcome of conventional radical radiotherapy for inoperable non-small cell lung cancer. A retrospective casenote review was carried out of all 69 patients treated between 1986 and 1992 at the Northern Ireland Centre for Clinical Oncology, Belfast, with radical radiotherapy for inoperable non-small cell lung cancer. The tumour dose ranged from 45 Gy to 67.5 Gy, delivered in 15-30 fractions, 5 days per week over 3-6 weeks. All patients were followed up for 5 years. The disease was TNM Stage T1-T4N0-N2M0. The majority of tumours (51) were squamous. Overall survival was 63.8% (44-patients; 95% confidence interval (CT) 51.3-75.2) at one year; median survival was 16 months and 5-year survival was 13% (nine patients; 95% CI 6.1-23.3). Five-year survival for the 36 patients with stage T1 or T2 disease was 5.6% (2 patients). Five-year survival for the 33 patients with stage T3 or T4 disease, all with tumours at or near the carina, was 21.2% (seven patients). A WHO performance status of 0 or 1 (P = 0.03, Cox proportional hazards model) was associated with a better chance of survival.

A phase II trial of four courses of preoperative chemotherapy in squamous or anaplastic carcinoma of the oesophagus.

We have reported the results of a previous Phase II trial of two courses of neoadjuvant mitomycin (6 mg/m2), ifosfamide (3 g/m2) and cisplatin (50 mg/m2) (MIC) in squamous or anaplastic carcinoma of the oesophagus. In this current study, we have investigated whether there was any clinical benefit in extending the preoperative treatment to four courses for patients who responded after two courses. Response was assessed by barium swallow, which was compared with previous barium swallows performed prior to any treatment and after the second course of MIC. Of an initial 43 patients, 27 (63%) were assessed as responders after two courses of MIC. Twenty of these 27 patients were entered into the study with a view to receiving two further courses of MIC prior to surgery. Seventeen completed four courses. Five patients were complete responders after two courses and remained complete responders after four courses. Twelve patients were partial responders after two courses; six of these became complete responders after four courses, five remained partial responders, and one showed progression. Haematological toxicity and alopecia were increased after extending the number of courses beyond two. On pathological assessment, three patients with a complete response after four courses, and one with a complete response after three courses, had microscopic clearance of tumour. Extension beyond two courses of neoadjuvant MIC gives an improvement in response, as judged by barium assessment, but increases toxicity, cost of treatment and delay before surgery. Although the numbers are small, the results suggest that a worthwhile improvement in the radiological response of squamous or anaplastic oesophageal tumours may be gained by proceeding beyond two courses of MIC. A randomized trial, with larger numbers of patients, is needed to show whether there is any improvement in radiological and pathological response rates and in survival to be gained by the extension of treatment beyond two courses.

Trends in the severity of self-poisoning.

Of 2947 patients admitted to a district general hospital over an 11-year period for the management of self-poisoning, 148 (5%) required intensive care unit (ICU) treatment. There was a significant increase in the number of self-poisonings admitted each year, whereas the number requiring ICU admission did not change. Therefore the proportion of patients requiring ICU admission fell significantly over the study period (P less than 0.0005). Of 898 patients admitted from 1973 to 1977, 62 (6.9%) were treated in ICU. Of 2049 patients admitted from 1978 to 1983, 86 (4.2%) required ICU treatment. It is felt that this trend is explained by a rise in parasuicidal self-poisonings. The impact of change in drug availability is evident in the significant reduction in ingestion of sedative barbiturates.

Aspartame's effects on behavioral thermoregulation in albino rats.

Aspartame (L-aspartyl-L-phenylalanine methyl ester) was administered intraperitoneally to 9 Sprague-Dawley rats partitioned into 2 studies (4 in Study 1 and 5 for a replication in Study 2) over a two-year period using a within-subjects, repeated-measures reversal design. Behavioral thermoregulation was assessed in a cold Skinner Box using 5-sec. exposures of microwave radiation [Specific Absorption Rate = 0.34 Watts/kg/(mW/cm2)] as reinforcing stimuli under a fixed-interval 2-min. schedule of positive reinforcement. Two factorial analyses of variance [5 (doses) x 8 (hours)] indicated that the main effect for the doses of aspartame (2, 4, 8, 16 mg/kg, and saline control) was not significant; yet, the interaction (dose x hours) was significant (p < .05). Tentatively, aspartame should not cause an uncomfortable rise in body temperature (as sugar can do) when consumed in common substances such as soft drinks, yogurt, tea, coffee, etc., in doses commensurate with "hedonic" sweetness.

The nicotinic acid provocation test and unconjugated hyperbilirubinaemia.

It has been suggested that the nicotinic acid provocation test is useful in the diagnosis of Gilbert's syndrome. We compared the response to intravenous nicotinic acid of patients with Gilbert's syndrome and with chronic liver disease. There was no significant difference in the mean rise in unconjugated serum bilirubin between the two groups. A sensitivity of 70% and specificity of 60% were obtained. All of 5 patients with chronic liver disease and a raised fasting unconjugated serum bilirubin had positive tests. We suggest that the nicotinic acid test is positive in unconjugated hyperbilirubinaemia regardless of cause. It is of no value in differentiating Gilbert's syndrome from liver disease.

Needle biopsy of the pleura in the diagnosis of pleural effusion.

Needle biopsy of the parietal pleura was undertaken in 64 patients with undiagnosed pleural effusion. An adequate specimen was obtained in 96% of procedures. This was diagnostic in 45% of those due to malignancy and in 50% of those due to tuberculosis. A second biopsy improved the combined diagnostic yield in these two diseases from 32% to 46%. Pleural fluid cytology was unhelpful in establishing the presence of a malignancy, and culture of the biopsy specimen was helpful in one case.

Outcome of patients admitted to an acute geriatric medical unit.

To find out what happens to patients admitted to an acute geriatric medical unit, all admissions during 1982 were reviewed. Demographic features were compared with those of the community served, and rehabilitation, inpatient mortality and mortality in the year following discharge were assessed. Inpatients accounted for 4% of the community aged over 65, and most patients were discharged back to the community. Inpatient mortality was 25% and mortality in the year following discharge was 23%, giving a two year mortality of 42%, which was similar in all age groups. The achievement of high rehabilitation rates was tempered by the considerable mortality rates following discharge.

Pathology of rectal adenocarcinoma following preoperative adjuvant radiotherapy and chemotherapy.

The study group comprised 13 patients (mean age 68 years) with clinically fixed and biopsy proven moderately differentiated rectal adenocarcinoma (8 high rectal, 5 low-mid rectal) who received synchronous courses of preoperative combination chemotherapy and pelvic radiotherapy (radiotherapy alone in 3 cases) over a period of 8-20 weeks prior to surgical resection. All cases showed varying degrees of mural and mesorectal fibrosis. Three cases did not differ otherwise from usual rectal adenocarcinoma while 4 had a 20-30% diminution in expected tumour area. In 6 cases tumour could not be definitely identified grossly--1 showed a 50% reduction in tumour bulk while 5 had only residual microscopic foci from 0.6-4 mm in maximum dimensions. Only 3 cases had involvement of the mesorectal circumferential radial margin. Four involved lymph nodes in 2 cases were partially hyalinised and calcified. Preoperative combination adjuvant therapy can produce marked regressive morphological changes in rectal adenocarcinoma. The implications of this are discussed.