Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic acid for the prevention of colorectal adenomas.

BACKGROUND: Aspirin may reduce the risk of several types of cancer. OBJECTIVES: To evaluate if folic acid is associated with risk of basal cell carcinoma (BCC). METHODS: BCC incidence was evaluated in a randomized, double-blind, placebo-controlled clinical trial of aspirin (81 mg daily or 325 mg daily for ~3 years) and/or folic acid (1 mg daily for ~6 years) for the prevention of colorectal adenomas among 1121 participants with a previous adenoma. BCC was confirmed by blinded review of pathology reports. RESULTS: One hundred and four of 958 non-Hispanic white participants were diagnosed with BCC over a median follow-up of 13·5 years. Cumulative incidence of BCC was 12% [95% confidence interval (CI) 7-17] for placebo, 16% (95% CI 11-21) for 81 mg aspirin daily and 15% (95% CI 10-20) for 325 mg aspirin daily [hazard ratio (HR) for any aspirin 1·45 (95% CI 0·93-2·26); HR for 81 mg daily 1·57 (95% CI 0·96-2·56); HR for 325 mg daily 1·33 (95% CI 0·80-2·20)]. BCC risk was higher with aspirin use in those without previous skin cancer but lower with aspirin use in those with previous skin cancer (Pinteraction = 0·02 for 81 mg aspirin daily; Pinteraction = 0·03 for 325 mg aspirin daily). Folic acid supplementation was unrelated to BCC incidence (HR 0·85; 95% CI 0·57-1·27). CONCLUSIONS: Neither aspirin nor folic acid treatment had a statistically significant effect on risk of BCC. Subgroup analysis suggested that chemopreventive effects of nonsteroidal anti-inflammatory drugs may be specific to those at high risk for BCC.

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort.

BACKGROUND: Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. OBJECTIVES: To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. METHODS: CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. RESULTS: Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04-1·30) of Breslow thickness vs. normal-weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00-1·27) and 1·17 (95% CI 1·03-1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m-2 , BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. CONCLUSIONS: This large case-series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values.

Patient-reported outcomes in long-term survivors of metastatic colorectal cancer needing liver resection.

BACKGROUND: Five-year survival after hepatic resection for colorectal cancer (CRC) liver metastases is good, but data on patient-reported outcomes are lacking. This study describes the long-term impact of liver surgery for CRC metastases on patient-reported outcomes. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For functional scales, mean scores out of 100 with 95 per cent c.i. were calculated; differences of 10 points or more were considered clinically significant. Responses to symptom scales and items were categorized as 'minimal' or 'severe'. Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total of 241 patients were recruited; nine (3·7 per cent) had unresectable disease and were excluded. Some 68 (42 men) of 80 long-term survivors participated; their mean age was 69·5 years and median follow-up was 8·0 (range 6·9-9·2) years. Values for baseline and 1-year patient-reported outcome data were similar. Scores for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87 to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting clinically significant improvements from baseline values of 17 (10 to 24), 12 (3 to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected less than 5 per cent of patients) for most patient-reported outcome scales or items, but persistent severe symptoms were noted for sexual function (2 per cent increase from baseline), peripheral neuropathy (2 per cent increase), constipation (10 per cent increase) and diarrhoea (5 per cent increase). CONCLUSION: Long-term survivors of metastatic colorectal cancer who have undergone liver surgery have excellent global quality of life, high levels of function and few symptoms.

A prospective study of patient reported outcomes in pancreatic and peri-ampullary malignancy.

BACKGROUND: The purpose of the present study was to describe the impact of treatment of pancreatic and peri-ampullary malignancy on patient reported outcomes (PRO). However, limited data are available describing the impact of curative or palliative therapy on pancreatic/peri-ampullary malignancy and quality of life. METHODS: Patients selected for pancreaticoduodenectomy (PD) completed the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire pre-surgery and 6 weeks, 3, 6, 12, 18, and 24 months postoperatively. Patients selected for palliative treatments completed the same questionnaire before treatment and monthly thereafter. Mean scores and 95 % confidence intervals (CI) were calculated for functional scales. Symptom scales and single items were categorized as either minimal or severe, and they were reported as proportions of patients experiencing severe symptoms with 95 % CI. RESULTS: A total of 100 patients (53 planned PD, 47 palliative) were enrolled. Of the 53 patients planned for surgery, 12 had tumors that were unresectable and 41 underwent pancreatoduodenectomy (PD). Seven patients were excluded because of benign histology or concurrent malignancy. Baseline questionnaire compliance was 70 %. For those undergoing PD, there were 53 complications, 7 deaths at 1 year, and 14 deaths at 2 years. Post-surgery most functions and symptoms deteriorated. Recovery in global health and most symptoms occurred by 3 months, and functional scales recovered by 6 months. Recovery of PRO was maintained in the survivors at 2 years. Palliative patients had poorer function and more symptoms at baseline; however, poor follow-up questionnaire compliance prevented further analysis of this group. CONCLUSIONS: Pancreaticoduodenectomy has a short-term negative impact on PRO that recovers within 6 months and is maintained at 2 years in survivors. Further work evaluating palliative and curative treatment in larger patient groups with disease-specific questionnaires is necessary.

Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma.

BACKGROUND AND AIMS: The incidence of oesophageal adenocarcinoma (OAC) has been increasing rapidly with a dismal survival rate of less than 20%. Understanding the genomic aberrations and biology of this cancer may enhance disease interventions. This study aimed to use genome-wide genomic and expression data to enhance the understanding of OAC pathogenesis and identify groups with differential outcomes. METHODS: Array-comparative genomic hybridisation (aCGH) analysis was carried out on 56 fresh frozen OAC resection samples with long-term clinical follow-up data. Samples with aberrations were further analysed with whole-genome single-nucleotide polymorphism arrays to confirm aCGH findings. Matched gene expression microarray data were used to identify genes with high copy number-expression correlations. Nested-multiplex PCR on DNA from microdissected specimens and fluorescence in situ hybridisation assays were used for target validation. Immunohistochemistry on the same cohort and independent samples (n=371) was used for subsequent validation. Kaplan-Meier survival analyses were performed based on aCGH data after unsupervised K-means clustering (K=5, 50 iterations) and immunohistochemistry data. RESULTS: aCGH identified 17 common regions (>5% samples) of gains and 11 common regions of losses, including novel regions in OAC (loci 11p13 and 21q21.2). Integration of aCGH data with matched gene expression microarray data highlighted genes with high copy number-expression correlations: two deletions (p16/CDKN2A, MBNL1) and four gains (EGFR, WT1, NEIL2, MTMR9). Immunohistochemistry demonstrated protein over-expression of targets with gains: EGFR (10%), WT1 (20%), NEIL2 (14%) and MTMR9 (25%). These targets individually (p<0.060) and in combination had prognostic significance (p=0.008). On the genomic level, K-means clustering identified a cluster (32% of cohort) with differential log(2) ratios of 16 CGH probes (p<4×10(-7)) and a worse prognosis (median survival=1.37 years; p=0.015). CONCLUSIONS: Integration of aCGH and gene expression data identified copy number aberrations and novel genes with prognostic potential in OAC.

Massive hemoptysis associated with foreign body removal.

Exsanguinating hemoptysis accompanied removal of an endobronchial foreign body in a 12-year-old child. Preparations to treat this complication should be made prior to removal of any foreign body of prolonged sojourn in the tracheobronchial tree.

Mitral valve replacement: a comparison of two prostheses.

Between November, 1965 and June, 1970, 175 patients underwent mitral valve replacement with the Smeloff-Cutter prosthesis (109 patients) or the toroidal valve (66 patients). The early mortality for patients with a toroidal mitral prosthesis was 18.2 percent (12 patients) and the late mortality 34.8 percent (23 patients). Among patients in whom Smeloff-Cutter mitral valves were inserted, the early mortality was 15.6 percent (17 patients) and the late mortality 23.9 percent (26 patients). During a follow-up period extending at least five years, thromboembolic complications occurred in 25.9 percent (14) of patients with toroidal valves and 7.6 percent (7) of patients with Smeloff-Cutter valves. Reoperation was necessary because of thrombosis of the prosthesis in seven patients with toroidal valves and two patients with Smeloff-Cutter valves. The incidence of endocarditis was the same in both groups. In this study, the Smeloff-Cutter mitral prosthesis proved to be superior to the toroidal valve because of a lower incidence of thromboembolism.

The surgical treatment of complicated peptic esophagitis.

Healing of stenosing peptic esophagitis was proved by endoscopy and biopsy in 22 of 27 patients treated by transthoracic Nissen fundoplication and esophageal dilation during a follow-up period extending to 14 years. Four additional patients did not have follow-up endoscopy because three expired from intercurrent disease before endoscopy could be carried out and one refused to have the procedure because of lack of symptoms. Postoperative reflux has not been demonstrated in any patient either endoscopically or by contrast studies. Dysphagia, requiring repeat dilation, occurred in two patients after operation. Transthoracic fundoplication with intraoperative stricture dilation is a reasonable alternative in treating complicated esophagitis.

Glossopharyngeal neuralgia with syncope.

Thirty-two cases of glossopharyngeal neuralgia complicated by syncope, cardiac arrhythmias or convulsions, singly or together, have been reported in the world literature. A further case is described and the clinical features of these thirty-three are reviewed. It is recommended that treatment should be undertaken as a matter of urgency. In the first place, Carbamezapine, with often the addition of Atropine, may prove effective. However, surgical intervention appears to give a better chance of permanent relief. Four alternative methods of surgery are discussed and the cervical or the intracranial approach recommended. Surgery should not be delayed in patients who fail to respond to medical treatment or in whom recurrence of symptoms occurs.

Psychological factors influence the success of coronary artery surgery.

Thirty-six patients with angina were investigated by treadmill exercise testing and coronary angiography prior to coronary artery surgery. Severity of angina was judged by interview and self-assessment visual analogue scale and all patients were psychiatrically assessed. Further physical and psychiatric assessments were made at 3 and 6 months postoperatively. Eleven patients (31%) had significant psychiatric morbidity preoperatively and these had worse symptom scores and exercise tolerance compared with non-psychiatric cases, despite equivalent coronary angiographic findings and left ventricular function. Post-operatively, exercise tolerance improved equally in both groups but psychiatric cases remained significantly more symptomatic. Psychiatric morbidity remained unchanged throughout the study. We conclude that almost one third of patients with severe angina have psychiatric morbidity which is associated with a poor symptomatic response to coronary artery surgery, despite objective improvement in exercise tolerance. Ways of improving the symptomatic response to surgery in patients with coexisting psychiatric morbidity should be studied.

Hepatobiliary cystadenomas.

INTRODUCTION: Hepatobiliary cystadenomas are rare cystic tumours that can arise from any portion of the biliary tract but most commonly develop intrahepatically. They typically cause non-specific symptoms and are often detected incidentally. Cystadenomas can be mistaken for simple hepatic cysts on radiological imaging, which leads to inadequate treatment. Hepatobiliary cystadenomas have a malignant predisposition and a high recurrence rate. Complete excision including hepatic resection is therefore generally recommended. METHODS: Three cases of hepatobiliary cystadenoma were identified at one unit over a six-month period. Their clinical details and management are reported. RESULTS: Three female patients are described aged 25, 37 and 73 years. One patient presented because of recurrent infection, one presented because of pressure related symptoms and one lesion was identified incidentally. All patients were investigated by ultrasonography and computed tomography (CT), two additionally had magnetic resonance imaging (MRI) and one had a liver biopsy. The tumours were 4-16cm in size and all lesions were excised by non-anatomical, parenchyma sparing resections. Histology revealed mixed epithelium with underlying ovarian-like stroma. CONCLUSIONS: The management of hepatic cystadenomas as well as operative and pathological findings are discussed. Preoperative ultrasonography, CT and MRI is recommended, and early referral for specialist hepatobiliary review is advised. Operative resection is also recommended and complete excision was achieved in these cases. This strategy is supported by the current literature and recurrence has been shown to be unlikely.

Neutrophil lymphocyte ratio in outcome prediction after emergency abdominal surgery in the elderly.

INTRODUCTION: Accurate prediction of outcome after emergency surgery in elderly patients may assist decision-making. Many scoring systems require post-operative data (e.g. P-POSSUM) whilst others have failed to gain widespread use. Recent reports suggest that C-reactive protein (CRP) and the neutrophil lymphocyte (N/L ratio) ratio may predict surgical outcome. METHODS: A retrospective review of all patients aged 80 years or over undergoing emergency abdominal surgery over a 22 month period was conducted. Outcome and clinical data were collected. Univariate, multivariate and recursive analyses were performed for outcome at 30 days, 6 months and 12 months. Findings were validated in a second independent dataset. RESULTS: 88 patients were included in the test dataset, median age 84 years. 30-day mortality was 31%, 6-month mortality 43% and 12-month mortality 50%. Univariate analysis identified N/L ratio, CRP, midline laparotomy, and surgical risk score to predict outcome at each time point. Recursive analysis showed, N/L ratio ≥22 best predicted 30-day outcome (p=0.0018). Multivariate analysis identified N/L ratio to be an independent predictor of 30-day outcome (p=0.004) yet CRP did not predict outcome at any time point. An independent dataset (n=84) confirmed N/L ratio to be a prognostic factor at 30 days (p=0.001), 6 months (p<0.001) and 12 months (p=0.001). CONCLUSION: N/L ratio is an easily calculable pre-operative measure that may have utility in the prediction of outcome after emergency abdominal surgery in the elderly. Further work to validate this measure in a larger, prospective setting and determine the underlying mechanisms that mediate outcome are necessary.

Normal inflammatory markers in appendicitis: evidence from two independent cohort studies.

OBJECTIVES: Acute appendicitis is a common surgical condition which can lead to severe complications. Recent work suggested that patients experiencing right lower abdominal pain, with normal white cell count (WCC) and C-reactive protein (CRP) are unlikely to have acute appendicitis and can be discharged. We present two independent data-sets that suggest that this strategy may not be risk-free. DESIGN: Retrospective cohort study of consecutive patients from two district general hospitals. Sensitivity and specificity of CRP, WCC and neutrophil count (NC) in predicting appendicitis were calculated. Markers were analysed using Fisher's exact test and Kruskul-Wallace test. SETTING: Two district general hospitals in the UK. PARTICIPANTS: Patients undergoing appendicectomy for suspected appendicitis. MAIN OUTCOME MEASURES: Inflammatory markers and appendix histology. RESULTS: A total of 297 patients were included. Appendicitis occurred in four patients with normal CRP, WCC and NC in centre A and 13 patients in centre B. The sensitivity of all three markers combined was 94% (centre A) and 92% (centre B). The specificity was 60% (centre A) and 64% (centre B). No single marker could differentiate uncomplicated and complicated appendicitis, but a raised NC or a CRP >35.5 mg/l predicted complicated appendicitis. CRP, WCC and NC combined differentiated between patients with a normal appendix, uncomplicated appendicitis and complicated appendicitis. CONCLUSIONS: Appendicitis in the presence of normal inflammatory markers is not uncommon. We disagree with the view of Sengupta et al. who suggest that patients with normal WCC and CRP are unlikely to have appendicitis, and recommend that clinicians be wary of normal inflammatory markers in patients with a high clinical suspicion of appendicitis.

An abdominal presentation of churg-strauss syndrome.

Churg-Strauss syndrome is a small and medium vessel vasculitis that is also known as allergic granulomatous angiitis. It most commonly presents with an asthma like symptoms. It was first described in Mount Siani Hospital, New York in 1951 by Jacob Churg and Lotte Stauss and was recognised after the study of a series of 13 patients who had asthma, eosinophilia, granulomatous inflammation necrotising systemic vasculitis and necrotising glomerulonephritis. We describe a case of Churg-Strauss syndrome presenting with abdominal pain and later during the hospital admission a mono-neuritis multiplex syndrome affecting the lower limbs. The patient presented in such an atypical fashion with abdominal signs and symptoms that they required laparotomy and the diagnosis was made after histological examination of tissue taken at the time of surgery. Treatment with immunosuppression and aggressive rehabilitation achieved a progressive recovery which continued on discharge from hospital.