Timing and detection of metachronous colorectal cancer

Background: Surveillance following surgery for colorectal cancer aims to detect treatable disease relapse or metachronous neoplasia. Metachronous cancers have been reported within a short duration of follow‐up, and may be due to missed lesions, seeding into polypectomy wounds or accelerated tumorigenesis related to genetic instability. The purpose of this study was to establish the timing and method of detection of metachronous cancers in a large population of patients in a surveillance database. Methods: This retrospective clinical study used patients with an elevated risk of colorectal neoplasia included in a colonoscopy‐based surveillance programme to identify those with two or more colorectal cancers, as well as the timing and method of detection of the tumours. Colonoscopy reports and histopathology results were reviewed to determine quality of bowel preparation, tumour location, and polypectomy data. Results: Fourteen (2.5%) of 569 patients with colorectal cancer developed metachronous malignant tumours, nearly half of which were identified within 3 years of follow‐up by surveillance colonoscopy or an interval faecal immunochemical test for globin. None of these had a previous polypectomy at the site of the second tumour, bowel preparation at the original colonoscopy was good in most cases, and no metachronous tumour occurred at a colonic flexure. Conclusion: Metachronous cancers can occur early during follow‐up after curative intent resection, and early colonoscopic surveillance may be warranted.     

Endocrine problems in pregnancy

This paper aims to describe the pathophysiology and management of the main endocrine complications of pregnancy. For each endocrine dysfunction, the issues with the fetus, the mother, obstetric complications, and the long term prognosis for the disease itself need to be considered. Key management issues are highlighted with each condition. Thyroid dysfunction and goitre are common while management is relatively straightforward. Adrenal, pituitary, and parathyroid diseases present less commonly in pregnancy. Early recognition of endocrine disease in pregnancy and appropriate management has the potential to improve outcome for the mother and fetus in the short and long term.     

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction: Implication for diagnosis of diastolic heart failure

BACKGROUND: Left atrial volume index (LAVI) is increasingly recognised as a relatively load-independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF). METHODS: 137 patients with suspected heart failure (HF), referred from the community for echocardiography, prospectively underwent Doppler echocardiography, LAVI and NTproBNP estimation. Raised LAVI and reduced LV systolic function were defined as >26 ml/m2 and LV EF <50% respectively. RESULTS: Of 137 patients, 21 were excluded (2 with significant mitral valve disease and 19 with atrial fibrillation). Of the remaining 116 subjects, 92 showed normal LV systolic function. The univariate predictors of serum log NTproBNP were age (p < 0.001), LA dimension (p = 0.001), LAVI (p < 0.001), A wave (p = 0.001), E:A (p = 0.07) and septal wall thickness (p = 0.004). However on multivariate analysis, LAVI was found to be the most consistent and significant predictor of NTproBNP. The area under the curve of the receiver operating characteristic (ROC) curve for NTproBNP in detecting patients with LVEF > or = 50% and LAVI >26 ml/m2 was 0.81 (p < 0.0001) and for patients with LAVI > 26 ml/m2 with and without LVEF > or = 50% was 0.82 (p < 0.0001). CONCLUSION: This data confirms that LAVI on resting echocardiography, specifically in patients with suspected HF and normal LV systolic function is a powerful independent predictor of LV diastolic dysfunction as predicted by serum NTproBNP. In a population with a high suspicion of diastolic heart failure, LAVI may significantly contribute to diagnostic precision.     

Multiple joint effusions associated with high-dose imatinib therapy in a patient with chronic myelogenous leukaemia

Imatinib mesylate is a small molecule tyrosine kinase inhibitor that has significant efficacy in the treatment of chronic myelogenous leukaemia (CML). However, it is likely that patients with CML will require prolonged and perhaps life-long therapy. In general, the side-effects of imatinib therapy have been mild to moderate, with the large majority of patients tolerating prolonged periods of therapy. However, a minority of patients are completely intolerant of therapy, while others are able to remain on therapy despite significant side-effects. Here, we describe a novel form of fluid retention presenting as multiple joint effusions in a patient with advanced phase CML on high-dose imatinib, as well as successful measures that were undertaken to control this adverse event. Although fluid retention, including periorbital oedema, pleural and pericardial effusions, as well as life-threatening cerebral oedema have been previously described and attributed to imatinib, this is the first case of imatinib-associated polyarticular effusions that we are aware of. Further work will be required to confirm a casual relationship between imatinib therapy and this novel side-effect, as well as to determine the underlying pathophysiologic mechanisms.     

Therapeutic Development in Cardiac Syndrome X: A Need to Target the Underlying Pathophysiology

Morbidity of patients with cardiac syndrome X (typical anginal‐like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal agents such as nitrates, calcium channel antagonists, classic β‐adrenoceptor blockers and nicorandil have been tried, with variable success. However, this might be related to a failure to target the underlying pathophysiology and, clearly, more effective therapies are needed. Supporting evidence for the important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has come from the recent observation that basal superoxide production predicts future cardiovascular events in this patient group. This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress. What's already known about this topic? ?Morbidity of patients with cardiac syndrome X is high. ?The important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X. What does this article add? ?This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress.     

Two sisters with IMAGe syndrome: cytomegalic adrenal histopathology, support for autosomal recessive inheritance and literature review

Adrenal hypoplasia congenita (AHC) is a rare condition and causes primary adrenal insufficiency. X-linked (OMIM 300200) and autosomal recessive (OMIM 240200) forms are recognized. Recently, an association between Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital abnormalities (IMAGe syndrome; OMIM 300290) has been described. We present the clinical features of two sisters with intrauterine growth restriction, AHC, and dysmorphic features. Interesting histopathologic findings of one sister are also presented. We suggest that IMAGe syndrome is the most plausible diagnosis and that autosomal recessive inheritance is likely. We analyzed genes that were postulated candidates for IMAGe syndrome (SF1, DAX-1, and STAR), and no mutations were found. Other cases of IMAGe syndrome are reviewed.     

CSNK1E/CTNNB1 Are Synthetic Lethal To TP53 in Colorectal Cancer and Are Markers for Prognosis

Two genes are called synthetic lethal (SL) if their simultaneous mutations lead to cell death, but each individual mutation does not. Targeting SL partners of mutated cancer genes can kill cancer cells specifically, but leave normal cells intact. We present an integrated approach to uncovering SL pairs in colorectal cancer (CRC). Screening verified SL pairs using microarray gene expression data of cancerous and normal tissues, we first identified potential functionally relevant (simultaneously differentially expressed) gene pairs. From the top-ranked pairs, ~ 20 genes were chosen for immunohistochemistry (IHC) staining in 171 CRC patients. To find novel SL pairs, all 169 combined pairs from the individual IHC were synergistically correlated to five clinicopathological features, e.g. overall survival. Of the 11 predicted SL pairs, MSH2-POLB and CSNK1E-MYC were consistent with literature, and we validated the top two pairs, CSNK1E-TP53 and CTNNB1-TP53 using RNAi knockdown and small molecule inhibitors of CSNK1E in isogenic HCT-116 and RKO cells. Furthermore, synthetic lethality of CSNK1E and TP53 was verified in mouse model. Importantly, multivariate analysis revealed that CSNK1E-P53, CTNNB1-P53, MSH2-RB1, and BRCA1-WNT5A were independent prognosis markers from stage, with CSNK1E-P53 applicable to early-stage and the remaining three throughout all stages. Our findings suggest that CSNK1E is a promising target for TP53-mutant CRC patients which constitute ~ 40% to 50% of patients, while to date safety regarding inhibition of TP53 is controversial. Thus the integrated approach is useful in finding novel SL pairs for cancer therapeutics, and it is readily accessible and applicable to other cancers.Abbreviations: CRC, colorectal cancer; IHC, immunohistochemistry; FDR, false discovery rate; TD, tumor-dependent; SL, synthetic lethal     

The impact of delayed diagnosis on the outcomes of oral cancer patients: a retrospective cohort study

The contemporary literature is discordant regarding the role of delayed diagnosis in the prognosis of patients with oral cancer. This study examined data on a previously reported cohort of 101 patients with oral squamous cell carcinoma diagnosed at a single institution between 2008 and 2010. The time interval between symptom onset and initial histological diagnosis (diagnostic delay) was recorded for each patient, as were demographic data and cancer features such as T stage, nodal status, and smoking status. The mean follow-up period was 4 years 10 months. The mean diagnostic delay was 4 months, mean overall survival was 5 years 6 months, and mean disease-specific survival was 4 years 9 months. No significant correlation was found between diagnostic delay and overall survival, disease-specific survival, or recurrence rates. Patients with node-positive disease were more likely to be diagnosed earlier, whereas women and non-smokers were more likely to have a delayed diagnosis. Inherent tumour biology is likely an important prognostic factor separate to diagnostic delay. Public education efforts should focus on symptom recognition and encourage early presentation for investigation of oral lesions, particularly for females and non-smokers, so that more aggressive tumours can be treated sooner to give the best chance at survival.     

Safety and efficacy of a laparoscopic cholecystectomy in the morbid and super obese patients

BackgroundAlthough a laparoscopic cholecystectomy (LC) is the gold standard treatment for symptomatic cholelithiasis, its safety and efficacy in the morbidly/super obese patients is unknown. The aim of this study was to investigate the safety and efficacy of an elective LC in the morbid/super obese patients.MethodsA retrospective review of the hospital electronic database and medical records was conducted searching for all elective LC from 2010 to 2013. The data collected included patient demographics and body mass index (BMI), length of hospital stay (LOS), duration of surgery (DOS), intra‐ and post‐operative complications, bile duct injuries, performance of an intra‐operative cholangiogram, the incidence of open conversion and the seniority of the operator.ResultsA total of 799 patients (76% female) with a mean age of 46 years and BMI of 31 were included in this study. There were significant differences in the median DOS between the three BMI groups; BMI < 26 [64 min; interquartile range (IQR) 54–83]; BMI 26–40 (72 min, IQR 58–91) and BMI > 40 (82 min, IQR 63–104), P < 0.001. There were no statistically significant differences in the LOS, peri‐operative complication rates, open conversions or bile duct injuries among the BMI groups.ConclusionsThis study showed that LC can be performed safely in the morbid/super obese patients.