P.C. Chandrasinghe

Colorectal cancer in the young, many questions, few answers

At a time where the incidence of colorectal cancer, a disease predominantly of developed nations, is showing a decline in those 50 years of age and older, data from the West is showing a rising incidence of this cancer in young individuals. Central to this has been the 75% increase in rectal cancer incidence in the last four decades. Furthermore, predictive data based on mathematical modelling indicates a 124 percent rise in the incidence of rectal cancer by the year 2030 - a statistic that calls for collective global thought and action. While predominance of colorectal cancer (CRC) is likely to be in that part of the large bowel distal to the splenic flexure, which makes flexible sigmoidoscopic examination an ideal screening tool, the cost and benefit of mass screening in young people remain unknown. In countries where the incidence of young CRC is as high as 35% to 50%, the available data do not seem to indicate that the disease in young people is one of high red meat consuming nations only. Improvement in our understanding of genetic pathways in the aetiology of CRC, chiefly of the MSI, CIN and CIMP pathway, supports the notion that up to 30% of CRC is genetic, and may reflect a familial trait or environmentally induced changes. However, a number of other germline and somatic mutations, some of which remain unidentified, may play a role in the genesis of this cancer and stand in the way of a clear understanding of CRC in the young. Clinically, a proportion of young persons with CRC die early after curative surgery, presumably from aggressive tumour biology, compared with the majority in whom survival after operation will remain unchanged for five years or greater. The challenge in the future will be to determine, by genetic fingerprinting or otherwise, those at risk of developing CRC and the determinants of survival in those who develop CRC. Ultimately, prevention and early detection, just like for those over 50 years with CRC, will determine the outcome of CRC in young persons. At present, aside from those with an established familial tendency, there is no consensus on screening young persons who may be at risk. However, increasing awareness of this cancer in the young and the established benefit of prevention in older persons, must be a message that should be communicated with medical students, primary health care personnel and first contact doctors. The latter constitutes a formidable challenge.

Pre-operative hypoalbuminaemia predicts poor overall survival in rectal cancer: a retrospective cohort analysis

BackgroundSerum albumin is a marker of nutrition and inflammation. It has recently emerged as a predictor of outcome after surgery for rectal cancer. Our aim was to evaluate if pre-operative serum albumin would predict survival after resection for rectal cancer.Method226 Patients with rectal cancer of all stages undergoing resection with curative intent were studied. Kaplan-Meier curves analysed survival based on a pre-operative albumin level of <35 g/L vs. >35 g/L. We sought for significant associations of survival with age, sex, stage, tumour site, use of neoadjuvant chemoradiation, microscopic positive resection margins, differentiation, angio, peri-neural, and lymphovascular invasion using individual variable analysis. Multifactorial analysis was performed using type III analysis with Weibull hazard model and Cox-proportional hazard model. Significance was assigned to a P value <0.05.ResultsOf 226 patients (median age- 59 years; range 19 – 88, Male - 54%), forty five (20%) had an albumin level < 35 g/L and was associated with a poor overall survival (P = 0.02). Mean survival in months for <35 g/L vs. >35 g/L was 64.7 (SE - 9.3) vs. 95.8 (SE – 7.0) and 5 year overall survival rates were 49% and 69%. Individual variable analysis revealed age, circumferential margin, stage, perineural, lympho-vascular and angio invasion to be also significant. With multifactorial analysis hypoalbuminaemia (HR = 0.58; 95% CI: 0.35 - 0.95, P = 0.03), advanced stage (HR = 2.0; 95% CI: 1.26 - 3.23, P < 0.01) and positive circumferential margin (HR = 2.2; 95% CI: 1.26 - 3.89, P < 0.01) remained significant.ConclusionPreoperative hypoalbuminaemia is an independent risk factor for poor overall survival in rectal cancer. Advanced tumour stage and circumferential margin positivity were the other associations with poor survival.

The prevalence of autoimmune thyroiditis after universal salt iodisation in Sri Lanka.

INTRODUCTION Sri Lanka is endemic for goiters. Iodine deficiency is thought to be the main cause. The global iodisation programme was implemented in the country in 1995. Several studies done in school children have shown a reduction in the goiter prevalence (3.8%) in the initial post iodisation period. An island wide, community based study was carried out to study the prevalence of goiters. METHODS A multistage cluster sampling method was used. Examination of goiters was done by two trained investigators and graded according to the WHO grading. Fine needle aspiration cytology of the goitres was also undertaken in the field. A sample of urine was collected from all participants. In a random sample of 153 individuals with a goiter, serum was checked for anti thyroid peroxidase antibodies. RESULTS Out of 5200 individuals screened, 426 had a clinically detectable goiter. Adjusted prevalence rate was 6.8%. Both serological and cytological evidence of autoimmune thyroiditis was seen in 19.6% of goiters. Mean urinary iodine concentration was 235 μg/l range 11.1 - 425 μg/l). Association between elevated antithyroperoxidase antibodies and median urinary iodine concentration was significant. CONCLUSION Goiter prevalence in Sri Lanka has increased after an initial drop following the iodisation. A significant proportion of goiters is due to AIT. Urinary excretion of Iodine in the community is high and has a positive correlation with the prevalence of aTPO anti vodies. Increase in AIT due to a high Iodine intake may account for the rise in goiter prevalence.

Obstructive jaundice caused by a biliary mucinous cystadenoma in a woman: a case report

IntroductionMucinous cystadenoma of the liver is a rare (less than 5%) neoplasm. This condition is more common in young women and accounts for non-specific symptoms. Cyst adenomas commonly affect the intrahepatic system (90%) and are rarely found in the extrahepatic biliary system or affecting both the systems.Case presentationA 39-year-old Sinhalese woman presented with features of obstructive jaundice and was found to have a biliary neoplasm on imaging. In the absence of a definitive diagnosis despite extensive imaging she underwent preoperative endoscopic biliary drainage followed by a left hemihepatectomy with Roux-en-Y hepaticojejunostomy. A pathological examination of the specimen revealed an obstruction of the bile duct caused by a biliary mucinous cystadenoma affecting both the intrahepatic and extrahepatic systems.ConclusionsBiliary mucinous cystadenoma rarely present with obstructive jaundice affecting both intrahepatic and extrahepatic ducts. Exhaustive investigation might not help in the diagnosis and may need to be treated based on clinical judgment. The definitive treatment modality is surgery due to its malignant potential. The operative procedure is technically demanding and is best performed at specialist centers to minimize complications.

The MACC1-SPON2 axis: A new biomarker and therapeutic target in colorectal cancer.

In this issue of the Journal, Schmid et al identify Spondin 2 (SPON2) as a prominent downstream signaling target of metastasis-associated in colon cancer 1 (MACC1) in colorectal cancer (CRC). It is shown that SPON2 mediates MACC1-induced CRC cell proliferation, invasion and metastasis in vitro and in vivo, while its high expression correlates with adverse disease free survival in clinical samples. Therefore, not only does this study shed further light into the complexity of colorectal carcinogenesis, but it also puts forward a potential novel prognostic biomarker to predict high-risk tumors before they metastasize. The MACC1/SPON2 axis may also have utility beyond an indicator of tumor aggressiveness and lends itself as a promising therapeutic target for colorectal and potentially other solid tumors.

Development of a model of three-dimensional imaging for the preoperative planning of TaTME

Since total mesorectal excision (TME) was first described in the early 1930s and later popularised by Heald [1], efforts have been made to standardise the technique, following the correct embryological planes and using appropriate landmarks. Laparoscopic and robotically assisted approaches to the rectum have gained popularity during recent years, compelling colorectal surgeons to develop their skills and knowledge. Transanal TME (TaTME) is a new addition to the approaches in rectal surgery. Despite being associated with several benefits in selected patients, TaTME requires advanced technical skills and, more importantly, knowledge of the pelvic structures, planes and spaces as they are encountered moving cephalad from the perineum. Magnetic resonance imaging (MRI) is the gold standard for imaging of the pelvis and pelvic floor, but understanding of relevant anatomy when performing a new technique may be hampered by difficulty in interpretation of two-dimensional (2D) images when considering three-dimensional (3D) structures. We describe a new tool that could help understanding of TaTME planes and preoperative planning.

Role of SMAD proteins in colitis-associated cancer: from known to the unknown.

Small mothers against decapentaplegic (SMAD) proteins are a family of signal transduction molecules in transforming growth factor β (TGFβ) ligand pathways that have been found to have a key role in the pathogenesis of inflammatory bowel disease (IBD). Long standing IBD predisposes individuals to colitis-associated colorectal cancer (CAC), an entity that possess unique characteristics compared to hereditary and sporadic cancer. The ligands of the TGFβ super family along with SMADs have also been implicated in several aspects of colorectal cancer formation. SMAD proteins are shown to be involved in a number of potentially carcinogenic mechanisms such as altering gene transcription, controlling stem cell differentiation to causing epigenetic changes. Modulation of these proteins has emerged as a novel therapeutic intervention for IBD although its effect on carcinogenesis remains elusive. This account reviews available evidence linking SMAD proteins to CAC and explores the potential areas for future research in this area.

Correction: The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas

[This corrects the article DOI: 10.18632/oncotarget.24257.].

Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first groups drugs were consistent with a treatment plan whereby all drugs received agreed with their tumors molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not (P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group (P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

Technical Tips and Tricks of Outpatients Treatments for Hemorrhoids

Hemorrhoids are a common condition affecting the anorectum. The clinician must accurately diagnose the condition and exclude more sinister causes responsible for the same symptoms. A focused history and thorough examination help in establishing a differential diagnosis. The treatment modality is guided by the degree of the hemorrhoids. Conservative measures should be employed, including dietary advice and toileting techniques, to treat acute inflammation and as a long-term method of reducing symptom recurrence and worsening disease. A wide range of out-patient therapies are available and all have been shown to be effective in experienced hands and when used in the correct clinical context. Here we present an approach to out-patient treatment C. A. Leo (*) · J. D. Hodgkinson · C. J. Vaizey · J. Warusavitarne Surgery, St Mark’s Hospital Academic Institute, London North West NHS Trust, Harrow, UK Department of surgery and cancer, Imperial College of London, London, UK e-mail: a.leo@nhs.net; cosimoleo@gmail.com; jonathanhodgkinson@nhs.net; cvaizey@nhs.net; j.warusavitarne@nhs.net P. Chandrasinghe Surgery, St Mark’s Hospital Academic Institute, London North West NHS Trust, Harrow, UK Department of surgery and cancer, Imperial College of London, London, UK Department of Surgery, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka e-mail: pcchandrasinghe@gmail.com # Springer International Publishing AG 2018 C. Ratto et al. (eds.), Hemorrhoids, Coloproctology 2, https://doi.org/10.1007/978-3-319-51989-0_14-1 1 methods including conservative treatments, medical therapies, and simple interventions.