Congenital hypertrophy of retinal pigment epithelium (CHRPE) in patients with familial adenomatous polyposis (FAP); a polyposis registry experience

BACKGROUND: Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition giving rise to multiple adenomatous polyps in the colon which invariably become malignant by the fourth decade. Congenital hypertrophy of retinal pigment epithelium (CHRPE) is one of its extra intestinal manifestations early in childhood seen, present in 90% of FAP population and is easy to detect. FINDINGS: Patients diagnosed with FAP and at risk first degree family members were screened for CHRPE using a slit lamp and indirect ophthalmoscopy. The retina of 17 diagnosed FAP patients and 13 individuals at risk were examined. The site and size of CHRPE lesions were documented. Thirteen (76%) of 17 FAP patients (male-10, female – 7, median age - 30 years; range 15-55 years) had CHRPE lesions; seven (54%) had bilateral CHRPE lesions and six (46%) had unilateral lesions. A single lesion was detected in 6 (46%) while 7 (54%) patients had multiple lesions. Of 13 at risk individuals (7- male, female-6 ; median age 34; range 16-52 years), one was positive for CHRPE and 12 were free of retinal lesions. The sensitivity of the presence of a CHRPE lesion in association with colonic polyps in FAP was 76%, specificity 92%, positive predictive value 93%, and negative predictive value 75%. CONCLUSIONS: This study found a high sensitivity and specificity for a CHRPE lesion to be associated with colonic polyps of FAP and hence a useful screening method in a burdened health-care system. The method is minimally invasive and simple and would be of particular value in screening children at risk for FAP

Overall Survival of Elderly Patients Having Surgery for Colorectal Cancer Is Comparable to Younger Patients: Results from a South Asian Population

Introduction. There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. Method. OS between two groups (≥70 versus <70 years) having surgery for CRC was analyzed. Demographics, tumour characteristics, and serological markers were considered as independent factors. Multivariable analysis was done using the Cox proportional hazard model. We also compared overall survival in the elderly versus those <60 and <50 years. Results. 477 patients, 160 elderly (55% male; median age 75, range 70–89) and 317 younger patients (49% male; median age 55, range 16 to 69), were studied. Overall survival in CRC patients ≥70 is comparable to <70 (P=0.45) and <60 years (P=0.08). Poor OS was observed in the ≥70 versus <50 years (P=0.03). TDM in the elderly was poor (P<0.05). Postoperative cardiac complication was the only determinant affecting survival in the elderly (P=0.01). Conclusion. OS in elderly CRC patients having surgery is not worse compared to <70 and <60 years although the TDM was higher. Postoperative cardiac complications significantly affected OS in those ≥70 compared to those <50 years. Chronological age alone should not negatively influence surgical decision-making in the elderly

Surgical Management of Small Bowel Crohn's Disease

Crohn's disease in the small bowel could present itself as an inflammatory stricture, a fibrotic stricture as penetrating disease or a combination of both. It is pertinent to differentiate the disease process as well as its extent to effectively manage the disease. Currently, a combination of medical and surgical therapies forms part of the treatment plan while the debate of which therapy is better continues. In managing the strictures, identification of the disease process through imaging plays a pivotal role as inflammatory strictures respond to anti-tumor necrosis factor (TNF) and biological agents, while fibrotic strictures require endoscopic or surgical intervention. Recent evidence suggests a larger role for surgical excision, particularly in ileocolic disease, while achieving a balance between disease clearance and bowel preservation. Several adaptations to the surgical technique, such as wide mesenteric excision, side to side or Kono-S anastomosis, and long-term metronidazole therapy, are being undertaken even though their absolute benefit is yet to be determined. Penetrating disease requires a broader multidisciplinary approach with a particular focus on nutrition, skincare, and intestinal failure management. The current guidance directs toward early surgical intervention for penetrating disease when feasible. Accurate preoperative imaging, medical management of active diseases, and surgical decision-making based on experience and evidence play a key role in success.</jats:p

Methylation changes in colitis associated cancer and its correlation to SMAD7

Ulcerative colitis (UC) is an inflammatory condition affecting the mucosa of the large bowel and the occurrence is linked to the increase of developing colitis associated cancer (CAC). The identification of biomarkers to predict those who are at risk of progressing to CAC is needed to assist in early decision making for restorative surgery and improved outcome following surgery. However, previous attempts at the identification of consistent genetic biomarkers have not been successful, due to non-reproducibility of the results. This could attribute partly to variability in tissues used and partly to the complex pathophysiology. The regenerative stress in UC mucosa resulting in multiple structural mutations in genes may also be a cause for the variability. Therefore, the first aim of this study was the identification of differentially methylated genes to be used as potential biomarkers of malignant transformation at a precancerous stage. Whole genome bisulphite sequencing was carried out on laser captured epithelial cells on a pilot cohort of 8 samples of normal, inflamed, dysplastic and malignant colonic mucosa. Each sample was matched with adjacent non-neoplastic mucosa or buffy coat from the same patient as controls. Sixty-three hypomethylated and six hypermethylated gene promoters were identified as differentially methylated in the samples compared to the normal epithelium. These methylation changes were unique to the diseased tissue and were consistently found in each stage of the disease, suggesting they could be used as biomarkers for CAC. Out of these genes, 7 hypomethylated and 4 hypermethylated genes were identified as strongly related to CRC pathways. Similarly, the analysis of gene body methylation allowed the identification of further 10 hypomethylated and 2 hypermethylated genes related to CRC pathways. Moreover the identified genes could be annotated to cell adhesion related molecular function and disease processes, including UC and epithelial cancers. Amongst proteins and pathways of clinical importance, TGFβ, a molecule with anti-inflammatory properties, is inhibited in UC-affected mucosa. Recently, SMAD7, the principal intracellular inhibitor of the TGFβ pathway, has been proposed as a therapeutic target in UC. However, SMAD7 is shown to influence CRC development and progression in a less understood manner. Furthermore, studies in breast cancer indicate that SMAD7 influences methylation patterns of cancer-associated genes. Therefore investigating the potential effect of SMAD7 on CAC and differential methylation of related genes would provide insight into its role in CAC. The second and third aims of this study were therefore was to observe the behaviour pattern of SMAD7 at different stages of CAC and analyse the methylation pattern of identified SMAD7-associated genes. Immunohistochemistry and in situ hybridisation was performed on 53 and 33 samples from non-inflamed, inflamed, dysplastic and cancer tissues, respectively. SMAD7 was biphasically expressed in different stages of CAC: high expression during the inflammation and cancer stages was associated with a lower expression in the non-inflamed UC and dysplastic tissues. On the other hand, the downstream molecule pSMAD3 did not show a reduction in expression suggesting an escape of TGFβ from the inhibitory effect of SMAD7 in UC. The evaluation of the methylation patterns in cancer-associated genes supposedly influenced by SMAD7 (CDH1, CLDN4, DNMT1, CGN) did not demonstrate a consistent pattern of differential methylation. This data has strong clinical implications, as the biphasic expression of SMAD7 during precancerous stages suggests further evaluation is needed prior to using an antisense to inhibit SMAD7 in the clinic. In conclusion, this pilot study identified 27 potential genes with differential methylation, of which the expression of some has already been validated with RT-qPCR. The consistency of the methylation pattern of these genes across all stages of CAC and their annotation to cancer and cancer related biological processes make them strong potential candidates for an early biomarker in CAC. An extension of the analysis in a wider samples cohort and complete validation of each target will be necessary to validate their efficacy and lead to developing a clinically useful gene panel to predict CAC.Open Acces

Needs assessment in surgical undergraduate teaching in a South Asian cohort; implications for social, cultural and resource based adaptation of learning methods

   Teaching and learning in higher education has undergone significant transformation during the past few decades. The novel concepts of student centred learning ha been accepted and adopted globally. However the evidence in this subject area is mainly derived from the western population. Research in the recent past has identified the conflicts of implementing these concepts across different cultures. A needs assessment was carried out amongst a cohort of medical undergrduates to regarding their lack of active participation in general in learning activities and small group discussions. Deficiency in language skills (34%), anxiety to make mistakes in public (46%) and reluctance to address the teachers directly (41%) were the leading reasons of lack of active participation. Several structural, resource and time related local factors were identified as reasons for poor contributions for the small group discussions. The student population however was more interested in conceptual learning versus an assessment-oriented teaching. The author discusses the requirement of cultural adaptation of the learning methods plus student orientation for higher education environment to suit socio-economic and cultural background of the locality based on these findings. </p

Laparoscopically detected and nonsurgically managed ileal perforation by an ingested fish bone: a case report

INTRODUCTION: Ileal perforation due to fish bone is a rare event. The condition is difficult to diagnose due to lack of specific clinical features and low sensitivity of imaging techniques. We report a case of ileal perforation by a fish bone that was detected laparoscopically and managed nonsurgically. CASE PRESENTATION: A 45-year-old Sinhalese man presented with acute onset right iliac fossa pain and fever for three days. On examination, he had significant right iliac fossa tenderness and guarding. His white cell count and C-reactive protein level were elevated and an ultrasound scan was indicative of a bowel mass formation. A clinical diagnosis of acute appendicitis was made and laparoscopic appendicectomy was scheduled. At initial survey, a thin spike-like structure was retrieved from the bowel mass, which was revealed to be a fish bone. Our patient was managed with antibiotics only and did not develop any complications. CONCLUSIONS: Ileal perforation due to fish bone is a rare condition that can mimic common conditions like appendicitis. Preoperative diagnosis is rarely made. The slow process of fish bone migration results in concomitant sealing of the perforation, reducing contamination. Use of laparoscopy may be useful in diagnosing this condition and preventing the morbidity of laparotomy in these patients

Complete migration of a composite mesh into small bowel incidentally found during laparotomy for colectomy in an asymptomatic patient: a case report

Abstract Background Composite meshes are used for incisional hernia repair because they enable intraperitoneal mesh placement due to their dorsal surface, which is made of inert material. We report, for the first time, to our knowledge, a case of composite mesh migration detected incidentally during a laparotomy for colon cancer in an asymptomatic patient. Case presentation Our patient was a 71-year-old South Asian man who underwent ventral mesh repair following a postoperative complication after right hemicolectomy for colon cancer. The patient was diagnosed with a metachronous sigmoid cancer 5 years later, for which he underwent laparotomy. During laparotomy, a migrated mesh was incidentally found and extracted from his proximal ileum without any evidence of abscess or fistula formation. Conclusion To our knowledge, this is the first report of an incidentally found migrated composite mesh from a bowel lumen in an asymptomatic patient. </jats:sec