Andrew Latchford
Derriford Hospital
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Featured researches published by Andrew Latchford.
Diseases of The Colon & Rectum | 2012
Andrew Latchford; Kay Neale; Robin K. S. Phillips; Susan K. Clark
BACKGROUND: Juvenile polyposis syndrome is phentoypically and genotypically heterogeneous. It is associated with an increased risk of GI cancers, and surveillance is recommended. Few data exist that detail the outcomes of surveillance in juvenile polyposis syndrome. OBJECTIVE: The aim of this study was to review clinical features, genetic mutations, and long-term outcome data in patients with juvenile polyposis syndrome. DESIGN: This study is a retrospective review. SETTING: The Polyposis Registry, St Mark’s Hospital, was used in the performance of this study. PATIENTS: Patients with juvenile polyposis syndrome who were followed up at our institution were included. RESULTS: Forty-four patients (27 male) from 30 kindreds were included. Fifteen were diagnosed by screening, and 29 presented symptomatically. Nineteen patients had SMAD4 mutation and 9 had BMPR1A mutation. Five patients (11%) had valvular heart disease. Telangiectasia/vascular abnormalities were observed in 4 (9%) patients, and macrocephaly was observed in 5 (11%). Six patients (14%) developed cancer; 4 had cancer at the time of diagnosis of juvenile polyposis syndrome, 3 developed cancer while on surveillance (1 patient had a second primary). All patients with advanced upper GI disease had SMAD4 mutations. Where germline mutation was known, all patients with telangiectasia had SMAD4 mutation. Seven patients required GI surgery at our institution: colectomy and ileorectal anastomosis (1), restorative proctocolecotomy (1), anteroposterior excision for rectal cancer (1), gastrectomy (2), and laparotomy and intraoperative enteroscopy (1). There were no complications of endoscopic surveillance. Colonic polyps predominated; 535 of 767 (69.8%) of colonic polyps were right sided. One patient had a solitary significant small-bowel polyp. Sixty-five juvenile polyps contained dysplasia (mild to moderate). Two patients had severe dysplasia or cancer found in carpeting polyps. LIMITATIONS: This is a retrospective review. The cohort size, although modest, is good for such a rare condition. CONCLUSION: Extraintestinal features are common. Gastrointestinal surveillance is safe. Most colonic polyps are right sided, and detecting dysplasia is uncommon. Carpeting polyps are of particular concern.
Clinical Gastroenterology and Hepatology | 2009
Andrew Latchford; Kay Neale; Allan D. Spigelman; Robin K. S. Phillips; Susan K. Clark
BACKGROUND & AIMS Most patients with familial adenomatous polyposis (FAP) develop duodenal adenomas; duodenal cancer is a major cause of mortality in this patient group. We reviewed cases of duodenal cancer in patients with FAP to identify factors that determine long-term cancer risk. METHODS Twenty FAP patients (12 male) were identified from a registry database search. Data from registry and medical notes and endoscopic and histopathologic reports were evaluated. RESULTS Of the cancers that developed in these patients, 11 were ampullary and 9 were duodenal. The median age at cancer diagnosis was 53 years. Seventeen patients died (median age at death, 57 y; median survival from diagnosis, 11 mo); the cause of death was metastatic or duodenal/ampullary cancer in 14 patients. Fifteen patients presented symptomatically (including 3 interval cancers while on surveillance). Two were diagnosed at surveillance and 3 were diagnosed during surgery performed for endoscopic features of advanced benign disease. Duodenal cancers were associated with a significantly lower mean colonic polyp count than ampullary cancers (496 +/- 282 vs 1322 +/- 735; P = .025); there appeared to be familial clustering of this cancer. When endoscopic data were available (n = 11 of 20), all ampullary cancers arose from ampullas greater than 1 cm. The Spigelman stage did not predict risk of ampullary cancer but did predict duodenal cancer (median stage 2 vs stage 4 for duodenal cancer). CONCLUSIONS Once cancer arises in patients with FAP, prognosis is poor, so cancer prevention should be the main goal. Surveillance intervals should reflect both Spigelman staging and ampullary disease.
Diseases of The Colon & Rectum | 2011
Andrew Latchford; Kay Neale; R. K. S. Phillips; Susan K. Clark
BACKGROUND: Peutz-Jeghers syndrome is characterized by GI polyps and mucocutaneous pigmentation and carries an increased risk of GI cancer. GI polyps may bleed or cause intussusception. Luminal GI surveillance is recommended, but there are few data detailing outcomes from GI surveillance in Peutz-Jeghers syndrome. OBJECTIVE: This study aimed to assess outcomes from GI surveillance in patients with Peutz-Jeghers syndrome. DESIGN: This study is a retrospective review, using hospital and registry notes and endoscopy and histology reports. SETTING: The investigation was conducted at a tertiary referral center. PATIENTS: All patients with Peutz-Jeghers syndrome who were followed up at St Marks hospital were included. MAIN OUTCOME MEASURES: The primary outcomes measured were surveillance procedures performed, complications, and long-term outcomes. RESULTS: Sixty-three patients from 48 pedigrees were included; the median age when patients were first seen was 20 years (range, 3–59). Only baseline investigations were performed in 12 patients. The remaining patients were followed up for 683 patient years, a median of 10 years (range, 2–41). Seven hundred seventy-six procedures were performed to assess the GI tract. These led to 5 double-balloon enteroscopies, 1 push enteroscopy, and 71 surgical procedures. Of the surgical procedures, 20 were performed as a result of baseline investigations, 12 arose from investigations of symptoms, and 39 were due to surveillance of asymptomatic patients. No emergency surgical interventions were performed. No luminal GI cancers were diagnosed. Of the 2461 polypectomies performed, 6 polyps contained atypia or dysplasia. Six complications arose from endoscopy or surgical intervention, requiring 5 laparotomies to manage these complications. CONCLUSION: GI surveillance in Peutz-Jeghers syndrome is relatively safe and avoids the need for emergency surgery for small-bowel polyps. The lack of GI cancers may reflect that surveillance and polypectomy have prevented cancer from developing, although the detection of neoplasia or dysplasia is uncommon.
Familial Cancer | 2011
Andrew Latchford; R. K. S. Phillips
The two main problems in the management of the gastrointestinal tract in patients with Peutz-Jeghers syndrome (PJS) are the long term cancer risk and managing polyp related complications, such as intussusception and bleeding. In this article we will focus mainly on the clinical management of these problems. We will highlight some of the controversies regarding gastrointestinal PJS polyps, cancer development and cancer risk. We will review the available literature, particularly focusing on clinical data, to provide insights into these controversies. We describe guidelines for the surveillance and management of gastrointestinal polyps in PJS and review the data behind current recommendations.
Familial Cancer | 2006
Amy McCart; Andrew Latchford; Emmanouil Volikos; Andrew Rowan; Ian Tomlinson; Andrew Silver
Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition predisposing to multiple adenomatous polyps of the colon. FAP patients frequently carry heterozygous mutations of the APC tumour suppressor gene. Affected individuals from a cohort of FAP families (n=22), where no germ-line APC mutation was detected by direct sequencing, were analysed by Multiplex Ligation-dependent Probe Amplification (MLPA). MLPA identified a previously unreported APC mutation involving duplication of exon 4. Subsequent analysis of cDNA from affected family members revealed expression of mutant mRNA species containing two copies of exon 4, resulting in a frameshift and premature stop codon. Bioinformatic analysis of the relevant APC genomic segment predicted a role for homologous recombination possibly involving Alu repeats in the generation of this genotype. Our results highlight the importance of MLPA as an adjunct to exon-by-exon sequencing in identifying infrequent mutational events in cancer predisposing genes.
Journal of Medical Genetics | 2007
Nirosha Suraweera; Andrew Latchford; Amy McCart; Pauline Rogers; Sarah L. Spain; Oliver M. Sieber; Robin K. S. Phillips; Ian Tomlinson; Andrew Silver
Background: Reproductive factors have been shown by epidemiology studies to alter colorectal cancer risk in women. Familial adenomatous polyposis (FAP) patients carry a germline adenomatous polyposis coli (APC) mutation predisposing to multiple adenoma formation in the intestine. The Min mouse provides a good model of FAP, and we recently reported a significant increase in intestinal tumour multiplicity in a recombinant line of mice following pregnancy. Aim: We considered whether reproduction modulates intestinal tract disease in a large cohort of female patients with FAP (n = 180). Results: Multiple regression analysis showed that the number of colonic polyps observed was not related to the person’s pregnancy status nor the position of their APC germline mutation. The proportion of women attaining a high Spigelman stage (3 or 4) was unrelated to having a pregnancy prior to attaining the maximum Spigelman stage (p = 0.6). On the other hand, having a pregnancy significantly increased the proportion of women that attained the highest Spigelman stage when their APC germline mutation occurred within the mutation cluster region or at or after codon 1020 (50%, 6/12, p = 0.005 and 42%, 13/31, p = 0.006, respectively; multivariable logistic regression). Conclusion: Our data suggest that reproduction may influence disease severity in the upper gastrointestinal tract in patients with FAP.
Endoscopy | 2018
R Rameshshanker; Zacharias P. Tsiamoulos; Andrew Latchford; Morgan Moorghen; Brian P. Saunders
Sessile serrated adenomas/polyps (SSA/ Ps) are frequently found in the proximal colon, where the wall is thinner and easily damaged by diathermy during polypectomy, which also carries a risk of delayed bleeding, perforation, and post-polypectomy syndrome. SSA/Ps are often flat with subtle, irregular edges making endoscopic assessment of their extent difficult [1]. This can lead to incomplete resection and risk of post-colonoscopy cancer [2]. Currently, cold snare resection (CSR) is considered the preferred technique to resect small polyps. It is safe, time efficient, and user friendly [3]. Recently, case series have highlighted the safety and efficiency of CSR for larger adenoE-Videos
Expert opinion on orphan drugs | 2014
Andrew Latchford; Robin K. S. Phillips
Introduction: Familial adenomatous polyposis (FAP) is a rare condition, characterised by the development of multiple adenomatous polyps in the colon and rectum but which also displays a number of extra-colonic manifestations. Undoubtedly, there have been major advances in our understanding and management of FAP. However, despite these advances patients with FAP have a fourfold mortality rate when compared with the general population. Areas covered: The published literature has been critically appraised, focusing on four main areas: genetic aspects of FAP, management of the colorectum, understanding and management of desmoids tumours and the management of duodenal disease in FAP. The progress in these areas that has been made over recent years has then been described, with regard to our scientific understanding as well as clinical management of the condition. Expert opinion: Expert opinion is provided regarding on-going clinical dilemmas. In particular, the expert opinion focuses on clinical management and areas of research that are required, which may directly influence clinical management of this condition, thereby improving the outcome of patients with FAP.
Archive | 2010
Andrew Latchford; Brian P. Saunders
Duodenal disease is becoming an increasingly important cause of morbidity and mortality in patients with FAP. Our current understanding of these lesions is poor and the reason for the lower malignant potential of duodenal polyps compared to colonic polyps in FAP is unexplained. In this chapter we review our current understanding of duodenal disease in FAP, its epidemiology, aetiology and natural history. We describe the sparse evidence regarding the management of these lesions and provide our recommendations for surveillance and management.
Human Molecular Genetics | 2007
Andrew Latchford; Emmanouil Volikos; Victoria A. Johnson; Pauline Rogers; Nirosha Suraweera; Ian Tomlinson; Robin K. S. Phillips; Andrew Silver