keith lindley | University College London (original) (raw)
Papers by keith lindley
Frontiers in Pediatrics
Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the ga... more Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of Basidiobolus. He made a full recovery with a combination of surgery and prolonged targeted antifungal medication.
Neurogastroenterology & Motility
Neurogastroenterology & Motility
BMC pediatrics, Feb 9, 2018
In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating ma... more In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating many hepatopancreaticobiliary (HPB) conditions. HPB disease is being diagnosed with increasing frequency in children but information about role of ERCP and EUS and their outcomes in this population remain limited. Therefore the aims of this study were to describe the paediatric ERCP and EUS experience from a large tertiary referral HPB centre, and to systematically compare outcomes with those of other published series. All patients <18 years undergoing an ERCP or EUS between January 1992-December 2014 were included. Indications for the procedure, rates of technical success, procedural adverse events and reinterventions were recorded in all cases. Ninety children underwent 111 procedures (87 ERCPs and 24 EUS). 53% (48) were female with a median age of 14 years (range: 3 months - 17 years). Procedures were performed under general anaesthesia (n = 48) or conscious sedation (n = 63). Common...
Pediatric Surgery International
To report outcomes of children with constipation refractory to medical management and manometrica... more To report outcomes of children with constipation refractory to medical management and manometrically proven distal colonic dysmotility, managed with rectosigmoidectomy followed by Duhamel operation (Duhamel). Children who underwent a Duhamel from 2009 onwards for intractable constipation and left colonic dysmotility were retrospectively reviewed. The primary end point was resolution of constipation, and secondary end point was postoperative complications. Continuous data were median (range). 11 patients (4 males) had Duhamel at 11 years (5-16) with constipation started from 2 years (1-8). Hirschsprung&amp;#39;s disease was excluded. All Duhamels were performed with a covering ileostomy: 9 following a Hartmann procedure, one following a previously failed reversal of Hartmann, and one Duhamel performed with a pre-existing ileostomy. All ileostomies were subsequently closed. Median resection length was 22 cm (11-31). Length of stay was 8 days (5-23). Follow-up was 5 years (0.5-7). Age at final review was 15 years (10-18). Resolution of constipation occurred in nine patients (4 required antegrade continence enemas (ACE), 5 with laxative); two had persistent constipation and faecal incontinence despite ACE, ultimately requiring an ileostomy. Two postoperative small bowel obstructions required laparotomy. Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.
European Journal of Pediatrics
Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a ma... more Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a matter of debate. Records of children treated for achalasia, over an 18-year period, were reviewed.Forty-eight children (median age at diagnosis 10 years; range 3-17 years) were identified. Twenty-eight patients were initially treated with Heller&amp;#39;s myotomy (HM) and 20 with balloon dilatation (BD). At last follow-up (median 3 years; range 1-5.5 years), 43.8% (21/48) of children were symptom free. The number of asymptomatic children was significantly higher among those treated initially with HM compared to BD (HM 15/28, 53.6% BD 6/20, 30%, p &amp;lt; 0.05). All children who underwent BD required HM due to symptom recurrence. The median (range) total number of procedures was significantly higher in the BD group (BD 3 (1-7); HM 1 (1-5); p &amp;lt; 0.05) with a shorter time to the second intervention (BD 14 months, 95%CI 4-24; HM 58 months, 95%CI 38-79; p &amp;lt; 0.05). Of 108 procedures, esophageal perforation occurred in two children after HM (two out of 48 HM procedures in total, 4%) and one child after BD (1/60, 1.7%). Less than half of children with achalasia are symptom free after initial treatment with either BD or HM. HM, however, when performed as first procedure, provided longer symptom-free period and reduced need for subsequent intervention. What is Known: • Balloon dilatation (BD) and Heller&amp;#39;s myotomy (HM) are safe and effective treatment options for achalasia. • Controversy, however, exists regarding the most effective initial therapeutic approach. What is New: • HM with or without fundoplication may represent the initial therapeutic approach of choice. • Initial BD may negatively affect the outcome of a subsequent HM.
Frontline Gastroenterology
News in Physiological Sciences, Oct 1, 1997
News in Physiological Science 12 197 203, 1997
In Pediatric Research, 2000
Journal of Crohn's and Colitis Supplements, 2009
The aim was to assess indications and clinical responses to the use of Infliximab in children wit... more The aim was to assess indications and clinical responses to the use of Infliximab in children with refractory inflammatory bowel disease (CD, UC, IC and others) to conventional medical treatment. Methods: We reviewed 50 case notes, median age 14.75 years (range 1.6 to 19.9 y, 28 male) in a 6 year period in our hospital. Results: The overall clinical response to Infliximab was 86% (36 patients, n = 42). Indications were Crohn's disease only (CD), response 16 out of 17 patients, fistulating CD 5/6, CD with Orofacial granulomatosis (OFG) 4/4, CD with Juvenile idiopathic arthritis (JIA) 2/2, Ulcerative colitis (UC) 4/5, Indeterminate colitis (IC) 4/5 and others 1/3. Median age at first Infliximab infusion was 13.9 y (range 1.5 to 17.10 y). Median duration of infusions was 9 months (range 1 to 33). 2 patients with UC and 2 with IC received additional Basiliximab infusions, for intractable bleeding and treatment failure. 32 patients (n = 50) had some form of immundysregulation. 38 patients (n = 46) received the standard regimen of infusions at weeks 0, 2 and 6 and then 8weekly thereafter at a dose of 5 mg/kg. All patients (n = 50) were on at least 2 immunosuppressive medications at 1st Infliximab infusion, 31 patients had 3 or more. None of the above patients had adverse reactions. Conclusion: Our findings suggest that Infliximab is an efficacious and safe treatment for intractable IBD and should be considered in patients unresponsive to conventional treatments.
Progress in Respiratory Research, 2005
Cystic fibrosis affects the epithelia of multiple organs including the gastrointestinal and respi... more Cystic fibrosis affects the epithelia of multiple organs including the gastrointestinal and respiratory tracts and can result in suppurative lung disease and severe pancreatic exocrine insufficiency. The pancreatic phenotype is variable with differing manifestations in pancreatic-sufficient (PS) and pancreatic-insufficient (PI) individuals and the possibility of progression from PS to PI phenotype with the passage of time.This chapter focuses on the
Journal of Pediatric Gastroenterology and Nutrition, 2015
Chronic constipation is one of the most common chronic disease in children. Most of cases are fun... more Chronic constipation is one of the most common chronic disease in children. Most of cases are functional, however some has problem of organic myopathic or neuropathic colon. Colonic transit study with oro-anal transit markers is the basic diagnostic tool for colonic dysmotility in clinical practice, colonic manometry is the recommended investigation in the next step. Nevertheless, the colonic manometry is considered more invasive, expensive and also unavailable in many countries. The aim of this study is to assess the diagnostic value of conventional method as colonic transit study compared with the novel high-resolution colonic manometry in diagnose colonic abnormalities. Fifty constipated children in Great Ormond Street hospital were retrospectively reviewed in demographic data and investigation result. The diagnosis of constipation was based on history and physical examination which followed Rome III criteria. All of enrolled patients received colonic manometry investigation before colonic transit study in order to reduce the bias. For colonic transit protocol, patients had to ingest a 10-markers capsule on 3 consecutive days and an abdominal x-ray was obtained on day 4. The cut-off values for abnormal segmental and total colonic transit time(CTT) were based on Arhan et al publication. Fifty constipated children with the mean age of 9.77 years (1.15-17.32) were included. Of all, 39(78%) patients had colonic abnormality detected by colonic manometry while 38(76%) patients had abnormal CTT.The sensitivity, specificity, and positive predictive value(PPV) of colonic transit study for abnormal total CTT were 46.2%, 72.7% and 85.7%, respectively. In aspect of abnormal segmental CTT, the sensitivity, specificity and PPV of right colon are 66.7%, 63.6% and 20%; left colon are 16.7%, 72.7% and 7.69%; and rectosigmoid colon are 29.4%, 68.8% and 66.7%, respectively. Colonic transit study seemed to have satisfied posttest probability to diagnose total colonic abnormality. However, for segmental CTT, this test might be invalid and the consideration to use as predictor of segmental abnormality was not recommended.
The Journal of Pediatrics, 2015
We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-... more We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-opaque marker test in children with constipation. All children underwent 2 radio-opaque marker-CTT tests, both in cleansed and uncleansed bowel state. Our findings confirm that the state of colonic fecal filling may significantly influence CTT.
Journal of pediatric gastroenterology and nutrition, 2015
Diagnosis of aerophagia is based on clinical symptoms and described in Rome III Criteria. The aim... more Diagnosis of aerophagia is based on clinical symptoms and described in Rome III Criteria. The aim of this study was to estimate the normal and pathological values for air swallows measured with pH-impedance in children. We analysed features of air swallowing in pH-impedance for patients hospitalized in the Great Ormond Street Hospital in 2008-2014, with the clinical symptoms of aerophagia, who have met the Rome III Criteria. Children with pH-impedance performed due to other gastrointestinal conditions (GORD, Abdominal pain, food allergy and asthma) and had normal studies comprised the control group. The exclusion criteria were: neurological, metabolic or genetic disorders, previous oesophageal surgery including fundoplication, connective tissue disorders and studies lasting less than 16 hours in durationAll studies were re analysed manually, meals were excluded from analysis. Total number of air swallows (in upright and recumbent position); mixed swallows, gastric belching and supra...
Clinical and Translational Allergy, 2015
Frontiers in Pediatrics
Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the ga... more Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of Basidiobolus. He made a full recovery with a combination of surgery and prolonged targeted antifungal medication.
Neurogastroenterology & Motility
Neurogastroenterology & Motility
BMC pediatrics, Feb 9, 2018
In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating ma... more In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating many hepatopancreaticobiliary (HPB) conditions. HPB disease is being diagnosed with increasing frequency in children but information about role of ERCP and EUS and their outcomes in this population remain limited. Therefore the aims of this study were to describe the paediatric ERCP and EUS experience from a large tertiary referral HPB centre, and to systematically compare outcomes with those of other published series. All patients <18 years undergoing an ERCP or EUS between January 1992-December 2014 were included. Indications for the procedure, rates of technical success, procedural adverse events and reinterventions were recorded in all cases. Ninety children underwent 111 procedures (87 ERCPs and 24 EUS). 53% (48) were female with a median age of 14 years (range: 3 months - 17 years). Procedures were performed under general anaesthesia (n = 48) or conscious sedation (n = 63). Common...
Pediatric Surgery International
To report outcomes of children with constipation refractory to medical management and manometrica... more To report outcomes of children with constipation refractory to medical management and manometrically proven distal colonic dysmotility, managed with rectosigmoidectomy followed by Duhamel operation (Duhamel). Children who underwent a Duhamel from 2009 onwards for intractable constipation and left colonic dysmotility were retrospectively reviewed. The primary end point was resolution of constipation, and secondary end point was postoperative complications. Continuous data were median (range). 11 patients (4 males) had Duhamel at 11 years (5-16) with constipation started from 2 years (1-8). Hirschsprung&amp;#39;s disease was excluded. All Duhamels were performed with a covering ileostomy: 9 following a Hartmann procedure, one following a previously failed reversal of Hartmann, and one Duhamel performed with a pre-existing ileostomy. All ileostomies were subsequently closed. Median resection length was 22 cm (11-31). Length of stay was 8 days (5-23). Follow-up was 5 years (0.5-7). Age at final review was 15 years (10-18). Resolution of constipation occurred in nine patients (4 required antegrade continence enemas (ACE), 5 with laxative); two had persistent constipation and faecal incontinence despite ACE, ultimately requiring an ileostomy. Two postoperative small bowel obstructions required laparotomy. Duhamel performed in children with manometrically proven distal colonic dysmotility yielded 82% resolution of refractory constipation; half of them subsequently needed ACE.
European Journal of Pediatrics
Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a ma... more Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a matter of debate. Records of children treated for achalasia, over an 18-year period, were reviewed.Forty-eight children (median age at diagnosis 10 years; range 3-17 years) were identified. Twenty-eight patients were initially treated with Heller&amp;#39;s myotomy (HM) and 20 with balloon dilatation (BD). At last follow-up (median 3 years; range 1-5.5 years), 43.8% (21/48) of children were symptom free. The number of asymptomatic children was significantly higher among those treated initially with HM compared to BD (HM 15/28, 53.6% BD 6/20, 30%, p &amp;lt; 0.05). All children who underwent BD required HM due to symptom recurrence. The median (range) total number of procedures was significantly higher in the BD group (BD 3 (1-7); HM 1 (1-5); p &amp;lt; 0.05) with a shorter time to the second intervention (BD 14 months, 95%CI 4-24; HM 58 months, 95%CI 38-79; p &amp;lt; 0.05). Of 108 procedures, esophageal perforation occurred in two children after HM (two out of 48 HM procedures in total, 4%) and one child after BD (1/60, 1.7%). Less than half of children with achalasia are symptom free after initial treatment with either BD or HM. HM, however, when performed as first procedure, provided longer symptom-free period and reduced need for subsequent intervention. What is Known: • Balloon dilatation (BD) and Heller&amp;#39;s myotomy (HM) are safe and effective treatment options for achalasia. • Controversy, however, exists regarding the most effective initial therapeutic approach. What is New: • HM with or without fundoplication may represent the initial therapeutic approach of choice. • Initial BD may negatively affect the outcome of a subsequent HM.
Frontline Gastroenterology
News in Physiological Sciences, Oct 1, 1997
News in Physiological Science 12 197 203, 1997
In Pediatric Research, 2000
Journal of Crohn's and Colitis Supplements, 2009
The aim was to assess indications and clinical responses to the use of Infliximab in children wit... more The aim was to assess indications and clinical responses to the use of Infliximab in children with refractory inflammatory bowel disease (CD, UC, IC and others) to conventional medical treatment. Methods: We reviewed 50 case notes, median age 14.75 years (range 1.6 to 19.9 y, 28 male) in a 6 year period in our hospital. Results: The overall clinical response to Infliximab was 86% (36 patients, n = 42). Indications were Crohn's disease only (CD), response 16 out of 17 patients, fistulating CD 5/6, CD with Orofacial granulomatosis (OFG) 4/4, CD with Juvenile idiopathic arthritis (JIA) 2/2, Ulcerative colitis (UC) 4/5, Indeterminate colitis (IC) 4/5 and others 1/3. Median age at first Infliximab infusion was 13.9 y (range 1.5 to 17.10 y). Median duration of infusions was 9 months (range 1 to 33). 2 patients with UC and 2 with IC received additional Basiliximab infusions, for intractable bleeding and treatment failure. 32 patients (n = 50) had some form of immundysregulation. 38 patients (n = 46) received the standard regimen of infusions at weeks 0, 2 and 6 and then 8weekly thereafter at a dose of 5 mg/kg. All patients (n = 50) were on at least 2 immunosuppressive medications at 1st Infliximab infusion, 31 patients had 3 or more. None of the above patients had adverse reactions. Conclusion: Our findings suggest that Infliximab is an efficacious and safe treatment for intractable IBD and should be considered in patients unresponsive to conventional treatments.
Progress in Respiratory Research, 2005
Cystic fibrosis affects the epithelia of multiple organs including the gastrointestinal and respi... more Cystic fibrosis affects the epithelia of multiple organs including the gastrointestinal and respiratory tracts and can result in suppurative lung disease and severe pancreatic exocrine insufficiency. The pancreatic phenotype is variable with differing manifestations in pancreatic-sufficient (PS) and pancreatic-insufficient (PI) individuals and the possibility of progression from PS to PI phenotype with the passage of time.This chapter focuses on the
Journal of Pediatric Gastroenterology and Nutrition, 2015
Chronic constipation is one of the most common chronic disease in children. Most of cases are fun... more Chronic constipation is one of the most common chronic disease in children. Most of cases are functional, however some has problem of organic myopathic or neuropathic colon. Colonic transit study with oro-anal transit markers is the basic diagnostic tool for colonic dysmotility in clinical practice, colonic manometry is the recommended investigation in the next step. Nevertheless, the colonic manometry is considered more invasive, expensive and also unavailable in many countries. The aim of this study is to assess the diagnostic value of conventional method as colonic transit study compared with the novel high-resolution colonic manometry in diagnose colonic abnormalities. Fifty constipated children in Great Ormond Street hospital were retrospectively reviewed in demographic data and investigation result. The diagnosis of constipation was based on history and physical examination which followed Rome III criteria. All of enrolled patients received colonic manometry investigation before colonic transit study in order to reduce the bias. For colonic transit protocol, patients had to ingest a 10-markers capsule on 3 consecutive days and an abdominal x-ray was obtained on day 4. The cut-off values for abnormal segmental and total colonic transit time(CTT) were based on Arhan et al publication. Fifty constipated children with the mean age of 9.77 years (1.15-17.32) were included. Of all, 39(78%) patients had colonic abnormality detected by colonic manometry while 38(76%) patients had abnormal CTT.The sensitivity, specificity, and positive predictive value(PPV) of colonic transit study for abnormal total CTT were 46.2%, 72.7% and 85.7%, respectively. In aspect of abnormal segmental CTT, the sensitivity, specificity and PPV of right colon are 66.7%, 63.6% and 20%; left colon are 16.7%, 72.7% and 7.69%; and rectosigmoid colon are 29.4%, 68.8% and 66.7%, respectively. Colonic transit study seemed to have satisfied posttest probability to diagnose total colonic abnormality. However, for segmental CTT, this test might be invalid and the consideration to use as predictor of segmental abnormality was not recommended.
The Journal of Pediatrics, 2015
We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-... more We evaluated the effect of bowel preparation on colonic transit time (CTT) measured by the radio-opaque marker test in children with constipation. All children underwent 2 radio-opaque marker-CTT tests, both in cleansed and uncleansed bowel state. Our findings confirm that the state of colonic fecal filling may significantly influence CTT.
Journal of pediatric gastroenterology and nutrition, 2015
Diagnosis of aerophagia is based on clinical symptoms and described in Rome III Criteria. The aim... more Diagnosis of aerophagia is based on clinical symptoms and described in Rome III Criteria. The aim of this study was to estimate the normal and pathological values for air swallows measured with pH-impedance in children. We analysed features of air swallowing in pH-impedance for patients hospitalized in the Great Ormond Street Hospital in 2008-2014, with the clinical symptoms of aerophagia, who have met the Rome III Criteria. Children with pH-impedance performed due to other gastrointestinal conditions (GORD, Abdominal pain, food allergy and asthma) and had normal studies comprised the control group. The exclusion criteria were: neurological, metabolic or genetic disorders, previous oesophageal surgery including fundoplication, connective tissue disorders and studies lasting less than 16 hours in durationAll studies were re analysed manually, meals were excluded from analysis. Total number of air swallows (in upright and recumbent position); mixed swallows, gastric belching and supra...
Clinical and Translational Allergy, 2015