David J. Humes

Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms

Abstract:  Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 – Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 – Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1– Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 – Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis.

Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation.

Background  Recurrent abdominal pain is reported by a third of patients with diverticulosis, particularly those with previous episodes of acute diverticulitis. The current understanding of the etiology of this pain is poor. Our aim was to assess visceral sensitivity in patients with diverticular disease and its association with markers of previous inflammation and neuropeptides.

Prospective randomized trial using cost-utility analysis of early versus delayed laparoscopic cholecystectomy for acute gallbladder disease.

This randomized controlled trial compared the cost–utility of early laparoscopic cholecystectomy with that for conventional management of newly diagnosed acute gallbladder disease.

Concurrent drug use and the risk of perforated colonic diverticular disease: a population-based case–control study

Objective To determine the risk of diverticular perforation associated with current and ever use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. Design, setting and participants Case–control analysis using conditional logistic regression analysis of data from the UK General Practice Research Database. The study involved 899 cases of incident diverticular perforation and 8980 population controls from 1990 to 2005. Main outcome measures Odds ratios (ORs) are presented for perforation associated with use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. Data were adjusted for smoking, comorbidity, prior abdominal pain and body mass index. Results A total of 899 patients with an incident diagnosis of perforated diverticular disease were identified. Current use of opiate analgesics (OR=2.16; 95% CI 1.55 to 3.01) and oral corticosteroids (OR=2.74; 95% CI 1.63 to 4.61) was associated with a two- and threefold increase in the risk of diverticular perforation, respectively. Current use of a calcium antagonist and aspirin were not associated with an increased risk of diverticular perforation. Current statin use was associated with a reduction in the risk of perforation (OR=0.44; 95% CI 0.20 to 0.95). Conclusion Perforated diverticular disease is a serious surgical emergency with current opiate analgesics and oral corticosteroids being strongly associated with an increased risk of diverticular perforation.

The Patient Health Questionnaire 12 Somatic Symptom scale as a predictor of symptom severity and consulting behaviour in patients with irritable bowel syndrome and symptomatic diverticular disease

Background  Anxiety, depression and nongastrointestinal symptoms are often prominent in irritable bowel syndrome (IBS), but their relative value in patient management has not been quantitatively assessed. We modified the Patient Health Questionnaire 15 (PHQ‐15) by excluding three gastrointestinal items to create the PHQ‐12 Somatic Symptom (PHQ‐12 SS) scale.

A Population-Based Study of Perforated Diverticular Disease Incidence and Associated Mortality

BACKGROUND & AIMS Perforated diverticular disease represents the most serious complication of diverticular disease, but little is known regarding its occurrence and mortality. We aimed to determine the incidence and mortality associated with diverticular perforation and the influence of comorbidity. METHODS We used a population-based cohort study using patients with perforated diverticular disease and population controls identified from 1990 to 2005 in the General Practice Research Database (GPRD). Incidence and mortality rates were modelled using Poisson and Cox regression. Comorbidity was quantified using the Charlson index. RESULTS We identified 953 incident patients. The overall incidence was 2.66 (95% confidence interval [CI]: 2.49-2.83) per 100,000 person-years. The incidence rates increased 2.28-fold (95% CI: 1.79-2.95) when corrected for age and sex between 1990 and 2005. The risk of death was highest in the first year with a 6-fold increase (hazard ratio [HR], 5.63; 95% CI: 4.68-6.77). Adjusted for age and sex, the risk of death in the first year was highest in those with lowest comorbidity (HR, 11.11; 95% CI: 8.06-15.31), but the absolute mortality rates were greatest in those with the highest comorbidity (263.1 per 1000 person-years). CONCLUSIONS The incidence of perforated diverticular disease has doubled over the period of the study. Patients presenting with a perforated diverticulum are 6 times more likely to die than the general population during the first year following perforation. Those who have the greatest comorbidity are the most likely to die; however, those with least comorbidity have an 11-fold increase in mortality in the first year.

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

INTRODUCTION The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes. METHODS Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 - July 2009) and after (August 2009 - July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality. RESULTS There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann-Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008-2009 to 6 (16.7%) in 2009-2010 (chi-squared test, p<0.0001). CONCLUSIONS The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.

Psychological and colonic factors in painful diverticulosis

The importance of psychological factors in symptom expression in diverticulosis is unknown. This follow‐up study assessed the relative importance of colonic and psychological factors in symptom expression.

Role of acute diverticulitis in the development of complicated colonic diverticular disease and 1-year mortality after diagnosis in the UK: population-based cohort study

Objective To determine the risk of developing complicated colonic diverticular disease (CCDD) with prior episodes of acute diverticulitis and determine the mortality of the spectrum of CCDD. Design Population-based cohort study. Setting Computerised records from the General Practice Research Database linked to Hospital Episode Statistics data from the UK. Participants Patients and controls registered in the General Practice Research Database from 1990 to 2007. Main outcome measures Mortality was calculated and Cox regression modelling used to provide adjusted HRs and 95% CI. Logistic regression was used to model the effect of prior acute diverticulitis on the development of complications. Results 2950 patients (1872 (63.5%) female) had a diagnosis of CCDD (8739 controls). A total of 1042 (35.3%) patients died compared with 2062 (23.6%) controls. Most excess deaths occurred in the first year after the complication. Patients with a perforation/abscess had a 4.5-fold increase in 1-year mortality (HR 4.55, 95% CI 3.74 to 5.52) compared with the general population, whereas those with a fistula or stricture had a 2.5-fold increase in mortality (fistula HR 2.60, 95% CI 1.47 to 4.62; stricture HR 2.41, 95% CI 1.86 to 3.11). Although most patients (2133 (72.3%)) had suffered no prior episodes of acute diverticulitis, increasing episodes of acute diverticulitis were associated with an increased risk of developing a fistula (two or more prior episodes, OR 1.54 95%, CI 1.08 to 2.19), but there was no clear relationship with stricture or perforation/abscess. Conclusions Although most patients have experienced no prior episodes of acute diverticulitis, fistula formation is preceded by bouts of inflammation. Excess 1-year mortality across the spectrum of CCDD compared with the general population is substantial.

Review article: the pathogenesis and management of acute colonic diverticulitis

Acute diverticulitis, defined as acute inflammation associated with a colonic diverticulum, is a common emergency presentation managed by both surgeons and physicians. There have been advances in both the medical and the surgical treatments offered to patients in recent years.