Increased mucosal eosinophils in colonic diverticulosis and diverticular disease.

AIMS: Eosinophils contribute to tissue homeostasis, damage, and repair. The mucosa of colonic diverticula has not been evaluated for eosinophils by quantitative histology. We aimed to investigate whether mucosal eosinophils and other immune cells are increased in colonic diverticula. METHODS: Hematoxylin and eosin stained sections from colonic surgical resections (n = 82) containing diverticula were examined. Eosinophils, neutrophils, and lymphocytes, in five high power fields in the lamina propria were counted at the base, neck, and ostia of the diverticulum and counts compared to non-diverticula mucosa. The cohort was further subgrouped by elective and emergency surgical indications. RESULTS: Following an initial review of 10 surgical resections from patients with diverticulosis, a total of 82 patients with colonic resections containing diverticula from the descending colon were evaluated (median age 71.5, 42 M/40F). Eosinophil counts for the entire cohort were increased in the base and neck (median 99 and 42, both P = <0.001) compared with the control location (median 16). Eosinophil counts remained significantly increased in the diverticula base (both P = <0.001) and neck (P = 0.01 and <0.001, respectively) in both elective and emergency cases. Lymphocytes were also significantly increased at the diverticula base compared to controls in both elective and emergency subgroups. CONCLUSION: Eosinophils are significantly and most strikingly increased within the diverticulum in resected colonic diverticula. While these observations are novel, the role of eosinophil and chronic inflammation is as yet unclear in the pathophysiology of colonic diverticulosis and diverticular disease.

Using the Patient Health Questionnaire to estimate prevalence and gender differences of somatic symptoms and psychological co-morbidity in a secondary inpatient population with abdominal pain.

BACKGROUND: Somatic disorders and somatic symptoms are common in primary care populations; however, little is known about the prevalence in surgical populations. Identification of inpatients with high somatic symptom burden and psychological co-morbidity could improve access to effective psychological therapies. METHODS: Cross-sectional analysis (n = 465) from a prospective longitudinal cohort study of consecutive adult admissions with non-traumatic abdominal pain, at a tertiary hospital in New South Wales, Australia. We estimated somatic symptom prevalence with the Patient Health Questionnaire-15 at three cut-points: moderate (⩾10), severe (⩾15) and 'bothered a lot' on ⩾3 symptoms; and psychological co-morbidity with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 at standard (⩾10) cut-points. We also examined gender differences for somatic symptoms and psychological co-morbidity. RESULTS: Prevalence was moderate (52%), female predominance (odds ratio = 1.71; 95% confidence interval = [1.18, 2.48]), severe (20%), no gender difference (1.32; [0.83, 2.10]) and 'bothered a lot' on ⩾3 symptoms (53%), female predominance (2.07; [1.42, 3.03]). Co-morbidity of depressive, anxiety and somatic symptoms ranged from 8.2% to 15.9% with no gender differences. CONCLUSION: Somatic symptoms were common and psychological triple co-morbidity occurred in one-sixth of a clinical population admitted for abdominal pain. Co-ordinated surgical and psychological clinical intervention and changes in clinical service organisation may be warranted to provide optimal care.

Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals.

BACKGROUND: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. METHODS: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. RESULTS: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). CONCLUSIONS: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

A systematic scoping review on natural killer cell function in colorectal cancer.

PURPOSE: Natural Killer (NK) cells are a vital part of immune surveillance and have been implicated in colorectal cancer development and prognosis. This systematic review aims to distil the literature on NK cells as it relates to colorectal cancer. METHODS: All published studies over 10 years relating to NK cells and colorectal cancer were reviewed. All studies publishing in English, searchable via pubmed or through reference review and reporting directly on the nature or function of NK cells in colorectal cancer patients were included. Outcomes were determined as alterations or new information regarding NK cells in colorectal cancer patients. RESULTS: Natural killer cells may be implicated in the development of colorectal cancer and may play a role in prognostication of the disease. NK cells are altered by the treatment (both surgical and medical) of colorectal cancer and it seems likely that they will also be a target for manipulation to improve colorectal cancer survival. CONCLUSIONS: NK cell morphology and function are significantly affected by the development of colorectal cancer. Observation of NK cell changes may lead to earlier detection and better prognostication in colorectal cancer. Further study is needed into immunological manipulation of NK cells which may lead to improved colorectal cancer survival.

Systematic Review on the Influence of Tissue Oxygenation on Gut Microbiota and Anastomotic Healing.

BACKGROUND: Anastomotic leak rates have not improved over several decades despite improvements in surgical techniques and patient care. The gut microbiome has been implicated in the development of leaks. The exact mechanisms by which tissue oxygenation affects gut microbial composition and anastomotic healing physiology are unclear. Also, commonly used carbon dioxide (CO2) is a known vasodilator that improves tissue oxygen tension. We performed a systematic review to determine the influence of hyperoxia, hypoxia, and hypercapnia on the gut microbiome and anastomotic healing. METHODS: A literature search was performed in MEDLINE, EMBASE, and COCHRANE to identify studies investigating the effects of hyperoxia, hypoxia, and hypercapnia on anastomotic healing and gut microbiota published between 1998 and 2018. Two reviewers screened the articles for eligibility and quality. Fifty-three articles underwent full text review, and a narrative synthesis was undertaken. RESULTS: Hyperoxia is associated with better anastomotic healing, increased gastrointestinal oxygen tension, and may reduce gut anaerobes. Hypoxia is associated with poor healing and increased gut anaerobes. However, it is unclear if hypoxia is the most important predictor of anastomotic leaks. Low pressure CO2 pneumoperitoneum and mild systemic hypercapnia are both associated with increased gastrointestinal oxygen tension and may improve anastomotic healing. We found no studies which investigated the effect of hypercapnia on gut microbiota in the context of anastomotic healing. CONCLUSIONS: Tissue oxygenation influences gut anastomotic healing, but little evidence exists to demonstrate the influence on the gut microbiome in the context of healing. Further studies are needed to determine if anastomotic microbiome changes with altered tissue oxygenation and if this affects healing and leak rates. If confirmed, altering tissue oxygenation through hyperoxia or hypercapnia could be feasible means of altering the microbiome such that anastomotic leak rates reduce.

Parental decision regret in childhood hypospadias surgery: A systematic review.

We conducted a systematic review of the literature to establish the prevalence of and predictive factors for parental decision regret in hypospadias surgery. A search strategy without language restrictions was developed with expert help, and two reviewers undertook independent study selection. Five studies were included in this review (four for quantitative analysis) with a total of 783 participants. The mean overall prevalence of parental decision regret was 65.2% (moderate to severe - 20.3%). Although significant predictors of regret were identified (post-operative complications, small size glans, meatal location, decision conflict between parents, parental educational level and others), they had unexplained discordance between studies. Parental decision regret after proximal hypospadias surgery and refusing surgery was inadequately reported. In conclusion, even though the prevalence of parental decision regret after consenting for the hypospadias repair appears to be high, risk factors associated with it were discordant suggesting imprecision in estimates due to unknown confounders.

Cell-Free DNA as a Diagnostic Blood-Based Biomarker for Colorectal Cancer: A Systematic Review.

BACKGROUND: Circulating tumour DNA (ctDNA) has emerged as an excellent candidate for the future of liquid biopsies for many cancers. There has been growing interest in blood-based liquid biopsy because of the potential of ctDNA to produce a noninvasive test that can be used for: the diagnosis of colorectal cancer, monitoring therapy response, and providing information on overall prognosis. The aim of this review was to collate and explore the current evidence regarding ctDNA as a screening tool for colorectal cancer (CRC). METHODS: A systematic review of published articles in English over the past 20 y was performed using Medline, Embase, and Cochrane databases on May 23, 2017. After a full-text review, a total of 69 studies were included. Two assessment tools were used to review and compare the methodological quality of these studies. RESULTS: Among the 69 studies included, 17 studies reviewed total cfDNA, whereas six studies looked at the DNA integrity index and 15 focused on ctDNA. There were a total of 40 studies that reviewed methylated cfDNA with 19 of these focussing specifically on SEPT9. CONCLUSIONS: The results of this review indicate that methylated epigenetic ctDNA markers are perhaps the most promising candidates for a blood-based CRC-screening modality using cell-free (cf) DNA. Methylated cfDNA appears to be less specific for CRC compared to ctDNA; however, they have demonstrated good sensitivity for early-stage CRC. Further research is required to determine which methylated cfDNA markers are the most accurate when applied to large cohorts of patients. In addition, reliable comparison of results across multiple studies would benefit from standardization of methodology for DNA extraction and PCR techniques in the future.

Time to colonoscopy for patients accessing the direct access colonoscopy service compared to the normal service in Newcastle, Australia.

BACKGROUND: The 2017 National Bowel Cancer Screening Program report records a median time from positive faecal occult blood test to colonoscopy of 53 days. There is some intrinsic delay in accessing specialist medical opinion prior to colonoscopy. AIM: To examine the effect of the introduction of a Direct Access Colonoscopy Service (DACS). METHODS: Using prospectively maintained databases, patients undergoing normal service (NS) colonoscopy and those referred to DACS were compared. The primary outcome measure was the time from general practitioner (GP) referral to colonoscopy. Secondary outcome measures included the proportion of patients who met the current recommended 30 days from GP referral to colonoscopy, and the proportion of patients who waited longer than 90 days. RESULTS: There were 289 patients in the NS group, and 601 patients who progressed on the DACS pathway. The demographics of both groups were comparable. DACS patients had a median waiting time of 49 days, significantly shorter than NS patients whose median wait was 79 days (P < 0.0001). Approximately 15.1% patients in the DACS group had their colonoscopy within 30 days from GP referral, significantly better than in the NS group (4.5%, P < 0.001). In the NS group, 41.2% patients waited longer than 90 days from GP referral to colonoscopy, compared with 16.3% in the DACS group (P < 0.001). CONCLUSION: DACS reduces waiting times to colonoscopy and is associated with an increased proportion of patients undergoing colonoscopy in a timely manner.

Direct access colonoscopy service for bowel cancer screening produces a positive financial benefit for patients and local health districts.

BACKGROUND: A direct access colonoscopy service (DACS) for the National Bowel Cancer Screening Program has become standard of care in Newcastle public hospitals because of the effect it has on time to colonoscopy. Cost-effectiveness has not been studied to date. AIM: The aim of this retrospective study was to analyse the cost-effectiveness of a DACS. METHODS: Data were collected for patients referred to DACS between January 2014 and June 2016, and patients who were treated on the normal service pathway in 2013 prior to the introduction of the process. A cost-benefit analysis from the patient's and local health district's perspective was undertaken. RESULTS: Introduction of the DACS produces a direct financial gain to patients in the form of reduced direct costs. It produces an indirect financial gain in terms of increased productivity if the patient is in work, and of increased leisure time if not in work. The DACS is modest income generating for the local health district, an evaluation which is sensitive to internal policies for distribution of government funding within a district. The DACS increases the availability of outpatient consultations to other patients, which is not a quantifiable economic benefit, but is likely to be an overall health benefit. CONCLUSION: The introduction of DACS in the public system in Australia is of financial benefit to patients and to the local health service provider. It is likely to produce health benefits to non-screening patients, by means of freeing consultations to be used for other indications.

Can CRP velocity in right iliac fossa pain identify patients for intervention? A prospective observational cohort study.

INTRODUCTION: Previous studies have shown single CRP measurements at time of presentation to have limited predictive benefit for appendicitis. Our objective was to determine the diagnostic utility of serial CRP measurements (to determine CRP velocity [CRPv]) in patients with right iliac fossa (RIF) pain. METHODS: A single-centre prospective observational study was conducted on adult patients admitted with RIF pain. CRP was measured on admission, at midnight, and the following morning. Appendicitis was diagnosed on histopathology, or diagnostic imaging in non-operatively managed patients. Therapeutic interventions included all appropriate operative procedures and effective non-operative treatment with antibiotics. Logistic regression was used to generate predictors of therapeutic intervention, and then used to create a new risk score incorporating CRPv. RESULTS: 98 of 112 (87.5%) participants had complete CRP data. 58 patients met the criteria for appendicitis (59.2%). Most patients presented with intermediate Modified Alvarado Scores (MAS) 5-6 (40.8%) or Appendicitis Inflammatory Response Scores (AIRS) 5-8 (49%). Our risk score had an AUROC of 0.88 (95% CI 0.81-0.96) in predicting therapeutic intervention. This score was superior to MAS, AIRS, and single admission biomarker measurements. Patients with an increasing CRPv had 14 times the odds (OR 14.07, 95% CI 0.63-315.2) of complicated appendicitis, and no cases of complicated appendicitis were observed in patients with a flat CRPv. CONCLUSIONS: CRP velocity is superior to single CRP at predicting intervention. Our v-Score shows promise as a decision making-aide by predicting the need for surgical intervention in RIF pain. A flat CRPv identifies a group of patients with a very low risk of complicated appendicitis.

Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial.

BACKGROUND: Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. OBJECTIVE: The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. DESIGN: This was a prospective, double-blind, placebo-controlled, randomized clinical trial. SETTINGS: The study was conducted at a tertiary referral university hospital in Australia. PATIENTS: Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). INTERVENTIONS: A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. MAIN OUTCOME MEASURES: The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. RESULTS: There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. LIMITATIONS: A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. CONCLUSIONS: Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is a well characterised genetic predisposition to early onset colorectal cancer (CRC) that is characterised by polyposis of the colon and rectum. Animal models have consistently suggested the role of modifier genes in determining disease phenotype, yet none have been substantiated in the human population. The mouse homologue of cluster of differentiation 36 (CD36) has been proposed as a modifier of disease in the MIN mouse model of FAP. METHODS: Three single nucleotide polymorphisms (SNPs); rs1049673, rs1761667 and rs1984112 in CD36, have been investigated in 275 FAP patients to determine if they were associated with age of polyposis or risk of developing disease. RESULTS: The results revealed a substantially lower age of polyposis diagnosis for patients belonging to the severe FAP group (harbouring adenomatous polyposis coli (APC) variants in the mutation cluster region (MCR)) and high age for patients in the attenuated familial adenomatous polyposis (AFAP) group for SNPs rs1761667 and rs1984112. CONCLUSIONS: This study provides evidence for patients belonging to the MCR and AFAP groups harbouring specific genotypes for SNPs in CD36 to initiate screening/treatment for FAP at much earlier (MCR) and much later (AFAP) ages than the norm in today's clinical practice. The findings need to be verified in an independent FAP patient cohort.

Transversus abdominis plane blockade in laparoscopic colorectal surgery: a double-blind randomized clinical trial.

INTRODUCTION: Adequate postoperative analgesia is essential for recovery following colorectal surgery. Transversus abdominis plane (TAP) blocks have been found to be beneficial in improving pain following a variety of abdominal operations. The objective of this study was to determine if TAP blocks are useful in improving postoperative recovery following laparoscopic colorectal surgery. MATERIALS AND METHODS: A prospective double-blind randomized clinical trial, involving 226 consecutive patients having laparoscopic colorectal surgery, was performed by a university colorectal surgical department. Patients were randomized to either TAP blockade using ultrasound guidance, or control, with the primary outcome being postoperative pain, as measured by analgesic consumption. Secondary outcomes assessed were pain visual analogue score (VAS), respiratory function, time to return of gut function, length of hospital stay, postoperative complications, and patient satisfaction. RESULTS: A total of 142 patients were followed up to trial completion (74 controls, 68 interventions). Patients were well matched with regard to demographics. No complications occurred as a result of the intervention of TAP blockade. There was no difference between groups with regards to analgesic consumption (161 mEq morphine control vs 175 mEq morphine TAP; p = 0.596). There was no difference between the two groups with regards to the secondary outcomes of daily VAS, respiratory outcome, time to return of gut function, length of hospital stay, postoperative complications, and patient satisfaction. CONCLUSION: We conclude that TAP blockade appears to be a safe intervention but confers no specific advantage following laparoscopic colorectal surgery.

A meta-analysis on the effect of sham feeding following colectomy: should gum chewing be included in enhanced recovery after surgery protocols?

BACKGROUND: Sham feeding has been shown to hasten the return of GI function following colorectal surgery, before the advent of enhanced recovery after surgery protocols. Few data exist regarding the efficacy of sham feeding in the modern era, with rapid postoperative feeding. OBJECTIVE: We sought to perform a meta-analysis on the effect of sham feeding in colorectal surgery, with a separate analysis on trials that used rapid postoperative feeding. DATA SOURCES: Cochrane, MEDLINE, EMBASE, Scopus, and PubMed were searched by using the terms gum OR sham feeding OR chew AND (colorect OR resect). STUDY SELECTION: All studies were randomized controlled trials (in any language) performed on adults, comparing standard care with gum chewing following colorectal resection. From 439 citations, 10 articles were included. INTERVENTION: The intervention was sham feeding by means of gum chewing. MAIN OUTCOME MEASURES: The outcome measures were time to return of flatus, time to first bowel movement, complication rates, length of hospital stay, readmission rates, and reoperation rates. RESULTS: Ten randomized controlled trials (n = 612) were included. Sham feeding resulted in a reduction in time to flatus of 31 minutes (p = 0.003) and time to first bowel movement of 30 minutes (p = 0.05). Sham feeding also resulted in a reduction in length of stay by 0.5 days (p = 0.007), and a reduction in complication rates (relative risk = 0.687, p = 0.017), although this appeared to be associated with publication bias. Analysis of trials that used rapid postoperative feeding (n = 282) revealed no difference in postoperative GI function. LIMITATIONS: This review was limited by the heterogeneity of postoperative feeding regimes, in addition to limited reporting by trials of postoperative morbidity. CONCLUSIONS: Sham feeding following colorectal surgery is safe, results in small improvements in GI recovery, and is associated with a reduction in the length of hospital stay. It confers no advantage if patients are placed on a rapid postoperative feeding regime.

Somatic symptom severity, depression and anxiety associations with pancreatitis and undifferentiated abdominal pain in surgical inpatients.

BACKGROUND: Somatic Symptom Disorder is a psychiatric diagnosis that describes the experience of physical symptoms and associated distress, that is disproportionate to recognized organic pathology. Somatic symptom severity (SSS) may be associated with some surgical diagnoses; particularly the complex pain associated with pancreatitis, or the diagnostic ambiguity of undifferentiated abdominal pain (UAP). We aimed to estimate the prevalence of SSS in different diagnostic groups in surgical inpatients with abdominal pain; and to estimate the magnitude and direction of any association of SSS, anxiety and depression. METHODS: Cross sectional analysis (n = 465) of adult admissions with non-traumatic abdominal pain, at a tertiary hospital in Australia. We estimated SSS with the Patient Health Questionnaire-15 (PHQ-15), depression with the Patient Health Questionnaire (PHQ-9) and anxiety with the General Anxiety Disorder (GAD-7), at standard cut-points ≥ 10; comparing acute pancreatitis (n = 20), chronic pancreatitis (n = 18) and UAP (n = 64) versus other causes of abdominal pain. RESULTS: Somatic symptoms were common, 52% having moderate and 19.6% severe SSS. There was an association between moderate SSS and pancreatitis (OR 2.11, 95% CI 1.05-4.25) and depressive symptoms and chronic pancreatitis (OR = 3.47, 95% CI 1.31-9.24). There was no significant association between the four mental health categories and UAP. CONCLUSIONS: SSS and psychological comorbidity were common in a surgical inpatients admitted for abdominal pain and equally represented across most diagnostic sub-groups. However, the pancreatitis sub-group had greater proportions with clinically significant SSS and depression, suggesting that they have a higher requirement for psychological assessment and intervention.