Feasibility of triple assessment of the anastomosis using an anastomotic checklist.

BACKGROUND: Colorectal cancer is the third most common cancer and the second highest cause of cancer mortality in Australia. Despite advances in colorectal surgery, anastomotic leak still occurs in low-risk patients and is a substantial cause of morbidity and mortality. Many operative strategies are used to assess anastomotic integrity such as an air leak test or intraoperative flexible sigmoidoscopy, however an objective anastomotic checklist is yet to be developed and studied. This study aims to develop a photodocumentary anastomotic specific checklist and determine its feasibility for implementation. METHODS: Patients undergoing left sided colorectal resections with primary anastomosis without a de-functioning ileostomy were prospectively included between May 2021 and December 2022. A photographic checklist assessing anastomotic perfusion, integrity via either air test or endoscopic image, evidence of complete operative doughnut specimens and the assessment of tension was implemented. The feasibility of an anastomotic checklist was externally validated by four independent colorectal surgeons from Australia, New Zealand and United States of America. RESULTS: The anastomotic checklist was completed in 44 patients. Mean age was 62 years, with 43% male and mean BMI 28. Operations included high anterior resection (45%), low anterior resection (18%), ultra-low anterior resection (20%), reversal of Hartmann's (11%). Median length of stay was 4 days. Complications post operatively were documented in six patients with anastomotic leak in 2% and wound infection in 6.8%. Intraclass correlation coefficients were poor amongst all reviewers with air leak and tension having no inter-reviewer correlation. CONCLUSION: The introduction of an anastomotic checklist was a feasible tool to systematically assess and document anastomotic integrity. Unfortunately, with the small sample size there was significant discrepancy in inter-observer variability, and this led to poor correlation regarding which patients were typically high risk requiring a temporary ileostomy. Larger studies on the implementation of an anastomotic checklist will be needed to evaluate if it is an inherently feasible approach and if there is an effect on anastomotic leak.

Pregnancy and stomas: a 9-year retrospective series at a major metropolitan hospital in Brisbane Queensland.

BACKGROUND: Over 42 000 Australians live with a stoma, and this number increases annually. Pregnancy in stoma patients is a rare but complex condition and there is limited published literature regarding surgical and obstetric complications in pregnant stoma patients. The aim of this paper was to review stoma outcomes, perinatal morbidity and mortality, and early postpartum period in pregnant stoma patients. METHODS: Data was retrospectively obtained on women of childbearing age, with a stoma, who had been pregnant and birthed in the last nine years at the Royal Brisbane and Women's Hospital between January 2014 to December 2022. Data recorded included patient demographics, type of stoma, indication for stoma, need for additional abdominal surgeries, method of conception, pregnancy complications, length of stay, neonatal outcomes and post pregnancy stomal complications. RESULTS: In total, there were 16 births from 13 mothers with stomas. Of 10 births to IBD patients, 40% experienced a serious stomal complication. Caesarean section (CS) rate was 90% for IBD and 83% for non-IBD. In-vitro fertilisation rates were 40% in IBD patients and 0% in non-IBD patients. The average gestational age at delivery was 36 weeks in IBD and 35 weeks non-IBD patients. Neonates delivered to IBD mothers had a birth weight under 2500g in 40% of cases and in non IBD mothers at 33.3% (p = 0.62). Of the sixteen births there was five complications (31.25%) associated with the stoma either during pregnancy or during the sixty-day postpartum period. CONCLUSION: Pregnancy in stoma patients is a rare occurrence and appears to be associated with high rates of CS, preterm delivery, low birth weight and stomal complication.

Is centralization for rectal cancer surgery necessary?

Rectal cancer surgery is complex and more technically challenging than colonic surgery. Over the last 30 years internationally, there has been a growing impetus for centralizing care to improve outcomes for rectal cancer. Centralizing care may potentially reduce variations of care, increase standardization and compliance with clinical practice guidelines. However, there are barriers to implementation at a professional, political, governance and resource allocation level. Centralization may increase inequalities to accessing healthcare, particularly impacting socioeconomically disadvantaged and rural populations with difficulties to commuting longer distances to "centres of excellence". Furthermore, it is unclear if centralization actually improves outcomes. Recent studies demonstrate that individual surgeon volume rather than hospital volume may be more important in achieving optimal outcomes. In this review, we examine the literature to assess the value of centralization for rectal cancer surgery.

Skin to origin of mesenteric artery study (STOMA): prospective study of distances between stoma location and proximal superior mesenteric artery.

BACKGROUND: Traditional siting of stomas, in the lower abdomen, has been guided by surgical dogma lacking evidence. In the lower abdomen, the combination of a thick and pendulous abdominal apron, can create a challenging and suboptimal site for a stoma. The anatomical determinant limiting delivery of a stoma to the abdominal skin is the distance of the SMA from the lower border of the pancreas. The aim of this cross-sectional study was to compare the distance between the traditional stoma site, and upper abdominal stoma sites, to both the superior mesenteric artery (SMA) origin and SMA at the inferior border of the pancreas on abdominal computed tomography (CT). METHODS: A cross-sectional study at a single academic university hospital of adult patients who underwent abdominal CT in Australia. RESULTS: Two hundred and thirteen patients were included. Stoma sites in the upper abdomen were 57-76 mm shorter to the origin of the SMA and inferior border of the pancreas than those positioned at the traditional stoma site (P < 0.001). The mean panniculus thickness in the upper abdomen was 10 mm thinner than in the lower abdomen and increased with increasing BMI (P < 0.001). The ratio between the distance from the xiphisternum to umbilicus, and the umbilicus to pubic symphysis, was 1.10; this ratio increased with increasing BMI. CONCLUSION: The distance of the SMA to the skin is always shorter in the upper abdomen compared to the traditional stoma site. Consideration should be given to placing stomas in the upper abdomen, particularly in overweight or obese patients.

Endoscopic findings after CT proven acute diverticulitis: a systematic review and meta-analysis.

BACKGROUND: Traditionally, international guidelines recommend patients with acute diverticulitis should be followed up with a colonoscopy 6-8 weeks after discharge. However, the need for an interval colonoscopy has been increasingly challenged in the setting of computed tomography (CT). Previous meta-analyses have included studies which combined suspected rather than imaging confirmed diverticulitis and often without correlation with endoscopic findings. This meta-analysis aims to investigate endoscopic findings of patients with CT confirmed diverticulitis. METHODS: An electronic search of Medline, PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, Clinicaltrials.gov and WHO ICTRP was performed up to October 18, 2021. Studies which reported CT confirmed acute diverticulitis in adults and who underwent endoscopic follow-up with either a colonoscopy or flexible sigmoidoscopy were included. Studies were excluded if diverticulitis was diagnosed by clinical grounds alone, ultrasound, barium enema, or other non-CT forms of imaging. RESULTS: A total of 68 studies with 13 905 patients were included. Median age was 58 years and male to female ratio was 0.84. Cancer was detected in 2.0% and advanced adenoma in 3.8%. Complicated diverticulitis had 9.2 higher odds of cancer compared to uncomplicated diverticulitis (95% CI 4.42-19.08, P < 0.001). Adenomas were detected in 17%. Of those diagnosed with colorectal cancer, 85% were concordant with the site of the diverticulitis on CT while 15% were incidental findings. CONCLUSION: Routine colonoscopic follow up should be recommended in medically fit patients who have CT proven acute diverticulitis due to the higher than population prevalence of colorectal cancer and advanced adenomas.

Virus-like Particles: Measures and Biological Functions.

Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically, the presence of virus-like particles has been inferred from total particle counts by microscopy, and infectious particle counts or plaque-forming-units (PFUs) by plaque assay; the resulting ratio of particles-to-PFUs is often greater than one, easily 10 or 100, indicating that most particles are non-infectious. Despite their inability to hijack cells for their reproduction, virus-like particles and the defective genomes they carry can exhibit a broad range of behaviors: interference with normal virus growth during co-infections, cell killing, and activation or inhibition of innate immune signaling. In addition, some virus-like particles become productive as their multiplicities of infection increase, a sign of cooperation between particles. Here, we review established and emerging methods to count virus-like particles and characterize their biological functions. We take a critical look at evidence for defective interfering virus genomes in natural and clinical isolates, and we review their potential as antiviral therapeutics. In short, we highlight an urgent need to better understand how virus-like genomes and particles interact with intact functional viruses during co-infection of their hosts, and their impacts on the transmission, severity, and persistence of virus-associated diseases.

Laparoscopic versus open cholecystectomy in pregnancy: a systematic review and meta-analysis.

BACKGROUND: The operative management of symptomatic cholelithiasis during pregnancy is either laparoscopic cholecystectomy (LC) or open cholecystectomy (OC). The aim of this systematic review and meta-analysis is to compare the outcomes of the laparoscopic and open approach for cholecystectomy during pregnancy. METHOD: A literature search was conducted using MEDLINE, PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL and Current Contents Connect using appropriate search terms. All comparative studies reporting maternal, fetal, and/or surgical complications were included. RESULTS: Eleven comparative studies, with a total of 10,632 patients, were included. The laparoscopic approach was performed at mean 18-week gestation and the open approach at mean 24-week gestation. LC was associated with decreased risks for fetal (OR 0.42; 95 % CI 0.28-0.63; p < 0.001), maternal (OR 0.42; 95 % CI 0.33-0.53; p < 0.001) and surgical (OR 0.45; 95 % CI 0.25-0.82, p = 0.01) complications. The average length of hospital stay (LOS) was: LC 3.2 days and OC 6.0 days (p = 0.02). The conversion rate from LC to OC was 3.8 %. CONCLUSION: The results of this first meta-analysis suggest that LC is associated with fewer maternal and fetal complications than OC during pregnancy. However, 91 % of included patients were in the first or second trimester at the time of surgery. These findings do not account for gestational age during pregnancy, which may be a significant confounding factor. The results support intervention for symptomatic gallstones in the first and second trimester with a laparoscopic approach.

Study design in evidence-based surgery: What is the role of case-control studies?

Randomized controlled trials (RCTs) are the gold standard in terms of study design, however, in the surgical setting conducting RCTs can often be unethical or logistically impossible. Case-control studies should become the major study design used in surgical research when RCTs are unable to be conducted and definitely replacing case series which offer little insight into surgical outcomes and disease processes.

Early laparoscopic cholecystectomy is superior to delayed acute cholecystitis: a meta-analysis of case-control studies.

BACKGROUND: Since the advent of laparoscopic cholecystectomy (LC) there has been continued debate regarding the management of acute cholecystitis with either early or delayed LC. Nearly all studies have demonstrated that early LC has a significantly shorter total length of hospital stay compared with delayed LC. Although previous randomized controlled trials and meta-analysis have shown clinical outcomes to favour early surgery, clinical practice continues to vary significantly worldwide. In addition, there is much confusion in the optimal timing for early LC with definitions of early varying from 72 h to 7 days. There have been numerous case-control studies investigating the timing of LC in acute cholecystitis. The aim of this paper is to pool the results from all case-control studies to investigate outcomes including mortality rates, complication rates, length of hospital stay and conversion rates to open procedures. METHODS: A search of electronic databases was performed for case-control studies published between 1985-February 2015. RESULTS: Results from 77 case-control studies showed statistically significant reductions in mortality, complications, bile duct leaks, bile duct injuries, wound infections, conversion rates, length of hospital stay and blood loss associated with early LC. Although LC within the 72-h window is optimal, patients operated after this window still benefit from early surgery compared to delayed surgery. The duration of symptoms in acute cholecystitis should not influence the surgeons' willingness to operate acutely. CONCLUSIONS: Early LC is clearly superior to delayed LC in acute cholecystitis. The most recent evidence-based practice strongly suggests that early LC should be standard of care in the management of acute cholecystitis.

Early Cholecystectomy Is Superior to Delayed Cholecystectomy for Acute Cholecystitis: a Meta-analysis.

INTRODUCTION: The timing of laparoscopic cholecystectomy for acute cholecystitis remains an issue for debate amongst general surgeons. The aim of this study was to compare clinical outcomes between early and delayed cholecystectomy for acute cholecystitis. The primary outcome measures included mortality rates, complication rates, length of hospital stay and conversion rates to open procedures. MATERIALS AND METHODS: A search of electronic databases was performed for randomised controlled trials. Fifteen studies were included. RESULTS: Early surgery has a decreased risk of wound infections (RR 0.57, 95 % CI 0.35-0.93, p=0.01) compared with delayed surgery but no difference in mortality, bile duct injuries, bile duct leaks and the risk of conversion to open surgery. Of patients in the delayed group, 9.7 % failed initial non-operative management and underwent emergency LC. Early surgery had a significantly reduced total hospital stay and mean hospital costs compared with delayed surgery. CONCLUSION: Early laparoscopic cholecystectomy in acute cholecystitis demonstrated decreased incidence of wound infections, a shorter total length of stay and decreased costs with no difference in the rates of mortality, bile duct injuries, bile leaks and conversions. These results support that early laparoscopic cholecystectomy is the best care and should be considered a routine in patients presenting with acute cholecystitis.

Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α1 and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α1-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α1 immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α1 immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression.

Chest radiographs for acute lower respiratory tract infections.

BACKGROUND: Acute lower respiratory tract infections (LRTIs) (e.g. pneumonia) are a major cause of morbidity and mortality and management focuses on early treatment. Chest radiographs (X-rays) are one of the commonly used strategies. Although radiological facilities are easily accessible in high-income countries, access can be limited in low-income countries. The efficacy of chest radiographs as a tool in the management of acute LRTIs has not been determined. Although chest radiographs are used for both diagnosis and management, our review focuses only on management. OBJECTIVES: To assess the effectiveness of chest radiographs in addition to clinical judgement, compared to clinical judgement alone, in the management of acute LRTIs in children and adults. SEARCH METHODS: We searched CENTRAL 2013, Issue 1; MEDLINE (1948 to January week 4, 2013); EMBASE (1974 to February 2013); CINAHL (1985 to February 2013) and LILACS (1985 to February 2013). We also searched NHS EED, DARE, ClinicalTrials.gov and WHO ICTRP (up to February 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of chest radiographs versus no chest radiographs in acute LRTIs in children and adults. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, extracted data and assessed risk of bias. A third review author compiled the findings and any discrepancies were discussed among all review authors. We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Two RCTs involving 2024 patients (1502 adults and 522 children) were included in this review. Both RCTs excluded patients with suspected severe disease. It was not possible to pool the results due to incomplete data. Both included trials concluded that the use of chest radiographs did not result in a better clinical outcome (duration of illness and of symptoms) for patients with acute LRTIs. In the study involving children in South Africa, the median time to recovery was seven days (95% confidence interval (CI) six to eight days (radiograph group) and six to nine days (control group)), P value = 0.50, log-rank test) and the hazard ratio for recovery was 1.08 (95% CI 0.85 to 1.34). In the study with adult participants in the USA, the average duration of illness was 16.9 days versus 17.0 days (P value > 0.05) in the radiograph and no radiograph groups respectively. This result was not statistically significant and there were no significant differences in patient outcomes between the groups with or without chest radiograph.The study in adults also reports that chest radiographs did not affect the frequencies with which clinicians ordered return visits or antibiotics. However, there was a benefit of chest radiographs in a subgroup of the adult participants with an infiltrate on their radiograph, with a reduction in length of illness (16.2 days in the group allocated to chest radiographs and 22.6 in the non-chest radiograph group, P < 0.05), duration of cough (14.2 versus 21.3 days, P < 0.05) and duration of sputum production (8.5 versus 17.8 days, P < 0.05). The authors mention that this difference in outcome between the intervention and control group in this particular subgroup only was probably a result of "the higher proportion of patients treated with antibiotics when the radiograph was used in patient care".Hospitalisation rates were only reported in the study involving children and it was found that a higher proportion of patients in the radiograph group (4.7%) required hospitalisation compared to the control group (2.3%) with the result not being statistically significant (P = 0.14). None of the trials report the effect on mortality, complications of infection or adverse events from chest radiographs. Overall, the included studies had a low or unclear risk for blinding, attrition bias and reporting bias, but a high risk of selection bias. Both trials had strict exclusion criteria which is important but may limit the clinical practicability of the results as participants may not reflect those presenting in clinical practice. AUTHORS' CONCLUSIONS: Data from two trials suggest that routine chest radiography does not affect the clinical outcomes in adults and children presenting to a hospital with signs and symptoms suggestive of a LRTI. This conclusion may be weakened by the risk of bias of the studies and the lack of complete data available.