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.

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.

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.

Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model.

BACKGROUND: Regardless of the availability of therapeutic options, the overall 5-year survival for patients diagnosed with pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have been used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions. Both frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit anti-neoplastic activity, and have been investigated as potential anti-cancer agents. The goals of this study are to identify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to evaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model. METHODS: Boswellia sacra gum resins were hydrodistilled at 78°C; and essential oil distillate fractions were collected at different durations (Fraction I at 0-2 h, Fraction II at 8-10 h, and Fraction III at 11-12 h). Hydrodistillation of the second half of gum resins was performed at 100°C; and distillate was collected at 11-12 h (Fraction IV). Chemical compositions were identified by gas chromatography-mass spectrometry (GC-MS); and total boswellic acids contents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated pancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic (subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability of Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic activities in animals were assessed by immunohistochemistry. RESULTS: Longer duration and higher temperature hydrodistillation produced more abundant high molecular weight compounds, including boswellic acids, in frankincense essential oil fraactions. Human pancreatic cancer cells were sensitive to Fractions III and IV (containing higher molecular weight compounds) treatment with suppressed cell viability and increased cell death. Essential oil activated the caspase-dependent apoptotic pathway, induced a rapid and transient activation of Akt and Erk1/2, and suppressed levels of cyclin D1 cdk4 expression in cultured pancreatic cancer cells. In addition, Boswellia sacra essential oil Fraction IV exhibited anti-proliferative and pro-apoptotic activities against pancreatic tumors in the heterotopic xenograft mouse model. CONCLUSION: All fractions of frankincense essential oil from Boswellia sacra are capable of suppressing viability and inducing apoptosis of a panel of human pancreatic cancer cell lines. Potency of essential oil-suppressed tumor cell viability may be associated with the greater abundance of high molecular weight compounds in Fractions III and IV. Although chemical component(s) responsible for tumor cell cytotoxicity remains undefined, crude essential oil prepared from hydrodistillation of Boswellia sacra gum resins might be a useful alternative therapeutic agent for treating patients with pancreatic adenocarcinoma, an aggressive cancer with poor prognosis.

Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells.

BACKGROUND: Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. METHODS: Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 °C for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. RESULTS: More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 °C hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra essential oil hydrodistilled at 100 °C was more potent than the essential oil prepared at 78 °C in inducing cancer cell death, preventing the cellular network formation (MDA-MB-231) cells on Matrigel, causing the breakdown of multicellular tumor spheroids (T47D cells), and regulating molecules involved in apoptosis, signal transduction, and cell cycle progression. CONCLUSIONS: Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. Suppression of cellular network formation and disruption of spheroid development of breast cancer cells by Boswellia sacra essential oil suggest that the essential oil may be effective for advanced breast cancer. Consistently, the essential oil represses signaling pathways and cell cycle regulators that have been proposed as therapeutic targets for breast cancer. Future pre-clinical and clinical studies are urgently needed to evaluate the safety and efficacy of Boswellia sacra essential oil as a therapeutic agent for treating breast cancer.