Aspirin chemoprevention in colorectal cancer: network meta-analysis of low, moderate, and high doses.

BACKGROUND: Colorectal cancer is the third most common cancer, with nearly 2 million cases worldwide and just under 1 million deaths in 2020. Several trials have demonstrated that aspirin has the potential to reduce the incidence and/or recurrence of colorectal cancer; however, the optimal aspirin dose is unclear. METHODS: Relevant studies were identified by searching MEDLINE, Embase and the Cochrane Library from database inception to 2 February 2022. Data from RCTs in which the incidence of colorectal cancer in patients without active colorectal cancer assigned to aspirin versus control were included. Two investigators independently identified studies and abstracted data. Study quality was assessed using Cochrane Collaboration risk-of-bias 2 tool. The study was performed according to PRISMA guidelines. Aspirin dose was stratified into low (50-163 mg/day), mid (164-325 mg/day), and high (500-1200 mg/day). RESULTS: Thirteen articles representing 11 RCTs (92 550 participants) were included, with studies assessing aspirin as primary prophylaxis in general or high-risk populations, and as secondary prophylaxis for metachronous colorectal cancer. There was a statistically significant reduction in colorectal cancer incidence in the high-dose aspirin group compared with the group that received no aspirin or placebo (OR 0.69, 95 per cent credible interval 0.50 to 0.96; surface under the cumulative ranking 0.82). There was no statistically significant difference between mid- and low-dose aspirin versus no aspirin/placebo. CONCLUSION: In this network meta-analysis of RCTs, high-dose aspirin was associated with a reduction in colorectal cancer incidence. However, this was based on a limited number of trials. This study did not show a statistically significant risk reduction in colorectal cancer incidence with mid- or low-dose aspirin.

Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial.

BACKGROUND & AIMS: Antibiotic treatment is the standard care for patients with uncomplicated acute diverticulitis. However, this practice is based on low-level evidence and has been challenged by findings from 2 randomized trials, which did not include a placebo group. We investigated the non-inferiority of placebo vs antibiotic treatment for the management of uncomplicated acute diverticulitis. METHODS: In the selective treatment with antibiotics for non-complicated diverticulitis study, 180 patients hospitalized for uncomplicated acute diverticulitis (determined by computed tomography, Hinchey 1a grade) from New Zealand and Australia were randomly assigned to groups given antibiotics (n = 85) or placebo (n = 95) for 7 days. We collected demographic, clinical, and laboratory data and answers to questionnaires completed every 12 hrs for the first 48 hrs and then daily until hospital discharge. The primary endpoint was length of hospital stay; secondary endpoints included occurrence of adverse events, readmission to the hospital, procedural intervention, change in serum markers of inflammation, and patient-reported pain scores at 12 and 24 hrs. RESULTS: There was no significant difference in median time of hospital stay between the antibiotic group (40.0 hrs; 95% CI, 24.4-57.6 hrs) and the placebo group (45.8 hrs; 95% CI, 26.5-60.2 hrs) (P = .2). There were no significant differences between groups in adverse events (12% for both groups; P = 1.0), readmission to the hospital within 1 week (1% for the placebo group vs 6% for the antibiotic group; P = .1), and readmission to the hospital within 30 days (11% for the placebo group vs 6% for the antibiotic group; P = .3). CONCLUSIONS: Foregoing antibiotic treatment did not prolong length of hospital admission. This result provides strong evidence for omission of antibiotics for selected patients with uncomplicated acute diverticulitis. ACTRN: 12615000249550.

Relationship between diversional stoma and mortality rate in Fournier's gangrene: a systematic review and meta-analysis.

PURPOSE: Fournier's gangrene (FG) is a rare potentially lethal necrotising infection of the perineum. While the gold standard management is early and aggressive surgical debridement, the evidence in the literature is unclear as to the role and outcomes of diversional stoma. METHODS: A systematic review was conducted to identify studies investigating the relationship between stoma formation and FG. Meta-analyses were performed using a random-effects model. RESULTS: Twenty-seven studies (n=1482) were included. There was no significant difference in disease severity scores between the stoma and no stoma groups. Mortality rate was significantly higher in patients who required diversional stoma (OR 1.71, 95% CI 1.13-2.59, p=0.01). Significantly more surgical procedures were performed on patients who underwent stoma formation, and the total hospital cost was also higher in this group. This study may have been limited by bias in patients with more fulminant course or sphincter damage requiring stoma as a medical necessity. CONCLUSION: These findings suggest that the use of diversional stoma in FG is a predictor of poor outcomes. This study demonstrated that mortality rate remained high and a diversional stoma did not reduce risk of mortality as suggested by smaller case series. Its use should therefore be individualised based on disease severity and sphincter damage.

Port site intramuscular abscess from retained gallstone post laparoscopic cholecystectomy - an unusual complication.

Perforation of the gallbladder and the spillage of gallstones can be a cause of ongoing morbidity and mortality in patients post cholecystectomy. We report on an unusual case of a 58-year-old male who developed a right upper quadrant lump 8 years after laparoscopic cholecystectomy which was eventually determined to be an abscess from a retained gallstone that had become embedded in the musculature of his abdominal wall. We have also discussed some of the considerations taken in the surgical management of this case.

Traumatic spigelian hernia complicated by caecal perforation and retroperitoneal haematoma-an unusual concurrence in blunt trauma.

Blunt abdominal injury can be a cause of significant morbidity and mortality in patients who have sustained trauma even at low velocity. We report on an unusual case of a 50-year-old male who developed a traumatic spigelian hernia and caecal perforation after falling off a pushbike and impacting on the handlebar. We have also discussed some of the considerations taken in the assessment and surgical management of this case.

The impact of variations in care and complications within a colorectal Enhanced Recovery After Surgery program on length of stay.

PURPOSE: Enhanced Recovery After Surgery (ERAS) has become standard of care in colorectal surgery. However, there is not a universally accepted colorectal ERAS protocol and significant variations in care exist between institutions. The aim of this study was to examine the impact of variations in ERAS interventions and complications on length of stay (LOS). METHODS: This study was a single-center review of the first 200 consecutive patients recruited into our prospectively collected ERAS database. The primary outcome of this study was to examine the rate of compliance to ERAS interventions and the impact of these interventions on LOS. The secondary outcome was to assess the impact of complications (anastomotic leak, ileus, and surgical site infections) on LOS. ERAS interventions, rate of adherence, LOS, readmissions, morbidity, and mortality were recorded, and statistical analysis was performed. RESULTS: ERAS variations and complications significantly influenced patient LOS on both univariate and multivariate analysis. ERAS interventions identified as the most important strategies in reducing LOS included laparoscopic surgery, mobilization twice daily postoperative day (POD) 0 to 1, discontinuation of intravenous fluids on POD 0 to 1, upgrading to solid diet by POD 0 to 2, removal of indwelling catheter by POD 0 to 2, avoiding nasogastric tube reinsertion and removing drains early. Both major and minor complications increased LOS. Anastomotic leak and ileus were associated with the greatest increase in LOS. CONCLUSION: Seven high-yield ERAS interventions reduced LOS. Major and minor complications increased LOS. Reducing variations in care and complications can improve outcomes following colorectal surgery.

An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission.

The initial immune response to HIV determines transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. By combining RNAscope, cyclic immunofluorescence, and image analysis tools, we quantify HIV transmission signatures in intact human colorectal explants within 2 h of topical exposure. We map HIV enrichment to mucosal dendritic cells (DCs) and submucosal macrophages, but not CD4+ T cells, the primary targets of downstream infection. HIV+ DCs accumulate near and within lymphoid aggregates, which act as early sanctuaries of high viral titers while facilitating HIV passage to the submucosa. Finally, HIV entry induces recruitment and clustering of target cells, facilitating DC- and macrophage-mediated HIV transfer and enhanced infection of CD4+ T cells. These data demonstrate a rapid response to HIV structured to maximize the likelihood of mucosal infection and provide a framework for in situ studies of host-pathogen interactions and immune-mediated pathologies.

Acute Gastroenteritis in the Etiology of Inflammatory Bowel Disease: Systematic Review and Meta-analysis.

Background: Inflammatory bowel disease (IBD) consists of a spectrum of disorders including ulcerative colitis and Crohn's disease, with a rising incidence worldwide. However, despite this prevalence the etiology of IBD remains uncertain. It has been suggested that an episode of gastroenteritis may precipitate IBD. Methods: Studies were identified using a literature search of Pubmed/Medline and Embase/Ovid. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was incidence of new-onset IBD after gastroenteritis. Secondary outcomes included incidence of IBD after bacterial, viral, and parasitic gastrointestinal infections. Results: Eleven studies (n = 923 608 patients) were included. Four studies assessed patients with gastroenteritis, subsequently developing IBD as the primary outcome. Patients with gastroenteritis had a higher incidence of subsequent IBD but this did not reach statistical significance (odds ratio [OR] 3.81, 95% CI 0.52-27.85, P = .19). Seven studies examined the incidence of antecedent gastroenteritis (primary outcome) in patients with a confirmed diagnosis of IBD, compared to the controlled population. There was no difference between incidence of antecedent gastroenteritis across the 2 population groups (OR 1.07, 95% CI 0.55-2.08, P = .85). There was no association between IBD and bacterial, viral, or parasitic infections. Conclusions: In summary, our meta-analysis has shown that there is considerable heterogeneity in the literature regarding the role of gastroenteritis in the development of IBD. Further higher quality studies need to be performed to ascertain the true nature of this.

MRI radiomics in the prediction of therapeutic response to neoadjuvant therapy for locoregionally advanced rectal cancer: a systematic review.

Introduction: The standard of care for locoregionally advanced rectal cancer is neoadjuvant therapy (NA CRT) prior to surgery, of which 10-30% experience a complete pathologic response (pCR). There has been interest in using imaging features, also known as radiomics features, to predict pCR and potentially avoid surgery. This systematic review aims to describe the spectrum of MRI studies examining high-performing radiomic features that predict NA CRT response.Areas covered: This article reviews the use of pre-therapy MRI in predicting NA CRT response for patients with locoregionally advanced rectal cancer (T3/T4 and/or N1+). The primary outcome was to identify MRI radiomic studies; secondary outcomes included the power and the frequency of use of radiomic features.Expert opinion: Advanced models incorporating multiple radiomics categories appear to be the most promising. However, there is a need for standardization across studies with regards to; the definition of NA CRT response, imaging protocols, and radiomics features incorporated. Further studies are needed to validate current radiomics models and to fully ascertain the value of MRI radiomics in the response prediction for locoregionally advanced rectal cancer.

Optimal Isolation Protocols for Examining and Interrogating Mononuclear Phagocytes From Human Intestinal Tissue.

The human intestine contains numerous mononuclear phagocytes (MNP), including subsets of conventional dendritic cells (cDC), macrophages (Mf) and monocytes, each playing their own unique role within the intestinal immune system and homeostasis. The ability to isolate and interrogate MNPs from fresh human tissue is crucial if we are to understand the role of these cells in homeostasis, disease settings and immunotherapies. However, liberating these cells from tissue is problematic as many of the key surface identification markers they express are susceptible to enzymatic cleavage and they are highly susceptible to cell death. In addition, the extraction process triggers immunological activation/maturation which alters their functional phenotype. Identifying the evolving, complex and highly heterogenous repertoire of MNPs by flow cytometry therefore requires careful selection of digestive enzyme blends that liberate viable cells and preserve recognition epitopes involving careful selection of antibody clones to enable analysis and sorting for functional assays. Here we describe a method for the anatomical separation of mucosa and submucosa as well as isolating lymphoid follicles from human jejunum, ileum and colon. We also describe in detail the optimised enzyme digestion methods needed to acquire functionally immature and biologically functional intestinal MNPs. A comprehensive list of screened antibody clones is also presented which allows for the development of high parameter flow cytometry panels to discriminate all currently identified human tissue MNP subsets including pDCs, cDC1, cDC2 (langerin+ and langerin-), newly described DC3, monocytes, Mf1, Mf2, Mf3 and Mf4. We also present a novel method to account for autofluorescent signal from tissue macrophages. Finally, we demonstrate that these methods can successfully be used to sort functional, immature intestinal DCs that can be used for functional assays such as cytokine production assays.

Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells.

Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a diverse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).

Accuracy of estimation of polyp size at colonoscopy.

BACKGROUND: The Cancer Council posits that the size of adenomas is a more robust marker of risk than histological characteristics. The purpose of our study is to assess the accuracy of estimation of polyp size at colonoscopy amongst different levels of endoscopists and compare this with histopathological size. METHODS: A retrospective review of prospectively collected data was performed. Specimens were included if they were (i) from patients aged 18 years or older, (ii) polyp obtained at colonoscopy, (iii) measured in quantitative units and (iv) the largest eligible polyp per patient. RESULTS: A total of 92 patients were included. Our results demonstrate that the relationship between the histological size of a polyp and an endoscopist's estimate depended upon seniority level (P = 0.001). Senior consultants tended to overestimate lesion size (P < 0.001), fellows/junior consultants tended to underestimate size (P = 0.010), whilst registrars' estimates demonstrated no systematic difference from histological size (P = 0.518). The ratio of a senior consultant's estimate of polyp size to histological size was on average 74% with their estimates ranging from 31% to 173%. The corresponding estimates are 123% (32-470%) for fellows/junior consultants and 107% (35-334%) for registrars. CONCLUSION: Our study demonstrates that senior consultants are more precise with more junior endoscopists having a great degree of variability in their practice. It is evident that there is a relationship between proceduralist experience and polyp size estimation. It is, therefore, important to consider the ways in which we can mitigate this learning curve and continue to develop technology to improve our accuracy.

Iatrogenic rectal injury associated with fleet enema administration masquerading as Fournier's Gangrene.

Rectal injuries secondary to fleet enemas are the result of a chemical irritation as well as mechanical trauma causing localized perforation and mucosal necrosis. These injuries can be managed expectantly. Fournier's Gangrene is a life-threatening, fulminant soft tissue infection of the genito-perineal region commonly secondary to a perianal infection, requiring extensive debridement of all affected tissue and judicious antibiotic therapy. This distinction is critical in the management of the current case, allowing for limited debridement and judicious observation without a resection of the injured rectum. A diverting colostomy allows for effective faecal management and minimizes contamination of the perineal wound.

A rare case of lupus-related gastrointestinal vasculitis presenting as rectal gangrene.

Systemic lupus erythematosus (SLE) related gastrointestinal vasculitis is a rare condition limited to case studies within the literature however, no cases of rectal gangrene and perforation have been previously described. A 32-year-old male presented with abdominal pain, vomiting and fevers. CT demonstrated free gas and free fluid around the rectum indicative of a perforation. He proceeded to urgent laparotomy, confirming a diagnosis of rectal infarction and perforation. Uniquely, the involved segment of gangrene extended from the rectosigmoid to the anorectal junction. A Hartmanns procedure was performed. Histopathology confirmed underlying stenosis of the rectal arteries secondary to chronic vasculitis related to the affected areas. The current case is a unique presentation of SLE-related vasculitis. It highlights the need to judiciously investigate SLE patients presenting with surgical acute abdomen.

A case of a colonic foreign body imitating diverticulitis.

We present a case of a 75-year-old male who was referred to an Emergency Department with possible diverticulitis. On further review of CT imaging, extensive sigmoid diverticulosis with mural thickening and inflammatory stranding was noted, with a linear dense foreign body present within the sigmoid lumen. The patient was managed with intravenous antibiotics and colonoscopic retrieval of the foreign body, which was lodged within a diverticulum. This case emphasizes the importance of early colonoscopic management of patients suspected to have a colonic foreign body. We then review the literature regarding colonic foreign bodies and the association with diverticulosis.

Acute surgical experience of Australian general surgical trainees.

BACKGROUND: A principle of Australian general surgical training is exposure to a variety of operative and clinical experiences. These are potentially being impacted upon by expanding post-fellowship training positions, mandatory reduced working hours, and advances in non-operative care. This study aims to report the recent acute surgical experience of Australian general surgical trainees. METHODS: A de-identified summary of general surgical trainee logbook data was obtained from General Surgeons Australia, over a 6-year period (2009-2014). Case volumes in operative and non-operative acute surgical cases were analysed, encompassing 5307 individual logbooks from 12 consecutive training terms. RESULTS: There was a mean of 112.2 ± 6.8 total major operative cases per trainee per term. There was an increase in case volumes reported from terms 1-8 (from 102.1 to 122.9), with the most recent reported volume being 117.8 cases per trainee in term 12. The total major operative primary operator rate increased from 35.5% in term 1 to 40.6% in term 8, with the most recent reported rate being 41.8% in term 12. Open and laparoscopic colorectal case volumes have remained stable. Operative trauma case volumes have increased. CONCLUSION: The acute surgical operative case experience of general surgical trainees has not declined. However, it should continue to be monitored in view of the changing scope of surgical practice.

Predicting non-sentinel lymph node metastasis in Australian breast cancer patients: are the nomograms still useful in the post-Z0011 era?

BACKGROUND: Axillary lymph node dissection (ALND) can be avoided in breast cancer patients with low-volume disease in the sentinel lymph nodes (SLNs) according to Z0011 trial. We believe that nomograms developed for predicting non-sentinel lymph node (NSLN) metastases can guide the axillary treatment in patients who do not fully match the criteria of Z0011 study. We identified risk factors and evaluated the performance of three nomograms to predict NSLN status in patients with positive SLNs. METHODS: Data from 526 breast cancer patients with positive SLNs who underwent ALND at two Australian hospitals from 2002 to 2015 were studied. Univariate and multivariate associations for NSLN metastasis were analysed. Predictive models evaluated were MD Anderson Cancer Centre (MDA), Helsinki University Hospital and Memorial Sloan Kettering Cancer Centre. RESULTS: Thirty-nine per cent of patients demonstrated NSLN metastasis. The multivariate analysis identified extranodal extension (OR 3.2, 95% CI 2.07-4.80), tumour size >2 cm (OR 2.5, 95% CI 1.66-3.89), macrometastasis (OR 1.9, 95% CI 1.09-3.47), positive SLN ratio >0.5 (OR 1.7, 95% CI 1.16-2.60) and lymphovascular invasion (OR 1.6, 95% CI 1.09-2.44) as independent predictors for NSLN metastasis. MDA nomogram showed the best discrimination (area under the curve of 0.74) and a 9% false negative rate for predicted probability of NSLN metastasis ≤10%. CONCLUSION: Our results suggest that presence of extranodal extension and tumour size >2 cm may influence the need of further axillary treatment. Conversely, ALND can be safety spared in low risk patients identified by MDA nomogram.

A Multifocal Pattern of Neuroendocrine Neoplasms Along the Appendix: A Series of Six Cases.

We present 6 cases with multifocal appendiceal neuroendocrine tumors, including their clinical and histopathological findings. To our knowledge, this is the first description of a multifocal pattern of a neuroendocrine neoplasm arising in the appendix. All patients presented in a setting requiring an acute appendectomy. The number of tumors ranged from 2 to 5. Histopathological examination revealed WHO (World Health Organization) grade 1 tumor in 3 patients and WHO grade 2 in the other 3 patients. The median duration of follow-up in these patients was 70 months (range = 6-192 months). No metastatic disease was observed. According to these findings, a multifocal pattern of neuroendocrine neoplasms along the appendix seems not to be a predictor for local advanced or metastatic disease.