Clinical significance of appendiceal diverticulum: a significant marker for appendiceal neoplasia in Australian patients.

INTRODUCTION: Diverticula of the appendix (DA) have a reported incidence of up to 2.1%. They are primarily detected incidentally, through imaging and intraoperative or histologic diagnosis. This study's objective was to examine the prevalence of DA, and its relationship with inflammation and neoplasia, as well as review the literature with respect to clinical outcomes and ability to identify DA preoperatively. METHODOLOGY: A retrospective search of all patients undergoing an appendicectomy for right lower quadrant pain at a single institution between 2004 and 2017 was conducted. Histopathology reports for evidence of DA, location of the DA, presence of inflammation, and any relationship between DA and neoplasms (adenoma, carcinoma, carcinoid, lymphoma, and mucinous neoplasm) within the appendix were reviewed. Clinical notes, operative records, and preoperative imaging were also reviewed. RESULTS: Two thousand seven hundred eleven patient were included in the study, with a mean age of 34 years, with acute appendicitis found in 82.5%. 31.6% of patients with DA had associated inflammation of the DA. DA was present in 57 patients (2.1%), with 55 patients in the total cohort having neoplasia (2.0%). Patients with DAs were ten times more likely to have appendicular neoplasm than patients without a DA (17.5 vs 1.8%; p < 0.0001, OR 11.8 95%, CI 5.6-24.8). CONCLUSION: This is the first Australian study demonstrating DAs are a significant marker of appendiceal neoplasm. Appendicectomy in all incidentally discovered diverticulum should be considered. Due to a paucity of data, research is required into this area to assess for the need for endoscopy following diagnosis.

Preceptorship in robotic colorectal surgery: experience from the Australian private sector.

This article describes a post-fellowship preceptorship training program to train sub-specialty colorectal surgeons in gaining proficiency in robotic colorectal surgery using a dual-surgeon model in the Australian private sector. The Australian colorectal surgeon faces challenges in gaining robotic colorectal surgery proficiency with limited exposure and experience in the public setting where the majority of general and colorectal surgery training is currently conducted. This training model uses graded exposure with a range of simulation training, wet lab training, and clinical operative cases to progress through both competency and proficiency in robotic colorectal surgery which is mutually beneficial to surgeons and patients alike. Ongoing audit of practice has shown no adverse impacts.

A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.

Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call "Whole Exome Genome Sequencing" (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

Acute diverticulitis in immunosuppressed patients: a 12-year management experience.

BACKGROUND: Diverticular disease of the colon occurs commonly in developed countries. Immunosuppressed patients are thought to be more at risk of developing acute diverticulitis, worse disease, and higher complications secondary to therapy. This study aimed to assess outcomes for immunosuppressed patients with acute diverticulitis. METHOD: A retrospective single-centre review was conducted of all patients presenting with acute diverticulitis at a major tertiary Australian hospital from 2006 to 2018. RESULT: A total of 751 patients, comprising of 46 immunosuppressed patients, were included. Immunosuppressed patients were found to be older (62.25 versus 55.96, p = 0.016), have more comorbidities (median Charlson Index 3 versus 1, P < 0.001), and undergo more operative management (13.3% versus 5.1%, P = 0.020). Immunosuppressed patients with paracolic/pelvic abscesses (Modified Hinchey 1b/2) were more likely to undergo surgery (56% versus 24%, P = 0.046), while in patients with uncomplicated diverticulitis, there was no difference in immunosuppressed patients undergoing surgery (6.1% versus 5.1% P = 0.815). Immunosuppressed patients were more likely to have Grade III-IV Clavien-Dindo complication (P < 0.001). CONCLUSION: Immunosuppressed patients with uncomplicated diverticulitis can be treated safely with non-operative management. Immunosuppressed patients were more likely to have operative management for Hinchey 1b/II and more likely to have grade III/IV complications.

A Systematic Review of Microwave Ablation for Colorectal Pulmonary Metastases.

BACKGROUND/AIM: Pulmonary metastases are the second most common site of metastasis in colorectal cancer after the liver, and microwave ablation (MWA) for its treatment has grown in popularity in patients who are not suitable for pulmonary metastatectomy. However, its long-term efficacy remains unknown. MATERIALS AND METHODS: A systematic review was conducted in July 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, EMBASE, Scopus, and Cochrane databases. Studies adopting MWA for colorectal cancer pulmonary metastases were included. RESULTS: A total of 488 lesions were ablated in 230 patients across eight studies. The median duration of ablation was 10 minutes. The mean length of stay in hospital was 2.3 days. Complications included pneumothorax in 128 (52%) patients; pneumonia, which occurred in 4 (1.7%) patients, and pulmonary haemorrhage in 23 (10.0%) patients. Complete remission was achieved in 85 (37.0%) patients, local control was achieved in 103 (44.8%) patients, and residual or progressive disease remained in 85 (37.0%). Survival post ablation at 1 year was 89.2% and at 3 years was 40.3%. Post-ablation disease-free survival was 43.2% at 3 years. CONCLUSION: MWA is an alternative treatment for pulmonary metastases of colorectal cancer. It has competitive theoretical properties and local recurrence rate compared to radiofrequency ablation.

Validation and reliability testing of a rating scale for objective assessment of performance in laparoscopic appendicectomy surgery.

BACKGROUNDS: To achieve a competency-based training paradigm, the ability to obtain reliable and valid quantitative assessments of intraoperative performance is required. Through this, weaknesses can be identified and practiced, and competency assessed. This study aimed to determine the validity and reliability an objective evaluation tool for assessment of performance in laparoscopic appendicectomy (LA). METHODS: A prospective single-blinded observational study design was used. Videos of inexperienced (performed <10 LAs) and experienced (performed >100 LAs) surgeons performing LA surgery were collected. Surgical performance during each recording was rated by two independent, blinded expert surgeons using the LA Rating Scale (LARS) and the modified Objective Structured Assessment of Technical Skill (OSATS) scale. RESULTS: The intraclass correlation coefficient (ICC) for LARS was 0.95 (95%CI 0.83-0.98). The ICC for each step ranged from 0.48 to 0.90, and the test-retest ICC for LARS was 0.91 (95%CI 0.69-0.98). Significant differences (P < 0.001) between median performance scores as rated by LARS were observed between the inexperienced and experienced surgeons. A Spearman's correlation coefficient of 0.87 (P < 0.001) was observed between LARS performance scores and modified OSATS scores. CONCLUSION: LARS demonstrated excellent inter-rater and test-retest reliability, and construct and concurrent validity and can be used to quantitatively evaluate performance during LA. This can potentially allow specific weaknesses to be identified and improved upon through deliberate practice. Progress can be tracked through re-evaluation and scores of expert surgeons can be used as performance goals for credentialing in LA.

Systematic review and meta-analysis of the association between diverticulosis of the appendix and neoplasia.

BACKGROUND: Diverticula of the appendix (DA) are infrequent and their clinical implications are often overlooked. Several studies have found a significantly increased prevalence of neoplasms in appendiceal specimens with diverticula. Despite the potential clinical implications, there is a paucity of literature. A systematic review and meta-analysis was performed to evaluate the prevalence of DA and its association with neoplasia. METHODS: A systematic search of literature (Cochrane, EMBASE, PubMed and Medline) reporting the prevalence of DA and association with neoplasia was performed in November 2019. Relevant articles were assessed in accordance with the PRISMA guidelines. Risk of bias assessment was carried out using modified Newcastle-Ottawa scale. Meta-analysis with risk ratio and random-effects model was performed using RevMan. RESULTS: The initial search identified 1122 potential articles of which 11 were appropriate for quantitative analysis. The prevalence rate of DA was 1.74%. The mean age of patients with DA and those without DA was 41.2 and 33.9 years, respectively. The ratio of male to female was 1.8:1. The prevalence of neoplasia in specimens without DA versus those with DA was 1.28% and 26.94%, respectively. Only four studies addressed the prevalence of locoregional neoplasia in the setting of DA compared to control. Meta-analysis with random-effects model demonstrated that pooled risk ratio was 25.46 (95% confidence interval 12.77-50.75, P < 0.00001). CONCLUSION: The strong association with neoplasia in this meta-analysis reinforces the clinical significance of DA. Surgeons, pathologists and radiologists should be mindful of this uncommon pathology and consider individualized patient management, until further evidence can direct clinical guidelines for the management of patients with DA.

Minimally invasive Venetian blinds ventral hernia repair with botulinum toxin chemical component separation.

BACKGROUND: Laparoscopic ventral repair is safe, with lower wound infection rates compared with open repair. 'Venetian blinds' technique of plication in combination with mesh reinforcement, is totally intra-corporeal, with hernia defect and sac plication to reduce seroma formation. While laparoscopic suturing of the abdominal wall can represent a technical challenge, pre-operative botulinum toxin A (BTA) injections as an adjunct can assist. This study aims to demonstrate feasibility and efficacy of this technique in abdominal wall hernia repair, with BTA adjunct in midline hernias. METHODS: A single-centre case series was conducted using minimally invasive 'Venetian blinds' technique for repair of complex ventral abdominal hernias. Twelve patients (seven midline, five non-midline) underwent repair (11 laparoscopic; one robotic). Midline hernias received BTA (200-300 units Botox) 4-6 weeks prior to surgery. Repairs were mesh-reinforced following fascial closure. RESULTS: Twelve (10 female, two male) patients, with a median age 72 years (range 31-83) and body mass index of 27.3 kg/m2 (range 22.8-61.7) were included. The median length of operation was 133 min (range 45-290) and length of hospital stay 3 days (range 1-28). To date there has been no recurrence of hernia. A single symptomatic seroma was treated with antibiotics and did not require mesh removal. One patient developed hospital-acquired pneumonia and pseudomembranous colitis. CONCLUSION: Minimally invasive 'Venetian blinds' technique has promising early results with both midline and non-midline ventral hernias. The addition of BTA is a novel and feasible combination for repair of midline ventral hernias.

C-reactive protein trajectory in the first 48 hours predicts the need for intervention in conservative management of acute diverticulitis.

BACKGROUND: C-reactive protein (CRP) is a useful marker for monitoring response to treatment in sepsis. The aim of this study was to examine the use of CRP trajectory in predicting the need for intervention in conservatively managed patients with acute diverticulitis (AD). METHODS: A retrospective review of patients with AD who were managed conservatively was performed. They were divided into four groups based on CRP relative to the median at day 0 and 2: 'Low rise' (levels below median at day 0 and 2), 'High rise' (levels above median at day 0 and 2), 'Rapid rise' (levels below median at day 0 but above median at day 2) and 'Decline' (levels above median at day 0 but below median at day 2). RESULTS: Intervention was required in 64 of 456 (14%) with 30 (48%) of these performed after day 2 of admission. There were 150 patients (54%) in the 'Low rise', 76 (27%) in the 'Decline', 26 patients (9%) in the 'Rapid rise' and 25 patients (9%) in the 'High rise' groups. Within these groups 5%, 8%, 19% and 32% of patients required intervention (P = 0.001). On multivariate analysis, patients with a pelvic abscess were more likely to need intervention (odds ratio 19.1 (confidence interval 6.2-59.4), P < 0.0001). CONCLUSION: The CRP trajectory during the initial 48 h of admission can predict the need for intervention in AD patients being managed conservatively. Patients with a 'Rapid rise' or 'High rise' in CRP from day 0 to 2 are more likely to need intervention.

RADProc: A computationally efficient de novo locus assembler for population studies using RADseq data.

Restriction site-associated DNA sequencing (RADseq) is a powerful tool for genotyping of individuals, but the identification of loci and assignment of sequence reads is a crucial and often challenging step. The optimal parameter settings for a given de novo RADseq assembly vary between data sets and can be difficult and computationally expensive to determine. Here, we introduce RADProc, a software package that uses a graph data structure to represent all sequence reads and their similarity relationships. Storing sequence-comparison results in a graph eliminates unnecessary and redundant sequence similarity calculations. De novo locus formation for a given parameter set can be performed on the precomputed graph, making parameter sweeps far more efficient. RADProc also uses a clustering approach for faster nucleotide-distance calculation. The performance of RADProc compares favourably with that of the widely used Stacks software. The run-time comparisons between RADProc and Stacks for 32 different parameter settings using 20 green-crab (Carcinus maenas) samples showed that RADProc took as little as 2 hr 40 min compared to 78 hr by Stacks, while 16 brown trout (Salmo trutta L.) samples were processed by RADProc and Stacks in 23 and 263 hr, respectively. Comparisons of the de novo loci formed, and catalog built using both the methods demonstrate that the improvement in processing speeds achieved by RADProc does not affect much the actual loci formed and the results of downstream analyses based on those loci.

Vitamin C deficiency in an Australian cohort of metropolitan surgical patients.

Vitamin C is an essential micronutrient in the human diet. While large population studies measuring vitamin C have been performed in other countries, there are few studies of deficiency in the Australian population. This study aimed to quantify vitamin C deficiency, identify scorbutic symptoms and examine dietary associations in a cohort of preoperative general surgical patients. Vitamin C levels were determined in a cohort of patients referred to a single surgeon between January 2011 and December 2013. Baseline data were collected along with data on fruit consumption, weekly citrus fruit intake and presence of scorbutic symptoms. A total of 309 patients were included in the study and 21.4% of our cohort showed a vitamin C level ≤11.4 µmol/L (deficient). Mean citrus fruit intake was significantly higher in the normal vitamin C groups (>28.4 µmol/L) and patients with vitamin C levels ≤28.4 were more likely to consume no fruit (p=0.0004) which was also significant on multivariate analysis. Neither age nor gender appeared predictive of suboptimal vitamin C levels. No symptoms were significantly related to vitamin C levels on multivariate analysis. Vitamin C deficiency was common in Australian adults attending a surgical practice within south western Sydney. Review of the Australian recommended daily allowance for vitamin C is suggested, not only in clinically well patients but particularly in ICU and hospital inpatients. Larger studies examining the prevalence and impact of vitamin C deficiency in the Australian population are required to further investigate these findings.

PMERGE: Computational filtering of paralogous sequences from RAD-seq data.

Restriction-site associated DNA sequencing (RAD-seq) can identify and score thousands of genetic markers from a group of samples for population-genetics studies. One challenge of de novo RAD-seq analysis is to distinguish paralogous sequence variants (PSVs) from true single-nucleotide polymorphisms (SNPs) associated with orthologous loci. In the absence of a reference genome, it is difficult to differentiate true SNPs from PSVs, and their impact on downstream analysis remains unclear. Here, we introduce a network-based approach, PMERGE that connects fragments based on their DNA sequence similarity to identify probable PSVs. Applying our method to de novo RAD-seq data from 150 Atlantic salmon (Salmo salar) samples collected from 15 locations across the Southern Newfoundland coast allowed the identification of 87% of total PSVs identified through alignment to the Atlantic salmon genome. Removal of these paralogs altered the inferred population structure, highlighting the potential impact of filtering in RAD-seq analysis. PMERGE is also applied to a green crab (Carcinus maenas) data set consisting of 242 samples from 11 different locations and was successfully able to identify and remove the majority of paralogous loci (62%). The PMERGE software can be run as part of the widely used Stacks analysis package.

Pancreatitis from intra-gastric balloon insertion: Case report and literature review.

INTRODUCTION: Intra-Gastric Balloon (IGB) is increasingly used as a non-operative management strategy in bariatric patients. However, as IGB use has become more prevalent, new potentially life-threatening adverse effects have emerged. We report a case of IGB-related acute pancreatitis from a tertiary referral hospital. A literature review of electronic databases was conducted to identify other cases PRESENTATION OF CASE: A 20-year-old female presented to the emergency department with acute onset of epigastric pain on day-1 post-insertion of an IGB (Orbera®). The diagnosis of acute pancreatitis was made on the basis of the clinical picture, with radiological and serological confirmation. Complete resolution of symptoms promptly followed endoscopic removal of the balloon. DISCUSSION: We examine all prior reported cases of IGB associated pancreatitis in the literature, as well as the impact of the particular balloon subtypes. Mass effect of the device on the pancreas or dislodgement of the rigid catheter into the second part of the duodenum appear to be the underlying cause in all cases. While there were no deaths reported, major sequelae have been noted, including presence of mucosal ischemia and failure to retrieve the balloon endoscopically, necessitating laparotomy. CONCLUSION: Although the incidence of IGB-induced pancreatitis is still rare, this complication which must be highlighted as a potentially serious adverse outcome.

A case report of endometriosis presenting as an acute small bowel obstruction.

INTRODUCTION: Endometriosis is a common and benign condition that causes significant morbidity to women of childbearing age. It uncommonly affects the gastrointestinal tract and rarely manifests as an acute small bowel obstruction. PRESENTATION OF CASE: A 46-year old female presented to the emergency department with signs and symptoms consistent with an acute small bowel obstruction. She had a paucity of background surgical history, having only had a laparoscopic cholecystectomy. Her CT demonstrated small bowel obstruction with a transition point in the distal ileum. Given the site of obstruction was remote from previous surgery, a high index of suspicion was maintained and early laparoscopy performed the same day. Operative findings were consistent with an endometrial stricture of the distal ileum and a formal resection was performed. DISCUSSION: Endometriosis that affects the gastrointestinal tract often presents with non-specific symptoms. This is a rare case of an acute small bowel obstruction as the index symptom of endometriosis in a peri-menopausal patient. This is the first case in the literature to describe same day laparoscopy and small bowel resection of such a case and a prolonged preoperative period and misdiagnoses previously described were avoided due to clinical suspicion. CONCLUSION: Endometriosis as a differential should be considered with a high index of suspicion in pre-menopausal women, particularly in patients with negligible previous surgical history. There should be a low threshold for early laparoscopy and resection of affected bowel in these patients.

A case report of gastric lymphocytic phlebitis, a rare mimic for malignancy.

INTRODUCTION: Lymphocytic phlebitis is a benign condition characterised by inflammation of the veins and rarely affects the gastrointestinal tract. Reported cases present as acute abdomen and involve the colon or small intestine. We report the fourth case of gastric lymphocytic phlebitis in the literature. PRESENTATION OF CASE: A 74-year-old female presented with eight weeks of abdominal pain. Findings at endoscopy were suggestive of a malignant ulcer on the greater curvature of antrum, while biopsies showed chronic gastritis without malignancy. Appearance at diagnostic laparoscopy was consistent with a malignant gastric ulcer with serosal changes. Due to persistent pain and the macroscopic appearance, she proceeded to have an open subtotal gastrectomy and D2 lymph node clearance. Despite macroscopic appearance, the microscopic examination demonstrated no malignancy, and was consistent with lymphocytic phlebitis with overlying ulceration. DISCUSSION: This case was a mimic for gastric malignancy, with the benign diagnosis only being made after surgical resection. Gastric lymphocytic phlebitis is a rare differential diagnosis for gastric ulcers when biopsies are negative, although preoperative diagnosis is difficult given the lesions do not involve the mucosa. CONCLUSION: If clinical history and endoscopic findings are suspicious for malignancy, despite normal biopsies, an aggressive surgical resection remains reasonable given the rarity gastric lymphocytic phlebitis.

megasat: automated inference of microsatellite genotypes from sequence data.

megasat is software that enables genotyping of microsatellite loci using next-generation sequencing data. Microsatellites are amplified in large multiplexes, and then sequenced in pooled amplicons. megasat reads sequence files and automatically scores microsatellite genotypes. It uses fuzzy matches to allow for sequencing errors and applies decision rules to account for amplification artefacts, including nontarget amplification products, replication slippage during PCR (amplification stutter) and differential amplification of alleles. An important feature of megasat is the generation of histograms of the length-frequency distributions of amplification products for each locus and each individual. These histograms, analogous to electropherograms traditionally used to score microsatellite genotypes, enable rapid evaluation and editing of automatically scored genotypes. megasat is written in Perl, runs on Windows, Mac OS X and Linux systems, and includes a simple graphical user interface. We demonstrate megasat using data from guppy, Poecilia reticulata. We genotype 1024 guppies at 43 microsatellites per run on an Illumina MiSeq sequencer. We evaluated the accuracy of automatically called genotypes using two methods, based on pedigree and repeat genotyping data, and obtained estimates of mean genotyping error rates of 0.021 and 0.012. In both estimates, three loci accounted for a disproportionate fraction of genotyping errors; conversely, 26 loci were scored with 0-1 detected error (error rate ≤0.007). Our results show that with appropriate selection of loci, automated genotyping of microsatellite loci can be achieved with very high throughput, low genotyping error and very low genotyping costs.

RAD sequencing reveals genomewide divergence between independent invasions of the European green crab (Carcinus maenas) in the Northwest Atlantic.

Genomic studies of invasive species can reveal both invasive pathways and functional differences underpinning patterns of colonization success. The European green crab (Carcinus maenas) was initially introduced to eastern North America nearly 200 years ago where it expanded northwards to eastern Nova Scotia. A subsequent invasion to Nova Scotia from a northern European source allowed further range expansion, providing a unique opportunity to study the invasion genomics of a species with multiple invasions. Here, we use restriction-site-associated DNA sequencing-derived SNPs to explore fine-scale genomewide differentiation between these two invasions. We identified 9137 loci from green crab sampled from 11 locations along eastern North America and compared spatial variation to mitochondrial COI sequence variation used previously to characterize these invasions. Overall spatial divergence among invasions was high (pairwise FST ~0.001 to 0.15) and spread across many loci, with a mean FST ~0.052 and 52% of loci examined characterized by FST values >0.05. The majority of the most divergent loci (i.e., outliers, ~1.2%) displayed latitudinal clines in allele frequency highlighting extensive genomic divergence among the invasions. Discriminant analysis of principal components (both neutral and outlier loci) clearly resolved the two invasions spatially and was highly correlated with mitochondrial divergence. Our results reveal extensive cryptic intraspecific genomic diversity associated with differing patterns of colonization success and demonstrates clear utility for genomic approaches to delineating the distribution and colonization success of aquatic invasive species.

Assessment of age in ulcerative colitis patients with ileal pouch creation - an evaluation of outcomes.

INTRODUCTION: The aim of the study was to determine if age at the creation of an ileal pouchanal anastomosis (IPAA) has an impact on the outcomes in patients with ulcerative colitis (UC). MATERIALS AND METHODS: A retrospective review of all patients who underwent IPAA for UC from 1999 to 2011 was performed. Long-term functional outcome was assessed using both the Cleveland Clinic and St Mark's incontinence scores. RESULTS: Eighty-nine patients, with a median age of 46 (range, 16 to 71) years, formed the study group. The median duration of disease prior to their pouch surgery was 7 (0.5 to 39) years. There were 57 (64%) patients who were aged ≤50 years old and 32 (36%) who were >50 years old. Fifty-seven (64%) patients developed perioperative complications of which 51 (89.5%) were minor. High ileostomy output (n = 21, 23.6%) and urinary symptoms (n = 13, 14.6%) were the most commonly encountered complications. The older patients were more likely to have an ASA score ≥3 and a longer length of stay. Although there was a higher incidence of complications in the older group of patients, the difference was not statistically significant. There were no significant differences in the incidence of severe complications. Forty-nine (55%) patients completed our questionnaire on the evaluation of their functional outcomes. There were no significant differences in the Cleveland Clinic and St Mark's incontinence scores between the older (n = 19, 38.8%) and younger (n = 30, 61.2%) patients. There were also no significant differences in the frequency of bowel movements during the day or overnight after sleep between the 2 groups. CONCLUSION: IPAA procedure for patients with UC can be safely performed. Long-term functional outcome is not significantly influenced by the age at which the IPAA was created.