Geraldine J. Ooi

Laboratory Risk Indicator for Necrotizing Fasciitis score for early diagnosis of necrotizing fasciitis in Darwin

Soft tissue infections are a major health burden in the Top End of the Northern Territory of Australia. Necrotizing fasciitis (NF) is associated with mortality rates from 8 to 40%. Early recognition and aggressive surgical debridement are the cornerstones of successful treatment. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, developed by Wong et al., uses six routine biochemical variables to aid early diagnosis. We aim to assess the diagnostic efficacy of the LRINEC score in our population.

Indications and efficacy of endoscopic vacuum-assisted closure therapy for upper gastrointestinal perforations.

Endoscopic vacuum‐assisted closure (EndoVAC) therapy is a recent innovation described for use in upper gastrointestinal perforations and leaks, with reported success of 80–90%. It provides sepsis control and collapses the cavity preventing stasis, encouraging healing of the defect. Whilst promising, initial reports of this new technique have not established clear indications, feasibility and optimal technique.

Response to Re: Laboratory Risk Indicator for Necrotizing Fasciitis score for early diagnosis of necrotizing fasciitis in Darwin: Letters to the Editor

Thank you for your insightful comments regarding the interpretation of the statistical tests in your Letter to the Editor. We acknowledge that the positive and negative predictive values are influenced by the prevalence of the disease. It is important to point out that although we reported positive and negative predictive values, we have reported and discussed all measures of diagnostic accuracy for the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score. This includes measures that are independent of disease prevalence, including sensitivity, specificity, likelihood ratios and the area under receiver operating characteristic (AUROC) curve. Our study showed that the LRINEC test has reasonable sensitivity, high specificity and an excellent AUROC curve, demonstrating good diagnostic accuracy. It is useful to take into account all these measures of diagnostic accuracy while utilizing the LRINEC score. The main take-home message we wish to emphasize from this study is that while the LRINEC test is a useful, easy test to perform with good diagnostic accuracy, it does not supersede clinical examination and maintaining a high clinical suspicion for the disease remains the gold standard for diagnosing necrotizing fasciitis.

Systematic review and meta‐analysis: non‐invasive detection of non‐alcoholic fatty liver disease related fibrosis in the obese

Non‐alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non‐invasive NAFLD tests. We aimed to review current evidence for common non‐invasive tests for NAFLD‐related fibrosis in obesity.

Extensive pneumatosis intestinalis: a benign bystander

Pneumatosis intestinalis is defined as the presence of gas in the bowel wall. Du Vernoi first described it in 1783, based on cadaveric dissection. It is a not a disease in itself, but a clinical sign that points to underlying pathology, whether benign or malignant. In the past, pneumatosis intestinalis are commonly diagnosed surgically via laparotomy or laparoscopy with findings of gas-filled cysts in the bowel wall. Its detection has exponentially increased with the advancement of radiological modalities, especially multi-detector computed tomography. Clinical presentation of pneumatosis varies depending on the underlying pathology.

Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty liver disease in severe and morbid obesity

IntroductionIn obese individuals, nonalcoholic fatty liver disease (NAFLD) is common but often goes undiagnosed, and therefore untreated. The presence of significant fibrosis is a key determinant of NAFLD progression, and liver steatosis has substantial cardiovascular implications. We aimed to determine the diagnostic accuracy of common noninvasive diagnostic tests for steatosis and fibrosis in the obese.MethodsWe recruited 182 severely and morbidly obese individuals undergoing bariatric surgery (age 44 ± 12 years, body mass index 45.1 ± 8.3 kg/m2). Medical history, blood tests and liver biopsy were taken on the day of surgery. Serum steatosis and fibrosis scores were calculated. In a subgroup of patients, transient elastography with controlled attenuation parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy (1H-MRS) (n = 49) were performed.Results1H-MRS had excellent diagnostic accuracy for steatosis, with strong correlation to steatosis (r = 0.647, p < 0.001), good AUROC (0.852, p = 0.001), sensitivity (81.3%) and specificity (87.5%). However, due to low feasibility in this cohort (65.3% success), this was substantially decreased with intention-to-diagnose analysis (sensitivity 50.0%, specificity 60.9%). CAP had good feasibility (80.5%), and performed better in intention-to-diagnose analysis (AUROC 0.688, sensitivity 84.8%, specificity 47.2%). Serum steatosis scores performed poorly, with comparable accuracy to ALT. For significant fibrosis, TE had the best accuracy (AUROC 0.903, p = 0.007), which remained reasonable after intention-to-diagnose analysis (sensitivity 100%, specificity 59.0%). A combination approach using CAP with ALT for steatosis and TE with Forn index for fibrosis yielded reasonable overall accuracy.Conclusions1H-MRS and TE/CAP had greatest accuracy for NAFLD-related steatosis and fibrosis. Failure rates in obesity significantly diminished diagnostic ability. Use of a combination of serum and imaging tests improved overall feasibility of assessment and diagnostic accuracy in obese individuals.

Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC

Summary Obesity is a major driver of cancer, especially hepatocellular carcinoma (HCC). The prevailing view is that non-alcoholic steatohepatitis (NASH) and fibrosis or cirrhosis are required for HCC in obesity. Here, we report that NASH and fibrosis and HCC in obesity can be dissociated. We show that the oxidative hepatic environment in obesity inactivates the STAT-1 and STAT-3 phosphatase T cell protein tyrosine phosphatase (TCPTP) and increases STAT-1 and STAT-3 signaling. TCPTP deletion in hepatocytes promoted T cell recruitment and ensuing NASH and fibrosis as well as HCC in obese C57BL/6 mice that normally do not develop NASH and fibrosis or HCC. Attenuating the enhanced STAT-1 signaling prevented T cell recruitment and NASH and fibrosis but did not prevent HCC. By contrast, correcting STAT-3 signaling prevented HCC without affecting NASH and fibrosis. TCPTP-deletion in hepatocytes also markedly accelerated HCC in mice treated with a chemical carcinogen that promotes HCC without NASH and fibrosis. Our studies reveal how obesity-associated hepatic oxidative stress can independently contribute to the pathogenesis of NASH, fibrosis, and HCC.

Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines: Pro-tumourigenic cytokines during gastric surgery

Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation.

Assessing quality of care in oesophago-gastric cancer surgery in Australia.

Outcomes of oesophago‐gastric cancer are poor and highly variable between centres. It is important that complex multimodal treatments are applied optimally. Low case volumes at Australian centres mean that the analysis of crude outcomes is an inadequate assessment of overall quality of care. Detailed analysis across a range of quality domains offers the opportunity to measure performance.

Gallstone ileus following therapeutic endoscopic retrograde cholangiopancreatography.

An 81-year-old man presented with a 1 day history of epigastric and right upper quadrant pain, with altered liver function tests (LFTs). His past history included a laparoscopic cholecystectomy 7 years ago, and an endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy 2 years ago for choledocholithiasis. There was no history of any other abdominal surgery. In the last 5 years, he had been diagnosed with a protein-losing enteropathy after extensive investigation for iron deficiency anaemia and loss of weight. His other co-morbidities were stable ischaemic heart disease and hypertension. On presentation, he had features of sepsis with hypotension and mild hypothermia. His initial blood tests showed markedly deranged LFTs (bilirubin 55 μmol/L, alkaline phosphatase 1046 U/L and gammaglutamyl transferase 805 U/L), with raised inflammatory markers (white cell count 14.5 × 10/L, neutrophils 12.0 × 10/L and CRP 110 mg/L). He was clinically diagnosed with ascending cholangitis. Fluid resuscitation and broad spectrum intravenous antibiotic therapy were initiated. An abdominal computed tomography (CT) scan was performed, which clearly demonstrated choledocholithiasis, with no other source of sepsis (Fig. 1, left). A magnetic resonance cholangiopancreatography (MRCP) confirmed a dilated common bile duct (CBD) (1.9 cm) with three large intraductal calculi. The patient went on to have an urgent ERCP, sphincterotomy and stone removal (Fig. 1, inset). Multiple stones were removed, reported to be between 2 and 3 cm in size. Over the next 2 days, he improved clinically and his LFTs began to normalize. Over the subsequent 4 days, he developed progressive abdominal distension with eventual obstipation and vomiting. An abdominal X-ray revealed multiple dilated small bowel loops with air fluid levels and pneumobilia in keeping with a small bowel obstruction and recent ERCP. A CT scan with contrast confirmed a small bowel obstruction with a transition point suggestive of an occluding midileum intraluminal lesion (Fig. 1, right). He was subsequently taken to theatre for an emergency laparotomy. At laparotomy, a 28 mm gallstone was found impacted in the mid-ileum (Fig. 2). Multiple mild strictures were found in the ileum that likely contributed to the obstruction. An enterotomy was performed to retrieve the stone and stricturoplasty performed. Small bowel biopsy revealed non-specific acute on chronic inflammation. His post-operative recovery was complicated by pneumonia, which settled with a short course of antibiotics. He was discharged to rehabilitation on post-operative day 14 after the operation. Gallstone ileus is an uncommon cause of small bowel obstruction, accounting for 1–4% of cases. Gallstone ileus following ERCP is exceedingly rare, due to the calibre of stones that can usually pass via the common bile duct. There are 13 cases of gallstone ileus following ERCP in the literature. In the majority, the calculi were retrieved from the common bile duct during ERCP, and left in the small bowel lumen, subsequently causing obstruction. Of note, five of the cases described sphincterotomy but unsuccessful stone retrieval. In these patients, calculi up to 3.5 cm were reported to have consequently passed unassisted into the duodenum through the endoscopic sphincterotomy. The time of obstruction varied from 1 day to 4 months after the procedure. The most common site of impaction is the ileum, due to its smaller diameter, tortuosity and less active peristalsis. Furthermore, factors that slow intestinal peristalsis or narrow the bowel may increase the risk of gallstone ileus, including ascites, decreased physical activity, radiation enteritis or anastomotic strictures. Management generally involves an operation for stone retrieval. In the majority of cases, a laparotomy with enterotomy and removal of calculi was performed. Prackup et al. described successful management with adhesiolysis of stricturing scar tissue and milking the gallstone into the caecum from the distal ileum. Small bowel resection was required in three cases with delayed diagnosis that were complicated by bowel perforation. The size of the calculi in these cases ranged from 2 to 3.1 cm. It is, however, noted that two cases of gallstone ileus following ERCP have been managed conservatively with success, with calculi measuring up to 2 cm. One