ORCID Profile
0000-0002-9087-0936
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Springer Science and Business Media LLC
Date: 08-12-2017
DOI: 10.1038/JP.2016.190
Abstract: To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2022
Publisher: Wiley
Date: 20-01-2020
DOI: 10.1111/ANS.15666
Abstract: Patients with liver cirrhosis are at a higher risk of perioperative anaesthetic and surgical complications. Surgical repair of abdominal wall hernias in these patients has been widely discouraged. The main objective of this study was to evaluate the post-operative outcomes of patients with liver cirrhosis after inguinal hernia repair at a single institution. A retrospective review of a prospectively maintained database of 31 patients with liver cirrhosis undergoing inguinal hernia repair between 2006 and 2016 was undertaken. Data in relation to patient demographics, clinicopathological characteristics, morbidity and mortality were collected. Thirty-one patients with median Model for End-stage Liver Disease score of 14 (7-36) underwent inguinal hernia repair within a 10-year period of our study. There was one mortality in a patient with Model for End-stage Liver Disease score of 36 who presented with a strangulated hernia. Only one patient required return to theatre for the evacuation of haematoma and one patient developed a recurrent hernia in 1-year follow up. Inguinal hernia repair in patients with cirrhosis is a safe procedure to perform in the elective setting. Nevertheless, significant consideration must be given in performing these operations in centres with liver transplant units due to their extensive experience in pre-operative optimization to reduce the risk of hepatic decompensation.
Publisher: Oxford University Press (OUP)
Date: 11-03-2019
DOI: 10.1093/DOTE/DOZ011
Abstract: Oral contrast studies are used to detect anastomotic leak (AL) postesophagectomy. However, recent evidence suggests oral contrast studies have low sensitivity in detecting ALs, and their false positive results can lead to unnecessary prolonged hospital stay. The objective of this study was to determine if oral contrast studies should be used routinely post-esophagectomy for cancer. A systematic literature search was conducted for studies published between January 1990 and June 2018. Data extracted for analyses included type of esophagectomy, operative morbidity (such as AL and pneumonia), mortality rates, timing of contrast study, and type of oral contrast used. The sensitivity, specificity, and positive and negative predictive values of routine oral contrast studies to detect AL were calculated using the aforementioned variables. Two hundred and forty-seven studies were reviewed with 16 studies included in the meta-analysis. Postoperative oral contrast study was performed in 94.0% of cases between day 5 and 7. The rates of early and delayed leaks were 2.4% (1.8%–3.3%) and 2.8% (1.8%–4.4%), respectively. Routine contrast studies have a sensitivity and specificity of 0.44 (0.32–0.57) and 0.98 (0.95–0.99), respectively. Analysis of covariates revealed that sensitivity is reduced in centers with a higher volume of cases (greater than 15 per year: 0.50 [0.34–0.75 p = 0.0008]) and specificity was higher in centers with a lower leak rate. Given its poor sensitivity and inability to detect early/delayed AL, oral contrast study should be used selectively with endoscopy and/or computerized tomography scan to assess surgical anastomoses following esophagectomy.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1053/J.GASTRO.2021.09.059
Abstract: Chronic inflammation is a known risk factor for gastrointestinal cancer. The evidence that nonsteroidal anti-inflammatory drugs suppress the incidence, growth, and metastasis of gastrointestinal cancer supports the concept that a nonsteroidal anti-inflammatory drug target, cyclooxygenase, and its downstream bioactive lipid products may provide one of the links between inflammation and cancer. Preclinical studies have demonstrated that the cyclooxygenase-2-prostaglandin E
Publisher: Public Library of Science (PLoS)
Date: 06-11-2013
Publisher: American Association for Cancer Research (AACR)
Date: 26-07-2021
DOI: 10.1158/1535-7163.MCT-21-0067
Abstract: APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactivation therapy. Currently, the detection of at least one TP53 mutation is an inclusion criterion for patient selection into most APR-246 clinical trials. Preliminary results from our phase Ib/II clinical trial investigating APR-246 combined with doublet chemotherapy [cisplatin and 5-fluorouracil (5-FU)] in metastatic esophageal cancer, together with previous preclinical studies, indicate that TP53 mutation status alone may not be a sufficient biomarker for APR-246 response. This study aims to identify a robust biomarker for response to APR-246. Correlation analysis of the PRIMA-1 activity (lead compound to APR-246) with mutational status, gene expression, protein expression, and metabolite abundance across over 700 cancer cell lines (CCL) was performed. Functional validation and a boutique siRNA screen of over 850 redox-related genes were also conducted. TP53 mutation status was not consistently predictive of response to APR-246. The expression of SLC7A11, the cystine/glutamate transporter, was identified as a superior determinant of response to APR-246. Genetic regulators of SLC7A11, including ATF4, MDM2, wild-type p53, and c-Myc, were confirmed to also regulate cancer-cell sensitivity to APR-246. In conclusion, SLC7A11 expression is a broadly applicable determinant of sensitivity to APR-246 across cancer and should be utilized as the key predictive biomarker to stratify patients for future clinical investigation of APR-246.
Publisher: Oxford University Press (OUP)
Date: 23-02-2022
DOI: 10.1093/BJS/ZNAC016
Abstract: Textbook outcome has been proposed as a tool for the assessment of oncological surgical care. However, an international assessment in patients undergoing oesophagectomy for oesophageal cancer has not been reported. This study aimed to assess textbook outcome in an international setting. Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018 to December 2018. Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. A multivariable binary logistic regression model was used to identify factors independently associated with textbook outcome, and results are presented as odds ratio (OR) and 95 per cent confidence intervals (95 per cent c.i.). Of 2159 patients with oesophageal cancer, 39.7 per cent achieved a textbook outcome. The outcome parameter ‘no major postoperative complication’ had the greatest negative impact on a textbook outcome for patients with oesophageal cancer, compared to other textbook outcome parameters. Multivariable analysis identified male gender and increasing Charlson comorbidity index with a significantly lower likelihood of textbook outcome. Presence of 24-hour on-call rota for oesophageal surgeons (OR 2.05, 95 per cent c.i. 1.30 to 3.22 P = 0.002) and radiology (OR 1.54, 95 per cent c.i. 1.05 to 2.24 P = 0.027), total minimally invasive oesophagectomies (OR 1.63, 95 per cent c.i. 1.27 to 2.08 P & 0.001), and chest anastomosis above azygous (OR 2.17, 95 per cent c.i. 1.58 to 2.98 P & 0.001) were independently associated with a significantly increased likelihood of textbook outcome. Textbook outcome is achieved in less than 40 per cent of patients having oesophagectomy for cancer. Improvements in centralization, hospital resources, access to minimal access surgery, and adoption of newer techniques for improving lymph node yield could improve textbook outcome.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2014
DOI: 10.1007/S10120-014-0388-5
Abstract: Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48 95% CI 0.32-0.70 p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70 9 % CI 0.47-1.04 p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with 4.6% for IPC group). However, these promising results need to be validated in larger prospective randomized trials.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Springer Science and Business Media LLC
Date: 02-10-2022
DOI: 10.1245/S10434-022-12562-5
Abstract: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15 + immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15 + cell count, tumor regression grade, and tumor grade. After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15 + ) counts. Our nomogram incorporating CD15 + cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68–0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69–0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69–0.91) and 0.78 (95% CI 0.7–0.86), respectively. Our nomogram incorporating CD15 + cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.
Publisher: Wiley
Date: 06-05-2013
DOI: 10.1111/ANS.12197
Abstract: Previous studies have suggested that patients with occult peritoneal metastases not seen on preoperative imaging have poor prognosis. In this study, we aim to evaluate the utility and impact of staging laparoscopy and peritoneal cytology in patients with gastric adenocarcinoma. A retrospective analysis of patients with gastric adenocarcinoma managed at two major metropolitan hospitals in Melbourne, Australia, between January 1999 and July 2010 was undertaken. The main outcome measures were the number of patients in whom laparoscopy and/or peritoneal cytology changed treatment intent, and the overall survival of patients with occult metastases detected by laparoscopy/cytology. Staging laparoscopy as an independent procedure was performed in 74.3% (148/199) of patients who had neither unequivocal metastases (M1) on preoperative imaging nor early T1 disease on endoscopic ultrasound. Laparoscopy/cytology detected occult metastases in 38 (25.6%) patients (27 macroscopic M1 and 11 microscopic M1 with positive peritoneal cytology only), leading to change in the treatment intent in 37 cases. The median overall survivals of patients with metastatic disease detected at staging laparoscopy (8.3 months, 95% confidence interval (CI) 5.4-16.5) or on peritoneal cytology (4.9 months, 95% CI 4.2-48) were as poor as those with M1 disease seen on preoperative imaging (6.7 months, 95% CI 4.2-8.9), P = 0.97. Laparoscopy and peritoneal cytology add incremental value to modern imaging in the staging of gastric adenocarcinomas by detecting occult metastatic disease. Their utility needs to be optimized to allow better treatment selection for gastric cancer patients.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.SURG.2022.05.020
Abstract: Wound complications are a common cause of postoperative morbidity and incur significant healthcare costs. Recent studies have shown that negative pressure wound dressings reduce wound complication rates, particularly surgical site infections, after elective laparotomies. The clinical utility of prophylactic negative pressure wound dressings for closed emergency laparotomy incisions remains controversial. This meta-analysis investigated the rates of wound complications after emergency laparotomy when a negative pressure wound dressing was applied. A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Registry, Web of Science, and Clinialtrials.gov databases were searched from January 1, 2005, to April 1, 2022. All studies comparing negative pressure wound dressings to standard dressings on closed emergency laparotomy incisions were included. A total of 1,199 (negative pressure wound dressings: 566, standard dressing: 633) patients from 7 (prospective: 4, retrospective: 3) studies were identified. Overall, the surgical site infection (superficial/deep) rate was 13.6% (77/566) vs 25.1% (159/633) in the negative pressure wound dressing versus standard dressing groups, respectively (odds ratio 0.43, 95% confidence interval 0.30-0.62). Wound breakdown (skin/fascial dehiscence) was significantly lower in the negative pressure wound dressing (7.7%) group compared to the standard dressing (16.9%) group (odds ratio 0.36, 95% confidence interval 0.19-0.72). The incidence of overall wound complications was significantly lower in the negative pressure wound dressing (15.9%) group compared to the standard dressing (30.4%) group (odds ratio 0.41, 95% confidence interval 0.28-0.59). No significant differences were found in hospital length-of-stay and readmission rates. Prophylactic negative pressure wound dressings for closed emergency laparotomy incisions were associated with a significant reduction in surgical site infections, wound breakdown, and overall wound complications, thus supporting its clinical use.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-08-2021
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-09-2022
Abstract: The mechanism of action of eprenetapopt (APR-246, PRIMA-1 MET ) as an anticancer agent remains unresolved, although the clinical development of eprenetapopt focuses on its reported mechanism of action as a mutant-p53 reactivator. Using unbiased approaches, this study demonstrates that eprenetapopt depletes cellular antioxidant glutathione levels by increasing its turnover, triggering a nonapoptotic, iron-dependent form of cell death known as ferroptosis. Deficiency in genes responsible for supplying cancer cells with the substrates for de novo glutathione synthesis ( SLC7A11 , SHMT2 , and MTHFD1L ), as well as the enzymes required to synthesize glutathione ( GCLC and GCLM ), augments the activity of eprenetapopt. Eprenetapopt also inhibits iron-sulfur cluster biogenesis by limiting the cysteine desulfurase activity of NFS1, which potentiates ferroptosis and may restrict cellular proliferation. The combination of eprenetapopt with dietary serine and glycine restriction synergizes to inhibit esophageal xenograft tumor growth. These findings reframe the canonical view of eprenetapopt from a mutant-p53 reactivator to a ferroptosis inducer.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2015
DOI: 10.1007/S00259-015-3211-6
Abstract: To assess the diagnostic utility of gastric distension (GD) FDG PET/CT in both patients with known gastric malignancy and those not known to have gastric malignancy but with incidental focal FDG uptake in the stomach. This retrospective analysis included 88 patients who underwent FDG PET/CT following GD with hyoscine N-butylbromide (Buscopan®) and water ingestion as part of routine clinical evaluation between 2004 and 2014. FDG PET/CT scans before and after GD were reported blinded to the patient clinical details in 49 patients undergoing pretreatment staging of gastric malignancy and 39 patients who underwent GD following incidental suspicious gastric uptake. The PET findings were validated by a composite clinical standard. In the 49 patients undergoing pretreatment staging of gastric malignancy, GD improved PET detection of the primary tumour (from 80 % to 90 %). PET evaluation of tumour extent was concordant with endoscopic/surgical reports in 31 % (interpreter 1) and 45 % (interpreter 2) using pre-GD images and 73 % and 76 % using GD images. Interobserver agreement also improved with GD (κ = 0.29 to 0.69). Metabolic and morphological quantitative analysis demonstrated a major impact of GD in normal gastric wall but no significant effect in tumour, except a minor increase in SUV related to a delayed acquisition time. The tumour to normal stomach SUVmax ratio increased from 3.8 ± 2.9 to 9.2 ± 8.6 (mean ± SD) with GD (p < 0.0001), facilitating detection and improved assessment of the primary tumour. In 25 (64 %) of the 39 patients with incidental suspicious gastric uptake, acquisition after GD correctly excluded a malignant process. In 10 (71 %) of the remaining 14 patients with persistent suspicious FDG uptake despite GD, malignancy was confirmed and in 3 (21 %) an active but benign pathology was diagnosed. GD is a simple way to improve local staging with FDG PET in patients with gastric malignancy. In the setting of incidental suspicious gastric uptake, GD is also an effective tool for ruling out malignancy and leads to the avoidance of unnecessary endoscopy.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2022
No related grants have been discovered for Carlos Cabalag.