ORCID Profile
0000-0001-9377-8521
Current Organisation
UNSW Graduate Research School
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Publisher: Hindawi Limited
Date: 12-09-2013
DOI: 10.1155/2013/598251
Abstract: The urokinase-type plasminogen activator receptor (uPAR) has been implicated in several processes in tumor progression including cell migration and invasion in addition to initiation of signal transduction. Since uPAR lacks a transmembrane domain, it uses the interaction with other proteins to modulate intracellular signal transduction. We have previously identified hSpry1 as a partner protein of uPAR, suggesting a physiological role for hSpry1 in the regulation of uPAR signal transduction. In this study, hSpry1 was found to colocalize with uPAR upon stimulation with epidermal growth factor (EGF), urokinase (uPA), or its amino terminal fragment (uPA-ATF), implicating a physiological role of hSpry1 in regulation of uPAR signalling pathway. Moreover, hSpry1 was able to inhibit uPAR-stimulated cell migration in HEK293/uPAR, breast carcinoma, and colorectal carcinoma cells. In addition, hSpry1 was found to inhibit uPAR-stimulated cell invasion in breast carcinoma and osteosarcoma cell lines. Increasing our understanding of how hSpry1 negatively regulates uPAR-stimulated cellular functions may determine a distinctive role for hSpry1 in tumour suppression.
Publisher: Hindawi Limited
Date: 1996
DOI: 10.1155/1996/52565
Abstract: Background: Wedge or other nonanatomic hepatic resections, performed in an attempt to spare functional parenchyma, often are not accomplished with clear resection margins and may be complicated by hemorrhage from the depth of the resection. Study Design: The current study describes a technique of cryoassisted hepatic resection that allows for controlled resection with well-defined margins. The early experience in managing 16 tumors in 13 patients is reported. Results: A cryoprobe is inserted into the tumor and freezing performed to a predetermined resection margin using ultrasound control. The ice ball, so formed, is then maintained and excised. The management of these 13 patients was associated with one intraoperative and two postoperative complications, including a death of a patient with cirrhosis who had infected ascites and died as a result of hepatic failure. Conclusions: Cryoassisted hepatic resection seems to be safe and allows resection with good tumor clearance and maximal preservation of functional parenchyma.
Publisher: Hindawi Limited
Date: 1990
DOI: 10.1155/1990/47243
Abstract: Five patients with hepatic (3), pelvic (1) or spinal (1) hydatid cysts received 10 mg/kg/d albendazole for 1–3 months prior to surgery. Daughter cysts were present in the spinal hydatid and in one patient with hepatic disease. Electron microscope examination of the cyst tissue of the pelvic and the 2 hepatic cysts lacking daughter cysts showed no evidence of germinal layer, and the protoscoleces were dead. The primary cyst of the hepatic hydatid with daughter cysts (1 month therapy) was also judged dead but some pieces of the daughter cyst germinal layer appeared normal and had unaffected protoscoleces. The daughter cyst tissue of the spinal hydatid (3 month therapy) appeared normal and the protoscoleces viable. In view of the undetermined viability of human hydatids before chemotherapy, treatment of longer than 1 month is advocated for hepatic cysts, particularly if daughter cysts are present, and longer therapy is indicated for spinal disease.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651
Abstract: Supplementary Methods
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/461041
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654
Abstract: Supplementary Figures S1-S13
Publisher: Hindawi Limited
Date: 2000
DOI: 10.1155/2000/60432
Abstract: Thirteen patients underwent hepatic cryotherapy and synchronous colonic resection. Two of the nine patients developed hepatic abscess – this is a rare complication of cryotherapy alone.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: American Association for Cancer Research (AACR)
Date: 07-10-2022
DOI: 10.1158/1078-0432.CCR-22-1206
Abstract: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Publisher: Hindawi Limited
Date: 1998
DOI: 10.1155/1998/61506
Abstract: The case of a male who had an open cholecystectomy complicated by presistent bile leak from an aberrant bile duct is presented. The persistence and volume of bile leak resulted in subsequent investigation of the biliary tree which demonstrated a cholangiocarcinoma of the right hepatic duct. This case is presented as an unusual presentation of cholangiocarcinoma and to highlight the value of modern techniques in imaging the biliary tree.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651.V1
Abstract: Supplementary Methods
Publisher: Wiley
Date: 21-08-2023
DOI: 10.1002/JSO.27416
Abstract: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal‐Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open–close laparotomy—those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility—those who underwent open–close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence‐free survival (OS, RFS). Prognostic scores were calculated for the 174‐patient external validation cohort. COMPASS was most accurate in predicting open–close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open–close prediction was 0.78 (95% confidence interval, CI: 0.68–0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52–0.71), and C‐statistic for OS was 0.65 indicating only possibly helpful discrimination. C‐statistic for RFS was 0.59 indicating poor discrimination. While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2021
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654.V1
Abstract: Supplementary Figures S1-S13
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/373826
Abstract: Sprouty (Spry) proteins, modulators of receptor tyrosine kinase signaling pathways, have been shown to be deregulated in a variety of pathological conditions including cancer. In the present study we investigated the expression of Spry1 and Spry2 isoforms in a panel of human ovarian cancer cell lines in vitro. Our western blot analysis showed nonuniform patterns of Spry expression in the cancer cells, none of which conformed to the pattern observed in the normal ovarian epithelial cells employed as the control. Among the seven cancer cell lines studied, Spry1 was expressed lower in four cell lines and higher in one as compared with the control. As for Spry2, four cell lines showed lower and two exhibited higher expression. Results from RT-PCR assay raised the possibility that Spry protein levels may not necessarily correspond with its expression at mRNA level. Our immunostaining study revealed that Spry2 was predominantly distributed within the whole cytoplasm in vesicular structures whereas Spry1 was found in both the cytoplasm and nucleus. This might provide clues to further investigation of Spry mode of action and/or function. Collectively, our study unveiled the differential expression of Spry1 and Spry2 proteins in various ovarian cancer cell lines.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 2021
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/950749
Abstract: The urokinase-type plasminogen activator receptor (uPAR) is a cell surface receptor which has a multifunctional task in the process of tumorigenesis including cell proliferation, adhesion, migration, and invasion. Many of the biological functions of uPAR necessitate interactions with other proteins. We have shown previously that uPAR interacts with HAX1 protein (HS-1-associated protein X-1). In the current study, to gain insight into the possible role of HAX1 overexpression in regulation of uPAR signal transduction pathway, several function assays were used. We found that, upon stimulation of uPAR, HAX1 colocalizes with uPAR suggesting a physiological role for HAX1 in the regulation of uPAR signal transduction. HAX1 overexpression augments cell proliferation and migration in uPAR-stimulated cells. Moreover, HAX1 over-expression augmented uPAR-induced cell adhesion to vitronectin as well as cellular invasion. Our results suggest that HAX1 over-expression may underlay a novel mechanism to regulate uPAR-induced functions in cancer cells.
Publisher: Hindawi Limited
Date: 1990
DOI: 10.1155/1990/67385
Abstract: Protoscoleces of Echinococcus granulosus were cultured in vitro in 500, 250 or 100 μ g/1 albendazole sulphoxide for 1, 3, 7, 10, 14d and then ‘recued’ (R) into drug-free medium for the remainder ofthe culture period. Successful minimum lengths of therapy were much longer than for praziquantel, and only at 500 μ g/1 was the 10dR treatment as effective as continuous therapy for 28d. Treatment with 100 μ g/1 both in continuous culture and in the ‘R’ experiments was ineffective over a 35d period. The results are compared with those from similar experiments using praziquantel.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645
Abstract: Supplementary Tables S1-S11
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2020
DOI: 10.1101/2020.09.07.286906
Abstract: SARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. Whilst vaccines are at the forefront of the therapeutic initiative, drug repurposing remains a promising approach for SARS-CoV-2 treatment. BromAc (Bromelain & Acetylcysteine) has synergistic action against glycoproteins by the synchronous breakage of glycosidic linkages and disulfide bonds. The spike protein of SARS-CoV-2, formed of glycoprotein and disulfide bridges for stabilization, represents an attractive target as it is essential for binding to the ACE2 receptor in host cells present in nasal mucosa. We sought to determine the effect of BromAc on the Spike and Envelope proteins and its potential to reduce infectivity in host cells. Recombinant Spike and Envelope proteins were treated by single agent and combination BromAc at 50 and 100 µg/20mg/mL and analyzed by electrophoresis. Ultraviolet analysis of disulfide bond reduction was performed for both Spike and Envelope proteins after treatment with Acetylcysteine. In vitro whole virus culture inactivation of pre-treated wild type and an S1/S2 Spike mutant SARS-CoV-2 with BromAc from 25 to 250 µg/20mg/mL was measured by cytopathic effect, cell lysis assay, and replication capacity by RT-PCR. Recombinant Spike and Envelope SARS-CoV-2 proteins were fragmented by BromAc at both 50 and 100 µg/20mg/mL whilst single agents had minimal effect. Spike and Envelope protein disulfide bonds were reduced by Acetylcysteine. In vitro whole virus culture of both wild type and Spike mutant SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. BromAc disintegrates SARS-CoV-2 Spike and Envelope proteins. In vitro tests on whole virus support this finding with inactivation of its replication capacity most strongly at 100 and 250 µg/20mg/mL BromAc, even in Spike mutant virus. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent. There is currently no suitable therapeutic treatment for early SARS-CoV-2 aimed to prevent disease progression. BromAc is under clinical development by the authors for mucinous cancers due to its ability to alter complex glycoproteins structure. The potential of BromAc on SARS-CoV-2 Spike and Envelope glycoproteins stabilized by disulfide bonds was examined and found to disintegrate recombinant Spike and Envelope proteins whilst reducing disulfide stabilizer bridges. BromAc also showed an inhibitory effect on wild-type and Spike mutant SARS-CoV-2 by inactivation of its replication capacity in vitro . Hence, BromAc may be an effective therapeutic agent for early SARS-CoV-2 infection, despite mutations, and even have potential as a prophylactic in people at high risk of infection.
Publisher: Hindawi Limited
Date: 1998
DOI: 10.1155/1998/12974
Abstract: Purpose : A prospective, randomized trial was performed to determine if intra-abdominal drainage catheters are necessary after elective liver resection. Patients and Methods : Between April 1992 and April 1994, 120 patients subjected to liver resection, stratified by extent of resection and by surgeon, were randomized to receive or not receive operative closed-suction drainage. Operative blood loss was not an exclusion criteria, and no patient who consented to the study was excluded. Results : Eighty-seven patients (73%) had resection of one hepatic lobe or more (27 lobectomies, 54 trisegmentectomies, and 6 bilobar atypical resections) and 33 had less than a lobectomy (8 wedge resections or enucleations, 9 segmentectomies, and 16 bisegmentectomies). Eighty-four patients (70%) had metastatic cancer and 36 patients (30%) had primary liver pathology. There were no differences in outcome, including length of hospital stay (no drain, 13.4 ± 0.9 days drain, 13.1 ± 0.8 days P not significant [NS]), mortality (no drain, 3.3% drain, 3.3%), complication rate (no drain, 43% drain, 48% n = NS), or requirement for subsequent percutaneous drainage (no drain, 18% drain, 8% P = NS). All infected collections ( n = 3) occured in operatively drained patients. Two other complications were directly related to the operatively placed drains. One patient developed a subcutaneous abscess at the drain site, and a second developed a subcutaneous drain tract tumor recurrence as the only current site of recurrence. Conclusion : In the first 50 consecutive resections performed since the conclusion of this trial, only 4 patients (8%) have required subsequent percutaneous drainage. We conclude that abdominal drainage is unnecessary after elective liver resection,
Publisher: Hindawi Limited
Date: 1995
DOI: 10.1155/1995/93283
Abstract: The use of cryotherapy for the treatment of some unresectable liver tumours has been clearly established as a therapeutic option. Intra-operative ultrasound has enhanced the process by enabling the surgeon to identify hepatic lesions and to allow visualisation of the freezing process to ensure that the cryolesion will include the tumour mass. The purpose of this paper is to provide a practical guide to surgeons who wish to perform cryotherapy of liver tumours. Patient selection and anaesthetic considerations are important. The surgeon should be able to deal with the complications of cryotherapy, particularly the intra-operative haemorrhage which may arise from cracking of the hepatic parenchyma as the iceball thaws. Follow-up is based on tumour marker assay and imaging of the liver and repeat cryotherapy can be considered for selected cases.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/540791
Abstract: Despite recent advances in the management of ovarian cancer, it remains the most lethal gynecologic malignancy. Vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in the progression of ovarian cancer leading to the eventual development of malignant ascites. On this basis, agents rendering VEGF ineffective by neutralizing VEGF (bevacizumab), blocking its receptors (aflibercept), or interfering with the postreceptor signaling pathways (sunitinib) provide us with the rational treatment options. These agents are generally used in combination with the standard chemotherapeutic drugs. Here, we discuss the basis of and the logic behind the use of these agents in the treatment of epithelial ovarian cancer, as well as their evaluation in different preclinical and clinical studies.
Publisher: Hindawi Limited
Date: 1996
DOI: 10.1155/1996/71637
Abstract: Intra-operative contact ultrasound is a sensitive method of detecting liver tumours. The aim of this study was to compare the sensitivity of open contact ultrasound (OUS) of the liver with laparoscopic contact ultrasound (LUS). Hypoechoic “lesions” were created in 5 fresh pig livers by inserting 28 grapes via small incisions in the inferior surface. The size (range 8–25 mm) and location of each grape was recorded. Scanning was undertaken in random order by two experienced independent observers with no knowledge of the size, number or position of the lesions, using an Aloka 650 series scanner and 7.5 MHz probes. The crude sensitivity with OUS was 96% and 100% respectively for the two observers, and 92% for each with LUS. One grape was interpreted as 2 seperate grapes on LUS by one observer. Absolute sensitivity (grapes identified in the correct location) was 86% and 93% respectively with OUS and 79% for each observer with LUS. LUS was almost as sensitive as OUS in this model of hepatic metastases.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645.V1
Abstract: Supplementary Tables S1-S11
Publisher: Hindawi Limited
Date: 1996
DOI: 10.1155/1996/24016
Abstract: Spontaneous liver rupture is uncommon, difficult to diagnose and carries a universally high mortality. It has been well documented to occur as a complication of primary or secondary hepatic malignancy. Similarly, there are 28 cases of ruptured haemangiomata described in the world literature. It is also well described in severe pregnancy-induced hypertension and is said to carry a mortality of 18% for patients treated by packing and drainage of the haematoma and 75% for patients treated with liver resection. Two female patients aged 60 and 61 presented to our accident and emergency department. One had a history of hypertension only and the other a history of a bleeding diathesis from the lupus anticoagulant. Both presented with hypotension and abdominal pain and both were diagnosed by abdominal CT scan. One was treated with hepatic artery ligation and t onade and the other with liver resection and correction of the coagulopathy. Neither had any evidence of a ruptured haemangioma or tumour at laparotomy or on histological examination, and both are alive and well. The conclusions to be drawn from this review and our own recent experience is that the treatment of choice for ruptured haemangiomata is liver resection and, for rupture during pregnancy, is t onade with packs and evacuation of the haematoma. Hepatic arteriography and embolisation, if possible, is a useful adjunct. Correction ofany coagulopathy is essential. We can only speculate that the aetiology in our patients was uncontrolled hypertension in one and coagulopathy in the other.
Publisher: Springer Science and Business Media LLC
Date: 08-2011
DOI: 10.1038/NATURE10251
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 05-2023
Publisher: Wiley
Date: 30-03-2022
Abstract: Retained surgical drains are an avoidable and serious cause of postoperative morbidity. This study aims to first report on our unit's experience in identifying and managing retained surgical drains and then consolidate current knowledge regarding retained surgical drains, causes and associated complications. A systematic review of the literature was performed through searches in electronic databases to identify studies that described incidents involving retained surgical drains. Data were extracted regarding patient and operative characteristics, drain complications and management. A total of 36 case reports and/or series were identified in the literature, with 39 in idual cases of retained surgical drains in patients undergoing abdominal, thoracic or orthopaedic procedures. The most common cause for retained drain was fracture of drain tubing. Patients presented with complications ranging from chronic pain, abscess or fistula formation, to migration of the drain fragment into a hollow viscus. In all cases an invasive intervention was required to remove the retained drain. Surgeons should be aware of retained surgical drains as an iatrogenic cause of postoperative morbidity. Contemporary surgical practice should include methods to prevent, identify and manage retained drains and associated complications.
Publisher: Hindawi Limited
Date: 1989
DOI: 10.1155/1989/79120
Abstract: Injection sclerotherapy is widely used in the treatment of oesophageal varices. However, few studies have compared the local toxicity of sclerosant agents which may be important if serious local complications are to be avoided. In this study the depth of injury caused by submucosal injection of increasing concentrations of sodium tetradecyl sulphate, polidocanol, 5% ethanolamine oleate and 5% varicosid in rabbits stomach, has been compared by histopathological examination. Macroscopic ulceration was seen in 14.6% of injection sites. Increasing concentrations of sodium tetradecyl sulphate and polidocanol produced increasingly extensive microscopic inflammation. Five percent varicosid caused more inflammation than 5% ethanolamine and only 3% polidocanol and 5% varicosid caused full thickness inflammation. Only 5% ethanolamine produced inflammation consistently confined to the mucosa and submucosa. On the basis of this study we feel that 5% ethanolamine is the most suitable agent for injection sclerotherapy.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.EJSO.2021.05.023
Abstract: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782.V1
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
No related grants have been discovered for David Lawson Morris.