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ABSTRACT: BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients. METHODS: Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS. RESULTS: Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n = 39), colorectal cancer (n = 28), primary peritoneal (n = 6), appendiceal cancer (n = 20), and mesothelioma (n = 7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3 % and OS was 50.9 %. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56 %, and there were no 30-day mortalities. CONCLUSIONS: CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.
Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor
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ABSTRACT: INTRODUCTION: In recent years, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance as a treatment modality for peritoneal carcinomatosis. In female patients, this procedure involves a total hysterectomy and bilateral saphingo-oophorectomy to remove the pelvic peritoneum. We present a case of an unfortunate female adolescent with peritoneal carcinomatosis who underwent cytoreductive surgery and HIPEC. In view of the compelling circumstance, an innovative surgical technique was used to attempt ovarian preservation. PRESENTATION OF CASE: A 14 year old girl with carcinoma of the sigmoid colon and peritoneal metastases was offered cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. In view of her age, ovarian preservation with subcutaneous transposition was performed during cytoreductive surgery. She is currently well 6 months post surgery and has resumed normal menstruation. We review the literature regarding ovarian preservation with subcutaneous transposition and discuss its benefit in pre-menopausal women undergoing peritonectomy and cytoreductive surgery for peritoneal carcinomatosis. DISCUSSION: Subcutaneous transposition of the ovary in pre-menopasual patients requiring cytoreductive surgery spares them the sequelae of surgical castration. The subcutaneous location of the transposed ovary conveys advantages such as the ease of ultrasound surveillance and removal in event of disease recurrence. It also retains the possibility of future conception as the transposed ovary can easily be accessed for ovum extraction with assisted reproductive techniques. CONCLUSION: Ovarian preservation with subcutaneous transposition is a technique worth considering in the treatment of pre-menopausal women who require cytoreductive surgery for peritoneal carcinomatosis.
International journal of surgery case reports. 01/2013; 4(3):305-307.
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ABSTRACT: Cancer is the leading cause of mortality in Singapore. The age-standardized incidence rates continue to increase as the population grows and ages, and the influence of environmental and lifestyle choices bear their consequences. The increase is most marked in colorectal, breast and prostate cancers, mirroring the most common cancers seen in other developed countries. The eradication of infectious disease such as hepatitis B, through the implementation of the hepatitis B immunization programme in 1985, has led to the decline in liver cancer. The Singapore Cancer Registry collates detailed information on newly diagnosed and existing cancer cases, enabling the study and understanding of cancer trends in the population and across the different ethnic groups. A coordinated approach to address cancer prevention and treatment through public education and increased awareness, screening and early detection, and the institution of appropriate multidisciplinary care, on a background of continued basic and clinical research is required to deliver quality cancer care.
Japanese Journal of Clinical Oncology 01/2013; · 1.78 Impact Factor
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ABSTRACT: PURPOSE: The liver and peritoneum are common sites of colorectal metastases. Hepatectomy for colorectal liver metastases (CLM) is considered gold standard treatment. We attempt to compare the survival outcomes for CLM patients after hepatectomy to that of patients with colorectal peritoneal metastases (CPM) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective review of patients with CPM and CLM who underwent surgery between January 2003 and May 2011 was performed. The overall (OS) and disease-free survivals (DFS) were compared. RESULTS: There were 22 patients with CPM who underwent CRS and HIPEC and 186 patients who underwent hepatectomy for CLM. Patients with CPM had a 3-year OS of 39 % and DFS of 27.7 %. CLM patients showed a 3-year OS of 58.5 % and a DFS of 28.8 %. Most recurrences for CPM occurred within 2 years, while CLM patients continue to develop systemic recurrences over 3 years, showing a gradual decline in DFS and OS during this period of time. CONCLUSION: Our results show that CRS and HIPEC for CPM confer good OS and DFS rates and that the DFS after CRS and HIPEC is comparable to that after hepatectomy for CLM.
Journal of Gastrointestinal Cancer 11/2012;
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Cellular and Molecular Life Sciences CMLS 05/2012; 67(9):1561-1561. · 6.57 Impact Factor
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ABSTRACT: Oral lesions are conventionally diagnosed using white light endoscopy and histopathology. This can pose a challenge because the lesions may be difficult to visualise under white light illumination. Confocal laser endomicroscopy can be used for confocal fluorescence imaging of surface and subsurface cellular and tissue structures. To move toward real-time "virtual" biopsy of oral lesions, we interfaced an embedded computing system to a confocal laser endomicroscope to achieve a prototype three-dimensional (3-D) fluorescence imaging system. A field-programmable gated array computing platform was programmed to enable synchronization of cross-sectional image grabbing and Z-depth scanning, automate the acquisition of confocal image stacks and perform volume rendering. Fluorescence imaging of the human and murine oral cavities was carried out using the fluorescent dyes fluorescein sodium and hypericin. Volume rendering of cellular and tissue structures from the oral cavity demonstrate the potential of the system for 3-D fluorescence visualization of the oral cavity in real-time. We aim toward achieving a real-time virtual biopsy technique that can complement current diagnostic techniques and aid in targeted biopsy for better clinical outcomes.
Journal of Biomedical Optics 05/2012; 17(5):056009. · 3.16 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. Although sorafenib has been shown to improve survival of patients with advanced HCC, this improvement is modest and patients eventually have refractory disease. This study aims at investigating the antitumor, antiangiogenesis and antimetastatic activities of dovitinib in preclinical models of HCC.
21-0208 and SK-HEP1 cells as well as patient-derived HCC models were employed to study the antitumor effect of dovitinib. Changes of biomarkers relevant to FGFR/VEGFR/PDGFR pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry.
Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibited basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2. In vivo, dovitinib potently inhibited tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways. Dovitinib also caused dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, dovitinib potently inhibited primary tumor growth and lung metastasis and significantly prolonged mouse survival.
Dovitinib demonstrated significant antitumor and antimetastatic activities in HCC xenograft models. This study provides a compelling rationale for clinical investigation in patients with advanced HCC.
Journal of Hepatology 03/2012; 56(3):595-601. · 9.26 Impact Factor
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IEEE Photonics Society (IPS) Journal of Selected Topics in Quantum Electronics. 01/2012;
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ABSTRACT: Oral lesions are conventionally diagnosed using white light endoscopy and histopathology. This sometimes poses a challenge because the lesions may be difficult to visualise under white light illumination. Laser confocal endomicroscopy can be used for confocal fluorescence imaging of surface and subsurface cellular and tissue structures. To move toward real-time “virtual” biopsy of oral lesions, we
interfaced an embedded computing system to a confocal laser endomicroscope to achieve a prototype 3-dimensional (3D) fluorescence imaging system. A Field-Programmable Gate Array computing platform was programmed to enable synchronization of cross-sectional image grabbing and Z-depth scanning, automate acquisition of confocal image stacks and perform volume rendering. Fluorescence imaging of the human and murine oral cavity was carried out using the fluorescent dyes fluorescein sodium and hypericin. Volume rendering of cellular and tissue structures from the oral cavity demonstrate the potential of the system for 3D fluorescence visualization of the oral cavity in real-time. We aim toward achieving a real-time virtual biopsy technique that can complement current diagnostic techniques and aid in targeted biopsy for better clinical outcomes.
Journal of Biomedical Optics 01/2012; · 3.16 Impact Factor
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ABSTRACT: PURPOSE OF STUDY: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. Although sorafenib has been shown to improve survival of patients with advanced HCC, this improvement is modest and patients eventually have refractory disease. The purpose of this study is to assess the anti-tumor and anti-angiogenic activities of foretinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) and c-Met inhibitor using mouse models of human HCC. EXPERIMENTAL TECHNIQUES: SK-HEP1 and 21-0208 HCC cells as well as patient-derived HCC models were employed to study the anti-tumor and antiangiogenic activities of foretinib. Changes of biomarkers relevant to hepatocyte growth factor (HGF) signaling pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. RESULTS: Treatment of SK-HEP1 cells with foretinib resulted in growth inhibition, G2/M cell cycle arrest, reduced colony formation and blockade of HGF-induced cell migration. In both orthotopic and ectopic models of HCC, foretinib potently inhibited tumor growth in a dose-dependent manner. Inhibition of angiogenesis correlated with inactivation of VEGFR-2/c-Met signaling pathways. Foretinib also caused elevation of p27 and Bim but reduced cyclin B1 expression and p-c-Myc, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, foretinib potently inhibited primary tumor growth and significantly prolonged mouse survival. DATA INTERPRETATIONS: Foretinib demonstrated significant antitumor activities in patient-derived HCC xenograft models. This study provides a compelling rationale for clinical investigation in patients with advanced HCC.
Angiogenesis 12/2011; 15(1):59-70. · 6.06 Impact Factor
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ABSTRACT: The cancer burden is increasing worldwide and there is a need to develop new technologies for cancer diagnosis. Confocal laser endomicroscopy (CLE) is a minimally invasive optical technique that enables in vivo confocal imaging of tissue structures. With the use of fluorescent dyes, the technique allows confocal fluorescence endomicroscopy of tissue from surface to sub-surface layers. CLE has been applied to the surveillance and diagnosis of cancer in numerous clinical studies recently, and also holds potential for optical and guided biopsy procedures. The first part of this mini review is focused on the application of CLE for cancer detection and surveillance. The second part is focused on the application of CLE to imaging of the oral cavity. We have previously demonstrated the potential of CLE for diagnostic imaging of oral cavity lesions. To move toward real-time 3D imaging, we interfaced an endomicroscope to an embedded computing system. The prototype system is capable of automated image acquisition and real-time volume rendering. Rendering results provide topographical and depth information. Our aim is to achieve a real-time 3D fluorescence imaging system that can be used for diagnostic imaging and guided biopsy procedures of oral cavity lesions in a clinical setting.
Selected Topics in Quantum Electronics, IEEE Journal of. 11/2011; PP(99):1-1.
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ABSTRACT: The aims of the study were to assess factors responsible for the reduction of preoperative anxiety in patients undergoing breast and abdominal surgeries. In particular, we investigated whether question prompt lists (QPL), patients' knowledge, or the communication skills of surgeons had effects on anxiety reduction.
Patients were randomly assigned to QPL and control groups. Anxiety was assessed on the State Trait Anxiety Inventory.
Both groups showed significant reduction in anxiety between initial consultation and one day prior to surgery, with QPL patients showing a trend towards a greater reduction of anxiety after surgery and a significant reduction at the first outpatient follow-up. Satisfaction with consultation and the doctor's ability to answer questions concerning diagnosis, and treatment were significantly associated with anxiety reduction.
Effective anxiety reduction hinged on doctors' communication abilities and patients' satisfaction with the consultation.
Asian Journal of Surgery 10/2011; 34(4):175-80. · 0.57 Impact Factor
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Willie Yu,
Waraporn Chan-On,
Melissa Teo,
Choon Kiat Ong,
Ioana Cutcutache,
George E Allen,
Bernice Wong,
Swe Swe Myint,
Kiat Hon Lim,
P Mathijs Voorhoeve,
Steve Rozen, Khee Chee Soo,
Patrick Tan,
Bin Tean Teh
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ABSTRACT: Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP.
WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector.
The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.
Genome biology 09/2011; 12(9):R96. · 6.63 Impact Factor
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Journal of Gynecologic Oncology 09/2011; 22(3):214-7. · 1.49 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest malignancy. Sorafenib has demonstrated 44% survival advantage over placebo and has emerged as a standard of care in advanced HCC. The therapeutic effects of sorafenib are however transient and hence additional treatment options are warranted. In this study, we aimed to compare the efficacy of sunitinib relative to sorafenib, two potent inhibitors of protein tyrosine kinases involved in tumor growth, metastasis, or angiogenesis. We reported that sorafenib and sunitinib suppressed tumor growth, angiogenesis, cell proliferation, and induced apoptosis in both orthotopic and ectopic models of HCC. However, the antitumor effect of 50 mg/kg sorafenib was greater than that of 40 mg/kg sunitinib. Sorafenib inhibited p-eIF4E Ser209, p-p38 Thr180/Tyr182 and reduced survivin expression. This was not seen with sunitinib. In addition, the antitumor and apoptotic effects of sorafenib, which are associated with upregulation of fast migrating Bim and ASK1 and downregulation of survivin, were greater than that of sunitinib. These observations explained in part the apparent superior anti-tumor activity of sorafenib compared to sunitinib. In conclusion, sunitinib demonstrated an inferior anti-tumor activity compared to sorafenib in ectopic and orthotopic models of human HCC. It remains to be seen whether such observations would be recapitulated in humans.
Current cancer drug targets 08/2011; 11(8):944-53. · 5.13 Impact Factor
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ABSTRACT: The localization of photosensitizers in the subcellular compartments during photodynamic therapy (PDT) plays a major role in the cell destruction; therefore, the aim of this study was to investigate the intracellular localization of Chlorin e6-PVP (Photolon™) in malignant and normal cells. Our study involves the characterization of the structural determinants of subcellular localization of Photolon, and how subcellular localization affects the selective toxicity of Photolon towards tumor cells. Using confocal laser scanning microscopy (CLSM) and fluorescent organelle probes; we examined the subcellular localization of Photolon™ in the murine colon carcinoma CT-26 and normal fibroblast (NHLC) cells. Our results demonstrated that after 30 min of incubation, the distribution of Photolon was localized mainly in the cytoplasmic organelles including the mitochondria, lysosomes, Golgi apparatus, around the nuclear envelope and also in the nucleus but not in the endo-plasmic reticulum whereas in NHLC cells, Photolon was found to be localized minimally only in the nucleus not in other organelles studied. The relationship between subcellular localization of Photolon and PDT-induced apoptosis was investigated. Apoptotic cell death was judged by the formation of known apoptotic hallmarks including, the phosphatidylserine externalization (PS), PARP cleavage, a substrate for caspase-3 and the formation of apoptotic nuclei. At the irradiation dose of 1 J/cm2, the percentage of apoptotic cells was 80%, respectively. This study provided substantial evidence that Photolon preferentially localized in the subcellular organelles in the following order: nucleus, mitochondria, lysosomes and the Golgi apparatus and subsequent photodamage of the mitochondria and lyso-somes played an important role in PDT-mediated apoptosis CT-26 cells. Our results based on the cytoplasmic organelles and the intranuclear localization extensively enhance the efficacy of PDT with appropriate photosensitizer and light dose and support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance.
International Journal of Oncology 07/2011; 39(4):821-31. · 2.40 Impact Factor
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ABSTRACT: Liposarcoma is the single most common soft tissue sarcoma in the retroperitoneum.
A retrospective review of patients with primary retroperitoneal liposarcoma treated between June 1990 and June 2005 were conducted to evaluate the clinical results of resection for retroperitoneal liposarcomas (RPLS) and the prognostic factors for disease recurrence and patient survival in an Asian population.
Twenty-one patients operated on for curative intent (12 Males, 9 Females; mean age: 52.4 years) were evaluated. Of these, 13 presented with tumors that were well differentiated (61.9%), 4 (19.0%) with myxoid/round cell, 3 (14.3%) with dedifferentiated and 1(4.8%) with pleomorphic morphology. The median tumor burden was 36 cm (9-83). Median follow-up time was 62 months. There was no peri-operative mortality and morbidity occurred in 6(28.6%) patients. Surgical margins were involved in 10(47.6%) patients. Resection of contiguous organs was required in 15(71.4%) to achieve gross surgical margins. Eleven out of the 21(52%) of the patients had recurrence of the tumor. Median disease-free survival was 19 months and the overall 3- and 5-year survival rate was 87% and 49% respectively.
An aggressive surgical approach in both primary and recurrent RPLS in our institution is associated with 3- and 5-year survival rate of 87% and 49% respectively. Contiguous organ resection is often required to achieve local control.
World Journal of Surgical Oncology 01/2011; 9:12. · 1.12 Impact Factor
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ABSTRACT: Presently, several systems for the prognostication of pancreatic endocrine neoplasms (PENs) exist and the most appropriate classification system has not been clearly defined. This study aims to validate the performance of the 2004 World Health Organization (WHO), European Neuroendocrine Tumor Society (ENETS), Memorial Sloan-Kettering Cancer Center (MSKCC), American Joint Committee for Cancer (AJCC) TNM staging and Bilimoria criteria in a cohort of patients with PENs who underwent surgery at a single institution.
This study is a retrospective review of 61 consecutive patients who underwent surgical treatment for PEN. Actuarial disease-specific survival (DSS) of all 61 patients and recurrence-free survival (RFS) of 53 patients who had curative resection were analysed.
On univariate analyses, tumour size ≥50 mm, non-curative resection, lymph node involvement, presence of distant metastases, presence of necrosis, mitotic count ≥2/10 hpf and poor differentiation were associated with decreased DSS. Tumour size ≥50 mm, lymph node involvement, lymphovascular invasion, presence of necrosis and mitotic count ≥2/10 hpf were associated with decreased actuarial RFS. All five staging systems were useful in stratifying the 61 patients according to actuarial DSS. However, the MSKCC grading and ENETS grading systems were not statistically significant in stratifying DSS in the 61 patients. In the 53 patients who underwent curative resection, the WHO, ENETS, MSKCC, AJCC staging and the MSKCC grading systems were successful in stratifying the patients according to actuarial RFS. However, the Bilimoria scoring and ENETS grading systems were not useful in prognosticating these 53 patients.
All five classification systems were useful for the prognostication of surgically treated PENs in our patient cohort.
ANZ Journal of Surgery 01/2011; 81(1-2):79-85. · 1.25 Impact Factor
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ABSTRACT: Oral lesions are conventionally diagnosed using white light endoscopy and histopathology of biopsy samples. Oral lesions are often flat and difficult to visualize under white light illumination. Moreover, histopathology is timeconsuming and there is a need to develop minimally invasive optical biopsy techniques to complement current techniques. Confocal laser endomicroscopy holds promise for virtual biopsy in disease diagnosis. This technique enables fluorescence imaging of tissue structures at microscopic resolution. We have developed a prototype real-time 3- dimensional (3D) imaging system using a laser endomicroscope interfaced with embedded computing. A Field- Programmable Gate Array computing platform has been programmed to synchronize cross-sectional image grabbing and Z-depth scanning, as well as automate acquisition of confocal image stacks. A PC was used for real-time volume rendering of the confocal image stacks. We conducted pre-clinical and pilot clinical studies to image the murine and human oral cavity. High quality volume renderings of the confocal image stacks were generated using 3D texture slicing. Tissue morphology and 3D structures could be visualized. The results demonstrate the potential of the system for diagnostic imaging of the oral cavity. This paves the way toward real-time virtual biopsy of oral lesions, with the aim to achieve same-day diagnosis in a clinical setting.
Proc. SPIE. 01/2011; 8086.
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ABSTRACT: Oral cancers are conventionally diagnosed using white light endoscopy and histopathology. However, oral lesions can be difficult to visualize under white light. Fluorescence imaging can complement current techniques by highlighting lesional areas. Hypericin is a plant-based photosensitizer that can be used for photodynamic therapy and fluorescence diagnostic imaging of cancer. We present hypericin fluorescence imaging techniques that can be used as minimally invasive techniques for diagnostic imaging of oral lesions and discuss their applications from endoscopy to real-time 3-dimensional (3D) endomicroscopy. Fluorescence endoscopy provides a macro view of the lesions while endomicroscopy provides details at the microscopic level. In endoscopy, digitized images were analyzed to extract the red to blue (R/B) intensity ratio, which was found to be a good image parameter to discriminate between normal, hyperplastic and malignant oral tissue, with sensitivity and specificity levels of
over 90%. Further development to interface the endoscope to a real-time image analysis system can enable same-day diagnosis in the clinic. An endomicroscope enables fluorescence imaging at the microscopic level and can highlight morphological differences between normal and lesion tissue. We are further developing an embedded computing system interfaced to an endomicroscope for real-time 3D luorescence visualization of tumors. A Field Programmable Gated Array and a special control circuit have been programmed to synchronize cross-sectional image grabbing and Z-depth scanning and automate acquisition of confocal image stacks, termed datasets. Real-time volume rendering of datasets was tested on a PC equipped with a Graphics Processing Unit. The results demonstrate the potential of the endomicroscope-embedded computing system for real-time visualization of 3D structures in the oral cavity. We anticipate that a real-time 3D endomicroscopy
system can complement white light and fluorescence endoscopy in a clinical setting by providing morphological details not visible by using endoscopy alone.
Journal of Medical Imaging and Health Informatics. 01/2011; 1:139--143.
