Emile Tan - Academia.edu (original) (raw)

Papers by Emile Tan

Colorectal Disease, Nov 29, 2021

The management of low anastomotic complications in a deep pelvis is a technical challenge. Transa... more The management of low anastomotic complications in a deep pelvis is a technical challenge. Transanal minimally invasive surgery (TAMIS) offers the advantage of "bottom-up" rectal mobilisation under superior laparoscopic visualisation [1,2]. This minimises dissection from the abdominal approach, which is hindered by adhesions, irradiation changes, and space constraints. However, patients who underwent TAMIS-assisted anastomotic reconstruction still had significant risks of anastomotic complications, highlighting the difficulty of the underlying problem.

International Journal of Colorectal Disease, Jun 6, 2023

Introduction: Pelvic floor disease affects many patients, with age, female gender and multiparity... more Introduction: Pelvic floor disease affects many patients, with age, female gender and multiparity being significant associations. This can present clinically as pelvic organ prolapse, internal and external rectal mucosal intussuception, obstructed defecation syndrome, rectocele, cystocele and urinary/faecal incontinence. Diagnostic and treatment strategies for the management of such disorders is significantly varied, and evidence for current surgical management is poor. This thesis explores diagnostic and operative strategies currently regarded as state of the art and examines a novel method of pelvic floor assessment using MRI-based statistical shaped modelling. Methods: Meta-analysis in accordance with Cochrane collaboration guidelines was performed to assess laparoscopic versus open techniques for urinary incontinence, as well as endoanal ultrasound (EUS) scanning versus MRI in the assessment of faecal incontinence. The efficacy of sacral nerve stimulation (SNS) was reviewed. In addition, decision analysis was performed to assess the cost-effectiveness of delayed versus immediate anal sphincter repairs, and current operative treatments for end-stage faecal incontinence, and operative strategies for end-stage incontinence. MRI-based statistical shaped biomechanical modelling was performed to assess normal pelvic floors in comparison with patients with obstructed defecation syndrome. 15 asymptomatic volunteers aged 18 to 60 years were scanned and compared against 7 with obstructed defecation (ODS). Finally, 7 patients who were treated surgically for ODS were reassessed 6 months post-operation. Results: There were significant benefits to laparoscopic colposuspension for urinary incontinence. EUS was superior to MRI at detecting internal sphincter lesions, but not for external sphincter lesions. Immediate sphincter repairs were more cost-effective than delayed repairs. The artificial bowel sphincter and end stoma were more acceptable to both patient and institution than dynamic graciloplasty. Patients with obstruc [...]

Asian Journal of Surgery, 2021

Background: Enhanced recovery after surgery (ERAS) is a structured programme using a multimodal, ... more Background: Enhanced recovery after surgery (ERAS) is a structured programme using a multimodal, evidence-based approach to improve post-operative outcomes. Successful implementation of ERAS can be challenging. We aimed to evaluate our initial experience with colorectal ERAS and explore the perspectives of specialist doctors and nurses. Methods: From 1 June 2017 to 31 December 2017, all patients who underwent elective colorectal resection and met the ERAS inclusion criteria at the Department of Colorectal Surgery, Singapore General Hospital, were included in the study. Short-term outcomes were compared between patients with >70% compliance to key ERAS components versus those with 70% compliance. Department staff were surveyed via questionnaire in July 2019. Results: Three hundred and fifteen patients were included in study. >70% ERAS compliance rate was achieved in 84 patients (26.7%). A higher compliance rate resulted in a significantly shorter length of stay of 6 (IQR 5e8) days vs. 7 (IQR 6e9.5) days (p ¼ 0.025) and lower readmission rate of 3.6% (n ¼ 3) vs. 4.8% (n ¼ 11) (p ¼ 0.042), as well as a trend towards reduced complication rate of 15.4% (n ¼ 13) vs. 22.0% (n ¼ 51) and earlier return to gastrointestinal function. There was a 100% questionnaire response amongst all 12 colorectal surgeons and 5 colorectal resident nurse practitioners. Conclusion: Increased adherence to the components of ERAS results in better early outcomes and may have long-term benefits on survival. Effective communication and professional support for the ERAS multidisciplinary team, as well as understanding healthcare workers' concerns and addressing longstanding practices, is essential for successful implementation of the programme.

Frontiers in Oncology, Mar 27, 2023

Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer morta... more Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is 'undruggable' due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its translocation to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. Herein, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells. Our results demonstrated that internalized anti-KRAS antibody inhibits KRAS function in tumor. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers.

World Journal of Gastrointestinal Surgery, May 27, 2023

Scientific Reports, Jan 11, 2021

Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and ... more Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and 2, was associated with worse prognosis in colorectal cancer (CRC). Nevertheless, their role in predicting metastasis in early-stage CRC is unclear. We measured the expression of CCAT1, CCAT2 and their oncotarget, c-Myc, in 150 matched mucosa-tumour samples of early-stage microsatellitestable Chinese CRC patients with definitive metastasis status by multiplex real-time RT-PCR assay. Expression of CCAT1, CCAT2 and c-Myc were significantly up-regulated in the tumours compared to matched mucosa (p < 0.0001). The expression of c-Myc in the tumours was significantly correlated to time to metastasis [hazard ratio = 1.47 (1.10-1.97)] and the risk genotype (GG) of rs6983267, located within CCAT2. Expression of c-Myc and CCAT2 in the tumour were also significantly up-regulated in metastasis-positive compared to metastasis-negative patients (p = 0.009 and p = 0.04 respectively). Nevertheless, integrating the expression of CCAT1 and CCAT2 by the Random Forest classifier did not improve the predictive values of ColoMet19, the mRNA-based predictor for metastasis previously developed on the same series of tumours. The role of these two lncRNAs is probably mitigated via their oncotarget, c-Myc, which was not ranked high enough previously to be included in ColoMet19. Abbreviations CRC Colorectal cancer CCAT1 Colon-cancer associated transcript 1 CCAT2 Colon-cancer associated transcript 2 HR Hazard ratio lncRNA Long non-coding RNAs NPV Negative predictive value OOB "Out-of-bag" PPV Positive predictive value ROC Receiver operating characteristic SNP Single nucleotide polymorphism TAD Topologically associating domains Colorectal Cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide, attributable mainly to metastasis to distal organs 1. Early stage (Stage I and II) CRC patients, whose cancers are confined to the colonic wall, are considered curative by surgery alone. However, up to 25% of these patients still

World Journal of Gastrointestinal Endoscopy, Feb 16, 2023

Neurourology and Urodynamics, 2008

Asian Journal of Surgery, 2023

BACKGROUND Incisional hernia is one of the common morbidities after major colorectal cancer surge... more BACKGROUND Incisional hernia is one of the common morbidities after major colorectal cancer surgery. We aim to compare the incidence of incisional hernias between laparoscopic and open surgery. We also aim to identify associated risk factors of incisional hernia among Asian population who has undergone major resection for colorectal cancer. METHODS Data of patients who had undergone major colorectal cancer surgery in year 2015 from a single institution was collected. Data were extracted from electronic clinical records from our institution's database. Incisional hernias were identified by clinical examination and computed tomography (CT) scan performed during post-operative follow up as part of colorectal cancer surveillance. Follow up data of up to 3 years were extracted. Univariate and multivariable logistic regression analysis were performed to identify associated risk factors for development of incisional hernia. Propensity score matching analysis was performed for laparoscopic and open resection. RESULTS 502 patients were included in the study. With a minimum follow up of 3 years, overall incisional hernia incidence rate of 13% was identified. Incisional hernias after laparoscopic and open surgery were 12.3% and 13.8% (p = 0.688) respectively. Univariate logistic regression analysis showed that body mass index (BMI) of >23kg/m2, ASA of III/IV and post-operative anastomotic leak were associated with development of incisional hernias. On multivariable analysis, female gender (OR 2.102, 95%CI: 1.155, 3.826), BMI of ≥23 kg/m2 (OR 2.862 95%CI: 1.582, 5.181), ASA III/IV (OR 2.052, 95%CI: 1.169, 3.602), were significantly associated with development of incisional hernia. Propensity scores matched analysis showed laparoscopic surgery did not significantly reduce the incidence of incisional hernia. CONCLUSION The overall incidence of incisional hernia seems lower in Asian population. Our study demonstrated no significant difference in incisional hernia rates between patients undergoing laparoscopic versus open colorectal cancer surgery. Female gender, higher BMI, and higher ASA are associated with increased risk of developing incisional hernia after major colorectal cancer resection.

Annals of coloproctology, Jun 30, 2021

Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict adverse survival outcomes among... more Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict adverse survival outcomes among patients with colorectal cancer (CRC). This study evaluates the prognostic value of NLR among patients with obstructing CRC who successfully underwent stenting before curative surgery. Methods: We retrospectively reviewed patients who underwent stenting before surgery. Patient demographics, tumor characteristics, perioperative outcomes, recurrence-free survival (RFS), and overall survival (OS) were analyzed. NLR was calculated from the differential white blood cell counts at least 4 days after successful stenting, before elective surgery. Optimal cutoff to dichotomize NLR was obtained by maximizing log-rank test statistic with recursive partitioning of Kaplan-Meier RFS and OS curves. The optimal cutoff for high NLR was ≥ 5 at presentation before stenting, and ≥ 4 after stenting. Results: Fifty-seven patients with localized obstructing CRC underwent successful endoscopic stenting before curative surgery. High NLR was associated with lymphovascular invasion (P = 0.006) and apical lymph node involvement (P = 0.034). Major perioperative complication(s) (hazard ratio [HR], 11.34; 95% confidence interval [CI], 2.49 to 51.56; P < 0.01) and high NLR (HR, 3.69; 95% CI, 1.46 to 9.35; P < 0.01) negatively impacted OS on univariate and multivariate analyses. High NLR negatively impacted RFS on univariate analysis (HR, 2.91; 95% CI, 1.29 to 6.60; P = 0.01). Conclusion: NLR of ≥ 4 after stenting is an independent prognostic factor among patients with obstructing localized CRC who are successfully decompressed by endoscopic stenting before curative surgery.

Anz Journal of Surgery, Dec 27, 2021

World journal of orthopedics, Apr 18, 2023

medRxiv (Cold Spring Harbor Laboratory), Jun 16, 2023

Colorectal cancer (CRC) is the third highest incidence cancer and leading cause of cancer mortali... more Colorectal cancer (CRC) is the third highest incidence cancer and leading cause of cancer mortality 1 worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic 1 factors are unclear. This study aims to identify metastasis-relevant genes and pathways for better management of 1 metastasis-prone patients. Multiple lines of evidence have indicated that germline variants play important role in 1 shaping the somatic (tumor) genome. A case-case genome-wide association study comprising 2677 sporadic 1 Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human 1 SNP6 microarray platform and analyzed with the correlation/trend test based on the additive model. Single 1 nucleotide polymorphism (SNP) variants with association testing-log10p-value ≥ 5 were imported into 1 Functional Mapping and Annotation (FUMA) for functional annotation which uncovered glycolysis as the top 2 hallmark geneset. Transcripts from two of the five genes profiled, HAX1 and HMMR, were significantly down-2 regulated in the metastasis-positive tumors. In contrast to disease-risk variants with minimal impact on survival, 2 HAX1 appeared to act synergistically with HMMR in significantly impacting metastasis-free survival. 2 Furthermore, examining the subtype datasets with FUMA and Ingenuity Pathway identified distinct pathways 2 demonstrating sexual dimorphism in CRC metastasis. Combining genome-wide association testing with in 2 silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as 2 features to develop subtype-specific metastasis-risk signatures for tailored management of Stage I-III CRC 2 patients.

Anz Journal of Surgery, Oct 29, 2022

BackgroundFaecal incontinence (FI) is a debilitating condition which reduces quality of life (QOL... more BackgroundFaecal incontinence (FI) is a debilitating condition which reduces quality of life (QOL). Conservative management with education, pelvic floor exercise and pharmacological agents are first‐line treatment. Following which, biofeedback therapy (BFT) is recommended. Although well described in the West, existing literature on its efficacy in Asian populations remains sparse. The primary aim of our study is to evaluate the efficacy of BFT in improvement of symptoms, QOL and overall satisfaction in our Asian population.MethodsPatients with moderate FI in Singapore General Hospital between 2012 and 2016 were enrolled. Rockwood FI quality of life scale (FIQL) and Wexner scale were used to evaluate QOL across four domains, and symptom severity respectively. They were scored at baseline and again after four sessions of BFT, with an additional overall satisfaction score (OSS).ResultsA total of 137 patients were included. Mean age was 62 years and 72.3% were female. Majority demonstrated improvement in Wexner score (68.6%) and FIQL (65%). Sixty‐five patients (47.4%) reported improvement in both. Positive correlation was found between Wexner score and OSS (r = 0.206), and Wexner score and FIQL across all four domains. Only one FIQL domain—coping/behaviour, showed statistically significant correlation with OSS (r = 0.263).ConclusionBFT is effective in our Asian population in both symptom reduction and improving QOL. Wexner score demonstrated low correlation with FIQL and OSS—suggesting that FI requires a multi‐dimensional approach beyond symptom treatment, of which ability to cope appears crucial. BFT, consistent with the biopsychosocial model, shows benefit in this regard.

Colorectal Disease, Jun 27, 2021

AimAs populations age and cancer management improves, long‐term survivorship and quality‐of‐life ... more AimAs populations age and cancer management improves, long‐term survivorship and quality‐of‐life (QOL) outcomes are becoming equally important as oncological results. Data from Asian populations are scarce. We aimed to evaluate the sexual health, gastrointestinal function and QOL amongst colorectal cancer survivors in a tertiary referral centre in Singapore.MethodAdults who had undergone elective curative surgery for non‐metastatic colorectal cancer at least 2 years prior were included. Exclusion criteria were cognitive disease, serious postoperative complications or recurrent cancer. Participants were invited to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC‐QLQ‐C30 and QLQ‐CR29. Using multiple bivariate analysis, r scores were used to examine relationship trends between QOL domains and survivor sociodemographic and disease‐specific characteristics.ResultsFrom February 2017 to July 2019, 400 responses were recorded. Median age and follow‐up duration were 64 years (range 32–90) and 78 months (interquartile range 49–113) respectively. Patients who had Stage III cancer had better overall QOL scores compared to Stage I/II. Rectal (vs. colon) cancer negatively influenced sexual health and gastrointestinal function, but did not appear to affect overall QOL. Amongst our cohort, 57% (n = 129) of men and 43% (n = 75) of women were sexually active. Markers of socioeconomic status, including employment, education and housing type, were found to significantly impact perception of various aspects of QOL.ConclusionKnowledge of factors which influence well‐being can identify individuals who may benefit from tailored management strategies. Regular patient–doctor contact may play a role in building and maintaining positive perspectives of cancer survivors. Normative data should be obtained from local populations to facilitate future comparative research.

International Journal of Colorectal Disease, Mar 29, 2023

Colorectal Disease, Mar 17, 2022

International Journal of Colorectal Disease, May 31, 2023