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1.
J Med Genet ; 61(3): 276-283, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-37890997

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aimed to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients. METHODS: A case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analysed with the correlation/trend test based on the additive model. SNP variants with association testing -log10 p value ≥5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation. RESULTS: Glycolysis was uncovered as the top hallmark gene set. Transcripts from two of the five genes profiled, hematopoietic substrate 1 associated protein X 1 (HAX1) and hyaluronan-mediatedmotility receptor (HMMR), were significantly upregulated in the metastasis-positive tumours. In contrast to disease-risk variants, HAX1 appeared to act synergistically with HMMR in significantly impacting metastasis-free survival. Examining the subtype datasets with FUMA and Ingenuity Pathway Analysis (IPA) identified distinct pathways demonstrating sexual dimorphism in CRC metastasis. CONCLUSIONS: Combining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of patients with stage I-III CRC.


Assuntos
Neoplasias Colorretais , Estudo de Associação Genômica Ampla , Humanos , Predisposição Genética para Doença , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Genes Neoplásicos , Polimorfismo de Nucleotídeo Único/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
2.
Dis Colon Rectum ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954475

RESUMO

BACKGROUND: Fecal incontinence has a devastating impact on quality of life and imposes a substantial socioeconomic burden. Best medical therapy including biofeedback therapy improves mild symptoms, with minimal impact on moderate to severe symptoms. Surgical management for incontinence carries a degree of morbidity resulting in low uptake and acceptability. While acupuncture is common practice in Singapore for numerous medical conditions, its role in fecal incontinence is relatively novel. In our local context, however, acupuncture is accessible, inexpensive, and potentially well-accepted as a treatment strategy. OBJECTIVE: To determine the effectiveness of Traditional Chinese Medicine acupuncture, compared to biofeedback therapy in the treatment of fecal incontinence. The secondary aim is to investigate the differences in quality of life following treatment. DESIGN: Randomized controlled trial. SETTING: Prospective, single institution study. PATIENTS: Patients with ≥2 episodes of fecal incontinence/week, or St Mark's incontinence score of ≥5 were recruited. Patients were randomized into biofeedback therapy which included 3 sessions over 10 weeks, or 30 sessions of acupuncture over 10 weeks. MAIN OUTCOME MEASURES: Incontinence episodes, St. Mark's Score and Fecal Incontinence Quality of Life scale. RESULTS: Eighty-five patients were randomized into biofeedback therapy (n=46) or acupuncture (n = 39). Demographics and baseline clinical characteristics were not different (p > 0.05). Overall median incontinence episodes were reduced in both, with the acupuncture arm reporting significantly fewer at week 15 (p < 0.001). Acupuncture also improved quality of life, with improvement in lifestyle, coping, depression, and embarrassment at week 15 (p < 0.05). While the St. Mark's score was significantly reduced in both arms at week 15 (p < 0.001), the acupuncture arm's score was significantly lower (p = 0.002). LIMITATIONS: Longer follow-up required. CONCLUSIONS: Acupuncture is clinically effective and improves quality of life in patients with fecal incontinence. See Video Abstract. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04276350.

3.
Colorectal Dis ; 26(4): 766-771, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38302860

RESUMO

AIM: Natural orifice specimen extraction (NOSE) in left-sided colorectal surgery requires application of the circular stapler anvil to the proximal bowel without exteriorization through an additional abdominal incision. We describe an intracorporeal method to secure the stapler anvil, termed the intracorporeal antimesenteric ancillary trocar (IAAT) technique. METHOD: The ancillary trocar is attached to the stapler anvil before introduction into the abdominal cavity through the anal or vaginal orifice. The colon is incised before the trocar spike is brought out through the antimesenteric surface 3-4 cm within the cut edge. A linear stapler is used to seal the bowel end. The ancillary trocar is detached and retrieved via the NOSE conduit. Following the NOSE procedure, a side-to-end colorectal anastomosis is performed with the transanal circular stapler. RESULTS: Ten consecutive patients underwent elective left-sided colorectal resection with IAAT for NOSE (seven transanal, three transvaginal) from January to June 2023. Median age and body mass index were 66 (range 47-74) years and 24.3 (range 17.9-30.8) kg/m2 respectively. Two (20%) patients underwent sigmoid colectomy for sigmoid volvulus while eight (80%) underwent anterior resection for colorectal cancer. Median operating time, operative blood loss and postoperative length of hospital stay were 170 (range 140-240) min, 20 (range 10-40) mL and 1 (range 1-3) day respectively. There were no postoperative complications, readmissions or reoperations. Median follow-up duration was 3 (range 1-6) months. CONCLUSION: The IAAT double-stapling side-to-end anastomotic technique is safe and feasible for patients undergoing left-sided colorectal resection with NOSE, resulting in good outcomes.


Assuntos
Anastomose Cirúrgica , Colectomia , Cirurgia Endoscópica por Orifício Natural , Humanos , Feminino , Pessoa de Meia-Idade , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/instrumentação , Idoso , Masculino , Cirurgia Endoscópica por Orifício Natural/métodos , Cirurgia Endoscópica por Orifício Natural/instrumentação , Colectomia/métodos , Colectomia/instrumentação , Colo/cirurgia , Instrumentos Cirúrgicos , Vagina/cirurgia , Grampeadores Cirúrgicos , Grampeamento Cirúrgico/métodos , Grampeamento Cirúrgico/instrumentação , Reto/cirurgia , Duração da Cirurgia
4.
Nature ; 557(7706): 575-579, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29769722

RESUMO

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39- CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells.


Assuntos
Efeito Espectador/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Antígenos de Neoplasias/imunologia , Antígenos Virais/imunologia , Apirase/análise , Apirase/deficiência , Apirase/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Separação Celular , Neoplasias Colorretais/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Linfócitos do Interstício Tumoral/metabolismo , Fenótipo
5.
Surg Endosc ; 38(5): 2632-2640, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503904

RESUMO

BACKGROUND: Oncological outcomes of stenting as a bridge to surgery (SBTS) remain a major concern, despite perioperative benefits it offers. This study aims to evaluate the differences in recurrence patterns and survival in patients with non-metastatic, obstructing left sided colon cancers treated by SBTS versus upfront emergency surgery (ES). METHODS: This is a retrospective, single-centre cohort study of 227 consecutive patients with non-metastatic, obstructing left sided colon cancer between 2007 and 2016. Primary outcomes were pattern of recurrence, and survival. Univariate, bivariate and multivariate logistic regression were done to determine relationships between factors and recurrence. Kaplan Meier curves and log rank tests were used to analyse survival outcomes. RESULTS: Of the 227 patients included, 62 underwent SBTS and 165 underwent upfront ES. There was a higher rate of peritoneal recurrence in SBTS group (27.4 vs 15.2% p = 0.034), with no difference observed in overall, liver or lung recurrences. No significant difference in overall survival (p = 0.11), cancer specific survival (p = 0.35), or recurrence free survival (p = 0.107) was observed. Univariate analysis showed that SBTS (OR 2.12, p = 0.036), diabetes mellitus (DM) (OR 2.58, p = 0.013), T4 (OR 2.81, p = 0.001), N + (OR 4.02, p = 0.001), lymphovascular invasion (OR 2.43, p = 0.011) contributed to a higher rate of peritoneal recurrence. Bivariate analysis showed synergistic relationship between T4 tumors and SBTS: in T4 tumors that underwent SBTS, the odds of having peritoneal recurrence was 6.8 times higher when compared to ES (p = 0.004); whilst in T2/3 tumors there was no significant difference observed (OR 1.33, p = 0.55). Multivariable analysis showed SBTS (OR 2.60, p = 0.04), DM (OR 2.88, p = 0.012), N + (OR 2.97, p = 0.026) were significant predictors for peritoneal recurrence. CONCLUSIONS: There are concerns over oncological safety of SBTS even with low rates of stent-related perforation. Higher rates of peritoneal recurrence are seen especially with T4 colon cancers treated with SBTS. SBTS, DM and nodal stage were significant predictors for peritoneal recurrence.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Recidiva Local de Neoplasia , Neoplasias Peritoneais , Stents , Humanos , Feminino , Masculino , Estudos Retrospectivos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/complicações , Neoplasias Peritoneais/secundário , Emergências , Resultado do Tratamento , Colectomia/métodos
6.
World J Surg ; 48(3): 585-597, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38501562

RESUMO

BACKGROUND: Heart Rate Variability (HRV) is a dynamic reflection of heart rhythm regulation by various physiological inputs. HRV deviations have been found to correlate with clinical outcomes in patients under physiological stresses. Perioperative cardiovascular complications occur in up to 5% of adult patients undergoing abdominal surgery and are associated with significantly increased mortality. This pilot study aimed to develop a predictive model for post-operative cardiovascular complications using HRV parameters for early risk stratification and aid post-operative clinical decision-making. METHODS: Adult patients admitted to High Dependency Units after elective major abdominal surgery were recruited. The primary composite outcome was defined as cardiovascular complications within 7 days post-operatively. ECG monitoring for HRV parameters was conducted at three time points (pre-operative, immediately post-operative, and post-operative day 1) and analyzed based on outcome group and time interactions. Candidate HRV predictors were included in a multivariable logistic regression analysis incorporating a stepwise selection algorithm. RESULTS: 89 patients were included in the analysis, with 8 experiencing cardiovascular complications. Three HRV parameters, when measured immediately post-operatively and composited with patient age, provided the basis for a predictive model with AUC of 0.980 (95% CI: 0.953, 1.00). The negative predictive value was 1.00 at a statistically optimal predicted probability cut-off point of 0.16. CONCLUSION: Our model holds potential for accelerating clinical decision-making and aiding in patient triaging post-operatively, using easily acquired HRV parameters. Risk stratification with our model may enable safe early step-down care in patients assessed to have a low risk profile of post-operative cardiovascular complications.


Assuntos
Cardiopatias , Humanos , Frequência Cardíaca/fisiologia , Projetos Piloto , Eletrocardiografia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Progressão da Doença
7.
Langenbecks Arch Surg ; 409(1): 172, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829526

RESUMO

AIM: Natural orifice specimen extraction (NOSE) is an alternative to conventional transabdominal retrieval. We aimed to compare outcomes following transvaginal specimen extraction (TVSE) and transabdominal specimen extraction (TASE) in minimally invasive abdominal surgery. METHODS: An electronic database search of PubMed, Embase and CENTRAL was performed from inception until March 2023. Comparative studies evaluating TVSE versus TASE in adult female patients were included. Studies involving transanal NOSE, endoluminal surgery, or TVSE with concomitant hysterectomy were excluded. Weighted mean differences (WMD) and odds ratio were estimated for continuous and dichotomous outcomes respectively. Primary outcomes were postoperative day 1 (POD1) pain and length of stay (LOS). Secondary outcomes were operative time, rescue analgesia, morbidity, and cosmesis. A review of sexual, oncological, and technical outcomes was performed. RESULTS: Thirteen studies (2 randomised trials, 11 retrospective cohort studies), involving 1094 patients (TASE 583, TVSE 511), were included in the analysis. Seven studies involved colorectal disease and six assessed gynaecological conditions. TVSE resulted in significantly decreased POD1 pain (WMD 1.08, 95% CI: 0.49, 1.68) and shorter LOS (WMD 1.18 days, 95% CI: 0.14, 2.22), compared to TASE. Operative time was similar between both groups, with fewer patients requiring postoperative rescue analgesia with TVSE. Overall morbidity rates, as well as both wound-related and non-wound related complication rates were better with TVSE, while anastomotic morbidity rates were comparable. Cosmetic scores were higher with TVSE. TVSE did not result in worse sexual or oncological outcomes. CONCLUSION: TVSE may be feasible and beneficial compared to TASE when performed by proficient laparoscopic operators, using appropriate selection criteria. Continued evaluation with prospective studies is warranted.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Vagina , Humanos , Feminino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Vagina/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Tempo de Internação , Duração da Cirurgia
8.
Int J Colorectal Dis ; 38(1): 151, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37256453

RESUMO

PURPOSE: Surgical site infection (SSI) impacts 5-20% of patients after elective colorectal surgery. There are varying reports on the effectiveness of oral antibiotics (OAB) with preoperative mechanical bowel preparation (MBP) in preventing SSI. We aim to determine the role of OAB and MBP in preventing SSI after elective colorectal surgery. We also determine if a specific OAB regimen will be more effective than others. METHODS: This study investigated the impact of OAB and MBP in patients undergoing elective colorectal surgery. PubMed, MEDLINE, Ovid, Cochrane Central Register of Controlled Trials, ACP Journal Club, and Embase databases were searched for randomized clinical trials (RCTs) published by June 2022. All RCTs comparing various preoperative bowel preparation regimens, including pairwise or multi-intervention comparisons, were included. To establish the role of OAB and MBP in preventing SSI, we conducted a Bayesian network meta-analysis on all RCTs. We further performed subgroup analysis to determine the most effective OAB regimen. RESULTS: Among included 46 studies with a total of 12690 patients, patients in the MBP + OAB group were less likely to have SSI than those having MBP-only (OR 0.55, 95% CrI 0.39-0.76), and without MBP and OAB (OR 0.52, 95% CrI 0.32-0.84). OAB regimen C (kanamycin + metronidazole) and A (neomycin + metronidazole) demonstrated a significantly reduced incidence of SSI, compared to regimen B (neomycin + erythromycin) with OR 0.24 (95% CrI 0.07-0.79) and 0.26 (95% CrI 0.07-0.99) respectively. CONCLUSIONS: OAB with MBP reduces the risk of SSI after elective colorectal surgery. Providing adequate aerobic and anaerobic coverage with OAB may confer better protection against SSI.


Assuntos
Antibacterianos , Cirurgia Colorretal , Humanos , Antibacterianos/uso terapêutico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Metronidazol , Cirurgia Colorretal/efeitos adversos , Metanálise em Rede , Catárticos/uso terapêutico , Antibioticoprofilaxia , Neomicina , Cuidados Pré-Operatórios/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Administração Oral
9.
Int J Colorectal Dis ; 38(1): 86, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36988723

RESUMO

PURPOSE: This study compares the cost-effectiveness of open, laparoscopic (LAP), laparoscopic-assisted (LAPA), hand-assisted laparoscopic (HAL), and robotic colorectal surgery using a network meta-analysis. METHODS: Randomized clinical trials (RCTs) evaluating the cost-effectiveness of comparing the five different approaches in colorectal surgery were included in a literature search until September 2022. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, odds ratio (OR), and 95% credible intervals (CrIs) were reported for total costs, surgical costs, operating time, length of stay (LOS), and postoperative outcomes. Cluster analysis was performed to examine the similarity and classification of surgical approaches into homogeneous clusters. The cophenetic correlation coefficient (cc) was evaluated to identify the most cost-effective clustering method. The primary outcomes assessed were: costs-morbidity, costs-mortality, and costs-efficacy, measuring total costs against postoperative complications, mortality rate, and LOS, respectively. RESULTS: 22 RCTs with 4239 patients were included. Open surgery had the lowest total costs, surgical costs, and operating time but the longest LOS and most postoperative complications. LOS was significantly decreased in LAP compared to open surgery (OR 0.67, 95% CrI 0.46-0.96). Robotic surgery resulted in the highest total costs, surgical costs, and most extended operative duration but the shortest LOS and lowest mortality. LAPA and robotic surgery were superior in the costs-morbidity analysis. HAL was associated with the worst costs-mortality profile. LAP, LAPA, and HAL were better in terms of costs-efficacy. CONCLUSION: Overall, LAP and LAPA are the most cost-effective approaches for colorectal surgery in terms of overall postoperative complications, mortality, and LOS.


Assuntos
Cirurgia Colorretal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Análise Custo-Benefício , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Laparoscopia/métodos , Tempo de Internação , Complicações Pós-Operatórias/etiologia
10.
Int J Colorectal Dis ; 38(1): 160, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37278975

RESUMO

PURPOSE: The growth of Singapore's geriatric population, coupled with the rise in colorectal cancer (CRC), has increased the number of colorectal surgeries performed on elderly patients. This study aimed to compare the clinical outcomes and costs of laparoscopic versus open elective colorectal resections in elderly CRC patients over 80 years. METHODS: A retrospective cohort study using data from the American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) identified patients over 80 years undergoing elective colectomy and proctectomy between 2018 and 2021. Patient demographics, length of stay (LOS), 30-day postoperative complications, and mortality rates were analysed. Cost data in Singapore dollars were obtained from the finance database. Univariate and multivariate regression models were used to determine cost drivers. The 5-year overall survival (OS) for the entire octogenarian CRC cohort with and without postoperative complications was estimated using the Kaplan-Meier curves. RESULTS: Of the 192 octogenarian CRC patients undergoing elective colorectal surgery between 2018 and 2021, 114 underwent laparoscopic resection (59.4%), while 78 underwent open surgery (40.6%). The proportion of proctectomy cases was similar between laparoscopic and open groups (24.6% vs. 23.1%, P = 0.949). Baseline characteristics, including Charlson Comorbidity Index, albumin level, and tumour staging, were comparable between both groups. Median operative duration was 52.5 min longer in the laparoscopic group (232.5 vs. 180.0 min, P < 0.001). Both groups had no significant differences in postoperative complications and 30-day and 1-year mortality rates. Median LOS was 6 days in the laparoscopic group compared to 9 days in the open group (P < 0.001). The mean total cost was 11.7% lower in the laparoscopic group (S$25,583.44 vs. S$28,970.85, P = 0.012). Proctectomy (P = 0.024), postoperative pneumonia (P < 0.001) and urinary tract infection (P < 0.001), and prolonged LOS > 6 days (P < 0.001) were factors contributing to increased costs in the entire cohort. The 5-year OS of octogenarians with minor or major postoperative complications was significantly lower than those without complications (P < 0.001). CONCLUSION: Laparoscopic resection is associated with significantly reduced overall hospitalization costs and decreased LOS compared to open resection among octogenarian CRC patients, with comparable postoperative outcomes and 30-day and 1-year mortality rates. The extended operative time and higher consumables costs from laparoscopic resection were mitigated by the decrease in other inpatient hospitalization costs, including ward accommodation, daily treatment fees, investigation costs, and rehabilitation expenditures. Comprehensive perioperative care and optimised surgical approach to mitigate the impact of postoperative complications can improve survival in elderly patients undergoing CRC resection.


Assuntos
Colectomia , Colo , Neoplasias Colorretais , Laparoscopia , Reto , Idoso , Idoso de 80 Anos ou mais , Humanos , Colectomia/economia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Custos e Análise de Custo , Laparoscopia/economia , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Colo/cirurgia , Reto/cirurgia
11.
Int J Colorectal Dis ; 38(1): 257, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882868

RESUMO

PURPOSE: In 2017, the National Surgical Quality Improvement Program (NSQIP) was introduced in the Department of Colorectal Surgery at Singapore General Hospital as a pilot quality improvement initiative. This study aimed to examine the cost-effectiveness of NSQIP by evaluating its effects on surgical outcomes, length of stay (LOS), and costs. METHODS: We retrospectively reviewed patients undergoing colorectal surgery (2017-2020). Patients were divided into two cohorts: pre-NSQIP (2017-2018) and post-NSQIP (2019-2020). Outcomes evaluated were 30-day postoperative complications, LOS, and costs. Total cost-savings from NSQIP intervention's impact on LOS were estimated using a decision model with a one-way sensitivity analysis. Multivariate logistic regression was performed to identify factors for prolonged LOS. RESULTS: 1905 patients underwent colorectal surgery, with 996 in the pre-NSQIP cohort and 909 in the post-NSQIP cohort. A significant reduction in overall postoperative complications of 4.7% was observed in the post-NSQIP cohort (36.5% vs. 31.8%, p = 0.029). Patients in the post-NSQIP cohort had a shorter median LOS (8.0 vs. 6.0 days, p < 0.001). The implementation of NSQIP resulted in an 8.5% decrease in prolonged LOS > 6 days (p < 0.001), saving S$0.31 million on LOS. Total costs per case were reduced by 20.8% following NSQIP (S$39,539.05 vs. S$31,311.93, p < 0.001). CONCLUSION: Implementing NSQIP has significantly reduced overall postoperative complications, LOS, and costs and achieved cost savings following colorectal surgery.


Assuntos
Cirurgia Colorretal , Humanos , Análise Custo-Benefício , Tempo de Internação , Melhoria de Qualidade , Estudos Retrospectivos , Singapura , Complicações Pós-Operatórias/etiologia , Hospitais
12.
Genes Chromosomes Cancer ; 60(2): 61-72, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33094510

RESUMO

Colorectal cancer (CRC) is a high incidence cancer and major cause of cancer mortality. Though disease-causing tumor suppressors for major syndromes are well characterized, about 10% of CRC is familial but without mutations in known tumor suppressors. We exhaustively screened 100 polyposis families for APC germline mutations and identified 13, which are APC mutation-negative, microsatellite-stable (MSS), and with undetectable mutation in known tumor suppressors. Whole exome sequencing in three probands uncovered two with germline frameshift NR0B2 mutations, c.293_301delTTGGGTTGGinsAC and c.227delT. Sanger Sequencing identified a third proband with NR0B2 c.157_166delCATCGCACCT frameshift mutation. All three mutations deleted the C-terminus activation/repression domain of NR0B2, thus are loss-of-function mutations. Real-time RT-PCR performed on tumor and matched mucosa of one patient revealed that NR0B2 downstream targets, SMAD3 was derepressed while GLI1 was downregulated in the colonic mucosa compared to healthy controls. Truncated NR0B2 molecule was predicted to have weakened binding with interacting partners SMAD3, GLI1, BCL2, and RXRα, implying perturbation of TGF-ß, Hedgehog, anti-apoptotic and nuclear hormone receptor signaling pathways. Immunostaining also revealed nuclear retention of the most severely truncated NR0B2 molecule compared to the wildtype. Microsatellite and sequencing analysis did not detect loss of wildtype allele in probands' tumors. The patient who acquired somatic KRAS mutation progressed rapidly whist the other two patients manifested with late-onset obesity and diabetes. We propose that haploinsufficiency of NR0B2 is associated with a novel CRC syndrome with metabolic phenotypes.


Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idade de Início , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Haploinsuficiência , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Mutação , Linhagem , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptor X Retinoide alfa/metabolismo , Proteína Smad3/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
13.
Int J Colorectal Dis ; 36(4): 689-700, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33495871

RESUMO

PURPOSE: After almost three decades since the first description of colonic stents, the controversies of its safe application continue to impede the readiness of adoption by clinicians for malignant left bowel obstruction. This review seeks to address some of the controversial aspects of stenting and its impact on surgical and oncological outcomes. METHODS: Medline, Embase, and CNKI were searched for articles employing SEMS for left colonic obstruction. Outcomes analyzed include success rates, complications, and long-term survival. Pooled risk ratio (RR) and 95% confidence interval (CI) were estimated. RESULTS: 36 studies were included with 2002 patients across seven randomized controlled trials and 29 observational studies. High technical (92%) and clinical (82%) success rates, and low rates of complications, including perforation (5%), were found. Those with > 8% perforation rates had poorer technical success rates than those with ≤ 8%, but there were no significant differences in 90-day in-hospital mortality and three and 5-year overall and disease-free survival. A significant increase was found in technical (RR = 1.094; CI, 1.041-1.149; p < 0.001) and clinical (RR = 1.158; CI, 1.064-1.259; p = 0.001) success rates when the duration between stenting and surgery was ≥ 2 weeks compared to < 2 weeks, but there were no significant differences in perforation rates, 90-day in-hospital mortality, and long-term survival. CONCLUSIONS: Colonic stenting is safe and effective with high success rates and low complication rates. However, outcomes of higher perforation rates and optimal timing from stent till surgery remain unclear, with only a few studies reporting on these outcomes, leaving areas for future research.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Humanos , Obstrução Intestinal/cirurgia , Stents/efeitos adversos , Resultado do Tratamento
14.
Colorectal Dis ; 23(9): 2348-2360, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34097342

RESUMO

AIM: As 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. METHOD: Adults 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. RESULTS: From 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. CONCLUSION: Knowledge 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.


Assuntos
Neoplasias Colorretais , Saúde Sexual , Criança , Pré-Escolar , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Qualidade de Vida , Inquéritos e Questionários , Sobreviventes
15.
Psychooncology ; 29(10): 1557-1563, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32596865

RESUMO

OBJECTIVES: This study aimed to provide an in-depth exploration of follow-up care experiences and supportive care needs in long-term colorectal cancer (CRC) survivors within multiethnic Asian communities. METHODS: Semi-structured in-depth interviews were conducted on a purposive sample of 30 long-term CRC survivors who had completed all treatment without recurrence ranging 2 to 17 years in Singapore. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted following grounded theory approach. RESULTS: Four themes represented the experience of the Asian long-term CRC survivors: (a) living with long-term consequences, (b) dealing with unceasing adaptation demands, (c) navigating a healthcare journey with limited direction, (d) regaining mastery through adversity. CRC and its treatment had profound physical impacts on some long-term survivors and these effected their psychological well-being. A sense of abandonment and vulnerability following the cessation of a 5-year follow-up care was repeatedly expressed. Participants defined recovery from CRC as not merely surviving but also having high physical function and full independence. They often sought less conventional remedies and medicine based on cultural beliefs rather than current evidence. Participants noted pervasive social stigma associated with CRC that impeded their inclusion in the workforce. CONCLUSIONS: Asian long-term CRC survivors experienced multiple challenges and needs relating to the care experience, information provision and workforce stigmatization, and several of which were unique to the Asian context. Future work will need to consider the implementation of culturally tailored cancer survivorship care plans that incorporate the specific needs of Asian CRC survivors.


Assuntos
Assistência ao Convalescente , Povo Asiático/psicologia , Sobreviventes de Câncer/psicologia , Neoplasias Colorretais/psicologia , Adaptação Fisiológica , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Qualidade de Vida/psicologia , Singapura
17.
Acta Chir Belg ; 119(1): 1-15, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30644337

RESUMO

AIM: To perform a review of the literature reporting on randomised controlled trials (RCTs) comparing treatments for faecal incontinence (FI) in adults. METHODS: A literature search of MEDLINE, Embase, Science Citation Index Expanded and Cochrane was performed in order to identify RCTs reporting on treatments for FI. RESULTS: The review included 60 RCTs reporting on 4838 patients with a mean age ranging from 36.8 to 88 years. From the included RCTs, 32 did not identify a significant difference between the treatments compared. Contradictory results were identified in RCTs comparing percutaneous posterior tibial nerve stimulation and transcutaneous tibial nerve stimulation versus sham stimulation, biofeedback-pelvic floor muscle training (BF-PFMT) versus PFMT, and between bulking agents such as PTQTM versus Durasphere®. In two separate RCTs, combination treatment of amplitude-modulated medium frequency stimulation and electromyography-biofeedback (EMG-BF), was noted to be superior to EMG-BF and low-frequency electrical stimulation alone. Combination of non-surgical treatments such as BF with sphincteroplasty significantly improved continence scores compared to sphincteroplasty alone. Surgical treatments were associated with higher rates of serious adverse events compared to non-surgical interventions. CONCLUSIONS: The current evidence has not identified significant differences between treatments for FI, and where differences were identified, the results were contradictory between RCTs.


Assuntos
Incontinência Fecal/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Int J Colorectal Dis ; 33(5): 645-648, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29470730

RESUMO

AIMS: Percutaneous tibial nerve stimulation (PTNS) and sacral nerve stimulation (SNS) are both second-line treatments for faecal incontinence (FI). To compare the clinical outcomes and effectiveness of SNS versus PTNS for treating FI in adults. METHOD: A literature search of MEDLINE, Embase, Science Citation Index Expanded and Cochrane was performed in order to identify studies comparing SNS and PTNS for treating FI. A risk of bias assessment was performed using The Cochrane Collaboration's risk of bias tool. A random effects model was used for the meta-analysis. RESULTS: Four studies (one randomised controlled trial and three nonrandomised prospective studies) reported on 302 patients: 109 underwent SNS and 193 underwent PTNS. All included studies noted an improvement in symptoms after treatment, without any significant difference in efficacy between SNS and PTNS. Meta-analysis demonstrated that the Wexner score improved significantly with SNS compared to PTNS (weighted mean difference 2.27; 95% confidence interval 3.42, 1.12; P < 0.01). Moreover, SNS was also associated with a significant reduction in FI episodes per week and a greater improvement in the Fecal Incontinence Quality of Life coping and depression domains, compared to PTNS on short-term follow-up. Only two studies reported on adverse events, reporting no serious adverse events with neither SNS nor PTNS. CONCLUSION: Current evidence suggests that SNS results in significantly improved functional outcomes and quality of life compared to PTNS. No serious adverse events were identified with either treatment. Further, high-quality, multi-centre randomised controlled trials with standardised outcome measures and long-term follow-up are required in this field.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal/fisiopatologia , Incontinência Fecal/terapia , Sacro/inervação , Nervo Tibial/fisiopatologia , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
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