A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening.

BACKGROUND: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. METHODS: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. RESULTS: The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. CONCLUSION: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.

Serum microRNA Levels as a Biomarker for Diagnosing Non-Alcoholic Fatty Liver Disease in Chinese Colorectal Polyp Patients.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.

High Levels of Tumor miR-187-3p-A Potential Tumor-Suppressor microRNA-Are Correlated with Poor Prognosis in Colorectal Cancer.

BACKGROUND: The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis among CRC patients. This study further investigated the clinicopathological significance of miR-187-3p in CRC. METHODS: MiR-187-3p levels in paired polyp/CRC/normal specimens or primary CRC/liver metastasis specimens were determined by qPCR, and correlated with the patient's clinicopathological and postoperative survival data. The clinical findings were validated using our validation cohort and data obtained from the TCGA or GEO databases. The functional effects of miR-187-3p were investigated through its overexpression in CRC cell lines. RESULTS: MiR-187-3p was significantly repressed in colorectal polyps and CRC when compared to adjacent normal tissue. Overexpression of miR-187-3p in CRC cell lines impaired colony formation, cell migration, and invasion, and induced chemosensitivity. Clinical analysis revealed that despite miR-187-3p being repressed in CRC, high tumor miR-187-3p levels were positively correlated with tumor stage and disease recurrence. Further analysis showed that miR-187-3p levels were lower in metastatic specimens when compared to paired primary CRC, suggesting that high tumor miR-187-3p levels resulted from the dissemination of metastatic tumor cells. Tumor miR-187-3p levels were positively correlated with peripheral inflammation-related blood markers. Finally, SPRY1 was identified as a novel target gene of miR-187-3p, and was involved in miR-187-3p-impaired CRC metastasis. CONCLUSIONS: This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers.

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients.

BACKGROUND: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients. METHODS: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR. CBX8 protein level in CRC and NAT specimens from 66 patients was determined by immunohistochemistry. CBX8 gene and protein levels were correlated with the patients' clinicopathological parameters and circulatory immune cell profiles. The association between CBX8 and pluripotency-associated genes was analyzed using the TCGA database. RESULTS: NAT CBX8 gene level positively correlated with TNM stage, tumor invasion, lymph node metastasis and distant metastasis, indicating its association with tumor progression and metastasis. There was no correlation between NAT CBX8 protein level and clinicopathological parameters. Moreover, a high level of CBX8 gene and protein in NAT both correlated with poor DFS and OS. There was an inverse correlation between CBX8 gene level and post-operative platelet counts and platelet to lymphocyte level, suggesting its association with systematic inflammation. Finally, TCGA analysis showed that CBX8 level was correlated with a couple of pluripotency-associated genes, supporting its association with cancer stemness. CONCLUSIONS: High NAT CBX8 is a poor prognostic factor for tumor progression and survival in CRC patients.

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

BACKGROUND: Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it's expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized. METHODS: We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC. RESULTS: MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3'UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells. CONCLUSION: MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.

CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling.

CD26 has been reported as a marker for colorectal cancer stem cells endowed with tumor-initiating properties and capable of colorectal cancer (CRC) metastasis. In this study, we investigated the functional effect of CD26 on CRC angiogenesis and metastasis, and the potential underlying mechanism. The functional effects of CD26 overexpression or repression were determined by a wound healing experiment, and cell migration and invasion assays in vitro and in mouse models. Differentially expressed genes regulated by CD26 were identified by genome-wide mRNA expression array and validated by quantitative PCR. CD26 functionally regulated CRC cell migration and invasion in vitro and angiogenesis and metastasis in vivo. Genome-wide mRNA expression array and qPCR showed that MMP1 was up-regulated in CD26+ subpopulation, and a subsequent experiment demonstrated the regulatory effect of CD26 on MMP1 in CRC cell lines with CD26 repression or overexpression. Furthermore, overexpression of CAV1 abrogated the CD26-regulated MMP1 induction in CRC cell lines. This study demonstrated the functional roles of CD26 in inducing CRC migration, invasion, angiogenesis and metastasis and identified the potential involvement of MMP1 and CAV1 in such process. CD26 is an attractive therapeutic target for combating tumor progression to improve the prognosis of CRC patients.

Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancer among the world. Accumulated somatic mutations during malignant transformation process endow cancer cells with increased growth, invasiveness and immunogenicity. These highly immunogenic cancer cells develop multiple strategies to evade immune attack. Through post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer development and progression but also manipulate anti-cancer immune response. This study aims to identify miRNAs associated with the colorectal cell malignant transformation process and their association with immune cell population using synchronous adjacent normal, polyp and CRC specimens. METHODS: We conducted a Low Density Array to compare the miRNA expression profile of synchronous colorectal adenoma, adenocarcinoma and adjacent normal colon mucosa collected from 8 patients, in order to identify candidate miRNAs involved in CRC progression. These findings were further validated in 14 additional patients and GEO dataset GSE41655. The relative abundance of dendritic cells, natural killer cells, neutrophil and macrophage was determined and correlated with dysregulated miRNA levels. RESULTS: MicroRNA microarray identified 39 miRNAs aberrantly expressed during the colorectal cell transformation process. Seven novel miRNAs were shortlisted, and dysregulation of miR-149-3p, miR-192-3p, miR-335-5p and miR-425 were further validated by the qPCR validation experiment and data retrieved from the GEO dataset. Furthermore, these miRNAs demonstrated certain associations with level of dendritic cells, natural killer cells, neutrophil and macrophage within the polyp or CRC specimens. CONCLUSION: This study revealed miRNA dysregulated during stepwise malignant transformation of colorectal mucosal cells and their association with immune cell population.

A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis.

Change in gene expression is inevitable in cancer development. With more studies demonstrating the contributions of cancer stem cells (CSCs) in colorectal cancer (CRC) development, this study is aimed at investigating whether rectal swab specimen serves as a tool for detection of dysregulation of CSC or stem cell (SC) markers and at evaluating its potential as a new promising screening method for high-risk patients. Expression levels of 15 pluripotency-associated genes were assessed by quantitative PCR in 53 rectal swab specimens referred for endoscopic screening. Dysregulated genes and joint panels based on such genes were examined for their diagnostic potentials for both polyp and CRC. Out of 15 genes, Oct4, CD26, c-MYC, and CXCR4 showed significantly differential expression among normal, polyp, and CRC patients. A panel of Oct4 and CD26 showed an AUC value of 0.80 (p = 0.003) in identifying CRC patients from polyp/normal subjects, with sensitivity and specificity of 84.6% and 69.2%. A panel of c-MYC and CXCR4 achieved CRC/polyp identification with an AUC value of 0.79 (p = 0.002), with a sensitivity of 82.8% and specificity of 80.0%. The sensitivity for polyp and CRC was 80.0% and 85.7%, respectively. Further analysis showed that higher c-MYC and CXCR4 level was detected in normal subjects who developed polyps after 5-6 years, in comparison with subjects with no lesion developed, and the AUC of the c-MYC and CXCR4 panel increased to 0.88 (p < 0.001), with sensitivity and specificity of 84.4% and 92.3%, respectively, when these patients were included in the polyp group. This study suggests that the Oct4 and CD26 panel is a promising biomarker for distinguishing CRC from normal and polyp patients, whereas the c-MYC and CXCR4 panel may identify polyp and CRC from normal individuals.

Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study.

BACKGROUND: There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients. METHODS: Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin. RESULTS: The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment. CONCLUSION: This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.

Rare complication of inflammatory bowel disease-like colitis from glycogen storage disease type 1b and its surgical management: A case report.

BACKGROUND: Glycogen storage disease (GSD) is an autosomal recessive inborn metabolic disorder. Patients with GSD are prone to hypoglycaemia, hyperlactacidemia and bleeding. GSD type 1b (GSD-1b) patients specifically can develop neutropenia, recurrent bacterial infection and inflammatory bowel disease (IBD). Documentation of the long-term outcomes of surgical management of GSD-1b has been scarce, especially for Asian patients. We herein describe a case of GSD-1b complicated by IBD-like colitis and coloduodenal fistula. The patient was managed successfully with surgical intervention. CASE SUMMARY: A 20-year-old Chinese lady confirmed by genetic testing to have GSD-1b was initially managed with uncooked cornstarch and granulocyte-colony stimulating factor. With recurrent abdominal symptoms, her condition was treated as clinical "Crohn's disease" with mesalazine, prednisolone and azathioprine conservatively. Colonoscopy showed a tight stricture at the hepatic flexure. Subsequent computerized tomographic colonography revealed a phlegmon at the ileocaecal region with a suspected coloduodenal fistula. Eventually an exploratory laparotomy was performed and severe colitis at the ascending colon with coloduodenal fistula was confirmed. Right hemicolectomy with primary anastomosis and repair of the duodenum were performed. Surgical management of complications from GSD-1b associated IBD-like colitis has rarely been described. First-line treatment would usually be conservative. Surgical intervention like hemicolectomy is mainly reserved for refractory cases. CONCLUSION: Surgical management of coloduodenal fistula in GSD-1b patients is a feasible and safe option when failed conservative management.

Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis.

INTRODUCTION: The difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery. METHOD: We conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated. RESULTS: In total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6). CONCLUSION: Right colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases - The Hong Kong experience and literature review.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief. METHODS: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival. RESULTS: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31). CONCLUSION: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.

Colonic perfusion assessment with indocyanine-green fluorescence imaging in anterior resections: a propensity score-matched analysis.

BACKGROUND: Colonic perfusion is crucial for anastomotic healing and this could be evaluated intraoperatively using indocyanine-green fluorescence imaging (ICG FI). The aim of this study was to ascertain whether the use of ICG FI resulted in the reduction of anastomotic complications, i.e. AL and anastomotic stricture. METHODS: Consecutive patients who underwent anterior resections or low anterior resections at our institution in the period from January 1st 2013 to December 31st 2018 were retrospectively reviewed. Surgery performed during the period from January 1st 2013 to December 31st 2015 did not involve the use of ICG FI (ICG-) while surgery during the period from January 1st 2016 to December 31st 2018 was performed with the use of ICG FI (ICG+). The anastomotic leakage rates of the two groups were compared after propensity score matching, taking into account the height of the anastomosis and any history of pelvic irradiation. RESULTS: There was a total of 258 and 317 patients who had surgery with and without ICG FI, respectively. There were 253 patients in each group after propensity score matching. The overall anastomotic leakage rate was 3.6% and 7.9% for ICG+ and ICG-, respectively, (p = 0.035). Subgroup analysis showed that the use of ICG FI was significantly associated with a lower anastomotic leakage rate in total mesorectal excision (TME), 4.7% versus 11.6%, p = 0.043, but not in non-TME resections, 3.5% versus 2.4%, (p = 0.612). ICG FI, together with sex and anastomotic height, were independent predictors of anastomotic leakage. CONCLUSIONS: The routine use of ICG FI was associated with a lower anastomotic leakage rate in anterior resections. The reduction in anastomotic leakage rate was mainly seen in TME.

Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles.

OBJECTIVE: Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. DESIGN: We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. RESULTS: We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. CONCLUSIONS: These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.

Low Anterior Resection Syndrome After Transanal Total Mesorectal Excision: A Comparison With the Conventional Top-to-Bottom Approach.

BACKGROUND: Advances in sphincter-saving procedures improved the quality of life of patients with rectal cancer. However, many of them experienced functional disturbances after surgery, including low anterior resection syndrome. OBJECTIVE: The aim of this study was to evaluate the severity of low anterior resection syndrome after transanal total mesorectal excision and compare it with the conventional transabdominal, top-to-bottom, total mesorectal excision. DESIGN: This was a single-center, retrospective analysis. SETTINGS: The study was conducted at a tertiary academic institution. PATIENTS: This study analyzed patients who underwent total mesorectal excision for mid to low rectal cancer from January 2016 to April 2018. Cases were matched one-to-one according to the tumor height and history of pelvic irradiation using the propensity score. MAIN OUTCOME MEASURES: The primary outcome measured was the severity of low anterior resection syndrome and fecal incontinence at 3, 6, and 12 months after surgery or stoma reversal, whichever was later. RESULTS: There were 35 patients in each group after matching; 67.1% were male, and 41.4% had neoadjuvant radiotherapy. At 3 months, the median low anterior resection syndrome score was 37 after transanal total mesorectal excision, which was significantly higher than the conventional approach, 32 (p = 0.045). Apart from this, the low anterior resection syndrome score, severity grading, and the Wexner score were comparable at 6 and 12 months. LIMITATIONS: A difference between the 2 groups might not be detected because of the study's small sample size and because of its retrospective nature. CONCLUSIONS: A higher low anterior resection syndrome score was observed after transanal total mesorectal excision at the initial 3-month period, but such a difference was not observed thereafter. This study showed that both surgical techniques had similar anal and bowel functional outcomes in the long run. However, because of the limited case number and study design, further study is needed to prove this. See Video Abstract at http://links.lww.com/DCR/B146. SÍNDROME DE RESECCIÓN ANTERIOR BAJA DESPUÉS DE LA ESCISIÓN MESORRECTAL TOTAL TRANSANAL: UNA COMPARACIÓN CON EL ABORDAJE CONVENCIONAL DE SUPERIOR A INFERIOR: Los avances en los procedimientos para salvar esfínteres mejoraron la calidad de vida de los pacientes con cáncer rectal. Sin embargo, muchos de ellos sufrieron trastornos funcionales después de la cirugía, incluyendo el síndrome de resección anterior baja.El objetivo de este estudio fue evaluar la gravedad del síndrome de resección anterior baja después de la escisión mesorrectal total transanal y comparar con la escisión mesorrectal total convencional transabdominal, de arriba a abajo.El estudio se realizó en una institución académica terciaria.Este fue un análisis retrospectivo de un solo centro de pacientes que se sometieron a una escisión mesorrectal total por cáncer rectal medio a bajo desde enero de 2016 hasta abril de 2018. Los casos fueron emparejados uno a uno de acuerdo con la altura del tumor y los antecedentes de irradiación pélvica con puntaje de propensión.La gravedad del síndrome de resección anterior baja y la incontinencia fecal a los 3, 6 y 12 meses después de la cirugía o la reversión del estoma, lo que ocurriera más tarde.Hubo 35 pacientes en cada grupo después del emparejamiento. El 67.1% eran hombres. El 41,4% tenía radioterapia neoadyuvante. A los tres meses, la puntuación media del síndrome de resección anterior baja fue de 37 después de la escisión mesorrectal transanal total, que fue significativamente mayor que el enfoque convencional, 32 (p = 0.045). Aparte de esto, la puntuación baja del síndrome de resección anterior, la clasificación de gravedad y la puntuación de Wexner fueron comparables a los 6 y 12 meses.Es posible que no se detecte una diferencia entre los dos grupos debido al pequeño tamaño de la muestra del estudio. La naturaleza retrospectiva del estudio.Se observó una puntuación más alta en el síndrome de resección anterior baja después de la escisión mesorrectal total transanal en el período inicial de tres meses, pero dicha diferencia no se observó posteriormente. Este estudio mostró que ambas técnicas quirúrgicas tuvieron resultados similares de funcionamiento anal e intestinal a largo plazo. Sin embargo, debido al número limitado de casos y al diseño del estudio, es necesario realizar más estudios para demostrarlo. Consulte Video Resumen en http://links.lww.com/DCR/B146.

Small RNA Profiling of piRNAs in Colorectal Cancer Identifies Consistent Overexpression of piR-24000 That Correlates Clinically with an Aggressive Disease Phenotype.

Piwi-interacting RNAs (piRNAs) represent a novel class of small non-coding RNAs (ncRNAs) that have been shown to have a deregulated expression in several cancers, although their clinical significance in colorectal cancer (CRC) remains unclear. With an aim of delineating the piRNA distribution in CRC, we conducted a systematic discovery and validation of piRNAs within two clinical cohorts. In the discovery phase, we profiled tumor and adjacent normal tissues from 18 CRC patients by deep sequencing and identified a global piRNA downregulation in CRC. Moreover, we identified piR-24000 as an unexplored piRNA that was significantly overexpressed in CRC. Using qPCR, we validated the overexpression of piR-24000 in 87 CRC patients. Additionally, we identified a significant association between a high expression of piR-24000 and an aggressive CRC phenotype including poor differentiation, presence of distant metastases, and a higher stage. Lastly, ROC analysis demonstrated a strong diagnostic power of piR-24000 in discriminating CRC patients from normal subjects. Taken together, this study provides one of the earliest large-scale reports of the global distribution of piRNAs in CRC. In addition, piR-24000 was identified as a likely oncogene in CRC that can serve as a biomarker or a therapeutic target.

How does lymph node yield affect survival outcomes of stage I and II colon cancer?

BACKGROUND: According to the American Joint Committee on Cancer staging for cancer of the colon, a minimum of 12 lymph nodes (LN) has to be sampled for accurate staging. This has bearing on the long-term prognosis and the need for adjuvant chemotherapy. The aim of this study was to revisit the association of lymph node yield and the long-term survival in patients with stages I and II, i.e. node-negative, colon cancer. METHOD: Consecutive patients who underwent elective or emergency curative resections for cancer of colon between the years 2003 and 2012 were retrospectively reviewed. Only patients with stage I or II diseases (AJCC 8th edition) were included. They were analysed in three groups, LN<12, LN12-19 and LN≥20. Their clinic-pathological characteristics were compared. The disease-free (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: There was a total of 659 patients included in the analysis. Twelve or more LN were found in 65.6% of the specimens. The mean follow-up was 83.9 months. LN≥20 had significantly better DFS (p = 0.015) and OS (p = 0.036), whereas LN<12 had similar DFS and OS when compared to LN12-19. The advantage in DFS and OS were mainly seen in those with stage II diseases. A lymph node yield of greater than 20 was one of the predictors of favourable DFS, hazard ratio 0.358; 95% CI 0.170-.756, p = 0.007. CONCLUSION: The lymph node yield had a significant association with survival outcomes. A lymph node yield of 20 or more was associated with better survival outcomes. On the other hand, lymph node yield less than 12 was not shown to have inferior survival outcomes when compared to those between 12 and 19.

Outcomes of colorectal cancer surgery in the nonagenarians: 20-year result from a tertiary center.

BACKGROUND: There is a foreseeable trend that life expectancy is on the rise in many parts of the world. More and more patients will present with colorectal cancer at extreme old age and advanced age is a well-known risk factor for adverse outcomes after surgery. The aim of this study is to evaluate the outcomes of colorectal cancer surgery in patients aged 90 or above. METHOD: A retrospective analysis of consecutive patients aged 90 or above who underwent operations for colorectal cancer between January 1996 and December 2015 was performed. The primary outcomes were the complications rate, 30-day and 180-day mortality rates. RESULTS: A total of 57 patients were included in the analysis. The majority of them were women (64.9%). The median age was 92 years. Most of the surgery was of curative intent (77.2%), performed under elective setting (57.9%) and with open approach (78.9%). 36.8% of patients had postoperative complications, with pneumonia being the commonest. The 30-day and 180-day mortality rate was 7 and 31.6% respectively. History of ischemic heart disease and surgery under emergency setting were predictors of postoperative complications. Pneumonia, preoperative leukocytosis and Charlson comorbidity score ≥ 9 were predictors of 180-day mortality. The one and two-year survival rate for elective surgery was 69.7 and 54.5% respectively. CONCLUSION: The outcomes of colorectal cancer surgery for nonagenarians could be favorable in a selected group of patients. Future study on better risk profiling and ways to improve outcomes is warranted.

A rare case of rectal prolapse after Deloyers procedure in a patient with Hirschsprung's disease: A case report.

INTRODUCTION: Deloyers procedure has been reported in the literature as a viable alternative to the more commonly performed Swenson, Soave and Duhamel methods. As of yet, the long term sequelae of this procedure for patients with Hirschsprung's disease have not been studied in depth. PRESENTATION OF CASE: We report the first case in the literatures of a 27-year-old man presenting with rectal prolapse due to colorectal anastomotic intussusception after Deloyers procedure for Hirschsprung's disease. DISCUSSION: Few studies with low case volume have been performed investigating the long term sequelae of Deloyers procedure as a mainstay in patients undergoing operative treatment for Hirschsprung's disease. This procedure allows for preservation of a longer segment of colon, in turn potentially improving absorption and continence compared to other methods. Studies are limited and as of yet the viability of Deloyers as a mainstay of treatment for Hirschsprung's disease is inconclusive. CONCLUSION: We report the first adult case of prolapsed colorectal anastomotic intussusception after Deloyers procedure for Hirschsprung's disease. Further study is required to delineate long-term complications and viability of this method in these patients.

The impact of indocyanine-green fluorescence angiogram on colorectal resection.

BACKGROUND: Perfusion plays an important role in anastomotic healing. Indocyanine-green fluorescence angiogram allows objective bowel perfusion assessment. This study aimed to investigate the impact of perfusion assessment on intraoperative decision during left-sided colorectal resections. METHOD: This was a prospective, single-centre, observational study recruiting patients with left-sided colorectal resections. Perfusion of bowel segment was assessed with ICG fluorescence angiogram prior to resection and anastomosis intra-operatively. The planned transection site and the actual transection site after perfusion assessment were compared. The decision for diversion stoma was also evaluated. RESULTS: 110 patients with cancer of the sigmoid colon (29.1%) and rectum (70.9%) were recruited. Total mesorectal excision was performed in 51.8% of patients. The transection site was revised in 34.5% of cases: 30.9% more proximally and 3.6% more distally. The median distance between the intended and actual transection sites was 2 cm (range 1-17 cm). A proximal revision in the transection site was more likely seen in rectal cancers (p = 0.036, OR 3.58, 95% CI 1.09-11.78) and relatively under-perfused left colon (p = 0.036, OR 1.01, 95% CI 1.01-1.02). Three (2.7%) patients were spared from a diversion stoma. The overall anastomotic leakage rate was 5.5%. CONCLUSION: ICG fluorescence angiogram altered operative decisions in a significant proportion of cases. The impact on transection site was more pronounced in patients with rectal cancers and those with relatively under-perfused colon.