Alterations in colorectal cancer virome and its persistence after surgery.

Viruses are a key component of the colon microbiome, but the relationship between virome and colorectal cancer (CRC) remains poorly understood. We seek to identify alterations in the viral community that is characteristic of CRC and examine if they persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for metagenomic analysis. The fecal virome of CRC patients demonstrated an increased network connectivity as compared to NC individuals. Co-exclusion of influential viruses to bacterial species associated with healthy gut status was observed in CRC, suggesting an altered virome induced a change in the healthy gut bacteriome. Network analysis revealed lower connectivity within the virome and trans-kingdom interactions in NC. After surgery, the number of strong correlations decreased for trans-kingdom and within the bacteria and virome networks, indicating lower connectivity within the microbiome. Some co-occurrence patterns between dominant viruses and bacteria were also lost after surgery, suggesting a possible return to the healthy state of gut microbiome. Microbial signatures characteristic of CRC include an altered virome besides an altered bacterial composition. Elevated viral correlations and network connectivity were observed in CRC patients relative to healthy individuals, alongside distinct changes in the cross-kingdom correlation network unique to CRC patients. Some patterns of dysbiosis persist after surgery. Future studies should seek to verify if dysbiosis truly persists after surgery in a larger sample size with microbiome data collected at various time points after surgery to explore if there is field-change in the remaining colon, as well as to examine if persistent dysbiosis correlates with patient outcomes.

A 10-year experience with anastomotic leaks in upper gastrointestinal surgery-Retrospective cohort study.

BACKGROUND: Anastomotic leak (AL) in upper gastrointestinal (UGI) surgery continues to be a diagnostic challenge. We seek to identify clinical parameters that predict AL and examine the effectiveness of investigations in evaluating AL following UGI surgeries. METHODS: 592 patients underwent UGI surgeries with an anastomosis between January 2011 and January 2021. Data on patient characteristics, surgery, postoperative investigations and outcomes were prospectively collected and analysed. RESULTS: The overall occurrence of AL was 6.4 %. Tachycardia >120 BPM (OR 6.959, 95 % CI 1.856-26.100, p = 0.004) and leukocyte count >19 × 109/L (OR 3.327, 95 % CI 1.009-10.967, p = 0.048) were independent predictors of AL. On multivariate analysis, patients whose anastomosis was deemed high risk and had pre-emptive investigation done postoperatively to exclude a leak were less likely to require intervention and were more likely to be managed conservatively (66.7 % vs 14.3 %, p = 0.025). Methylene blue test, oral contrast study and Computed Tomography scan with intravenous and oral contrast had 50.0 %, 20.0 % and 9.1 % false negative results, while esophagogastroduodenoscopy had none. There was no misdiagnosed AL when more than 1 investigation (n = 15, 39.5 %) were performed. CONCLUSION: Our study demonstrates that the presence of a triad including desaturation, tachycardia and leucocytosis predicts for AL following UGI surgery and for confirmation of a leak, evaluation with 2 or more investigation is needed. A practice of evaluating high risk anastomosis prior to commencement of feeding decreased the need for surgical intervention and improves success of conservative treatment.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Safely Implementing a Program of Pure Laparoscopic Donor Right Hepatectomy: The Experience From a Southeast Asian Center.

Laparoscopic donor right hepatectomy (LDRH) is a technically challenging procedure. There is increasing evidence demonstrating the safety of LDRH in high-volume expert centers. We report our center's experience in implementing an LDRH program in a small- to medium-sized transplantation program. Methods: Our center systematically introduced a laparoscopic hepatectomy program in 2006. We started with minor wedge resections followed by major hepatectomies with increasing complexities. In 2017, we performed our first laparoscopic living donor left lateral sectionectomy. Since 2018, we have performed 8 cases of right lobe living donor hepatectomy (laparoscopy-assisted: 4 and pure laparoscopic: 4). Results: The median operative time was 418 (298-540) min, whereas the median blood loss was 300 (150-900) mL. Two patients (25%) had surgical drain placed intraoperatively. The median length of stay was 5 (3-8) d, and the median time to return to work was 55 (24-90) d. None of the donors sustained any long-term morbidity or mortality. Conclusions: Small- to medium-sized transplant programs face unique challenges in adopting LDRH. Progressive introduction of complex laparoscopic surgery, a mature living donor liver transplantation program, appropriate patient selection, and the invitation of an expert to proctor the LDRH are necessary to ensure success.

Single-incision transgastric resection for gastric gastrointestinal stromal tumors in anatomically challenging locations.

Surgical resection is the mainstay treatment for resectable gastrointestinal stromal tumors (GISTs). However, resection in anatomically challenging locations, such as near the gastroesophageal junction, lesser curve and fundus, remain technically challenging. We herein report the outcomes of the largest series of patients who underwent single-incision transgastric resection of an intraluminal gastric GIST. Our reduced-port resection technique for intraluminal GISTs in these anatomically challenging locations involves a single incision in the left hypochondrium, deepened to access the gastric lumen, with the surgery completed in a transgastric manner. A total of 22 patients received surgery with this technique at the National University Hospital in Singapore from November 2012 to September 2020. The median operative time was 101 (range 50-253) min, with no conversions to open surgery, median lesion size 3.6 (range 1.8-8.2) cm and median postoperative length of stay 5 (range 1-13) days. There was no 30-day mortality and no recurrence during the follow-up period. Our laparoscopic approach for reduced-port transgastric excision of intraluminal GISTs allows for adequate surgical clearance, convenient extraction and secure gastrostomy closure with low morbidity.

Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher ARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising from ARID1A loss. DESIGN: Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures of ARID1A inactivation across molecular subtypes. Single-cell transcriptomic profiles of ARID1A-mutated GCs were analysed to examine tumour microenvironmental changes arising from ARID1A loss. Genome-wide ARID1A binding and chromatin profiles (H3K27ac, H3K4me3, H3K4me1, ATAC-seq) were generated to identify gastric-specific epigenetic landscapes regulated by ARID1A. Distinct cancer hallmarks of ARID1A-mutated GCs were converged at the genomic, single-cell and epigenomic level, and targeted by pharmacological inhibition. RESULTS: We observed prevalent ARID1A inactivation across GC molecular subtypes, with distinct mutational signatures and linked to a NFKB-driven proinflammatory tumour microenvironment. ARID1A-depletion caused loss of H3K27ac activation signals at ARID1A-occupied distal enhancers, but unexpectedly gain of H3K27ac at ARID1A-occupied promoters in genes such as NFKB1 and NFKB2. Promoter activation in ARID1A-mutated GCs was associated with enhanced gene expression, increased BRD4 binding, and reduced HDAC1 and CTCF occupancy. Combined targeting of promoter activation and tumour inflammation via bromodomain and NFKB inhibitors confirmed therapeutic synergy specific to ARID1A-genomic status. CONCLUSION: Our results suggest a therapeutic strategy for ARID1A-mutated GCs targeting both tumour-intrinsic (BRD4-assocatiated promoter activation) and extrinsic (NFKB immunomodulation) cancer phenotypes.

Alterations in co-abundant bacteriome in colorectal cancer and its persistence after surgery: a pilot study.

There is growing interest in the role of gut microbiome in colorectal cancer (CRC), ranging from screening to disease recurrence. Our study aims to identify microbial markers characteristic of CRC and to examine if changes in bacteriome persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for analysis by bacterial 16S rRNA gene sequencing. Bacterial richness and diversity were reduced, while pro-carcinogenic bacteria such as Bacteroides fragilis and Odoribacter splanchnicus were increased in CRC patients compared to NC group. These differences were no longer observed after surgery. Comparison between pre-op and post-op CRC showed increased abundance of probiotic bacteria after surgery. Concomitantly, bacteria associated with CRC progression were observed to have increased after surgery, implying persistent dysbiosis. In addition, functional pathway predictions based on the bacterial 16S rRNA gene data showed that various pathways were differentially enriched in CRC compared to NC. Microbiome signatures characteristic of CRC comprise altered bacterial composition. Elements of these dysbiotic signatures persists even after surgery, suggesting possible field-change in remnant non-diseased colon. Future studies should involve a larger sample size with microbiome data collected at multiple time points after surgery to examine if these dysbiotic patterns truly persist and also correlate with disease outcomes.

Evolving perspectives on stool testing for colorectal cancer: a qualitative systematic review.

OBJECTIVES: Colorectal cancer is one of the leading causes of cancer-related deaths globally. A multitude of screening methods has been devised for early diagnosis, including the faecal immunochemical test (FIT). This qualitative review aims to discover the barriers and facilitators to the utility of the FIT from the general population's perspective. METHODS: Authors searched five electronic bases (Medline, Embase, CINAHL, PsycINFO and Web of Science) till December 2019. The search was conducted using key search terms and qualitative and mixed-method studies were included. Two independent reviewers screened articles and conducted quality appraisal. Data were synthesised thematically. RESULTS: A total of 11 articles that reported users' views on FIT kits were included. Three themes were generated from the included articles: FIT kit factors, patients' perception of colorectal cancer screening, and social health support system. The nature of the test and the supplementary information was found to affect the utilisation of the test. User's awareness and perspectives towards cancer and screening were found to have impacted the adoption of the FIT kit. Social support and local healthcare systems were also found to have influenced the use of FIT. CONCLUSION: This systematic review focuses on addressing and understanding the perception of FIT from first-hand accounts. Since its inception, FIT screening has increased colorectal cancer screening uptake due to its increased reliability and the simplicity of the test. However, there is a need to increase the uptake of FIT kits through increasing accessibility of the screening process and considering the holistic patient experience.

Curative treatment for metastatic colorectal cancer in the young population: is it worth it?

BACKGROUND: A significant proportion of patients with colorectal cancer (CRC) presents with metastatic disease. In younger patients, a more aggressive approach is often adopted in an attempt to achieve cure and improve survival. The aim of this paper is to review the management and outcomes of young patients with metastatic CRC. METHODS: All patients under 50 years diagnosed with CRC in a single institution from January 2007 to December 2015 were reviewed. Patient demographics, details of their treatments, progress and outcomes of treatment were collected for our review. RESULTS: There were 154 newly diagnosed CRC patients who were <50 years old during the study period. Thirty-three patients (21.4%) had stage IV disease on presentation. Seventeen (51.5%) of these 33 patients were treated with curative intent; 9 (52.9%) of whom underwent upfront surgical resection alone while the remaining 8 (47.1%) patients had neoadjuvant therapy followed by surgical resection. Among the 16 patients who were treated with palliative intent, 9 (56.3%) had surgery while 7 (43.7%) had definitive chemo- or radio-therapy. There was no significant difference in the median survival of patients treated with curative and palliative intent (29 vs. 24 months, P=0.140). CONCLUSIONS: Young CRC patients with stage IV disease typically survive for 2 years upon diagnosis. Those who were treated and underwent surgery with curative intent have a slightly longer but not statistically significant median survival than those treated with palliative intent. The role of aggressive treatment in these young patients with metastatic patients merits further evaluation.

Does persistent anti-HBc positivity influence the prognosis of HBsAg-negative hepatocellular carcinoma? comparative outcomes of anti-Hbc positive versus anti-Hbc negative non-B non-C HCC.

BACKGROUND: To compare the presentations and outcomes of anti-HBc seropositive Hepatocellular Carcinoma (HBc-HCC) with anti-HBc seronegative (NHBc-HCC) patients in HBsAg negative Non-HBV Non-HCV (NBNC-HCC) HCC population. METHODS: 515 newly diagnosed HCC patients from January 2011 to September 2016 were retrospectively reviewed. 145 (66.5%) NHBc-HCC and 73 (33.5%) HBc-HCC patients were identified. Patient demographics, disease characteristics, details of treatments, recurrence and survival outcomes were analysed. RESULTS: A significantly lower proportion of HBc-HCC patients were diagnosed through surveillence (6.8% vs 26.2%, p = 0.001). HBc-HCC patients were less likely cirrhotic (p < 0.001), portal hypertensive (p < 0.001), ascitic (p = 0.008) and thrombocytopenic (p = 0.003). A higher proportion of HBc-HCC patients had treatment with curative intent (46.6% vs 30.3%, p = 0.018) and surgery (39.7% vs 16.6%, p < 0.001). Although HBc-HCC patients had larger median tumor size (74.0 mm vs 55.0 mm, p = 0.016) with a greater proportion of patients having tumors ≥5 cm, there was no difference in the overall median survival (19.0 months vs 22.0 months, p = 0.919) and recurrence rates (38.2% vs 40.9%). CONCLUSION: Isolated anti-HBc seropositivity in HbsAg negative patients tend to present incidentally with delayed diagnoses resulting in larger tumors, but their long-term survival remain comparable.

Young colorectal cancer patients often present too late.

PURPOSE: Current screening and health education strategies on colorectal cancer (CRC) remain focused on individuals >50 years old. However, CRC in young adults is not uncommon. This paper aims to explore how CRC presents in young adults and their clinical outcomes. METHODS: All patients aged <50 years diagnosed with CRC from January 2007 to December 2015 were reviewed. Patient demographics, clinical symptoms, and outcomes of treatment were collected. RESULTS: Of 1367 patients diagnosed with CRC, 154 (11.6%) were aged <50 years. The median age of diagnosis was 45 years (range, 19-49). The majority (61%) of the patients presented acutely via the emergency department and the three most common presenting symptoms were abdominal pain (n = 94; 61.0%), change in bowel habits (n = 74; 48.1%), and per rectal bleeding (n = 69; 44.8%). Most of the primary cancers were left sided (n = 122, 79.2%) in location and 33 (21.4%) patients had metastatic disease on presentation. 138 (89.6%) patients were treated with curative intent, including 17 (51.5%) with metastatic disease on presentation. There were 31 (22.5%) patients who developed disease recurrence at a median duration of 10.0 (range, 0.5-94.0) months. The younger group (<45 years old) were more likely to present acutely and had more aggressive tumor biology. CONCLUSIONS: The majority of young CRC patients present acutely and their presenting symptoms are often vague. There is a need to educate young adults on the possibility of harboring CRC and its typical presenting symptoms to enable earlier detection.