Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Melanosis coli: Harmless pigmentation? A case-control retrospective study of 657 cases.

The association of melanosis coli with the development of colorectal polyps remains uncertain.From a total of 18263 patients who had received colonoscopy in our hospital, 219 with melanosis coli cases and 438 controls matched by age and sex (at 1:2 ratio) were included in this study. The association of incidence, number, location, and pathology of colorectal neoplasm with grades and distribution of melanosis coli were analyzed.Melanosis coli was associated with significantly more colorectal polyps than control, a higher incidence of numerous colorectal polyps (number ≥ 20) (7.3% vs 0.5%; p < 0.001), and higher number of small colorectal polyps (diameter ≤ 5 mm; p < 0.01). Patients with melanosis coli had higher incidences of low-grade adenomas (31.1% vs 23.3%, p < 0.05) and non-adenoma polyps (20.1% vs 12.8%, p < 0.05) than the controls. On multivariate analysis, melanosis coli was independently associated with increased detecting rates of low grade adenoma (OR = 1.54; 95%: 1.06-2.23; p < .05), non-adenoma polyp (OR = 1.72; 95%: 1.11-2.70; p < .05) and numerous polyps (OR = 16.2, 95%: 3.66-71.6; p < .05). There was no significant difference in the incidence of high-grade adenomas or adenocarcinomas in the two population groups, but the numbers of these lesions were insufficient to permit firm conclusions. No significant differences in incidence, number, and pathology of colorectal polyps between individuals with melanosis coli of three different grades of severity were found. Melanosis located predominantly in the right colon had an interestingly lower incidence of colonic polyps in right colon than did melanosis located predominantly in the left colon or total colon (8.9% vs. 26.3%, 24.0%, p < 0.05). Patients with melanosis coli had significantly more nonspecific distal ileal ulcers than did controls (8.0% vs 0%, p < 0.001).Melanosis coli is associated with a higher incidence and number of colonic non-adenoma polyps and low-grade adenomas, and higher incidence of distal ileal ulcers. Melanosis coli may not be a harmless pigmentation, but a sign of chronic injury of colonic and intestinal mucosa

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

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

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&rsquo; 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

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

Identification and evaluation of a serum microRNA panel to diagnose colorectal cancer patients.

Screening plays a crucial role in the early detection of colorectal cancer, greatly reducing mortality rates. The objective of this study was to identify a non-invasive diagnostic method utilizing serum microRNA expression for the diagnosis of colorectal cancer patients. The study consisted of three stages. In the first stage, 129 patients with colorectal cancer and 129 normal subjects were recruited as the training set for the development of a blood miRNA panel. The second stage involved recruiting 200 patients from each group as the validation cohort. Finally, a blinded study was conducted in the third stage, with 260 patients recruited to determine the predictive value of our miRNA panel. Serum samples were prospectively collected from colorectal cancer patients and normal subjects between 2017 and 2021 at Queen Mary Hospital in Hong Kong. Quantitative PCR was utilized to detect the serum levels of candidate microRNAs, and a multiple linear regression model was employed to formulate a serum microRNA panel for diagnosing colorectal cancer patients. The performance of the panel was evaluated using ROC analysis. Our study showed that the values of three pairs of serum microRNAs, namely miR-106b-5p/miR-1246, miR-106b-5p/miR-16 and miR-106b-5p/miR-21-5p, exhibited statistically significant differences between colorectal cancer patients and normal subjects. A serum microRNA panel formulated from these three pairs of microRNAs demonstrated high accuracy in diagnosing colorectal cancer patients from normal subjects, with an AUC of approximately 0.9. The serum miRNA test proved to be a feasible and promising non-invasive biomarker for the diagnosis of colorectal cancer patients in comparison to normal subjects

Melanosis coli: Harmless pigmentation? A case-control retrospective study of 657 cases

<div><p>Backgrounds and aims</p><p>The association of melanosis coli with the development of colorectal polyps remains uncertain.</p><p>Methods</p><p>From a total of 18263 patients who had received colonoscopy in our hospital, 219 with melanosis coli cases and 438 controls matched by age and sex (at 1:2 ratio) were included in this study. The association of incidence, number, location, and pathology of colorectal neoplasm with grades and distribution of melanosis coli were analyzed.</p><p>Results</p><p>Melanosis coli was associated with significantly more colorectal polyps than control, a higher incidence of numerous colorectal polyps (number ≥ 20) (7.3% vs 0.5%; p < 0.001), and higher number of small colorectal polyps (diameter ≤ 5 mm; p < 0.01). Patients with melanosis coli had higher incidences of low-grade adenomas (31.1% vs 23.3%, p < 0.05) and non-adenoma polyps (20.1% vs 12.8%, p < 0.05) than the controls. On multivariate analysis, melanosis coli was independently associated with increased detecting rates of low grade adenoma (OR = 1.54; 95%: 1.06–2.23; p < .05), non-adenoma polyp (OR = 1.72; 95%: 1.11–2.70; p < .05) and numerous polyps (OR = 16.2, 95%: 3.66–71.6; p < .05). There was no significant difference in the incidence of high-grade adenomas or adenocarcinomas in the two population groups, but the numbers of these lesions were insufficient to permit firm conclusions. No significant differences in incidence, number, and pathology of colorectal polyps between individuals with melanosis coli of three different grades of severity were found. Melanosis located predominantly in the right colon had an interestingly lower incidence of colonic polyps in right colon than did melanosis located predominantly in the left colon or total colon (8.9% vs. 26.3%, 24.0%, p < 0.05). Patients with melanosis coli had significantly more nonspecific distal ileal ulcers than did controls (8.0% vs 0%, p < 0.001).</p><p>Conclusion</p><p>Melanosis coli is associated with a higher incidence and number of colonic non-adenoma polyps and low-grade adenomas, and higher incidence of distal ileal ulcers. Melanosis coli may not be a harmless pigmentation, but a sign of chronic injury of colonic and intestinal mucosa.</p></div

Association of melanosis coli with detecting rates of colonic polyps of different histological types.

<p>Association of melanosis coli with detecting rates of colonic polyps of different histological types.</p

Multivariate analysis of risk factors for development of colonic polyps.

<p>Multivariate analysis of risk factors for development of colonic polyps.</p