Influence of the COVID-19 pandemic on the timing of surgical triage, tumor stage, and therapy of patients with colon carcinoma.

PURPOSE: With the onset of the COVID pandemic in Germany in March 2020, far-reaching restrictions were imposed that limited medical access for patients. Screening examinations such as colonoscopies were greatly reduced in number. As rapid surgical triage after diagnosis is prognostic, our hypothesis was that pandemic-related delays would increase the proportion of advanced colon cancers with an overall sicker patient population. METHODS: A total of 204 patients with initial diagnosis of colon cancer were analyzed in this retrospective single-center study between 03/01/2018 and 03/01/2022. Control group (111 patients, pre-COVID-19) and the study group (93 patients, during COVID-19) were compared in terms of tumor stages, surgical therapy, complications, and delays in the clinical setting. The data were presented either as absolute numbers or as median for constant data. RESULTS: A trend towards more advanced tumor stages (T4a p = 0.067) and a significant increase of emergency surgeries (p = 0.016) with higher rates of ileus and perforation (p = 0.004) as well as discontinuity resections (p = 0.049) during the pandemic could be observed. Delays in surgical triage after endoscopic diagnosis were seen during the 2nd lockdown (02/11/20-26/12/20; p = 0.031). CONCLUSION: In summary, the results suggest delayed treatment during the COVID-19 pandemic, with the infection pattern of COVID appearing to have a major impact on the time between endoscopic diagnosis and surgical triage/surgery. Adequate care of colon cancer patients is possible even during a pandemic, but it is important to focus on structured screening and tight diagnosis to treatment schedules in order to prevent secondary pandemic victims.

IMC-MDA: Prediction of miRNA-disease association based on induction matrix completion.

To comprehend the etiology and pathogenesis of many illnesses, it is essential to identify disease-associated microRNAs (miRNAs). However, there are a number of challenges with current computational approaches, such as the lack of "negative samples", that is, confirmed irrelevant miRNA-disease pairs, and the poor performance in terms of predicting miRNAs related with "isolated diseases", i.e. illnesses with no known associated miRNAs, which presents the need for novel computational methods. In this study, for the purpose of predicting the connection between disease and miRNA, an inductive matrix completion model was designed, referred to as IMC-MDA. In the model of IMC-MDA, for each miRNA-disease pair, the predicted marks are calculated by combining the known miRNA-disease connection with the integrated disease similarities and miRNA similarities. Based on LOOCV, IMC-MDA had an AUC of 0.8034, which shows better performance than previous methods. Furthermore, experiments have validated the prediction of disease-related miRNAs for three major human diseases: colon cancer, kidney cancer, and lung cancer.

Seven bacterial response-related genes are biomarkers for colon cancer.

BACKGROUND: Colon cancer (CC) is a common tumor that causes significant harm to human health. Bacteria play a vital role in cancer biology, particularly the biology of CC. Genes related to bacterial response were seldom used to construct prognosis models. We constructed a bacterial response-related risk model based on three Molecular Signatures Database gene sets to explore new markers for predicting CC prognosis. METHODS: The Cancer Genome Atlas (TCGA) colon adenocarcinoma samples were used as the training set, and Gene Expression Omnibus (GEO) databases were used as the test set. Differentially expressed bacterial response-related genes were identified for prognostic gene selection. Univariate Cox regression analysis, least absolute shrinkage and selection operator-penalized Cox regression analysis, and multivariate Cox regression analysis were performed to construct a prognostic risk model. The individual diagnostic effects of genes in the prognostic model were also evaluated. Moreover, differentially expressed long noncoding RNAs (lncRNAs) were identified. Finally, the expression of these genes was validated using quantitative polymerase chain reaction (qPCR) in cell lines and tissues. RESULTS: A prognostic signature was constructed based on seven bacterial response genes: LGALS4, RORC, DDIT3, NSUN5, RBCK1, RGL2, and SERPINE1. Patients were assigned a risk score based on the prognostic model, and patients in the TCGA cohort with a high risk score had a poorer prognosis than those with a low risk score; a similar finding was observed in the GEO cohort. These seven prognostic model genes were also independent diagnostic factors. Finally, qPCR validated the differential expression of the seven model genes and two coexpressed lncRNAs (C6orf223 and SLC12A9-AS1) in 27 pairs of CC and normal tissues. Differential expression of LGALS4 and NSUN5 was also verified in cell lines (FHC, COLO320DM, SW480). CONCLUSIONS: We created a seven-gene bacterial response-related gene signature that can accurately predict the outcomes of patients with CC. This model can provide valuable insights for personalized treatment.

Colon and rectal cancer treatment patterns and their associations with clinical, sociodemographic and lifestyle characteristics: analysis of the Australian 45 and Up Study cohort.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer globally and the second leading cause of cancer death. We examined colon and rectal cancer treatment patterns in Australia. METHODS: From cancer registry records, we identified 1,236 and 542 people with incident colon and rectal cancer, respectively, diagnosed during 2006-2013 in the 45 and Up Study cohort (267,357 participants). Cancer treatment and deaths were determined via linkage to routinely collected data, including hospital and medical services records. For colon cancer, we examined treatment categories of "surgery only", "surgery plus chemotherapy", "other treatment" (i.e. other combinations of surgery/chemotherapy/radiotherapy), "no record of cancer-related treatment, died"; and, for rectal cancer, "surgery only", "surgery plus chemotherapy and/or radiotherapy", "other treatment", and "no record of cancer-related treatment, died". We analysed survival, time to first treatment, and characteristics associated with treatment receipt using competing risks regression. RESULTS: 86.4% and 86.5% of people with colon and rectal cancer, respectively, had a record of receiving any treatment ≤2 years post-diagnosis. Of those treated, 93.2% and 90.8% started treatment ≤2 months post-diagnosis, respectively. Characteristics significantly associated with treatment receipt were similar for colon and rectal cancer, with strongest associations for spread of disease and age at diagnosis (p<0.003). For colon cancer, the rate of "no record of cancer-related treatment, died" was higher for people with distant spread of disease (versus localised, subdistribution hazard ratio (SHR)=13.6, 95% confidence interval (CI):5.5-33.9), age ≥75 years (versus age 45-74, SHR=3.6, 95%CI:1.8-7.1), and visiting an emergency department ≤1 month pre-diagnosis (SHR=2.9, 95%CI:1.6-5.2). For rectal cancer, the rate of "surgery plus chemotherapy and/or radiotherapy" was higher for people with regional spread of disease (versus localised, SHR=5.2, 95%CI:3.6-7.7) and lower for people with poorer physical functioning (SHR=0.5, 95%CI:0.3-0.8) or no private health insurance (SHR=0.7, 95%CI:0.5-0.9). CONCLUSION: Before the COVID-19 pandemic, most people with colon or rectal cancer received treatment ≤2 months post-diagnosis, however, treatment patterns varied by spread of disease and age. This work can be used to inform future healthcare requirements, to estimate the impact of cancer control interventions to improve prevention and early diagnosis, and serve as a benchmark to assess treatment delays/disruptions during the pandemic. Future work should examine associations with clinical factors (e.g. performance status at diagnosis) and interdependencies between characteristics such as age, comorbidities, and emergency department visits.

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial.

BACKGROUND: Despite the introduction of new monoclonal antibodies and oral therapies for the treatment of ulcerative colitis, clinical remission rates remain low, underscoring the need for innovative treatment approaches. We assessed whether guselkumab plus golimumab combination therapy was more effective for ulcerative colitis than either monotherapy. METHODS: We did a randomised, double-blind, controlled, proof-of-concept trial at 54 hospitals, academic medical centres, or private practices in nine countries. Eligible adults (aged ≥18 to 65 years) had a confirmed diagnosis of ulcerative colitis at least 3 months before screening and moderately-to-severely active ulcerative colitis (Mayo score 6-12) with a centrally-read baseline endoscopy subscore of 2 or higher. Patients were randomly assigned (1:1:1) using a computer-generated randomisation schedule to combination therapy (subcutaneous golimumab 200 mg at week 0, subcutaneous golimumab 100 mg at weeks 2, 6, and 10, and intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab monotherapy 100 mg every 8 weeks for 32 weeks), golimumab monotherapy (subcutaneous golimumab 200 mg at week 0 followed by subcutaneous golimumab 100 mg at week 2 and every 4 weeks thereafter for 34 weeks), or guselkumab monotherapy (intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab 100 mg every 8 weeks thereafter for 32 weeks). The primary endpoint was clinical response at week 12 (defined as a ≥30% decrease from baseline in the full Mayo score and a ≥3 points absolute reduction with either a decrease in rectal bleeding score of ≥1 point or a rectal bleeding score of 0 or 1). Efficacy was analysed in the modified intention-to-treat population up to week 38, which included all randomly assigned patients who received at least one (partial or complete) study intervention dose. Safety was analysed up to week 50, according to study intervention received among all patients who received at least one (partial or complete) dose of study intervention. This trial is complete and is registered with ClinicalTrials.gov, NCT03662542. FINDINGS: Between Nov 20, 2018, and Nov 15, 2021, 358 patients were screened for eligibility, of whom 214 patients were randomly assigned to combination therapy (n=71), golimumab monotherapy (n=72), or guselkumab monotherapy (n=71). Of the 214 patients included, 98 (46%) were women and 116 (54%) were men and the mean age was 38·4 years (SD 12·0). At week 12, 59 (83%) of 71 patients in the combination therapy group had achieved clinical response compared with 44 (61%) of 72 patients in the golimumab monotherapy group (adjusted treatment difference 22·1% [80% CI 12·9 to 31·3]; nominal p=0·0032) and 53 (75%) of 71 patients in the guselkumab monotherapy group (adjusted treatment difference 8·5% [-0·2 to 17·1; nominal p=0·2155). At week 50, 45 (63%) of 71 patients in the combination therapy group, 55 (76%) of 72 patients in the golimumab monotherapy group, and 46 (65%) of 71 patients in the guselkumab monotherapy group had reported at least one adverse event. The most common adverse events were ulcerative colitis, upper respiratory tract infection, headache, anaemia, nasopharyngitis, neutropenia, and pyrexia. No deaths, malignancies, or cases of tuberculosis were reported during the combination induction period. One case of tuberculosis was reported in the combination therapy group and one case of colon adenocarcinoma was reported in the guselkumab monotherapy group; both occurred after week 12. Two deaths were reported after the final dose of study intervention (poisoning in the combination therapy group and COVID-19 in the guselkumab monotherapy group). INTERPRETATION: Data from this proof-of-concept study suggest that combination therapy with guselkumab and golimumab might be more effective for ulcerative colitis than therapy with either drug alone. These findings require confirmation in larger trials. FUNDING: Janssen Research and Development.

Endoscopic evaluation during the COVID-19 pandemic: Observational study of the experience in community practices.

Endoscopic screening is used widely to minimize the rates of colorectal cancer cases and deaths. During highly virulent infectious disease pandemics such as the coronavirus disease 2019 (COVID-19) pandemic, it is essential to weigh the risks and benefits of receiving endoscopy, especially in regions with moderately high viral infection rates. An observational study was conducted to assess the number of patients seen for endoscopic procedure at 2 of our surgery centers. Reasons for their procedure were collected in addition to information regarding any positive COVID-19 cases. This study considers the rate of severe acute respiratory syndrome coronavirus 2 infection along with the number of colorectal cancer cases encountered at a community endoscopy center to suggest that the benefits of undergoing endoscopic evaluation may outweigh the risks of attending an endoscopy procedure during the COVID-19 pandemic. One of the main reasons patients underwent endoscopic procedure was for colon cancer screenings (41.9%), and 5 of 1020 patients seen during the observation period were diagnosed with cancer. Of these 1020 patients, 8 were found to have positive tests for COVID-19 within 2 to 4 weeks after their procedure.

The consequences of the Covid-19 pandemic on elective surgery for colon cancer.

AIM OF THE STUDY: This study presents the impact of the Covid-19 pandemic on elective surgical treatment of patients diagnosed with colon cancer, in a University Clinic of Surgery. MATERIAL AND METHODS: The data from patients who underwent an elective surgery procedure for colon cancer during the pandemic period (26.02.2020-01.10.2021) was analyzed. This period was compared with the same interval for the years 2016-2017 and 2018-2019. RESULTS: There was a significant decrease in the number of patients that underwent an elective surgery for colon cancer during the pandemic. The Covid-19 generated pandemic has influenced the number of days from diagnosis to treatment, preoperative and postoperative hospitalization. There was an increase in the number of patients with severe symptoms, with complete or incomplete ileus. The number of lymphatic nodes harvested increased during the last period of study, being correlated with the advanced cancer stage. CONCLUSIONS: The Covid-19 pandemic had an influence on the management of the patients with colon cancer undergoing an elective surgery procedure. Firstly, their number decreased compared to the other periods, and they presented more severe symptoms. The duration of the surgical act was extended, but the postoperative stay was shortened. KEY WORDS: Colon cancer, Covid-19 Pandemic, Duration of surgery, Elective surgery.

Streptococcus gallolyticus-related spinal epidural abscess.

Spinal epidural abscess (SEA) is a surgical emergency if it causes paraplegia. Staphylococcus aureus and streptococci are the most common causes. Streptococcus gallolyticus has been reported to cause SEA only on three occasions earlier-all were associated with endocarditis or colonic malignancy. We report an older woman with diabetic ketoacidosis who presented with poorly localised back pain, fever and altered sensorium. Her lumbar puncture revealed frank pus, and MRI showed an SEA. She could not be weaned from mechanical ventilation post-surgical decompression, and she succumbed to ventilator-associated pneumonia. A triad of fever, back pain and neurological deficit should lead one to consider intraspinal suppuration. This report is the first S. gallolyticus-related SEA from India and the first in literature that was not associated with either endocarditis or colonic malignancy.

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital.

OBJECTIVE: To obtain annual incidence trends, understand clinicopathological characteristics, and forecast the future burden of colorectal cancer (CRC) in Indonesia. DESIGN: 11-year retrospective cross-sectional study. SETTING: A national referral hospital in Jakarta, Indonesia. PARTICIPANTS: Data from 1584 eligible cases were recorded for trends and forecasting analyses; 433 samples were analysed to determine clinicopathological differences between young (<50 years) and old (≥50 years) patients. METHODS: Trend analyses were done using Joinpoint software, expressed in annual percentage change (APC), and a regression analysis was executed to generate a forecasting model. Patients' characteristics were compared using χ2 or non-parametric tests. MAIN OUTCOMES: Analysis of trends, forecasting model, and clinicopathological features between the age groups. RESULTS: A significant increase in APC was observed among old patients (+2.38%) for CRC cases. Colon cancer increased remarkably (+9.24%) among young patients; rectal cancer trends were either stable or declining. The trend for right-sided CRC increased in the general population (+6.52%) and old patients (+6.57%), while the trend for left-sided CRC was stable. These cases are expected to be a significant health burden within the next 10 years. Patients had a mean age of 53.17±13.94, 38.1% were young, and the sex ratio was 1.21. Prominent characteristics were left-sided CRC, tumour size ≥5 cm, exophytic growth, adenocarcinoma, histologically low grade, pT3, pN0, inadequately dissected lymph nodes (LNs), LN ratio <0.05, no distant metastasis, early-stage cancer, no lymphovascular invasion, and no perineural invasion (PNI). Distinct features between young and old patients were found in the histological subtype, number of dissected LN, and PNI of the tumour. CONCLUSIONS: Epidemiological trends and forecasting analyses of CRC cases in Indonesian patients showed an enormous increase in colon cancer in young patients, a particularly concerning trend. Additionally, young patients exhibited particular clinicopathological characteristics that contributed to disease severity.

The influence of the Covid-19 pandemic on the 90-day mortality rate after emergency surgery for colon cancer.

The Covid-19 pandemic had a significant impact on the treatment of colon cancer. This was due to the redistribution of doctors and medical resources to empower the treatment of Sars-CoV-2-infected patients. Moreover, the restrictions imposed by the authorities on the general population and hospitals were other key elements that had to be taken into consideration. The surgical activity was massively reduced for both elective and emergency surgeries during the pandemic; initially, the elective ones were postponed. This study aimed to analyze the impact of the Covid-19 pandemic on the 90-day postoperative mortality rate of patients who underwent emergency surgery for colon cancer in the First General Surgery Clinic of Pius Brinzeu County Hospital Timisoara. For conducting this study, data from patients who underwent emergency surgery for colon cancer between 26.02.2020-01.10.2021 and the same period of 2016-2017 and 2018-2019 were collected and analyzed, with a p<0.05 being considered statistically significant. As a result, the 90-days postoperative mortality rate increased to 34.5% during the pandemic. A 22.55% rate was observed during 2016-2017 and an 18.4% rate in 2018-2019. In addition, during the pandemic, correlations w ere identified between the presence of 90-day postoperative mortality and severe symptomatology when presenting to the hospital, stage of the disease, and Charlson comorbidity index. All these aspects influenced the 90-days mortality rate of patients undergoing emergency surgery to treat colon cancer during the pandemic.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Uterine cervix metastasis from primary colon adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Metastases to the female genital tract from extragenital primary tumors are unusual. We report a rare case of uterine cervix metastasis from colon adenocarcinoma and discuss diagnostic and therapeutic issues. CASE REPORT: We report a case of a 38-year-old North African Caucasian woman treated for a non-metastatic colon adenocarcinoma. She had a sigmoidectomy and incomplete adjuvant chemotherapy. Six months later, she consulted with vaginal bleeding caused by a cervical tumor, which was confirmed to be metastatic disease, and the patient underwent decompressive and hemostatic radiotherapy. CONCLUSION: Uterine cervix metastasis from primary colon adenocarcinoma is rare. The resection remains the standard protocol for the local treatment of resectable metastatic disease. Otherwise, systemic therapy is the preferable option.

COVID-CCD-Net: COVID-19 and colon cancer diagnosis system with optimized CNN hyperparameters using gradient-based optimizer.

Coronavirus disease-2019 (COVID-19) is a new types of coronavirus which have turned into a pandemic within a short time. Reverse transcription-polymerase chain reaction (RT-PCR) test is used for the diagnosis of COVID-19 in national healthcare centers. Because the number of PCR test kits is often limited, it is sometimes difficult to diagnose the disease at an early stage. However, X-ray technology is accessible nearly all over the world, and it succeeds in detecting symptoms of COVID-19 more successfully. Another disease which affects people's lives to a great extent is colorectal cancer. Tissue microarray (TMA) is a technological method which is widely used for its high performance in the analysis of colorectal cancer. Computer-assisted approaches which can classify colorectal cancer in TMA images are also needed. In this respect, the present study proposes a convolutional neural network (CNN) classification approach with optimized parameters using gradient-based optimizer (GBO) algorithm. Thanks to the proposed approach, COVID-19, normal, and viral pneumonia in various chest X-ray images can be classified accurately. Additionally, other types such as epithelial and stromal regions in epidermal growth factor receptor (EFGR) colon in TMAs can also be classified. The proposed approach was called COVID-CCD-Net. AlexNet, DarkNet-19, Inception-v3, MobileNet, ResNet-18, and ShuffleNet architectures were used in COVID-CCD-Net, and the hyperparameters of this architecture was optimized for the proposed approach. Two different medical image classification datasets, namely, COVID-19 and Epistroma, were used in the present study. The experimental findings demonstrated that proposed approach increased the classification performance of the non-optimized CNN architectures significantly and displayed a very high classification performance even in very low value of epoch.

Colon cancer treatment in Sweden during the COVID-19 pandemic: A nationwide register-based study.

AIM: The COVID-19 pandemic has reduced the capacity to diagnose and treat cancer worldwide due to the prioritization of COVID-19 treatment. The aim of this study was to investigate treatment and outcomes of colon cancer in Sweden before and during the COVID-19 pandemic. METHODS: In an observational study, using the Swedish Colorectal Cancer Registry, we included (i) all Swedish patients diagnosed with colon cancer, and (ii) all patients undergoing surgery for colon cancer, in 2016-2020. Incidence of colon cancer, treatments and outcomes in 2020 were compared with 2019. RESULTS: The number of colon cancer cases in Sweden in April-May 2020 was 27% lower than the previous year, whereas no difference was observed on an annual level (4,589 vs. 4,763 patients [-4%]). Among patients with colon cancer undergoing surgery in 2020, the proportion of resections was 93 vs. 94% in 2019, with no increase in acute resections. Time from diagnosis to elective surgery decreased (29 days vs. 33 days in 2020 vs. 2019). In 2020, more patients underwent a two-stage procedure with a diverting stoma as first surgery (6.1%) vs. (4.4%) in 2019 (p = 0.0020) and more patients were treated with preoperative chemotherapy (5.1%) vs. (3,5%) 2019 (p = 0.0016). The proportion of patients that underwent laparoscopic surgery increased from 54% to 58% (p = 0.0017) There were no differences in length of stay, surgical complications, reoperation, ICU-stay or 30-day mortality between the years. CONCLUSION: Based on nationwide annual data, we did not observe adverse effects of the COVID-19 pandemic on colon cancer treatment and short time outcomes in Sweden.

Epidemiologic disparities in colon cancer screening and adherence during the COVID-19 pandemic: a retrospective cohort analysis.

BACKGROUND: Colorectal cancer (CRC) is the second-leading cause of death in the USA. CRC screening remains underutilized, especially in underinsured populations. Screening has been heavily disrupted during the COVID-19 pandemic. PURPOSE: The goal is to explore the impact of the pandemic on ethnic and gender disparities in CRC screening. METHODS: Patients were identified 1 year before and after COVID-19 precautions began, using March 1, 2020, as the inflection point. The primary inclusion criterion was an ordered colonoscopy. The outcome of interest was a colonoscopy performed. Differences by year and race were assessed using chi-square analysis. A cohort of 1549 patients (899 in pre-COVID; 650 in post-COVID) between age 45 and 75 for whom a colonoscopy was ordered was selected from EHR at a large institution. RESULTS: There was a 51% reduction in screening colonoscopies performed. White patients had a decrease of 49%, and African Americans had a 55% reduction. Stool testing increased from 47% prior to the pandemic to 94% during the pandemic representing a greater than 100% increase in stool testing uptake. CONCLUSION: The true impact of COVID-19 on colorectal cancer is yet to be uncovered as future mortality estimates from CRC are ongoing. Due to the widespread closure of endoscopy centers and delay in screening, we believe that the pandemic worsened the screening disparities most prevalent among minority populations. Our study points to the drastic reduction of screening for all races, especially for African Americans.

Impact of the COVID-19 Pandemic on Colorectal Cancer Care in the Netherlands: A Population-based Study.

INTRODUCTION: The COVID-19 pandemic disrupted health care services worldwide. In the Netherlands, the first confirmed COVID-19 infection was on February 27, 2020. We aimed to investigate the impact of the pandemic on colorectal cancer care in the Netherlands. METHODS: Colorectal cancer patients who were diagnosed in 25 hospitals in weeks 2 to 26 of the year 2020 were selected from the Netherlands Cancer Registry (NCR) and divided in 4 periods. The average number of patients treated per type of initial treatment was analyzed by the Mantel-Haenszel test adjusted for age. Median time between diagnosis and treatment and between (neo)adjuvant therapy and surgery were analyzed by the Mann Whitney test. Percentages of (acute) resection, stoma and (neo)adjuvant therapy were compared using the Chi-squared test. RESULTS: In total, 1,653 patients were included. The patient population changed during the COVID-19 pandemic regarding higher stage and more clinical presentation with ileus at time of diagnosis. Slight changes were found regarding type of initial treatment. Median time between diagnosis and treatment decreased on average by 4.5 days during the pandemic. The proportion of colon cancer patients receiving a stoma significantly increased with 6.5% during the pandemic. No differences were found in resection rate and treatment with (neo)adjuvant therapy. CONCLUSION: Despite the disruptive impact of the COVID-19 pandemic on global health care, the impact on colorectal cancer care in the Netherlands was limited.

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest.

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.

Functional assessment of miR­1291 in colon cancer cells.

miR­1291 exerts an anti­tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR­1291 in CRC cells was investigated. It was identified that miR­1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR­1291 induced cell apoptosis. A luciferase reporter assay revealed that miR­1291 directly bound the 3'­untranslated region sequence of doublecortin­like kinase 1 (DCLK1). miR­1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR­1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR­1291 induced CDK inhibitors p21WAF1/CIP1 and p27KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21WAF1/CIP1 and p27KIP1. Intravenous administration of miR­1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD­1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21WAF1/CIP1 and p27KIP1 protein with treatment of miR­1291. Taken together, the results indicated that miR­1291 served an anti­tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR­1291 may be a promising nucleic acid medicine against CRC.

Impact of two waves of Sars-Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals.

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.