Impact of preoperative factors and waiting time on post-appendectomy complications: a retrospective study.

BACKGROUND: Several factors are associated with increased postoperative complications after appendectomies. However, few studies combined these potential factors for comprehensive prediction of surgical outcomes. Whether high-risk patients benefit from a shorter waiting time for surgery remains unclear. This study aimed to explore the impact of surgical waiting time and potential risk factors on postoperative complications. METHODS: A total of 1343 patients diagnosed with acute appendicitis requiring an emergent appendectomy were included from 2013 to 2018. The preoperative risk factors associated with postoperative complications were selected and the probability of postoperative complications was calculated by multivariate logistic regression model. Patients were divided into four groups based on the risk (high & low) and time to surgery (> 12 & ≤12 hours). The odds ratios for complications were evaluated between groups. RESULTS: The selected risk factors included age, neutrophil-lymphocyte ratio, systemic inflammatory response syndrome and abdominal pain duration. Compared with low-risk patients with time to surgery ≤12 hours, high-risk patients with time to surgery > 12 hours had significant increased overall postoperative complication rate (16.85% vs. 8.16%, p = 0.002) and a trend toward increased surgical site infection rate (10.99% vs. 6.46%, p = 0.058). When operated within 12 hours, there was no difference in outcomes between high- and low-risk patients. On the other hand, time to surgery > 12 hours did not increase complication rate in low-risk patients. CONCLUSIONS: The surgical outcome may be affected by preoperative factors and time to surgery. It is suggested that high-risk patients receive appendectomy within 12 hours to avoid increased postoperative complications.

Cognitive Function in Patients at Different Stages of Treatment for Colorectal Cancer: A Comparative Cross-Sectional Study.

OBJECTIVES: To compare subjective and objective cognitive functions among patients at the following three stages of treatment for colorectal cancer (CRC): new diagnosis (Group A), ≤2 years since chemotherapy completion (Group B), and >2 years since chemotherapy completion (Group C). DATA SOURCES: A comparative cross-sectional approach was used in this study. The Functional Assessment of Cancer Therapy-Cognitive Function questionnaire and neuropsychological assessments were used to assess patients' subjective cognitive function, attention, memory, and executive functions. A total of 63 patients with stage I to III CRC were recruited from a medical center in northern Taiwan. We performed one-to-one-to-one propensity score matching to identify 36 individuals as eligible for this study. A generalized estimating equation was used to compare subjective and objective cognitive functions. CONCLUSION: We observed no significant between-group differences in subjective cognitive function and objective performance in overall cognition and memory. Group B had significantly longer reaction time in attention and processing speed than did Group A. Adjuvant chemotherapy had significantly deleterious effects on attention and processing speed in patients with CRC. These cognitive symptoms last for approximately 2 years after the completion of chemotherapy. IMPLICATIONS FOR NURSING PRACTICE: The early detection of cancer-related cognitive impairment is necessary for managing symptom distress. Future studies with a large sample size and longitudinal design may elucidate the trajectory of specific cognitive functions. Developing nursing interventions aimed at improving attention and executive function in patients with CRC are needed.

Resilience process in individuals with colorectal cancer: a qualitative study.

PURPOSE: Resilience is a positive outcome in giving individuals strength to adapt to cancer and have better various aspects of health-related quality of life. However, research focusing on resilience in relation to colorectal cancer (CRC) is limited. Therefore, the aim of this study was to explore the process of resilience in individuals with CRC. METHOD: Sixteen individuals diagnosed with stage Ι to III CRC within the last five years were recruited from a CRC surgical outpatient department in a medical center in Northern Taiwan. Semi-structured interviews were used to explore the resilience process of living with CRC. Recorded interviews were transcribed verbatim and were analyzed using modified grounded theory. FINDINGS: Resilience is a dynamic three-phase process, including impact of CRC, adaptation or maladaptation following CRC, and growth from CRC experience. Resilience strategies (i.e., attitude adjustment, developing personal strategies to conquer CRC and side effects, setting new goals in life, and viewing death as a normal process), avoidance behaviors, and passive waiting strategy were shown across the resilience process. CONCLUSIONS: All individuals showed negative impacts during CRC diagnosis and treatments, but some individuals used the resilience strategies in helping to promote positive adjustment and redirect to develop their resilience process. Furthermore, resilient and maladaptive individuals may change the situation depending on which strategies are used and on the progression of CRC because resilience is dynamic. Oncology clinicians should help individuals use resilience strategies to smoothly go through the resilience process.

Intraoperative Detection of Surgical Gauze Using Deep Convolutional Neural Network.

During laparoscopic surgery, surgical gauze is usually inserted into the body cavity to help achieve hemostasis. Retention of surgical gauze in the body cavity may necessitate reoperation and increase surgical risk. Using deep learning technology, this study aimed to propose a neural network model for gauze detection from the surgical video to record the presence of the gauze. The model was trained by the training group using YOLO (You Only Look Once)v5x6, then applied to the testing group. Positive predicted value (PPV), sensitivity, and mean average precision (mAP) were calculated. Furthermore, a timeline of gauze presence in the video was drawn by the model as well as human annotation to evaluate the accuracy. After the model was well-trained, the PPV, sensitivity, and mAP in the testing group were 0.920, 0.828, and 0.881, respectively. The inference time was 11.3 ms per image. The average accuracy of the model adding a marking and filtering process was 0.899. In conclusion, surgical gauze can be successfully detected using deep learning in the surgical video. Our model provided a fast detection of surgical gauze, allowing further real-time gauze tracing in laparoscopic surgery that may help surgeons recall the location of the missing gauze.

ATMIN enhances invasion by altering PARP1 in MSS colorectal cancer.

Genomic instability is a key cancer indicator. It results from defects in the DNA damage response (DDR) and increased replication stress. Herein, we examined how ataxia-telangiectasia mutated interactor (ATMIN), a DDR pathway involved in mismatch repair-proficient (microsatellite stability [MSS]), acts in colorectal carcinoma (CRC). Firstly, ATMIN mRNA expression was detected in CRC specimens with MSS characteristics, and the effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were gauged in MSS cell lines. To understand the molecular mechanism, co-immunoprecipitation analyses in vitro were employed. Interestingly, ATMIN expression was positively correlated with advanced stages (P < .001), lymph node metastases (P = .002), and deeper invasion (P = .037) in MSS tumors; and significantly changed the cell motility in vitro. In the high-throughput analysis, ATMIN was found to act on the Wnt signaling pathway via PARP1. PAPR1 inhibition, in turn, significantly decreased invasion abilities resulting from ATMIN overexpression in cancer cell. Taken together, ATMIN, which alters the Wnt signaling pathway regulating CRC progression, plays as a crucial prognostic factor in MSS tumors.

Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control study.

BACKGROUND: Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis. METHODS: A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled. RESULTS: 18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients (p < 0.001). Diagnosis tool depends on colonoscopy were much less in PSRCCR group than control group (44.4% vs 93%, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p = 0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4%, p < 0.001) and lymphovascular invasion (77.8 vs 44.4%, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3%, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8%, p < 0.001). CONCLUSION: For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.

A pilot study of metabolomic pathways associated with fatigue in patients with colorectal cancer receiving chemotherapy.

PURPOSE: The aim of this pilot study was to evaluate for differences in metabolomic profiles between fatigued and non-fatigued patients with colorectal cancer (CRC) during chemotherapy (CTX). METHOD: Patients were recruited from the department of surgery in a large medical center in Taiwan. In this longitudinal pilot study, the Fatigue Symptom Inventory and fasting blood samples were collected at three assessments (i.e., prior to surgery (T0), three months (T1) and six months (T2) after surgery). Metabolomic profile analysis was used. Multilevel regression and pathway analyses were performed to identify differences in metabolomic profiles between the fatigued and non-fatigued groups. RESULTS: Of the 49 patients, 55.1% (n = 27) were in the fatigue group. All of the 15 metabolites that had statistically significant group × time interactions in the differential metabolite analysis were entered into the pathway analysis. Two pathways were enriched for these metabolites, namely galactose metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. CONCLUSIONS: The results from this pilot study suggest that pathways involved in galactose metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis are associated with cancer-related fatigue (CRF) in patients with CRC during CTX. These findings are consistent with the hypotheses that alterations in energy metabolism and increases in inflammation are associated with the development and maintenance of CRF.

A Resilience Model for Patients With Colorectal Cancer: A Structural Equation Modeling Analysis.

BACKGROUND: Patients with colorectal cancer (CRC) experience multiple symptoms. Resilience is a positive health outcome that can assist patients to face and adapt to their disease. OBJECTIVE: The purpose of this study was to evaluate a proposed resilience model for patients with CRC. METHODS: Patients (n = 416), who were given a diagnosis of stage Ι to III CRC within the past 5 years, were recruited from 2 medical centers in Northern Taiwan. Symptom Severity Scale, Fatigue Symptom Inventory, and Center for Epidemiological Studies Depression scale were used to assess the risk factors of symptom severity, fatigue, and depressive symptoms, respectively. Cancer Behavior Inventory and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale were used to assess the protective factors of self-efficacy for coping with cancer and spiritual well-being, respectively. Resilience was assessed using the Resilience Scale. Structural equation modeling was used to evaluate the proposed resilience model for patients with CRC. RESULTS: The initial structural equation modeling fit indices did not support the proposed model. In the revised model, depressive symptoms was a partial mediator between protective factors and resilience with an acceptable model fit (comparative fit index, 0.968; root mean square error of approximation, 0.085; standardized root mean square residual, 0.034). CONCLUSIONS: Patients with CRC who had higher levels of protective factors had higher levels of resilience. This study provides new information on the role of depressive symptoms as a partial mediator between protective factors and resilience. IMPLICATIONS FOR PRACTICE: Oncology nurses need to evaluate for depressive symptoms as well as protective factors and resilience in patients with CRC.

Multielectrode Radiofrequency Ablation for Resectable Metachronous Liver Metastasis from Colorectal Cancer.

The outcome of radiofrequency ablation (RFA) for liver metastases from colorectal cancer (CRLM) has been thought to be inferior to metastasectomy. However, the recent development of multielectrode RFA (multi-RFA) systems has made the ablation zone larger and more complete. Thus, we assessed the survival benefits of this modality in cases of metachronous CRLM. This retrospective study assessed patients diagnosed with resectable metachronous CRLM between 2013 and 2016; 132 patients were categorized by treatment for liver metastases: multi-RFA (n = 68), hepatectomy (n = 34), or systemic treatment only (n = 30). Therapeutic effectiveness, outcomes, and intervention-related complications were compared between groups. Median overall survival (OS), recurrence-free survival (RFS), and intrahepatic recurrence-free survival (IHRFS) were 69.8, 85.2, and 59.7 months for the hepatectomy group; 53.4, 41.3, and 32.3 months for the multi-RFA group; and 19.1, 7.1, and 7.1 months for the systemic treatment group. No significant differences were observed between the multi-RFA and hepatectomy groups after a median follow-up of 59.8 months. This study demonstrated that multi-RFA and hepatectomy provide similar survival benefits for patients with resectable CRLM. Multi-RFA may represent a reliable treatment option for the management of resectable liver metastases.

ATMIN Suppresses Metastasis by Altering the WNT-Signaling Pathway via PARP1 in MSI-High Colorectal Cancer.

BACKGROUND: Constant DNA damage occurs in cells, and the cells are programmed to respond constitutively. This study explored the roles of ataxia-telangiectasia mutated interactor (ATMIN), one of the impaired pathways involving the DNA damage response (DDR) in mismatch repair-deficient [microsatellite instability (MSI)-high] colorectal carcinoma (CRC). METHODS: Expression of ATMIN messenger RNA (mRNA) was detected in CRC specimens with microsatellite instability (MSI) characteristics. The effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were evaluated in MSI-high cell lines, and liver metastasis ability was investigated in vivo. Protein-protein interactions were assessed by coimmunoprecipitation analyses in vitro. RESULTS: Decreased ATMIN expression was positively correlated with advanced stage of disease (P < 0.05), lymph node metastases (P < 0.05), and deeper invasion (P < 0.05) in MSI-high tumors. Transient or stable ATMIN knockdown significantly increased cell motility. Moreover, in the high-throughput microarray and gene set enrichment analysis, ATMIN was shown to act on the Wnt-signaling pathway via PARP1. This cascade influences ß-catenin/transcription factor 4 (TCF4) binding affinity in MSI-high tumors, and PARP1 inhibition significantly decreased the number of metastases from ATMIN knockdown cancer cells. CONCLUSIONS: The results not only indicated the critical role of ATMIN, but also shed new light on PARP1 inhibitors, providing a basis for further clinical trials of MSI-high CRC.

CD28 engagement inhibits CD73-mediated regulatory activity of CD8+ T cells.

CD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28-CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.

Recurrence Outcomes Less Favorable in T1 Rectal Cancer than in T1 Colon Cancer.

BACKGROUND: With the implementation of screening programs worldwide, diagnosis of early-stage colorectal cancer steadily increased, including T1 cancer. Current T1 cancer treatment does not differ according to anatomic location. We therefore compared the disease-free survival of T1 cancer arising from the rectum versus the colon. METHODS: The hospital-based study included subjects with T1 cancer at National Taiwan University Hospital from 2005 to 2014. Clinical, colonoscopy, and histopathology were reviewed for patients with a mean follow-up time of 7.1 (0.7-12.9) years. We conducted Kaplan-Meier analysis to compare the risk of recurrence by cancer location and Cox regression analysis to identify risk factors for T1 cancer recurrence. RESULTS: The final cohort included a total of 343 subjects with T1 cancer (mean age, 64.9 ± 11.7 years; 56.1% male), of whom 25 underwent endoscopic resection alone. Of the subjects who underwent surgery, 50 had lymph node metastasis and 268 did not. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer (p = .022). Rectal location and larger neoplasm size were independent risk factors for recurrence, with hazard ratios of 4.84 (95% confidence interval, 1.18-19.92), and 1.32 (95% confidence interval, 1.06-1.65), respectively. The occurrence of advanced histology did not differ between T1 rectal and colon cancers (p = .58). CONCLUSION: T1 cancers arising from the rectum had less favorable recurrence outcomes than those arising from the colon. Further studies are needed to examine whether adjuvant radiotherapy or chemotherapy can reduce the risk of recurrence in T1 rectal cancer. IMPLICATIONS FOR PRACTICE: Current T1 colorectal cancer treatment and surveillance do not differ according to anatomic location. Clinical, colonoscopy, and histopathology were reviewed for 343 patients with T1 cancer with a mean follow-up time of 7.1 years. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer. Moreover, the rectal location was an independent risk factor for recurrence. T1 cancers from the rectum had less favorable recurrence outcomes than those arising from the colon. It is critical to clarify whether adjuvant therapy or more close surveillance can reduce recurrence risk in T1 rectal cancer.

A novel tumor suppressor role of myosin light chain kinase splice variants through downregulation of the TEAD4/CD44 axis.

Myosin light chain kinase (MLCK) regulates actinomyosin contraction. Two splice variants of long MLCK are expressed in epithelial cells and divergently regulate gut barrier functions; reduced MLCK levels in human colorectal cancers (CRC) with unclarified significance have been reported. CRC are solid tumors clonally sustained by stem cells highly expressing CD44 and CD133. The aim was to investigate the role of MLCK splice variants in CRC tumorigenesis. We found lower MLCK1/2 and higher CD44 expression in human CRC, but no change in CD133 or LGR5. Large-scale bioinformatics showed an inverse relationship between MYLK and CD44 in human sample gene datasets. A 3-fold increased tumor burden was observed in MLCK(-/-) mice compared with wild-type (WT) mice in a chemical-induced CRC model. Primary tumorspheres derived from the MLCK(-/-) mice displayed larger sizes and higher CD44 transcript levels than those from the WT mice. Bioinformatics revealed binding of TEAD4 (a transcriptional enhancer factor family member in the Hippo pathway) to CD44 promoter, which was confirmed by luciferase reporter assay. Individually expressing MLCK1 and MLCK2 variants in the MLCK-knockout (KO) Caco-2 cells inhibited the nuclear localization of TEAD4 cofactors, VGLL3 and YAP1, respectively, and both variants reduced the CD44 transcription. Accelerated cell cycle transit was observed in the MLCK-KO cells, whereby expression of MLCK1/2 variants counterbalanced the cell hyperproliferation. In conclusion, MLCK1/2 variants are novel tumor suppressors by downregulating the TEAD4/CD44 axis via reducing nuclear translocation of distinct transcriptional coactivators. The reduction of epithelial MLCKs, especially isoform 2, may drive cancer stemness and tumorigenesis.

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

BACKGROUND: CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied. METHODS: We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC. RESULTS: Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m2) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m2 was significantly associated with CIMP-high CRC in younger patients. CONCLUSIONS: We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m2 and CIMP-high CRC in patients younger than 50 years.

Downstaged ypT0-2N0 rectal cancer after neoadjuvant chemoradiation therapy may not need adjuvant chemotherapy: a retrospective cohort study.

PURPOSE: Current guidelines suggest that adjuvant chemotherapy (AC) be administered to all locally advanced (clinically T3-4 or N-positivity) rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT) and radical surgical resection regardless of the final pathological staging (yp staging). This study aimed to evaluate the necessity of AC for ypT0-2N0 rectal cancer. METHODS: Patients with ypT0-2N0 rectal cancer, who received nCRT and radical surgical resection, were recruited retrospectively at a university hospital. The main outcome was to evaluate the 5-year overall survival (OS) and disease-free survival (DFS) between ypT0-2N0 rectal cancer patients with AC and those without AC. We also identified potential independent prognostic factors associated with poor outcomes. RESULTS: One hundred and ten ypT0-2N0 rectal cancer patients (ypT0: n = 6; ypT1: n = 44; ypT2: n = 60) were followed up for a median of 60 months. No significant difference was observed in DFS and 5-year OS between patients with AC and those without AC. The risk of recurrence was associated with the postoperative pathological staging (0% with ypT0, 2.4% with ypT1, and 10% with ypT2). In the multivariate analysis, retrieval of < 12 lymph nodes was an independent favorable prognostic factor, which correlated with a higher OS (HR: 2.263; 95% CI: 1.093-4.687, P = 0.028). Intra-tumor lymphovascular and perineural invasion were poor prognostic markers for shorter DFS (HR: 5.940; 95% CI: 1.150-30.696, P = 0.033). CONCLUSION: Postoperative AC is not required for patients with ypT0-2N0 rectal cancer downstaged by nCRT, especially in those without poor prognostic factors.

Trifluridine/tipiracil in combination with local therapy may be a favorable option for refractory metastatic colorectal cancer patients: A case report.

RATIONALE: Currently, the 5-year survival rate remains poor for patients with metastatic colorectal cancer (mCRC), and the purpose of therapy is to prolong survival while maintaining the quality of life. Trifluridine/tipiracil, an oral drug combining trifluorothymidine and a thymidine phosphorylase inhibitor, is indicated as salvage therapy for mCRC patients who have progressed after all available regimens. Combination of local treatments with systemic therapy such as trifluridine/tipiracil represents an apt management strategy for mCRC patients. PATIENT CONCERNS: A 72-year-old man diagnosed with stage IV rectal adenocarcinoma (KRAS mutation) with peritoneal carcinomatosis and liver metastases developed resistance to 2 lines of treatment (bevacizumab/irinotecan/S-1 and bevacizumab/oxaliplatin/HDFL [high-dose 24-hour infusion of 5-fluorouracil and leucovorin regimen]) within 5 months. DIAGNOSIS: Refractory stage IV rectal adenocarcinoma. INTERVENTIONS: Systemic treatment of trifluridine/tipiracil has been given for approximately 15 months in addition to radiotherapy, Yttrium-90 radioembolization, and trans-arterial chemoembolization for peritoneal and liver metastases. OUTCOMES: After 15 months, the patient was still taking trifluridine/tipiracil for disease control with a good quality of life. LESSONS: Trifluridine/tipiracil plus other appropriate local therapy may significantly prolong patients survival with a satisfactory quality of life for patients with refractory mCRC. The favorable safety profile of trifluridine/tipiracil renders it a suitable option to be combined with other local therapies for metastatic lesions.

Glucose Metabolites Exert Opposing Roles in Tumor Chemoresistance.

Reprogrammed glucose metabolism and increased glycolysis have been implicated in tumor chemoresistance. The aim was to investigate the distinct roles of the glucose metabolites pyruvate and ATP in chemoresistance mechanisms, including cell death and proliferation. Our data showed higher glucose transporters in colorectal cancer (CRC) from non-responsive patients than those responsive to chemotherapy. Human CRC cell lines exposed to 5-fluorouracil (5-FU) displayed elevated cell viability and larger tumors in xenograft mouse models if cultured in high-glucose medium. Glucose conferred resistance to 5-FU-induced necroptosis via pyruvate scavenging of mitochondrial free radicals, whereas ATP replenishment had no effect on cell death. Glucose attenuated the 5-FU-induced G0/G1 shift but not the S phase arrest. Opposing effects were observed by glucose metabolites; ATP increased while pyruvate decreased the G0/G1 shift. Lastly, 5-FU-induced tumor spheroid destruction was prevented by glucose and pyruvate, but not by ATP. Our finding argues against ATP as the main effector for glucose-mediated chemoresistance and supports a key role of glycolytic pyruvate as an antioxidant for dual modes of action: necroptosis reduction and a cell cycle shift to a quiescent state.

Using serum placenta growth factor could improve the sensitivity of colorectal cancer screening in fecal occult blood negative population: A multicenter with independent cohort validation study.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease-related mortality; however, its sensitivity and compliance are unsatisfactory. METHODS: This study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result. RESULTS: Serum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable. CONCLUSION: Serum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool-based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening.

Three Nurse-administered Protocols Reduce Nutritional Decline and Frailty in Older Gastrointestinal Surgery Patients: A Cluster Randomized Trial.

OBJECTIVE: To evaluate the effects of the modified Hospital Elder Life Program (mHELP) comprising 3 nurse-administered protocols in older patients undergoing gastrointestinal (GI) surgery. DESIGN: Cluster randomized trial. SETTING: Two 36-bed GI wards at a university-affiliated medical center in Taiwan. PARTICIPANTS: Older patients (≥65 years, N = 377) were recruited if they were scheduled for elective GI surgery with an expected length of hospital stay >6 days. After transferring to the GI ward after surgery, participants were randomly assigned to the mHELP or control group (1:1) by room rather than individually because most patient units are double- or triple-occupancy rooms. INTERVENTION: The mHELP protocols (early mobilization, oral and nutritional assistance, and orienting communication) were administered daily with usual care by a trained nurse until hospital discharge. The control group received usual care only. MEASURES: Outcomes were in-hospital nutritional decline, measured by body weight and Mini-Nutritional Assessment (MNA) scores, and Fried's frailty phenotype. Return of GI motility was examined as a potential mechanism contributing to observed outcomes. RESULTS: Participants (mean age = 74.5 years; 56.8% male) primarily underwent colorectal (56.5%), gastric (21.2%), and pancreatobiliary (13.8%) surgery. Participants who received the mHELP [for a median of 7 days (interquartile range = 6-10 days)] had significantly lower in-hospital weight loss and decline in MNA scores (weight -2.1 vs -4.0 lb, P = .002; score -3.2 vs -4.0, P = .03) than the control group. The mHELP group also had significantly lower rates of incident frailty during hospitalization (12.0% vs 21.7%, P = .022), and persistent frailty (50.0% vs 92.9%, P = .03). Participants in the mHELP group had trends toward an accelerated return of GI motility. CONCLUSION AND IMPLICATIONS: The mHELP effectively reduced nutritional decline, prevented new frailty, and promoted recovery of frailty present before admission. These nurse-administered protocols might be useful in other settings, including conditions managed at home or in nursing facilities.