Search

Purpose: Although minimally invasive colorectal surgery has been proven to have a shorter hospital stay and fewer short-term complications than open surgery, the advantages of laparoscopic surgery for colorectal cancer patients undergoing hemodialysis have not been validated. This study compared the outcomes of open and laparoscopic approaches in these patients. Materials and methods: Between January 2007 and December 2020, we retrospectively analyzed the clinical data of 78 hemodialysis patients who underwent curative-intent, elective colorectal surgery. Patients were divided into two groups according to the surgical method: open and laparoscopic. Results: Postoperative morbidity (p = 0.480) and mortality (p = 0.598) rates and length of hospital stay (28.8 vs. 27.5 days, p = 0.830) were similar between the groups. However, laparoscopic surgery patients had a shorter return to clear liquid, full liquid, or soft food time than open surgery patients (p < 0.001, p = 0.007, and p = 0.002, respectively). Disease-free survival and long-term cancer-specific survival rates were also similar between the two groups (p = 0.353 and p = 0.201, respectively). Multivariate analysis revealed that intraoperative blood transfusion was a risk factor for severe complications and mortality (OR 6.055; p = 0.046), and the odds ratio (OR) of laparoscopic surgery was not significantly greater than that of open surgery (OR = 0.537, p = 0.337). Conclusion: Although laparoscopic surgery did not result in hemodialysis patients having a shorter postoperative hospital stay, our results suggest that the laparoscopic approach is as safe as open surgery for hemodialysis patients and may be beneficial for shortening the return time to food intake. [ABSTRACT FROM AUTHOR]

Studies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis. Data from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan–Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery. The 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors. This study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors. [ABSTRACT FROM AUTHOR]

Purpose: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. Results: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57–0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7–1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54–0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23–10.10; p = 0.02). Conclusions: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted therapy and chemotherapy are the mainstays of treatment to improve the survival of patients with metastatic colorectal cancer (mCRC). When RAS and BRAF genes are normal, a molecular target treatment with an anti-EGFR antagonist is prescribed. Anti-EGFR antagonists induce skin responses in 50–70% of patients. There is an ongoing debate about whether the severe skin reactions brought on by anti-EGFR antagonists are associated with overall survival (OS) and progression-free survival (PFS). mCRC patients who received anti-EGFR therapy between October 2017 and October 2018 were retrospectively evaluated. Treatment with an anti-EGFR medication in the first-line setting was significantly associated with OS and PFS. In grades 1 and 2, there was no difference in the incidence of acne between males and females, although in grades 3 and 4, males were at a higher risk than females. In this study, skin toxicity did not predict the effectiveness of the anti-EGFR medication. The primary treatment for metastatic colorectal cancer (mCRC) consists of targeted therapy and chemotherapy to improve survival. A molecular target drug with an anti-epidermal growth factor receptor (EGFR) antagonist is recommended when the RAS and BRAF genes are normal. About 50–70% of patients using anti-EGFR antagonists will experience skin reactions. Some studies have shown that severe skin reactions caused by anti-EGFR antagonists may be linked to overall survival (OS) and progression-free survival (PFS), but the results are still uncertain. These data of mCRC patients who underwent anti-EGFR therapy between October 2017 and October 2018 were analyzed retrospectively. A total of 111 patients were included in this study. The survival results showed that gender, age, body mass index, primary tumor site, and recurrence did not significantly affect OS and PFS. However, the first-line anti-EGFR inhibitor treatment was significantly associated with OS (p < 0.001) and PFS (p < 0.001). There was no significant difference in the incidence of acne between males and females in grades 1 and 2, while males have a greater risk in grades 3 and 4 than females (20.3 vs. 4.8%; p-value = 0.041). Skin toxicity was not a predictor of anti-EGFR treatment response in this investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammatory reactions may lead to systemic inflammation and cancer growth. Some inflammatory indicators are effective predictors of colorectal cancer in ordinary clinical practice. The objective of this study is to evaluate the utility of a novel cancer-inflammation prognostic index (CIPI) marker derived from multiplying carcinoembryonic antigen by the neutrophil-to-lymphocyte ratio value obtained for non-metastatic colorectal cancer. Patients who underwent radical resection for stage I to stage III primary colorectal cancer between January 1995 and December 2018 were included in this study for further investigation. The group with a high CIPI had considerably lower relapse-free survival and overall survival rates, as well as a greater incidence of recurrence. Both univariate and multivariate analyses found that a high CIPI was an independent prognostic factor for survival analysis. This research is the first to demonstrate that CIPI is an independent factor that can be used to predict the outcome of colorectal cancer. Inflammatory reactions play a crucial role in cancer progression and may contribute to systemic inflammation. In routine clinical practice, some inflammatory biomarkers can be utilized as valuable predictors for colorectal cancer (CRC). This study aims to determine the usefulness of a novel cancer-inflammation prognostic index (CIPI) marker derived from calculating carcinoembryonic antigen (CEA) multiplied by the neutrophil-to-lymphocyte ratio (NLR) values established for non-metastatic CRCs. Between January 1995 and December 2018, 12,092 patients were diagnosed with stage I to III primary CRC and had radical resection—they were all included in this study for further investigation. There were 5996 (49.6%) patients in the low-CIPI group and 6096 (50.4%) patients in the high-CIPI group according to the cutoff value of 8. For long-term outcomes, the high-CIPI group had a significantly higher incidence of recurrence (30.6% vs. 16.0%, p < 0.001) and worse relapse-free survival (RFS) and overall survival (OS) rates (p < 0.001). High CIPI was an independent prognostic factor for RFS and OS in univariate and multivariate analyses. This research is the first to document the independent significance of CIPI as a prognostic factor for CRC. To ensure that it works, this CIPI needs to be tested on more CRC prediction models. [ABSTRACT FROM AUTHOR]

AIM: The ERAS protocol consists of multiple items that aim to improve the outcomes of patients receiving surgery. Adhering to the protocol is difficult. We wondered whether surgeons practicing the ERAS protocol in a group would improve patient outcomes. Methods: All patients who underwent colorectal resection for benign disease or malignancy from November 2017 to December 2018 were collected and reviewed retrospectively. According to the physician's ward round strategy, the patients were categorized into two groups, either by solo practice or group practice. Results: This study enrolled 724 patients and divided them into two groups according to the practice method: group practice (n = 256) and solo practice (n = 468). The group practice cohort had less postoperative morbidity (14.0% vs. 21.4%, p = 0.048) and shorter postoperative hospital stays (mean: 6.6 ± 3.2 vs. 8.6 ± 5.5, p < 0.05) than the solo practice cohort. Group practice (p < 0.001), natural orifice specimen extraction (NOSE) procedure (p < 0.001), and blood loss >50 mL (p = 0.039) significantly affected discharge within 5 days postoperatively in multivariate analyses. Conclusions: Group practice based on a modified ERAS protocol shortens postoperative hospital stays with fewer morbidities compared with solo practice in which patients receive elective minimally invasive colorectal surgery. [ABSTRACT FROM AUTHOR]

Purpose: Molecular composition of circulating small extracellular vesicles (EVs) does not merely reflect the cells of origin, but also is enriched in specific biomolecules directly associated with the cellular transformation. However, while most of the currently identified EV-miRs are only geared towards one-dimensional disease detection, their application for long-term tracking and treatment response monitoring has been largely elusive. Methods: We established and optimized a rapid, sensitive and robust liquid biopsy sampling method, and further used small RNA sequencing to comprehensively catalogue EV-miRomes in association with the progression and outcome of metastatic colorectal cancer (mCRC). Results: By cross-comparison of EV-miRomes (n = 290) from multi-stage and longitudinal cohorts, we uncovered a 15-EV-miR signature with dual detection and long-term monitoring of tumor size progression for mCRC. From this panel, EV-miR-320c was uncovered as a strong clinical marker – aside from its diagnostic power and a therapeutic monitoring performance superior to carcinoembryonic antigen (CEA), its high expression has also been linked to lower overall survival and a greater likelihood of disease recurrence. Further, integrative analyses of tissue transcriptomic and liquid biopsy implicated this 15-EV-miR signature in programming the mesenchymal–epithelial transition (MET) for distant localization of the metastasized cells and also in creating a tumor-favoring metastatic niche. Conclusion: Our clinically-oriented delineation of the mCRC-associated circulating EV-miRomes systematically revealed the functional significance of these liquid biopsy markers and further strengthen their translational potential in mCRC therapeutic monitoring. [ABSTRACT FROM AUTHOR]

Background: Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes. Methods: We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN−) group and another 980 in the LN-positive (LN+) group. Results: LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN− group. LN− patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN− group (LN− vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN− vs. LN+ 19.5% vs. 24.3%; p = 0.890). Conclusions: Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN− patients. LN+ patients had poorer long-term outcomes compared with that in LN− patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN− patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Impaired kidney function is associated with different diseases. However, its impact on colorectal cancer has not been clarified. In order to understand the effect of preoperative kidney function on the outcome of patients with cancer, we analyzed colorectal cancer patients with localized or regional diseases.Materials and Methods: In total, 3731 stage I to III colorectal cancer (CRC) patients were analyzed in Chang Gung Memorial Hospital. Modification of Diet in Renal Disease (MDRD) formula was used for estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) analysis for kidney function cut-off value; Chi-square method, independent t test, or analysis of variance (ANOVA) method for clinicopathological factors; Kaplan-Meier method for disease-free survival (DFS); Cox proportional hazard model for multivariate analysis.Results: Among colon cancer patients, low eGFR (MDRD <70) was associated with more male patients, T2 stage, patients without adjuvant chemotherapy, and patients with elevated creatinine level. Low eGFR is a significant risk factor only for stage III colon cancer (hazard ratio 1.70, 95% CI: 1.28-2.26; P < 0.001). Furthermore, postoperative adjuvant chemotherapy did not significantly increase 5-year DFS for both high and low eGFR groups in stage II patients (5 yrs DFS, 94.8% vs. 84.1%, P = 0.098 for high eGFR subgroup; and 75.0% vs. 75.8%, P = 0.379 for low eGFR subgroup). However, significant improvement of 5-yrs DFS after chemotherapy was found in low eGFR stage III colon cancer patients (64.7% vs. 39.4%, P < 0.001 for low eGFR subgroup). In contrast, no significant DFS difference was caused by chemotherapy for high eGFR stage III subgroup (70.5% vs. 63.9%, P = 0.110).Conclusions: Although low eGFR is an independent risk factor for stage III colon cancer. However, the adjuvant chemotherapy impacts on stage III colon cancer patients differently according to eGFR status. [ABSTRACT FROM AUTHOR]

Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB) “smart coating” to capture viable circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs. [ABSTRACT FROM AUTHOR]

Simple Summary: As the effect of laparoscopic surgery on elderly patients with colorectal cancer (CRC) remains unclear, this propensity score–weighted cohort study revealed that laparoscopic surgery is a favorable method for elderly patients with CRC than open surgery in terms of less pulmonary-related postoperative morbidity and mortality, less hospital stay and similar oncological outcomes. Advanced age is a risk factor for major abdominal surgery due to a decline in physical function and increased comorbidities. Although laparoscopic surgery provides good results in most patients with colorectal cancer (CRC), its effect on elderly patients remains unclear. This study aimed to compare the short- and long-term outcomes between open and laparoscopic surgeries in elderly patients with CRC. Total 1350 patients aged ≥75 years who underwent curative resection for stage I–III primary CRC were enrolled retrospectively and were divided into open surgery (846 patients) and laparoscopy (504 patients) groups. After propensity score weighting to balance an uneven distribution, a competing risk analysis was used to analyze the short-term and long-term outcomes. Postoperative mortality rates were lower in the laparoscopy group, especially due to pulmonary complications. Postoperative hospital stay was significantly shorter in the laparoscopy group than in the open surgery group. Overall survival, disease-free survival, and competing risk analysis showed no significant differences between the two groups. Laparoscopic surgery for elderly patients with CRC significantly decreased pulmonary-related postoperative morbidity and mortality in this large cohort study. Laparoscopic surgery is a favorable method for elderly patients with CRC than open surgery in terms of less hospital stay and similar oncological outcomes. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the leading causes of cancer-related death worldwide. The early diagnosis of colon cancer not only reduces mortality but also reduces the burden related to the treatment strategies such as chemotherapy and/or radiotherapy. However, when the microscopic examination of the suspected colon tissue sample is carried out, it becomes a tedious and time-consuming job for the pathologists to find the abnormality in the tissue. In addition, there may be interobserver variability that might lead to conflict in the final diagnosis. As a result, there is a crucial need of developing an intelligent automated method that can learn from the patterns themselves and assist the pathologist in making a faster, accurate, and consistent decision for determining the normal and abnormal region in the colorectal tissues. Moreover, the intelligent method should be able to localize the abnormal region in the whole slide image (WSI), which will make it easier for the pathologists to focus on only the region of interest making the task of tissue examination faster and lesser time-consuming. As a result, artificial intelligence (AI)-based classification and localization models are proposed for determining and localizing the abnormal regions in WSI. The proposed models achieved F-score of 0.97, area under curve (AUC) 0.97 with pretrained Inception-v3 model, and F-score of 0.99 and AUC 0.99 with customized Inception-ResNet-v2 Type 5 (IR-v2 Type 5) model. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) screening by immuno-fecal occult blood tests (iFOBTs) begins at age 50 in average-risk persons. However, the incidence of early-onset CRC has risen; of the cases, at least half are sporadic CRC without a family history. The authors of this study found a high percentage of de novo germline mutation in young sporadic CRC patients, as well as in sporadic colorectal polyp and control groups. All the mutated genes contribute to various DNA-repair pathways, hinting that a loss of genomic integrity play a crucial role in the development of CRC. The early identification of cancer-susceptible individuals by multigene panels in younger individuals who may be missed under current iFOBT screening could contribute to preventing CRC. Given recent increases in the proportion of early-onset colorectal cancer (CRC), researchers are urgently working to establish a multi-gene screening test for both inherited and sporadic cancer-susceptible individuals. However, the incidence and spectrum of germline mutations in young sporadic CRC patients in East Asian countries and, especially, in sporadic polyp carriers and normal individuals are unknown. Peripheral blood samples were collected from 43 colonoscopy-proved normal controls and from 50 polyp patients and 49 CRC patients with no self-reported family history of cancer. All participants were under 50 years old. Next-generation sequencing with a panel of 30 CRC-associated susceptibility genes was employed to detect pathogenic germline mutations. The germline mutation carrier rates were 2.3%, 4.0%, and 12.2% in the normal, polyp, and cancer groups, respectively. A total of seven different mutations in six DNA repair pathway-related genes (MLH1, BRCA1, BRCA2, CHEK2, BLM, and NTHL1) were detected in nine participants. One frameshift mutation in BRCA2 and one frameshift mutation in the CHEK2 gene were found in a normal control and two colorectal polyp patients, respectively. One young sporadic CRC patient carried two heterozygous mutations, one in MLH1 and one in BRCA1. Three mutations (MLH1 p.Arg265Cys, MLH1 p.Tyr343Ter and CHEK2 p.Ile158TyrfsTer10) were each found in two independent patients and were considered "founder" mutations. This is the first report to demonstrate high percentage of germline mutations in young sporadic colorectal polyp, CRC, and general populations. A multi-gene screening test is warranted for the proactive identification of cancer-predisposed individuals. [ABSTRACT FROM AUTHOR]

Background: Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection. Methods: Twenty-one variants in five CRC-associated genes were selected for the sDNA panel. Cell line DNA and matched mutation-confirmed tissue and stool samples from 34 patients were used for accuracy assessment (cohort 1). The clinical performance of the sDNA assay was further evaluated in 101 independent FIT-positive stool samples (cohort 2). Results: In cohort 1, we obtained a 62% mutation concordance rate in paired tissue and stool samples of the CRC group, regardless of the FIT status. In cohort 2, 100% specificity in normal controls with positive FIT results was observed. By weighting the FIT value and the presence of a given variant type in stool and then summing the two scores, we found that a one-increment increase in the score was associated with a 4.538-fold risk (95% CI = 2.121–9.309) for malignancy in the FIT-positive setting. Conclusions: Our highly specific sDNA assay can help prioritize the most at-risk FIT-positive persons to receive prompt colonoscopic confirmation of CRC. [ABSTRACT FROM AUTHOR]