Association between sidedness and survival among chemotherapy refractory metastatic colorectal cancer patients treated with trifluridine/tipiracil or regorafenib.

BACKGROUND: The impact of sidedness on survival of later-line treatment in patients with metastatic colorectal cancer (mCRC) is undetermined. This study aimed to investigate the association between sidedness and survival among chemotherapy refractory patients with mCRC treated with trifluridine/tipiracil (TAS-102) or regorafenib or both. PATIENTS AND METHODS: Patients with mCRC treated with TAS-102 or regorafenib between 2015 and 2020 was retrospectively collected. Patients were stratified into TAS-102 first and regorafenib first, then subdivided into TAS-102 followed by regorafenib (T-R) and regorafenib followed by TAS-102 (R-T) groups. The oncologic outcomes were presented with time-to-treatment failure (TTF) and overall survival (OS). RESULTS: After matching, 376 TAS-102 patients and 376 regorafenib patients were included for outcomes comparison. TTF had insignificant differences while OS was significantly different between TAS-102 and regorafenib groups. Median TTF and OS were 1.9 months versus 2.0 months (P = .701) and 9.1 months versus 7.0 months (P = .008) in TAS-102 and regorafenib, respectively. The OS benefits were consistent regardless primary tumor location. Subgroup analysis with 174 T-R patients and 174 R-T patients was investigated for treatment sequences. TTF and OS had significant differences in both groups. Median TTF and OS were 8.5 months versus 6.3 months (P = .001) and 14.4 months versus 12.6 months (P = .035) in T-R and R-T groups, respectively. The TTF and OS benefits were persisted regardless primary tumor location. CONCLUSION: TAS-102 first provided a better survival benefit in chemotherapy refractory patients with mCRC across all sidedness. Further prospective studies are warranted to validate our conclusions.

Fecal Incontinence and Quality of Life in Adults With Rectal Cancer After Lower Anterior Resection.

PURPOSE: The purpose of this study was to explore the prevalence of fecal incontinence (FI) and its impact on health-related quality of life in rectal cancer patients following low anterior resection surgery for colorectal cancer. DESIGN: Descriptive, cross-sectional study. SUBJECTS AND SETTING: Patients who were diagnosed with rectal cancer and underwent low anterior resection were recruited from a 1264-bed hospital in southern Taiwan. Potential participants were mailed a questionnaire survey. They were followed up 8 to 16 months postoperatively. Some clinical data were collected via retrospective review of their medical records. METHODS: Questionnaires were mailed to 172 patients, and 71 with colorectal cancer underwent low anterior resection and agreed to participate and completed questionnaires in the research, reflecting a return rate of 41%. Data were collected on demographic characteristics and disease-related variables. Participants were asked if they had experienced FI during the past week. Fecal incontinence health-related quality of life was measured using the Cleveland Clinic Incontinence Score (CCIS) and the Fecal Incontinence Quality of Life Index. Completion of the questionnaire required approximately 15 minutes. RESULTS: More than half of the 71 participants (n = 45; 63.4%) experienced incontinence of flatus, 42.3% (n = 30) reported incontinence of liquid stool, and 14.1% (n = 10) stated that they experienced incontinence of solid stool. Based on mean CCIS scores, 35.2% (n = 25) experienced moderate to severe FI. One-third wore pads to contain FI and 21.1% changed daily activities because of FI. Nearly two-thirds reported FI during the week prior to completing the research questionnaire. The average Fecal Incontinence Quality of Life Index cumulative score was significantly lower in the FI group (2.62 ± 0.61) than in the without-FI group (3.32 ± 0.77; P < .001), as were all subscale mean scores (all P < .01-.001). CONCLUSIONS: Fecal incontinence is prevalent among persons undergoing low anterior resection for colorectal cancer. Persons with FI report poor health-related quality of life compared to persons who retained fecal continence. Health care providers should assess these patients for FI and treat or refer those who experience this common problem.

Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored. METHODS: To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study. RESULTS: Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro. CONCLUSIONS: Dwelling time had a significant effect on the occurrence of EMT on MCs.

Impact on inadequate lymph node harvest on survival in T4N0 colorectal cancer: A would-be medical center experience in Taiwan.

Insufficient lymph node harvest (< 12) may lead to incorrect classification of stage I and II disease. Many studies have indicated a poor prognosis with inadequate lymph node harvest in stages I to III, but few studies have demonstrated the relationship between low lymph node harvest and T4 disease. This study aimed to identify the influence of insufficient number of lymph nodes harvested on survival in T4N0 colorectal cancer. We enrolled patients with T4N0 colorectal cancer who underwent radical resection between 2010 and 2016. A total of 155 patients were divided into 2 groups; 142 patients had ≥ 12 harvested lymph nodes, and the other 13 had < 12 lymph nodes. All patients were followed up for at least 5 years. The primary outcome was the impact of the number of lymph nodes harvested on disease-free survival and overall survival, which were investigated using Kaplan-Meier survival techniques. There were no significant differences in recurrence rate, emergent or elective surgery, laparoscopic or open surgery, or chemotherapy between the 2 groups. Kaplan-Meier analyses showed no statistical differences in 5-year disease-free survival (P = .886) and 5-year overall survival (P = .832) between the groups. There were no significant differences in disease-free survival and overall survival between patients with adequate (≥ 12) and inadequate (< 12) lymph node harvest in T4N0 colorectal cancers.

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

The impact of a multispecialty operative team on colorectal cancer surgery: A retrospective study from a would-be medical center in Taiwan.

Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015. The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients. A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups. A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15). The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.

An Observational Study of Trifluridine/Tipiracil-Containing Regimen Versus Regorafenib-Containing Regimen in Patients With Metastatic Colorectal Cancer.

Background: There are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC. Material and method: Patients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Results: A total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months (P = 0.006) and 9.2 versus 6.8 months (P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% (P < 0.001) and 72% versus 43% (P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival. Conclusions: Our results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results.

High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT.

For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.

Utility of RGNEF in the Prediction of Clinical Prognosis in Patients with Rectal Cancer Receiving Preoperative Concurrent Chemoradiotherapy.

Rectal cancer is a heterogeneous malignancy with different clinical responses to preoperative concurrent chemoradiotherapy (CCRT). To discover the significant genes associated with CCRT response, we performed data mining of a transcriptomic dataset (GSE35452), including 46 rectal cancer patients who received preoperative CCRT and underwent standardized curative resection. We identified ARHGEF28 as the most significantly upregulated gene correlated with resistance to CCRT among the genes related to Rho guanyl-nucleotide exchange factor activity (GO:0005085). We enrolled 172 patients with rectal cancer receiving CCRT with radical surgery. The expression of ARHGEF28 encoded protein, Rho guanine nucleotide exchange factor (RGNEF), was assessed using immunohistochemistry. The results showed that upregulated RGNEF immunoexpression was considerably correlated with poor response to CCRT (p = 0.018), pre-CCRT positive nodal status (p = 0.004), and vascular invasion (p < 0.001). Furthermore, high RGNEF expression was significantly associated with worse local recurrence-free survival (p < 0.0001), metastasis-free survival (MeFS) (p = 0.0029), and disease-specific survival (DSS) (p < 0.0001). The multivariate analysis demonstrated that RGNEF immunoexpression status was an independent predictor of DSS (p < 0.001) and MeFS (p < 0.001). Using Gene Ontology enrichment analysis, we discovered that ARHGEF28 overexpression might be linked to Wnt/ß-catenin signaling in rectal cancer progression. In conclusion, high RGNEF expression was related to unfavorable pathological characteristics and independently predicted worse clinical prognosis in patients with rectal cancer undergoing CCRT, suggesting its role in risk stratification and clinical decision making.

Overexpression of MLPH in Rectal Cancer Patients Correlates with a Poorer Response to Preoperative Chemoradiotherapy and Reduced Patient Survival.

Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

Haemorrhoidectomy: prevalence and risk factors of urine retention among post recipients.

AIMS AND OBJECTIVES: The purpose of this study was to explore the prevalence and risk factors of urine retention among posthaemorrhoidectomy recipients. BACKGROUND. Haemorrhoids are one of the most common functional disorders of the anus. The Haemorrhoidectomy surgical procedure is one of the primary treatments for more severe haemorrhoidal occurrences, such as for third- and/or fourth-degree haemorrhoid conditions. Urine retention is a common acute complication after operation, but rare study conducted by nurses in Taiwan to explore the prevalence and risk factors. DESIGN: A retrospective chart review was conducted. METHODS: Data from a prospectively maintained database on patients who had undergone haemorrhoidectomy between April 2004 - August 2008 were retrospectively analysed. A total of 469 charts were used in this analysis. The following outcomes were studied: patient profiles, haemorrhoid type and severity, anaesthesia methods, length of operating room stay, urine retention and management, intravenous fluid given during operation and length of stay. Results. The overall urinary retention rate was 32.8% (n = 153). Significant risk factors associated with postoperative urinary retention included severity of haemorrhoid and anaesthesia methods. Logistic regression analysis revealed that epidural anaesthesia (p = 0.008), spinal anaesthesia (p = 0.016) and haemorrhoids with a severity of three degrees or higher (p = 0.017) were predictors of urinary retention post haemorrhoidectomy. CONCLUSIONS: Acute urinary retention can have an adverse effect on a patient's quality of care. Careful follow-up of patients with these risk factors can help nurses spot posthaemorrhoidectomy urinary retention early. RELEVANCE TO CLINICAL PRACTICE: The prevalence of acute urinary retention post haemorrhoidectomy is common. Surgical ward nurses should therefore take the responsibility regarding the impact of urinary retention and seeking appropriate nursing interventions of induced urination.

Delayed ischemic gangrene change of distal limb despite optimal decompressed colostomy constructed in obstructed sigmoid colon cancer: a case report.

Creating blow-hole colostomy for decompression could provide a time-saving and efficient surgical procedure for a severely debilitated case with a completely obstructed colorectal cancer. Complications are reported as prolapse, retraction, and paracolostomal abscess. However, complication with an ischemic distal limb has not been reported. We report a case of critical intra-abdominal disease after decompressed colostomy for relieving malignant sigmoid colon obstruction; a potential fatal condition should be alerted. A 76-year-old male visited our emergency department for symptoms related to obstructed sigmoid colon tumor with foul-odor vomitus containing fecal-like materials. An emergent blow-hole colostomy proximal to an obstructed sigmoid lesion was created, and resolution of complete colon obstruction was pursued. Unfortunately, extensive abdominal painful distention with board-like abdomen and sudden onset of high fever with leukocytopenia developed subsequently. Such surgical abdomen rendered a secondary laparotomy with resection of the sigmoid tumor along with an ischemic colon segment located proximally up to the previously created colostomy. Eventually, the patient had an uneventful postoperative hospital stay. In the present article, we have described an emergent condition of sudden onset of distal limb ischemia after blow-hole colostomy and concluded that despite the decompressed colostomy would resolve acute malignant colon obstruction efficiently; impending ischemic bowel may progress with a possible irreversible peritonitis. Any patient, who undergoes a decompressed colostomy without resection of the obstructed lesion, should be monitored with leukocyte count and abdominal condition survey frequently.

Vitamin D can ameliorate chlorhexidine gluconate-induced peritoneal fibrosis and functional deterioration through the inhibition of epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients' peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition. METHODS: Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1α,25(OH)2D3 treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-ß1 (TGF-ß1) in the absence or presence of 1α,25(OH)2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined. RESULTS: 1α,25(OH)2D3 ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of α-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH)2D3 also ameliorated TGF-ß1-induced decrease in E-cadherin expression, increase in Snai1 and α-SMA expression, intracellular F-actin redistribution, and migration activity in vitro. CONCLUSION: 1α,25(OH)2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.

Incidence trends and predictors for cost and average lengths of stay in colorectal cancer surgery.

AIM: To evaluate the changing trends and outcomes of colorectal cancer (CRC) surgery performed at a large single institution in Taiwan. METHODS: This study retrospectively analyzed 778 patients who received colorectal cancer surgery at E-Da Hospital in Taiwan from 2004 to 2009. These patients were from health examination, inpatient or emergency settings. The following attributes were analyzed in patients who had undergone CRC surgical procedures: gender, age, source, surgical type, tumor number, tumor size, number of lymph node metastasis, pathologic differentiation, chemotherapy, distant metastases, tumor site, tumor stage, average hospitalization cost and average lengths of stay (ALOS). The odds ratio and 95% confidence intervals were calculated to assess the relative rate of change. Regression models were employed to predict average hospitalization cost and ALOS. RESULTS: The study sample included 458 (58.87%) males and 320 (41.13%) females with a mean age of 64.53 years (standard deviation, 12.33 years; range, 28-86 years). The principal patient source came from inpatient and emergency room (96.02%). The principal tumor sites were noted at the sigmoid colon (35.73%) and rectum (30.46%). Most patients exhibited a tumor stage of 2 (37.28%) or 3 (34.19%). The number of new CRC surgeries performed per 100000 persons was 12.21 in 2004 and gradually increased to 17.89 in 2009, representing a change of 46.52%. During the same period, the average hospitalization cost and ALOS decreased from $5303 to $4062 and from 19.7 to 14.4 d, respectively. The following factors were associated with considerably decreased hospital resource utilization: age, source, surgical type, tumor size, tumor site, and tumor stage. CONCLUSION: These results can be generalized to patient populations elsewhere in Taiwan and to other countries with similar patient profiles.

The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.

AIM: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. MAIN METHODS: The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. KEY FINDINGS: Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. SIGNIFICANCE: WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.