The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.

Prognostic Value of EGFR Expression for Patients With Stage III Colorectal Cancer Receiving Fluoropyrimidine Metronomic Maintenance Therapy After Radical Resection and Adjuvant Oxaliplatin-Based Chemotherapy.

This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m², twice daily, on days 114 every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockout of the EGFR gene, we analyzed the capacities of cell proliferation and migration. Relapse and survival were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent associated factor of relapse and survival as well as a prognostic factor of disease-free survival and overall survival. Significant intergroup differences in survival were only observed in patients with positive EGFR expression. Thus, our findings suggest EGFR expression is a prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. Analysis of EGFR expression in these patients helps identify potential candidates who may receive the optimal survival benefit from metronomic maintenance therapy.

Predictive Value of ERCC1, ERCC2, and XRCC Expression for Patients with Locally Advanced or Metastatic Gastric Cancer Treated with Neoadjuvant mFOLFOX-4 Chemotherapy.

The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.

Apical Lymph Nodes in the Distant Metastases and Prognosis of Patients with Stage III Colorectal Cancer with Adequate Lymph Node Retrieval Following FOLFOX Adjuvant Chemotherapy.

The aim of the study was to assess apical lymph nodes (APNs) for predicting distant metastases in patients with stage III colorectal cancer (CRC) curatively treated with FOLFOX adjuvant chemotherapy and adequate lymph node retrieval. We investigated the correlation between APN metastasis and clinical outcomes. This retrospective study examined 97 patients. All patients were followed until death, loss to follow-up, or May 2017. Clinicopathological variables, including the APN status, were assessed. Multivariate logistic regression model was used to identify the independent risk factors for APN and distant metastases, and Cox proportional regression model was used to evaluate the association between APN metastasis and oncologic outcomes. Multivariate analyses revealed the N2 stage as an independent predictor of APN metastasis [P = 0.036; odds ratio (OR): 3.016; 95% confidence interval (CI): 1.076-8.499], while APN metastasis was an independent risk factor for distant metastases (P < 0.001; OR: 13.876; 95% CI: 3.815-50.475). Furthermore, APN metastasis was an independent risk factor for poorer disease-free survival (DFS) and overall survival (OS) (P < 0.001 and P = 0.005, respectively). The liver (31.6%) was the most common site of distant metastases in patients with APN metastases. APN metastasis is an important prognostic factor for node-positive CRC; it enhanced the distant metastases in patients with stage III CRC curatively treated with adequate lymph node retrieval following FOLFOX adjuvant chemotherapy. Therefore, for patients with stage III CRC involving APN metastasis, prospectively randomized trials are mandatory to investigate different therapeutic strategies in addition to conventional FOLFOX adjuvant chemotherapy.

Optimization of a multigene biochip for detection of relapsed and early relapsed colorectal cancer.

BACKGROUND: With the recent development of molecular markers, strategies for identifying patients with colorectal cancer (CRC) having a high risk of postoperative early relapse (within 1 y) and relapse have been improved. We previously constructed a multigene biochip with 19 candidate genes. The objective of the present study was to optimize a multigene biochip for detecting the risk of postoperative early relapse and relapse in patients with CRC. METHODS: We included 357 patients with stage I-III CRC who underwent curative resection at a single institution between June 2010 and May 2015. During each follow-up, a postoperative surveillance strategy including the National Comprehensive Cancer Network recommendations and a multigene biochip was used. A statistical algorithm was developed to select candidate biomarkers for an optimal combination. RESULTS: After a 30.9-mo median follow-up, 67 patients (18.8%) had postoperative relapse, of whom 25 (7.0%) relapsed within 1 y after operation and accounted for 37.3% of all relapsed patients. Of the 19 circulating biomarkers, ELAVL4, PTTG1, BIRC5, PDE6D, CHRNB1, MMP13, and PSG2, which presented significant predictive validity, were selected for combination. The expression of the seven-biomarker biochip resulted in area under the receiver operating characteristic curve values of 0.854 (95% confidence interval: 0.756-0.952) for early relapse and 0.884 (95% confidence interval: 0.830-0.939) for relapse. Moreover, the sensitivity, specificity, and predictive accuracy levels were 84.0%, 83.1%, and 83.2% for early relapse and 76.1%, 91.0%, and 88.2% for relapse (P = 0.415, 0.006, and 0.054, respectively). The median lead times before the detection of postoperative early relapse and relapse were 3.8 and 10.4 mo, respectively. CONCLUSIONS: From 19 circulating biomarkers, we optimized seven contemporary circulating biomarkers. The prediction model used for the early and accurate identification of Taiwanese patients with CRC having a high risk of postoperative early relapse and relapse seems to be feasible and comparable.

Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer.

BACKGROUND: Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC. METHODS: We retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. RESULTS: Median age was 64 years (45-86 years) and median follow-up period was 23.5 months (5.0-49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and disease-free survival rates were 88.7% and 73.6%, respectively. CONCLUSIONS: Our results demonstrated that neoadjuvant chemoradiotherapy is feasible and safe. A prominent pCR rate with an acceptable toxicity profile suggests that the multimodality therapy might be a treatment option for patients with LACC.

Decreased peritherapeutic VEGF expression could be a predictor of responsiveness to first-line FOLFIRI plus bevacizumab in mCRC patients.

OBJECTIVE: Bevacizumab is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus bevacizumab has led to improve outcomes for mCRC patients and is a common choice for first-line treatment of mCRC, previous research has established no prominent biomarker that can help to select patients who may benefit from bevacizumab in order to improve cost-effectiveness and therapeutic outcomes. The aim of this study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC) expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its potential role as a predictive biomarker. METHODS: A total of 57 mCRC patients who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line neoadjuvant regimen were enrolled and clinical outcome data analyzed. RESULTS: Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic VEGF expression (P < 0.001) were significantly predictive factors of responders. Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients with decreased peri-therapeutic VEGF expression was significantly better than the rate for those patients with no peri-therapeutic VEGF expression alterations (P = 0.033). CONCLUSIONS: Decreased peri-therapeutic VEGF expression in mCRC patients could probably be used to predict responsiveness to bevacizumab and subsequent PFS in clinical practice.

Relationships between SMAD3 expression and preoperative fluoropyrimidine-based chemoradiotherapy response in locally advanced rectal cancer patients.

BACKGROUND: SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-ß target genes, playing a significant role in mediating the activities of TGF-ß. In this study, we assessed the roles of TGF-ß1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy. METHODS: Using immunohistochemistry, we examined TGF-ß1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2-4). RESULTS: A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479-35.229). Furthermore, a poor response (pathological tumor regression grades of 0-1) was an independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI 1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival (P = 0.023). CONCLUSIONS: Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.

Prospective, randomized, study of ampicillin-sulbactam versus moxifloxacin monotherapy for the treatment of community-acquired complicated intra-abdominal infections.

BACKGROUND: The ideal antimicrobial treatment for intra-abdominal infections (IAIs) in the setting of fast-paced emergency departments (EDs) should be effective, convenient, and of limited resource utilization. Antibiotic monotherapy is a feasible option for this. We conducted a study in which we compared two regimens for antibiotic monotherapy recommended by published guidelines in ED patients with community-acquired, complicated IAIs (cIAIs). METHODS: The study was a prospective, randomized, study of ampicillin-sulbactam versus moxifloxacin for cIAIs. After the diagnosis of cIAI was established, patients were assigned randomly to receive either moxifloxacin 400 mg intravenously (IV) qd followed by moxifloxacin 400 mg orally (PO) qd, or ampicillin-sulbactam 1.5 g IV qid followed by ampicillin-sulbactam 750 mg PO q12h. Source control procedures were used for all patients and all had complete follow-up. The primary efficacy variable for the study was the clinical response at the test-of-cure visit. RESULTS: A total of 116 patients were enrolled for prospective evaluation and randomized assignment to treatment with ampicillin-sulbactam (n=55) or moxifloxacin (n=61). At the test-of-cure evaluation, the overall clinical failure rate was 13.8%. The clinical failure rates in the ampicillin-sulbactam and moxifloxacin groups were 16.4% (9/55) and 11.5% (7/61), respectively (p=0.446). With regard to infection site, the clinical failure rate in cIAIs consisting of lower gastrointestinal (GI) tract infection was significantly lower in the moxifloxacin than in the ampicillin-sulbactam group (4.3% vs. 19.6%; p=0.024). According to multivariable analysis, independent risk factors for treatment failure were the time to ED presentation >24 h (odds ratio [OR] 6.8; 95% CI 1.3-36.2; p=0.024) and ampicillin-sulbactam therapy (OR 9.5; 95% CI 1.1-76.6; p=0.033). CONCLUSIONS: A significant difference existed in the clinical responses of the two groups. As compared with ampicillin-sulbactam, moxifloxacin was more effective for the treatment of community-acquired cIAIs of the lower GI tract. A higher risk of treatment failure for antibiotic therapy was found for patients presenting to the ED with symptoms of cIAIs lasting >24 h. Alternative antimicrobial agents should be considered for treating these patients.