Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Preservation versus resection of Denonvilliers' fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial.

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers' fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Unusually large paraganglioma complicated with successive catecholamine crises: A case report and review of the literature.

Background: Paragangliomas are rare neuroendocrine tumors that could secret catecholamines. Hypertension and heart failure caused by the catecholamine crisis are fatal cardiovascular events. However, silent paragangliomas that lack typical symptoms of catecholamine pose a significant diagnostic challenge. Case summary: A 45-year-old woman who presented with more than 1-year history of abdominal discomfort was suspected of having a gastrointestinal stromal tumor by a local hospital since a vast metastatic mass occupied her left abdomen. Thus, she was recommended to our hospital. After completing the gastroscopy, she unexpectedly developed acute heart failure and was transferred to the Intensive Care Unit (ICU) where the initial diagnosis of paraganglioma was considered through path. However, a second catecholamine crisis due to constipation led to acute heart failure again. After anti-heart failure therapy and rigorous preoperative preparation, surgery was arranged to remove the tumor. Postoperative pathology confirmed the paraganglioma, and the patient was discharged from the hospital in good condition. Conclusion: We reported a rare case of huge retro-peritoneal paraganglioma with successive catecholamine crises and acute heart failure. This was probably the largest retro-peritoneal paraganglioma since the 1980s. Besides, we were the first to use surgical drawing to illustrate its complex anatomical adjacent relationship of retro-peritoneal paraganglioma. Our case emphasizes the inclusion of extra-adrenal paraganglioma in the differential diagnosis of retroperitoneal tumors. In suspected paragangliomas, catecholamine testing is preferable to invasive procedures including gastroscopy and biopsy to avoid triggering a catecholamine crisis. Surgical resection is the primary treatment. We highlight the priority of dealing with the venous reflux branches of the tumor to prevent the release of catecholamines into the blood. In particular, preoperative preparation plays a vital role in managing paraganglioma. Moreover, it is necessary to schedule genetic testing and clinical follow-up due to the metastatic potential of paragangliomas.

The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.

BACKGROUND: This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. METHODS: Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. RESULTS: During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). CONCLUSIONS: The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Effect of Denonvilliers' Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results of Chinese PUF-01 Randomized Clinical Trial.

OBJECTIVE: To compare the outcomes of laparoscopic total mesorectal excision (L-TME) with Denonvilliers' fascia (DVF) preservation versus resection on urogenital function of male patients with rectal cancer. BACKGROUND: The protective effect of DVF during L-TME on pelvic autonomic nerves and postoperative urogenital function remains controversial. METHODS: Between August 26, 2015 and July 18, 2019, 253 male patients with cT1-4 (T1-2 for anterior wall) N0-2M0 rectal cancer from 11 institutions were enrolled, and randomly assigned to L-TME with DVF preservation (Exp-group, n = 123) or resection procedures (Con-group, n = 130). Urinary function was assessed by residual urine volume, maximal flow rate, and International Prostate Symptom Score; sexual function was assessed by 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading. RESULTS: The Exp-group patients showed a lower urinary dysfunction rate (6.8% vs 25.4%, P = 0.003), higher maximal flow rate (16.25 ±â€Š8.02 vs 12.40 ±â€Š7.05 mL/s, P = 0.007), and lower International Prostate Symptom Score (6.55 ±â€Š5.86 vs 8.57 ±â€Š5.85, P = 0.026) than the Con-group patients at 2 weeks after surgery. The incidence of erectile dysfunction (IIEF-5 ≤ 11) at 12 months after surgery was lower in the Exp-group than in the Con-group (12.5% vs 34.2%, P = 0.023); Exp-group manifested superior IIEF-5 (16.63 ±â€Š6.28 vs 12.26 ±â€Š6.83, P = 0.018). The incidence of ejaculation dysfunction was lower in the Exp-group than in the Con-group at 12 months after surgery (10.0% vs 29.4%, P = 0.034). CONCLUSIONS: DVF preservation during L-TME revealed protective effects on postoperative urogenital function, and could be a better choice for male rectal cancer patients with specific staging and location. TRIAL REGISTRATION NUMBER: NCT02435758.

[Association between serotonin transporter promoter gene polymorphism and clinicopathological factors and effect of the polymorphism on the prognosis of colorectal cancer patients].

OBJECTIVE: To examine the association between the genotype (LL, LS and SS) of serotonin transporter promoter gene polymorphism(5-HTTLPR) and clinicopathological factors, and to investigate the effect of 5-HTTLPR on the prognosis of colorectal cancer patients. METHODS: Data of peripheral blood samples of 161 colorectal cancer patients at the Second Affiliated Hospital of Guangzhou Medical University from October 2009 to January 2014 were collected retrospectively. The genotyping of 5-HTTLPR was determined by PCR and agarose gel electrophoresis. Coincidence Chi-square test was used to examine the 5-HTTLPR genotype with Hardy-Weinberg law. Chi-square test and Cox multifactor model were used to analyze the association of 5-HTTLPR genotype with clinicopathology and prognosis. All the patients were informed and agreed to participate in the study. This study was approved by the Hospital Ethics Committee (2015056). RESULTS: Of 161 colorectal cancer patients, 89 were male and 72 were female; the median age was 64 (25-85) years; 86 (53.5%) cases were colon cancer and 75 (46.5%) were rectal cancer. Genotype was LL in 12 cases, LS in 59 cases and SS in 90 cases, which complied with the law of Hardy-Weinberg genetic balance (χ²=0.288, P=0.592). Univariate analysis showed that 5-HTTLPR gene polymorphism was only associated with lymph node metastasis [lymph node metastasis rate: LL and LS genotype 21.1% (15/71);SS genotype 40.0% (36/90), χ²= 6.532, P=0.011]. The 3-year and 5-year overall survival rates of whole patients were 71% and 63% respectively. Multivariate analysis revealed that the SS genotype was an independent risk factor affecting the overall survival of colorectal cancer patients(HR=1.933, 95%CI:1.090-3.428, P=0.024). CONCLUSION: Among genotypes of 5-HTTLPR gene, colorectal cancer patients with SS genotype have higher risk of lymph node metastasis and poorer prognosis.

The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage â -â ¢ colorectal cancer.

AIM: The effects of circulating eosinophils and basophils on cancer survival are unclear. Here, we aimed to explore the impacts of eosinophils and basophils on prognosis of stage I-III colorectal cancer (CRC) patients. METHODS: From February 2003 to March 2013, 569 stage I-III CRC patients were enrolled in this retrospective study. The associations between pretreatment circulating eosinophils, basophils and CRC overall survival (OS), disease-free survival (DFS) were investigated. Moreover, the prognostic value of combined eosinophils/basophils and neutrophil to lymphocyte ratio (NLR)/platelet to lymphocyte ratio (PLR) was investigated. RESULTS: Kaplan-Meier methods showed the associations of eosinophils < 0.095 × 109 /L and shorter OS (P < 0.0001), eosinophils < 0.055 × 109 /L and shorter DFS (P < 0.0001), basophils < 0.015 × 109 /L and shorter OS (P = 0.001), basophils < 0.015 × 109 /L and shorter DFS (P = 0.005). Cox regression model showed that eosinophils < 0.095 × 109 /L (hazard ratio [HR], 1.723; 95% confidence intervals [CI] = 1.177-2.523) and basophils < 0.015 × 109 /L (HR, 1.714; 95% CI = 1.152-2.548) were independent prognostic factors for OS, and eosinophils < 0.055 × 109 /L (HR, 2.309; 95% CI = 1.587-3.361) and basophils < 0.015 × 109 /L (HR, 1.397; 95% CI = 1.003-1.945) were independent prognostic factors for DFS, respectively. The combined eosinophil-PLR (HR, 2.611; 95% CI = 1.328-5.130) and basophil-PLR (HR, 2.520; 95% CI = 1.240-5.123) were the independent prognostic factors for OS. The combined eosinophil-NLR (HR, 2.770; 95% CI = 1.528-5.019) and eosinophil-PLR (HR, 4.788; 95% CI = 2.458-9.329) were the independent prognostic factors for DFS. CONCLUSION: Pretreatment circulating eosinophils < 0.095 × 109 /L/0.055 × 109 /L and circulating basophils < 0.015 × 109 /L have significant impacts on prognosis of stage I-III CRC patients.

HES1 Promotes Colorectal Cancer Cell Resistance To 5-Fu by Inducing Of EMT and ABC Transporter Proteins.

Background and Aim: Hairy enhancer of split-1 (HES1) is a downstream transcriptional factor of Notch signaling pathway, which was found to be related to chemoresistance. This study was aimed to investigate the role of HES1 in chemoresistance of colorectal cancer (CRC). Methods: Tissue microarray was used to analyze the clinical significance of HES1 in radical resected (R0) stage II/III CRC patients that received adjuvant chemotherapy. 5-fluorouracil (5-Fu) chemoresistance was examined in CRC cell lines (RKO and HCT8, LOVO) with stable over-expression and inhibition of HES1 gene by cytotoxicity test. Gene expression microarray was used to investigate the enriched pathways and different expressed of genes in cells with over-expressed HES1. Expression changes of the chemoresistance related genes were confirmed by qPCR and western blot analysis. Results: Stage II CRC patients with higher HES1 expression showed higher recurrence rate after chemotherapy. Colon cancer cell lines which over-expressed HES1 were more resistant to 5-Fu treatment in vitro. Gene expression microarray revealed that HES1 was related to the signaling pathways of epithelial-mesenchymal transition (EMT) and drug metabolism. Immunofluorescence assay showed HES1 over-expression lead to depressed E-cadherin and elevated N-cadherin. QPCR and western blot analysis confirmed that ABCC1, ABCC2 and P-gp1 were induced after HES1 over-expression. Conclusions: HES1 promotes chemoresistance to 5-Fu by prompting EMT and inducing of several ABC transporter genes. HES1 might be a novel therapeutic target in CRC treatment.

[Impact of platelet count on prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy].

OBJECTIVE: To analyze the impact of platelet count on the prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy. METHODS: Clinical and follow-up data of 286 patients with stage II-III colorectal cancer receiving adjuvant FOLFOX chemotherapy from March 2003 to October 2011 were analyzed retrospectively. Associations of baseline blood platelet count before chemotherapy and nadir blood platelet count during chemotherapy with relapse and death after adjuvant chemotherapy were analyzed by ROC curve and the optimal cutoff was selected. The association of the blood platelet count and the prognosis was analyzed by Kaplan-Meier and Cox regression model. RESULTS: ROC curve showed the baseline blood platelet count was associated with recurrence (AUC=0.588, P=0.034). The optimal cutoff affecting recurrence was 276×10(9)/L. Kaplan-Meier showed those with baseline platelet count >276×10(9)/L receiving adjuvant chemotherapy had worse disease free survival (DFS) than those with baseline platelet count ≤276×10(9)/L, whose 5-year disease free survival(DFS) was 66% and 80% respectively (P=0.013). Cox regression analysis revealed baseline platelet count >276×10(9)/L was an independent unfavorable factor for DFS of adjuvant chemotherapy in colorectal cancer (HR=1.865, 95% CI: 1.108-3.141, P=0.019). CONCLUSION: Colorectal cancer patients receiving adjuvant chemotherapy with baseline platelet count >276×10(9)/L have worse prognosis.

Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer.

AIMS: To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer. METHODS: In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model. RESULTS: The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P < 0.0001). No association between other lifestyle factors and pretreatment PLR was found. CONCLUSIONS: A higher frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer.

[Metastatic lymph node ratio and outcome of surgical patients with stage III colorectal cancer].

OBJECTIVE: Evaluate the prognostic value of lymph node ratio (LNR) in patients undergoing resection of stage III colorectal cancer. METHODS: The clinicopathological and follow-up data were collected from 174 surgical patients with stage III colorectal cancer. The 5-year disease-free survival (DFS) and overall survival (OS) were evaluated using Kaplan-Meier method. The impact of LNR and clinicopathological factors on DFS and OS were evaluated using univariate and multivariate analysis. RESULTS: After a median follow-up of 62.5 months, the 5-year DFS and OS of the patients were 51.8% and 56.3%, respectively. The median number of lymph nodes harvested and the median number of positive lymph nodes examined were 10 and 3, respectively. The patients were stratified into 4 groups according to LNR quartiles (LNR1, LNR≤0.125; LNR2, 0.1250.500), whose 5-year DFS and OS were 64.2%, 53.5%, 41.8%, and 25.7% (P<0.05) and 68.1%, 60.8%, 49.2%, and 32.7% (P<0.05), respectively. Multivariate analysis identified age, T stage and LNR as the independent predictors of both DFS and OS. Subgroup analysis showed that LNR had an independent prognostic value on DFS and OS irrespective of the number of lymph nodes harvested. CONCLUSION: LNR is an independent prognostic factor for survival in patients with stage III colorectal cancer and is superior to the pN category in TNM staging.

[Clinicopathological features and prognosis of colorectal cancer patients with preoperative cancer-related anemia].

OBJECTIVE: To analyze the clinicopathological features and prognosis of colorectal cancer patients with preoperative cancer-related anemia. METHODS: Clinical data of 354 patients with colorectal cancer in the Second Affiliated Hospital of Guangzhou Medical College from January 2003 to July 2009 were analyzed retrospectively. Those with hemoglobin(Hb)<120 g/L before surgery were defined as cancer-related anemia. RESULTS: Of the 354 colorectal cancer cases, 195 were males and 159 were females. The median age was 65(range 22-92) years. Preoperative cancer-related anemia tended to be occurred in female(P<0.01) and those with preoperative albumin ≤35 g/L (P<0.01), right colon cancer(P<0.01) and full-thickness invasion(P<0.05). Cox regression analysis showed preoperative cancer-related anemia was an independent unfavorable factor for overall survival (HR=1.60, 95% CI:1.05-2.44; P<0.05), but not for disease-free survival (HR=1.43, 95% CI:0.97-2.12; P>0.05) in colorectal cancer. CONCLUSIONS: Preoperative cancer-related anemia plays an important role in the development and prognosis of colorectal cancer and great attention should be paid to clinical practice.