The mechanisms of cell death of rat cortical neurons chronically exposed to the β-amyloid (βA) biologically active fragment β-(25–35) involve oxidative stress. We examined the influence of culture conditions on the neuroprotective activity of antioxidants against β-(25–35) toxicity. Common radical scavengers such as N-acetylcysteine (250 μM) and N-t-butyl-phenylnitrone (500 μM) only protected cortical cells cultured in the presence of fetal calf serum (FCS) from βA insult. The neuroprotective effect of lazaroids (U74389G and U83836E), 21-aminosteroids with antioxidant activity, was tested in cells grown with or without FCS. U74389G did not interfere with β-(25–35) toxicity in either condition, while U83836E at a very low concentration (15 nM) protected cortical cells exposed to the β peptide only when the neurons were cultured in the presence of FCS. These data show that a lazaroid can prevent β-(25–35) toxicity and that the antioxidants exerted their protective effect in certain conditions.

Colorectal cancer is one of the common malignant tumors in China, and its incidence is increasing with years. As the second most common metastatic site of colorectal cancer, peritoneum is difficult to diagnose early and with a poor prognosis. Systemic intravenous chemotherapy was used as the main treatment strategy for peritoneal metastasis in the past, but its systemic toxic and side effects were obvious, and it could not effectively control tumor progression. In recent years, the continuous development of surgical techniques, concepts, and equipment, as well as the introduction of new chemotherapy drugs and targeted drugs have significantly improved the quality of life and prognosis of patients with peritoneal metastasis of colorectal cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively eradicated the intraperitoneal free cancer cells and subclinical lesions, while reducing systemic side effects of chemotherapy drugs, and achieve the radical cure of the tumor at the macro and micro levels to the greatest extent. It has been used as the first-line treatment program for peritoneal metastasis of colorectal cancer at home and abroad. This article focuses on the analysis and summary of the survival efficacy, prognostic factor analysis, and chemotherapy safety of CRS+ HIPEC in the treatment of colorectal cancer peritoneal metastasis. The existing problems and controversies of HIPEC therapy are discussed simultaneously.

The treatment of locally advanced rectal cancer (LARC) is extremely challenging, and it is difficult to achieve satisfactory results with surgical resection alone. In recent years, the diagnosis and treatment of LARC tends to be multi-disciplinary (MDT) mode. The emerging neoadjuvant treatment strategy is a milestone. At present, the preferred treatment for LARC is neoadjuvant chemoradiotherapy combined with total mesorectal excision. This article summarizes the main treatments of LARC neoadjuvant therapy, hoping to provide reference for clinical diagnosis and treatment.

Objective: To explore the clinical safety and feasibility of overlapped delta-shaped anastomosis (ODA) in totally laparoscopic right hemicolectomy (TLRHC). Methods: From May 2017 to October 2019, of the 219 patients who underwent TLRHC at the Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 104 cases underwent ODA (ODA group) and 115 cases underwent conventional extracorporeal anastomosis (control group) were compared the surgical outcomes, postoperative recovery, pathological outcomes and perioperative complications. Results: The length of the skin incision in the ODA group was significantly shorter than that in the control group [(5.6±0.9) cm vs. (7.1±1.7) cm, P<0.05], and the time to first flatus and first defecation after surgery in the ODA group was significantly earlier than that in the control group [(1.7±0.7) days vs. (2.0±0.7) days; (3.2±0.6) days vs. (3.3±0.7) days, P<0.05]. While the anastomosis time, operation time, intraoperative blood loss, the time of first ground activities, the number of bowel movements within 12 days after surgery, postoperative hospital stay, tumor size, the distal and proximal margins, the number of lymph node harvested and postoperative TNM stage in the ODA group did not differ from that of the control group (P>0.05). The postoperative complication rates of patients in the ODA group and the control group were 3.8% (4/104) and 4.3% (5/115), respectively, and the difference was not significant (P>0.05). Conclusion: The application of ODA technology in TLRHC can significantly shorten thelength of skin incisionand the recovery time of bowel function, and can obtain satisfactory short-term efficacy.

Objective: To investigate the expression of cortactin in colorectal cancer and its correlation with clinicopathological parameters and prognosis. Methods: The expressions of cortactin in normal colorectal mucosal tissue and colorectal cancer tissue in paraffin-embedded tissue microarray from 319 patients who were diagnosed as colorectal cancer and treated in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2009 was detected by immunohistochemistry. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for multivariate analysis. Results: The positive expression rates of cortactin in colorectal cancer tissue and normal colorectal mucosal tissue were 61.1% (195/319) and 5.6% (18/319, P<0.001), respectively. T-stage, N-stage, American Joint Committee on Cancer (AJCC) stage, degree of tumor differentiation, neural invasion and preoperative carcinoembryonic antigen (CEA) levels were associated with the expression of cortactin (P<0.05). The positive expression of cortactin was associated with poorer disease-free survival (P=0.036) and overall survival (P=0.043), and the effect was more significant in patients with stage Ⅱ to Ⅲ. For patients with stage Ⅱ-Ⅲ colorectal cancer, postoperative adjuvant therapy was associated with disease-free survival (P=0.007) and overall survival (P=0.015). The vascular tumor embolus, pathological type, preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival (P<0.05). The age, AJCC stage, preoperative CEA level and cortactin expression were independent influencing factors for overall survival (P<0.05). Preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival and overall survival (P<0.05). Conclusion: Cortactin is expressed in colorectal cancer and in stage Ⅱ-Ⅲ patients, it is a potential predictor of colorectal cancer prognosis.

Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy of NAC prior to CRS+HIPEC for patients with synchronous colorectal PM. Methods Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. The clinicopathologic characteristics, perioperative parameters, and survival rates of patients who underwent CRS+HIPEC with NAC (NAC group) and patients who underwent CRS+HIPEC without NAC (non-NAC group) were compared. Results The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P = 0.031), and more patients achieved complete cytoreduction (80.0% vs 46.9%, P = 0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates ( P > 0.05). However, patients who received NAC had lower platelet counts (151.9 vs 197.7 × 10 9 /L, P = 0.036) and neutrophil counts (4.7 vs 7.2 × 10 9 /L, P = 0.030) on postoperative day 1. More patients survived for 2 years in the NAC group than in the non-NAC group (67.4% vs 32.2%, respectively, P = 0.044). However, the completeness of cytoreduction score (HR, 2.99; 95% CI, 1.14–7.84; P = 0.026), rather than NAC, was independently associated with overall survival (OS) in the multivariate analysis after controlling for confounding factors. Conclusion NAC administration before CRS+HIPEC can be regarded as safe and feasible for patients with colorectal PM with comparably low mortality rates and acceptable morbidity rates. Nevertheless, large-sample randomized controlled studies are needed to confirm whether the administration of NAC before CRS+HIPEC confers a survival benefit to patients.

Chuanduo Zhao Department of Colorectal Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing Sicheng Zhou Department of Colorectal Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing Hao Su Department of Colorectal Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing Jianwei Liang Department of Colorectal Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing Zhixiang Zhou (  drzhixiangzhou@126.com ) Department of Colorectal Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing

Background This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. Results In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01–1.14; P =0.015) and grade 3–4 postoperative complications (HR, 1.86, 95% CI, 1.22–3.51; P =0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01–1.02; P < 0.001) was identified as an independent risk factor for developing high-grade complications. Conclusion Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.

Background The use of surgery in patients with colorectal cancer (CRC) aged ≥90 years remains controversial. This study aimed to evaluate the short-term postoperative and long-term oncologic outcomes of CRC surgery in patients within this age group. Methods A total of 151 consecutive nonagenarian patients who underwent CRC surgery were included from 3 different hospitals. The Comprehensive Complication Index (CCI) was used to grade postoperative complications. Univariate and multivariate analyses were conducted to identify factors associated with CCI and overall survival (OS). Results The patients had a mean age of 92.8 years (standard deviation ±1.9 years). Forty-six patients (30.5%) underwent emergency surgery, and 105 patients (69.5%) underwent elective surgery. The postoperative complications rate was 66.2% (100/151), and the mean CCI was 26.3 (±30.8). Twenty-three patients (15.2%) died postoperatively, and the perioperative mortality rates for elective surgery and emergency surgery were 7.6% (8/105) and 32.6% (15/46), respectively (P<0.001). The 1-, 3-, and 5-year survival rates were 77.5%, 53.9%, and 38.6%, respectively. Multivariate analysis revealed emergency surgery and American Society of Anesthesiologists (ASA) score to be predictors of postoperative complications. Advanced tumor stage, palliative surgery, ASA score ≥4, and CCI >17 were associated with poor OS. Conclusions CRC surgery should not be denied to nonagenarian patients. Surgical treatment can be performed with acceptable morbidity and mortality, and achieves long-term survival in a select group.

Macrophages are among the most abundant immune cells in colorectal cancer (CRC). Re-educating tumor-associated macrophages (TAMs) to switch from protumoral to anti-tumoral activity is an attractive treatment strategy that warrants further investigation. However, little is known about the key pathway that is activated in TAMs. In this study, infitrating CD206+ TAMs in CRC were sorted and subjected to RNA-seq analysis. Differentially expressed genes were found to be enriched in unfolded protein response/endoplasmic reticulum stress response processes, and XBP1 splicing/activation was specifically observed in TAMs. XBP1 activation in TAMs promoted the growth and metastasis of CRC. Ablation of XBP1 inhibited the expression of the pro-tumor cytokine signature of TAMs, including IL-6, VEGFA, and IL-4. Simultaneously, XBP1 depletion could directly inhibit the expression of SIRPα and THBS1, thereby blocking "don't eat me" recognition signals and enhancing phagocytosis. Therapeutic XBP1 gene editing using AAV2-sgXBP1 enhanced the anti-tumor activity. Together, XBP1 activation in TAMs drives CRC progression by elevating pro-tumor cytokine expression and secretion, as well as inhibiting macrophage phagocytosis. Targeting XBP1 signaling in TAMs may be a potential strategy for CRC therapy.

Objective This study aimed to evaluate the safety and feasibility of radical surgery and explore prognostic factors affecting cancer-specific survival (CSS) in colorectal cancer (CRC) patients over 80 years old. Methods From January 2010 to December 2020, a total of 372 elderly CRC patients who underwent curative resection at the National Cancer Center were enrolled and classified into a control group (BMI <24 kg/m 2 ) and an overweight group (BMI ≥24 kg/m 2 ). Preoperative clinical features, perioperative outcomes and postoperative pathological characteristics were collected and compared between the two groups. Results The control group and overweight group comprised 219 and 153 patients, respectively. There was no significant difference between the two groups of patients in terms of operative time (153.0 vs 142.3 min, P =0.226), intraoperative bleeding (67.8 vs 69.3 ml, P =0.873) or other surgical outcomes or grade 3-4 postoperative complications (11.1% vs 14.6%, P =0.326). The 5-year CCS of patients in the overweight group was significantly worse than that of the control group (63.3% vs 80.0%, P =0.046). The multivariate analysis showed that CCS was significantly affected by BMI (HR: 2.30; 95% CI, 1.27-4.17; P =0.046) and N stage (HR: 2.97; 95% CI, 1.48-5.97; P =0.002) Conclusion The results of this study demonstrated that radical resection for CRC is safe and feasible for patients over 80 years of age. The increase in BMI does not increase the difficulty of surgery or postoperative complications. BMI and N stage were independent prognostic factors for elderly CRC patients after radical resection.

Purpose Cytoreductive surgery (CRS) added with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the survival rate of certain patients with peritoneal metastasis (PM). However, the perioperative safety and long-term survival of this intricate and possibly life-threatening procedure in elderly patients (≥65 years) remain controversial. Methods Patients with PM due to appendiceal or colorectal tumours who underwent CRS/HIPEC were evaluated systematically at the National Cancer Center of China and the Huanxing Cancer Hospital between June 2017 and June 2019. The recruited subjects were retrospectively categorized into elderly (age ≥65) and non-elderly (age<65) groups according to their age. Clinical and pathological features, postoperative outcomes, and prognoses were gathered and analysed. Results Both groups had similar overall morbidity (56.0% vs 38.7%, P=0.130) and grade 3/4 morbidity (28.0% vs 20.0%, P=0.403) after CRS/HIPEC. However, more patients in the elderly group suffered from ileus postoperatively (16.0% vs 2.6%, P=0.033). After a follow-up period of a median of 20 months, it was concluded that elderly patients had significantly worse 3-year overall survival (OS) than non-elderly patients (16.3% vs 51.4%, P=0.001). Independent prognostic factors were identified to be a high peritoneal carcinomatosis index (PCI) score (HR, 1.10, 95% CI, 1.04–1.16; P=0.001) and age ≥65 (HR, 2.42, 95% CI, 1.32–4.45; P=0.004) were independent prognostic factors through cox regression analysis. Conclusion CRS and HIPEC are related with an elevated prevalence of postoperative ileus but not with the overall morbidity or the grade 3/4 morbidity in elderly patients. However, since worse survival outcomes were observed more commonly in elderly patients compared to younger patients from CRS+HIPEC, this complex and potentially life-threatening procedure should be considered carefully in patients aged ≥65 years.

Objective:To compare the short-term outcome of total laparoscopic and open loop ileostomy reversal.Methods:A retrospective review was performed for 60 consecutive patients who underwent loop ileostomy reversal between January 2018 to August 2020, at Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Twenty-seven patients were treated with total laparoscopic loop ileostomy while 33 patients were open cases. The baseline characteristics, operative outcomes, postoperative recovery and postoperative complications of these patients were identified and retrospectively analyzed.Results:All patients had been successfully accomplished loop ileostomy reversal without discontinued operation. No perioperative related death cases were found in the whole group. There was no significant difference in the clinical characteristics between the two groups. The length of incision in the total laparoscopic surgery group was significantly shorter than that in the traditional open surgery group [(5.7±1.4) cm vs. (7.8±1.1) cm, t=-6.622], and the difference was statistically significant (P＜0.001). There were significant differences between the two groups in the first ground activities [1 (1~1) d vs. 1(1~2) d], first flatus passage [2(1~3) d vs. 2(2~3) d], postoperative hospitalization days [6(5~7) d vs. 7(6~9) d], the postoperative complications [3.7% (1/27) vs. 24.2% (8/33)]. The total operative time of laparoscopic surgery group was longer than that of the traditional open surgery group [(98.0±24.5) min vs. (89.4±17.5) min], but the difference was not statistically significant. (P＞0.05)Conclusion:This retrospective study demonstrated that total laparoscopic loop ileostomy reversal might be a safe and feasible procedure, with a lower postoperative complications and a shorter postoperative hospitalization time.

Abstract Background The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. Methods Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. Results A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3–4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15–4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06–4.17, P = 0.047). Conclusion CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.

Background: The impact of self-expandable metal stent (SEMS) for malignant right colonic obstruction remains undefined. The aim of this study was to compare short-term postoperative and long-term oncologic outcomes of colonic stenting as a bridge to surgery (SBTS) and urgent colectomy for patients with malignant right-sided obstruction.Methods: A total of 98 consecutive patients who underwent SEMS placement during the period 2004-2015 from three hospitals were included. For comparative analyses, patients were matched (1:2) with 196 patients treated with emergency colectomy from our prospective database.Results: The two groups were comparable in terms of demographics and tumor characteristics. The proportion of patients who underwent laparoscopic colectomy was higher in SBTS group than urgent colectomy group (75.5% vs. 37.2%; p < 0.001). Patients treated with SBTS were less likely to have a temporary stoma constructed (3.1% vs. 10.7%; p = 0.024). SBTS was associated with significantly less median estimated blood loss (90 vs. 100 ml; p = 0.029), shorter length of hospital stay (11 vs. 12 days; p < 0.001), lower overall postoperative complication rate (18.4% vs. 31.3%; p = 0.018), and wound-related complication rate (5.1% vs. 14.3%; p = 0.019) compared with urgent surgery. Reoperation rate, 30-day mortality, and lymph nodes harvested were not significantly different between two groups. Disease-free survival rate and overall survival rate were similar between the two groups.Conclusions: SEMS insertion is safe and feasible for treating malignant right-sided obstruction. SBTS is associated with better short-term outcomes and equivalent long-term oncologic results compared with urgent colectomy.

Abstract Background The efficacy of lateral pelvic lymph node dissection (LPND) for mid-low rectal cancer and the prognosis of patients with lateral pelvic lymph node metastasis (LPNM) remain controversial. The goal of this study was to evaluate the efficacy of LPND for stage II or III middle-low rectal cancer and investigate the impact of LPNM on survival outcomes. Methods Data from 858 consecutive patients who were diagnosed with stage II–III mid-to-low rectal cancer and underwent curative resection were reviewed. After propensity matching, 125 matched pairs were selected and divided into the total mesorectal excision (TME) group and TME + LPND group for evaluation. According to the location of lymph node (LN) metastasis, 250 patients were divided into the N0 group, mesorectal-LN group and LPN group. In addition, the survival data of 100 patients with stage IV rectal cancer who underwent curative resection were also reviewed to compare prognostic differences. Results The prognosis of patients in the TME + LPND group did not improve significantly in terms of local recurrence rate (4.8% vs. 4.0%, P = 0.758), distant metastasis rate (18.4% vs. 18.4%, P = 1.000) or 5-year recurrence-free survival (RFS) (63.1% vs. 66.2%, P = 0.269). Overall, 89 (35.6%), 129 (51.6%), and 22 (8.8%) patients were classified into the N0, mesorectal-LN, and LPN groups, respectively. When the mesorectal LN and LPN groups were subdivided, RFS was not significantly different between the internal LPN and N1 groups (70.8% vs. 62.5%, P = 0.905). There was no significant difference in RFS between the external group and the stage IV group (31.6% vs. 22.5%, P = 0.302), but RFS in the former group was significantly worse than that in the N2 group (31.6% vs. 40.4%, P = 0.044). Conclusion No differences were observed regarding any recurrence or RFS between the TME group and TME + LPND group. Although LPNM was an independent poor prognostic factor for RFS, patients limited to internal iliac LN metastasis appeared to achieve a survival benefit from LPND and could be regarded as regional LN metastasis. Patients with LPNM other than the internal iliac LN had a poor prognosis; the prognosis was significantly worse than that of N2 and slightly better than that of stage IV.

*These authors contributed equally to this work Purpose: Cytoreductive surgery (CRS) added with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the survival rate of certain patients with peritoneal metastasis (PM). However, the perioperative safety and long-term survival of this intricate and possibly life-threatening procedure in elderly patients (≥65 years) remain controversial. Methods: Patients with PM due to appendiceal or colorectal tumours who underwent CRS/ HIPEC were evaluated systematically at the National Cancer Center of China and the Huanxing Cancer Hospital between June 2017 and June 2019. The recruited subjects were retrospectively categorized into elderly (age ≥65) and non-elderly (age<65) groups according to their age. Clinical and pathological features, postoperative outcomes, and prognoses were gathered and analysed. Results: Both groups had similar overall morbidity (56.0% vs 38.7%, P=0.130) and grade 3/ 4 morbidity (28.0% vs 20.0%, P=0.403) after CRS/HIPEC. However, more patients in the elderly group suffered from ileus postoperatively (16.0% vs 2.6%, P=0.033). After a followup period of a median of 20 months, it was concluded that elderly patients had significantly worse 3-year overall survival (OS) than non-elderly patients (16.3% vs 51.4%, P=0.001). Independent prognostic factors were identified to be a high peritoneal carcinomatosis index (PCI) score (HR, 1.10, 95% CI, 1.04–1.16; P=0.001) and age ≥65 (HR, 2.42, 95% CI, 1.32–4.45; P=0.004) were independent prognostic factors through cox regression analysis. Conclusion: CRS and HIPEC are related with an elevated prevalence of postoperative ileus but not with the overall morbidity or the grade 3/4 morbidity in elderly patients. However, since worse survival outcomes were observed more commonly in elderly patients compared to younger patients from CRS+HIPEC, this complex and potentially life-threatening procedure should be considered carefully in patients aged ≥65 years.

Abstract Aim It is still controversial whether the addition of lateral pelvic lymph node (LPN) dissection (LPND) to total mesorectal excision (TME) can provide a survival benefit after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients with pathological lateral lymph node metastasis (LPNM). Methods Patients with clinically suspected LPNM who underwent nCRT followed by TME + LPND were systematically reviewed and divided into the positive LPN group (n = 15) and the negative LPN group (n = 58). Baseline characteristics, clinicopathological data and survival outcomes were collected and analysed. Results Of the 73 patients undergoing TME + LPND after nCRT, the pathological LPNM rate was 20.5% (15/73). Multivariate analysis showed that a post-nCRT LPN short diameter ≥ 7 mm (OR 49.65; 95% CI 3.98–619.1; P = 0.002) and lymphatic invasion (OR 9.23; 95% CI 1.28–66.35; P = 0.027) were independent risk factors for pathological LPNM. The overall recurrence rate of patients with LPNM was significantly higher than that of patients without LPNM (60.0% vs 27.6%, P = 0.018). Multivariate regression analysis identified that LPNM was an independent risk factor not only for overall survival (OS) (HR 3.82; 95% CI 1.19–12.25; P = 0.024) but also for disease-free survival (DFS) (HR 2.33; 95% CI 1.02–5.14; P = 0.044). Moreover, N1-N2 stage was another independent risk factor for OS (HR 7.41; 95% CI 1.63–33.75; P = 0.010). Conclusions Post-nCRT LPN short diameter ≥ 7 mm and lymphatic invasion were risk factors for pathological LPNM after nCRT. Furthermore, patients with pathological LPNM still show an elevated overall recurrence rate and poor prognosis after TME + LPND. Strict patient selection and intensive perioperative chemotherapy are crucial factors to ensure the efficacy of LPND.

Objective:To investigate the expression of glutathione peroxidases 4 (GPX4) in colon adenocarcinoma and its relationship with clinicopathological features and prognosis of patients.Methods:The data set of colon adenocarcinoma was obtained from The Cancer Genome Atlas (TCGA) database to analyze the expression of GPX4 in colon adenocarcinoma tissues and its predictive value for overall survival (OS). A total of 93 colon adenocarcinoma tissues and 87 adjacent mucosa tissues after operation from November 2009 to May 2010 provided by the National Human Genetic Resources Sharing Service Platform were selected. The expression of GPX4 protein was detected by using tissue chip immunohistochemistry. The relations between the expression of GPX4 protein and the clinicopathological features and OS of colon adenocarcinoma patients were analyzed. Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. The nomogram for predicting OS rate was established and drawn.Results:The analysis of data from TCGA database showed that in 380 cases of colon adenocarcinoma, the expression of GPX4 in colon adenocarcinoma tissues were higher than that in the normal colonic mucosa tissues [the value of fragments per kilobase of exon per million fragments mapped (FPKM): 85.654 (20.351-356.237) vs. 56.230 (48.783-63.931)], and the difference was statistically significant ( Z = -6.150, P<0.05). The OS in GPX4 high-expression group (FPKM ≥83.614) were poorer than that in GPX4 low-expression group (FPKM < 83.614) (median OS time: 84.40 months vs. 94.03 months, 5-year OS rate: 58.6% vs. 72.7%), and the difference was statistically significant ( P<0.05). Tissue chip immunohistochemical staining results show that the high-expression rate of GPX4 protein in colon adenocarcinoma tissues was higher than that in adjacent normal tissues [38.0% (35/92) vs. 7.3% (6/82)], and the difference was statistically significant ( χ2 = 22.727, P<0.01); the high-expression rate of GPX4 protein in left colon adenocarcinoma tissues was higher than that in right colon adenocarcinoma tissues [47.2% (25/53) vs. 25.6% (10/39), and the difference was statistically significant ( χ2 = 4.42, P = 0.036); the 5-year OS rate of patients in GPX4 high-expression group was lower than that in GPX4 low-expression group (25.7% vs. 57.9%), and the difference was statistically significant ( χ2 = 9.051, P<0.05). Multivariate Cox proportional hazards regression model analysis showed that lymph node metastasis (stage N 1-N 3) ( HR = 2.241, 95% CI 1.242-4.046, P = 0.007) and high expression of GPX4 ( HR = 2.783, 95% CI 1.598-4.848, P<0.01) were independent factors affecting the poor prognosis of colon adenocarcinoma patients. The above factors were used to establish a nomogram for predicting the prognosis of patients with colon adenocarcinoma, the C index was 0.739, indicating that the nomogram had good predictive performance. Conclusion:The expression of GPX4 is up-regulated in colon adenocarcinoma tissues, and its high expression is related to the malignant biological behavior of the tumor and poor prognosis.