Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C‐X‐C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti‐PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.
PurposeThe aim of this study was to investigate the clinical and radiological incidence of parastomal hernia and to analyze the risk factors for parastomal hernia.MethodsWe reviewed retrospectively 108 patients with end colostomy from January 2003 to June 2010. Age, sex, surgical procedure type, body mass index (kg/m2), stoma size, and respiratory comorbidity were documented.RESULTSThere were 61 males (56.5%) and 47 females (43.5%). During an overall median follow-up of 25 months (range, 6 to 73 months), 36 patients (33.3%) developed a radiological parastomal hernia postoperatively and 29 patients (26.9%) presented with a clinical parastomal hernia. In multivariate analysis, gender (odds ratio [OR], 6.087; P = 0.008), age (OR, 1.109; P = 0.009) and aperture size (OR, 6.907; P < 0.001) proved to be significant and independent risk factors after logistic regression analysis.ConclusionThis study showed that the incidence of radiological parastomal hernia is higher than clinical parastomal hernia. Risk factors for parastomal hernia proved to be female, age, and aperture size.
We analyzed the changes in absolute lymphocyte count and its changes over time in 139 patients treated with preoperative chemoradiotherapy for locally advanced rectal cancer. The baseline absolute lymphocyte count was defined as the median of absolute lymphocyte count levels measured during 30 days before preoperative chemoradiotherapy. Absolute lymphocyte count at 1 month, 0.5 to 1 year, 1 to 2 years, and 2 to 3 years were determined by the median values of the absolute lymphocyte counts during the respective periods. Absolute lymphocyte count decreased after delivering preoperative chemoradiotherapy, reached minimum level at 1 month, and then gradually increased after the completion of chemoradiotherapy. Baseline absolute lymphocyte count had significant correlations with the absolute lymphocyte count of every period (range of coefficient, 0.41-0.64, P < .001). The overall survival of the group with high baseline absolute lymphocyte count was significantly higher than that of the group with low baseline absolute lymphocyte count (5-year overall survival: 82.4% vs 62.9%, P = .012). In multivariable analyses, the baseline absolute lymphocyte count remained as a significant prognostic factor for overall survival, favoring the group with a high baseline absolute lymphocyte count (hazard ratio = 0.405, P = .017). This study showed that the level of baseline absolute lymphocyte count was an independent prognostic factor, and it correlated with the absolute lymphocyte counts across varying periods of treatments and follow-up in patients treated with preoperative chemoradiotherapy for rectal adenocarcinoma.
The preoperative NLR is a prognostic factor predicting DFS and CSS in patients with stage I colorectal cancer who underwent curative surgery.
PurposeThe aim of this study was to investigate the clinical and radiological incidence of parastomal hernia.MethodsWe reviewed, retrospectively, 83 patients with end colostomy operated on from January 2003 to June 2009 at Ajou University hospital. Age, sex, surgical procedure type, body mass index (weight/length2), stoma size, and respiratory co-morbidity were documented. We compared the incidence of radiological and clinical parastomal hernia.ResultsThere were 47 males (56.6%) and 36 females (43.4%). During an overall median follow-up of 30 months (range, 6 to 45 months), 24 patients (28.9%) developed a radiological parastomal hernia postoperatively and 20 patients (24.1%) presented clinical symptoms. Using computed tomography (CT) classification, the groups were as follows: type 0 (40, 48.2%), type Ia (19, 22.9%), type Ib (8, 9.6%), type II (4, 4.8%) and type III (12, 14.5%), with 63 asymptomatic patients and 20 symptomatic patients. The aperture size was significantly different between symptomatic and asymptomatic patients (76.45 mm vs. 49.41 mm; P = 0.000). There was a significant correlation between aperture size and the radiological type (P = 0.003).ConclusionThis study showed the incidence of radiological parastomal hernia is acceptable compared to previous studies. CT classification may be useful to evaluate parastomal hernia.
PurposeThe use of barium enemas to confirm the anastomotic integrity prior to ileostomy closure is still controversial. The purpose of the study was to determine the utility of routine contrast enema prior to ileostomy closure and its impact on patient management in patients with a low pelvic anastomosis.MethodsOne hundred forty-five patients had a temporary loop ileostomy constructed to protect a low colorectal or coloanal anastomosis following low anterior resection for rectal cancer. All patients were evaluated by physical examination, proctoscopy, and barium enema prior to ileostomy closure.ResultsThe median time from ileostomy creation to closure was 8 months. Five (3.5%) of the 144 patients were found to have clinically relevant strictures at the colorectal anastomosis on routine barium enema. One patient (0.7%) showed anastomotic leak on their barium enema. Overall, 141 patients (97.9%) had an uncomplicated postoperative course. Postoperative complication occurred in three patients (2.1%). None of them showed abnormal barium enema finding, which suggested that routine contrast enema examination did not predict postoperative complication.ConclusionRoutine barium enema evaluation of low pelvic anastomoses before loop ileostomy closure did not provide any additional information for postoperative colorectal anastomotic complication.
In patients with low rectal cancers undergoing ULAR plus coloanal anastomosis, bowel dysfunctions were severe. Bowel dysfunctions improved over time, but most patients still experienced major bowel dysfunctions even 36 months after surgery. Risk factors for bowel dysfunctions were old age, male sex, adjuvant chemoradiation therapy, and ULAR. Therefore, ULAR should be performed in carefully selected patients with low-lying rectal cancer.
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