Tumor immune microenvironment of primary colorectal adenocarcinomas metastasizing to the liver or lungs.

BACKGROUND: Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). METHODS: RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. RESULTS: Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. CONCLUSIONS: Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

Serum Testosterone Levels Are Negatively Correlated with International Prostate Symptom Score and Transitional Prostate Volume.

OBJECTIVES: To investigate the correlation of serum total testosterone levels with International Prostate Symptom Score and prostate volume in aging men. METHODS: A cross-sectional study was conducted in 50 men who had participated in a medical examination. Prostate specific antigen levels, International Prostate Symptom Score, total/transitional prostate volume, body mass index, maximal flow rate, and serum total testosterone levels were evaluated. The correlation between serum total testosterone levels and additional parameters was statistically analyzed. RESULTS: The median age and total testosterone levels were 60.4 years (interquartile range: 55.0-68.0 years) and 4.3 ng/mL (interquartile range: 3.6-5.1 ng/mL), respectively. Total testosterone levels showed a significant negative correlation with body mass index, transitional prostate volume, International Prostate Symptom Score (including voiding/storage sub scores). On multivariate linear regression models, the total testosterone level was associated with body mass index and total International Prostate Symptom Score. CONCLUSIONS: As total testosterone levels decrease, both International Prostate Symptom Score and transitional prostate volume increase significantly. These findings provide evidence of the presence of more severe lower urinary tract symptoms and larger transitional prostate volume in aging men.

Resection after preoperative chemotherapy versus synchronous liver resection of colorectal cancer liver metastases: A propensity score matching analysis.

This study aimed to determine the prognostic effects of preoperative chemotherapy for colorectal cancer liver metastasis (CLM).We retrospectively evaluated 2 groups of patients between January 2006 and August 2012. A total of 53 patients who had ≥3 hepatic metastases underwent resection after preoperative chemotherapy (preoperative chemotherapy group), whereas 96 patients who had ≥3 hepatic metastases underwent resection with a curative intent before chemotherapy for CLM (primary resection group). A propensity score (PS) model was used to compare the both groups.The 3-year disease-free survival (DFS) rates were 31.7% and 20.4% in the preoperative chemotherapy and primary resection groups, respectively (log-rank = 0.015). Analyzing 32 PS matched pairs, we found that the DFS rate was significantly higher in the preoperative chemotherapy group than in the primary resection group (3-year DFS rates were 34.2% and 16.8%, respectively [log-rank = 0.019]). Preoperative chemotherapy group patients had better DFSs than primary resection group patients in various multivariate analyses, including crude, multivariable, average treatment effect with inverse probability of treatment weighting model and PS matching.Responses to chemotherapy are as important as achieving complete resection in cases of multiple hepatic metastases. Preoperative chemotherapy may therefore be preferentially considered for patients who experience difficulty undergoing complete resection for multiple hepatic metastases.

Utility of indocyanine-green fluorescent imaging during robot-assisted sphincter-saving surgery on rectal cancer patients.

BACKGROUND: There have been few studies describing the use of indocyanine green (ICG) fluorescent imaging during robot-assisted (RA) sphincter-saving operations (SSOs) and assessing its potential role in reducing anastomotic leak (AL). METHODS: A consecutive cohort of 436 rectal cancer patients who underwent curative RA SSOs were prospectively enrolled during 2010-2014, including 123 patients with ICG imaging (ICG+ group) and 313 patients without ICG imaging (ICG- group). RESULTS: ICG imaging appeared to be helpful in identifying competent perfusion of the bowel adjacent to the anastomosis in 13 patients (10.6%) who might be susceptible to bowel ischaemia, including restrictive mesocolon. AL was remarkably greater in the ICG- group compared with the ICG+ group (5.4% vs 0.8%; p = 0.031). CONCLUSIONS: ICG imaging during RA SSO provides accurate real-time knowledge of the perfusion status at or near the anastomosis, specifically reducing AL in patients who may incur bowel ischaemia. Copyright © 2015 John Wiley & Sons, Ltd.

Outcomes of ultra-low anterior resection combined with or without intersphincteric resection in lower rectal cancer patients.

PURPOSE: We evaluated the current practice of ultra-low anterior resection (uLAR) in patients with lower rectal cancer and compared uLARs using mostly transabdominal approach with or without intersphincteric resection (ISR). METHODS: A total of 624 consecutive lower rectal cancer patients undergoing curative uLAR were prospectively enrolled as ISR+ vs. ISR- groups (329 vs. 295 patients) between 2005 and 2012. The ISR+ group additionally received levator-sphincter reinforcement after distal resection. RESULTS: The circumferential resection margin (CRM) + rate (≤1 mm) was 2.1 % in the two groups. Postoperative ileus occurred more in the ISR- group than in the ISR+ group (p = 0.02). Substantial erectile dysfunction occurred 1.8 times more frequently in the ISR- group than in the ISR+ group (32 vs. 18.1 %; p = 0.01) among male patients at 2 years postoperatively. The urge to defecate volume and maximal tolerance volume, closely correlated with maximal squeezing pressure and/or mean resting pressure, did not differ between patients with and without chemoradiotherapy until 24 months postoperatively. Nevertheless, the urge to defecate volume was lesser in the ISR- group than in the ISR+ group at 24 months postoperatively (p = 0.022). For 301 patients in which >5 years had elapsed postoperatively, the mean 5-year local recurrence rate was 4.3 %, and the 5-year disease-free and overall survival rates were 78.9 and 92 %, respectively, without differences between the two groups. CONCLUSIONS: Compared with uLAR without ISR, the transabdominal ISR with levator-sphincter reinforcement provides a safe resection plane with competent CRM, concurrently reduces substantial complications, and marginally promotes recovery of neorectal function.

A comparison of the technical and oncologic validity between robot-assisted and conventional open abdominoperineal resection.

PURPOSE: This study was to ascertain whether a robot-assisted (RA) approach to APR might facilitate a cylindrical APR by enabling a deeper pelvic dissection during an abdominal approach, concurrently comparing the feasibility and short-term oncologic outcomes. METHODS: Forty-eight consecutive patients with lower rectal cancer who had undergone curative APR (21 RA vs. 27 open) were prospectively enrolled. The short-term operative outcomes and oncologic feasibility were evaluated and compared. A levator muscle excision was performed concomitantly with the abdominal procedure in the RA group and with the perineal procedure in the open group. RESULTS: No patients in the RA group experienced intraoperative perforation or required conversion to open APR. Overall, a cylindrical APR was performed in 72 % of patients, and subtotal excision of the levator muscle, i.e., either one or both sides of the puborectalis and pubococcygeus muscles, was more likely in the RA group (P = 0.019). A positive CRM was exclusively identified in four open APR patients. The mean number of retrieved lymph nodes was greater in the RA group (20 vs. 16, P = 0.035). There was no difference in perineal morbidity between the two groups (P = 0.445). CONCLUSIONS: The RA approach facilitates an efficient excision in the pelvic region than open APR during the abdominal procedure. The RA approach also demonstrated a trend toward improved oncologic outcomes with equivalent postoperative morbidities than with the open approach.

Completely abdominal intersphincteric resection for lower rectal cancer: feasibility and comparison of robot-assisted and open surgery.

BACKGROUND: Most previous studies of intersphincteric resection (ISR) adopted a two-stage procedure involving abdominal and transanal approaches. We performed completely abdominal ISR via open and a robot-assisted (RA) approaches as treatments for lower rectal cancer (LRC). The RA approach might enable deep dissection and facilitate ISR in patients with restrictive pelvic anatomy. METHODS: A consecutive cohort of 222 LRC patients who underwent completely abdominal ISR (RA ISR, n = 108; open ISR, n = 114) was enrolled prospectively, and their short-term outcomes were evaluated. RESULTS: In a multivariate analysis, ISR was performed more frequently in the RA than in the open group (82.6 vs. 67.9 %, p = 0.008). The number of harvested lymph nodes was >12 in both groups. A positive distal resection margin was not observed in either group, and a positive circumferential resection margin was found in one patient in the RA group. Overall morbidity did not differ between the groups. Moderate to severe sexual dysfunction occurred 2.7-fold more frequently in the open group (p = 0.023) among male patients ≤65 years. Mean Wexner's fecal incontinence scores at postoperative months 6 and 12 were greater in the open group than in the RA group (p < 0.05). CONCLUSIONS: Completely abdominal ISR may be feasible in the treatment of LRC, based on a short-term study. Furthermore, RA ISR had equivalent oncological outcomes and slightly improved functional recovery relative to open ISR.