Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon.

BACKGROUND: The purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding. METHODS: This retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations. RESULTS: The two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P <  0.001) and RFS (75.0% vs. 61.9%, P <  0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P <  0.001) and RFS (77.3% vs. 66.2%, P <  0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P <  0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P <  0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon. CONCLUSIONS: NLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.

Long-Term Trends and Predictors of Medical Resource Utilization and Medical Outcomes in Inguinal Hernia Repair: A Nationwide Cohort Study.

BACKGROUND: Few studies have comprehensively and systematically analyzed nationwide samples. This study purposed to explore temporal trends and predictors of medical resource utilization and medical outcomes in these patients to obtain data that can be used to improve healthcare policies and to support clinical and administrative decision-making. METHODS: This study used nationwide population data contained in the Longitudinal Health Insurance Database of Taiwan. The 14,970 inguinal hernia repair patients were enrolled in this study (age range, 18-100 years) from 1997 to 2013 in Taiwan. After temporal trends analysis of demographic characteristics, clinical characteristics, and institutional characteristics, predictors of postoperative medical resource utilization and medical outcomes were evaluated through multiple linear regression analysis and Cox regression analysis. RESULTS: The prevalence of inguinal hernia repair per 100,000 population significantly decreased from 195.38 in 1997 to 39.66 in 2013 (p < 0.05). Demographic characteristics, clinical characteristics, and institutional characteristics were significantly associated with postoperative medical resource utilization and medical outcomes (p < 0.05). Of these characteristics, both surgeon volume and hospital volume had the strongest association. CONCLUSIONS: The inguinal hernia repair prevalence rate gradually decreased during the study period. Demographic characteristics, clinical characteristics, and institutional characteristics had strong associations with postoperative medical resource utilization and medical outcomes. Furthermore, hospital volume and surgeon volume had the strongest associations with postoperative medical resource utilization and medical outcomes. Additionally, providing the education needed to make the most advantageous medical decisions would be a great service not only to patients and their families, but also to the general population.

Monthly tegafur-uracil maintenance for increasing relapse-free survival in ypStage III rectal cancer patients after preoperative radiotherapy, radical resection, and 12 postoperative chemotherapy cycles: a retrospective study.

BACKGROUND: Current advancements in neoadjuvant therapy and total mesorectal excision have engendered increased local control. However, the survival benefit of preoperative radiotherapy (RT; 5 × 5 Gy) in rectal cancer patients remains inadequate, primarily because of systemic recurrence. In this retrospective single-center study, the effects of monthly tegafur-uracil maintenance (≥6 cycles) after 12 fluorouracil-based adjuvant chemotherapy cycles on 3-year relapse-free survival (RFS) was estimated in ypStage III rectal cancer patients. METHODS: Of ypStage III rectal cancer patients who received preoperative RT (5 × 5 Gy) in January 2006-December 2015, those who had ypStage III cancer after preoperative radiation, radical resection, and postoperative chemotherapy were enrolled; excluded patients had ypStage I and II rectal cancer, had double cancer, had synchronous distant metastasis, had local excision, received preoperative chemoradiation, and were lost to follow-up within 1 year after cancer treatment. Included patients received either maintenance therapy or observation after postoperative chemotherapy. The primary endpoint was the effect of maintenance therapy on 3-year RFS. We set the median follow-up duration to be 69.7 (range, 15.4-148.3) months. RESULTS: Of 259 ypStage III rectal cancer patients, 102 (59 men and 43 women) were enrolled based on the inclusion criteria. The maintenance and observation groups comprised 55 and 57 patients, respectively (mean age = 62.2 and 65.7 years, respectively; p = 0.185). The 3-year RFS observed in the maintenance group (85.1%) was longer than that observed in the observation group (67.5%; p = 0.039). Multivariate analysis proved the following to be independent prognostic factors for RFS: higher metastatic lymph node ratio (LNR ≥0.3), tegafur-uracil maintenance (≥6 cycles), and lower rectal cancer (< 6 cm from the anal verge). The higher the rectal cancer location (≥6 cm from the anal verge) was, the higher the tegafur-uracil maintenance survival benefit became (p = 0.041). Moreover, lower cancer location (< 6 cm from the anal verge) and LNR ≥0.3 were both associated with a trend of longer RFS after tegafur-uracil maintenance therapy (p = 0.164 and 0.113, respectively). CONCLUSIONS: After the execution of fluorouracil-based adjuvant chemotherapy, administering monthly tegafur-uracil (≥6 cycles) may improve the 3-year RFS of ypStage III rectal cancer patients.

Common habitual behaviors and synchronous colorectal cancer risk: a retrospective case-control study.

PURPOSE: The association of habitual behaviors with the prevalence of synchronous colorectal cancer (sCRC) is unknown. Here, we investigated whether these behaviors, which are known risk factors for colorectal polyps, may be related to sCRC risk. METHODS: We enrolled 17,093 patients who underwent cancer treatment between January 1995 and December 2016 and examined the association of age, sex, familial history of hereditary colorectal cancer (CRC), and status of three common habitual behaviors (smoking and alcohol and coffee consumption) with the prevalence of sCRC. RESULTS: Of the enrolled patients, 960 (5.6%) patients had sCRC. The independent risk factors for sCRC prevalence included advanced age, male sex, hereditary CRC, smoking, and daily alcohol consumption of more than one bottle (> 600 mL). Contrary to these factors, daily coffee consumption of more than one cup seemed to provide a protection from sCRC. In the Kaplan-Meier test, the significantly worse 5-year overall survival (OS) was noted in smokers with stage 0-III CRC. The effect of alcohol consumption on 5-year OS was significant in stages II and III. Compared with those without daily coffee consumption, patients with daily coffee consumption had significantly higher 5-year OS in stages I (93.0% vs. 86.4%), II (87.1% vs. 77.2%), III (71.5% vs. 61.9%), and IV (18.0% vs. 13.0%). CONCLUSIONS: sCRC prevalence was significantly associated with habitual behaviors. Patients with smoking or with daily alcohol consumption of one bottle had higher sCRC prevalence than did those without these habits. Coffee consumption could be a protective factor for lowering sCRC risk.

Using Ancestry-Informative SNPs to Quantify Introgression of European Alleles into North American Red Foxes.

A recent study demonstrated that British red foxes introduced to the mid-Atlantic coastal plain (ACP) of the eastern United States during the late 18th century successfully interbred with indigenous American red foxes despite half a million year's divergence. However, a large disparity in frequency of European mitochondria (27%) versus Y chromosomes (1%) left unclear the magnitude of genetic exchange. We sought to quantify genomic introgression using 35 autosomal and 5 X-chromosome ancestry-informative markers (AIMs) in conjunction with diagnostic Y chromosome single nucleotide polymorphism (Y-SNP) markers to characterize the modern state of red foxes in the eastern United States and to gain insight into the potential role of reproductive barriers. European admixture was highest in the ACP and apparently restricted to the central eastern United States. We estimated only slightly (and nonsignificantly) European ancestry in autosomal than X-chromosome markers. European ancestry from autosomal and X-chromosome markers (36.4%) was higher than the corresponding mitochondrial (mt) DNA estimate (26.4%) in the ACP. Only 1 of 124 males (<1%) in the ACP had European Y chromosomes, which was similar to the neighboring regions, in which 2 of 99 (2%) males carried a European Y chromosome (the same haplotype). Although we could not rule out drift as the cause of low European Y-chromosome frequency, results were also consistent with F1 male infertility. In the future, more extensive genomic sequencing will enable a more thorough investigation of possible barrier genes on the X chromosome as well as throughout the genome.

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells.

BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. METHODS: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. RESULTS: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, ß-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. CONCLUSION: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.

A proteomics approach to identifying novel protein targets involved in erinacine A-mediated inhibition of colorectal cancer cells' aggressiveness.

Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells' aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A-treated and untreated groups. In addition, erinacine A time-dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A-induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up-regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells.

Selective ß2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt/ERK1/2 Signaling, G1-Phase Arrest, and Apoptosis.

The stress-upregulated catecholamines-activated ß1- and ß2-adrenergic receptors (ß1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of ß1/2-ARs signaling for the treatment of CRC and elucidated the significance of ß2-AR expression in CRC in vitro and in clinical samples. The impacts of ß1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of ß2-AR but not ß1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of ß2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of ß2-AR have a unique pattern in CRC comparing to other cancers. ß2-AR antagonism selectively suppresses the growth of CRC accompanying active ß2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of ß2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, ß2-AR blockage might be a potential therapeutic strategy for combating the progressions of ß2-AR-dependent CRC.

Interleukin-17 induces CC chemokine receptor 6 expression and cell migration in colorectal cancer cells.

The CC chemokine receptor 6 (CCR6) and its ligand CCL20 are involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. In addition, interleukin-17 (IL-17), produced by a T cell subset named "Th17," has been identified as an important player in inflammatory responses, and has emerged as a mediator in inflammation-associated cancer. However, the relevance of IL-17 in the development and progression of CRC still remains to be explored. This study aimed to investigate the effect of IL-17 on the cell migration of CRC cells. Human CRC HCT-116 cells were used to study the effect of IL-17 on CCR6 expression and cell migration in CRC cells. IL-17 treatment induced migration of HCT-116 cells across the Boyden chamber membrane and increased the expression level of the CCR6. Inhibition of CCR6 by small interfering RNA (siRNA) and neutralizing antibody inhibited IL-17-induced cell migration. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK and p38 pathways are critical for IL-17-induced CCR6 expression and cell migration. Promoter activity and transcription factor ELISA assays showed that IL-17 increased NF-κB-DNA binding activity in HCT-116 cells. Inhibition of NF-κB activation by specific inhibitors and siRNA blocked the IL-17-induced CCR6 expression. Our findings support the hypothesis that CCR6 up-regulation stimulated by IL-17 may play an active role in CRC cell migration.

The Efficacy of Postoperative Adjuvant Chemotherapy for Patients with pT3N0M0 Upper Tract Urothelial Carcinoma.

PURPOSE: Nephroureterectomy with bladder cuff excision may not be sufficient as monotherapy for patients with pT3N0M0 upper tract urothelial carcinoma. The efficacy of postoperative adjuvant chemotherapy in this setting remains controversial. We evaluated the efficacy of adjuvant chemotherapy for patients with pT3N0M0 upper tract urothelial carcinoma in overall, cancer specific and recurrence-free survival. MATERIALS AND METHODS: We retrospectively reviewed records on 171 consecutive patients with pT3N0M0 upper tract urothelial carcinoma treated with radical nephroureterectomy between 2004 and 2014 at 2 branches of the same institution. Postoperative adjuvant chemotherapy was gemcitabine/cisplatin or cisplatin/fluorouracil/leucovorin. Overall, cancer specific and recurrence-free survival rates were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis. RESULTS: Postoperative adjuvant chemotherapy was administered in 60 patients vs nonadjuvant therapy in 111 patients. Median followup was 35.8 months. Between the adjuvant and nonadjuvant treatment groups there were statistically significant differences in 5-year cancer specific (80.5% vs 57.6%, p = 0.010) and recurrence-free (74.4% vs 52.9%, p = 0.026) survival rates. Although there was no statistically significant difference in overall survival (71.9% vs 49.0%, p = 0.072), there was a trend of better overall survival in the patients who received postoperative chemotherapy. On multivariable analysis age (p = 0.018), tumor location (p = 0.003) and adjuvant chemotherapy (p = 0.001) were predictors of cancer specific survival. CONCLUSIONS: Adjuvant chemotherapy improves cancer specific and recurrence-free survival in patients with pT3N0M0 upper tract urothelial carcinoma after radical nephroureterectomy.

Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells.

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. RESULTS: Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity. CONCLUSIONS: Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.

Proteomic analysis of the effects of baicalein on colorectal cancer cells.

Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicalein's target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein-treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein-treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6). Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

Stromal cell-derived factor-1/CXC receptor 4 and ß1 integrin interaction regulates urokinase-type plasminogen activator expression in human colorectal cancer cells.

The stromal cell-derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) axis has been shown to play a role in colorectal cancer progression. In addition, the protease urokinase-type plasminogen activator (uPA) is an important factor in tumor cell invasion and metastasis. However, the mechanism by which SDF-1 mediates uPA expression in human colorectal cancer cells remains unknown. We investigated the molecular mechanism governing the interaction between SDF-1 stimulation and uPA expression in three human colon cancer cell lines (DLD-1, SW48, and COLO 205). We found that SDF-1 stimulation led to an increase in the expression and secretion of uPA in these cells. Experiments involving specific inhibitors and small interfering RNA demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways are critical for SDF-1-induced uPA expression. Analysis of transcription factor binding using ELISA and chromatin immunoprecipitation assays revealed that SDF-1 increased Sp1- and AP-1-DNA-binding activities in DLD-1 cells. Inhibition of Sp1 and AP-1 activation blocked the SDF-1-induced expression and activity of the uPA promoter. The effect of SDF-1 on DLD-1 signaling and uPA expression was mediated by the CXCR4/ß1 integrin axis. In summary, our findings elucidate the mechanisms of SDF-1/CXCR4 downstream signaling and provide insights into the function of SDF-1 in colon cancer cells.

Does body mass index impact the number of LNs harvested and influence long-term survival rate in patients with stage III colon cancer?

BACKGROUND: The aim of this study is to evaluate whether different body mass index (BMI) values affect lymph node (LN) retrieval and whether such variations influence long-term survival in Asian patients. METHOD: From January 1995 to July 2003, 645 stage III colon cancer patients were enrolled in our study. Patients were stratified into four groups: Obese (BMI ≧ 27 kg/m(2)), overweight (24 ≤ BMI < 27 kg/m(2)), normal (18.5 ≤ BMI < 24 kg/m(2)), and underweight (BMI < 18.5 kg/m(2)). RESULTS: Mean BMI in the cohort was 23.3 kg/m(2). Mean number of LNs harvested was 23.1, 19.5, 19.8 and 28.1 in the normal, overweight, obese and underweight groups, respectively. There was a significant difference in the mean number of LNs harvested when comparing the overweight and underweight groups to the normal group (p = 0.013 and p = 0.04, respectively). Females were overrepresented in the underweight group (p = 0.011), and patients who had proximal colon cancers were more frequently underweight (p = 0.018). The mean number of LNs harvested varied by cases of right hemicolectomy (p = 0.009) and proximal cancer location (p = 0.009) for different BMI groups. Multivariate analysis showed that underweight, proximal colon cancer, well- or moderately differentiated adenocarcinoma and stage IIIC cancer were significant variables for adequate LN recovery. BMI was not significantly associated with relapse-free survival (p = 0.523) or overall survival (p = 0.127). CONCLUSION: BMI is associated with LN harvest but is not an independent variable in stage III colon cancer survival.

Metastasis at the colostomy site: a rare case report.

Metastasis at the colostomy site is rare. Most reported patients with such metastases undergo abdominoperineal resection and this kind of metastases happened after a longer period post-cancer surgery. In our patient, because it happened during a short interval between rectal cancer surgery and stoma closure, colostomy site metastasis probably occurred owing to ablative cancer cell reflux and seeding from the obstruction during decompressive colostomy rather than local, lymphatic or haematogenous spread. Meticulous histologic analyses to rule out undetected, concomitant polyps and metachronous cancer are very important for patients with obstructive colorectal cancer who undergo decompressive colostomy. The potential risk of colostomy site metastasis during staged surgery for obstructive colorectal cancer remains uncertain; however, the result from this case report raises the question of such a risk for further studies in a greater number of patients.

The development of an eye movement-based deep learning system for laparoscopic surgical skills assessment.

The development of valid, reliable, and objective methods of skills assessment is central to modern surgical training. Numerous rating scales have been developed and validated for quantifying surgical performance. However, many of these scoring systems are potentially flawed in their design in terms of reliability. Eye-tracking techniques, which provide a more objective investigation of the visual-cognitive aspects of the decision-making process, recently have been utilized in surgery domains for skill assessment and training, and their use has been focused on investigating differences between expert and novice surgeons to understand task performance, identify experienced surgeons, and establish training approaches. Ten graduate students at the National Taiwan University of Science and Technology with no prior laparoscopic surgical skills were recruited to perform the FLS peg transfer task. Then k-means clustering algorithm was used to split 500 trials into three dissimilar clusters, grouped as novice, intermediate, and expert levels, by an objective performance assessment parameter incorporating task duration with error score. Two types of data sets, namely, time series data extracted from coordinates of eye fixation and image data from videos, were used to implement and test our proposed skill level detection system with ensemble learning and a CNN algorithm. Results indicated that ensemble learning and the CNN were able to correctly classify skill levels with accuracies of 76.0% and 81.2%, respectively. Furthermore, the incorporation of coordinates of eye fixation and image data allowed the discrimination of skill levels with a classification accuracy of 82.5%. We examined more levels of training experience and further integrated an eye tracking technique and deep learning algorithms to develop a tool for objective assessment of laparoscopic surgical skill. With a relatively unbalanced sample, our results have demonstrated that the approach combining the features of visual fixation coordinates and images achieved a very promising level of performance for classifying skill levels of trainees.

Intracavernous Injection of Autologous Platelet-Rich Plasma Ameliorates Hyperlipidemia-Associated Erectile Dysfunction in a Rat Model.

INTRODUCTION: Hyperlipidemia is associated with an increased risk of erectile dysfunction (ED) mediated by endothelial damage. Platelet-rich plasma (PRP) contains numerous angiogenic growth factors. Currently, evidence supporting the use of PRP for ED treatment is limited. AIM: We investigated PRP in a rat model of hyperlipidemia-associated ED. METHODS: Thirty 2-month-old male Sprague-Dawley rats were randomly divided into 3 groups. 20 rats were fed a high-fat diet for 5 months and were randomly divided into 2 groups: (i) rats in the H group received supernatant injection into the corpus cavernosum weekly for 4 weeks; (ii) rats in the H + PRP group received PRP injection into the corpus cavernosum weekly for 4 weeks. 10 rats were fed a standard diet for 5 months and received supernatant injection into the corpus cavernosum weekly for 4 weeks (N group). 7 days after the 4th injection, all rats underwent erectile function testing and then euthanasia. MAIN OUTCOME MEASURES: Erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP). Serum and penile tissue were collected for metabolic variable assessment and histochemical examination, respectively. RESULTS: Intracavernous pressure/MAP and area under the curve/MAP ratios were significantly higher in the N and H + PRP groups than in the H group. Insulin-like growth factor-1, brain-derived neurotrophic factor, and vascular endothelial growth factor levels were significantly higher in the H + PRP group than in the N and H groups. Corporal neuronal nitric oxide synthase, endothelial nitric oxide synthase, and endothelial cells were weakly expressed in the H group compared with the N and H + PRP groups. Intracorporal oxidative stress and apoptotic index were significantly higher in the H group than in the N and H + PRP groups. CONCLUSIONS: This preclinical evidence suggests that clinical trials of PRP in men with ED should be considered. PRP may play a role in ED management. Huang YC, Wu CT, Chen MF, et al. Intracavernous Injection of Autologous Platelet-Rich Plasma Ameliorates Hyperlipidemia-Associated Erectile Dysfunction in a Rat Model. Sex Med 2021;9:100317.

Metastatic lymph node ratio is a more precise predictor of prognosis than number of lymph node metastases in stage III colon cancer.

OBJECTIVE: The objective of this study is to assess the value of metastatic lymph node ratio (LNR) in predicting disease-free survival (DFS) in patients with stage III adenocarcinoma of the colon. MATERIALS AND METHODS: From 1995 to 2003 inclusively, a total of 624 patients featuring stage III adenocarcinoma of the colon underwent curative resection. Of the 624 patients, an adequate number of lymph nodes (n > or = 12) had been harvested in 490 patients. These patients were stratified into LNR groups 1 (LNR < or = 0.4), 2 (0.4 < LNR < or = 0.7), and 3 (LNR > 0.7). Kaplan-Meier survival curve and log-rank test were used to evaluate the prognostic value of LNR. A Cox regression model was used for multivariate analyses. RESULTS: The 5-year DFS rate was 66.7% for patients with LNR1, 35.1% for those with LNR2, and 0% for patients with LNR3 (p < 0.0001). In T3/4LNR1 patients (n = 411), there was no difference in survival between those with N1 stage and those with N2 stage. Cox proportional hazards regression analysis revealed that N stage (number of positive lymph nodes) was not a significant factor when LNR was taken into consideration. CONCLUSIONS: LNR is a more precise predictor of 5-year DFS than number of positive lymph nodes (N stage) in patients with stage III colon cancer.

Flavopereirine Suppresses the Growth of Colorectal Cancer Cells through P53 Signaling Dependence.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. The outcome of CRC patients remains poor. Thus, a new strategy for CRC treatment is urgently needed. Flavopereirine is a ß-carboline alkaloid extracted from Geissospermum vellosii, which can reduce the viability of various cancer cells through an unknown mode of action. The aim of the present study was to investigate the functional mechanism and therapeutic potential of flavopereirine on CRC cells in vitro and in vivo. Our data showed that flavopereirine significantly lowered cellular viability, caused intrinsic and extrinsic apoptosis, and induced G2/M-phase cell cycle arrest in CRC cells. Flavopereirine downregulated Janus kinases-signal transducers and activators of transcription (JAKs-STATs) and cellular myelocytomatosis (c-Myc) signaling in CRC cells. In contrast, the enforced expressions of constitutive active STAT3 and c-Myc could not restore flavopereirine-induced viability reduction. Moreover, flavopereirine enhanced P53 expression and phosphorylation in CRC cells. CRC cells with P53 knockout or loss-of-function mutation significantly diminished flavopereirine-mediated viability reduction, indicating that P53 activity plays a major role in flavopereirine-mediated CRC cell growth suppression. Flavopereirine also significantly repressed CRC cell xenograft growth in vivo by upregulating P53 and P21 and inducing apoptosis. In conclusion, flavopereirine-mediated growth suppression in CRC cells depended on the P53-P21, but not the JAKs-STATs-c-Myc signaling pathway. The present study suggests that flavopereirine may be efficacious in the clinical treatment of CRC harboring functional P53 signaling.

Prognostic significance of unintentional body weight loss in colon cancer patients.

The aim of the present study was to investigate whether unintentional body weight loss (BWL) provides additional clinical information in terms of tumor progression and prognosis in non-metastatic colon cancer. In the present study, a total of 2,406 consecutive colon cancer patients without metastasis were retrospectively enrolled. Unintentional BWL was defined as loss of >5% of body weight within the last 6-12 months, or defined subjectively upon fulfillment of at least two of the following: Evidence of change in clothing size and corroboration of the reported weight loss by family or friend. This category was recorded as present ('with') or absent ('without'). Logistic regression analysis was performed to determine the correlation between BWL and the tumor characteristics and post-operative outcomes of patients with colon cancer. The Cox regression model was used to determine the association of BWL with long-term survival of colon cancer patients. A significant association between BWL and tumor location [right vs. left: Odds ratio (OR)=1.62; P<0.001], tumor size (≥5 vs. <5 cm: OR=2.17; P<0.001), and tumor stage based on the tumor-nodes-metastasis system (T3-T4 vs. T1-T2: OR=2.02; P<0.001). Post-operative morbidity and mortality were not significantly influenced by BWL. Multivariate analysis revealed that BWL was significantly associated with overall survival [with vs. without BWL: Hazard ratio (HR)=1.178; P=0.036] and relapse-free survival (with vs. without BWL: HR=1.332; P=0.003). In conclusion, BWL in patients with colon cancer is not just a symptom, but it is also correlated with tumor location, size and depth, and is a prognostic factor for poor outcomes including overall survival and tumor relapse.