Search

Abstract Background Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell‐to‐cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. Methods We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre‐operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR‐203 expression levels in CRC tissues and pre‐operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR‐203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR‐203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. Results A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35–89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well‐established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour–node–metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P

Objectives: Restorative proctocolectomy and ileal pouch-anal anastomosis is frequently performed in patients with ulcerative colitis and factors suspected of increasing the risk of postoperative infectious complications. Using a three-stage approach may result in improvement in overall outcomes, because this leads to improvement in nutritional status and reduction of immunosuppressive doses. However, the influence of preoperative nutritional status on postoperative infectious complications after this procedure has not been examined. The aim of this study was to clarify the potential associations between nutritional status and postoperative infectious complications in patients with ulcerative colitis undergoing proctectomy with ileal pouch-anal anastomosis. Methods: The records of 110 patients who had undergone proctectomy with ileal pouch-anal anastomosis from January 2000 to March 2018 in Mie University and met the eligibility criteria were reviewed and possible associations between postoperative infectious complications and clinical factors were assessed. Results: Of the remaining 110 patients, 18 (16.4%) had developed postoperative infectious complications. Multivariate analysis revealed that operative bleeding 270 g and prognostic nutritional index

Abstract Background Adenosine-to-inosine (A-to-I) RNA editing is catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes. Recent evidence suggests that RNA editing of antizyme inhibitor 1 (AZIN1) RNA is emerging as a key epigenetic alteration underlying cancer pathogenesis. Methods We evaluated AZIN1 RNA editing levels, and the expression of its regulator, ADAR1, in 280 gastric tissues from 140 patients, using a RNA editing site-specific quantitative polymerase chain reaction assays. We also analyzed the clinical significance of these results as disease biomarkers in gastric cancer (GC) patients. Results Both AZIN1 RNA editing levels and ADAR1 expression were significantly elevated in GC tissues compared with matched normal mucosa (P

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Objectives: Anti-tumor necrosis factor (TNF) antibodies have shown efficacy in the prevention of recurrence of Crohn's disease after intestinal resection. However, some patients develop surgical recurrence despite this therapy. We aimed to evaluate the risk factors for recurrence of Crohn's disease requiring surgery while receiving post-operative anti-TNF therapy. Methods: We performed a retrospective evaluation of 164 patients who had received post-operative anti-TNF maintenance therapy between 2002 and 2016. We classified Crohn's disease-related re-operation as surgical recurrence and analyzed its risk factors using the Cox proportional hazard model. Results: Of the 164 participants, 128 had received infliximab and 36 had received adalimumab maintenance therapy. We obtained follow-up data over a mean of 60.2 months. The proportion of patients with surgical recurrence at 5 years was 14.9%. The only independent risk factor for surgical recurrence, which we identified was post-operative smoking habit (odds ratio, 5.03; 95% CI, 1.14-12.8; P=0.033). Conclusions: Post-operative smoking may be a significant risk factor for post-operative surgical recurrence of Crohn's disease while receiving anti-TNF maintenance therapy.

This pilot study aimed to develop a new technique, complete laparoscopic total mesorectal excision (TME) with an intersphincteric resection (ISR) and coloplasty pouch anal anastomosis to avoid any further abdominal incision other than laparoscopic port sites, and to assess the impact on short-quality of life and oncological outcomes of this technique. After laparoscopic TME, large bowel was dissected at the level of the promontory. Then, laparoscopic construction of the coloplasty pouch was performed. Simultaneously, a rectal specimen with ISR was excised using the transanal approach. Coloplasty pouch was gently pulled from pelvic thorough anal and a hand-sewn coloplasty pouch anal anastomosis was created. We had performed 8 surgeries using the new technique. Though one patient developed pelvic infections, but intestinal continuity could be maintained and no local and distant recurrence was recognized in other patients. We foresee this novel approach to have significant clinical potential for lower rectal cancer patients with ISR.

Neutrophil extracellular traps (NETs) are fibrous mesh-like, web-like, or string-like structures which are composed of DNA, histones, and granule proteins such as neutrophil elastase or myeloperoxidase. When activated by phorbol myristate acetate, interleukin-8, lipopolysaccharide (LPS), and various pathogens, neutrophils release NETs. We reported that NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. In general, extracellular DNAs are used as a surrogate marker of NETs. Here, we describe a protocol regarding quantitative procedures of extracellular DNAs released from ex vivo neutrophils activated by LPS using fluorometric double-stranded DNA (dsDNA) quantification assay.

Neutrophil extracellular traps (NETs) are extracellular DNAs decorated with nuclear and granular proteins such as histones, neutrophil elastase or myeloperoxidase. They exhibit fibrous mesh-like, web-like, or string-like structures. Here, we describe our protocol regarding visualization of ex vivo NETs released from neutrophils activated by lipopolysaccharide (LPS) using fluorescence microscopy.

Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC) patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC,

Neutrophil extracellular traps (NETs) represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer.

Background: Malnutrition can adversely affect treatment responses and oncological outcomes in cancer patients. However, among patients with rectal cancer who undergo chemoradiotherapy (CRT), the significance of peri-treatment nutrition assessment as a predictor of treatment response and outcome remains unclear. Objective: The aim of this study was to determine whether the Prognostic Nutrition Index (PNI) based on peri-treatment serum can be used as a predictor of treatment response and outcome in patients with rectal cancer who undergo CRT. Design, Setting, and Patients: We analyzed 114 patients with rectal cancer who received preoperative CRT followed by total mesorectal excision at our institution. Results: Post-CRT PNI was significantly lower than pre-CRT PNI in rectal cancer patients. Although post-CRT PNI did not significantly correlate with either overall survival or disease-free survival, low pre-CRT PNI was significantly associated with shorter overall survival and disease-free survival in this population and was also an independent risk factor for ineffectiveness of long-course preoperative CRT. Finally, low pre-CRT PNIs were a stronger indicator of poor prognosis and early recurrence in patients with pathological lymph node metastasis (who generally need to receive postoperative chemotherapy), than in those with no pathological lymph node metastasis. Conclusion: Pretreatment PNI could be useful in evaluating and managing patients with rectal cancer who undergo CRT followed by curative resection. [ABSTRACT FROM AUTHOR]

Preoperative chemoradiotherapy (CRT) with total mesorectal excision (TME) is the widely accepted treatment for rectal cancer (RC) in Western countries. However, there remains controversy as to whether preoperative CRT is useful in tumors that extend beyond the mesorectum, including metastasis to the lateral pelvic lymph nodes (LPLN). The aim of this study was to assess the prognostic significance of LPLN enlargement in patients with RC who receive preoperative CRT followed by TME without LPLN dissection. We evaluated the prognostic effect of radiographic LPLN enlargement before and after CRT, as well as the patients' clinicopathological and genetic profiles. Of the 104 patients investigated, pretreatment imaging identified 19 (18%) as LPLN-positive (>7 mm in diameter). Of these 19 patients, 7 (37%) exhibited LPLN downsizing to <7 mm following CRT. The median follow-up period was 52 months. The 5-year cancer-specific survival (CSS) or relapse-free survival (RFS) did not differ significantly between patients who did and those who did not have positive LPLN on pretreatment imaging. However, LPLN that remained positive after CRT were significantly associated with poorer 5-year CSS (73 vs. 84%, respectively; P=0.0052) and RFS (32 vs. 78%, respectively; P=0.0264). None of the patients whose LPLN were downsized to <7 mm following CRT developed recurrence; however, those with positive LPLN after CRT had a 55% higher recurrence rate, characterized by delayed local recurrence, a pattern that may be affected by certain chemokines. In conclusion, changes in initially positive LPLN (>7 mm) may predict the prognosis of patients with RC who receive preoperative CRT-TME. LPLN positivity after CRT was associated with shorter CSS and RFS. Strategies to improve patient survival may include selective LPLN dissection or more aggressive multimodality therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is predominantly a disease of the elderly. Elderly patients may also exhibit poorer outcomes due to the increased burden of comorbidities, functional dependency and limited life expectancy. The aim of this study was to evaluate the outcome of laparoscopic surgery in elderly patients with CRC. A total of 148 patients who underwent laparoscopic surgery at our institution between January, 2000 and December, 2011 were enrolled. We compared the differences between elderly patients (aged >75 years, n=48) and non-elderly patients (aged <75 years, n=100) and evaluated the demographics and disease-related operative and prognostic data. Postoperative complications occurred in 24 (16.2%) of the 148 patients. The American Society of Anesthesiologists score and comorbidity were found to be significantly correlated with complications and the multivariate analysis demonstrated that pulmonary disease, but not age, was an independent factor affecting postoperative complications (odds ratio = 3.21, 95% confidence interval: 1.02-10.14, P=0.0470). Patients with pulmonary comorbidities also exhibited similar rates of postoperative complications compared with 259 matched patients who underwent open surgery during same period (41.2 vs. 46.7%, respectively; P=0.7547). In conclusion, chronological age alone should not be considered a contraindication for laparoscopic surgery for CRC in elderly patients. In addition, selection criteria for laparoscopic CRC surgery in elderly as well as non-elderly patients should include pulmonary comorbidities. [ABSTRACT FROM AUTHOR]

Chronic inflammation increases the risk of developing several gastrointestinal malignancies. Chemokines that are produced by colonic epithelial cells play significant roles in the maintenance and repair of the epithelial barrier. The present study aimed to clarify whether the expression of CCL20 and its receptor, CCR6, was correlated with the development of ulcerative colitis (UC)-associated neoplasia. A total of 93 patients with UC who underwent proctocolectomies were enrolled in the present study. Immunohistochemical analysis for CCL20 and CCR6 expression in the rectal mucosa was performed and the correlation between expression and the pathogenesis of UC-associated neoplasia was investigated. A total of 16 (17.2%) patients presented with UC-associated neoplasia. The immunohistochemistry (IHC) score for CCL20 was significantly increased in the patients with a mild form of the disease (P=0.0363). The IHC score for CCL20 expression in the patients with UC-associated neoplasia was higher compared with the patients without neoplasia (P=0.0294). In contrast, there was no significant correlation between CCR6 expression and the clinicopathological variables. The logistic regression analysis revealed that a high IHC score for CCL20 expression in the rectal mucosa and a disease duration of more than eight years were significantly correlated with the development of UC-associated neoplasia (P<0.05). The results suggest that an evaluation of CCL20 expression in the rectal mucosa may be useful to identify patients who are at a high risk for developing UC-associated neoplasia. However, a selection bias existed in the present study due to the fact that the patient population that was enrolled was not representative of a typical surveillance patient population. [ABSTRACT FROM AUTHOR]

In vivo real-time visualization of the process of angiogenesis in secondary tumors in the same living animals presents a major challenge in metastasis research. We developed a technique for intravital imaging of colorectal liver metastasis development in live mice using two-photon laser scanning microscopy (TPLSM). We also developed time-series TPLSM in which intravital TPLSM procedures were performed several times over periods of days to months. Red fluorescent protein-expressing colorectal cancer cells were inoculated into the spleens of green fluorescent protein-expressing mice. First- and second-round intravital TPLSM allowed visualization of viable cancer cells (red) in hepatic sinusoids or the space of Disse. Third-round intravital TPLSM demonstrated liver metastatic colonies consisting of viable cancer cells and surrounding stroma with tumor vessels (green). In vivo time-course imaging of tumor angiogenesis in the same living mice using time-series TPLSM could be an ideal tool for antiangiogenic drug evaluation, reducing the effects of interindividual variation. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Surgical site infections (SSIs) occur more frequently in surgery for patients with ulcerative colitis than in regular colon surgery. We report here on a joint study that was prospectively conducted by six facilities to verify that performing leukocytapheresis (LCAP) therapy immediately following surgery regulates neutrophil activity and acts to suppress the occurrence of SSIs. Methods  LCAP was performed using Cellsorba EX with nafamostat mesilate as an anticoagulant; therapy was begun within 2 h postoperatively. Subjects were 143 patients undergoing surgery in cases of ulcerative colitis (LCAP group, 40 patients; control group, 103 patients). Results  1) With regard to the SSI incidence rate, SSIs occurred in 4 of 37 patients (10.8%) in the LCAP group overall, whereas they occurred in 29 of 103 patients (28.2%) in the control group overall; in the LCAP group, the occurrence of SSIs tended to be suppressed (P = 0.069). With 2-stage surgery in particular, SSIs occurred in the LCAP group in 1 of 28 patients (3.6%) and in the control group in 21 of 86 patients (24.4%); in the LCAP group, the occurrence of SSIs was significantly lower (P = 0.013). The length of postoperative hospitalization was 24.9 ± 11.1 days for the 36 patients in the LCAP group and 31.2 ± 14.6 days for the 103 patients in the control group; the length was significantly reduced in the LCAP group (P = 0.018). 2) From pre-surgery to day 1 of hospitalization, the granulocyte elastase level rose both in patients who experienced SSIs and in patients who did not experience them. It remained high in patients who experienced SSIs in comparison with patients who did not experience SSIs and was significantly higher prior to LCAP in particular. 3) While LCAP was being performed, there were adverse events in 5 of 40 patients (12.5%), but these were all transient; it was determined that LCAP presented no problems in terms of safety. Conclusion  LCAP therapy was effective in suppressing the occurrence of SSIs following 2-stage surgery for ulcerative colitis and also reduced the length of postoperative hospitalization. [ABSTRACT FROM AUTHOR]

Abstract  The aim of the present review was to investigate whether host-tumor interactions are causal or consecutive clinical factors associated with surgical stress that influence the long-term survival after a curative resection of colorectal cancer. A Medline/PubMed search was conducted to identify the relevant articles investigating the factors related to surgical stress and their effects on the long-term survival after a curative resection of colorectal cancer. The intraoperative state is defined as a cytokine storm in which ongoing local cytokine production occurs at the site of the tumor, thus further enhancing the autocrine cytokine loop for angiogenic factor production. The postoperative state is defined as tissue regeneration in which surgery-related clinical events enhance the systemic induction of inflammatory cytokines, which in turn synergistically exaggerate the local activation of tumor growth factors. Host-tumor interactions under surgical stress may act synergistically as potent tumor growth factors, and may thus influence long-term survival. Controlling surgical insults and/or regulating perioperative inflammatory responses may therefore lead to new therapeutic approaches for controlling disease recurrence. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the expression pattern of Toll-like receptors (TLRs) in the pouch mucosa of ulcerative colitis patients in comparison with that in the ileum mucosa of noninflammatory bowel disease patients. Pouch mucosal biopsy specimens were collected from postoperative patients who had undergone surgery for ulcerative colitis. Normal ileum specimens were collected from colon cancer patients. The specimens were assessed by immunofluorescence histochemistry using TLR2, TLR3, TLR4, and TLR5 polyclonal antibodies. The normal ileal mucosa constitutively expressed TLR3 and TLR5, whereas TLR2 and TLR4 were barely detectable. In the mucosa of active pouchitis, TLR2 and TLR4 was strongly upregulated, and TLR4 was upregulated even in a noninflamed pouch. No TLR3 or TLR5 expression was detectable. These data suggest that pouchitis may be associated with distinctive changes in selective TLR expression in the pouch mucosa, and that TLR4 alterations in the innate response system may contribute to the pathogenesis of these disorders in particular. [ABSTRACT FROM AUTHOR]

Megacolon, resulting in severe constipation, is one of the most common manifestations of Chagas' disease. We herein report a case of megacolon with fecaloma in a 39-year-old Brazilian man who presented with severe constipation. He underwent a total proctocolectomy and ileal J-pouch anal anastomosis. Histologically, there was a marked thickening of the proper muscle layer, and a moderate decrease in the myoenteric nerve plexuses and neurons in the megacolon area. A feasible outcome has been achieved after a 1-year follow-up. A total proctocolectomy with ileal J-pouch anal anastomosis may therefore be one of the useful strategies for the surgical treatment of patients with chagasic megacolon. [ABSTRACT FROM AUTHOR]

The article focuses on anastomotic leak (AL) after esophagectomy and discusses blood flow evaluation using indocyanine green-guided imaging in order to determine optimal site for gastric conduit anastomosis to prevent the leak. Topics discussed include the role of poor blood supply as a risk factor for AL, the use of the intensity of fluorescein in imaging, and the perfusion in the body.