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Abstract Aims The prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short‐ and long‐term outcomes in patients with CRC. Methods This was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease‐free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection. Results Increased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease‐free and overall survival. Similar outcomes were observed in a subanalysis focused on high‐risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score‐matching analysis validated the impact of IBI on the prognosis in CRC patients. Conclusion We established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow‐up.

Abstract Background and aims Crohn's disease (CD)‐associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger‐onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD‐associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC. Methods CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD‐associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old). Results Younger‐onset CDAAC (YO‐CDAAC) patients were significantly more likely to have a poor outcome than those with older‐onset CDAAC (OO‐CDAAC) in terms of both disease‐free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09–4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05–3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO‐CDAAC (p = 0.012 and 0.0031, respectively). Conclusions YO‐CDAAC may have a poorer prognosis compared with OO‐CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.

Live imaging of experimental animals is now possible thanks to recent technological advances that overcome the limitations of conventional histological analysis. In contrast to conventional histological microscopy techniques, this intravital approach can reveal previously unknown morphogenetic and functional processes in live tissues. In addition, this approach can capture real-time information on these processes, compared with conventional histological microscopy and other techniques that only provide snapshots in time. We used multi-photon laser-scanning microscopy (MPLSM) for in vivo real-time imaging of intra-abdominal organs, and investigated the intravital microscopic changes in various disease-model mice, referred to as ‘dynamic pathology’. For example, we used this technology to examine bacterial translocation in dextran sodium sulfate (DSS)-induced colitis, thrombus formation in laser-induced endothelial injury, neutrophil extracellular traps, the dynamics of circulating free DNA in a model of DSS-induced colitis, and to obtain a comprehensive understanding of the development and blood flow dynamics of the small intestinal microcirculation in a mouse model of necrotizing enterocolitis. This mini review summarizes the in vivo observation methods that we have developed to observe the dynamic pathology in various disease-model mice using MPLSM.

Abstract Aim The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results The study included 296 patients with ovarian metastasis. The 3‐y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3‐y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P

Abstract Background Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. Case presentation Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. Conclusion DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery.

Abstract Background Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. Case presentation A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. Conclusions Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Abstract Aim To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods This multi‐institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Abstract Aim This study was performed to evaluate the oncological impact of surgical site infection (SSI) and pneumonia on long‐term outcomes after esophagectomy. Methods The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 407 patients with curative stage I/II/III esophageal cancer at 11 centers from April 2013 to March 2015. We investigated the association of SSI and postoperative pneumonia with oncological outcomes in terms of relapse‐free survival (RFS) and overall survival (OS). Results Ninety (22.1%), 65 (16.0%), and 22 (5.4%) patients had SSI, pneumonia, and both SSI and pneumonia, respectively. The univariate analysis demonstrated that SSI and pneumonia were associated with worse RFS and OS. In the multivariate analysis, however, only SSI had a significant negative impact on RFS (HR, 1.63; 95% confidence interval, 1.12–2.36; P = 0.010) and OS (HR, 2.06; 95% confidence interval, 1.41–3.01; P

Abstract Background The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD‐associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse‐free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16–3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28–3.63, p = 0.004). Conclusions Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.

Abstract Aim To investigate the impact of postoperative infection (PI), surgical site infection, and remote infection (RI), on long‐term outcomes in patients with colorectal cancer (CRC). Methods The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 1817 curative stage I/II/III CRC patients from April 2013 to March 2015. Patients were divided into the No‐PI group and the PI group. We examined the association between PI and oncological outcomes for cancer‐specific survival (CSS) and overall survival (OS) using Cox proportional hazards models and propensity score matching. Results Two hundred and ninety‐nine patients (16.5%) had PIs. The 5‐year CSS and OS rates in the No‐PI and PI groups were 92.8% and 87.6%, and 87.4% and 83.8%, respectively. Both the Cox proportional hazards models and propensity score matching demonstrated a significantly worse prognosis in the PI group than that in the No‐PI group for CSS (hazard ratio: 1.60; 95% confidence interval: 1.10‐2.34; P = .015 and P = .031, respectively) but not for OS. RI and the PI severity were not associated with oncological outcomes. The presence of PI abolished the survival benefit of adjuvant chemotherapy. Conclusions These results suggest that PI after curative CRC surgery is associated with impaired oncological outcomes. This survival disadvantage of PI was primarily derived from surgical site infection, not RI, and PI induced lower efficacy of adjuvant chemotherapy. Strategies to prevent PI and implement appropriate postoperative treatment may improve the quality of care and oncological outcomes in patients undergoing curative CRC surgery.

A 76-year-old Japanese man presented with a 6-year history of a sore throat. He was treated at several clinics without any improvement before being referred to us. Physical examination revealed widespread erosions and ulcers from the palate to the larynx. Approximately 25 × 15 mm in size, erosive lesions were present on the retroauricular regions, forearms, and glans penis. Pseudomembranous conjunctivitis was also observed. The skin biopsy revealed a partial cleft formation below the epidermis, suggesting subepidermal bullous disease. Immuno-serological tests were negative for anti-desmoglein 1 (Dsg1), anti-Dsg3, anti-BP180, and anti-BP230 antibodies by ELISAs. A whole-body examination revealed gastric cancer. The possibility of mucous membrane pemphigoid (MMP) or paraneoplastic pemphigus (PNP) was considered. Indirect immunofluorescence using rat bladders showed positive IgG reactivity with cell surfaces on the transitional epithelia. Immunoblotting using recombinant proteins of laminin-332 showed both IgG and IgA reactivities with laminin-α3, and immunoblotting using normal human epidermal extract showed double-positive reactivities with envoplakin and periplakin for both IgG and IgA antibodies. Based on the clinical and histopathological features and results of various immuno-serological tests, our case was diagnosed as anti-laminin-332-type MMP with serological findings of PNP. Twenty days after laparoscopic gastrectomy, treatment with oral methylprednisolone 32 mg/day was initiated, and mucosal and skin lesions improved.

Abstract Background Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC. Methods We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies. Results We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation. Conclusions We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.

Objectives: Systemic inflammatory response is strongly associated with poor oncological outcome in colorectal cancer (CRC). Perioperative inflammation caused by surgical stress can lead to the development of postoperative infectious complications (PIC) as well as cancer-related inflammation. We aimed to evaluate the prognostic potential of perioperative systemic inflammation by calculating the time-dependent cumulative C-reactive protein (CRP) levels during the perioperative period. Methods: We analyzed clinicopathological data from 540 patients with CRC who underwent potentially curative surgery at our institution. The time-dependent aggregated CRP level was denoted “cumulative CRP,” which represents the area under the line of time (days) and the CRP levels preoperatively and on postoperative days 1, 3, and 7. Results: Cumulative CRP was significantly higher in patients with CRC undergoing open surgery than in patients undergoing laparoscopic surgery. In multivariate analysis, high cumulative CRP was an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in both the laparoscopic and open surgery groups. Patients with CRC and high cumulative CRP had significantly poorer DFS and OS than those with low cumulative CRP, including those patients without PIC. Conclusions: Cumulative CRP is an independent predictive marker of OS and DFS in patients with CRC who undergo curative surgery.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Abstract Background Intrapelvic aberrant needles are rare in clinical practice. Long-term foreign bodies in the abdominal cavity may form granulation tissue or an abscess, and may cause organ injury. Therefore, such foreign bodies need prompt removal. Case presentation A 26-year-old male athlete was referred to our hospital for investigation of an aberrant acupuncture needle in the gluteus. The needle was unable to be removed during acupuncture treatment, and the end broke off and remained in the gluteus. Abdominal X-ray examination showed a thin, 40-mm-long, metallic foreign body resembling an acupuncture needle. Abdominal computed tomography showed an abnormal shadow in the gluteus. However, it was unclear whether the tip of the needle reached the pelvic cavity. Thus, it was decided to surgically extract the needle via laparoscopic surgery under X-ray guidance as a safe and minimally invasive method. Although X-ray fluoroscopy confirmed that the aberrant needle was located in the gluteus, the needle could not be felt with the forceps, as the peritoneum surrounding the needle had granulomatous changes due to inflammation. Therefore, the retroperitoneum was further dissected to search for the needle. Once the needle was identified, its flexibility enabled it to be easily removed by grasping it directly with a needle holder. The length of the aberrant needle was 40 mm. The postoperative course was uneventful, and the patient was discharged from hospital on postoperative day 2. Conclusions When a foreign body remains in the gluteus and its tip touches intrapelvic organs, such as the rectum, it is critical to determine the best approach for its safe removal. Given the anatomical location of the foreign body and the patient background, laparoscopic removal was considered the best approach in the present case.

Abstract Aim The clinical significance of the geriatric nutritional risk index (GNRI) in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy (CRT) followed by curative surgery has not been comprehensively evaluated. Methods This retrospective study enrolled 93 LARC patients diagnosed with clinical lymph node metastasis. The GNRI formula was as follows: 1.489 × albumin (g/l) + 41.7 × current weight/ideal weight. Patients were categorized as GNRI low (GNRI 104.25) according to the receiver operating characteristic (ROC) curve for survival analysis. The impact of GNRI status on the prognostic outcomes of curative surgery for LARC was examined. Results There were 55 (59.14%) and 38 (40.86%) patients in the GNRI high and low groups, respectively. Of the investigated demographic factors, age, pathological tumor invasion, and presence of recurrence were significantly associated with the GNRI value. In Kaplan–Meier analysis, overall survival (OS) and disease-free survival (DFS) were significantly shorter in the GNRI low group (OS: p = 0.00020, DFS: p = 0.0044, log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a low GNRI was an independent risk factor for poor OS (hazard ratio (HR) = 3.22; 95% confidence interval (CI), 1.37–8.23; p = 0.0068) and DFS (HR = 2.32; 95%CI = 1.15–4.79; p = 0.018). Although use of adjuvant therapy has no impact on prognosis (OS: p = 0.26, DFS: p = 0.29), low GNRI showed shorter OS and DFS in patients with pathological lymph node metastasis [ypN(+)] (OS: p = 0.033, DFS: p = 0.032, log-rank test). Conclusions GNRI is a useful marker for LARC patients diagnosed with clinical lymph node metastasis and treated by preoperative CRT followed by curative surgery. GNRI is a useful tool to identify high risk of recurrence for improving the survival in LARC patients.

Abstract Fusobacterium nucleatum (Fn) is frequently found in colorectal cancers (CRCs). High loads of Fn DNA are detected in CRC tissues with microsatellite instability-high (MSI-H), or with the CpG island hypermethylation phenotype (CIMP). Fn infection is also associated with the inflammatory tumor microenvironment of CRC. A subtype of CRC exhibits inflammation-associated microsatellite alterations (IAMA), which are characterized by microsatellite instability-low (MSI-L) and/or an elevated level of microsatellite alterations at selected tetra-nucleotide repeats (EMAST). Here we describe two independent CRC cohorts in which heavy or moderate loads of Fn DNA are associated with MSI-H and L/E CRC respectively. We also show evidence that Fn produces factors that induce γ-H2AX, a hallmark of DNA double strand breaks (DSBs), in the infected cells.

Abstract Background Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. Aim To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. Methods This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch–anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. Results Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). Conclusion IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Abstract Advances in surgical and adjuvant therapies have resulted in a dramatic improvement in outcomes of rectal cancer in terms of both oncology and functional preservation. Surgery plays a central role in therapy as it is the only means of achieving a complete cure. These surgical advancements result from extensive pioneering research in the fields of anatomy and physiology. Much history lies behind the recent surgical breakthroughs of total mesorectal excision (TME) and intersphincteric resection (ISR). This article outlines the changes that have taken place in surgical therapies for rectal cancer over more than a century based on clinical trials performed to provide scientific evidence for these therapies.

Abstract Background The purpose of this study is to identify perioperative marker predicting postoperative surgical site infection (SSI) including with anastomotic leakage (AL) in curative colon cancer patients, laparoscopically. Methods In total, 135 colon cancer patients (stage I–III) undergoing curative laparoscopic surgery between January 2004 and December 2013 were enrolled in this study. We collected data on clinicopathological factors, laboratory data on pre and postoperative day 3 (POD3) and tumor markers levels to assess the relation to surgical site infection (SSI) including with anastomotic leakage (AL). Results SSI and AL occurred in 16 cases (5.6%) and 4 cases (3%), respectively. SSI and AL were not association with clinicopathological factors. Within laboratory data and tumor markers preoperatively, high neutrophil counts were significantly associated with SSI (P

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

Background: Preoperative hypoalbuminemia is a well-known risk factor for anastomotic leakage after colorectal surgery, but the association between perioperative albumin level and anastomotic leakage has not been fully investigated in curative colorectal cancer (CRC) patients. Methods: In total, 200 CRC patients (Stage I–III) undergoing curative laparoscopic surgery between January 2004 and December 2013 were enrolled in this study. We collected data on surgical factors, perioperative levels of serum albumin and inflammatory markers, and perioperative factors affecting hypoalbuminemia from 196 CRC patients to assess the relation to anastomotic leakage. Results: Anastomotic leakage occurred in 11 cases (5.6%) and the frequency was higher in rectal cancer patients (p = 0.0044). There was no significant difference of preoperative serum albumin level between the anastomotic leakage group (AL) and the nonanastomotic leakage group (NAL). Postoperative serum albumin levels in AL were significantly lower than in NAL [postoperative day (POD) 0, p = 0.0004; POD1, p = 0.0001; POD3, p = 0.0004; and POD7, p = 0.0021]. On multivariate analysis, lower average level of serum albumin on POD1 and POD3 {odds ratio (OR) [95% confidence interval (CI)] = 7.53 (1.60–55.80), p = 0.0095}, higher average level of serum white blood cells on POD1 and POD3 [OR (95% CI) = 7.24 (1.40–59.25), p = 0.0165], and surgery for rectal cancer [OR (95% CI) = 15.18 (3.26–93.99), p = 0.0004] were independent risk factors for anastomotic leakage. Conclusion: Lower early postoperative serum albumin levels are a potentially valuable indicator of anastomotic leakage in CRC patients undergoing curative surgery.

Abstract Background Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may be important epigenetic regulators of gene expression in human cancers; however, their functional and clinical significance in colorectal cancer (CRC) remains unknown. Methods We performed piRNA expression profiling in paired cancer and normal tissues through small RNA-sequencing. The clinical significance of candidate piRNAs was investigated, and independently validated in 771 CRC patients from three independent cohorts. The biological function of piRNAs was characterized in cell lines, followed by identification and validation of downstream target genes in CRC tissues. Results We identified piR-1245 as a novel and frequently overexpressed noncoding RNA in CRC, and its expression significantly correlated with advanced and metastatic disease. Patients with high piR-1245 expression experienced significantly shorter overall survival, and multivariate analysis identified its expression to serve as an independent prognostic biomarker in CRC. Functionally, piR-1245 acts as an oncogene and promotes tumor progression, and gene expression profiling results identified a panel of downstream target-genes involved in regulating cell survival pathway. Based upon piRNA:mRNA sequence complementarity, we identified a panel of tumor suppressor genes (ATF3, BTG1, DUSP1, FAS,NFKBIA, UPP1, SESN2, TP53INP1 and MDX1) as direct targets of piR-1245, and successfully validated an inverse correlation between their expression and piR-1245 in CRC. Conclusions We for the first time have identified the role for a PIWI-interacting noncoding RNA, piR-1245, as a novel oncogene and a potential prognostic biomarker in colorectal cancer.

Abstract Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

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.

A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection. [ABSTRACT FROM AUTHOR]

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC.

Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by cutaneous and muscle manifestations. The association between DM and malignancy has been well recognized for many years. The clinical course of paraneoplastic DM may be affected by malignancies, although the cause and effect relationship between exacerbation of DM and cancer progression is uncertain. Herein, we report a 44-year-old woman who presented with progressive DM associated with rectal cancer. After curative resection of rectal cancer, DM symptoms resolved. Three months after surgery, blood test surveillance showed elevation of serum carcinoembryonic antigen levels, although the patient remained asymptomatic. One month later she had a DM flare-up, and multiple lung and liver metastases were found. She immediately underwent cancer chemotherapy with prednisolone therapy for DM. However, her condition deteriorated and she was unable to swallow. Percutaneous endoscopic gastrostomy was constructed, allowing alimentation and oral delivery, which made it possible to keep her on chemotherapy. She had remarkable response for unresectable metastases 8 weeks after the administration of chemotherapy. Seven months after onset of recurrence, her condition improved considerably and she had stable disease. Moreover, she can now eat food of soft consistency. Our case provides further support for the clinical importance of cancer chemotherapy for patients who have progressive DM and unresectable rectal cancer.