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Introduction: There are little data concerning the long-term outcome of single-incision laparoscopic surgery (SILS) for colon cancer. Therefore, we investigated not only the short-term outcomes but also the long-term outcomes of SILS for right-side colon cancer. Methods: We retrospectively compared short- and long-term outcomes of SILS and conventional laparoscopic surgery (CLS) for right-sided colon cancer in our institution. Intergroup differences of short-term outcomes were evaluated using χ2 or Fisher exact tests and 2-sample Student t tests. The disease-free survival rates (long-term outcome) of stage II and III patients were estimated using the Kaplan-Meier method and compared using log-rank tests. Results: There were 290 operations conducted for right-side (cecum and ascending) colorectal cancers from April 2011 to July 2018. Open surgery was performed in 12 cases from start to the operation. SILS was performed in 196 cases and CLS in 55 cases. One patient underwent intraoperative conversion from SILS to laparotomy for bleeding control. In addition, 1 port was added to SILS in 3 cases. These 4 cases were included in the analysis as the SILS group according to the principle of intent to treat. Background: Factors including age, gender, body mass index, performance status, and tumor stage were not statistically different between the SILS and CLS groups. In short-term outcomes, the number of harvested lymph nodes was not statistically different. SILS required less operating time (p < 0.001) and resulted in a reduced bleeding volume (p < 0.001). There was no statistical difference in the frequency of overall complications (p = 0.06). The disease-free survival of stage II and III patients was not statistically different between the 2 groups. Conclusions: With the proper adaptation of SILS by an experienced surgeon, the short- and long-term outcomes of SILS were not inferior to those of CLS. Therefore, SILS could be a treatment option for right-sided colon cancer.

Background The robotic system has been applied in the treatment of gastric cancer (GC), and the procedure has been found to be safe and feasible. Situs inversus totalis (SIT) is a relatively rare autosomal recessive congenital anomaly. We successfully performed robot-assisted proximal gastrectomy (RAPG) and handsewn double-flap esophagogastrostomy for GC in a patient with SIT. Case presentation A 71-year-old woman was referred to us with an asymptomatic ulcerative lesion in the upper body of the stomach. Computed tomography revealed that she had SIT. She was diagnosed with cT1bN0M0, cStageIA gastric cancer. RAPG with lymph node dissection and handsewn double-flap esophagogastrostomy was performed. Robotic surgery enabled the surgeon to perform the surgery without changing his position and experiencing any confusion resulting from the patient’s reversed anatomy. It took 448 min, and no intraoperative complications occurred. Her postoperative course was uneventful; she was discharged on postoperative day 10. The final pathologic report showed pT1b1N0M0, pStage IA. Conclusions This is the first case describing RAPG with handsewn double-flap esophagogastrostomy for a SIT patient with early GC.

Lessons Learned The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. Background Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival. Results In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6–84.4–74.5–85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusion Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.

Introduction Sarcomatoid carcinoma (SC) is a rare subtype of malignant neoplasm with a poor prognosis that involves both carcinomatous and sarcomatous components. Although it may develop in various organs, SC in the large intestine has rarely been reported. It is not rare for patients with SC to have distant metastasis, reflecting its highly aggressive oncologic features, but cases with brain metastasis on initial visit are rare. In this report, we described a case of SC in the transverse colon with brain metastases whose initial symptom was neurological disorder, and reviewed 31 reported cases of SC. Case presentation A 70-year-old man was admitted to our hospital with the chief complaints of gait disorder and severe dizziness. Head magnetic resonance imaging revealed tumor masses in the anterior lobe and cerebellum. A large tumor in the transverse colon was detected by colonoscopy and abdominal enhanced computed tomography (CT), and was diagnosed as undifferentiated adenocarcinoma by histology. Laparoscopic extended right hemicolectomy was performed to remove the obstruction, and the resected specimens revealed an invasive tumor consisting of a mixture of carcinomatous and sarcomatous components. According to the immunopathological study, the patient was diagnosed with SC. The clinical course was extremely aggressive, and the patient died on the 28th postoperative day because of disease progression. Conclusion To the best of our knowledge, this is the first case of SC in the transverse colon with a neurological disorder derived from brain metastases. This experience may contribute to the guidance regarding proper therapeutic options for SC.

Paraduodenal hernia is traditionally repaired via conventional laparotomy. Recently, several reports described the repair of paraduodenal hernia via laparoscopic surgery with multiple ports. Due to development of the technique and devices for laparoscopic surgery, single-incision laparoscopic surgery (SILS) has been applied to various operations, including cholecystectomy, appendectomy, and procedures for colorectal cancer. Here, we report treatment of a left paraduodenal hernia via SILS. A 23-year-old man presented with abrupt onset of abdominal pain, nausea, and vomiting. Computed tomography revealed a mass of intestinal loops enveloped by a thin capsule on the left of the abdominal cavity. Blood circulation in the jejunal loops was preserved, and no dilatation of the jejunum was observed. Physical and radiographic examination indicated the possibility of left paraduodenal hernia; we performed paraduodenal hernia repair using SILS. After we confirmed that there was no strangulation or gangrenous change in the bowel on laparoscopic examination, we reduced the incarcerated jejunum loops via an atraumatic method. The postoperative course was uneventful, and the patient was discharged 8 days after the operation. This disease affects relatively young patients, rendering this operation attractive from the viewpoint of cosmetic benefits and minimal invasion. Paraduodenal hernia repair via SILS is feasible, safe, and may constitute an alternative method for paraduodenal hernia without necrotic change.

Objectives We previously reported the feasibility of neoadjuvant capecitabine and oxaliplatin plus bevacizumab as a treatment for locally advanced rectal cancer (UMIN000003219). The aim of this study is to investigate the prognostic relevance of neoadjuvant chemotherapy followed by total mesorectal resection (TME). Methods Twenty-five patients of our prior multicenter prospective study of neoadjuvant chemotherapy followed by TME enrolled to this study. We analyzed the adjuvant chemotherapy regimen, and the duration between surgery and initial chemotherapy treatment. Five-year progression-free survival and overall survival were estimated using the Kaplan-Meier method. Results Among survivors, the median follow-up time was 66 months. Recurrence occurred in six patients, all of whom had suboptimal tumor regression after neoadjuvant chemotherapy. Five patients died from other causes. The rate of local recurrence and distant metastasis was 17.4% and 8.7%, respectively. Five-year progression-free survival was 70.0%, and 5 year overall survival was 84.0%. Conclusions We report the long-term survival of patients who received neoadjuvant chemotherapy without radiation followed by TME, revealing a generally favorable prognosis.

Older or frail patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC). We here assessed the efficacy and safety of 5-fluorouracil (5-FU)–leucovorin plus bevacizumab in such patients. The study (OGSG 0802) was designed as a single-arm, open-label, multicenter phase II trial. Eligible patients had mCRC and at least one of the following: an age of ≥ 65 years, an Eastern Cooperative Oncology Group performance status of 1 or 2, a serum albumin level of ≤ 3.5 g/dL, incompatibility with oxaliplatin or irinotecan, and a history of abdominal or pelvic radiotherapy. Patients received 5-FU (600 mg/m2) and l-leucovorin (200 mg/m2) on days 1, 8, and 15 together with bevacizumab (5 mg/kg) on days 1 and 15 every 4 weeks. The primary end point was objective response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Forty-one patients were enrolled and eligible. Median age was 76 years (range 56–90 years), and 51% of patients had a performance status of 0. The ORR was 36.6% [95% confidence interval (CI) 22.1–53.1%], median PFS was 9.4 months (95% CI 7.4–17.7 months), and median OS was 24.0 months (95% CI 19.9 months—not reached). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%), anorexia (10%), leukopenia (7%), and mucositis/stomatitis (7%). There were no treatment-related deaths. Weekly 5-FU–leucovorin with biweekly bevacizumab may be a tolerable and effective treatment option for older or frail patients with mCRC.

Background Locally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC. Methods Since 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated. Results The mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195). Conclusions PET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

Laparoscopic liver resection (LLR) has been reported as a safe, minimally invasive, and effective surgery for the management of liver tumor. However, the efficacy and safety of laparoscopic repeat liver resection (LRLR) for recurrent liver tumor are unclear. Here, we analyzed the surgical results of LRLR. From June 2010 to May 2019, we performed 575 LLR surgeries in our department, and 454 of them underwent pure LLR for the single tumor. We classified the patients who received pure LLR for the single tumor into three groups: LRLR (n = 80), laparoscopic re-operation after previous abdominal surgery (LReOp; n = 136), and laparoscopic primary liver resection (LPLR; n = 238). We compared patient characteristics and surgical results between patients undergoing LRLR, LReOp and LPLR. We found no significant differences between LRLR and LPLR in the conversion rate to laparotomy (p = 0.8033), intraoperative bleeding (63.0 vs. 152.4 ml; p = 0.0911), or postoperative bile leakage rate (2.50 vs. 3.78%; p = 0.7367). We also found no significant difference in the surgical results between LReOp and LPLR. However, the number of patients undergoing the Pringle maneuver was lower in the LRLR group than the LPLR group (61.3 vs. 81.5%; p = 0.0004). This finding was more pronounced after open liver resection than laparoscopic liver resection (38.9 vs. 67.7%; p = 0.0270). The operative time was significantly longer in patients with proximity to previous cut surface than patients with no proximity to previous cut surface (307.4 vs. 235.7 min; p = 0.0201). LRLR can safely be performed with useful surgical results compared to LPLR.

Doublecortin-like kinase 1 (DCLK1) promotes tumour proliferation in human colorectal cancer (CRC). To elucidate the mechanism and clinical relevance of this association, we performed expression analysis using commercially available colon carcinoma cell lines (SW480, HCT116, CaCO2, SW48 and SKCO1) and immunohistochemical analysis of 200 resected CRC samples for correlation with clinical features. DCLK1 showed a high level of expression, especially in SW480 and HCT116 cells. Silencing DCLK1 expression using short hairpin DCLK1 (shDCLK1) RNA inhibited the growth and invasion capacities of these cell lines, which showed signs of entering into the mesenchymal–epithelial transition (MET). We found evidence of a strong correlation of DCLK1 expression with that of Tribbles homolog 3 (TRIB3), and silencing TRIB3 also led to the MET phenotype in these cells. In the clinical samples, compared with samples showing low expression of DCLK1, high expression was associated with poor prognosis in terms of overall and recurrence-free survival (P < 0.0001). The results of univariate and multivariate analysis suggested that high expression of DCLK1 in clinical colon cancer samples was tied to poor prognosis, cancer invasion depth and lymph node metastasis. DCLK1 expression correlates with malignant grade of colon cancer and offers a potential treatment target.

We examined the association between pathological lateral pelvic lymph node (LPLN) metastasis and the LPLN diameter in patients with locally advanced rectal cancer (LARC) who received a neoadjuvant chemotherapy (NAC) regimen based on oxaliplatin as induction chemotherapy. We aimed to determine whether or not the LPLN size predicts LPLN metastasis in NAC cases. We retrospectively examined data from 3 institutes for 60 patients with LARC who received mesorectal excision and LPLN dissection after NAC. We evaluated the LPLN size on magnetic resonance imaging (MRI) scans acquired before and after NAC. We performed multivariate analyses to analyze the relationship between the LPLN size and clinicopathological factors. For patients with visible LPLNs, the median short-axis diameter (SA) was significantly reduced from 5.1 mm (range 2.0–17.4) before NAC to 3.7 mm (range 2.1–19.0) after NAC (p = 0.0479). SA diameters were significantly larger in pathological LPLNs than in healthy LPLNs, both before (p = 0.0002) and after NAC (p

We assessed the feasibility and safety of single-site laparoscopic surgery for patients with colorectal cancer who required perioperative heparinization. This retrospective study reviewed the medical records of 390 patients who underwent single-site laparoscopic surgery for colorectal cancer from January 2010 to December 2016. Antithrombotic drugs were stopped preoperatively and heparin was administered according to the operative risk of each patient, based on consultation with the cardiologist physician or neurosurgeon. Propensity score modeling was utilized to adjust for baseline characteristics. Of 390 patients, 29 were treated with standard bridging intravenous heparin therapy. Propensity matching identified 119 patients: 22 patients in the heparinization group and 97 in the control group. The matched groups were not significantly different in operation times, bleeding volumes, or conversion rate. The mean postoperative hospital stay was 17.9 days in the heparinization group and 9.5 days in the control group (p = 0.034). Postoperative bleeding was observed in 4 patients (18.2%) in the heparinization group and 11 patients (11.4%) in the control group (p = 0.646), while other complications were similar in the two study groups (p = 0.502). Of these other complications, thromboembolic events were observed in two patients in the heparinization group and one patient in the control group. We found that single-site laparoscopic surgery for colorectal cancer with heparinization was feasible and safe. Heparinization did not increase the risk of postoperative bleeding complications, but postoperative hospital stay was prolonged.

Aim To investigate the frequency and risk factors of perioperative, symptomatic venous thromboembolism (VTE) after gastroenterological surgery. Methods We assessed the frequency of and risk factors for VTE after eight gastroenterological procedures (total 516 217 cases including, gastrectomy, total gastrectomy, hepatectomy, esophagectomy, right hemicolectomy, low anterior resection, pancreaticoduodenectomy, and acute pan‐peritonitis surgery) based on data from the National Clinical Database. Data collected between 2011 and 2013 (382 124 cases) were used as a test set, and data from 2014 (134 093 cases) were used as a validation set. Results The frequency of deep vein thrombosis (DVT) was 0.3% (382 124 cases), and the incidence of pulmonary embolism (PE) was 0.2% (382 124 cases) ranging from 0.1% to 0.7% for DVT and from 0.1% and 0.3% for PE among eight surgeries, respectively. Analyses using pre‐and intra‐operative factors identified the top three risk factors for VTE as esophagectomy, pancreaticoduodenectomy, and hepatectomy. Using pre‐, intra‐, and postoperative factors, the second through fourth risk factors were sepsis, prolonged ventilation >48 hours and readmission within 30 days. The highest risks factor for PE using pre‐, intra‐, and postoperative factors were any cardiac events. Unplanned intubation was the fourth risk factor. Conclusion The risk for DVT and PE differed for each surgical procedure. VTE and PE risk factors changed after considering postoperative factors. It may be necessary to reconsider the prophylaxis depending on whether the complication occurs after surgery, particularly breathing and cardiac complications.

Paroxysmal nocturnal hemoglobinuria is a rare and life-threatening disorder of acquired hemolytic anemia. Surgery is one of the major clinical situations that trigger hemolytic attack. Eculizumab is a humanized monoclonal antibody that binds the complement protein C5 and prevents complement-mediated hemolysis via inhibition of the terminal complement cascade. A 76-year-old woman received a diagnosis of ascending colon cancer during the search for the cause of right lower abdominal pain. She had received a diagnosis of paroxysmal nocturnal hemoglobinuria and been followed for 26 years at our hospital. We planned to start eculizumab for perioperative management in order to reduce the risk of the patient developing hemolytic crisis as a result of surgery. We administered 600 mg of eculizumab on the 15th, 8th, and 1st preoperative days. The levels of serum complement and lactate dehydrogenase decreased with the first administration of eculizumab. Laparoscopic right hemicolectomy was performed successfully. The patient had good postoperative progress. We administered 600 mg of eculizumab on the 6th postoperative day and 900 mg of eculizumab on the 13th postoperative day. She was discharged from hospital on the 16th postoperative day. We started use of eculizumab before surgery for safety in the management of the operation and during the perioperative period. When we enforce the elective operation for patients with paroxysmal nocturnal hemoglobinuria who do not start treatment of eculizumab, we recommend the use of eculizumab for perioperative management of patients with paroxysmal nocturnal hemoglobinuria.

We aimed to evaluate the short-term outcome of colorectal resection in very elderly patients, aged 85 years or older. As the population ages, the number of elderly patients with colorectal cancer (CRC) is increasing in Japan. At this time, it is unclear whether or not laparoscopic colorectal resection is safe for this very elderly patient population. From January 2005 to November 2014, a total of 20 patients aged 85 years or older underwent laparoscopic colorectal resection at Osaka University Hospital. Pre- and postoperative clinical data and outcomes were collected retrospectively. There were no intraoperative or postoperative deaths. In 2 cases, the laparoscopic procedure was converted to open surgery. Postoperative complications occurred in 6 patients. Two patients developed an infection at the surgical site. Among the 4 patients who underwent low anterior resection (LAR), 2 experienced postoperative anastomotic leakage. Two other patients developed a lung infection and urinary tract infection, respectively. Laparoscopic colectomy for very elderly patients with CRC appears to involve tolerable risk. However, special caution is advisable for patients who may undergo LAR.

Introduction Intestinal obstruction in pregnancy is very rare, but the maternal mortality rate and the fetal loss rate are high. Therefore, an early diagnosis and appropriate treatments for small bowel obstructions (SBOs) during pregnancy are crucial for the mothers and fetuses. On the other hand, laparoscopic surgeries are widely used in pregnant patients, although laparoscopic surgeries for SBOs can have higher risks of complications. Then, reduced port surgery (RPS) can reduce the risk of intestinal injury by minimizing the number of ports the operator could not control alone. There is no previous report of RPS for SBOs in pregnant patients. We report on a pregnant patient with a strangulated SBO treated with RPS without complications. Case presentation A 37-year-old Japanese pregnant woman complaining of severe abdominal pain was admitted by ambulance. Her gestational age was 9 weeks. Her medical history included surgery for acute perforated appendicitis and deep vein thrombosis due to anti-thrombin III deficiency. Abdominal computed tomography revealed a strangulated SBO. We performed RPS and the cause of strangulated SBO was a string at the postoperative site of the appendectomy. The ischemic region of the small bowel recovered after we cut the string and released the adhesion. The patient's postoperative course was uneventful and the fetus was not harmed. Conclusion This is the first report of RPS performed for the pregnant patient with the strangulated SBO. Our findings indicate that RPS is a feasible treatment for strangulated SBOs in pregnant women.

Aim Appendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long‐term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non‐mucinous adenocarcinomas. Methods Patients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group. Results A total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non‐mucinous adenocarcinomas. Five‐year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non‐mucinous adenocarcinomas. OS was significantly shorter among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5‐year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non‐mucinous adenocarcinomas, 5‐year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Conclusion Our present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non‐mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non‐mucinous adenocarcinomas, but not for mucinous adenocarcinomas.

Background/Aims: Endoscopic recurrence (ER) after intestinal resection for Crohn’s disease (CD) precedes the clinical recurrence, and the severity of ER correlates with the severity of the subsequent clinical recurrence. This study aimed to identify risk factors related to early ER after intestinal resection for CD and to create a prediction model. Methods: The patients who underwent intestinal resection for CD between April 2008 and April 2017 and took endoscopic evaluation between 6 and 12 months after surgery were retrospectively analyzed. Results: A total of 15 out of 52 (29%) patients developed early ER. A univariate analysis demonstrated that early ER was significantly correlated with history of prior intestinal resections for CD (p = 0.005), low preoperative albumin levels (p = 0.035), and excessive perioperative inflammation (i.e., high C-reactive protein levels in both preoperative and postoperative periods; p = 0.034). Based on these clinical factors, a nomogram for predicting early ER was created with the area under the curve 0.808. Conclusion: We developed a novel predictive nomogram for early ER after intestinal resection for CD. This prediction model might assist clinicians in managing patients with CD after an intestinal resection. Additional validation studies are currently being developed.

Objectives: The aim of this study was to determine the recommended dose (RD) of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer. Method: Patients received irinotecan and oxaliplatin (85 mg/m2) on day 1, and capecitabine (1,000 mg/m2 orally twice daily) on days 1–7 of a biweekly schedule. Three dose levels, ranging from 100 to 150 mg/m2, were explored for irinotecan in sequential cohorts of 6 patients. Dose-limiting toxicities (DLTs) were assessed in the first cycle to determine the RD. Results: Six patients were enrolled. The DLT was grade 3 febrile neutropenia, which was observed in 2 of the 6 patients at dose level 1. The RD of irinotecan was defined as 150 mg/m2. Toxicity was manageable: the most common grade ≥3 toxicities were neutropenia (2 patients), anemia (1 patient), and anorexia (1 patient). Nodal downstaging (cN+ to ypN0) was detected in 2 patients and the T stage was downstaged in 3 patients. Conclusions: XELOXIRI is a feasible and active regimen for patients with locally advanced rectal cancer. Febrile neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2.

Polymerase (Pol) III dependent transcription controls the abundance of transfer RNAs, 5S ribosomal RNA and small non coding RNAs within cells, and is known to serve an essential role in the maintenance of intracellular homeostasis. However, its contribution to cancer progression has not been extensively explored. The present study demonstrated that the evolutionarily conserved MAF1 homolog, negative regulator of RNA Pol III (MAF1) may be closely associated with malignant potential and poor prognosis in colorectal cancer (CRC). Notably, immunohistochemical analysis of 146 CRC surgical specimens revealed that high expression levels of MAF1 were associated with advanced tumor depth, lymph node metastasis, distant metastasis and poor prognosis. In vitro loss of function assays revealed that MAF1 knockdown suppressed chemoresistance and migration of CRC cancer cells. Furthermore, detailed analysis of an independent CRC dataset (n=615) demonstrated that the prognostic impact of MAF1 gene expression was particularly marked in microsatellite instability (MSI)-positive patients, who benefit from immune checkpoint blockade. High expression levels of MAF1 were revealed to be an independent prognostic indicator in MSI-positive CRC. These findings suggested that MAF1 may have an essential role in CRC progression, particularly in MSI positive cases.

Background The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis. Methods Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination. Results Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity. Conclusions The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Trifluridine/tipiracil (FTD/TPI) improves the overall survival (OS) of metastatic colorectal cancer (mCRC) patients. Additionally, FTD/TPI plus bevacizumab (BEV) has demonstrated promising efficacy for mCRC patients who are refractory to standard chemotherapy. Chemotherapy-induced neutropenia (CIN) has been reported to be an indicator of efficacy for FTD/TPI. This study investigated whether CIN was an indicator of efficacy for FTD/TPI plus BEV. We reviewed chemo-refractory mCRC patients who were treated with FTD/TPI alone (monotherapy) or FTD/TPI plus BEV (combination) at our institution and compared the safety and efficacy of the two. Progression-free survival (PFS) and OS were analyzed using Kaplan–Meier curves. We also investigated correlations between CIN and outcomes. In total, 56 patients received FTD/TPI, among whom 24 and 32 were treated with monotherapy and combination therapy, respectively. The median PFS was 1.8 and 4.7 months for the monotherapy and combination arms, respectively (hazard ratio [HR]: 0.28; 95% confidence interval [CI]: 0.15–0.51; P

The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis. RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b also potently inhibited inflammation, and it efficiently targeted CD11c+ dendritic cells (DCs) among various types of immune cells in the inflamed mucosa. RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the production of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and subsequent activation, which is critical in IBD pathogenesis. In vivo experiments using a non-natural artificial microRNA sequence revealed that targeting of DCs in the inflamed colon is an exceptional feature of sCA. This study suggests that sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD treatment. Keywords: microRNA-29a, microRNA-29b, DSS colitis, supercarbonate apatite, dendritic cells

Minimally invasive treatment is getting more and more important in an aging society. The purpose of this study was to explore the possibility of ICG loaded on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen species (ROS) production and temperature rise were also evaluated to explore the underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature increase after laser irradiation was 27.1°C and 23.1°C in sCA-ICG and ICG, respectively (control DW: 5.7°C). A significant increase in ROS generation was noted in cell cultures treated with sCA-ICG plus irradiation compared with those treated with ICG plus irradiation (P < 0.01). Uptake of ICG in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro and in vivo. The fluorescence signals of ICG in the tumor, liver, and kidney faded away in both treatments by 24 hours. Finally, the HT29 tumors treated with sCA-ICG followed by irradiation exhibited drastic tumor growth retardation (P < 0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts with the other nanoparticles remaining in normal organs for a long time. Mol Cancer Ther; 17(7); 1613–22. ©2018 AACR.

We previously demonstrated that miR-29b-3p is a hopeful miRNA-based therapy against colorectal cancer. In this study, we aimed to clarify a value of miR-29b-1-5p as a next-generation treatment, especially for KRAS-mutant colorectal cancer. RT-PCR assay showed that the expression of miR-29b-3p was high, and its partner strand, miR-29b-1-5p, level was only negligible in clinical colorectal cancer samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS-mutant colorectal cancer cell lines DLD1 and SW480 and KRAS wild-type HT29 cells. Proliferative activity was further examined by either miR-29b-1-5p strand or its opposite complementary sequence because miR-29b-1-5p is a passenger miRNA and may have no physiologic function. We found that completely opposite complementary strand to miR-29b-1-5p, but not miR-29b-1-5p, possessed a potent antitumor effect and named this byproduct miRNA sequence “MIRTX.” MIRTX directly targeted the 3′-UTR of CXCR2 and PIK3R1 mRNA and suppressed the NF-κB signaling pathway in KRAS-mutated colorectal cancer cells. MIRTX induced apoptosis in DLD1 with downregulation of antiapoptotic BCL2, BCL-xL, and MCL1 and upregulation of cleaved caspase-3 and cleaved PARP. In mouse xenograft models, systemic administration of MIRTX using a super carbonate apatite as a delivery vehicle significantly inhibited tumor growth of DLD1 and HT29 cells without any particular toxicities. In conclusion, these findings indicate that inhibition of NF-κB signaling by this novel miRNA-based therapeutic could be a promising treatment against refractory KRAS-mutant colorectal cancer and KRAS wild-type colorectal cancer. Mol Cancer Ther; 17(5); 977–87. ©2018 AACR.

Introduction: Intramural metastasis (IM) is common in esophageal cancer, and it is an important factor in determining the resection area and tumor malignancy. However, IM is rare in rectal cancer; therefore, little is known about IM in rectal cancer, and the clinical significance remains unclear. Case Presentation: We describe a case of rectal cancer with distally spreading IM. A 58-year-old man consulted a primary care physician, with a chief complaint of constipation; tests revealed a high carcinoembryonic antigen value. A colonoscopy revealed a type 2, advanced rectal tumor, which covered two-thirds of the circumference of the upper rectum. In addition, 3 protruding lesions were observed under the normal mucosa on the anal side of the primary tumor. A laparoscopic low anterior resection was performed. Pathologic findings showed that the primary tumor was a moderate-to-well-differentiated adenocarcinoma with a cribriform structure. The 3 lesions on the anal side found under normal mucosa were separate from the primary tumor, but morphologically similar to the primary adenocarcinoma; therefore, these were diagnosed as IMs. Based on a review of previous case reports, rectal carcinomas were often accompanied by vascular invasions and lymph-node metastases. Moreover, in rectal cancer, tumors with IMs often show vascular invasion. Therefore, we assumed that IM could be a marker of poor prognosis. Conclusion: This study revealed that, in surgery, detection of a distally spreading IM is an important finding for determining the optimal surgical resection margin.

A 67-year-old man who presented with a bloody stool was diagnosed with ascending colon cancer. He had previously experienced thoracic and abdominal aortic dissections, which were treated with thoracic and abdominal aortic grafts and superior mesenteric artery revascularization. We performed a laparoscopic right hemicolectomy with a D3 lymph node dissection. During the laparotomy, we identified the superior mesenteric artery and an enlarged anterior superior pancreaticoduodenal artery. Injury to the latter artery could lead to severe ischemia in multiple organs; therefore, it was crucial to identify the primary feeding artery and vascular anatomy before and during surgery. We chose the laparoscopic right hemicolectomy to avoid injuring the anterior superior pancreaticoduodenal artery and the intra-abdominal abscess. This case study was the first to describe a laparoscopic hemicolectomy after thoracic and abdominal aortic grafts and superior mesenteric artery revascularization.

A 69-year-old woman with focal infrarenal aortic stenosis was diagnosed with rectosigmoid cancer. Because radical resection for colon cancer required dissection of vessels that supplied blood flow to the legs, revascularization by aortic stent placement was performed before the colectomy. We subsequently performed laparoscopic low anterior resection without any complications. Two and a half years after colectomy, however, the patient developed colonic ischemia due to thrombosis of the dilated marginal artery that served as a collateral artery before stenting. We performed laparoscopic partial colectomy, including the resection of the dilated marginal artery filled with thrombus. An abnormally dilated ex-collateral artery was thought to have caused vessel occlusion, presumably due to an imbalance in blood flow and vascular diameter.

// Yujiro Nishizawa 1, 2, * , Masamitsu Konno 2, 3, * , Ayumu Asai 2, 3 , Jun Koseki 3 , Koichi Kawamoto 1, 2 , Norikatsu Miyoshi 1 , Hidekazu Takahashi 1 , Naohiro Nishida 1 , Naotsugu Haraguchi 1 , Daisuke Sakai 2 , Toshihiro Kudo 2 , Taishi Hata 1 , Chu Matsuda 1 , Tsunekazu Mizushima 1, 4 , Taroh Satoh 2 , Yuichiro Doki 1 , Masaki Mori 1 and Hideshi Ishii 2, 3 1 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 2 Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 3 Department of Disease Data Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 4 Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan * These authors contributed equally to this work Correspondence to: Hideshi Ishii, email: hishii@gesurg.med.osaka-u.ac.jp Masaki Mori, email: mmori@gesurg.med.osaka-u.ac.jp Keywords: YTHDF1; colorectal cancer; c-MYC; proliferation; chemosensitivity Received: August 31, 2017 Accepted: October 28, 2017 Published: December 21, 2017 ABSTRACT Recent studies that have emerged on the diversity of RNA modification in tumors suggest their eligibility as bona fide targets in diagnosis and drug discovery. N6-methyladenosine (m 6 A) was first reported and is most common in epitranscriptome modification of various RNAs. The YT521-B homology (YTH) domain family are representative m6A-binding proteins, but how the YTH domain family is involved in cancer remains to be clearly understood. Given that clinical sequence data in colorectal cancer indicate that overexpression of YTHDF1 is outstanding among other family members, we studied the role of Ythdf1 and the transcriptional control of YTHDF1. Immunostaining of Ythdf1 showed that its expression was associated with various malignant tumor behaviors, such as depth, lymph node metastasis, and poorer cancer stages. The study of patient survival indicated that patients with high Ythdf1 expression had significantly poorer overall survival. The results indicated that Ythdf1 expression is an independent prognostic factor of patients. The in vitro study showed that the knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. Importantly, the study upstream of the YTHDF1 gene indicated that an oncogenic transcription factor c-Myc was associated with YTHDF1 in both expression and chromatin immunoprecipitation data. Moreover, the knockdown experiments of c-Myc showed the inhibition of YTHDF1, supporting a notion of c-Myc-driven YTHDF1 axis significance. These data suggest that m6A reader Ythdf1 plays a significant role in colorectal cancer progression.

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET–CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUVmax after chemotherapy)/(SUVmax before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUVmax in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was

A 54-year-old female patient was hospitalized with a chief complaint of anal discomfort. Based on biopsy results, she was diagnosed with highly differentiated adenocarcinoma, and colonoscopy findings indicated a type 3 rectal tumor. We observed a right pelvic kidney on enhanced abdominal CT. We began a laparoscopic operation but converted to an open operation after resecting the right pelvic renal artery by mistake. After low anterior resection, urologists performed angioplasty of the right renal pelvic artery. The patient was discharged on postoperative day 16, after the preservation of right renal function had been confirmed. This case strongly suggests that it is important to understand the positional relationship of the inferior mesenteric and renal arteries by preoperative assessment using either 3-D CT angiography or magnetic resonance angiography.

Lateral lymph node dissection (LLND) is performed for advanced rectal cancers in Japan; however, it can cause sexual and urinary dysfunction. The incidence of lateral LN metastasis is estimated at 7–13.9%; therefore, excessive rectal surgery with LLND should be avoided, especially for prophylactic purposes. To identify the patients who require LLND, we examined metastases in perirectal LNs by using a one-step nucleic acid amplification (OSNA) assay to predict lateral LN metastases. Twenty-five patients who underwent surgery with bilateral LN dissection due to T3–T4 rectal cancers were prospectively included in this study. Twenty-two patients (88.0%) received preoperative chemotherapy. Among 1052 LNs from 25 patients (median 40 per case), 135 perirectal LNs (median 6 per patient) were divided into three pieces and analyzed by OSNA, reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen mRNA, and pathological examination after surgery. These results were compared with the pathological diagnosis of lateral LNs. Lateral LN metastases were present in 4 of 25 patients (16.0%). All of these patients were positive by OSNA for perirectal LN metastases. The OSNA assay had a sensitivity of 100%, specificity of 86%, positive predictive value of 57%, and negative predictive value (NPV) of 100% for predicting lateral LN metastases. The findings from this prospective study suggest that the OSNA assay of perirectal LNs may be useful for determining when LLND is necessary because of its high NPV, even in patients treated with preoperative chemotherapy.

Background: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). Methods: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24). Noninflamed and inflamed colonic tissues were obtained from surgically resected specimens of patients with UC (n = 13). Among LinCD45HLA-DR intestinal lamina propria cells, CD14 cells and CD103 DCs were sorted and analyzed for microRNA expression of cytokines and toll-like receptors by quantitative real-time polymerase chain reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-γ production and Foxp3 expression by naive T cells cultured with CD14 cells and CD103 DCs were analyzed. Results: CD103 DCs in the normal colon showed lower expression of toll-like receptors and proinflammatory cytokines than CD14 cells. Coculture with naive T cells revealed that CD103 DCs generated Treg cells. CD103 DCs from patients with UC did not generate Treg cells, but they induced IFN-γ-, IL-13-, and IL-17-producing CD4 T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P < 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05). Conclusions: In patients with UC, CD103 DCs show the impaired ability to generate Treg cells, but exhibit a colitogenic function inducing Th1/Th2/Th17 responses. These findings show how human CD103 DCs could contribute to the pathogenesis of UC.

The Golgi-associated PDZ- and coiled-coil motif-containing (GOPC) protein controls the intracellular trafficking of numerous integral membrane proteins. Knockdown of GOPC increases activation of the mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 pathway and cancer cell progression in colorectal cancer. The present study aimed to clarify the correlation between GOPC expression and prognosis in colorectal cancer. Total RNA was extracted from 153 clinical colorectal cancer specimens and GOPC expression was evaluated using reverse transcription-quantitative polymerase chain reaction. The correlation between GOPC expression and clinicopathological factors was analyzed, along with the association of GOPC expression with overall survival (OS) and with recurrence-free survival (RFS). Lower expression of GOPC was significantly associated with a high frequency of venous invasion (P=0.001) and to poorer OS and RFS based on Kaplan-Meier analysis. In addition, multivariate analyses using a Cox proportional hazards model identified lower expression of GOPC to be an independent prognostic factor for colorectal cancer (hazard ratio=2.800; 95% confidence interval; 1.121–7.648; P=0.027). Lower expression of GOPC revealed a high frequency of venous invasion and associated with poorer prognosis for patients with colorectal cancer.

A 73-year-old man with lower abdominal pain was diagnosed at our hospital with sigmoid colon cancer. He had previously undergone radical cystectomy with Indiana pouch construction and gastrectomy to treat bladder cancer and gastric cancer, respectively. We performed a laparoscopic Hartmann's operation with Japanese D3 lymph node dissection. We observed severe adhesion in the abdominal cavity; adhesions between the urostomy and sigmoid colon were particularly severe. The tumor had invaded to the distal rectum, which had adhered to the pubic bone and the previously reconstructed urinary pouch. By performing careful and persistent laparoscopic dissection, we completed the operation without damaging the urostomy and with no remnant tumor tissue (R0). The postoperative course was uneventful, and the patient was doing well with no evidence of cancer recurrence 1 year after surgery.

Background: We previously reported that GTA-446 may be a useful biomarker for early detection of colorectal cancer. In the present study, we confirmed the clinical feasibility of GTA-446 as a screening tool for colorectal cancer with a novel measurement system developed for clinical use. We also improved sensitivity by analysing GTA-446 levels according to gender. Methods: Serum samples were collected from 225 colorectal cancer patients and 916 healthy volunteers to measure GTA-446 levels by flow injection analysis–mass spectrometry. Results: GTA-446 levels were downregulated in colorectal cancer patients compared with the healthy volunteers, and in females compared with the males in both groups. Receiver operating characteristic curve analysis revealed an optimal cut-off of 2.72 μmol l−1 in males and 1.87 μmol l−1 in females, with a large area under the curve of 0.89–0.93. The sensitivity and specificity were 90.4% and 84.9% for males, 85.2% and 80.5% for females, and 83.3% and 84.8% for all subjects, respectively. Conclusions: GTA-446 is a clinically relevant biomarker for colorectal cancer with high sensitivity when analysed by gender. Thus, GTA-446 is a promising tool for primary colorectal cancer screening to identify populations at a higher risk of colorectal cancer, with an emphasis on early detection.

An elemental diet (ED) can suppress inflammation in patients with Crohn’s disease (CD); however, adherence to this diet is difficult. We examined the correlation between ED adherence and the postoperative recurrence of CD. The subjects of this study were 38 patients who underwent intestinal resection with anastomosis. We defined ED adherence as consuming the average daily ED dose (≥900 kcal/day) for 2 years after surgery. Patients who did not adhere to the ED were allocated to the non-ED group. We diagnosed symptomatic recurrence using the CD activity index and endoscopic recurrence using the Rutgeerts’ score. The ED and non-ED groups comprised 21 and 17 patients, respectively, with ED adherence of 55.3% (21/38). At the initial endoscopy, symptomatic and endoscopic recurrence rates were 4.8 and 14.3%, respectively, in the ED group, and 23.5 and 41.2%, respectively, in the non-ED group (P = 0.152 and P = 0.078, respectively). The overall symptomatic recurrence-free duration was significantly longer than the endoscopic recurrence-free duration (P = 0.022). Symptomatic and endoscopic recurrence-free durations were longer in the ED group than in the non-ED group (P = 0.003 and P = 0.021, respectively), and ED adherence was a prognostic factor for endoscopic recurrence (HR = 2.777, 95% CI = 1.036–8.767, P = 0.042). Maintaining ED adherence for 2 years after surgery improved the symptomatic and endoscopic recurrence-free durations.

We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2–8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934). The recommended dose of capecitabine was determined to be 2000 mg/m2. Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1–10.9 months], and median overall survival was 18.9 months (95% CI 11.6–28.4 months). Response rate was 17.4% (95% CI 6.4–28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (

Purpose Laparoscopic surgery is now practiced widely because of its lower postoperative morbidity. As flexible endoscopy during laparoscopic surgery minimizes surgical trauma further, training in endoscopy will become more important for surgeons. Thus, we designed a physical simulator, the Noda–Kitada–Suzuki (NKS) model, which could provide the more realistic insertion of a colonoscope. Methods We designed a colonoscopy simulator, based on information from computed tomography colonography scans of the anatomy and kinetic properties of the colon and rectum. Results The transparent skeleton body of the NKS model provides instant visual feedback to the operator and the trainer. Our novel colonoscopy simulator replicates the realistic and reproducible insertion of a colonoscope from the rectum to cecum, providing authentic views of the Houston’s valves, the flexures, and mucosal folds. This was verified through an objective questionnaire, with 14 of 16 colonoscopists preferring the NKS model over the previous CM15 model for training purposes. Moreover, the Modified Colonoscopy Simulator Realism Questionnaire analysis confirmed that the NKS model was significantly more realistic than the CM15 for 7 (21.2%) of the 33 items when assessed by 12 colonoscopists. Conclusion The NKS model provides a realistic training platform and may improve the quality of training in colonoscopy. Electronic supplementary material The online version of this article (doi:10.1007/s00595-017-1517-7) contains supplementary material, which is available to authorized users.

Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease. Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally. Tregs and CD103+ dendritic cells were analyzed in the mesenteric lymph nodes (MLNs), spleen, and colonic lamina propria (CLP). Activation of latent TGF-β by ASCs was analyzed in vitro using ELISA. siRNA technology was used to create ASCs in which TSP-1 or integrinαv was knocked down in order to investigate the involvement of these proteins in the activation of latent TGF-β. In addition, TSP-1-knockdown ASCs were administered to mice with colitis to assess their clinical efficacy in vivo. Systemic administration of ASCs significantly lessened the clinical and histopathological severity of colitis. ASCs were distributed throughout the lymphatic system in the MLNs and spleen. Tregs were increased in the MLNs and CLP, but CD103+ dendritic cells were not significantly altered. The ASCs activated latent TGF-β. TSP-1 knockdown impaired TGF-β activation in vitro and abrogated the therapeutic effects of the ASCs in vivo. Furthermore, Tregs were not increased in the MLNs and CLP from mice treated with TSP-1-knockdown ASCs. These results demonstrate that ASCs induce Tregs by activating latent TGF-β via TSP-1, independent of CD103+ dendritic cell induction.

It is unclear whether the number or distribution of lymph node metastases can provide a more accurate prognosis. The aim of this study was to evaluate the prognostic impact of inferior mesenteric artery (IMA) lymph node metastasis (LNM) in sigmoid colon and rectal cancer. We included 188 patients who underwent curative resection for stage III sigmoid colon and rectal cancer between January 2001 and December 2012. Patients were divided into 2 groups based on the presence of IMA-LNM (LNM-positive versus LNM-negative group). Clinicopathologic characteristics, 3-year recurrence-free survival and 5-year overall survival rates, and recurrence patterns were compared between the 2 groups. Of 188 patients, 9 patients (4.79%) were in the LNM-positive group. After curative resection, 3-year recurrence-free survival and 5-year overall survival rates were significantly lower in the LNM-positive group compared to the LNM-negative group (44.44% versus 69.98%, P = 0.016 for 3-year recurrence-free survival and 48.61% versus 81.73%, P = 0.018 for 5-year overall survival). Multivariate analysis revealed that the presence of IMA-LNM (P = 0.04), not the number of LNMs (P = 0.153), was an independent prognostic factor for recurrence-free survival. The para-aortic LNM rate was significantly higher in the LNM-positive group (P = 0.0078). IMA-LNM is an independent predictor of survival for stage III sigmoid colon and rectal cancer patients. Evaluation of IMA-LNM enables accurate estimation of patient prognosis and enhances appropriate postoperative therapy.

BACKGROUND Small bowel adenocarcinoma (SBA) is rare. For unresectable or recurrent SBA, systemic treatment is the only potentially promising option. PATIENTS AND METHODS This retrospective study included 13 patients with SBA treated at our Institute. All patients received fluorouracil- or fluoropyrimidine-based regimens. We analyzed associations between the progression-free interval (PFI) and therapeutic regimen (n=17) and patient characteristics. RESULTS The 5-year overall survival of patients with SBA was 23.5%. The 5-year relapse-free survival of patients with curatively resected (R0 or R1) SBA (n=6) was 45%. Patients with unresectable or recurrent SBA (n=10) had a median overall survival time of 28.0 months. No factor was significantly associated with PFI, except the number of treatment regimens required: patients that received only one line of treatment survived significantly longer than those receiving multiple lines. CONCLUSION Fluorouracil- or fluoropyrimidine-based regimens might effectively treat unresectable or recurrent SBA. We did not investigate any additive agents that might have increased efficacy of these regimens.