Oral antibiotics and a low-residue diet reduce the incidence of anastomotic leakage after left-sided colorectal surgery: a retrospective cohort study.

PURPOSE: Anastomotic leakage is a potential complication after colorectal surgery. We investigated the effects of oral antibiotics and a low-residue diet on the incidence of anastomotic leakage after left-sided colorectal surgery. METHODS: Outcomes were retrospectively compared between 64 patients who underwent mechanical bowel preparation alone (group A) and 183 patients who underwent mechanical bowel preparation with addition of oral kanamycin and metronidazole (group B) on the day before left-sided colorectal surgery. After surgery, patients in group A received a normal diet containing dietary fiber and those in group B received a low-residue diet. The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were rates of other postoperative complications, length of postoperative hospital stay, and laboratory data. RESULTS: Anastomotic leakage, surgical site infection, and diarrhea were less common in group B than in group A (4.9% vs 18.8%, 6.6% vs 23.4%, and 25.7% vs 43.8%, respectively). Postoperative C-reactive protein levels were significantly lower in group B. The median postoperative hospital stay was significantly shorter in group B than in group A (8 days vs 9 days, P = 0.010). Adaptive double least absolute shrinkage and selection operator regression revealed that use of preoperative oral antibiotics and a postoperative low-residue diet were associated with lower incidence of anastomotic leakage (odds ratio 0.163, 95% confidence interval 0.062-0.430; P < 0.001). CONCLUSION: Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.

Smad ubiquitination regulatory factor 2 (Smurf2) plays various roles in cancer progression. However, the correlation between Smurf2 and clinical outcomes has not been determined in patients diagnosed with colorectal cancer and colorectal liver metastases. We analyzed 66 patients with colorectal cancer who developed liver metastases. Smurf2 expression was assessed using immunohistochemical analysis of primary and metastatic liver tumors. High Smurf2 expression in both primary and metastatic tumors was significantly associated with longer overall survival time and time to surgical failure. Multivariate analyses revealed that low Smurf2 expression in primary tumors was an independent predictor of poor prognosis. In vitro experiments using colon cancer cell lines demonstrated that short interfering RNA knockdown of Smurf2 increased cell migration and tumor sphere formation. Western blot analyses revealed that Smurf2 knockdown increased the protein expression of epithelial cell adhesion molecule (EpCAM). Thus, in summary, high Smurf2 expression in cancer cells was found to be an independent predictor of better prognosis in patients with primary colorectal cancer and consequent liver metastases. The tumor-suppressive role of Smurf2 was found to be associated with cell migration and EpCAM expression; hence, Smurf2 can be considered a positive biomarker of cancer stem cell-like properties.

Preoperative evaluation of vascular anatomy of right colic vessels using enhanced computed tomographic colonography.

PURPOSE: The purpose of this study is to define the blood vessels from a surgical perspective and show the frequency of vascular anatomical anomalies as well as the positional relationship with the surrounding organs, including the number of jejunal veins that cross the dissection area in our series. MATERIALS AND METHODS: From January 2016 to December 2018, 126 patients who received ileocecal resection or right hemicolectomy for colonic cancer in our institution were retrospectively analyzed by preoperative enhanced computed tomographic colonography images that were obtained using an 80-detector row CT scanner and workstation. The ileocolic artery/vein, right colic artery/vein and middle colic artery/vein were defined as the vessels that flow directly from or into the superior mesenteric artery/vein. All colic veins that flowed into the gastro-colic trunk were defined as accessory right colic veins. RESULTS: The accessory right colonic vein existed more than two in 62.6% of cases. In 11 cases (8.9%), the inflow point of the ileocecal vein was on the ventral side of the pancreas. There was one jejunal vein that straddled the dissection area in 31% and two in 6.3%. CONCLUSION: This study elucidated the vascular anatomy and positional relationship with surrounding organs that is required in central vascular ligation during complete mesocolic excision for right sided colon cancer.

Carbon Ion Radiotherapy for Locally Recurrent Rectal Cancer of Patients with Prior Pelvic Irradiation.

BACKGROUND: This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC). METHODS: Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20-74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy [RBE] per fraction). RESULTS: All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years. CONCLUSION: Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.

[Investigation for Arc of Riolan-Conserving High Ligation Using Simulation CT Colonography in Preoperative Colorectal Cancer].

BACKGROUND AND PURPOSE: Simulation computed tomography colonography(sCTC), which combines CTC and 3-dimensional vascular imaging, is popular for the surgery of colorectal cancer. We experience anomaly, called arc of Riolan(aR), rarely but its definition and details are unclear. Using sCTC, we identified aR and investigated the simulation of aR-conserving high ligation. PATIENT AND METHOD: The patients were 3 cases of sigmoid colorectal cancer with aR in 369 patients who underwent sCTC before colorectal cancer surgery. We identified the running morphology of aR. And we classified Griffiths' point as presence(P)and absence(A). Narrow or mesh-shaped artery which were ischemic risk factors of intestinal tract was P groups and normal artery was A groups in the marginal artery of splenic flexure. We simulated aR-conserving lymph node dissection using sCTC. RESULT: Case 1. The patient was 60-year-old man with rectal cancer, cT4aN1M0, Stage Ⅲa. The running morphology of aR was between the left branch of middle colic artery(MCA lt)and LCA. Griffiths point: P. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT3N1M0, Stage Ⅲa. Case 2. The patient was 65-year-old woman with sigmoid colon cancer, cT3N2M0, Stage Ⅲb. The running morphology of aR was between MCA lt and IMA. Griffiths point: P. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT3N2M0, Stage Ⅲb. Case 3. The patient was 75-year-old woman with sigmoid colon cancer, cT1bN0M0, Stage Ⅰ. The running morphology of aR was between first jejunal artery and IMA. Griffiths point: A. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT1bN0M0, Stage Ⅲb. CONCLUSION: Using sCTC, we could identify the various running morphology of aR and simulate aR-conserving lymph node dissection in high ligation.

Randomized phase II study of tegafur-uracil/leucovorin versus tegafur-uracil/leucovorin plus oxaliplatin after curative resection of high-risk stage II/III colorectal cancer (SOAC-1101 trial).

PURPOSE: This randomized phase II trial compared tegafur-uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer. METHODS: From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/m2 oxaliplatin on days 1 and 15, 300 mg/m2/day UFT and 75 mg/day LV on days 1-28, every 35 days for five cycles) or UFT/LV. The primary study endpoint was disease-free survival. RESULTS: The 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P < 0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P < 0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups. CONCLUSIONS: TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer. TRIAL REGISTRATION: UMIN ID: 000007696, date of registration: April 10, 2012.

Histogram Analysis of Diffusion-Weighted MR Imaging as a Biomarker to Predict Survival of Surgically Treated Colorectal Cancer Patients.

BACKGROUND: Structural abnormality is a well-recognized feature of malignancy. On the other hand, diffusion-weighted MRI (DWI) has been reported as a tool that can reflect tumor biology. AIMS: The purpose of this study is to apply histogram analysis to DWI to quantify structural abnormality of colorectal cancer, and evaluate its biomarker value. METHODS: This is a retrospective study of 80 (46 men and 34 women; median age: 68.0 years) colorectal cancer patients who underwent DWI followed by curative surgery at the Chiba University Hospital between 2009 and 2011. Median follow-up time was 62.2 months. Histogram parameters including signal intensity of kurtosis and skewness of the tumor were measured on DWI at b = 1000, and mean apparent diffusion coefficient value (ADC) of the tumor was also measured on ADC map generated by DWIs at b = 0 and 1000. Associations of tumor parameters (kurtosis, skewness, and ADC) with pathological features were analyzed, and these parameters were also compared with overall survival (OS) and relapse-free survival (RFS) using Cox regression and Kaplan-Meier analysis. RESULTS: ADC of the tumor did not have significant associations with any pathological factors, but kurtosis and skewness of signal intensity in the tumor was significantly different between tumors with distant metastases and those without (4.23 ± 1.31 vs. 3.24 ± 1.32, p = 0.04; 1.09 ± 0.39 vs. 0.57 ± 0.58, p = 0.03). Kurtosis of the tumor was significantly correlated with OS and RFS (p = 0.04, p = 0.03, respectively), and skewness was significantly correlated with OS (p = 0.03) in Cox regression analysis. Higher kurtosis or higher skewness of the tumor was associated with worse OS in Kaplan-Meier analysis (p = 0.01, p = 0.009, log-rank). In subset analysis, there were 50 patients (32 men and 18 women) of lymph node-negative colorectal cancers (≤ stage II); skewness of signal intensity in the tumor was associated with OS using univariate Cox regression analysis (p = 0.04). CONCLUSIONS: Histogram analysis of DWI can be a prognostic biomarker for colorectal cancer.

Treatment Outcome of Resection of Disseminated Peritoneal Metastases from Colorectal Cancer.

AIM: To show the treatment outcomes of disseminated nodule resection for peritoneal metastasis of colorectal cancer and describe the details of cured cases. PATIENTS AND METHODS: From January 2001 to December 2016, patients who underwent disseminated nodule resection of colorectal adenocarcinoma with no macroscopic residual tumor in our institution were retrospectively analyzed for clinicopathological factors associated with prognosis. RESULTS: Forty-one cases were included in this study. The 3-year relapse-free survival was 12.5%, and the 5-year overall survival was 38.4%. In a multivariate analysis, lack of post-operative adjuvant chemotherapy and pre-operative carbohydrate antigen 19-9 over 100 IU/l were extracted as independent factors associated with short relapse-free survival, respectively. Among 41 cases, 32 were followed-up 5 years after surgery and five (15.6%) survived without relapse and were regarded as 'cured'. CONCLUSION: More than a few cases of colorectal peritoneal metastasis, which is thought to be difficult to cure, were cured by resection of disseminated nodules without resorting to highly invasive treatment.

High expression of Krüppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer.

Krüppel-like factor 5 (KLF5) plays an oncogenic role and has diverse functions in cancer cells. However, correlation between KLF5 and clinical outcome has not been determined in patients with colorectal cancer and colorectal liver metastasis. Herein, we analyzed 65 patients with colorectal cancer who developed colorectal liver metastasis. Clinical effects were assessed through immunohistochemical analysis of primary colorectal cancer lesions and metastatic liver lesions. High expression of KLF5 in these tissues correlated with the presence of vascular invasion, elevated serum carbohydrate antigen 19-9 levels, large diameters of metastatic liver tumors, and poor prognosis following surgery. Multivariate analyses revealed that high expression of KLF5 was an independent prognostic factor. Increased expression of KLF5 in both colorectal cancer primaries and colorectal liver metastasis was significantly associated with shorter overall survival time and time to surgical failure. Krüppel-like factor 5 expression positively correlated with Ki-67 and c-Myc expression in colorectal cancer tissues. In vitro experiments with colon cancer cell lines showed that siRNA knockdown of KLF5 inhibited cell proliferation. Western blot analyses revealed that knockdown of KLF5 expression reduced cyclin D1 and c-Myc expression. It also impaired the stem cell-like properties of cancer cells in tumorsphere formation assays. Furthermore, anoikis assay indicated that KLF5 contributed to anoikis resistance. High KLF5 expression is associated with poor prognosis in patients with colorectal cancer and liver metastasis by promoting cell proliferation and cancer stem cell-like properties.

[A Case of Rectal Cancer with Collet-Sicard Syndrome].

The case was a woman in her 50s. Total pelvic resection was performed for advanced rectal cancer(cT4b[vagina]N3M0, cStage Ⅲc), after neoadjuvant chemoradiation therapy. Five months after the operation, she was unable to stand due to severe back pain. Spinal MRI revealed multiple bone metastases and lumbar fractures. In addition, dysphagia and dysarthria rapidly progressed almost simultaneously with back pain. Initially, brain metastasis was suspected, but head MRI revealed Collet-Sicard syndrome due to skull base metastasis. Irradiation to the skull base and high cervical spine, thoracolumbar spine was started. After irradiation, her back pain and cranial nerve symptoms improved. She was discharged and received palliative treatment. About a month after discharge, she was hospitalized for recurrent dysphagia and died on day 5 of hospitalization. Collet-Sicard syndrome is caused by damage to the cranial nerves Ⅸ to Ⅻ and is often caused by a tumor. Trauma, vasculitis, and internal carotid artery dissection have been reported as other causes. Symptoms such as hoarseness, dysarthria, tongue atrophy, dysphagia, and headache have been reported. Collet-Sicard syndrome due to bone metastasis of colorectal cancer were very rare, and we found only one other report. We report our case with some literature considerations.

Clinical utility of transanal indocyanine green near-infrared fluorescence imaging for evaluation of colorectal anastomotic perfusion.

BACKGROUND: Although indocyanine green (ICG) fluorescence imaging has been reported to be useful for assessing colorectal perfusion, unstable quantification remains an issue. We performed ICG fluorescence observation from the luminal side and examined the usefulness of the transanal approach. METHODS: A total of 69 patients who underwent left-side colon surgery were enrolled in this cohort study. After the anastomosis had been constructed, ICG 0.2 mg/kg was injected intravenously. The anastomotic site was then observed by a scope inserted transanally. The following items were examined in the areas of the anastomotic site with the highest- and lowest-fluorescence intensity: maximum fluorescence (Fmax), time from ICG injection to Fmax (Tmax), time from start of dyeing to Fmax (ΔT), and the contrast pattern of the mucosa. RESULTS: Anastomotic leakage (AL) occurred in nine cases. Tmax and ΔT values of the lowest-fluorescence area in the distal intestine showed significant differences in the cases with AL (P = 0.015 and P = 0.040, respectively). Regarding the contrast pattern of the mucosa of the lowest-fluorescence area in the proximal and distal intestine, the patients in whom the vessels were not depicted in the area had a significantly higher incidence of AL than those in whom vessels were depicted in the area (P = 0.031 and P = 0.030, respectively). Some of the areas in which vessels were not depicted by ICG fluorescence observation from the luminal side corresponded to the points of leakage. There were heterogeneous changes that might not be grasped by observation from the serosal side. CONCLUSION: Transanal ICG fluorescence imaging can evaluate perfusion over the entire circumference of the anastomosis in detail and aid in assessing the risk of AL. Therefore, the examination of the detailed low-perfusion area enables us to take measures for AL and to search for safer operative managements.

Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study.

OBJECTIVES: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. METHODS: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m2/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. RESULTS: The S-1 recommended dose was 80 mg/m2/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. CONCLUSIONS: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present.

A randomized controlled, open-label early phase II trial comparing incidence of FOLFIRI.3-induced diarrhoea between Hangeshashinto and oral alkalization in Japanese patients with colorectal cancer.

WHAT IS KNOWN AND OBJECTIVE: We conducted a pilot clinical trial to investigate whether Hangeshashinto (TJ-14) could be substituted for oral alkalization in patients scheduled to undergo chemotherapy by FOLFIRI.3 regimen for colorectal cancer (CRC). METHODS: Patients with CRC were randomized 1:1 to a TJ-14 (7.5 g/day) group or an oral alkalization (sodium bicarbonate, 1.8 g/day; ursodeoxycholic acid, 300 mg/day) group. The primary endpoint was incident of late-onset diarrhoea. A total of 30 patients were randomized to either the TJ-14 group or the alkalization group. RESULTS AND DISCUSSION: There was no statistical difference in age, concomitantly used drugs or UGT1A1 genotypes between the groups. In the alkalization group (n = 15), the frequency of grade 0/1/2 and grade 3 diarrhoea was 73% and 27%, respectively. In the TJ-14 group (n = 14), the frequency of grade 0/1/2 and grade 3 diarrhoea was 79% and 21%, respectively. Grade 4 diarrhoea was not observed in either group. There was no statistically significant difference in other adverse events or in response to FOLFIRI.3 between the groups. WHAT IS NEW AND CONCLUSION: This pilot trial suggests that TJ-14 is a promising alternative treatment option to reduce FOLFIRI.3-induced late-onset diarrhoea, although additional clinical study with a larger number of patients is necessary to confirm these results.

MarmoDetector: A novel 3D automated system for the quantitative assessment of marmoset behavior.

BACKGROUND: Callithrix jacchus, generally known as the common marmoset, has recently garnered interest as an experimental primate model for better understanding the basis of human social behavior, architecture and function. Modelling human neurological and psychological diseases in marmosets can enhance the knowledge obtained from rodent research for future pre-clinical studies. Hence, comprehensive and quantitative assessments of marmoset behaviors are crucial. However, systems for monitoring and analyzing marmoset behaviors have yet to be established. NEW METHOD: In this paper, we present a novel multimodal system, MarmoDetector, for the automated 3D analysis of marmoset behavior under freely moving conditions. MarmoDetector allows the quantitative assessment of marmoset behaviors using computerised tracking analysis techniques that are based on a Kinect system equipped with video recordings, infrared images and depth analysis. RESULTS: Using MarmoDetector, we assessed behavioral circadian rhythms continuously over several days in home cages. In addition, MarmoDetector detected acute, transient complex behaviors of alcohol injected marmosets. COMPARISON TO EXISTING METHOD: Compared to 2D recording, MarmoDetector detects activities more precisely and is very sensitive as we could detect behavioral defects specifically induced by alcohol administration. CONCLUSION: MarmoDetector facilitates the rapid and accurate analysis of marmoset behavior and will enhance research on the neural basis of brain disorders.

Usefulness of Renal Autotransplantation for Radiotherapy-induced Renovascular Hypertension.

We experienced a young woman with congestive heart failure (CHF) caused by renovascular hypertension (RVH) and subsequent hypertensive heart disease. She underwent tumor resection and intraoperative radiation therapy because of neuroblastoma at age 2. She was diagnosed with RVH and hypertensive heart disease due to radiation-induced renal artery stenosis at age 12. Thereafter, she was hospitalized with CHF caused by uncontrolled RVH at age 19, and renal autotransplantation with extraction of left kidney was performed after the recovery of CHF. Her blood pressure has been well controlled without CHF readmission during four years of follow-up after the operation.

[Transverse Colectomy with D2 Lymph Node Dissection with a Small Incision Using Body Surface 3D-Simulation CT Colonography].

BACKGROUND: Laparoscopic transverse colectomy is technically difficult. In mini-laparotomy surgery, colectomy for midtransverse colon cancer can easily be performed, but exact D2 lymph node dissection is very difficult for a variety of vessels in the transverse colon. Using 3D-CT imaging, we present a case of D2 lymph node dissection where mini-laparotomy transverse colectomy was performedby a small incision similar to that usedin laparoscopic surgery. METHOD: The patient was a 60-yearoldwoman with early transverse colon cancer, which was locatedin the mid-transverse colon. Surgical treatment was plannedfor pT1b(1.5mm)andpVM1 in pathological findings after EMR. Using CT colonography(CTC), the location of the primary tumor was identified. Using simulation CTC(sCTC), composedof CTC and 3D imaging of the arteries andveins, the dominant artery was identified and D2 lymph node dissection was simulated. In addition, body surface 3D imaging and permeable surface 3D imaging of the abdominal trunk were performed. Using body surface 3D-sCTC, composedof sCTC and body surface 3D imaging, the minimum incision to enable D2 lymph node dissection was simulated. RESULT: Using sCTC, it was identified that the dominant artery was the right branch of the middle colic artery(MCA Rt)andthe accompanying vein was branchedfrom the gastrocolic trunk(GCT). D2 lymph node dissection to separate the branching root of MCA Rt and the accompanying vein was simulated. Next, surgical incision was simulated using body surface 3D-sCTC. Because the branching roots of MCA Rt andGCT were locatedabout 5 cm cranial from the upper rim of the navel, a 7 cm upper abdominal midline incision was designed in addition to a 2 cm umbilical incision. Mini-laparotomy transverse colectomy with a 7 cm incision was performedin accordance with the simulation. The operation time was 2 hours and5 1 minutes, andbloodloss was due to occult bleeding. The patient was discharged 7 days after surgery without complications, and the final diagnosis was pT1bN0M0, StageⅠwith no recurrence for 4 years and2 months after surgery. The cranial incision from the upper rim of the navel has shrank about 3 cm, and the umbilical incision is not noticeable. CONCLUSION: D2 lymph node dissection of minilaparotomy transverse colectomy can be a treatment option for early transverse colon cancer through using body surface 3DsCTC.

Endoscopic Diagnostic Support System for cT1b Colorectal Cancer Using Deep Learning.

OBJECTIVE: This study aimed to use convolutional neural network (CNN), a deep learning software, to assist in cT1b diagnosis. METHODS: This retrospective study used 190 colon lesion images from 41 cases of colon endoscopies performed between February 2015 and October 2016. Unenhanced colon endoscopy images (520 × 520 pixels) with white light were used. Images included 14 cTis cases with endoscopic resection and 14 cT1a and 13 cT1b cases with surgical resection. Protruding, flat, and recessed lesions were analyzed. AlexNet and Caffe were used for machine learning. Fine tuning of data to increase image numbers was performed. Oversampling for the training images was conducted to avoid impartiality in image numbers, and learning was carried out. The 3-fold cross-validation method was used. Sensitivity, specificity, accuracy, and area under the curve (AUC) values in the receiver operating characteristic curve were calculated for each group. RESULTS: The results were the average of obtained values. With CNN learning, cT1b sensitivity, specificity, and accuracy were 67.5, 89.0, and 81.2%, respectively, and AUC was 0.871. CONCLUSION: Quantitative diagnosis is possible using an endoscopic diagnostic support system with machine learning, without relying on the skill and experience of endoscopists. Moreover, this system could be used to objectively evaluate endoscopic diagnoses.

Multiple animal positioning system shows that socially-reared mice influence the social proximity of isolation-reared cagemates.

Social relationships are a key determinant of social behaviour, and disruption of social behaviour is a major symptom of several psychiatric disorders. However, few studies have analysed social relationships among multiple individuals in a group or how social relationships within a group influence the behaviour of members with impaired socialisation. Here, we developed a video-analysis-based system, the Multiple-Animal Positioning System (MAPS), to automatically and separately analyse the social behaviour of multiple individuals in group housing. Using MAPS, we show that social isolation of male mice during adolescence leads to impaired social proximity in adulthood. The phenotype of these socially isolated mice was partially rescued by cohabitation with group-housed (socially-reared) mice, indicating that both individual behavioural traits and those of cagemates influence social proximity. Furthermore, we demonstrate that low reactive behaviour of other cagemates also influence individual social proximity in male mice.

[Dawn of Cancer Clinical Sequencing in Chiba University Hospital].

Genome medicine has been attractingmuch of attention in Japan. The combination of molecular targetingdrug s and somatic mutations has been developed for cancer treatment, which was introduced clinically with evidence by cancer type. Several cancer somatic mutations can be identified in a single test inexpensively using next-generation sequencing(NGS). Drug approval not based on organs but on cancer genome analysis has been practiced mainly in the United States, and is also being implemented in Japan. However, cancer treatment strategies using molecular targeting drugs and the associated diagnosis are limited in each type of cancer. Furthermore, the benefit of NGS, which is an improved and inexpensive technique, is still insignificant in Japan. However, the clinical biobank system was initiated in 2011 to prepare the era of cancer genome medicine in our department. The quality of biological samples was strictly controlled by the standardized sampling procedures, which can be used by the researchers accordingto their convenience. Furthermore, the cooperative research involvingcommercial corporations has been started.

The frequency of promoter DNA hypermethylation is decreased in colorectal neoplasms of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by numerous colorectal adenomatous polyps with predisposition to the development of colorectal cancer (CRC). Here, we conducted genome-wide DNA methylation analysis of FAP neoplasms, including seven cancer samples and 16 adenoma samples, using an Infinium 450K BeadArray. As controls for sporadic colorectal neoplasms and mucosae, we used Infinium 450k data from 297 CRC samples, 45 colorectal adenoma samples, and 37 normal mucosa samples with reference to The Cancer Genome Atlas and other databases. Unsupervised two-way hierarchical clustering analysis of FAP and sporadic CRC/adenoma revealed that CRC was classified into four DNA methylation epigenotypes (MEs): high-ME (HME), intermediate-ME (IME), low-ME (LME), and normal-like ME (NME). Five FAP neoplasms (two cancer and three adenoma) were clustered with IME, whereas 18 FAP neoplasms (five cancer and 13 adenoma) were clustered into NME. IME FAP neoplasms significantly correlated with KRAS mutations, similar to sporadic CRC. Within IME cases, however, aberrant DNA methylation was significantly less frequent in FAP neoplasms than sporadic neoplasms, and these unmethylated genes included WNT family genes and several types of oncogenes. In summary, FAP neoplasms were classified into at least two molecular subtypes, i.e., NME in the majority of cases showing mostly no aberrant methylation and IME in some cases accompanied by KRAS mutations but less frequent aberrant DNA methylation than sporadic neoplasms, suggesting that FAP may follow a tumorigenesis pathway different from that of sporadic CRC.