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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.

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.

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. The purpose of this study is to apply histogram analysis to DWI to quantify structural abnormality of colorectal cancer, and evaluate its biomarker value. 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. 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). Histogram analysis of DWI can be a prognostic biomarker for 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.

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.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.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).Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

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.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.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%.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.

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. 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. 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. 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.

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.

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.

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.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.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.Using sCTC, we could identify the various running morphology of aR and simulate aR-conserving lymph node dissection in high ligation.

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. 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. 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. TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer. UMIN ID: 000007696, date of registration: April 10, 2012

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.From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/mThe 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 (P0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P0.01). 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.TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer.UMIN ID: 000007696, date of registration: April 10, 2012.

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.

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.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.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.D2 lymph node dissection of minilaparotomy transverse colectomy can be a treatment option for early transverse colon cancer through using body surface 3DsCTC.

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., Nozomi Endo, Waka Ujita et al. present a video-based system for analysing social behaviour of groups of mice. They find that male mice reared in isolation have impaired social proximity in adulthood, but this is partially rescued by cohabitation with socially-reared mice.

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.

There are several reports on the usefulness of diverting ileostomy for decreasing the incidence of anastomotic leakage and the severity of pelvic peritonitis. However, a number of complications induced by ileostomy itself have also been reported, including a special condition induced by obstruction at the outlet of the stoma known as "outlet obstruction." In this study, we examined the frequency and risk factors of this complication based on the data of ileostomy cases in our institution. Methods One hundred and seven patients who received ileostomy creation at our department from January 2010 to December 2015 were included. The incidence of outlet obstruction and risk factors were analyzed. Results Outlet obstruction occurred in 18 cases (16.8%). The incidence was significantly higher in total colectomy or proctocolectomy cases as well as in those with left side construction and laparoscopic surgery than in other patients in a univariate analysis. However, in a multivariate analysis, no risk factors were extracted. Conclusions To determine the true cause of this disease, a prospective study with a large number of cases is needed. Since multiple terms are used for this condition, resulting in confusion, a consensus on the appropriate terms is also important.

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., High KLF5 expression in cancer cells is an independent predictor of poor prognosis in patients with primary colorectal cancer and related liver metastases. The malignant potential of cells with high Krüppel‐like factor 5 expression might be the result of high proliferative activity and cancer stem cell‐like properties, which likely occur owing to enhanced cyclin D1 and c‐Myc expression.

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.

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.

It is reported that simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional(3D)vascular imaging, is useful in colorectal cancer surgery. However, it is difficult to create 3D vascular images using non-contrast CT. Laparoscopic transverse colectomy is said to be technically difficult. Mini-laparotomy surgery for mid-transverse colon cancer is quite easy to perform. However, exact D2 lymph node dissection is very difficult. We present a case of D2 lymph node dissection during mini-laparotomy transverse colectomy performed using S-CTC, which involves the creation of 3D vascular images using non-contrast CT.The patient was a 77-year-old man with transverse colon cancer located in the mid-transverse colon, cT2N0M0, Stage Ⅰ. He had coexisting chronic renal failure. Non-contrast CT was performed prior to surgery, and the images were processed using workstation Zaiostation2.Both the artery and the vein created from non-contrast CT could be visualized clearly until the marginal vessels. Using noncontrast S-CTC in combination with CTC and 3D artery imaging, it was identified that the dominant artery was the left branch of the middle colic artery(MCA Lt), while the right branch of the MCA(MCA Rt)and accessory MCA(AMCA)were 10 cm or more apart. The fusion of 3D artery and vein imaging made it evident that the vein accompanying MCA Lt branched from the superior mesenteric vein. Using non-contrast S-CTC, D2 lymph node dissection, dissection of the branching root of MCA Lt and the vein at the same level was simulated. Thus, mini-laparotomy transverse colectomy was performed through a 7 cm incision, in accordance with the simulation.Non-contrast S-CTC was useful for performing D2 lymph node dissection during mini-laparotomy transverse colectomy.

A 54-year-old man receiving dialysis for diabetic nephropathy underwent surgery for sigmoid cancer. Nine months later, he was diagnosed with multiple liver metastases. He underwent 2 courses of FOLFIRI plus panitumumab(Pmab)as first-line therapy, 15courses of capecitabine plus bevacizumab(Bmab)as second-line therapy, and 27 courses of Pmab as third-line therapy. He developed various complications throughout the disease course, such as heart disease, diabetic gangrene in both legs, and abscess of liver metastasis. The tumor marker levels after each event were higher than the previous event and subsequently decreased with the resumption of chemotherapy. However, after 27 courses of Pmab, his liver and para-aortic lymph node metastases exacerbated, and he ultimately died from a poor general condition at 42 months after the initial recurrence of liver metastasis. Evidence regarding the safety and pharmacokinetics of chemotherapy in dialysis patients is insufficient at present. Herein, we report a case of metastatic colon cancer in a patient on hemodialysis along with a literature review.

// Kiyoko Takane 1,2 , Keisuke Matsusaka 1 , Satoshi Ota 3 , Masaki Fukuyo 1 , Yao Yue 4 , Motoi Nishimura 4 , Eiji Sakai 1,7 , Kazuyuki Matsushita 4 , Hideaki Miyauchi 5 , Hiroyuki Aburatani 8 , Yukio Nakatani 3,6 , Tadatoshi Takayama 2 , Hisahiro Matsubara 5 , Kiwamu Akagi 9 and Atsushi Kaneda 1,8 1 Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan 2 Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan 3 Department of Pathology, Chiba University Hospital, Chiba, Japan 4 Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan 5 Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan 6 Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan 7 Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan 8 Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 9 Division of Molecular Diagnosis, Saitama Cancer Center, Saitama, Japan Correspondence to: Atsushi Kaneda, email: // Keywords : CIMP, colorectal cancer, DNA methylation, familial adenomatous polyposis (FAP), KRAS Received : July 02, 2016 Accepted : August 17, 2016 Published : August 22, 2016 Abstract While sporadic colorectal cancer (CRC) is classified into several molecular subtypes, stratification of familial colorectal tumors is yet to be well investigated. We previously established two groups of methylation markers through genome-wide DNA methylation analysis, which classified sporadic CRC and adenoma into three distinct subgroups: high-, intermediate-, and low-methylation epigenotypes. Here, we investigated familial adenomatous polyposis (FAP), through quantitative methylation analysis of 127 samples (16 cancers, 96 adenomas, and 15 benign mucosa from 14 patients with FAP) using six Group-1 and 14 Group-2 methylation markers, APC , BRAF , and KRAS mutation analysis, and CTNNB1 and TP53 immunohistochemical analysis. All the 14 patients presented with APC germline mutation. Three were from the same family and presented the same APC mutation. FAP tumors lacked BRAF -mutation(+) high-methylation epigenotype and were classified into two methylation epigenotypes. While 24 of 112 tumor samples showed intermediate-methylation epigenotype significantly correlating with KRAS -mutation(+) ( P =3×10 -4 ), 88 tumor samples showed low-methylation epigenotype correlating with the absence of KRAS - and BRAF -mutations. Similar to sporadic CRC, CTNNB1 was frequently activated at the adenoma stage, and TP53 mutation occurred during cancer development from adenoma. Whereas some patients showed a single epigenotype in all tumors throughout the colon, tumors with two distinct epigenotypes developed within a family with the same APC mutation or even within one patient. Methylation accumulation significantly correlated with proximal location and older age. These results indicate that there are at least two distinct molecular subtypes of FAP tumors, resembling sporadic CRC and independent from the APC germline mutation status.

Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of HCV in patients who are liver transplant recipients. In the present study, we investigated HCV eradication via interferon-free therapies with DAAs in two HCV patients with advanced liver fibrosis following renal transplantation. In both cases, the interferon-free regimens with DAAs were effective in eradicating HCV in the patients after kidney transplantation. No adverse events caused by interferon were identified with the exception of anemia. Interferon-free regimens with DAAs for recurrent HCV in patients following kidney transplantation are relatively safe and effective. However, attention should be focused on anemia during these treatments.

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.

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.

Left hemicolectomy is a standard surgical method for cancer of the descending colon. Resection involves the region from the left side of the transverse colon to the sigmoid colon. Although laparoscopic hemicolectomy is widely used, it is difficult to determine an appropriate resection range during surgery because of the limited visual field. Simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional vascular imaging, enables the surgeon to clearly identify the position of the primary lesion and dominant vessel. We present 3 cases of cancer of the descending colon with different affected sites and lesion grades, in which appropriate dissection of the large intestine and treatment of the vessels was simulated by S-CTC, enabling laparoscopic surgery in accordance with the simulation. Case 1: Splenic flexure, cT1bN0M0, Stage I . The dominant vessels were identified by S-CTC as accompanying vessels branching from the accessary middle colic artery(A-MCA)and inferior mesenteric vein(IMV). The left branch of the MCA and the left colic artery(LCA)were 10 cm or more apart. A D2-type dissection was performed, and simulation was conducted for dissection of the branching root of the vein and the same level of the A-MCA. Case 2: Mid-descending colon, cT3N0M0, Stage II . The dominant A-MCA and LCA were identified with S-CTC. The intestinal tract was dissected to 5 cm from the dominant artery, and D3-type dissection was simulated with a retained inferior mesenteric artery(IMA)for preservation of the sigmoid colon. Case 3: Site adjacent to the sigmoid colon, cT3N0M0, Stage II . S-CTC identified the first sigmoid artery(S1)as the dominant artery, and revealed that the LCA and IMV were defective and that the A-MCA was 10 cm or more apart. Simulation of S1 selective resection was conducted such that D3-type dissection was performed, with a retained IMA for preservation of the sigmoid colon. In all 3 cases, laparoscopic surgeries were performed in accordance with the simulation. S-CTC was useful for optimal preservation of the intestinal tract and vascular supply in laparoscopic surgery for descending colon cancer.

To compare the results of abdominal wall closure using interrupted synthetic short-term vs. long-term tensile strength-retaining absorbable sutures. The subjects were 55 patients undergoing elective laparotomy through a midline vertical incision for gastric or colon cancer surgery between November 2008 and August 2010, at our hospital. After providing informed consent, the patients were randomized for suturing with Polysorb®, which provides short-term tensile strength, or with PDS®II, which provides long-term strength. The primary outcome analyzed was the incidence of incisional hernia or wound dehiscence. There were 28 patients allocated to the Polysorb group and 27 to the PDS II group. Postoperative wound dehiscence was noted in two patients (3.6 %). Five of 51 patients (9.8 %) suffered incisional hernia within 1 year after surgery, 6 of 41 patients (14.6 %) within 2 years, and 6 of 35 patients (17.1 %) within 3 years. There was no significant per year difference in the incidence of incisional hernia or wound dehiscence between the groups. Outcomes were favorable in both groups and not inferior to reported outcomes of larger-scale studies. Verification of the equivalence between the two types of suture material necessitates larger-scale studies that adopt the same suture methods.

Because there is little absorption of orally administered vancomycin hydrochloride (VCM) through the normal intestinal microvillus membrane, the pharmacokinetics of VCM absorbed from the digestive tract are mostly unknown. Here we report a case of severe colitis and renal insufficiency in which the serum concentration of VCM reached the supratherapeutic range after oral administration. A 54-year-old man receiving outpatient chemotherapy for rectal cancer was admitted to our hospital for severe sepsis and acute renal failure. Multimodal therapy including continuous renal replacement therapy (CRRT) and mechanical ventilation was initiated, and oral VCM administration (0.5 g every 6 h) was begun for suspected severe pseudomembranous colitis with large amounts of watery stool. Despite continued CRRT, the serum VCM concentration increased to 30.6 μg/mL after 4 days. Based on pharmacokinetic analysis, the bioavailability of VCM was estimated to be over 54.5%. Colonoscopy showed that the mucosa was severely damaged throughout the large intestine, resulting in considerable exudation of plasma and blood. This case indicates the need for careful and early monitoring during high-dose oral VCM administration to patients with severe mucosal injury and renal insufficiency.

We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model.We investigated whether fibrocytes were involved in the pathogenesis of Crohn's disease.Human surgical intestinal specimens were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI antibodies. Cultured human fibrocytes were prepared by culturing peripheral CD14(+) monocytes.In the specimens of patients with Crohn's disease, the fibrocyte/total leukocyte percentage was significantly increased in inflammatory lesions (22.2 %, p0.01) compared with that in non-affected areas of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of circulating fibrocytes/total leukocytes were significantly higher in patients with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4(+) and intercellular adhesion molecule 1(+) fibrocyte numbers were significantly increased in Crohn's disease, suggesting that circulating fibrocytes have a higher ability to infiltrate injured sites and traffic leukocytes. In cultured fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis factor (TNF)-α mRNA (17.0 ± 5.7-fold) and ColI mRNA expression (12.8 ± 5.7-fold), indicating that fibrocytes stimulated by bacterial components directly augmented inflammation as well as fibrosis.Fibrocytes are recruited early in the inflammatory phase and likely differentiate into fibroblasts/myofibroblasts until the fibrosis phase. They may enhance inflammation by producing TNF-α and can directly augment fibrosis by producing ColI.

A 75-year-old woman with abdominal pain and vomiting was admitted to our hospital. Colonoscopy showed an advanced colon cancer that encompassed the entire circumference of the descending colon’s lumen. The patient was diagnosed with occlusive ileus associated with the colon cancer. She had been watched for liver cirrhosis due to the hepatitis C virus and received radiofrequency ablation therapy for hepatocellular carcinoma (HCC) 6 years previously. Although she exhibited a gradual increase in serum levels of α-fetoprotein and PIVKA-II starting 2 years before admission, no tumors were detected in the liver by abdominal ultrasonography and computed tomography. On admission, contrast-enhanced computed tomography revealed not only the colon cancer but also a tumor adjacent to the cecum. Both tumors were successfully removed by surgery and a pathological analysis revealed that the cecum tumor was poorly-differentiated HCC. The serum levels of α-fetoprotein and PIVKA-II declined markedly after the operation and no masses considered as peritoneal metastasis have been detected to date. This is the first report of the simultaneous resection of disseminated HCC and colon cancer.

Background: It has not been elucidated whether the clinical efficacy of oral fluoropyrimidines for adjuvant chemotherapy of colorectal cancer varies with tumor biological characteristics. Patients and Methods: A multicenter randomized trial was performed comparing oral tegafur/gimeracil/oteracil (S-1) and uracil-tegafur/ leucovorin (UFT/LV) as adjuvant therapy for stage III colorectal cancer. Postoperative survival was compared based on the 5-FU-related mRNA levels in cancer tissues. Results: Among patients with tumor expressing dihydropyrimidine dehydrogenase (DPD) mRNA within the 66.7th percentile (lower 2/3) of all cases, overall survival (OS) was significantly better in the S-1 than in the UFT/LV group. In the S-1 group, patients with low DPD-expressing tumors had significantly better OS than those with highly expressing tumors. Patients with low thymidine synthase (TS)-expressing tumors had significantly better OS than those with highly expressing tumors. Conclusion: The efficacy of oral fluoropyrimidines as adjuvant chemotherapy for colorectal cancer may be influenced by the level of 5-FU-related mRNA in cancer tissues.

Aim This study aimed to assess the ability of preoperative axial computed tomography (CT) to predict surgical difficulty in bringing the ileal pouch to the level of the anus during restorative proctocolectomy (RPC). Method Patients who underwent RPC with an ileal pouch-anal anastomosis (or ileal pouch-anal canal anastomosis) in our institution between January 2008 and April 2014 were enrolled. The patients were divided into two groups, including those in whom CT indicated potential difficulty in extending the pouch downwards (extension difficult (ED) group) and patients with no CT evidence of potential difficulty (normal group). The groups were compared for clinical factors and the thickness of the slices of CT showing the root of the superior mesenteric artery, the point of communication of the ileocaecal artery with the marginal artery (tICA) and the anal verge (AV). Receiver-operating characteristic analysis was performed, and a cut-off value was calculated for predicting the degree of difficulty in bringing the ileal pouch down to the anal canal. Results Thirty-four patients were entered in the study. The ED group included significantly taller patients and more with familial adenomatous polyposis than the normal group. The distance between tICA and AV was significantly longer in the ED group, with a cut-off of 21 cm giving a sensitivity of 100% and a specificity of 83.3%. Conclusion The distance between tICA and AV measured by axial CT can be a useful predictor for the difficulty in bringing the ileal pouch down to the anus during RPC.

In our institution, steroids are administered before resection of primary colorectal cancer lesions with synchronous unresectable hepatic metastases in order to avoid severe postoperative complications and hepatic failure. We herein report the results of the treatment.Thirty-eight colorectal cancer patients with synchronous unresectable hepatic metastases were divided into 2 groups: Group S (patients who received steroids in the perioperative period) and Group N (other patients). The clinicopathological features, post-operative course, and survival were compared between the 2 groups. Hydrocortisone sodium succinate was administered twice a day from immediately before laparotomy until the second postoperative day.The number of patients with severe hepatic metastases and extra-hepatic metastases was significantly higher in Group S. No significant differences were observed between the 2 groups regarding the incidence of severe postoperative complications or the overall survival. Among 25 patients with liver dysfunction, the complication rate was significantly lower and survival was significantly longer in Group S compared to Group N.The perioperative administration of steroids to colorectal cancer patients with synchronous unresectable hepatic metastases may reduce the complication rate and may thus improve survival, especially in patients with liver dysfunction.

D2 lymph node dissection in laparoscopic surgery for early colon cancer requires selective vessel dissection, making it technically very difficult. Using surgical simulation-CT colonography (simulation-CTC), we could perform laparoscopic assisted sigmoid colectomy preserving the inferior mesenteric artery (IMA) and vein (IMV) more accurately and safely. The case described here was a type 0-Ip sigmoid colon cancer with a tumor size of 13 mm. Endoscopic mucosal resection was performed to confirm a pathological diagnosis of pT1b (4,000 mm) and v1. Sigmoid colectomy was planned, and simulation-CTC was performed, which demonstrated that the cancer was located in the proximal sigmoid colon and supplied by the first sigmoid colon artery (S1). To maintain the blood flow to the distal sigmoid colon, selective S1 resection preserving the IMA and IMV was planned. At the operation, S1, which branches off from the IMA near the bifurcation of the abdominal aorta, was dissected, and the vein accompanying S1, which branches from the IMV in the same area as S1, was dissected. The operation was performed accurately according to the plan, showing that simulation-CTC can be very useful.

This single-institution experience retrospectively reviewed the outcomes in 21 patients with primary duodenal adenocarcinoma. Twelve patients underwent curative surgery, and 9 patients underwent palliative surgery at the Chiba University Hospital. The maximum follow-up period was 8650 days. All pathologic specimens from endoscopic biopsy and surgical specimens were reviewed and categorized. Twelve (57.1%) patients underwent curative surgery (R0): 4 pancreaticoduodenectomies (PD), 4 pylorus-preserving PDs (PpPD), 2 local resections of the duodenum and 2 endoscopic mucosal resections (EMR). Palliative surgery was performed for 9 patients (42.9%) following gastro-intestinal bypass. The median cause-specific survival times were 1784 days (range 160–8650 days) in the curative surgery group and 261 days (range 27–857 days) in the palliative surgery group (P = 0.0003, log-rank test). The resectability of primary duodenal adenocarcinoma was associated with a smaller tumor size, a lower degree of tumor depth invasiveness, and less spread to the lymph nodes and distant organs.