Hepatic Colon Research Articles

Gastrocolic Ligament Lymph Node Dissection for Transverse Colon and Hepatic Flexure Colon Cancer: Risk of Nodal Metastases and Complications in a Large-Volume Center

Gastrocolic Ligament Lymph Node Dissection for Transverse Colon and Hepatic Flexure Colon Cancer: Risk of Nodal Metastases and Complications in a Large-Volume Center

Chronic Nonhealing Colonic Ulcer

A 53-year-old man presented with a positive fecal occult blood test and denied having symptoms of fever, abdominal pain, fullness, nausea, diarrhea, or constipation. Colonoscopy showed a single irregular polypoid lesion with a deep central ulcer in the hepatic flexure colon (Figure A). The rest of the colonic mucosa appeared normal. The biopsy specimen was negative for colon cancer or inflammatory bowel diseases such as Crohn’s disease. Next, a barium enema was performed, which unexpectedly revealed a fistula tract between the hepatic flexure colon and the gallbladder (Figure B, arrow).

Argon plasma coagulation for successful treatment of bile leakage after subtotal cholecystectomy

BackgroundSubtotal cholecystectomy is an effective surgical method to decrease the risk of complications for gallbladders that are difficult to remove. However, there is a risk for postoperative refractory bile leakage through the gallbladder stump. Here, we report a new management technique involving the use of argon plasma coagulation (APC) to stop bile leakage after a subtotal cholecystectomy.Case presentationA 74-year-old man was referred to our hospital for abdominal pain and fever. Contrast-enhanced computed tomography of the abdomen showed fluid collection, such as an abscess, surrounding the gallbladder and hepatic flexure colon. The patient was diagnosed with colonic perforative peritonitis, and he underwent emergency surgery. On laparotomy, the abscess was observed outside of the hepatic flexure colon and gallbladder necrosis was detected. The neck of the gallbladder and the area close to the hepatoduodenal ligament was severely inflamed prohibiting dissection. The hepatic flexure colon was part of the abscess wall, and resection was needed. A subtotal cholecystectomy and right hemicolectomy confirmed peritonitis caused by cholecystic perforation. The mucous membrane of the gallbladder neck that remained was necrotic or detached. Therefore, the stump of the gallbladder was closed by primary sutures without cauterization of the mucosa. On postoperative day 6, bile leakage from the gallbladder stump was revealed. Percutaneous and endoscopic retrograde cholangiography drainage were performed. However, the liquid, which seemed to be secreted from the mucosa of the remnant gallbladder, was continuously obtained. We used APC to cauterize the gallbladder mucosa through the fistula of the abdominal drainage tube. Bile leakage and mucus discharge were improved after three rounds of APC cauterization.ConclusionsAPC effectively treated refractory bile leakage from a gallbladder stump after subtotal cholecystectomy for severe cholecystitis.

Cytotoxicity, Docking Study of New Fluorinated Fused Pyrimidine Scaffold: Thermal and Microwave Irradiation Synthesis.

Azolopyrimidines are imposed on the arena of drugs treated for cancer. The urgent need to discover new selective anticancer agents, paved the way to explore the antitumor significance of such fused systems. From the synthetic point of view, Microwave facilitated technique for synthesis is very strongly associated with green method in chemistry field. Our aim is to synthesize bioactive compounds using docking simulation run by MOE program to explore the binding mode of the most active enzyme inhibitor among the target compounds. In addition to the use of conventional heating, the MARS system of CEM utilized for Microwave irradiation that is equipped with a multi-mode platform with a magnetic stirring plate and a rotor that allows the parallel processing of many vessels per batch. All the synthesized compounds were tested for their anticancer activity against hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-116). Screening against the cancer cell lines was performed, using doxorubicin as a reference drug. Docking studies were conducted using MOE software. A novel series of fluorinated fused-pyrimidine namely, pyrazolopyrimidine, triazolopyrimidine and pyrimidobenzimidazole were designed and synthesized conventionally and under microwave irradiations. The mechanistic pathways as well as the structure of all products were debated and demonstrated based on all possible spectral data. In-vitro examination of the novel prepared derivatives versus the three different human cancer cell lines [hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-116)] was evaluated to estimate their actual activity. We have developed a simple, facile, and efficient procedure for the formation of new series of azolopyrimidines. All spectra of all products were investigated deliberately to confirm their structures. The anti-cancer activity has been examined against three cancer cell lines e.g. HepG-2, MCF-7 and HCT116. Molecular modeling study was carried out in order to rationalize the in vitro anti-tumor results.

Does transverse colon cancer spread to the extramesocolic lymph node stations?

Background Transverse colon cancers show behavioral differences in terms of the involvement of extramesocolic lymph nodes since they are closely related to all three embryological planes. These tumors have also been observed in the gastroepiploic-omental (GEOM) region, outside their usual regional areas. We will evaluate this new metastatic route in our own cases. Methods Thirty-four patients (16 female, 18 male) that presented to our clinic with hepatic flexure, transverse colon, and splenic flexure cancer between October 2011 and May 2017 were included in the study. Type of surgery, histopathology, and factors causing metastasis, morbidity, and mortality were evaluated. Results Cancer was located in the transverse colon in 20 patients (58.8%), hepatic flexure in 10 (29.4%), and splenic flexure in four (11.7%). Lymph node positivity in the GEOM region was present in four patients: in the infrapyloric region and pancreatic head, close to the hepatic flexure in three patients; and the midline of GEOM, close to the inferior body of the pancreas in one patient. Perineural invasion (p < .05) and N stage (p < .05) were associated with GEOM region metastasis. Tumor localization and age significantly increased pleural effusion. Conclusions In transverse colon and both flexural tumors, we recommend planning the surgery according to the localization of the tumor and including the GEOM, infrapyloric and infrapancreatic areas. It is possible to discuss whether to perform extended excision for all or only selected patients. The best approach seems to be to evaluate the co-factors to manage these patients.

Risk of Developing Hepatocellular Carcinoma following Depressive Disorder Based on the Expression Level of Oatp2a1 and Oatp2b1.

Background Accumulating evidence from prospective epidemiological studies has showed that depression disorder (DD) is a risk factor for cancer. The aim of this study is to explore the association of DD and the overall occurrence risk of hepatocellular carcinoma (HCC) and the mechanism. Methods In this study, 60 mice were randomly divided into four groups: Control group, DD group, HCC group, HCC-DD group. Mice received a chronic dose of reserpine to establish depression model, followed by Diethylnitrosamine and Carbon tetrachloride administration to establish HCC models. Behavioral depression was assessed by sucrose preference test (SPT) and the expression of Serotonin 1A (5-HT1A) receptor in the hippocampal. The expression of Oatp2a1 and Oatp2b1 in the digestive system tissues was detected by PCR and western blotting. Results Reserpine-administrated mice had a reducing sucrose preference at Day 14 compared with blank mice (P<0.05). The expression of 5-HT1A receptor in the hippocampal was decreased in DD mice compared with blank mice. The survival analysis indicated that the HCC mice with DD have poorer survival rate compared with the HCC mice. Compared with HCC mice, the expression of Oatp2a1 and Oatp2b1 was lower in liver and stomach tissue and higher in hepatic carcinoma and colon tissue of HCC-DD mice (P<0.05), and the expression of Oatp2a1 was higher in the spleen tissue of HCC-DD mice while the expression of Oatp2b1 was lower (P<0.05). However, no difference was found in the expression of Oatp2a1 and Oatp2b1 in the small intestine tissue between HCC group and HCC-DD group. Conclusions DD was the adverse factors for the overall occurrence risk of HCC. Mechanistically, be the downregulation of Oatp2a1 and Oatp2b1 in liver tissue induced by DD might be involved.

Edgeworthia gardneri (Wall.) Meisn. water extract improves diabetes and modulates gut microbiota

Ethnopharmacological relevanceIn Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia. Aim of the studyThis study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community. Materials and methodsChemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated. ResultsUHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups. ConclusionsE. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus.

Metastatic Prostate Cancer Presenting as Solitary Hepatic Flexure Colon Polyp

An 84 year old man with a past medical history of prostate cancer with lytic bone lesions and GERD, was brought from his nursing home to the emergency room with maroon stool. He was found to be tachycardic and normotensive. Initial bloodwork revealed anemia with a hemoglobin of 6.9g/dL; patient's previous baseline was 10.5g/dL three weeks earlier. The patient was admitted to the floor and resuscitated with IV fluids, two units of packed red blood cells, and an intravenous drip of proton pump inhibitor. Persistent maroon stool was noted on rectal exam. The patient underwent EGD, which found Los Angeles Classification grade B esophagitis with no bleeding in the lower third of the esophagus, large hiatal hernia, gastritis and duodenitis. No source of bleeding was identified on EGD, so the patient underwent colonoscopy. Colonoscopy showed extensive diverticulosis in the sigmoid, descending and transverse colon without active bleeding. Additionally, there was one 4mm, sessile, non-bleeding polyp at the hepatic flexure, which was completely resected with cold biopsy forceps. Pathologic examination of the specimen showed positive staining for PSA, PSAP, AE1/3 and CD10 focally and negative staining for CD3, CD5, CD20, kappa/lambda and CDX2. This constellation of findings was determined to be consistent with grade 5 metastatic prostate carcinoma. Microscopically the metastatic cancer had discohesive cells infiltrating the lamina propria and submucosal space. Concomitant serum PSA found to be 314 ng/mL. The patient's hemoglobin stabilized, no further bleeding was noted, and he was discharged to follow with his private oncologist as an outpatient. Prostate cancer most commonly metastasizes through local invasion or hematogenous spread to bone, distant lymph nodes, lung and liver. While prostate cancer is known to cause local invasion of the adjacent colonic mucosa, it is not known to produce distant colonic metastases. This case illustrates one of the only documented cases of a prostate carcinoma metastasizing to a distant site in the colon. Previous cases have not shown an isolated colonic polyp, outside of the rectum, identified as metastatic prostate cancer. Such a determination would have a significant effect on subsequent oncologic management. Additionally, this case highlights the importance of considering comorbid conditions during the assessment, treatment and follow up of colonic polyps, as they may give rise to atypical pathology.1868_A Figure 1. 4mm sessile polyp found in the hepatic flexure of colon on colonoscopy. Polyp was removed with cold biopsy forceps.1868_B Figure 2. Hepatic flexure polypectomy specimen, fixed in formalin, with PSA immunohistochemical staining.

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.

Localized Adenomyomatosis of Gallbladder Mimicking Advanced Hepatic Flexure Colon Cancer: A Case Report

Localized Adenomyomatosis of Gallbladder Mimicking Advanced Hepatic Flexure Colon Cancer: A Case Report

Risk Factors and Oncologic Outcomes of Anastomosis Leakage After Laparoscopic Right Colectomy.

We estimated the incidence of anastomosis leakage and explore possible risk factors and oncologic outcomes following laparoscopic right-side colon resection among colon cancer patients. We retrospectively analyzed 423 patients who were diagnosed with appendiceal, cecal, ascending, or hepatic flexure colon cancer who underwent laparoscopic colonic resection and anastomosis between September 2006 and July 2014. We compared short-term and long-term outcomes between no-leakage and leakage groups. There were 16 cases of right-side anastomosis leakage in a total 423 colon cancer cases (3.78%). The risk of leakage was increased in smokers (odds ratio=6.592, P=0.007) and with a longer operating time (odds ratio=1.024, P<0.001). There were no significant differences between the groups in local recurrence (P=0.106), overall survival (P=0.055), or cancer-specific survival (P=0.235). Smoking and long operating time are risk factors for right-side colon anastomosis. There were no significant differences in oncologic outcomes.

An Uncommon Cause for Colonic Ischemia

We present a case of Polyarteritis Nodosa (PAN) in a hepatitis B negative patient presenting as ischemic colitis with delay in diagnosis leading to renal failure. There have been less than 10 cases reported in literature.A 49 year old male with a history of hypertension with resultant chronic kidney disease Stage 2 and rheumatoid arthritis (on Prednisone) presented to our hospital with generalized malaise, intermittent nausea and vomiting along with loose stools for the past 1 month. He noted a 30lb weight loss over the previous few months. Labs were notable for normocytic anemia, leukocytosis and acute kidney injury ( Creatinine of 3.4 from a baseline of 1.5). Urinalysis showed trace protein, no WBC or RBC with negative urine eosinophils. His renal function improved with hydration, however his gastrointestinal symptoms persisted. Work up revealed no infections and he underwent a colonoscopy which revealed ulcerated mass like lesions in the hepatic, transverse and sigmoid colon. Biopsies revealed ischemic colitis. He underwent an abdominal aortogram with carbon dioxide which showed no evidence of mesenteric stenosis. His renal function underwent progressive rapid decline necessitating a kidney biopsy revealing necrotizing arteritis consistent with a diagnosis of polyarteritis nodosa (PAN). He was started on hemodialysis and immunosuppresion with steroids and cyclosporine. His gastrointestinal symptoms resolved. A repeat follow up colonoscopy revealed normal colonic mucosa. PAN usually presents as ischemic disease in the small bowel and much more rarely in the colon. Colonic presentation can be mistaken for IBD in younger patients and atherosclerotic ischemic colitis in older patients as in this patient. Unlike some other vasculitides such as Wegener granulomatosis, remission can be obtained with PAN if diagnosed early. This patient was started on an immunosuppression regimen, which suppressed recurrence of GI symptoms, however was too late to salvage kidney function. In patients who present with a constellation of laboratory findings in the setting of ischemic colitis a broad differential should be obtained and repeat deep biopsies should be taken to confirm diagnosis of a vasculitis. A delay in diagnosis can lead to life changing consequences and even death.

Abstract 45: Preventing and treating hepatic metastatic colon and pancreatic cancers by targeting cell metabolism

Abstract One fundamental change in cancer cells in oncogenesis is the alteration of glucose metabolism. With few exceptions, cancer cells exhibit aerobic glycolysis. A majority of pyruvate derived from glycolysis is converted to lactate instead of entering mitochondria for oxidative phosphorylation. This feature of cancer cells is also referred as “the Warburg effect”. The functional significance of the inefficient metabolic mode to cancer cells is becoming clear. In essence, reduction in the flux of pyruvate into mitochondria prevents complete oxidation of glucose. This increases production of NADPH and metabolic intermediates required for biosynthesis of macromolecules essential for cell proliferation. Pyruvate flux into mitochondria can be dramatically enhanced through mitochondrial uncoupling, a process that allows protons cross the mitochondrial inner membrane without producing ATP. As a result, mitochondrial uncoupler promotes “futile” oxidation of acetyl-CoA, leading to complete glucose oxidation. Therefore, safe mitochondrial uncouplers could be potent anti-cancer agents by antagonizing the function of the Warburg effect. Here we tested this novel cancer chemotherapeutic strategy with niclosamide ethanolamine (NEN), a well-characterized mitochondrial uncoupler with an excellent safety profile, and one of its derivative (OXY-1) in culture cell models and a mouse model. Mouse colon cancer cells (MC38) and mouse pancreatic cells (Panc02) were treated with NEN and OXY-1. At effective mitochondrial uncoupling concentrations, NEN and OXY-1 reduced cells viability, induced cell cycle arrest, and reduced clonegenicity. Moreover, NEN and OXY-1 also inhibited cell migration. These effects were associated with the activation of AMPK and reduction of NADPH/NADP ratio. We further examined the anti- cancer effect of NEN and OXY-1 on a metastatic cancer mouse model. First, we tested if the uncouplers are effective in inhibiting cancer growth. The MC38 or Panc02 cells were injected into the liver of NOD mice. Oral treatment of OXY-1 (800 ppm in food) significantly reduced tumor size and tumor incidence in mouse liver. We then tested if these drugs could inhibit tumor metastasis. MC38 or Panc02 cells were intrasplenically injected into the mice and the tumor metastasis to liver was analyzed. Oral NEN (2000 ppm in food) or OXY-1 (800 ppm in food) either totally prevented tumor metastasis to liver or drastically reduced metastatic tumor numbers and tumor volume. Taken together, our results strongly suggest that the safe and mild mitochondrial uncouplers NEN and OXY-1 could be effective in preventing and treating hepatic metastasis of colon and pancreatic cancers. Our results may provide a new and attractive way for preventing and treating these incurable tumors. Citation Format: AMER H. ALASADI, Jingjing Guo, Hanlin Tao, Shengkan Jin. Preventing and treating hepatic metastatic colon and pancreatic cancers by targeting cell metabolism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 45.

Intra-Abdominal Hydatidosis: Hydatid Cyst Related to Right Hepatic Colon Lumen

Hydatid disease is very common in endemic areas and is one of the most frequent parasitoses in Turkey. We present a rare case of hydatidosis related to the right hepatic colon lumen. Hydatid cysts were present on the liver, in the right adrenal region, and also on the hepatic flexura, surrounded by the right colon and omentum. In our case, a cyst adjacent to the ascending colon had ruptured into the colon lumen and developed a cystocolonic communication. Cysts may not always be detectable by ultrasound (US); adrenal and right colonic cysts may not be detected, depending on the patient’s colonic gas superposition factors or other reasons related to the operator. In our case, multiple hydatid cysts and cystocolonic communication of complications of the cyst were found with multidetector computerized tomography (MDCT), and then, a colonoscopy identified the cystocolonic communication. These results reveal the important role of CT in the differential diagnosis process

Antimicrobial and antitumor activity and diversity of endophytic fungi from traditional Chinese medicinal plant Cephalotaxus hainanensis Li.

Endophytes from Cephalotaxus hainanensis Li, an important source of anti-leukemia drugs, have not been widely explored. In this study, 265 endophytic fungal isolates from C. hainanensis Li were screened for antimicrobial activities against tilapia, banana, rice, and rape and for antitumor activities against human leukemia cell lines (K562, NB4, and HL-60). Diversity was also analyzed. The results showed that 17.7% of the endophytic fungi had antimicrobial activities against at least three different test microbes, and activity against Fusarium oxysporum RKY102 was the highest at 15.8%. Cytotoxicity against at least one tumor cell line tested was observed in 18.5% of the endophytic fungi; with the highest value of 10.6% against K562. The endophytic fungal strains also showed relatively high activities against K562, NB4, and HL-60 while relatively fewer strains were cytotoxic against the human hepatic Hep-G2 and colon LoVo cancer cell lines. Thirty endophytic fungal strains showed both high antimicrobial and antitumor activities. Moreover, the analyses of the diversity of the 30 highly active strains showed they belonged to 20 species from 14 genera, and this is the first report of endophytic fungi Albonectria rigidiuscula, Colletotrichum magnisporum, and Nemania diffusa being isolated from Cephalotaxus plants. These findings suggest that natural antibacterial products for humans and tilapia; antifungal compounds for rice, rape, and banana; and antitumor compounds for leukemia therapy could be isolated from fungal strains derived from C. hainanensis Li.

Comparison of Long-Term Follow Up of Laparoscopic Versus Open Colectomy for Transverse Colon Cancer

Clinical Outcomes of Surgical Therapy (COST) was a landmark study demonstrating that laparoscopic-assisted colectomy had oncologic outcomes similar to those of open colectomy for colon cancer, but transverse colon cancers (TCCs) were excluded from that study. Oncologic results of a laparoscopic resection for TCC are unknown. This single-institution retrospective 3:1 case-matched review examined patients treated for TCC from January 1, 1996, to April 15, 2009. Laparoscopic colectomy (LC) and open colectomy (OC; extended right, extended left, and total abdominal) cases completed for Stage I to III adenocarcinoma of the transverse colon (hepatic flexure, transverse colon, and splenic flexure) were analyzed. Patients were matched for age, tumor location, and stage. Primary endpoints were overall survival and disease-free survival. Secondary endpoints were length of stay and pathologic parameters. One hundred and twenty-three OC cases were matched with 41 LC cases. There were four conversions (9.7%) in the LC group. Length of stay was reduced by 28% in the LC group (P = 0.02). Complication rate and severity were similar between the two groups (29% vs 24%; P = 0.68). Lymph node harvest was higher in the LC group than in the OC group (23.3 vs 18.6; P = 0.03). All pathologic margins were clear, and no local recurrence was found in either group. Five-year overall survival (61% vs 59%; P = 0.39) and disease-free survival (88% vs 82%; P = 0.23) were similar in the two groups. Short-term recovery was faster and lymph node harvest was improved in the LC group. Thus, laparoscopic management of TCC is a safe and feasible procedure.

Clean Colon Software Program (CCSP), Proposal of a standardized Method to quantify Colon Cleansing During Colonoscopy: Preliminary Results.

Background and study aims: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale. Patients and methods: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software. Results: The cleansing score of the prelavage colonoscopies was 1.56 ± 0.52 and the postlavage one was 2,08 ± 0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ± 0.69) was dirtier than left colon segment prelavage (2.07 ± 0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 – 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 – 0.89). Conclusions: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

Cholecystocolic fistula caused by gallbladder carcinoma: Preoperatively misdiagnosed as hepatic colon carcinoma

Cholecystocolic fistula secondary to gallbladder carcinoma is extremely rare and has been reported in very few studies. Most cholecystocolic fistulae are late complications of gallstone disease, but can also develop following carcinoma of the gallbladder when the necrotic tumor penetrates into the adjacent colon. Although no currently available imaging technique has shown great accuracy in recognizing cholecystocolic fistula, abdominopelvic computed tomography may show fistulous communication and anatomical details. Herein we report an unusual case of cholecystocolic fistula caused by gallbladder carcinoma, which was preoperatively misdiagnosed as hepatic flexure colon carcinoma.

Research of hepatocyte nuclear factor 4α in digestive system tumors

Hepatocyte nuclear factor 4α is a transcription factor of the nuclear hormone receptor superfamily and plays a very important role in the differentiation and development of the digestive system as well as the polarity regulation,which is considered to be a tumor suppressor gene.It also plays a very important role in digestive tumorigenesis,invasion and metastasis of hepatic carcinoma,colon cancer and gastric cancer,which is closely associated with epithelial-to-mesenchymal transition,the regulation of cell proliferation and wnt signaling pathway.HNF4α expression and its regulation mechanism in the digestive system tumors are now the research focus. Key words: Hepatocyte nuclear factor 4α ; Digestive system neoplasms

Abstract 1110: Colorectal liver metastases induce a systemic phase shift of the biological clock

Abstract Circadian clock genes drive cyclic expression of 10-15% of the transcriptome. Disruption of the circadian clock may deregulate the cell's normal functions and can lead to carcinogenesis, indicating that clock genes also act as tumor suppressor genes. In previous work, we have shown that circadian rhythmicity is disrupted in C26 colon carcinoma cell-derived hepatic metastases, as compared to the non-cancerous tissue of the liver. It has been suggested that neoplastic tissue can influence the circadian clock of adjacent tissues, causing a tissue specific phase shift. A better understanding of how tumors affect the circadian system may help elucidate the role of the clock in cancer patients suffering from fatigue and sleep disorders. Therefore, we have examined the circadian clock in liver and kidney tissue of mice carrying hepatic C26 colon carcinoma cell metastases. Male BALB/c mice were divided into two groups. In group 1, hepatic metastases were induced by injecting C26 colorectal carcinoma cells into the spleen. Group 2 was sham operated. Three weeks after (sham) surgery, animals were sacrificed over a 24-hour period (6 time points, n=4 per time point) and liver and kidneys were collected to compare circadian rhythmicity in control and tumor bearing animals. RNA was isolated and qRT-PCR was performed to determine the expression levels of 5 clock genes (Rev-Erbα, Per1, Per2, Bmal1, Cry1) and 3 clock controlled genes (Dbp, p21 and Wee1). Liver and kidney tissue of healthy control mice showed normal 24-hour oscillations of all clock genes, consistent with normal circadian rhythmicity. Liver and kidney tissue of tumor-bearing mice, as compared to control mice, showed a marked phase difference in clock rhythms. In the liver we observed a 4-hour phase advance for Bmal1, Rev-Erbα and Dbp. In contrast in the kidney, there was a 4-hour phase delay for Bmal1, Rev-Erbα, Cry1 and DBP, and a 8 hour delay for Per2. These data show that colorectal liver metastases induce a phase advance in the liver, and a phase delay in the kidney . This suggests a systemic effect of the tumor on peripheral clocks. This difference in clock phase between tumor-bearing mice and healthy controls may provide new clues to further understand the role of the clock for fatigue and sleep problems in cancer patients, but may also give opportunities to administer chemotherapeutic treatment in a chronotherapeutical setting . Citation Format: Sander A. Huisman, F. Tamanini, A. Ahmadi, J.N.M. IJzermans, G.T.J. van der Horst, R.W.F. de Bruin. Colorectal liver metastases induce a systemic phase shift of the biological clock. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1110. doi:10.1158/1538-7445.AM2014-1110