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Rectovaginal fistula (RVF) and vesicovaginal fistula (VVF) are infrequent but distressing complications after pelvic surgery. However, their adequate treatment is not well described. Here, we simultaneously encountered and successfully treated RVF and VVF after radical surgery for rectal cancer. A 70-year-old woman underwent low anterior resection (LAR) combined with resection of the uterus, the bilateral adnexa, and the upper side of the vagina, as well as diverted ileostomy for rectal cancer. A month after the surgery, she developed urinary incontinence and underwent medical treatment, but her symptoms did not improve. Evaluation with contrast enema before stoma closure revealed the presence of RVF and VVF. We repaired the VVF and RVF via transabdominal and transperineal approaches. After 6 months, ileostomy was closed and the patient had no recurrence of cancer and fistula. In LAR with hysterectomy and resection of the vaginal wall, there is a risk of RVF and VVF. The excision and closure of the fistula tract and omental flap can be effective to treat both fistulae.

Isolated para-aortic lymph node (PLN) recurrence from colorectal cancer (CRC) is rare, with no currently validated treatments. Few reports have described the successful resection of isolated PLN involvement from CRC following chemotherapy. We report the case of a 63-year-old man who underwent sigmoidectomy for sigmoid colon cancer at our hospital. Pathological examination demonstrated advanced sigmoid colon cancer with metastatic involvement in both of the tested PLNs. Palliative chemotherapy was initiated four weeks after surgical resection, with administration of the FOLFIRI regimen. Four years after the operation, computed tomography (CT) revealed an enlarged PLN below the left renal vein. As PLN enlarged to 15 mm in the minor axis on a CT scan in 2014 after receiving a total of 156 courses of the FOLFIRI regimen, we considered the enlarged PLN to represent an isolated metastasis. Accordingly, lymph node resection was performed with microscopically negative margins. The patient maintained a good quality of life without any side effects throughout the whole course of his treatment and remains disease-free at 24 months without chemotherapy after resection of the isolated PLN. Curative resection following chemotherapy may improve survival of carefully selected advanced CRC patients with locoregional recurrence, such as isolated PLN involvement.

Although self-expanding metallic stents (SEMS) are useful tools for relieving large bowel obstructions in patients with colorectal cancer (CRC), their efficacy in a palliative setting has not been validated. This meta-analysis aimed to evaluate the feasibility of SEMS as a palliation for unresectable CRC patients with bowel obstructions and to determine their contribution to the prognosis of CRC, compared with surgical intervention. We conducted a literature search of the PubMed and Cochrane Library databases. We selected all controlled trials that compared SEMS with surgical interventions as palliative treatments in unresectable obstructive CRC patients. The primary outcome was early complications, and the secondary outcomes were mortality, other morbidities, and long-term survival rates. Ten studies met our inclusion criteria. SEMS significantly reduced the risk of early complications (odds ratio [OR] 0.34; 95 % confidence interval [CI] 0.20–0.58 %; P

Background: The Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. Recently, ATM was reported to correlate with breast cancer metastasis by regulating phosphorylated Snail which was known as a marker of epithelial-mesenchymal transition (EMT), however, it remains unclear in colorectal cancer (CRC). In this study we attempted to clarify the impact of ATM on the mechanism of EMT in CRC. Methods: Potential ATM levels were evaluated in human CRC cells (HT29 and SW480) by qPCR and western blot analysis. Cells were induced EMT by treated with TGF-b, were confirmed by the change of EMT markers (i.e. N-cadherin, E-cadherin, Snail and twist). Next, ATM levels were down-regulated by siRNA and the impact on EMT were evaluated by EMT markers. Invasive potential was evaluated by scratch assay. Results: HT29 showed significantly higher levels of ATM comparing to SW480 (p = 0.042). N-cadherin (p = 0.065), Snail (p = 0.034) and twist (p = 0.052) were highly observed in HT-29, while similar level of E-cadherin in SW480 (p = 0.692). Scratch assay revealed that approximately 4 times high migration was observed in HT29. TGF-b induced EMT such as elevation of N-cadherin and Snail (E-cadherin was not affected), leading to promotion of cell migration in SW480. ATM was successfully 48.4% down-regulated (p = 0.001) in SW480, which resulted in reducing cell migration (p = 0.033). Conclusions: ATM might be a critical regulator of EMT in colorectal cancer invasion. Citation Format: Hidena Takahashi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Masashi Yahagi, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa. Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5193. doi:10.1158/1538-7445.AM2015-5193

529 Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.

558 Background: Muscle volume loss (MVL) is observed in end-stage cancer patients as cachexia. However, the impact of MVL on tumor response and survival still remains unclear during chemotherapy in metastatic colorectal cancer (mCRC) patients. The aim of this study is to evaluate correlation between MVL and oncologic outcomes in mCRC patients. Methods: A total of 91 mCRC patients who received first-line chemotherapy were identified in our prospective registry between February 2007 and April 2013. Skeletal muscle index at the level of L3 vertebra (SMI) was calculated by muscle volume normalized by stature at the time of the induction of first-line chemotherapy (bSMI) and first evaluation of tumor response (fSMI). Patients whose SMI decreased more than 10% were classified as MVL group. The impact of these variables on oncologic outcomes (overall survival [OS], progression free survival [PFS], and tumor response rate [RR]) were analyzed. Results: Mean bSMI and fSMI were 35.0 (SD: 7.11) cm2/m2, and 34.2 (SD: 6.85) cm2/ m2, respectively. Eighteen patients were classified into the MVL group. The patients in MVL group significantly responded to the chemotherapy (RR of MVL: 11.1% vs. RR of non-MVL: 49.3%, p < 0.01). There was no significant difference in terms of high grade adverse effect between MVL and non-MVL group. Patients in MVL group had a significant shorter median PFS (MVL: 5.5 [2.5 - 10.1] months vs. non-MVL: 12.8 (3.8-80.5) months, p < 0.01) and median OS (MVL: 13.9 [6.2-61.2] months vs. non-MVL: 29.3 (8.2-94.0) months, p < 0.01). Multivariate analysis demonstrated that patients with MVL had significantly worse prognostic factor (OS: HR 3.51 [1.99-6.21], p < 0.01 and PFS: HR 8.27 [2.91-23.5], p < 0.01. Conclusions: The findings of this study suggested that MVL after the induction of the first line chemotherapy could be a novel predictive factor for chemotherapy response and prognosis. Further investigation should be required to clarify the mechanistic background.

556 Background: Liver dysfunction is one of the irritating adverse effects in chemotherapy for colorectal cancer. Polymorphisms of UGTIA1, which is related to metabolism of CPT-11 in the liver, cause severe adverse events. In addition, long-term induction of CPT-11 may involve steatohepatitis. Thus, it is critical to surrogate liver dysfunction in chemotherapy including CPT-11. In this current study, we evaluated whether NAHLD fibrosis score (NFS) which is liver fibrosis marker of nonalcoholic steatohepatitis, is feasible for predicting the effects and adverse events of chemotherapy including CPT-11 for colorectal cancer. Methods: From January 2007 to May 2013, of 118 patients who were diagnosed with unresectable advanced/recurrent colorectal cancer in our hospital, we retrospectively analyzed 89 patients who underwent first line chemotherapy including CPT-11. We statistically analyzed the value of the pretreatment NFS on response rate (RR), progression-free survival (PFS), and hematologic or non-hematologic toxicity of chemotherapy including CPT-11. Results: The median NFS was -1.302 (range=-5.158 to 2.62). Multivariate analysis revealed that NFS was an independent negative predictive marker for RR (coef -0.373 (-0.712 to -0.035), p = 0.031), although no contribution of NFS was observed to PFS (coef 0.958(0.786|1.168), p=0.672). In terms of the adverse events, high value of NFS is an independent risk factor in hematological toxicity (coef 0.93 (0.20 to 1.65), p = 0.012), while not in non-hematological toxicity (coef 0.198 (-0.218|0.613), p=0.351). Conclusions: The pretreatment NFS might be a feasible for predicting response and hematological toxicity in first line chemotherapy including CPT-11 against colorectal cancer.

610 Background: In colorectal cancer (CRC), liver metastasis is one of the critical prognostic factors. However, its pathogenesis still remains unclear. “Stream line theory” is known to be in the liver, where the bloodstream from superior and inferior mesenteric vein make a laminar flow in portal vein, and pour into the right and left hepatic vein, respectively. Recently we have elucidated that stream line theory might affect the pattern of liver metastasis in CRC. We anticipated that the way how to administrate anticancer drug also influence on the effectiveness for liver metastasis in CRC, namely oral administrated drug is absorbed in small intestine and delivered to the right lobe in the liver mainly. We hypothesized that oral intake of anticancer drug suppressed especially recurrence in the right hepatic lobe. The aim of this study is to elucidate the specific pattern of recurrence after curative resection of CRC depending on the way to administrate anticancer drug as adjuvant chemotherapy (AC). Methods: Between January 2003 and September 2013, of 365 patients who were received AC following R0 excision of primary CRC in our institution, we analyzed 94 patients who were diagnosed recurrence. They were divided into 2 groups: 64 patients were received only oral anticancer drug as AC following curative resection of CRC (PO group), and the others are distributed into IV group. A comparative review of clinicohistopathological factors and recurrence pattern were statistically performed. Results: Preoperative CEA levels were significantly higher in IV group than PO group (3.3 vs. 7.6, p=0.03). No other difference was observed in background factor of 2 groups. Comparing the recurrence pattern, 11 (17.2%) were diagnosed recurrence in the right hepatic lobe in PO group while 11 (36.7%) in IV group. There was significantly lower incidence of recurrence in the right hepatic lobe in PO group comparing with IV group (HR=2.79, 95% CI=0.92 to 8.37; p=0.04). Conclusions: AC by oral anticancer drug might specifically suppressed recurrence in the right hepatic lobe behind “stream line theory” in which oral anticancer drug is absorbed in small intestine and mainly drained into the right hepatic lobe.

Background A cavenous hemangioma of the appendix (CHA) is rare. The clinical pathophysiology and adequate management of a CHA have not been sufficiently explained since reports on CHA are scarce. Case presentation A 56-year-old woman presented with chronic right lower quadrant pain. Abdominal contrast-enhanced computed tomography revealed a thickened appendix (1.5 cm in diameter) and some focal calcifications in the appendiceal wall. No acute inflammatory signs were visible around the appendix. For diagnosis and treatment, we performed a laparoscopic surgery. Intraoperative findings included purple granular lesions that were spread diffusely along the surface of the appendix. Since these lesions were spread to the terminal ileum, laparoscopic ileocecal resection was performed. Upon macroscopic inspection, purple-colored, raspberry-like lesions were found diffusely on the serosal surface of the appendix. No lesions were found on the mucosal surface. Hematoxylin and eosin staining indicated the presence of blood-filled sinus-like spaces largely in the subserosal layer. Immunohistochemistry analysis indicated that CD34-positive cells lined these spaces. Given these findings, we diagnosed the patient with a diffuse cavernous vascular malformation of the appendix. Conclusions CHA is difficult to diagnose. A laparoscopic approach may be useful for both the diagnosis and treatment of the disease.