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The aim of this study was to evaluate the ability of texture analysis using pretreatment 18F-FDG PET/CT to predict prognosis in patients with surgically treated rectal cancer. We analyzed 94 patients with pathologically proven rectal cancer who underwent pretreatment 18F-FDG PET/CT and were subsequently treated with surgery. The volume of interest of the primary tumor was defined using a threshold of 40% of the maximum standardized uptake value (SUVmax), and conventional (SUVmax, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and textural PET features were extracted. Harmonization of PET features was performed with the ComBat method. The study endpoints were overall survival (OS) and progression-free survival (PFS), and the prognostic value of PET features was evaluated by Cox regression analysis. In the follow-up period (median 41.7 [interquartile range, 30.5–60.4] months), 21 (22.3%) and 30 (31.9%) patients had cancer-related death or disease progression, respectively. Univariate analysis revealed a significant association of (1) MTV, TLG, and gray-level co-occurrence matrix (GLCM) entropy with OS; and (2) SUVmax, MTV, TLG, and GLCM entropy with PFS. In multivariate analysis including clinical characteristics, GLCM entropy (≥ 2.13) was the only relevant prognostic PET feature for poor OS (hazard ratio [HR]: 4.16, p = 0.035) and PFS (HR: 2.70, p = 0.046). GLCM entropy, which indicates metabolic intratumoral heterogeneity, was an independent prognostic factor in patients with surgically treated rectal cancer. Compared with conventional PET features, GLCM entropy has better predictive value and shows potential to facilitate precision medicine.

The descending branch of the left colic artery (dLCA) is under-recognized and has not been clearly defined. The dLCA is often confused with the sigmoid artery (SA) originating from the left colic artery (LCA). We clarified the anatomical characteristics of the dLCA and searched for surrogate measures to identify it. Arterial phase, venous phase, and three-dimensional images of abdominal arteries were created in 411 patients using contrast-enhanced computed tomography (CT). We analyzed the branching patterns of the inferior mesenteric artery (IMA) based on CT. The dLCA was defined as the artery originating from the LCA that flows into the marginal artery along the descending colon. We tested three candidate diagnostic measures for the dLCA using positional relationships and the segment length of vessels. Arteries from the LCA were present in 360 patients, among which 459 dLCAs and 165 SAs were identified in 333 and 146, respectively. By the first measure of identifying the artery with its root lateral to the inferior mesenteric vein (IMV) as the dLCA, the sensitivity, specificity, and accuracy rate were 94%, 87%, and 92%, respectively. The second measure of identifying the artery with its root higher than the root of the IMA as the dLCA and the third of identifying the artery with its root located > 27.6 mm from the root of LCA as the dLCA yielded lower accuracy rates (69% and 89%, respectively). Our study demonstrated that dLCAs are prevalent (93%) and may be easily found lateral to the IMV in clinical practice.

Summary: Background: It is unclear whether neoadjuvant chemoradiation for lower rectal cancer causes a deterioration in urinary function. This study aimed to prospectively compare the postoperative urinary function of patients with lower rectal cancer treated by surgery after neoadjuvant chemoradiation with that of patients treated with surgery alone. Method: Urinary function was assessed before treatment and 1, 3, and 6 months after surgery by calculating the changes in the scores of the seven items of the International Prostatic Symptom Score (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) and Quality of life index. Results: Among 123 patients with lower rectal cancer treated with chemoradiotherapy plus surgery and surgery alone between 2014 and 2016, 29 eligible patients in the surgery after neoadjuvant chemoradiation group and 34 eligible patients in the surgery alone group were analyzed. The changes in each item score at 1, 3, and 6 months after surgery were similar between the two treatment groups. The scores of all items were already recovered at 6 months after surgery, except for weak stream and straining in the Surgery + chemoradiotherapy group and nocturia in the Surgery-alone group. Conclusion: Neoadjuvant chemoradiotherapy for lower rectal cancer did not affect postoperative urinary function. Keywords: Rectal cancer, Urinary function, Chemoradiation, Neoadjuvant, International prostatic symptom score

The aim of this study was to evaluate the ability of texture analysis using pretreatmentWe analyzed 94 patients with pathologically proven rectal cancer who underwent pretreatmentIn the follow-up period (median 41.7 [interquartile range, 30.5-60.4] months), 21 (22.3%) and 30 (31.9%) patients had cancer-related death or disease progression, respectively. Univariate analysis revealed a significant association of (1) MTV, TLG, and gray-level co-occurrence matrix (GLCM) entropy with OS; and (2) SUVmax, MTV, TLG, and GLCM entropy with PFS. In multivariate analysis including clinical characteristics, GLCM entropy (≥ 2.13) was the only relevant prognostic PET feature for poor OS (hazard ratio [HR]: 4.16, p = 0.035) and PFS (HR: 2.70, p = 0.046).GLCM entropy, which indicates metabolic intratumoral heterogeneity, was an independent prognostic factor in patients with surgically treated rectal cancer. Compared with conventional PET features, GLCM entropy has better predictive value and shows potential to facilitate precision medicine.

The primary tumor location (PTL) has attracted increasing attention in recent years for colorectal cancer (CRC) patients. Although the underlying mechanisms for differences caused by PTL remain still unclear, right-sided colon (RCC) and left-sided colon (LCC) are now considered as distinct entities because of their different molecular profile and clinical response to surgery and chemotherapy. In this article, we review the influence of PTL particularly on surgical management of primary and metastatic CRC settings. For nonmetastatic CRC, RCC could be a slightly superior prognostic factor after curative resection in stage I-II CRC, while RCC could be an inferior prognostic factor in stage III CRC with worse survival after recurrence, suggesting the oncological aggressiveness of recurrent RCC. For metastatic CRC, RCC could be a predictor of worse survival after hepatectomy of liver metastases from CRC with aggressive recurrence pattern and lower chance of re-resection. In lung metastases from CRC, the role of PTL still remains uncertain because of the limited number of studies. As to the impact of PTL on survival outcome after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal metastases from CRC, a discrepancy exists among studies and further investigation will be needed. The very simple clinical factor of PTL could provide important information for the prediction of the survival outcome after surgery in CRC. Further clinical and basic research will facilitate the clinical application of PTL in a more specified and personalized manner.

Background: The differential diagnosis for a colonic submucosal tumor (SMT) can include many types of cancer. We report a case of a perivascular epithelioid cell tumor (PEComa), a rare mesenchymal neoplasm that demonstrates SMT morphology, in the ascending colon.Case presentation: A mass was incidentally detected by computed tomography (CT) in a 53-year-old man. Colonoscopy revealed an SMT with central ulceration in the ascending colon, and 18F-fluoro-2-deoxy-D-glucose positron emission tomography CT demonstrated a high maximum standardized uptake value of 7.33. Preoperative diagnosis was inconclusive. Given the malignant potential of the tumor, we performed a laparoscopic right hemicolectomy with D3 lymph node dissection. The tumor was 5.5 cm × 4.1 cm and located in the submucosa and muscular propria. There was no lymph node metastasis (0/46). Based on the positive immunohistochemical stainings of both melanocytic (HMB45) and muscle (desmin) markers, we diagnosed the tumor as a PEComa. In the 17 months since surgical resection, the patient has not experienced recurrence, but careful observation should continue because of the malignant potential of the tumor.Conclusions: Although rare, a PEComa should be considered in the differential diagnosis of colonic SMT. Immunohistochemical staining of melanocytic and muscle markers is useful for the diagnosis.

Prognosis after peritoneal metastases in colorectal cancer is worse than that after lung or liver metastases. Previously, we demonstrated the safety of intraperitoneal (ip) administration of paclitaxel (PTX) combined with mFOLFOX6/CapeOX plus bevacizumab for colorectal cancer with peritoneal metastasis in a phase-I trial. Here, we evaluated the efficacy of this chemotherapy. We enrolled six patients with histologically confirmed peritoneal metastases secondary to colorectal cancer. PTX was administered through a peritoneal access port, in combination with oxaliplatin-based systematic chemotherapy. Response rate, progression-free survival, 1-year survival rate, frequency of improvement in peritoneal cancer index (PCI), and cytology in peritoneal lavage were evaluated. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry on July 1, 2016 (UNIN000022924). Three patients received the mFOLFOX6–bevacizumab regimen, whereas the other three received the CapeOX–bevacizumab regimen. The response rate was 25%. PCI score improved in 50% of the cases. Peritoneal lavage cytology that was positive in five patients before initiating the chemotherapy turned negative during chemotherapy in all patients. One-year survival rate was 100%, progression-free survival was 8.8 months (range, 6.8–12 months), and median survival time was 29.3 months. The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.

Objective This study aimed to assess the learning curve of robotic rectal surgery, a procedure that has gained increasing focus in recent years because it is expected that the advanced devices used in this approach provide advantages resulting in a shorter learning curve than that of laparoscopic surgery. However, no studies have assessed the learning curve of robotic rectal surgery, especially when lateral lymph node dissection is required. Design This was a nonrandomized, retrospective study from a single institution. Setting All consecutive patients who underwent robotic rectal or sigmoid colon surgery by a single surgeon between February 2012 and July 2016 in the University of Tokyo Hospital were enrolled. The learning curve for console time was assessed using a cumulative sum analysis and multiple linear regression analysis. Participants A total of 131 consecutive patients underwent robotic rectal or sigmoid colon surgery performed by a single experienced surgeon. Of these, 41 patients received lateral lymph node dissection. Results A cumulative sum plot for console time demonstrated that the learning period could be divided into 3 phases: Phase I, Cases 1 to 19; Phase II, Cases 20 to 78; and Phase III, Cases 79 to 131. Multiple linear regression analysis indicated that console time decreased significantly from one phase to another (Phase I-II, Δconsole time 83.0 minutes; Phase II-III, Δconsole time 40.1 minutes). Other factors affecting console time included body mass index, operative procedure, and lateral lymph node dissection, but not neoadjuvant therapy (such as chemoradiotherapy) or depth of invasion. Lateral lymph node dissection required an additional 138.4 minutes. Conclusions Our findings suggest that the first phase of the learning curve consists of the first 19 cases, which seems sufficient to master the manipulation of robotic arms and to understand spatial relationships unique to the robotic procedure.

Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis. Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m2 of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy. Among the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed. The adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.

Introduction Chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer; however, the optimal chemotherapy sequence to administer simultaneously with radiotherapy remains unclear. We conducted a phase I/II study to test a new regimen, TEGAFIRI (combination tegafur, uracil [UFT], leucovorin [LV], irinotecan), for patients with locally advanced rectal cancer. Patients and Methods A total of 22 patients with locally advanced lower rectal adenocarcinoma were enrolled in the present study. The radiation dose was 50.4 Gy in 28 fractions. UFT (300 mg/m2/d) and LV (75 mg/body weight/d) were administered orally 3 times daily. Irinotecan was administered as an intravenous infusion at 3 escalating dose levels. The initial dose was 50 mg/m2 (level 1; n = 7), the intermediate was 70 mg/m2 (level 2; n = 8), and the maximum was 80 mg/m2 (level 3; n = 7). The drug was administered on days 1, 15, 29, and 43. Results Dose-limiting toxicity was not observed at any dosing level. The most frequent adverse event was leukopenia (50%), followed by diarrhea (45.5%), anal pain (31.8%), and neutropenia (27.3%). All were well-managed with the appropriate drugs. The total pathologic complete response rate was 22.7%, and the proportion of good responders was 28.6%, 50%, and 71.4% at levels 1, 2, and 3, respectively. None of the patients experienced local recurrence. The 5-year relapse-free and overall survival rates were 80.4% and 80.8%, respectively. Conclusion TEGAFIRI is a promising CRT regimen that results in marked tumor regression and good local control. Moreover, its adverse events are well-tolerated.

Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological type of more than half of the cases was moderately differentiated adenocarcinoma, which is known to be aggressive. Among 41 cases with available data on liver metastasis, eight patients had synchronous liver metastasis, and liver metastatic recurrence after surgical resection was indicated in 10 patients. This liver metastatic rate was high compared to general colorectal cancer. However, 11 of 43 patients with venous tumor thrombosis could survive for more than 2 years after the diagnosis, although five of the 11 patients had liver metastasis. A long survival can be anticipated for patients following complete tumor resection and adjuvant chemotherapy. A greater accumulation of cases will help elucidate the characteristics of colorectal cancer with venous tumor thrombosis and improve the treatment strategy. Keywords: colorectal cancer, liver metastasis, tumor thrombosis

Objective We aimed to clarify the prognostic impact of primary tumor location on recurrence after curative surgery and subsequent survival in patients with nonmetastatic colon cancer. Summary of background data Right and left colon cancers are suggested to be oncologically different; however, their prognostic differences have been conflictingly reported. Methods A total of 5664 patients with curatively resected stage II-III colon cancer were reviewed, retrospectively. Relapse-free survival (RFS) after primary surgery and cancer-specific survival (CSS) after recurrence were compared between patients with right and left colon cancer. Patients' backgrounds were matched using propensity scores. Results Although patients with right colon cancer had more advanced disease, their 5-year RFS rate was significantly superior compared with that in those with left colon cancer (83.9% vs 81.1%, P = 0.019). However, the 5-year CSS after recurrence rate was significantly inferior in patients with right colon cancer compared with that in those with left colon cancer (30.6% vs 43.6%, P = 0.016). Conclusions The primary tumor location of nonmetastatic colon cancer might have different prognostic implications for the rates of recurrence after curative resection and cancer-specific mortality after recurrence.

Objectives To clarify the surgical outcomes and risk factors for anastomotic leakage (AL) following laparoscopic anterior resection (Lap-AR) for the treatment of rectal cancer. Methods We retrospectively reviewed the records of 175 consecutive primary rectal cancer patients who had undergone Lap-AR at our institution between April 2012 and November 2015. Patient, tumor, and surgical variables were analyzed using univariate analyses. Results Of 175 patients, 116 were men (66.3%). All four patients who had AL (2.3%) were men and current smokers with heavy smoking histories. In three of the AL cases, preoperative total colonoscopy was impossible owing to tumor obstruction, and the other case had concomitant obstructive colitis after oral bowel preparation. Univariate analysis identified tumor size, tumor obstruction, and smoking history as factors significantly associated with AL development. Conclusions Tumor size, tumor obstruction, and smoking history were risk factors for AL following Lap-AR for the treatment of primary rectal cancer.

A Dieulafoy lesion of the rectum is a very rare entity that can cause massive lower gastrointestinal (GI) hemorrhage. Identifying the bleeding point is sometimes difficult because these lesions are very small. We herein describe an 82-year-old man with active hemorrhage due to a rectal Dieulafoy lesion. He was referred to our hospital because of persistent hematochezia from the morning of that day. He had a history of atrial fibrillation, chronic heart failure, diabetes mellitus, and hyperuricemia. Prompt multidetector-row computed tomography (MDCT) enabled us to detect active bleeding from the lower rectum. Subsequently, colonoscopy revealed an exposed vessel in the lower rectum without surrounding ulceration, and hemostasis was successfully achieved using a hemostatic forceps with soft coagulation. After hemostasis had been achieved, the patient recovered and was discharged without complications and rebleeding. He is doing well 6 months after discharge from the hospital. Sequential examination by MDCT and colonoscopy is considered an efficient treatment strategy for patients with active lower GI bleeding.

Background Systemic chemotherapy increases the possibility of resection in patients with initially unresectable colorectal cancer (CRC), especially patients with hepatic metastasis. However, the predictive factors and prognosis of conversion to resection after chemotherapy in patients with various organ metastases remain largely unknown. Patients and Methods We reviewed the data from metastatic CRC (mCRC) patients who had received oxaliplatin- or irinotecan-based systemic chemotherapy from 2005 to 2016. The predictors for conversion to surgery were assessed by multivariate analyses. Cancer-free survival and overall survival after the initiation of treatment were compared between patients who had undergone successful conversion therapy and those who had undergone surgery first for resectable stage IV CRC. Results Of 99 mCRC patients receiving first-line chemotherapy, 23 underwent secondary surgical resection. Single organ metastasis, the presence of liver metastases, and the use of biologic agents were independent predictors of successful conversion therapy. The long-term survival of patients who underwent successful secondary surgery did not differ significantly from that of the 112 patients with resectable stage IV CRC who had undergone surgery first. Conclusion Liver metastases and single organ metastasis were more likely to be resected after chemotherapy than were other metastatic lesions in mCRC. The use of biologic agents contributed to the increased conversion rate. Successful conversion resulted in outcomes similar to those of resectable stage IV CRC.

Summary Introduction Pulmonary hypertension (PH) is a disease with a poor prognosis and is a risk for perioperative heart and respiratory failure. Few reports exist regarding a colectomy performed in patients with PH. Herein, we report two cases of colectomy performed in patients with severe PH, accompanied with marked edema of the colonic stoma after surgery. Case presentation In case 1, a 54-year-old patient with sigmoid cancer and severe primary PH underwent Hartmann's operation. After the operation, his stoma became markedly edematous and ulcerated. Swelling of the stoma became gradually reduced, and the patient was discharged from hospital 36 days after the operation. In case 2, a 62-year-old patient with upper rectal cancer and severe PH also underwent Hartmann's operation; his stoma became markedly edematous without ulceration. Conclusion Marked edema of the colonic stoma was observed in two cases with severe PH, with ulceration of the mucosa observed in one case. It was considered reasonable to avoid anastomosis in cases with severe PH.

Background/aim Several risk factors for recurrence have been identified in stage II colorectal cancer. However, in contrast to stage III, the benefits of adjuvant chemotherapy for these patients remain controversial. We hypothesized that the different impacts of chemotherapy may be due to different patterns of recurrence between these stages. The aim of this study was to characterize recurrence in high-risk stage II colorectal cancer (CRC) in comparison with stage III. Patients and methods A total of 442 patients with curatively resected stage III and high-risk stage II CRCs were evaluated. The recurrence site and frequency were compared between these stages. The risk factors of recurrence by site were identified using multivariate analyses. Results During the follow-up (median: 6.4 years), 31% of stage III and 13% of high-risk stage II patients manifested recurrence. Recurrence in the liver, lung, and distant lymph nodes was significantly more frequent in stage III (18%, 12%, 11%) than in high-risk stage II (7%, 6%, 3%). Stage III was independently associated with recurrence in these organs. In contrast, the rate of peritoneal recurrence was 5% in both stages. Conclusion Clinicians should be aware that high-risk stage II CRC has a similar risk of postoperative recurrence in the peritoneum to Stage III CRC.

Despite extensive research on cancer stem cells in colorectal cancer, the impact of stem cell markers on patient survival remains unclear, particularly in those with distant metastasis. In this study, we focused on colon cancer with peritoneal metastasis and investigated the association between the expression of CD133, aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-protein coupled receptor-5 (Lgr5), and disease prognosis. Putative stem cell marker expression was immunohistochemically evaluated in samples from 142 primary tumours and 75 peritoneal nodules. The associations between the expression of these markers and clinicopathological characteristics, overall survival and disease-free survival were analysed. The expression of CD133, ALDH1 and Lgr5 was found to be positive in 55.6, 47.2 and 78.9% of the primary tumour samples, respectively. While their expression was not associated with overall survival, disease-free survival was significantly worse in the CD133‑negative group (36.1 vs. 13.7%, P=0.041). Multivariable analysis confirmed that a negative CD133 expression was an independent risk factor for a reduced disease-free survival (P=0.005). Furthermore, the benefit of systemic chemotherapy was significantly greater in the CD133-negative group (P=0.039). On the whole, our data indicated that patients with colon cancer with CD133-negative expression had a reduced disease-free survival. Thus, we propose that CD133 expression may be a useful clinical biomarker in the treatment of colon cancer with peritoneal metastasis.

Colorectal cancer (CRC) is one of the most common cancers globally as well as in Japan and has shown a pattern of increasing incidence and mortality rates. Therefore, guidelines for CRC are considered to be crucial for establishing standard medical treatment not only in Japan but also around the world. In this article, we explain the features of the representative guidelines in Japan (Japanese Society for Cancer of the Colon and Rectum [JSCCR]), the USA (National Comprehensive Cancer Network [NCCN]) and Europe (European Society for Medical Oncology [ESMO]) and review the differences among these guidelines for CRC. We focus, in particular, on the descriptions of local treatments, including endoscopic treatment for CRC and transanal excision for lower rectal cancer; surgical treatments with lymph node dissection, including management of lower rectal cancer with lateral lymph node metastasis and laparoscopic surgery; and chemotherapy. Although the guidelines share basic principles, some details are different. Consulting the guidelines of various regions from around the world may aid in more precise and effective examination of the details and backgrounds of our own native guidelines.

Background and aim Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia. Methods We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups. Results Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96). Conclusions Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.

Introduction Although temporary ileostomy is widely used to prevent complications due to anastomotic leakage after middle and low rectal cancer surgery, some patients fail to achieve stoma closure after primary surgery. The aim of this study was to identify the risk factors for permanent stoma following low anterior resection (LAR) or intersphincteric resection (ISR) with a temporary ileostomy for rectal cancer, while focusing on the time course, to develop a nomogram that can predict the rate of unreversed ileostomy 1 year after initial surgery. Method A total of 212 consecutive rectal cancer patients who underwent LAR or ISR with or without a temporary stoma between 2012 and 2015 at the University of Tokyo Hospital were retrospectively reviewed. Data analyses were performed using JMP Pro 11.0 and R 3.0.1 with rms and Hmisc packages to identify the risk factors for diverting ileostomy resulting in un-reversed stoma, and to develop a nomogram using these factors. Results Among 212 patients, diverting ileostomy and colostomy were performed in 116 and 11 patients, respectively, and a stoma was not created in 85 patients. Among the ileostomy cases, 94 underwent stoma reversal, and the median interval from initial surgery to stoma closure was 6.9 months. Three patients eventually underwent stoma re-creation, and hence, 25 patients had permanent stoma. The following variables were correlated with the stoma non-reversal rate and were included in the nomogram: depth of invasion ( p = 0.02), presence of metastatic organs ( p = 0.07), and preoperative chemoradiotherapy ( p = 0.03). The nomogram C-index was 0.612, indicating moderate predictive ability. Conclusions The most common factors preventing stoma closure included distant metastasis or rectal cancer recurrence. The nomogram developed in the present study can help identify rectal cancer patients with high risk of stoma non-reversal.

Gastrointestinal stromal tumors (GISTs) of the vermiform appendix are rare, measuring

Aim Mitochondrial dysfunction plays a central role in carcinogenesis in numerous cancer-related diseases. We examined the copy number variation of mitochondrial DNA (mtDNA) and the expression of energy-producing genes in relation to ulcerative colitis (UC)-associated carcinogenesis. Materials and methods We studied 17 patients with UC-associated adenocarcinoma (UC-Ca) and 16 without UC-associated adenocarcinoma (UC-nonCa). The copy number of mtDNA in non-dysplastic mucosa in both groups was quantified by an array-based digital polymerase chain reaction (PCR) assay. Simultaneously, gene expression related to mitochondrial energy metabolism was determined by a PCR array. Results We observed a higher copy number of mtDNA in non-dysplastic mucosa in the UC-Ca group compared to the UC-nonCa group (484.2 vs. 747.7 copies/cell, p=0.022). The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of UC-associated adenocarcinoma by mtDNA copy number were 43.8%, 100%, 100%, and 60.9%, respectively. We observed an increased expression of mitochondrial genes related to energy metabolism together with an increased copy number of mtDNA. Conclusion Mitochondrial function and its metabolic process play essential roles in UC carcinogenesis and are possible risk markers for the development of colitic cancer.

Background/Aims: The neoadjuvant therapy for locally advanced rectal cancer has been changed from radiotherapy (RT) to chemoradiotherapy (CRT). This study is aimed at evaluating the benefit of CRT in patients with stage II or III lower rectal cancer, with regard to the impact on recurrence. Methods: A total of 474 patients with clinical stage II or III lower rectal cancer who received either preoperative RT (n = 221) or CRT (n = 253) followed by total mesorectal excision were identified from our institutional database. Propensity score analysis was performed to mitigate selection biases. Results: Among stage II patients, the CRT group showed a significantly lower 5-year local recurrence rate than the RT group (3.0 vs. 14.8%, p = 0.002). In contrast, among stage III patients, the CRT group showed a significantly lower 5-year distant recurrence rate than the RT group (27.8 vs. 42.6%, p = 0.04) and also a better 5-year recurrence-free survival (64.2 vs. 48.3%, p = 0.03). Conclusions: Addition of concurrent chemotherapy to preoperative RT significantly enhanced the local control in stage II patients and decreased distant recurrence in stage III patients. The oncological benefit of CRT may differ between patients with stage II or III rectal cancer.

Leriche syndrome is a disease of aortoiliac occlusion, which causes diminished femoral pulses, impotence and claudication. As blood flow to the rectum is also decreased in Leriche syndrome, reconstruction with anastomosis may be complicated by ischemia when performing rectal cancer surgery. The inferior epigastric arteries often provide collateral circulation to the lower limbs in patients with Leriche syndrome, therefore, attention should be paid not to injure them during trocar insertion when performing laparoscopic surgeries. The present study is a report on three cases of patients with colorectal cancer who were successfully treated with laparoscopic surgeries. The first case was of a 71-year-old man with rectal cancer. A preoperative computed tomography (CT) scan revealed occlusion of the aorta below the origin of the inferior mesenteric artery. The blood flow to the lower limbs was supplied through collateral arteries, including the inferior epigastric arteries and the deep circumflex iliac arteries. A laparoscopic Hartmann's operation was performed successfully following marking of the inferior epigastric arteries using ultrasonography to avoid damaging them during trocar insertion. The second case involved a 70-year-old man with three colorectal cancers of the transverse and sigmoid colon and rectum. A CT scan revealed occlusion of the aorta below the origin of the renal arteries. Laparoscopic assisted low anterior resection and left hemicolectomy with colostomy were performed. The final patient was a 61-year-old man with rectal cancer. As the right internal iliac artery was patent, the patient underwent laparoscopic assisted low anterior resection. All the patients were discharged from the hospital without complications. It is important to visualize the image the blood flow via CT angiography and to mark collateral arteries using ultrasonography preoperatively in patients with Leriche syndrome for whom laparoscopic surgery was planned for to treat colorectal cancer.

Colorectal cancer resembling submucosal tumor (SMT) is very rare. We herein report two cases of small colon carcinoma resembling SMT (80-year-old female and 67-year-old male), which massively invaded into the submucosal layer and accompanied marked lymphatic invasion and lymph node metastasis. We also reviewed the reported cases of colorectal carcinoma resembling SMT (SMT-like group, n=70) and analyzed the clinicopathological characteristics of this group compared with typical colorectal carcinoma cases operated at our institution (control group, n=1723). Tumors in the SMT-like group were significantly smaller in size compared with the control group; the median diameter measured 22mm vs. 37mm (P0.01), respectively. Histologically, although the tumors in the SMT-like group were small in diameter, they almost all invaded into the submucosal (T1) or deeper layer (T2-4), and the rate of poorly differentiated adenocarcinoma or mucinous adenocarcinoma was significantly higher than that in the control group (48.6% vs. 7.7%; P0.01). In the subgroup analysis of T1 tumors, the rate of lymphatic invasion in the SMT-like group was also significantly higher than that in the control group (43.8% vs. 15.4%; P0.01). Carcinoma resembling SMT appears to be invasive and has a high risk of lymphatic invasion even if small in size. Therefore, surgical treatment with dissection of the regional lymph nodes might be necessary in cases with any signs of massive submucosal invasion.

Perforation of jejunal diverticulum is a rare complication. Here, we report a case of jejunal diverticulum penetration with surrounding ectopic pancreas. An 83-year-old female patient was admitted to our department with acute onset of severe abdominal pain lasting for half a day. Abdominal computed tomography showed outpouching of the small intestine that contained air/fluid, with multiple surrounding air bubbles in the mesentery of the small intestine. She was diagnosed with penetration of the small intestine, and an emergency laparotomy was indicated. The penetrated jejunal diverticulum was identified ~20-cm distal to the ligament of Treitz. Partial resection of the jejunum was performed, and her postoperative course was uneventful. The pathological findings confirmed diverticulum penetration into the mesentery and severe inflammation at the site, with surrounding ectopic pancreas. Furthermore, the pancreatic ducts were opened through the penetrated diverticulum. This rare case shows that the ectopic pancreas might have caused penetration of jejunal diverticulum owing to the pancreatic duct opening through the diverticulum.

// Yuzo Nagai 1, 2 , Eiji Sunami 1 , Yoko Yamamoto 1 , Keisuke Hata 1 , Satoshi Okada 1 , Koji Murono 1 , Koji Yasuda 1 , Kensuke Otani 1 , Takeshi Nishikawa 1 , Toshiaki Tanaka 1 , Tomomichi Kiyomatsu 1 , Kazushige Kawai 1 , Hiroaki Nozawa 1 , Soichiro Ishihara 1 , Dave S.B. Hoon 2 , Toshiaki Watanabe 1 1 Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Department of Translational Molecular Medicine, Div. Molecular Oncology, John Wayne Cancer Institute, Saint John’s Hospital and Health Center, Santa Monica, CA, USA Correspondence to: Toshiaki Watanabe, email: toshwatanabe@yahoo.co.jp Keywords: colorectal cancer, cell-free DNA, LINE-1, hypomethylation, plasma Received: October 12, 2016 Accepted: December 20, 2016 Published: January 02, 2017 ABSTRACT Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360–0.380) vs. 0.332 (0.325–0.339), P < 0.0001; stage III/IV: 0.372 (0.365–0.388) vs. 0.332 (0.325–0.339), P < 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection.

Highlights • The most definitive feature of LMS is immunohistochemical positivity for desmin and SMA, and negativity for DOG 1, CD34, S-100 protein, and c-kit. • It is crucial to diagnose leioyosarcoma precisely based on immunohistochemistry, and thereby distinguish it from GIST. • Lymphadenectomy appears to be important for high-risk LMSs to perform R0 resection., Introduction Leiomyosarcoma of the gastrointestinal tract is very rare, with a reported frequency of less than 0.1% of all malignancies of the colorectum. It is important to diagnose leiomyosarcoma definitively by immunohistochemical profiling of smooth muscle actin, desmin, and CD34. True leiomyosarcoma of the colorectum diagnosed by immunnohistochemical profiling is extremely rare that only 13 reports have been published in reviews of resected gastrointestinal mesenchymal tumors after 1998. In addition, lymph node involvement is rare in patients with leiomyosarcoma. Herein we report an aggressive case of LMS in a rectosigmoid lesion with lymph node metastasis. Case presentation A 76-year-old woman visited our hospital complaining of intermittent anal bleeding that had lasted 5 months. Image studies aiming at examining the cause of her anal bleeding revealed a tumor located between the right ovary, uterus, and the rectosigmoid. Histopathology of biopsied materials from the colonoscopy suggested a malignant tumor of mesenchymal origin. Surgical resection was performed with curative intent. The tumor was diagnosed as leiomyosarcoma by pathological examination. Moreover, one of the 31 regional lymph nodes retrieved was metastasized by leiomyosarcoma. Eight months later, follow-up CT scans revealed multiple recurrent lesions in the liver and peritoneum. Despite systematic chemotherapy, she deceased 12 months after the surgery. Conclusion It is crucial to diagnose leioyosarcoma precisely based on immunohistochemistry, and thereby distinguish it from GIST. Although lymph node metastasis is rare, lymphadenectomy appears to be important for high-risk LMSs to perform R0 resection. Further investigation on leiomyosarcoma cases so far is required to establish standard treatment strategies.

Objective: Difficulties are associated with the management of brain metastasis (BM), which portends a poor prognosis in the treatment of colorectal cancer (CRC). The aim of the present study was to identify risk factors for BM in CRC and evaluate the outcomes of various treatment modalities. Methods: We retrospectively reviewed data on a total of 2,238 patients with primary CRC who underwent surgical resection at our hospital between 1999 and 2014. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate analyses using Cox proportional hazards models. Results: Three patients (0.1%) had BM at the initial diagnosis, and 23 patients (1.2%) developed metachronous BM during the median follow-up period of 44.6 months. Lung and bone metastases were identified as independent predictive factors for BM. Median survival after the diagnosis of BM was 7.4 months. Stereotactic radiosurgery, administered to 41% of the patients with BM, was associated with a better postdiagnostic survival. Conclusion: CRC patients with metastasis to the lung or bone were at a higher risk of BM. Because the survival is still limited, it is crucial to determine the treatment strategy in consideration of the characteristics of each therapy and quality of life in CRC patients with BM.

Objective: Clinical trials demonstrated that 6-37% of the patients with colorectal liver-limited metastases underwent surgical resection after first-line chemotherapy. However, limited information is available on the conversion of colorectal cancer patients with lung metastases to resection by systemic chemotherapy. Methods: We retrospectively investigated 156 patients with unresectable colorectal cancer who received oxaliplatin- or irinotecan-based first-line systemic chemotherapy with or without antibodies in our department between January 2007 and December 2015. The conversion rate to surgery and chemotherapeutic regimens and periods were analyzed with respect to the target organ. Results: In addition to 4 patients who achieved complete response, 73 exhibited tumor shrinkage of any extent. Twenty patients underwent secondary surgery, all of whom received targeting antibodies. In 75 patients with liver metastases, 18 (24%) were converted to resection after chemotherapy for a median of 110 days. In contrast, 4 (7%) out of 56 patients with lung metastases underwent resection after chemotherapy for a median of 449 days. Conversion was an independent prognostic factor in patients with lung metastases. Conclusion: The conversion rate to resection was lower for colorectal cancer patients with lung metastasis by systemic chemotherapy, which required a longer duration than for those with liver metastases.

The metastasis of rectal cancer to the anus is rare. Here, we report a case of advanced rectal cancer, which had a diffuse venous invasion with anal metastasis and multiple lymph node and liver metastases. The patient was a 72-year-old woman who complained of perianal pain and fresh blood in the stools for 6 months. She had neither history of fistula-in-ano nor anal surgery. Digital examination revealed a 2-cm tumor at the 7 o'clock position, and the barium enema and colonoscopy confirmed advanced rectal cancer. Abdominal computed tomography revealed thickness of the upper rectum wall, right inguinal lymph node of 10 mm and multiple liver metastases. Laparoscopically assisted anterior resection, anal tumor resection, and right inguinal lymph node resection were performed, and the histopathological examination of the resected primary and metastatic tumors confirmed similar findings of moderately differentiated adenocarcinoma, suggestive of metastasis of the rectal cancer to the anal region. In the next procedure, she had the liver lesions resected. This case suggested the importance of the careful examination of the anus during colonoscopy, or digital examination for the detection of anal metastasis.

To evaluate the advantages of laparoscopic surgery for rectal cancer in obese patients. We collected clinical data from consecutive patients who underwent anterior resection for rectal cancer between 2008 and 2015 to compare the surgical outcomes of a laparoscopic surgery group (LG) with those of an open surgery group (OG) stratified by obesity. Obesity was defined as a body mass index ≥25. A total of 268 patients were analyzed, with 157 in the LG (44 obese and 113 non-obese) and 111 in the OG (25 obese and 86 non-obese). The rates of complications between the LG and the OG were 18.5 vs. 11.6 % (p = 0.18) for the non-obese patients and 18.2 vs. 20.0 % (p = 1.0) for the obese patients, respectively, without a significant difference. Operative time was longer in the LG than in the OG, but the difference between the non-obese and obese patients was not significant, being 266 vs. 189 min (p

The middle rectal artery is a very important anatomical structure in rectal cancer surgery. It is the only vessel that penetrates through the proper rectal fascia into the pelvic cavity, and therefore threatens the integrity of total mesorectal excision. Moreover, it is very closely related to the lateral lymphatic drainage root. The definition of the middle rectal artery is ambiguous, and different frequencies, origins, and trajectories have been reported in various papers. The frequency of the middle rectal artery is reported to range from 12 to 97 %. Traditionally, the middle rectal artery is described as an artery that penetrates the pelvic plexus from the lateral side along with the lateral ligament; the frequency of this lateral type of middle rectal artery ranges from 20 to 30 %. However, the reports that describe higher frequency values also consider another type of middle rectal artery, which penetrates the neuro-vascular bundle from the antero-lateral direction; this antero-lateral type of middle rectal artery tends to be a small vessel, and frequently forms a common trunk with the prostatic artery. With advancements in endoscopic surgery, the knowledge of the precise anatomy of this structure is becoming more crucial for optimal rectal cancer surgery.

The use of intraoperative colonoscopy has increased alongside progress in the development of colonoscopy-associated devices and techniques, including the colonoscope itself. In the present review, we focus on four circumstances in which intraoperative colonoscopy is beneficial to colorectal surgery: (i) intraoperative determination of a tumor's location; (ii) observation of the proximal colon in cases of obstructive colorectal cancer; (iii) confirmation of the integrity of anastomosis; and (iv) novel surgical techniques that combine laparoscopic and endoscopic surgery. In light of the findings of our review, a combination of colonoscopy and surgery-especially laparoscopic surgery-is expected to facilitate the optimal handling of a variety of colorectal tumors, ranging from benign cases to advanced and obstructive cases.

Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

Proliferating cancer cells are exposed to nutrient deprivation. Numerous previous studies have demonstrated how nutrient deprivation affects cancer cells; however, immune cells exposed to the identical conditions have not been completely examined. Furthermore, T-helper 2 lymphocyte predominance in certain neoplastic diseases has been reported; however, the mechanism remains unclear. The present study aimed to confirm whether nutrient deprivation affected proliferation and cytokine secretion of peripheral blood lymphocytes (PBLs). The proliferation of PBLs from healthy donors, cultured in a medium containing various glucose levels, was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. The expression levels of interleukin (IL)-4 and interferon (IFN)-γ among CD4(+) T cells, cultured with or without glucose and activated with phorbol 12-myristate 13-acetate and ionomycin, were examined using an intracellular cytokine staining method. The proliferation of PBLs cultured in a medium containing