山口 博紀

Introduction Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days. She additionally manifested vomiting, high fever, and right abdominal pain within two weeks thereafter, and was diagnosed with perforation of the intestine. Emergency operation was carried out for panperitonitis due to perforation of one of the multiple colon ulcers. Multidisciplinary postoperative treatment could not save her life. Pathological examination suggested that cytomegalovirus infection as well as cholesterin embolization contributed to the rapid progression of colitis. Discussion There have been only a limited number of case reports of CMV enteritis in SLE. Moreover, only two SLE patients on multiple medications have been reported to experience gastrointestinal perforation. Viral infections, including CMV, can induce clinical manifestations resembling SLE and for this reason we suspect that there are potentially many more patients misdiagnosed and/or unreported. Conclusion Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs.

Background/Aims: The incidence of colorectal cancer (CRC) in young people is increasing, indicating an urgent need for understanding young-onset CRC. This study serves to clarify the characteristics and prognosis of young CRC patients. Methods: Using a detailed database, various clinicopathological findings including symptoms, family history and prognosis of 70 young CRC patients under 50 years who underwent surgical resection between 2005 and 2011 were compared to 786 old CRC patients over 50 years. For the comparison of prognosis, a matched 1: 4 case-control study adjusting for gender, tumor location, tumor differentiation type, and Union For International Cancer Control stage was conducted. Results: The young group had a higher proportion of rectal cancer (51.4 vs. 36.4%, p = 0.004) and a higher positive rate for the Amsterdam criteria II (7.1 vs. 1.9%, p = 0.02) than the old group. There was no significant difference in overall survival (OS) or cancer-specific survival (CSS) between the young and old groups (5-year OS: 84.7 vs. 76.9%, p = 0.18; 5-year CSS: 84.7 vs. 82.8%, p = 0.55). Conclusion: This study may add a new perspective to understanding young-onset CRC. The prognosis of young CRC patients was equivalent to that of old CRC patients. (C) 2016 S. Karger AG, Basel

Introduction We report our experience involving a case of relatively rare anorectal malignant melanoma with skipped lesion. Presentation of case The patient was a 72-year-old man who had visited a local clinic complaining of a mass in the anal region, whereupon he was referred to our hospital on suspicion of a malignant melanoma. Close examination revealed a 25-mm black type 1 tumor one-third the size of the circumference of the anal canal and located externally to it. We performed transanal resection of the tumor and confirmed a diagnosis of malignant melanoma. Notably, multiple macular black lesions spaced away from the main lesion were observed during surgery in half of the circumference of the anal canal, from the tumor to the pectinate line. A biopsy of the area also revealed malignant melanoma therefore, we performed abdominoperineal resection. Pathological diagnosis indicated a submucosal depth the patient was thus diagnosed with T4 N2c M0 stage IIIb malignant melanoma and was followed on an outpatient basis. Discussion Patients with anorectal malignant melanoma have very poor prognoses owing to early lymph node metastasis and hematogenous metastasis. Our case illustrates that small anorectal malignant melanoma lesions can spread from the main lesion and invade the mucosa examinations may sometimes miss such skipped lesions. Conclusion Skipped lesions can occur in anorectal melanomas thus, careful scrutiny of such lesions is required. Moreover, lesion resection is critical for anorectal malignant melanomas.

Background: Recent studies have proposed that the use of the lymphocyte-to-monocyte ratio (LMR) is a good prognostic indicator for patients with nonmetastatic colorectal cancer (CRC). In the present study, we aimed to evaluate the prognostic impact of the LMR in stage IV CRC patients who have undergone curative resection. Methods: We performed a retrospective review of 117 stage IV CRC patients who underwent curative resection at our institute between 1997 and 2012. Patients were divided into a lowLMR group and a high-LMR group according to their LMR. The cutoff value of the LMR was determined based on receiver operating characteristics curve analysis. The relationships between the LMR and disease-free survival (DFS) and cancer-specific survival (CSS) rates were assessed. Results: The cutoff value for LMR was 3.00. DFS was not significantly different between the high-and low-LMR groups (P = 0.277). By contrast, CSS was significantly better in the high-LMR group than in the low-LMR group (P = 0.001). Multivariate analysis indicated that the LMR was an independent prognostic factor for CSS in patients with stage IV CRC who had undergone curative resection (hazard ratio: 2.75; 95% confidence interval: 1.40-5.44; P = 0.004), but not for DFS. Conclusions: The preoperative LMR is a simple and useful prognostic indicator in patients with stage IV CRC who have undergone curative resection. (C) 2015 Elsevier Inc. All rights reserved.

Background. This study aimed to clarify differences in prognostic factors, metastatic features, and recurrence rates between histologic types in patients with stage 4 colorectal cancer (CRC) who had undergone curative resection. Methods. The data from 1131 patients with stage 4 colorectal cancer from the databases of referral institutions were analyzed. The patients were divided into two groups according to histologic types as follows: patients with poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma (Por/Muc/Sig) and patients with well-differentiated or moderately differentiated adenocarcinoma (Wel/Mod). Differences in clinicopathologic features, relapse-free survival (RFS) rates, and cancer-specific survival (CSS) rates between the groups were evaluated. Results. Although RFS did not differ between the Por/Muc/Sig and Wel/Mod groups, CSS was significantly shorter in the Por/Muc/Sig group's than in the Wel/Mod group, and survival after recurrence was significantly worse in the Por/Muc/Sig group than in theWel/Mod group. The incidence of peritoneal or local recurrence was significantly higher for the Por/Muc/Sig patients, whereas the resection recurrence rate was 16.4 %. Multivariate analysis suggested that histologic type was an independent prognostic factor for survival after recurrence. Conclusions. The patients with Por/Muc/Sig CRC synchronous metastasis had significantly shorter survival times than the patients with other CRC histologies, even if the metastases were curatively resected.

Background: Recently, two meta-analysis reports have suggested that CD133 expression in the primary tumor is significantly associated with shorter survival in colorectal cancer (CRC), and that CD133 may play an important role in CRC progression. However, the expression of CD133 in lymph node metastases as well as in primary tumors in CRC remains to be elucidated. Materials and Methods: We analyzed CD133 expression in both primary tumors and lymph node metastases in stage III CRC by immunohistochemistry, and its correlation with clinicopathological factors and outcomes. Results: Through immunohistochemistry we demonstrated that 69.6% of CRC primary tumors and 62.3% of lymph node metastases were CD133-positive. High CD133 expression in lymph node metastases was significantly associated with the number of lymph node metastases. Moreover, patients with CD133-negative staining of either primary tumor or lymph node metastases had a higher overall survival rate than those with CD133-positive staining, although this finding was not statistically significant. Conclusion: CD133-positive cancers may be more aggressive than CD133-negative ones during the process of lymph node metastasis. Further investigation of the role of CD133-positive cells in lymph node metastases in CRC is required.

AIM: To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinical practice. METHODS: We conducted electronic searches for journal articles on colorectal cancer (CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed. RESULTS: We discuss the currently available CRC-associated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms. CONCLUSION: The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice.

The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase. studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase. studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase. study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase. studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Geometric frustration, in which competing interactions give rise to degenerate ground states, potentially induces various exotic quantum phenomena in magnetic materials. Minimal models comprising triangular units, such as triangular and Kagome lattices, have been investigated for decades to realize novel quantum phases, such as quantum spin liquid. A pentagon is the second-minimal elementary unit for geometric frustration. The realization of such systems is expected to provide a distinct platform for studying frustrated magnetism. Here, we present a spin-1/2 quantum pentagonal lattice in the new organic radical crystal alpha-2,6-Cl-2-V [=alpha-3-(2,6-dichlorophenyl)-1,5-diphenylverdazyl]. Its unique molecular arrangement allows the formation of a partially corner-shared pentagonal lattice (PCPL). We find a clear 1/3 magnetization plateau and an anomalous change in magnetization in the vicinity of the saturation field, which originate from frustrated interactions in the PCPL.

Background Perianal hidradenitis suppurativa (PHS) is a chronic recurrent inflammatory disease of the apocrine glands present in the skin and soft tissue adjacent to the anus. It is often misdiagnosed or treatment is delayed, resulting in the formation of an abscess or, in the worst case, leading to sepsis. It is difficult to treat perianal lesions merged with fistulae completely due to its high recurrence rate. Therefore, we should diagnose it correctly and treat it with appropriate methods. Presentation of case We report two cases of PHS with anal fistulae that were examined preoperatively using magnetic resonance imaging (MRI) and treated safely by surgery without any recurrence. Discussion The anal sphincter area cannot be visualized and evaluated directly by fistulography. Also CT has only limited resolution, making it difficult to distinguish between soft tissues and inflammatory streaks. Endosonography is not suitable for the examination of supra-sphincteric or extra-sphincteric extensions, as it is limited by insufficient penetration of the ultrasonic beams. MRI can demonstrate the entire course of the fistulae owing to its high contrast resolution. Conclusion Our findings support the idea that PHS with complicated anal fistulae can be diagnosed accurately using MRI and treated safely and completely with surgery.

The platelet to lymphocyte ratio (PLR) is a potential prognostic marker in a number of different cancers. The aim of this study was to evaluate the prognostic impact of the PLR in patients with stage II colorectal cancer (CRC) who have undergone curative resection but not adjuvant chemotherapy. A retrospective review was performed on 234 patients with stage II CRC who underwent curative resection, but not adjuvant chemotherapy, in our institute. The patients were divided into low and high PLR groups, and patient survival as well as several clinicopathological factors were compared between the groups. Disease-free survival (DFS) and cancer-specific survival (CSS) were analyzed by using the Kaplan-Meier method, and multivariate analysis was performed by using the Cox proportional hazard model. The cutoff value of the PLR determined by using a receiver-operating characteristic curve analysis was 25.4. DFS and CSS were significantly better in patients with a low PLR compared to patients with a high PLR (P = 0.002 and P = 0.011, respectively). On multivariate analysis, we identified the PLR as an independent prognostic factor for DFS and CSS, with a hazard ratio of 2.65 (95 % confidence interval [CI], 1.26-5.45; P = 0.011) and 3.61 (95 % CI, 1.08-12.64; P = 0.038, respectively). The PLR is a good prognostic indicator in patients with stage II CRC who have undergone curative surgery but not adjuvant chemotherapy.

Aim: The postoperative administration of oxaliplatin reduces the frequency of relapse in selected patients with colorectal cancer following surgical resection. However, factors associated with recurrence despite adjuvant therapy are largely unknown. Patients and Methods: We investigated 68 patients who were pathologically diagnosed with stage II or III colorectal cancer and received oxaliplatin-including chemotherapy, FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) or CapeOX (capecitabine and oxaliplatin), after curative surgery. Results: Nineteen patients developed recurrence during the median follow-up period of 17.8 months. Multivariate analyses using the Cox proportional-hazards model revealed that primary tumor size >= 45 mm was a significant predictor of recurrence (hazard ratio = 3.16, 95% confidence interval = 1.06-11.54, p = 0.039). A primary tumor of 45 mm or more in size was associated with poor recurrence-free survival. Conclusion: Our results suggest that large colorectal carcinoma needs to be recognized as a high-risk factor for recurrence even after surgery and subsequent treatment with oxaliplatin.

Despite the development of new therapies, including anti-TNF alpha antibodies and immunosuppressants, a substantial proportion of patients with ulcerative colitis (UC) still require surgery. Restorative proctocolectomy with ileal-pouch anal anastomosis is the standard surgical treatment of choice for UC. With the advent of laparoscopic techniques for colorectal surgery, ileal-pouch anal anastomosis has also been performed laparoscopically. This paper reviews the history and current trends in laparoscopic surgery for UC. The accumulation of experience and improvement of laparoscopic devices have shifted the paradigm of UC surgery towards laparoscopic surgery over the past decade. Although laparoscopic surgery requires a longer operation, it provides significantly better short and long-term outcomes. The short-term benefits of laparoscopic surgery over open surgery include shorter hospital stays and fasting times, as well as better cosmesis. The long-term benefits of laparoscopy include better fecundity in young females. Some surgeons favor laparoscopic surgery even for severe acute colitis. More efforts are being made to develop newer laparoscopic methods, such as reduced port surgery, including single incision laparoscopic surgery and robotic surgery.

We recently reported a specific mechanism that RAD54B, an important factor in homologous recombination, promotes genomic instability via the degradation of p53 protein in vitro. However, clinical significance of RAD54B in colorectal cancer (CRC) remains unclear. Thus we analyzed RAD54B gene expression in CRC patients. Using the training set (n = 123), the optimal cut-off value for stratification was determined, and validated in another cohort (n = 89). Kaplan-Meier plots showed that distant recurrence free survival was significantly lesser in high RAD54B expression group compared with that of low expression group in both training (P = 0.0013) and validation (P = 0.024) set. Multivariate analysis using Cox proportional-hazards model showed that high RAD54B expression was an independent predictor in both training (hazard ratio, 4.31; 95% CI, 1.53-13.1; P = 0.0060) and validation (hazard ratio, 3.63; 95% CI, 1.23-10.7; P = 0.021) set. In addition, a negative significant correlation between RAD54B and CDKN1A, a target gene of p53, was partially confirmed, suggesting that RAD54B functions via the degradation of p53 protein even in clinical samples. This study first demonstrated RAD54B expression has potential to serve as a novel prognostic biomarker, particularly for distant recurrence in CRC patients.

Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology.

Anal canal adenoma is an extremely rare disease that has the potential to transform into a malignant tumor. We herein presented a rare case of metachronous multiple adenomas of the anal canal. A 48-year-old woman underwent total colonoscopy following a positive fecal blood test. A 9-mm villous polyp arising from the posterior wall of the anal canal was removed by snare polypectomy. Histologically, the tumor was tubulovillous adenoma with high-grade dysplasia and the cut end was negative for tumor cells. Six years later, an elevated lesion, macroscopically five millimeters in size, was detected in the left wall of the anal canal in a follow-up colonoscopy. Local excision of the tumor was performed, and the lesion was pathologically confirmed to be tubular adenoma with high-grade dysplasia limited to the mucosa. The patient is currently alive without any evidence of recurrence for six months after surgery. Although she had a past history of cervical cancer, the multiple tumors arising in the anal canal were unlikely to be related to human papilloma virus infection. Our case report underscores the importance of careful observations throughout colonoscopy to detect precancerous lesions, particularly in anatomically narrow segments.

The frequency of intraperitoneal free tumor cells (IPTC) is considered to reflect the severity of peritoneal metastasis (PM). We quantified the relative number of IPTC against leukocytes in peritoneal fluid and evaluated its clinical relevance in gastric cancer (GC) patients, particularly those with PM. Cells recovered from ascites or peritoneal lavage fluid were immunostained with monoclonal antibodies (mAb) to CD45 and CD326 (EpCAM). Using flow cytometry (FACS), CD326(+) and CD45(+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated in a total of 506 samples obtained from 300 patients with GC and 33 patients with liver cirrhosis (LC). Median (M) of the TLR of the initial samples obtained from 199 patients with PM(+) GC was 1.32 % (0-1,868.44 %), which was significantly higher than that in patients with PM(-) GC (M = 0 %, 0-0.35 %; n = 101) or LC (M = 0 %, 0-0.031 %; n = 33). In 104 PM(+) patients who received combination chemotherapy including intraperitoneal paclitaxel, the TLR was repeatedly measured in peritoneal fluid obtained from the port. In these patients, the TLR showed a strong correlation with clinical features as well as cytological findings and carcinoembryonic antigen messenger RNA status. Finally, the median survival time of the 11 patients with initial TLR > 10 % was significantly shorter than that of the 52 patients with TLR < 10 % (271 vs. 627 days; p = 0.0002). The TLR excellently reflected tumor burden in the peritoneal cavity, and could be a reliable biomarker to determine the outcome, as well as the effectiveness, of chemotherapy in patients with PM(+) GC.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment for patients with ulcerative colitis (UC). The purpose of this study was to investigate the long-term functional outcomes and quality of life (QOL) associated with hand-sewn and stapled IPAA. Ninety-one patients with UC had undergone IPAA using hand-sewn anastomosis with mucosectomy (32 patients) or stapled anastomosis (59 patients) from January 1988 to May 2010. Patients were evaluated according to patient characteristics, postoperative complications, functional outcomes and QOL. The QOL of patients were evaluated using the Medical Outcomes Study Short Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Numbers of patients with colorectal cancer or dysplasia were significantly greater in the hand-sewn IPAA group (P < 0.01). These patients had longer disease durations and were older (both P < 0.01). There was no difference in the incidence of complications between the groups, except for a greater incidence of postoperative anal fistula in the stapled group (P = 0.03). In the early postsurgery period, both the frequency of bowel movements and the rate of soiling were significantly higher in the hand-sewn group, but in a later period, there was no difference in these events >3 years after surgery. The SF-36 and IBDQ results were similar in the two groups, indicating that hand-sewn and stapled IPAA result in similar QOL in the late postoperative period. Postoperative complications, functional outcomes, and long-term QOL were similar in patients who had received hand-sewn or stapled IPAA.

Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer (CRC) with unresectable metastasis (mCRC). The aim of this study was to investigate the prognostic impact of primary tumor resection in various subgroups of mCRC patients. A total of 1982 patients with mCRC from January 1997 to December 2007 were retrospectively evaluated. The impact of primary tumor resection on cancer-specific survival (CSS) was analyzed using propensity score analysis to mitigate selection bias. Covariates in the models for propensity scores included treatment period, age, gender, tumor location, depth, lymph node metastasis, number of metastatic organs, and carcinoembryonic antigen (CEA) levels. Among the whole patient population, primary tumor resection significantly improved CSS [hazard ratio (HR) 0.46, 95 % confidence interval (CI) 0.32-0.66, p < 0.01]. However, primary tumor resection did not significantly improve CSS in the following subgroups: patients treated in the first 5 years of the study (HR 0.56, 95 % CI 0.28-1.13, p = 0.08), patients aged > 65 years (HR 0.72, 95 % CI 0.36-1.42, p = 0.31), female patients (HR 0.60, 95 % CI 0.31-1.17, p = 0.13), patients with right-sided colon cancer (HR 0.68, 95 % CI 0.39-1.20, p = 0.17), and patients without nodal involvement (HR 0.54, 95 % CI 0.25-1.17, p = 0.09). Our study suggests that primary tumor resection improves the survival of patients with mCRC. However, the prognostic benefit is different among patient subpopulations.

Background: The incidence of anastomotic leakage in rectal surgery is around 10 percent. Poor blood supply to the anastomosis, high anastomotic pressure and tension, increased operative blood loss, long operative time, and male sex are risk factors of anastomotic leakage. In the present study, we examined anastomotic leakage cases in rectal surgery at our institute and tried to ascertain the risk factors. Methods: Three hundred fifty-seven consecutive patients who underwent rectal resection with anastomosis between January 2008 and October 2013 were included in the study. Patients were divided into two groups according to the existence of anastomotic leakage. Clinicopathological features, operative procedures, and intraoperative outcomes were compared between the two groups. Regarding intraoperative procedure, we focused on the ligation level of the inferior mesenteric artery, installing a transanal drainage tube in the rectum, and constructing a diverting stoma. Results: Anastomotic leakage occurred in eight patients. All of them were male (p=0.0284). There were no statistical differences in other characteristics of the patients or tumors, in operative procedures, or in intraoperative outcomes. Conclusions: In the present study, no statistically significant risk factors for anastomotic leakage in rectal surgery were detected, except for male sex. However, the rate of anastomotic leakage at our institute was revealed to be rather low. Our exertion to preserve good blood flow and to prevent high tension and pressure on the anastomosis in operation may have led to this result.

Objective: To construct a predictive model of postoperative colorectal neoplasm development using a nomogram. Background: Although patients with colorectal cancer (CRC) are known to be at high risk of developing metachronous adenoma or CRC, no statistical model for predicting the incidence of postoperative colorectal lesions has been reported. Methods: A total of 309 CRC patients who underwent surgical resection received regular endoscopic follow-up to detect the development of metachronous adenoma or adenocarcinoma. The patients were divided into the derivation set (n = 209) and the validation set (n = 100). The nomogram to predict the 3- and 5-year adenoma-free survival rates was constructed using the derivation set, and a calibration plot and concordance index (c-index) were calculated. The predictive utility of the nomogram was validated in the validation set. Results: Sex, age, and number of synchronous lesions at the time of surgery for primary CRC were adopted as variables for the nomogram. The nomogram showed moderate calibration, with a c-index of 0.709 in the derivation set and 0.712 in the validation set. Conclusions: A nomogram based on sex, age, and number of synchronous lesions at the time of surgery has the ability to predict postoperative adenoma-free survival.

The lymph node ratio (LNR) was proposed as a prognostic indicator in Stage III colorectal cancer (CRC) patients in recent studies. The purpose of this study was to evaluate the prognostic impact of the LNR in Stage IV CRC patients who have undergone curative resection. A retrospective review of 119 Stage IV CRC patients who underwent curative resection in our institute from 1997 to 2009 was performed. Patients were divided into two groups (low LNR and high LNR) by means of their median LNR. A disease-free survival (DFS) and an overall survival (OS) were analyzed using the Kaplan-Meier curve; multivariate analysis was performed using the Cox proportional hazard model. The cutoff value for the LNR was 0.111. For the entire study group, the 5-year DFS was 22 % and the 5-year OS was 65 %. DFS was not significantly different between patients in the low LNR group and the high LNR group (25 and 19 %, respectively; P = 0.317), but OS was significantly higher in the low LNR group patients compared with the high LNR group patients (77 and 54 %, respectively; P < 0.001). Using multivariate analysis, we identified the LNR as an independent prognostic factor for OS, with a hazard ratio of 3.08 (95 % CI 1.38-8.19; P = 0.005). LNR is a potent prognostic indicator for stratification in Stage IV CRC patients who have undergone curative resection.

It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression.

Background: Alpha-fetoprotein (AFP)-producing rectal cancer is very rare, and this type of cancer frequently metastasizes to the liver with a poor prognosis. To date, only 11 cases of AFP-producing colorectal cancer have been reported. Case presentation: A 41-year-old woman was first presented to the hospital for anal bleeding. An elevated tumor with a central shallow depression in the lower rectum was detected by colonoscopy. Transanal excision was performed, and the histology revealed adenocarcinoma. Further immunohistopathological examination revealed that the tumor was an AFP-producing adenocarcinoma of the rectum. Although local resection was performed 2 months before the diagnosis of AFP tumor, the serum AFP level was normal. The depth of the submucosal invasion was 5,000 mu m, and there was venous invasion. Also, no lymphatic invasion was detected. Therefore, additional surgical resection with lymph node dissection was conducted, and the patient underwent laparoscopic intersphincteric resection. No residual cancer was identified in the surgical specimens, and there was no evidence of lymph node metastasis. The patient was discharged 18 days postoperatively, and 12 months after the operation, there are no signs of recurrence. Conclusion: To the best of our knowledge, this is the first case of an AFP-producing rectal cancer that was diagnosed at an early stage.

Background: Although secretory phospholipase A2 (sPLA2) has been shown to be involved in various biological processes, its specific roles in sub-types of cancer development remain to be elucidated. Materials and Methods: We examined the expression of sPLA2 group III (GIII) in 142 patients with colorectal cancer using immunohistochemistry, and its correlation with clinicopathological features and outcomes. In addition, we examined the co-expression of sPLA2GIII and sPLA2GX using serial tissue sections to clarify the roles of both proteins in colorectal carcinogenesis. Results: In 66 cases, diffuse staining of sPLA2GIII was seen; this was defined as the group with high expression. High expression was associated with a significantly higher rate of lymph node metastasis (p=0.02) and poorer survival (p=0.03) compared with low expression. Patients with low sPLA2GIII and high sPLA2GX expression had a significantly higher survival rate than those with high sPLA2GIII and low sPLA2GX expression (p=0.038). Conclusion: sPLA2GIII expression may be used as a risk factor for lymph node metastasis and a prognostic marker in colorectal cancer. In addition, sPLA2GIII and sPLA2GX may play opposing roles in colorectal carcinogenesis.

Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing colorectal surgery. However, the association of ABT with SSI in patients undergoing abdominoperineal resection (APR) and total pelvic exenteration (TPE) still remains to be evaluated. Here, we aim to elucidate this association. The medical records of all patients undergoing APR and TPE at our institution in the period between January 2000 and December 2012 were reviewed. Patients without SSI (no SSI group) were compared with patients who developed SSI (SSI group), in terms of clinicopathologic features, including ABT. In addition, data for 262 patients who underwent transabdominal rectal resection at our institution in the same period were also enrolled, and their data on differential leukocyte counts were evaluated. Multivariate analysis showed that intraoperative transfusion was an independent predictive factor for SSI after APR and TPE (P = 0.004). In addition, the first-operative day lymphocyte count of patients undergoing APR, TPE, and transabdominal rectal resection was significantly higher in nontransfusion patients compared with transfusion ones (P = 0.026). ABT in the perioperative period of APR and TPE may have an important immunomodulatory effect, leading to an increased incidence of SSI. This fact should be carefully considered, and efforts to avoid allogeneic blood exposure while still achieving adequate patient blood management would be very important for patients undergoing APR and TPE as well.

The aim of this study was to clarify patient factors contributing to complications after laparoscopic surgery for colorectal cancers. A total of 333 colorectal cancer patients who underwent laparoscopic colorectal resection between January 2007 and December 2012 were enrolled. The association between patient factors and the incidence of complications were analyzed. Postoperative complications were divided into 2 categories: infectious complications and noninfectious complications. The overall complication rate was 13% and mortality rate 0%. Multivariate analysis showed that body mass index > 25 kg/m(2) [odds ratio (OR) = 3.02, P = 0.0254] and tumor location (right colon cancer/rectal cancer: OR = 0.11, P = 0.0083) were risk factors for infectious complications; in addition, male sex (OR = 3.91, P = 0.0102) and cancer stage (stage 2/stage 4: OR = 0.17, P = 0.0247) were risk factors for noninfectious complications. This study shows that different patient factors are associated with the risk of different types of complications.

Although the incidence of synchronous abdominal aortic aneurysm (AAA) and malignancies is increasing, there has been no clear consensus in the surgical treatment of such patients. The focus on surgical treatments with minimal invasiveness, such as endovascular aneurysm repair (EVAR) for AAA and laparoscopic colectomy for colorectal cancer, has increased; however, the clinical applicability of combination treatment with EVAR and laparoscopic colectomy has not been established. A 61-year-old man was diagnosed with AAA, advanced sigmoid colon cancer, and coronary artery stenosis. Because the patient also had chronic renal failure with nephrotic syndrome, among several other comorbidities, surgery was considered to be associated with high risks in this patent. Sequential treatments with percutaneous coronary intervention, EVAR, and laparoscopic colectomy were successfully performed. Staged treatment of EVAR followed by laparoscopic colectomy may be a promising strategy for high-risk patients with AAA associated with malignancy.

Solitary fibrous tumors (SFTs) rarely develop in the pelvis. When they do arise, they are usually treated using surgery, although SFTs are often very large by the time of diagnosis, which makes surgical excision difficult. We report a case of a 63-year-old man who was referred to our hospital for the treatment of a giant tumor of the pelvis. Computed tomography (CT) revealed a 30 x 25 x 19 cm sized hypervascular tumor that almost completely filled the pelvic cavity. The diagnosis of SFT was made by CT-assisted needle biopsy. The feeding arteries of the tumor were embolized twice. The first embolization aimed to reduce the tumor volume, while the second one was planned a day prior to the surgery to obtain hematostasis during the operation. Tumor resection was then performed. The blood loss during the operation was 440 ml, and there was no uncontrollable bleeding. The postoperative course was uneventful. No recurrence of SFT was observed during a 2-year follow-up.

Background. A positive cytology of peritoneal lavage fluid (CY1) is a poor prognostic factor in patients with gastric cancer (GC). We have recently reported that CY1 often changes to negative (CY0) following combination chemotherapy including intraperitoneal (IP) paclitaxel (PTX), which results in marked prolongation of survival in GC patients with peritoneal dissemination (P1). Methods. A total of 95 P1 GC patients who received combination chemotherapy with S-1 and intravenous and IP PTX were enrolled. Peritoneal lavage fluid was periodically examined cytologically at the start of every cycle of chemotherapy, and the impact of CY status on patient outcome was retrospectively evaluated. Results. Seventy-three (76.8 %) of 95 patients were diagnosed as CY1 before initial treatment. Median survival time (MST) of the CY1 group was significantly shorter than that of the CY0 group (19.1 vs. 32.5 months, P = 0.033). Cytological status changed from CY1 to CY0 in 68 (93.2 %) of 73 CY1 patients during the whole treatment period and MST of patients who showed a negative change was significantly longer than that of the unchanged group (20.0 vs. 13.0 months, P = 0.0017). In 64 patients who achieved CY0 by IP PTX regimen, the median time to achieve CY0 was 1.4 months, and patients who achieved a negative change within 1 month showed a particularly good outcome (MST = 26.1 months). Conclusions. Periodic cytological examination of peritoneal lavage fluid is clinically useful to evaluate the efficacy of treatment as well as to predict the outcome of patients with P1 GC.

Background: The function of phosphatidylserine-specific phospholipase A1 (PS-PLA(1)), a phospholipase that acts specifically on phosphatidylserine and produces lysophosphatidylserine, a lysophospholipid mediator, has not been fully elucidated. We evaluated the role of PS-PLA(1) in oncogenesis and metastasis of colorectal cancer (CRC). Materials and Methods: Specimens from 85 patients with CRC were immunostained with a monoclonal antibody against PS-PLA(1). The correlation between PS-PLA(1) expression and the clinicopathological variables was analyzed. Results: Tumor depth and hematogenous metastasis independently positively correlated with PS-PLA(1) expression. High PS-PLA(1) expression was associated with shorter disease-free survival, although it was not an independent predictive factor. Conclusion: PS-PLA(1) expression in CRC is associated with tumor invasion and metastasis.

BACKGROUND: Although neoadjuvant chemoradiotherapy (CRT) has become a standard procedure to downstage locally advanced rectal cancer prior to surgery, markers to predict the response to CRT have not been fully identified. The aim of this study was to identify predictive factors of response to CRT, especially focusing on peripheral blood leukocyte subsets. METHODS: A total of 45 consecutive patients diagnosed with primary rectal cancer were prospectively enrolled and received CRT followed by curative resection. The numbers of each lymphocyte subset in peripheral blood pre- and post-CRT were analyzed using flow cytometry. According to the pathological response to CRT, patients were classified into high (Hi-R) and low (Lo-R) response groups. RESULTS: Hi-R cases had significantly higher numbers of pre-CRT lymphocytes (p = 0.018), T lymphocytes (p = 0.009) and helper T lymphocytes (Th lymphocytes, p = 0.015) compared to the Lo-R cases. With the receiver-operating characteristic curve for numbers of pre-CRT T lymphocytes, the area under the curve (AUC) was 0.733, and the optimal cutoff value was 1196/μl, with 76.5% sensitivity, 67.8% specificity, 59.1% positive and 82.6% negative predictive values. The numbers of pre-CRT Th lymphocytes and cytotoxic lymphocytes were both independent predictors of the high CRT response in the multivariate analysis. CONCLUSIONS: In addition to the direct cytotoxicity of CRT, recent studies have demonstrated the induction of an immunological host response, which also contributed to the tumor regression induced by CRT. Our result suggested the potential role of circulating T lymphocytes in predicting the response to CRT in colorectal cancer patients.

Background. Peritoneal dissemination and positive peritoneal lavage cytology are associated with poor prognosis in colorectal cancer. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) is often used as a marker to detect micrometastases. We aimed to evaluate the prognostic significance of CEA mRNA in the peritoneal lavage of colon cancer patients. Methods. Colon cancer patients (n = 201) who underwent curative operative resection between August 2009 and February 2013 were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. Results. Positive CEA mRNA in peritoneal lavage was an independent risk factor for overall recurrence-free survival in colon cancer (1, < .0001). Positive CEA mRNA was a risk factor for poorer overall recurrence in stage II and III patients (P = .04 and P = .02, respectively). Moreover, among stage III patients with positive CEA mRNA, the postoperative chemotherapy group had significantly lower overall and peritoneal recurrence rates than the no postoperative chemotherapy group (P = .001). Conclusion. Positive cm mRNA in peritoneal lavage was associated with high overall recurrence rates in stage II and III colon cancer Further study is necessary to determinate the efficacy of aggressive postoperative chemotherapy for stage II and III colon cancerpatients with positive CEA mRNA.

BACKGROUND: The branching of the inferior mesenteric artery and vein varies among individuals. Three-dimensional CT angiography is a less invasive modality than traditional angiographic examination to assess the artery and vein. OBJECTIVE: We aimed to demonstrate the clinical applicability of CT angiography by evaluating bifurcations of the inferior mesenteric artery and the positional relationship between the inferior mesenteric artery and vein. DESIGN: This was a prospective observational study of patients undergoing preoperative CT angiography. SETTINGS: This study was conducted at a single tertiary care institution in Japan. PATIENTS: A total of 471 consecutive patients who underwent preoperative CT angiography from April 2012 to December 2013 were prospectively enrolled. MAIN OUTCOME MEASURES: The branching pattern of the inferior mesenteric artery, the positional relationship between the inferior mesenteric artery and vein, and the associations between inferior mesenteric artery length and clinical features were evaluated. RESULTS: The length of the inferior mesenteric artery varied widely, from 10.1 to 82.2 mm. In 41.2% patients, the left colic artery arose independently from the sigmoid artery, and in 44.7% of the patients, the left colic artery and sigmoid artery had a common trunk, whereas the left colic artery did not exist in 5.1%. The left colic artery was located lateral to the inferior mesenteric vein at the level of the origin of the inferior mesenteric artery in 73.0% of the patients. The incidence of a short inferior mesenteric artery was significantly increased in men with high BMIs (75.0%). LIMITATIONS: Three-dimensional reconstruction was performed by the use of a single software, and angiographic examination was not performed. Therefore, accuracy and reliability of the 3-dimensional reconstruction could not be established for each modality. CONCLUSIONS: Using 3-dimensional CT angiography, preoperative understanding of the anatomic vascular variations can be easily obtained, which would help surgeons to safely perform laparoscopic surgery in the left-side colon and rectum.

A 57-year-old woman without any past medical history underwent abdominoperineal resection for rectal cancer in our department. On postoperative day 15, the patient complained of sudden abdominal pain, and high fever was noted in addition to the appearance of erythema around the stoma. The diagnosis of phlegmon was made, and antibiotic infusion was started. However, a few days later, the patient developed hypovolemic shock with hypoalbuminemia and hemoconcentration. Fasciotomy was performed to exclude the necrotizing fasciitis, though all cultures were negative. Upon exclusion of the differential diagnoses, idiopathic systemic capillary leak syndrome (ISCLS) was diagnosed. She was successfully treated with massive fluid infusion under ventilation and continuous hemodiafiltration. Here, we report the first case of ISCLS that occurred during the postoperative period of colorectal surgery.

We herein report the case of a 42-year-old man with a one-year history of ulcerative colitis who presented with exacerbated bloody diarrhea, a productive cough and increasing breathing difficulties. Colonoscopy revealed typical deep ulcers in the rectosigmoid colon and atypical multiple sucker-like ulcers in the transverse colon, and computed tomography of the chest demonstrated wall thickening of the trachea and bronchi. In addition, bronchoscopy showed ulcers in the trachea, and histopathology disclosed findings of necrosis and inflammation of the subepithelial tissue of the trachea. Based on these findings, the patient's respiratory symptoms were strongly suspected to be due to ulcerative colitis-related tracheobronchitis. Treatment with systemic corticosteroids subsequently resulted in a rapid clinical improvement.

A 16-year-old boy was diagnosed with Crohn's disease. Treatment with oral mesalazine was started at 3 g per day; however, he complained of high fever, a nonproductive cough, and left shoulder pain after 2 weeks. His chest radiography and chest computed tomography showed cardiomegaly and left pleural effusion, while an echocardiogram revealed pericardial effusion. Because no infection was detected by thoracentesis and the drug lymphocyte stimulation tests for mesalazine were positive, the patient was diagnosed with mesalazine-induced pleuropericarditis. After the cessation of mesalazine, the clinical symptoms and laboratory findings quickly improved.

Intraperitoneal (IP) chemotherapy for peritoneal carcinomatosis (PC) from gastrointestinal cancer has been investigated and applied clinically for several decades. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy have been considered to be the optimal treatment options for selected patients with colorectal and gastric cancers with PC. Accumulating evidence suggests that the administration of IP paclitaxel for patients with PC from gastric cancer may improve the patient survival. The pharmacokinetics of such treatment should be considered to optimize IP chemotherapy. In addition, newly emerging molecular-targeted therapies and research into new drug delivery systems, such as nanomedicine or controlled absorption/release methods, are essential to improve the effects of IP chemotherapy. This review summarizes the current status and future prospects of IP chemotherapy for the treatment of gastrointestinal cancer.

This study reviewed 1059 patients with colorectal cancers (CRCs) to evaluate the age-related changes in the clinicopathologic features, according to the gender. The presence of concomitant adenoma was the only independent age-related factor in men (P = .0044), whereas the presence of right-sided CRC was the only one in women (P < .0001). The results suggest the oncologic background difference between men and women among the elderly. Introduction: Although several reports have documented the increased incidence of right-sided colorectal cancer (CRC) in the elderly, especially in women, the gender-specific, age-related changes in the characteristics of CRCs, especially related to the cancer localization, have not been fully investigated. This study evaluated the age-related changes in the clinicopathologic features of CRCs, according to the gender. Materials and Methods: A total of 1059 consecutive patients with CRCs who were admitted to the authors' surgical department between February 2005 and June 2012 were retrospectively reviewed. The patients were divided into male (n = 632) and female (n = 427) groups and then according to the age group, and the correlation between the age group and the other clinicopathologic features was analyzed by univariate and multivariate analysis. Results: The number of concomitant adenomas found was significantly increased along with increasing age in men, and the presence of concomitant adenoma was the only independent age-related factor of male CRC in the multivariate analysis (P = .0044). In contrast, in women, the location of the CRC progressively shifted to the right side (proximal colon) with increasing age, and the presence of right-sided CRC was the only independent factor of female CRC in the multivariate analysis (P < .0001). Conclusion: There was a significant gender-specific difference in the age-related changes in the characteristics of CRC. Increasing the number of concomitant adenomas and the shift of CRC localization to the proximal colon were the gender-specific characteristics of male and female CRC, respectively.

Introduction: We report a rare case of delayed abdominal wall abscess after abdominoperineal resection (APR) for rectal cancer. Case description: A 63-year-old woman was diagnosed with rectal cancer and received chemo-radiotherapy, followed by APR. One year after surgery, the patient complained of pain and skin redness in the lower abdomen. A low-density mass lesion with 5.9-cm diameter was found in the lower abdominal wall by computed tomography, which showed high uptake on positron-emission tomography. These findings suggested the possibilities of either delayed abscess formation or abdominal wall recurrence of rectal cancer with central necrosis. Percutaneous drainage was performed. The content was a purulent exudate, without neoplastic cells in the cytology. The lesion quickly disappeared after the drainage, and no recurrence of the tumor was observed for more than 2 years. Discussion and evaluation: In this case, the un-absorbable yarn, such as silk, has not been used during the operation, no foreign body was retained in the abdominal wall, and there was no associated inflammatory bowel disease. Use of neoadjuvant chemoradiotherapy was the only possible cause of delayed abscess formation in this case. Conclusion: In case local recurrence is suspected by imaging modalities in the postoperative of colorectal cancer, especially those with precedent chemoradiotherapy or radiotherapy, although rare, the possibility of a delayed abscess formation should also be considered.

Background: Lysophosphatidylserine (lysoPS) is a type of lysophospholipid mediator, which is involved in allergic conditions and tumor progression. We investigated the physiological function of lysoPS on colorectal cancer (CRC) cell lines, as well as the involved receptor and signaling pathways. Materials and Methods: Expression of lysoPS receptors on six cell lines was examined by reverse transcription-polymerase chain reaction (RT-PCR). The physiological functions of lysoPS were investigated, and experiments using small interfering RNA (siRNA) or inhibitors of the signaling pathways were conducted. Results: Among the three lysoPS receptors, GPR34 was highly expressed on all cell lines. LysoPS stimulated the chemotactic migratory ability. Wortmannin inhibited the migratory ability, as well as the GPR34 knock-down, strongly suggestive of the involvement of this receptor in the PI3K/Akt pathway. Conclusion: The involved receptor and pathways in the migratory ability in response to lysoPS was demonstrated, which opens premises for targeting as a new strategy for prevention and treatment of colorectal cancer.

Background. Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer with unresectable metastasis (mCRC). Prognostic significance of lymph node dissection (LND) in mCRC has not been examined previously. The aim of this study was to investigate the prognostic impact of primary tumor resection and LND in mCRC. Methods. A total of 1,982 patients with mCRC from January 1997 to December 2007 were retrospectively studied. The impact of primary tumor resection and LND on overall survival (OS) was analyzed using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. Covariates in the models for propensity scores included treatment period, institution, age, sex, carcinoembryonic antigen, tumor location, histology, depth, lymph node metastasis, lymphovascular invasion, and number of metastatic organs. Results. In a multivariate analysis, primary tumor resection and treatment in the latter period were associated with an improved OS, and age over 70 years, female sex, lymph node metastasis, and multiple organ metastasis were associated with a decreased OS. In the propensity-matched cohort, patients treated with primary tumor resection showed a significantly better OS than those without tumor resection (median OS 13.8 vs. 6.3 months; p = 0.0001). Furthermore, among patients treated with primary tumor resection, patients treated with D3 LND showed a significantly better OS than those with less extensive LND (median OS 17.2 vs. 13.7 months; p < 0.0001). Conclusions. It was suggested that primary tumor resection with D3 LND improves the survival of patients with mCRC.

Colon cast passage, which is the spontaneous passage of a full-thickness, infarcted colonic segment per rectum, is a rare occurrence. The main cause is acute ischemic colitis resulting from a circulation compromise. Most of the colon cast cases reported were secondary to abdominal aortic aneurysm repairs or colorectal surgery. We report a case of an 80-year-old woman with ischemic colitis who excreted a 20-cm colon cast. In most cases that involve a colon cast containing a muscle layer component, invasive therapy is required owing to colonic obstruction or stenosis. However, in the present case, the colon cast consisted only of a mucosa layer and was not associated with severe stenosis or obstruction; therefore, it was successfully treated by conservative therapy. Histologic examination of the colon segment may be crucial in determining the appropriate treatment.

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics. The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated. Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06-2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44-9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41-4.40; P = 0.0019). Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.

BACKGROUND: Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. OBJECTIVE: We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. DESIGN: This study was conducted at a single tertiary care institution in Japan. SETTING: This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. PATIENTS: A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. MAIN OUTCOME MEASURES: The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. RESULTS: The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p < 0.0001 and p = 0.001). In terms of local tumor recurrence, those diagnosed as high responders by the pathologic response grade, Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSIONS: Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

To develop a drug-delivery system for the prolonged retention of intraperitoneally (i.p.) administered cisplatin (CDDP) to deliver intraperitoneal chemotherapy against peritoneal carcinomatosis effectively. CDDP was encapsulated inside an in situ cross-linkable hyaluronic acid (HA)-based hydrogel. The gelation and degradation kinetics of the hydrogel and the release kinetics of CDDP were investigated in vitro, and the antitumor effect was investigated in a mouse model of peritoneal dissemination of human gastric cancer. The gelation time varied according to the concentration of two polymers: HA-adipic dihydrazide and HA-aldehyde. CDDP was released from the hydrogel for more than 4 days. A cell proliferation assay showed that the polymers themselves were not cytotoxic toward MKN45P, a human gastric cancer cell line. By mixing the two polymers in the peritoneum, in situ gelation was achieved. The weight of peritoneal nodules decreased in the hydrogel-conjugated CDDP group, whereas no significant antitumor effect was observed in the free CDDP group. In situ cross-linkable HA hydrogels represent a promising biomaterial to prolong the retention and sustain the release of intraperitoneally administered CDDP in the peritoneal cavity and to enhance its antitumor effects against peritoneal dissemination.