Lateral node metastasis in low rectal cancer as a hallmark to predict recurrence patterns.

BACKGROUND: Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. METHODS: We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. RESULTS: Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). CONCLUSIONS: Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.

A Case of Immediate Anastomotic Leakage After Low Anterior Resection for Rectal Cancer.

A man in his seventies was referred to our hospital for radical therapy for advanced rectal cancer with multiple liver metastases. A colonic stent had already been placed in his rectum at the previous hospital because of malignant colorectal obstruction, so our therapeutic strategy was to perform systematic chemotherapy after resection of the primary tumor. Laparoscopic low anterior resection with a covering stoma was performed under general anesthesia. At about one hour after the surgery, the patient had sudden abdominal pain with watery diarrhea, and a similar discharge from his drainage tube. We suspected peritonitis caused by bowel perforation and emergency surgery was performed. The operative findings showed that his peritonitis was caused by anastomotic leakage from the rectum. Radical lavage of the abdominal space and reconstruction of colostomy was performed. The patient gradually recovered and we were able to start systematic chemotherapy at one month after the surgery. Anastomotic leakage immediately after anterior resection caused by watery diarrhea is rare, and it may be concerned with several issues. The covering stoma is intended to stop anastomotic leakage but it cannot prevent all cases of leakage especially when obstruction is present. We recommend that preventive measures be taken against anastomotic leakage, including intraoperative leakage tests or anal decompression tube placement.

Mismatch repair proteins expression and tumor-infiltrating T-cells in colorectal cancer.

Microsatellite instability (MSI) and tumor mutational burden (TMB) are indicators of the tumor mutational load, which can lead to immune cell recruitment. By contrast, the number of tumor-infiltrating T cells (TITs) is indicative of the host immune response to tumor cells. The present study evaluated if the expression of mismatch repair (MMR) proteins can be used as a precise tool to assess immunogenicity in the tumor microenvironment. A total of 73 colorectal cancer cases were enrolled in the present study. MMR protein expression was assessed using four-antibodies immunohistochemistry (IHC) targeting MLH1, MSH2, MSH6 and PMS2. TIT was assessed through IHC by counting CD3+ and CD8+ cells in tumor. The enrolled cases were classified into four groups according to MMR and TIT status i) Mismatch repair-proficient (pMMR) and a high number of TITs (pMMR/TIT-H); ii) pMMR and a low number of TITs (pMMR/TIT-L); iii) mismatch repair-deficient (dMMR) and TIT-H (dMMR/TIT-H); and iv) dMMR/TIT-L]. The present study evaluated the clinicopathological characteristics of the four groups, in addition to the difference of TMB. TMB analysis was counted the number of the somatic mutations through multi-genes panel using next-generation sequencing. Clinicopathological characteristics, including age, sex, pathological depth of invasion and lymph node metastasis, were not found to be statistically different between dMMR/TIT-H and dMMR/TIT-L groups. Tumors among pMMR/TIT-H group were associated with poorly differentiation compared with those in pMMR/TIT-L group (P=0.025). The median TMB among the dMMR/TIT-H group was the highest in four groups but the median TMB was <10 muts/Mb in dMMR/TIT-L, pMMR/TIT-H and pMMR/TIT-L groups, respectively. However, one tumor in the pMMR/TIT-H group showed high TMB. The present findings suggest that assessing MMR status alone may not be sufficient to precisely evaluate the antitumor immune response in the tumor microenvironment.

Non-invasive Monitoring of Pouchitis After Total Proctocolectomy Using Fecal Calprotectin Levels.

BACKGROUND: Fecal calprotectin (FC) is the most widely used marker for evaluating the disease activity of ulcerative colitis (UC). However, studies on FC in pouchitis after total proctocolectomy are scarce. We aimed to examine the correlations between the FC level and clinical findings and Pouchitis Disease Activity Index (PDAI) in UC patients who underwent total proctocolectomy (TP) with ileal pouch-anal canal anastomosis (IPAA) or ileal pouch-anal canal anastomosis (IACA). METHODS: Between April 2008 and March 2018, 15 patients, consisting of 8 males and 7 females, with an average age at operation of 46.5 years, participated in this study. The average observation period was 68.3 months. The subjects underwent FC level measurements and endoscopic examinations. RESULTS: The mean FC level was 418.69 µg/g (range: 10-1650 µg/g). Pouchitis was found in one (6.6%) patient, as detected by endoscopy. Among the 15 cases, FC levels were positively correlated with white blood cell count as well as albumin and C-reactive protein levels. There was a significant positive correlation between the PDAI score and FC levels (p<0.05). The median FC level was 111 mg/g in those with pouchitis, which was significantly higher than the 16 mg/g in those without pouchitis (p<0.05). Moreover, a significant positive correlation was found between the endoscopic findings of inflammation and FC levels (p<0.00005). CONCLUSION: FC levels were correlated with the PDAI score, blood testing data, and endoscopic findings, suggesting that the FC level could be a useful index of postoperative pouchitis and ileal pouch condition in patients undergoing TP with IPAA as UC treatment.

Chitinase 3-like 1, Carcinoembryonic Antigen-related Cell Adhesion Molecule 6, and Ectopic Claudin-2 in the Carcinogenic Processes of Ulcerative Colitis.

BACKGROUND/AIM: The cumulative cancerous rate of colitis-associated cancer (CAC) has increased exponentially in patients with ulcerative colitis (UC). We have investigated the factors involved in the carcinogenic processes of CAC among UC patients. PATIENTS AND METHODS: A total of 42 UC patients who underwent surgical treatments between January 2001 and December 2010 at Kurume University Hospital (Fukuoka, Japan) were enrolled. We conducted this study using 3 cases of CAC out of 42 UC cases and 1 case of colorectal cancer. cDNA microarray analyses were performed using normal, inflamed, and cancerous tissues from surgical CAC specimens and protein expression was confirmed by immunohistochemical analyses. RESULTS: cDNA microarray revealed 32 genes that were dominantly expressed in tumorous regions of CAC. Gene ontology analysis revealed that these genes were involved in inflammatory responses and cytokine-cytokine receptor interactions. Chitinase 3-like1 (CHI3L1), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), and Claudin-2 (CLND2) were selected from CAC-related genes as candidate molecules. Immunostaining revealed strong expression of each protein in cancerous regions. CONCLUSION: In this study, we identified CAC-related genes and found that CHI3L1, CEACAM6, and CLND2 were expressed in patient samples. All the above genes were associated with adherent invasive Escherichia coli (AIEC), which suggested that these molecules are likely involved in AIEC infection. Further analyses would be required to reveal unknown mechanisms of CAC-related genes in the tumor microenvironment.

Optimizing nodal and staging classification in low rectal cancers with lateral node metastasis: multicentre retrospective cohort study.

BACKGROUND: Patients with lateral node metastasis in low rectal cancers have a poor prognosis. However, variability in patient survival in terms of lateral metastatic status has not been thoroughly investigated. This study was conducted to assess the prognostic value of lateral node involvement and to review nodal classification. METHODS: Patients with stage III low rectal cancers who underwent lateral node dissection were retrospectively reviewed. Two cohorts were set: the first one (1995-2006) was selected using a Japanese multi-institutional database and was used for development of a new nodal system, and the second (2007-2013) was collected from referral institutions for validation of findings. Variables correlated with poor prognosis were investigated. Next, a modified classification of lateral-positive nodal cancers was created. Finally, this new classification was compared with TNM and Japanese classification-based systems according to the Akaike information criterion (AIC) and concordance index (c-index). RESULTS: Overall, 742 and 508 patients were selected for cohorts 1 and 2, respectively. Based on the analyses on cohort 1, patients with two or more lateral metastatic nodes partially spreading into regions outside of internal iliac area exhibited poor prognosis; accordingly, a modified N classification was created, where TNM-N1 and N2a cancers with this feature were upgraded, respectively, to N2a and N2b. The modified N classification yielded the most favourable indices (AIC = 2661.08; c-index = 0.6477) compared with the TNM (AIC = 2662.36; c-index = 0.6457) and Japanese classification-based systems (AIC = 2684.06; c-index = 0.6302). All findings were confirmed by analysing cohort 2. CONCLUSION: A modified nodal system is proposed to account for the significance of lateral node metastasis.

Analysis of risk factors for anastomotic leakage after lower rectal Cancer resection, including drain type: a retrospective single-center study.

BACKGROUND: We investigated the correlations between surgery-related factors and the incidence of anastomotic leakage after low anterior resection (LAR) for lower rectal cancer. METHODS: A total of 630 patients underwent colorectal surgery between 2011 and 2014 in our department. Of these, 97 patients (15%) underwent LAR and were enrolled in this retrospective study. Temporary ileostomy was performed in each patient. RESULTS: Anastomotic leakage occurred in 21 patients (21.7%). Univariate analysis showed a significant association between operative duration (p = 0.005), transanal hand-sewn anastomosis (p = 0.014), and operation procedure (p = 0.019) and the occurrence of leakage. Multivariate regression reanalysis showed that underlying disease (p = 0.044), transanal hand-sewn anastomosis (p = 0.019) and drain type (p = 0.025) were significantly associated with the occurrence of leakage. The propensity-score analysis showed that closed drainage were 6.3 times more likely to have anastomotic leakage than open drainage in relation to the amount of postoperative drainage (ml), according to the inverse probability of treatment-weighted analysis. CONCLUSIONS: Our results indicate that underlying disease, transanal hand-sewn anastomosis, and closed drain may be a risk and predictive factors for anastomotic leakage after LAR for lower rectal cancer. The notable finding was that closed drainage was related to the occurrence of anastomotic leakage and closed drainage was correlated with less volume of postoperative drain discharge than open drain.

Mutant KRAS Promotes NKG2D+ T Cell Infiltration and CD155 Dependent Immune Evasion.

BACKGROUND/AIM: Roles for mutant (mt) KRAS in the innate immune microenvironment in colorectal cancer (CRC) were explored. MATERIALS AND METHODS: Human CRC HCT116-derived, mtKRAS-disrupted (HKe3) cells that express exogenous mtKRAS and allogenic cytokine-activated killer (CAK) cells were co-cultured in 3D floating (3DF) culture. The anti-CD155 antibody was used for function blocking and immuno histochemistry. RESULTS: Infiltration of CAK cells, including NKG2D+ T cells, into the deep layer of HKe3-mtKRAS spheroids, was observed. Surface expression of CD155 was found to be up-regulated by mtKRAS in 3DF culture and CRC tissues. Further, the number of CD3+ tumor-infiltrating cells in the invasion front that show substantial CD155 expression was significantly larger than the number showing weak expression in CRC tissues with mtKRAS. CD155 blockade decreased the growth of spheroids directly and indirectly through the release of CAK cells. CONCLUSION: CD155 blockade may be useful for therapies targeting tumors containing mtKRAS.

Mesocolic hernia following retroperitoneal laparoscopic radical nephrectomy: A case report.

INTRODUCTION: Small bowel obstruction (SBO) caused by an internal hernia through a mesocolon after retroperitoneal laparoscopic nephrectomy (RLN) is rare. PRESENTATION OF CASE: A 66-year-old man who had undergone RLN with bladder cuff excision for a left renal pelvic cancer. After the surgery, he experienced SBO repeatedly. Contrast-enhanced computed tomography (CT) and gastrografin contract radiography through a long tube showed an internal hernia through the mesocolon to the retroperitoneal space where the resected left kidney had been located. We performed a subsequent surgery for the internal hernia. Postoperative course was uneventful and currently he has no recurrence of herniation 6 months post-operatively. DISCUSSION: Mesenteric defects that cause an internal hernia can be created inadvertently during RLN when the colon is mobilized medially, and the kidney is being detached from retroperitoneum. The removal of a kidney leads to a potential retroperitoneal space to which small intestine can migrate. While there is no absolute necessity in mobilizing the colon during the retroperitoneal laparoscopic approach, there is still a risk of making mesocolic defects directly in the retroperitoneal space. CONCLUSION: We need to perform operations with sufficient anatomical knowledge of retroperitoneal fascia and careful surgical techniques. The critical thing to prevent an internal hernia following RLN is to close the mesenteric defects intraoperatively. It is also important to suspect an internal hernia and do proper examinations promptly when patients had the symptoms of SBO after nephrectomy.

Questionnaire Survey from the 1st Kurume University Inflammatory Bowel Disease Center Educational Lecture.

INTRODUCTION: The number of inflammatory bowel disease (IBD) patients is increasing steadily in Japan, and it is expected that patient groups and patient education will improve the quality of life of patients and IBD care. The 1st Kurume University IBD Center educational lecture was held and a questionnaire survey was administered at this lecture. METHODS: We asked 78 participants to answer a questionnaire survey on the occasion of the 1st Kurume University IBD Center educational lecture. RESULTS: We obtained responses from 56 (71.8%) participants; 31 (55.4%) had IBD [21 (37.4%) had ulcerative colitis (UC) and 10 (17.9%) had Crohn's disease (CD)]. Most participants were female (37, 66%). The age range with the highest number of participants was 40 to 69 (27, 48.2%). Most had heard about this educational lecture through "notification by the patient's doctor" 23 (41.1%). A total of 30 (53.6%) of participants answered "good" about the lecture content, while 50 (89.7%) of participants answered "very good" and "good" about the impression of this lecture. Meanwhile, 10 (32.3%) of patients were interested in patient groups. The percentage of patients who were interested in patient groups was higher in patients with CD 4 (66.7%) than those with UC 2 (33.3%). CONCLUSION: We held the 1st Kurume University IBD center educational lecture. Further studies are needed to assess whether educational lectures and/or patient groups can improve patients' quality of life (QOL) and IBD care in our hospital.

Sinusoidal Obstruction Syndrome and Postoperative Complications Resulting from Preoperative Chemotherapy for Colorectal Cancer Liver Metastasis.

BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Y­box­binding protein 1 inhibits apoptosis and upregulates EGFR in colon cancer.

Y­box­binding protein 1 (YB­1) is a DNA/RNA­-binding protein and an important transcription and translation factor in carcinogenesis. However, the biological function and molecular correlation of YB­1 in colorectal cancer are not fully understood. The aim of the present study was to determine the significance of YB­1 expression and its biological role in colorectal cancer. Cell proliferation, migration and apoptosis were examined upon knockdown of YB­1 expression in different colon cancer cell lines that had different genetic backgrounds. Since the properties of different colon cancer cell lines with specific RAS/RAF gene mutations downstream epidermal growth factor receptor (EGFR) may differ from wild­type colorectal cancer, it is critical to study the role of YB­1 with respect to the mutational status of RAS. The results indicated that the suppression of YB­1 decreased cell proliferation (P<0.05) and migration (P<0.05) regardless of the status of RAS/RAF in the HT29, HCT116 and CaCo2 cell lines. In contrast, YB­1 knockdown altered the expression of apoptosis­related genes and the expression of EGFR was detected in the cell lines expressing wild­type RAS/RAF but not in those expressing mutated RAS/RAF. These results indicated that YB­1 plays an important role in cell proliferation, migration, apoptosis and EGFR expression in colorectal cancer. Furthermore, apoptosis and EGFR expression may be affected by the mutational status of RAS/RAF and controlled through YB­1.

Correction to: The Immunoscore is a Superior Prognostic Tool in Stages II and III Colorectal Cancer and is Significantly Correlated with Programmed Death-Ligand 1 (PD-L1) Expression on Tumor-Infiltrating Mononuclear Cells.

In the original article, Akihiko Kawahara's first name is incorrect. It is correct as reflected here.

The Immunoscore is a Superior Prognostic Tool in Stages II and III Colorectal Cancer and is Significantly Correlated with Programmed Death-Ligand 1 (PD-L1) Expression on Tumor-Infiltrating Mononuclear Cells.

BACKGROUND: In colorectal cancer (CRC), the indication for immune checkpoint inhibitors is determined by the microsatellite instability status of the tumors. However, an optimal biomarker for their indication has not been fully identified to date. This study aimed to establish the clinicopathologic importance of the Immunoscore (IS) in CRC and to clarify the relationships between the IS, programmed death-ligand 1 (PD-L1) expression, and tumor-associated macrophages. METHODS: In 132 cases, CRC was diagnosed and surgically treated in our department from 2009 to 2010. Immunohistochemical staining using primary antibodies PD-L1, CD3, CD8, CD68, and CD163 was performed. The IS was determined according to the proposal of an international task force. Statistical analyses were performed to investigate the correlation between the IS, clinicopathologic variables, and expression of immune checkpoint molecules. RESULTS: The overall survival (OS) and relapse-free survival (RFS) in the high-IS group (I3-4) were significantly better than in the low-IS group (I0-2) (OS: P = 0.0420; RFS: P = 0.0226). The positivity rate for PD-L1 on tumor cells (tPD-L1) was only 0.8%, whereas that for PD-L1 on interstitial tumor-infiltrating mononuclear cells (iPD-L1) was 18.2%. The iPD-L1-positive group showed significantly better survival in terms of both OS and RFS than the iPD-L1-negative group (OS: P = 0.0278; RFS: P = 0.0253). The findings showed significant correlation between the IS and iPD-L1 expression (P < 0.0001). CONCLUSIONS: The study found that a high IS was a good indicator of a better prognosis and significantly correlated with iPD-L1 expression in CRC.

[A Case of Postoperative Recurrence of Rectal Cancer in Which Desensitization Therapy Was Effective against Oxaliplatin Allergy in L-OHP].

The case involved a 44-year-old man who underwent intersphincteric resection and lateral lymph node dissection for rectal cancer. Pathological diagnosis revealed a well-differentiated adenocarcinoma comprising KRAS wild type, and pT2N0M0 (pathological Stage I). CapeOX (capecitabine plus oxaliplatin[L-OHP]), and bevacizumab therapy was initiated because of local recurrence. Although a partial response (PR) was observed, the therapy was terminated after 6 courses because of the development of hand-foot syndrome. FOLFIRI and cetuximab therapy was initiated after cancer recurrence was observed during a follow up. As the therapeutic efficiency is characterized by stability (stable disease: SD), and the tumor reduction effect observed was not sufficient, we performed an abdominoperineal resection to achieve local control. However, a left hydronephrosis occurred due to the pelvic recurrence, necessitating the emergency hospitalization of the patient. Because resistance to L-OHP was not confirmed, mFOLFOX6 and bevacizumab therapy was introduced in hopes of the effect of the former. As Grade 2 allergy (erythema) appeared immediately after the L-OHP was administered during the 3 courses, treatment was discontinued. We the reinitiated the treatment along with the desensitization therapy from the 4 courses. A total of 27 courses of mFOLFOX6 and bevacizumab therapy were administered until the state of disease progression (progression disease: PD) was determined. PR was defined as the best therapeutic efficiency. In some cases, discontinuation of treatment is necessary as observed in the present case due to the onset of L-OHP allergies, even if the overall effect of the treatment is expected to be good. Our case is essentialas it demonstrates the successfulness of desensitization therapy for L-OHP allergies.

Mina53 nuclear localization is an important indicator of prognosis in patients with colorectal cancer after adjuvant chemotherapy.

The aim of this study was to investigate the status of the c­Myc­related molecule Mina53 and the clinical impact of Mina53 nuclear localization in patients with stage II and III colorectal cancer (CRC). Patients (n=250) who underwent complete resection of CRC at our department were enrolled in this study, and tissue microarray samples were constructed from resected specimens. Mina53 expression in the nuclei of tumor cells was analyzed using immunohistochemistry (IHC). Patients were classified into Mina53 nuclear localization­-positive and ­negative groups, and statistical correlations with clinicopathological factors were investigated. Relapse­free survival (RFS) was compared using the Kaplan­Meier method and the Cox proportional hazard model. Tumor recurrence was significantly higher in the Mina53­positive group than in the Mina53­negative group. Moreover, in RFS analysis, patients in the Mina53­positive group exhibited significantly poorer prognosis than patients in the Mina53­negative group. In the univariate analysis, histological type, adjuvant chemotherapy status, carcinoembryonic antigen (CEA) status, and Mina53 status were prognostic factors for RFS. Furthermore, in the subgroup analysis, patients in the Mina53­positive group with stage III disease treated with adjuvant chemotherapy exhibited significantly poorer prognosis in RFS than patients in the Mina53­negative group. In the univariate and multivariate analyses, histological type and Mina53 status were significantly associated with RFS. Thus, our findings revealed that Mina53 was an important indicator of prognosis in patients with stage III CRC treated with adjuvant chemotherapy.

Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using magnetic resonance imaging and risk factors for metastasis: Multicenter study of the Lymph Node Committee of the Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: The goal of the study was to examine prediction of lateral pelvic lymph node (LPLN) metastasis from lower rectal cancer using a logistic model including risk factors for LPLN metastasis and magnetic resonance imaging (MRI) clinical LPLN (cLPLN) status, compared to prediction based on MRI alone. METHODS: The subjects were 272 patients with lower rectal cancer who underwent MRI prior to mesorectal excision combined with LPLN dissection (LPLD) at six institutes. No patients received neoadjuvant therapy. Prediction models for right and left pathological LPLN (pLPLN) metastasis were developed using cLPLN status, histopathological grade, and perirectal lymph node (PRLN) status. For evaluation, data for patients with left LPLD were substituted into the right-side equation and vice versa. RESULTS: Left LPLN metastasis was predicted using the right-side model with accuracy of 86.5%, sensitivity 56.4%, specificity 92.7%, positive predictive value (PPV) 61.1%, and negative predictive value (NPV) 91.2%, while these data using MRI cLPLN status alone were 80.4, 76.9, 81.2, 45.5, and 94.5%, respectively. Similarly, right LPLN metastasis was predicted using the left-side equation with accuracy of 83.8%, sensitivity 57.8%, specificity 90.4%, PPV 60.5%, and NPV 89.4%, and the equivalent data using MRI alone were 78.4, 68.9, 80.8, 47.7, and 91.1%, respectively. The AUCs for the right- and left-side equations were significantly higher than the equivalent AUCs for MRI cLPLN status alone. CONCLUSIONS: A logistic model including risk factors for LPLN metastasis and MRI findings had significantly better performance for prediction of LPLN metastasis compared with a model based on MRI findings alone.

The Primary Result of Prospective Randomized Multicenter Trial of New Spray-Type Bio-absorbable Adhesion Barrier System (TCD-11091) Against Postoperative Adhesion Formation.

BACKGROUND: Postoperative adhesions are the major cause of postoperative complications including intestinal obstruction, infertility, and chronic pelvic pain. In order to reduce postoperative adhesions, Terumo Corporation (Tokyo, Japan) has developed an adhesion barrier system (TCD-11091) which is easy to use at the treatment site in various surgical procedures including laparoscopic surgeries. We conducted a prospective randomized single-blind study in patients who underwent laparotomy with ileostomy. METHODS AND RESULTS: One hundred twenty-six patients were randomly assigned to TCD-11091 group (n = 62) or non-treatment group (n = 62). Patient backgrounds were similar between the groups. At the time of ileostomy closure (the second-look surgery), the observation was performed on 55 in the TCD-11091 group and 43 in the control group. The incidence of adhesions observed at the second-look surgery was significantly lower in the TCD-11091 group (52.7 versus 90.7%; p < 0.001). For the secondary endpoints, the incidence of wide extent adhesions (grade 2 or higher) was significantly reduced (38.2 versus 79.1%; p < 0.001). Regarding the severity of adhesions, the incidence of grade 2 or higher adhesions was also significantly lower in the TCD-11091 group (47.3 versus 88.4%; p < 0.001). No differences in the incidence of adverse events were found between the TCD-11091 group and the non-treatment group (85.2 versus 75.4%; p = 0.225). CONCLUSIONS: Use of TCD-11091 was safe and associated with significantly lower incidence of adhesion and severity of adhesions compared with non-treatment procedure.

Clinicopathological and Corresponding Genetic Features of Colorectal Signet Ring Cell Carcinoma.

Europe and the United States have high morbidity rates of colorectal cancer, it being the third most common new cancer among both men and women each year. Colorectal cancer morbidity is also high in Japan. Advances in surgery, chemotherapy, and molecular targeted drugs have extended the prognosis of colorectal cancer, although the effects of these treatments remain poor in some patients. Colorectal cancer almost always presents as differentiated adenocarcinoma, although one tissue type, signet-ring cell carcinoma, occurs rarely. Overall, colorectal signet-ring cell carcinoma is very infrequent among cases of colorectal cancer, however, its prognosis is reported as being extremely poor. Several reports have addressed its clinicopathological and typical genetic characteristics, such as mutation of viral oncogene Kirsten rat sarcoma (KRAS) gene, but there have been few comprehensive investigations of its characteristics and genetic background. In this review, we examine features of colorectal signet-ring cell carcinoma by summarizing its clinical and genetic characteristics.

Perineural Invasion Is a Prognostic Factor and Treatment Indicator in Patients with Rectal Cancer Undergoing Curative Surgery: 2000-2011 Data from a Single-center Study.

BACKGROUND/AIM: The aim of the present study was to investigate whether perineural invasion (PNI) was a prognostic index for patients who underwent curative surgery for Dukes' grade B and C rectal cancer. PATIENTS AND METHODS: A total of 645 patients with rectal cancer between January 2000 and December 2011; 363 with Dukes' B or C stages who did not undergo chemoradiotherapy were reviewed. RESULTS: Of 363 patients, 83 (22.9%) were PNI-positive. The 5-year overall survival and disease-specific survival rates were significantly worse for patients with PNI-positive Dukes' B or C disease compared to those with PNI-negative disease. There was no significant difference in the recurrence pattern (hematogenous or lymphatic spread), but patients with PNI-positive disease had a significantly higher rate of recurrence compared to those with PNI-negative disease (p<0.001). CONCLUSION: PNI was a significant prognostic factor in rectal cancer, and the PNI status in primary rectal cancer pathology specimens should be considered for therapy stratification.