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.

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.

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.

Survival after initial lung metastasectomy for metastatic colorectal cancer in the modern chemotherapeutic era.

BACKGROUND: A clear survival benefit has been reported for lung metastasectomy for colorectal cancer, and several clinicopathological prognostic factors have been proposed in the past. However, clinical advances, such as chemotherapy and radiographic imaging, should have improved patient outcome and may have altered prognosticators. This study aimed to assess patient survival and determine prognostic factors for survival and recurrence in patients who underwent initial lung metastasectomy for colorectal cancer in the modern clinical era. METHODS: Clinicopathological data and outcomes of 59 patients who underwent curative initial lung metastasectomy for colorectal cancer from 2004 to 2012 at a single institution in Japan were retrospectively investigated. Survival was estimated using the Kaplan - Meier method, and Cox proportional hazards regression models were used to estimate the prognostic impacts of each variable in univariate and multivariate analysis. RESULTS: The 5-years overall and disease-free survival rates were 54.3 and 40.6%, respectively. A disease-free interval < 24 months after colorectal cancer resection (P = 0.004) and a serum carcinoembryonic antigen ≥ 5.0 ng/mL before initial lung metastasectomy (P = 0.015) were independent predictors for poor overall survival. Moreover, the disease-free interval after colorectal cancer resection < 24 months (P = 0.010) and a colorectal cancer with N2 stage disease (P = 0.018) were independently associated with poor disease-free survival. On the other hand, the number of lung metastasis was not identified as a poor prognostic factor for both overall and disease-free survival. CONCLUSIONS: Our findings demonstrated similar or slightly better overall survival, and substantially favorable disease-free survival as compared with past reports. Poor prognostic factors for overall survival appeared not to differ from those of past studies, although this modern series did not determine the number of lung metastasis as a poor prognostic factor, which should be investigated in future studies. Moreover, initial lung metastasectomy is not expected to be a curable treatment for patients with both a short disease-free survival after colorectal cancer resection and colorectal cancers with N2 stage disease.

Selection of Lymph Node-Positive Cases Based on Perirectal and Lateral Pelvic Lymph Nodes Using Magnetic Resonance Imaging: Study of the Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: To investigate the optimum cutoff for lymph node size to identify cases positive for perirectal lymph node (PRLN) and lateral lymph node (LPLN) metastasis of lower rectal cancer on magnetic resonance imaging (MRI). METHODS: The subjects were 449 patients who underwent preoperative MRI. Mesorectal excision was performed in all patients (combined with lateral pelvic lymph node [LN] dissection in 324) between 2004 and 2013 at 6 institutes. Cases were classified as cN positive and cN negative on the basis of the short axis of the largest LN being greater than or equal to a cutoff or less than a cutoff, respectively. PRLN and LPLN diagnoses using 5 and 10 mm cutoffs were compared with histologic diagnoses. Of the 449 patients, 55 received preoperative chemoradiotherapy. MRI was only performed after this therapy in all of these patients. RESULTS: For PRLNs, 5 and 10 mm cutoffs gave area under the curve (AUC) values of 0.6364 and 0.5794, respectively. The 5 mm cutoff gave a significantly higher AUC value (P = 0.0152), with an accuracy of 63.7 %, sensitivity of 72.6 %, and specificity of 54.7 %. For right LPLNs, the respective AUC values were 0.7418 and 0.6326 (P = 0.0034), and the variables (5 mm cutoff) were 77.6, 68.6, and 79.7 %. For left LPLNs, AUC values were 0.7593 and 0.6559, respectively (P = 0.0057), and the variables (5 mm cutoff) were 79.3, 70.8, and 81.0 %. CONCLUSIONS: Identification of LN-positive cases on the basis of PRLN and LPLN sizes was superior at a short-axis 5 mm cutoff. Size-based diagnosis of LN metastasis is simple and useful, but further investigation is needed to clarify whether it is superior to diagnosis based on morphology, such as shape, border, and signal intensity.

A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. METHODS: The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. RESULTS: A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). CONCLUSIONS: This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

The important risk factor for lateral pelvic lymph node metastasis of lower rectal cancer is node-positive status on magnetic resonance imaging: study of the Lymph Node Committee of Japanese Society for Cancer of the Colon and Rectum.

PURPOSE: This study seeks to evaluate lateral pelvic lymph node (LPLN) and perirectal lymph node (PRLN) status on magnetic resonance imaging (MRI) as potential risk factors for lymph node metastasis. METHODS: The subjects were 394 patients with lower rectal cancer who underwent MRI prior to mesorectal excision (combined with lateral pelvic lymph node dissection in 272 patients) at 6 institutes. No patients received neoadjuvant therapy. Cases were classified as cN(+) and cN(-) based on the short axis of the largest lymph node ≥5 and <5 mm, respectively. LPLN and PRLN status and other clinicopathologic factors were analyzed by multivariate logistic regression. The importance of identified risk factors for lymph node metastasis was examined using the area under the curve (AUC). RESULTS: Independent risk factors for right LPLN metastasis included histopathological grade (G3 + G4), pPRLN(+), M1, cLPLN(+) [odds ratio (OR) 10.73, 95 % confidence interval (CI) 4.59-27.1], and those for left LPLN metastasis were age (<64), histopathological grade (G3 + G4), pPRLN(+), and cLPLN(+) (OR 24.53, 95 % CI 9.16-77.7). ORs for cLPLN(+) were highest. The AUCs for right and left cLPLN status of 0.7484 (95 % CI 0.6672-0.8153) and 0.7904 (95 % CI 0.7088-0.8538), respectively, were significantly higher than those for other risk factors. In contrast, the ORs for cPRLN(+) and cPRLN status of 2.46 (95 % CI 1.47-4.18) and 0.6396 (95 % CI 0.5917-0.6848) were not much higher than for other factors. CONCLUSIONS: An LPLN-positive status with a short axis ≥5 mm on MRI is an important predictor of LPLN metastasis, but PRLN status is not a strong predictor of PRLN metastasis.

Histopathological predictors for local recurrence in patients with T3 and T4 rectal cancers without preoperative chemoradiotherapy.

BACKGROUND AND OBJECTIVES: Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR. METHODS: A total of 796 stage II/III patients with pT3 and pT4 rectal cancer who did not undergo preoperative chemoradiation were enrolled. LR was defined as intra-pelvic recurrence only. Histopathological factors related to LR were investigated. RESULTS: LR was found in 25 patients (6.1%) with stage II and 54 patients (13.9%) with stage IIIB/IIIC. In patients with stage II, distance of mesorectal extension (DME) >4 mm (P = 0.011) and positive venous invasion (P = 0.035) were independent factors that predicted LR. In patients with stage IIIB/IIIC, circumferential resection margin (CRM) ≤1 mm (P = 0.003) and positive lymphatic invasion (P = 0.006) were independent factors. The cumulative 5-year LR rate was higher (11.9%) in patients with a combination of DME > 4 mm and/or positive venous invasion for stage II (P < 0.001), and was also higher in patients with a combination of CRM≤1 mm and/or positive lymphatic invasion for stage IIIB and IIIC (22.2%; P < 0.002, and 34.3%; P < 0.006, respectively). CONCLUSIONS: Important histopathological predictors for LR in patients with pT3 and pT4 rectal cancer were different at each stage.

Technical tips for intersphincteric resection: how to take out the rectum.

Intersphincteric resection (ISR) is an ideal technique that preserves the anus, regardless of whether the internal anal sphincter is removed. However, it is difficult to dissect the anterior wall of the rectum from the adjacent organs. We herein describe a safe and useful ISR technique which draws out the rectum through the anus. The intersphincteric space (ISS) between the internal and external anal sphincter muscles was first transabdominally dissected. Next, the transanal dissection was advanced into the ISS bilaterally from the posterior side without dissecting the anterior wall of the anal canal, and the sigmoid colon and rectum were drawn out through the anus. Dissection between the anterior wall of the rectum and prostate/vagina could be easily performed under direct vision. This technique enables the dissection without any risk of a positive surgical margin or unexpected bleeding, and avoids injury to adjacent organs. This technique seems to be a safe and useful dissection technique for approaching the anterior wall of the anal canal.

External sphincter resection for lower rectal and anal canal adenocarcinoma: achieving anal preservation with oncological and functional satisfaction.

Intersphincteric resection (ISR) has recently been performed for very low rectal cancer, whereas abdominoperineal resection (APR) is typically reserved for cancers extremely close to the anal verge and/or when the depth of tumor invasion is suspected to involve the intersphincteric space. This is because impairment of anal function is considered unavoidable if the external sphincter (ES) is excised. We describe our technique of ISR with ES resection and discuss its outcomes. This surgical technique may offer major clinical advantages to selected patients and should be considered as an alternative to APR, although careful consideration of anal function is required.

Extramural extension as indicator for postoperative adjuvant chemotherapy in Stage IIA (pT3N0) colon cancer.

The usefulness of adjuvant chemotherapy (CMT) in patients with Stage IIA colon cancer remains unclear. The present study aimed to investigate extramural extension as an indicator for adjuvant CMT. Data were reviewed from 202 consecutive patients with Stage IIA colon cancer that underwent curative surgery between 1995 and 2007. The distance of the extramural extension (DEE) was measured histologically. The optimal prognostic cut-off point of the DEE for oncologic outcomes was statistically determined. The eligible surviving patients had been followed for a median period of 75 months (range: 2-210 months). Patients were subdivided into two groups according to the optimal cut-off point; DEE ≤5 mm (pT3a) and DEE >5 mm (pT3b). The pT3b was the most powerful independent risk factor for postoperative recurrence (P = 0.0324, HR: 3.04, 95% CI: 1.098-8.408), and was significantly correlated with distant metastasis (P = 0.0161 HR: 5.19, 95% CI: 1.765-15.239). The recurrence-free and cancer-specific 5-year survival rates in patients with pT3b were significantly lower than in patients with pT3a (81.5% vs. 95.4%, P = 0.0003 and 85.9% vs. 97.4%, P = 0.0007, respectively). pT3b could be an important risk factor for distant metastasis in Stage IIA colon cancer. Postoperative adjuvant CMT may be indicated for patients with pT3b.

Intersphincteric resection for very low rectal cancer: a systematic review.

Radical surgical treatment for very low rectal cancer near the anus has generally involved abdominoperineal resection. Various sphincter-saving operations have been developed for such tumors to optimize the patients' postoperative quality of life. Current protocols focus on intersphincteric resection (ISR), which differs from conventional hand-sewn coloanal anastomosis (CAA) after low anterior resection. However, the efficacy of ISR remains unclear. The surgical, oncologic, and functional outcomes after intersphincteric resection (ISR) were reviewed. This review of the current literature was conducted by searching the PubMed online database. Articles focusing specifically on conventional hand-sewn CAA were excluded from this study. The mean mortality rate is <2 %, and the mean morbidity rate ranges from 7.7 to 38.3 %. The mean local recurrence rate varies widely from 0 to 22.7 %, with a mean follow-up duration of 40-94 months. The mean disease-free and overall 5-year survival rates are 69-86 and 79-97 months, respectively. Functional outcomes are generally acceptable, but accurate evaluation is extremely difficult due to the absence of unified appraisal methods. ISR appears surgically, oncologically and functionally acceptable. However, more experience and better understanding of the oncology, anal physiology, and pelvic anatomy are necessary to achieve successful outcomes without complications, and to improve patient survival.

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.

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.

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.

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.

Challenges in staging systems for colorectal cancer: clinical significance of metastatic lymph node number in colorectal cancer and mesorectal extension in rectal cancer.

In many countries, treatment for cancer is performed based on staging systems in which the degree of cancer development is defined objectively. A common staging system is thus needed to compare outcomes. The staging system for colorectal cancer in Japan has been made to enhance consistency with the TNM classification, and the categorization of metastatic lymph nodes and depth of invasion have been revised in recent years. Although these are important factors that determine disease stage, relationships between each factor and recurrence have shown differing prognoses. In our retrospective study, the prognosis of a group with only one metastatic lymph node was significantly better compared to a group with > or = 2 metastatic lymph nodes. In addition, rectal cancer with mesorectal extension >5 mm showed low relapse-free survival rates and high recurrence rates. The validity of staging systems should thus be inspected from various perspectives.