Clinical Significance of the Preoperative Inflammatory Burden Index in Esophageal Cancer.

INTRODUCTION: The inflammatory burden index (IBI) serves as a prognostic marker for several cancers. Here, we evaluated the predictive value of preoperative IBI associated with the surgical and oncological outcomes of patients with esophageal cancer (EC). METHODS: The IBI was formulated as C-reactive protein × neutrophil/lymphocyte. We retrospectively analyzed preoperative IBI of 147 EC patients receiving esophagectomy between 2008 and 2018. Cox proportional hazards models and multivariable logistic regression were employed to identify independent risk factors of surgical site infection and prognosis. RESULTS: Increased preoperative IBI significantly correlated with higher tumor stage. Patients with high IBI experienced shorter overall survival (p = 0.0002) and disease-free survival (p = 0.002) compared with those with low IBI. In the adjusted Cox proportional hazards regression models, increased IBI served as an independent prognostic factor for overall survival (hazard ratio, 3.56; 95% confidence interval, 1.79-7.34; p = 0.0003) and disease-free survival (hazard ratio, 3.03; 95% confidence interval, 1.60-5.92; p = 0.007). Multivariable analysis identified preoperative high IBI which served as an independent risk factor for overall surgical site infection (odds ratio, 2.53; 95% confidence interval, 1.00-6.38; p = 0.049). CONCLUSION: Preoperative IBI may serve as a useful predictor of prognosis and surgical site infection of patients with EC after esophagectomy.

Robotic versus open and laparoscopic pelvic exenterations for pelvic cancer: a multicenter propensity-matched analysis in Japan.

BACKGROUND: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. METHODS: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. RESULTS: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien-Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). CONCLUSION: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors.

Promoter methylation levels of microRNA-124 in non-neoplastic rectal mucosa as a potential biomarker for ulcerative colitis-associated colorectal cancer in pediatric-onset patients.

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.

[Stage â £ Gastric Cancer with Long Term Survival by Conversion Surgery-A Case Report].

A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.

[A Case Report of Organ Preservation by Total Neoadjuvant Therapy and Local Excision for Lower Rectal Cancer].

In our department, total neoadjuvant therapy(TNT), which is a combination of preoperative chemotherapy and preoperative chemoradiotherapy(nCRT), has been introduced for the purpose of local and systemic disease control for lower rectal cancer. For patients in whom a clinical complete response(cCR)was obtained by TNT, we avoid the surgery and preserve organs, and follow-up strictly under the informed consent(watch and wait). In addition, for patients with remarkably reduced primary lesions(near cCR)without lymphadenopathy after TNT, the option of omitting total mesorectal excision (TME)and performing organ preservation by local excision can be introduced. Here, we report a case in which near cCR was obtained by TNT and organ preservation was performed by local excision. A 67-year-old man with lower rectal cancer(AV 5 cm, 15 mm, type 2, cT2N0M0, cStage Ⅰ)was referred to our department with a desire to preserve the anus. TNT with nCRT→CAPOX was performed, and near cCR was obtained. After that, full thickness local excision of the residual disease was performed by transanal minimally invasive surgery(TAMIS). The final pathological diagnosis was Rb, 0.7 mm, por2, ypT1a, ypPM0, ypDM0, ypRM0. No recurrence is recognized for 3 years and 10 months after the operation.

[The Watch and Wait Strategy for Lower Rectal Cancer Patients Who Achieved Clinical Complete Response after Chemotherapy to Treat Inguinal Lymph Node Metastasis following Total Neoadjuvant Therapy-A Case Report].

The watch and wait strategy(W&W)is optional non-operative management for lower advanced rectal cancer patients who have achieved clinical complete response(cCR)following neoadjuvant treatment. However, the clinical implication of surgical intervention for the primary lesion is not well elucidated when distant metastasis appears with complete remission of the primary lesion. We report a case of a 47-year-old-woman with lower rectal cancer presenting inguinal lymph node metastasis after total neoadjuvant therapy(TNT)and managed through W&W after achieving cCR following chemotherapy. TNT was performed as a preoperative treatment for lower advanced rectal cancer, cT3N2aM0, cStage Ⅲb. Although the primary lesion and mesenteric lymph node metastasis completely disappeared, bilateral inguinal lymph node metastasis appeared immediately after TNT. The patient was treated with FOLFOX plus panitumumab for rectal cancer with RAS and BRAF wild-type. Four months after chemotherapy, the inguinal lymph node metastasis disappeared, and W&W was used for the management. She stayed alive without recurrence 1 year and 9 months after chemotherapy.

Cumulative perioperative lymphocyte/C-reactive protein ratio as a predictor of the long-term outcomes of patients with colorectal cancer.

PURPOSE: Systemic inflammatory response influences cancer development and perioperative surgical stress can affect the survival of patients with colorectal cancer (CRC). We developed a system to cumulatively assess perioperative inflammatory response and compare the prognostic value of various cumulative inflammatory and nutritional markers in patients with CRC. METHODS: We assessed perioperative cumulative markers using the trapezoidal area method in 307 patients who underwent surgery for CRC and analyzed the results statistically. RESULTS: The cumulative lymphocyte to C-reactive protein (CRP) ratio (LCR) predicted survival more accurately than other well-established markers (sensitivity: 80.0%, specificity: 69.3%; area under the curve (AUC): 0.779; P < 0.001). A low cumulative LCR was correlated with factors associated with disease development, including undifferentiated histology, advanced T stage, lymph node metastasis, distant metastasis, and advanced TNM stage classification. A decreased cumulative LCR was an independent prognostic factor for both overall survival (OS) (Hazard Ratio (HR):5.21, 95% confidence interval [CI] 2.42-11.2; P < 0.0001) and disease-free survival (DFS) (HR: 1.88, 95% CI 1.07-3.31; P = 0.02), and its prognostic significance was verified in a different clinical setting. The cumulative LCR was correlated negatively with the intraoperative bleeding volume (P < 0.0001, R = -0.4). Combined analysis of cumulative and preoperative LCR could help stratify risk for the oncological outcomes of CRC patients. CONCLUSIONS: The findings of this study demonstrate the value of the cumulative LCR in the postoperative management of patients with CRC.

The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis.

BACKGROUND: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. AIM: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. METHODS: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. RESULTS: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). CONCLUSION: IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Modified Martius flap procedure for refractory ileal pouch-vestibular fistula: a report of three cases.

PURPOSE: Pouch-vaginal or vestibular fistula is an uncommon, but devastating complication that occurs in women after ileal J pouch-anal anastomosis. The management of these fistulae is challenging, and it is associated with high recurrence and pouch loss rates. This report describes the use of the modified Martius flap procedure for three patients with ulcerative colitis who developed refractory pouch-vestibular fistulae. RESULTS: Three patients with ulcerative colitis, who underwent total colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis, developed pouch-vestibular fistulae. The fistulae originated in the pouch-anal anastomosis site in all three cases. We performed fistulectomy and transvaginal closure with sphincteroplasty followed by the modified Martius flap procedure under diversion ileostomy. No complications occurred after ileostomy closure, and the postoperative anal function was good. CONCLUSION: The modified Martius flap procedure is among the best options for patients with ulcerative colitis who develop refractory pouch-vestibular fistula as a complication of mucosal proctectomy.

Impact of sarcopenia on surgical site infection after restorative proctocolectomy for ulcerative colitis.

PURPOSE: The coexistence of sarcopenia is associated with postoperative complications, including infection after abdominal surgery. We evaluated the association between sarcopenia and surgical site infection (SSI) after surgery for ulcerative colitis. METHODS: The subjects of this retrospective study were 69 patients who underwent restorative proctocolectomy with perioperative abdominal computed tomography (CT). Sarcopenia was diagnosed by measuring the cross-sectional area of the right and left psoas muscles as the total psoas muscle area on CT images. We assessed whether sarcopenia was associated with SSI and clinical factors, including nutritional and inflammatory markers. RESULTS: The lowest quartiles defined as sarcopenia in men and women were 567.4 and 355.8 mm2/m2, respectively. According to this classification, 12 men and 6 women had sarcopenia. Patients with sarcopenia had a lower body mass index (p = 0.0004) and a higher C-reactive protein concentration (p = 0.05) than those without sarcopenia. SSIs were identified in 12 patients (17.3 %) and included six pelvic abscesses and seven wound infections. According to multivariate analysis, sarcopenia was an independent risk factor for SSI (odds ratio = 4.91, 95 % confidence interval 1.09-23.5, p = 0.03). CONCLUSION: Sarcopenia is predictive of SSI after pouch surgery for ulcerative colitis.

Outcome and functional prognosis of pelvic sepsis after ileal pouch-anal anastomosis in patients with ulcerative colitis.

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure for ulcerative colitis, but pouch failure or pelvic sepsis still occurs in some patients. We conducted this study to investigate the cause of pouch failure and evaluate defecatory function after pelvic sepsis. METHODS: A total of 234 patients who underwent restorative proctocolectomy were enrolled. We analyzed the cause of pouch failure, as well as defecatory function and manometric outcomes, with and without the complication of pelvic sepsis. RESULTS: Pelvic sepsis developed in 29 (12.3%) of the 234 patients who underwent restorative proctocolectomy (pelvic sepsis group). The pelvic sepsis led to pouch failure in two of these patients (as a vaginal fistula in one and ileo-anal anastomotic leakage in one). Of the remaining majority of patients who did not suffer pelvic sepsis (control group), nine suffered pouch failure (as vaginal fistula in four, perianal abscess in two, pouch-spinal marrow fistula in one, and chronic pouchitis in two). There were no significant differences in defecatory function or manometric outcomes between the two groups. In the pelvic sepsis group, stool frequency was significantly correlated with white blood cell count (P = 0.01) and the duration until onset of pelvic sepsis (P < 0.01). CONCLUSIONS: Pelvic sepsis after restorative proctocolectomy for ulcerative colitis does not affect defecatory and manometric function, but control of the inflammation caused by pelvic sepsis is integral for defecatory function.

Elevated serum concentration of monocyte chemotactic protein 4 (MCP-4) as a novel non-invasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer.

PURPOSE: Despite recent progress in the diagnosis and treatment of colorectal cancer (CRC), the prognosis remains poor, and metastatic recurrence is the leading cause of poor prognosis. We systemically evaluated the levels of differentially-expressed serum cytokines using array-based techniques to identify a novel and reliable serum biomarker with which to predict metastasis and poor outcomes of CRC. METHODS: We examined cytokine profiling using preoperative serum from two different cohorts to identify differentially-expressed serum cytokines in patients with metastatic CRC. In the validation phase, serum monocyte chemotactic protein-4 (MCP-4) concentration was assessed in 194 patients by enzyme-linked immunosorbent assay, and its relationships with clinicopathological findings were investigated. RESULTS: In discovery phase, three cytokines were differentially expressed in serum from patients with metastatic CRC. In validation phase, high MCP-4 was significantly associated with older age, advanced T stage, distant metastasis, and UICC stage. Cox regression analysis showed that elevated MCP-4 was an independent prognostic factor of disease-free survival and overall survival. Furthermore, logistic regression analysis revealed that high serum MCP-4 was an independent predictor of distant metastasis. CONCLUSION: Quantification of serum MCP-4 concentration might support the early detection/prediction of recurrence and may contribute to the prediction of clinical outcomes in CRC. J. Surg. Oncol. 2016;114:483-489. © 2016 Wiley Periodicals, Inc.

Prognostic relevance of stromal CD26 expression in rectal cancer after chemoradiotherapy.

BACKGROUND: CD26 is a transmembrane glycoprotein whose role in various types of malignancies, along with the potential therapeutic and diagnostic targets, has been evaluated. Preoperative chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the rate of disease recurrence remains high. The aim of this study was to clarify the association between CD26 expression and rectal cancer after preoperative CRT. METHODS: A total of 85 patients with rectal cancer who had undergone preoperative CRT were enrolled in this study. We investigated CD26 expression in residual tumors and the surrounding stromal tissue using immunohistochemistry. Additionally, stromal CD26 gene expression was assessed by real-time quantitative polymerase chain reaction. RESULTS: Patients with high CD26 expression in cancer tissue more frequently had serosal invasion, vascular invasion, and a poor pathological response. High expression of CD26 in the tumor stroma was significantly correlated with histology and tumor recurrence. High CD26 expression in the stroma, but not the tumor itself, was significantly correlated with a poor prognosis. Patients expressing CD26 in the tumor stroma, based on transcriptional analysis, also had a significantly poorer prognosis than those without the expression. In multivariate analysis, lymph node metastasis and high stromal CD26 expression were identified as independent prognostic factors in patients with rectal cancer after neoadjuvant CRT. CONCLUSION: Stromal CD26 expression after preoperative CRT was significantly associated with tumor recurrence and prognosis in rectal cancer patients. Our data suggest that stromal CD26 plays an important role and is a potential therapeutic target in tumor relapse.

Implication of programmed cell death ligand 1 expression in tumor recurrence and prognosis in rectal cancer with neoadjuvant chemoradiotherapy.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) regulates immune responses through interaction with its receptor. PD-L1 is not only a predictor of poor prognosis but also a new therapeutic target in several malignancies. Neoadjuvant chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the disease recurrence rate remains high. The aim of this study was to retrospectively evaluate the correlation between PD-L1 expression and clinicopathological variables in rectal cancer after neoadjuvant CRT. MATERIALS AND METHODS: A total of 90 rectal cancer patients who underwent neoadjuvant CRT were enrolled in this study. We evaluated PD-L1 expression using immunohistochemistry. Moreover, we investigated the correlation between PD-L1 expression and tumor-infiltrating T cells, and between CD8- and Foxp3-positive cells. RESULTS: Patients with high PD-L1 expression more frequently had vascular invasion and tumor recurrence compared to patients with low PD-L1 expression (P = 0.0225 and P = 0.0051). High PD-L1 expression was significantly associated with poor recurrence-free and overall survival (P = 0.0027 and P = 0.0357). Multivariate analysis revealed lymph node metastasis and high PD-L1 expression as independent risk factors for tumor recurrence (P = 0.0102 and P = 0.0374). Numbers of infiltrating CD8-positive cells in patients with high PD-L1 expression were significantly lower than in patients with low PD-L1 expression (P = 0.0322). CONCLUSION: Our data suggest that inhibition of PD-L1 may be a new immunotherapeutic strategy to reduce tumor recurrence and improve prognosis in patients with rectal cancer after neoadjuvant CRT.

Secondary pouchitis in a pediatric patient successfully treated by salvage surgery.

Apart from primary pouchitis, patients with secondary pouchitis caused by surgical complications require surgical management. The use of abdomino-anal salvage surgery to treat secondary pouchitis caused by surgical complications in pediatric patients with ulcerative colitis (UC) has not been reported in detail. A girl was diagnosed with UC at 8 years old. She underwent restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at 9 years old. She presented at 12 years old because of chronic antibiotic-refractory pouchitis. The fistula and stricture failed to improve despite multiple local salvage surgeries and ileostomy construction. At 15 years old, she underwent redo IPAA. The patient was well at 20 years old with no signs of pouchitis. Early treatment by abdomino-anal salvage surgery might be indicated to improve quality of life in pediatric patients with secondary pouchitis caused by surgical complication unresponsive to defunctioning and local salvage surgery.

Clinical features and management of afferent limb syndrome after ileal pouch-anal anastomosis for ulcerative colitis.

PURPOSE: Afferent limb syndrome (ALS) is a type of small bowel obstruction (SBO) caused by obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis (IPAA). The aim of this study was to reveal the clinical features and management of ALS. METHODS: Of 320 patients undergoing IPAA for ulcerative colitis, we analyzed data from patients presenting with SBO. RESULTS: Six of 19 patients with SBO were diagnosed with ALS. All patients with ALS presented with recurrent intermittent obstructive symptoms before admission, whereas 15 % of patients without ALS presented with these symptoms (P < 0.0005). Among the six patients with ALS, four patients required surgery, although they underwent transanal decompression for each episode of obstruction. The proportion of surgery was higher in the ALS group (P < 0.01). Acute angulation of the afferent limb was recognized in four cases and followed by fixation of the afferent limb. No further surgery was required in any patient following the last fixation. CONCLUSIONS: SBO after IPAA may be caused by acute angulation of the afferent limb of the ileal J-pouch. Most patients with ALS may eventually require fixation of the afferent limb due to acute angulation of the afferent limb.

RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer.

Rac GTPase-activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration and metastasis. This study investigated the function and clinical significance of RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time PCR. Finally, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa and increased according to tumor node metastasis stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.

Angiopoietin-Like Protein 2 Acts as a Novel Biomarker for Diagnosis and Prognosis in Patients with Esophageal Cancer.

BACKGROUND: Angiopoietin-like protein 2 (ANGPTL2) mediates chronic inflammation. Tumor cell-derived ANGPTL2 promotes tumor invasion and angiogenesis. Overexpression of ANGPTL2 in tumor cells is associated with tumor progression and has been recognized in lung, breast, colon, and gastric cancer. However, to our knowledge the functional and clinical significance of ANGPTL2 expression has not been investigated in patients with esophageal cancer (EC). METHODS: First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA. Next, ANGPTL2 expression in EC tissues (n = 71) was evaluated by immunohistochemistry (IHC in patients with EC (n = 71). Finally, serum ANGPLT2 levels from patients with EC (n = 71) and healthy controls (n = 35) were evaluated using enzyme-linked immunosorbent assay. RESULTS: Knockdown of ANGPTL2 expression decreased the proliferative, invasive, and migration capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in patients with a high T stage, squamous cell carcinoma, and high TNM stage. Patients with high ANGPTL2 expression had significantly poorer overall and disease-free survival than those with low expression. Furthermore, high ANGPTL2 expression in EC tissues was an independent predictive marker for a poor prognosis. On the other hand, the serum ANGPTL2 level in patients with EC was significantly higher than that in healthy controls, and allowed for highly accurate discrimination between patients with and without EC. However, no significant association between serum ANGPTL2 levels and clinicopathological findings was observed in patients with EC. CONCLUSIONS: We have demonstrated novel evidence for the clinical significance of ANGPTL2 as a biomarker in patients with EC.

FK506-Binding Protein 5 mRNA Levels in Ileal Mucosa Are Associated with Pouchitis in Patients with Ulcerative Colitis.

BACKGROUND: Although the pathogenesis of pouchitis is incompletely understood, steroid and FK506 therapy are significantly associated with pouchitis. These medical treatments are regulated by the FK506-binding protein (FKBP) 4 and FKBP5 genes. AIM: This study aimed to evaluate the relationship between pouchitis and FKBP4 and FKBP5 mRNA expression in ileal mucosa at the time of colectomy. METHODS: Ileal mucosa specimens were collected from 71 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis. FKBP4 and FKBP5 mRNA expression was evaluated. The relationship between mRNA expression and clinicopathological factors, including developed pouchitis, was investigated. RESULTS: Of these 71 patients, 25 (35.2 %) patients developed pouchitis in a mean duration of 20.2 months (range 0-68 months). FKBP4 mRNA levels in patients who received an immunomodulator were significantly higher than those in untreated patients (0.167 ± 0.060 vs 0.131 ± 0.065, p = 0.009). However, FKBP5 mRNA levels in patients who received a three-stage operation were significantly lower than those in the other patients (1.97 ± 1.15 vs 2.70 ± 1.12, p = 0.02). A total dose of prednisolone >9.4 g (HR 2.84, p = 0.02) before colectomy and FKBP5 mRNA level higher than the median (HR 4.49, p = 0.01) were identified as factors related to pouchitis. CONCLUSIONS: FKBP5 mRNA levels in ileal mucosa at the time of colectomy are significantly associated with pouchitis and may be a predictive factor for developing pouchitis.