Clinical feasibility of the preoperative C-reactive protein-albumin-lymphocyte index to predict short- and long-term outcomes of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a major leading cause of cancer-related death worldwide. Systemic inflammation and the nutrition-based score are feasible prognostic markers for malignancies. Emerging evidence has also revealed the C-reactive protein-albumin-lymphocyte (CALLY) index to be a prognostic marker for several cancer types. However, its clinical significance to predict surgical and oncologic outcomes of patients with GC remains unclear. METHODS: We assessed the preoperative CALLY index in 426 patients with GC who received gastrectomy. RESULTS: A low preoperative CALLY index was significantly correlated to all well-established clinicopathologic factors for disease development, including an advanced T stage, the presence of venous invasion, lymphatic vessel invasion, lymph node metastasis, distant metastasis, and an advanced TNM stage. A low preoperative CALLY index was also an independent prognostic factor for overall survival (hazard ratio [HR], 2.64; 95 % CI, 1.66-4.2; P < .0001) and disease-free survival (HR, 1.76; 95 % CI, 1.01-3.05; P = .045). In addition, a low preoperative CALLY index was an independent predictive factor for postoperative surgical site infection (odds ratio, 2.64; 95 % CI, 1.42-4.89; P = .002). CONCLUSION: The preoperative CALLY index is valuable for perioperative and oncologic management of patients with GC.

Prediction of Post-Gastrectomy Pancreatic Complications: A Preoperative Imaging Study Based on Computed Tomography.

BACKGROUND: Postoperative pancreas-related complications (PPRCs) are common after laparoscopic gastrectomy (LG) in patients with gastric cancer. We estimated the anatomical location of the pancreas on a computed tomography (CT) image and investigated its impact on the incidence of PPRCs after LG. METHODS: We retrospectively reviewed the preoperative CT images of 203 patients who underwent LG for gastric cancer between January 2010 and December 2017. From these images, we measured the gap between the upper edge of the pancreatic body and the root of the common hepatic artery. We evaluated the potential relationship between PPRCs and the gap between pancreas and common hepatic artery (GPC) status using an analysis based on the median cutoff value and assessed the impact of GPC status on PPRC incidence. We performed univariate and multivariate analyses to identify predictive factors for PPRC. RESULT: Postoperative pancreas-related complications occurred in 11 patients (5.4%). The median of the optimal cutoff GPC value for predicting PPRC was 0 mm; therefore, we classified the GPC status into two groups: GPC plus group and GPC minus group. Univariate analysis revealed that sex (male), C-reactive protein (CRP) > .07 mg/dl, GPC plus, and visceral fat area (VFA) > 99 cm2 were associated with the development of PPRC. Multivariate analysis identified only GPC plus as independent predictor of PPRC (hazard ratio: 4.60 [95% confidence interval 1.11-31.15], P = .034). CONCLUSION: The GPC is a simple and reliable predictor of PPRC after LG. Surgeons should evaluate GPC status on preoperative CT images before proceeding with laparoscopic gastric cancer surgery.

Clinical implications of C-reactive protein-albumin-lymphocyte (CALLY) index in patients with esophageal cancer.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory nutritional biomarker. This study aimed to investigate the potential clinical significance and oncological prognostic role of the preoperative CALLY index in patients with esophageal cancer. METHODS: We analyzed the preoperative CALLY index in 146 patients with esophageal cancer. The CALLY index and clinicopathological variables were analyzed by the Mann-Whitney U test, and associations between the CALLY index and survival outcomes were analyzed by Kaplan-Meier analysis and log-rank tests. Univariate and multivariate analyses of prognostic variables were conducted using Cox proportional hazards regression. RESULTS: A lower preoperative CALLY index was significantly correlated with patient age, advanced T stage, presence of lymph node metastasis, neoadjuvant therapy, lymphatic invasion, and advanced stage classification. The preoperative CALLY index decreased significantly in a stage-dependent manner. Patients with esophageal cancer with a low CALLY index had poorer overall survival, disease-free survival than those with a high CALLY index. Multivariate analysis showed that a low CALLY index was an independent prognostic factor for overall survival, disease-free survival and an independent predictor of postoperative surgical site infection. CONCLUSIONS: Preoperative CALLY index is a useful marker to guide the perioperative and postoperative management of patients with esophageal cancer.

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.

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-reaction protein x 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 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.

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases.

BACKGROUND: Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. CASE PRESENTATION: Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. CONCLUSION: DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery.

Robot-assisted laparoscopic abdominoperineal resection for anal canal cancer associated with Crohn's disease: A case report.

A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection.

[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.

Prognostic potential of METTL3 expression in patients with gastric cancer.

Methyltransferase-like 3 (METTL3) is a crucial component of the m6A methyltransferase complex, which serves pivotal roles in tumor progression. The present study investigated the prognostic significance of METTL3 expression in gastric cancer (GC). The expression levels of METTL3 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 158 patients with GC. Propensity score matching (PSM) analysis was performed to clarify its prognostic potential. METTL3 gene expression was also investigated in fresh frozen specimens from another independent cohort of 57 patients with GC to establish its clinical relevance. Knockdown of METTL3 by small interfering RNA transfection was performed to evaluate its function in vitro. METTL3 expression was significantly higher in cancerous tissues compared with in corresponding normal mucosa (P<0.0001), and high METTL3 expression was an independent prognostic factor for overall and disease-free survival in the FFPE cohort of patients with GC. PSM analysis revealed that elevated METTL3 expression was significantly associated with poor survival outcomes, which was subsequently validated in another cohort of fresh frozen specimens. Knockdown of METTL3 inhibited proliferation, invasion, migration and anoikis resistance in GC cells. In conclusion, METTL3 expression may be used as a clinically feasible prognostic marker and could serve as a potential therapeutic target in patients with GC.

Combined assessment of muscle quality and quantity predicts oncological outcome in patients with esophageal cancer.

BACKGROUND: Sarcopenia consists of two dysregulation patterns of body composition, myopenia and myosteatosis. The aim of this study is to compare the preoperative status of various body composition indexes including our newly developed modified intramuscular adipose tissue content (mIMAC) to investigate these clinical values in esophageal cancer patients. METHOD: We assessed preoperative psoas muscle mass index (PMI), IMAC, and mIMAC in 150 esophageal cancer patients. RESULTS: Preoperative high IMAC and low mIMAC status were significantly associated with older age. Preoperative decreased mIMAC was significantly associated with advanced T classification and the presence of distant metastasis and low preoperative mIMAC was an independent prognostic factor for poor overall survival and disease-free survival in esophageal cancer patients. Combined assessment of preoperative mIMAC with PMI could help stratify risk for oncological outcomes. Finally, preoperative PMI and mIMAC were positively correlated with various nutritional factors in esophageal cancer patients. CONCLUSION: Combined assessment between preoperative PMI and mIMAC could stratify risk for oncological outcomes, and preoperative mIMAC might be surrogate marker for aging and nutritional status in esophageal cancer patients.

[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.

Clinical utility of lymphocyte to C-reactive protein ratio in predicting survival and postoperative complication for esophago-gastric junction cancer.

BACKGROUND: There are still no useful predictive biomarkers for esophago-gastric junction (EGJ) cancer. We compared 15 candidate inflammation-based markers and investigated the clinical impact of the selected biomarker. METHODS: One hundred three patients with EGJ cancer between 2002 and 2020 were enrolled, and associations between clinicopathological data and inflammatory biomarkers were retrospectively analyzed. Area under the curve (AUC) values of 15 candidate biomarkers were compared in receiver operating characteristic (ROC) curves regarding overall survival (OS). Clinical impacts of the selected marker were further investigated regarding long-term prognosis, postoperative complications, and preoperative chemotherapy effects. RESULTS: Lymphocyte/CRP ratio (LCR) demonstrated the highest AUC (0.68552) and was chosen as a candidate biomarker. The high LCR group (LCR >4610) demonstrated significantly better OS (p < 0.0001) and relapse-free survival (RFS) (p < 0.0001) compared with the low LCR group (LCR ≤4610), and preoperative LCR was an independent prognostic factor for both OS (HR 4.97, 95% CI:2.24-11.58; p < 0.0001) and RFS (HR 2.84, 95% CI:1.33-6.14, p = 0.007) in EGJ cancer patients. Another cut-off value was established for postoperative complications, and the incidence rates were significantly higher in the low LCR group (LCR ≤12000) than in the high LCR group (LCR >12000) for all postoperative complications, infectious complications, and surgical site infection (p = 0.013, p = 0.016, and p = 0.030, respectively). Furthermore, patients with decreased LCR after preoperative chemotherapy demonstrated significantly worse RFS compared with patients with increased LCR (p = 0.043). CONCLUSIONS: LCR is a potential biomarker to predict long-term prognosis as well as occurrence of postoperative complications in patients with EGJ cancer.

Prognostic significance of CD8+ tumor-infiltrating lymphocytes and CD66b+ tumor-associated neutrophils in the invasive margins of stages I-III colorectal cancer.

Tumor-infiltrating immune cells play an essential role in cancer progression and may help supplement the Tumor, Node, Metastasis (TNM) classification for cancer prognosis. Currently, there are numerous conflicting reports discussing the significance of tumor-associated neutrophils (TANs) in colorectal cancer (CRC). In particular, the role of TANs in the invasive margin is unclear. The present study investigated the prognostic significance of CD66+ TANs and CD8+ tumor-infiltrating lymphocytes (TILs) in the invasive margin of 103 patients with CRC. By using immunohistochemistry, survival analysis was performed on CD8+ TILs and CD66+ TANs individually, as well as models including TILs and TANs simultaneously. The findings indicated that the densities of CD8+ TILs and CD66b+ TANs in the invasive margin may provide significant prognostic value for predicting survival. Moreover, the combined evaluation of CD8+ TILs and CD66b+ TANs in the invasive margin could further improve the validity for the prediction of oncological outcomes. In addition, multivariate analysis revealed that simultaneous low tumor infiltration by CD8+ TILs and CD66b+ was an independent predictive factor for overall survival (HR=4.17, 95% CI, 1.55-12.5; P=0.004) and disease-free survival (HR=2.75, 95% CI, 1.27-6.12; P=0.01). Given the importance of CD8+ TILs and CD66b+ TANs in the tumor microenvironment, the assessment of their densities in the invasive margin may serve as a valuable prognostic marker for CRC.

Clinical Relevance of Myopenia and Myosteatosis in Colorectal Cancer.

Sarcopenia was initially described as a decrease in muscle mass associated with aging and subsequently also as a consequence of underlying disease, including advanced malignancy. Accumulating evidence shows that sarcopenia has clinically significant effects in patients with malignancy, including an increased risk of adverse events associated with medical treatment, postoperative complications, and a poor survival outcome. Colorectal cancer (CRC) is one of the most common cancers worldwide, and several lines of evidence suggest that preoperative sarcopenia negatively impacts various outcomes in patients with CRC. In this review, we summarize the current evidence in this field and the clinical relevance of sarcopenia in patients with CRC from three standpoints, namely, the adverse effects of medical treatment, postoperative infectious complications, and oncological outcomes.

TPX2 is a prognostic marker and promotes cell proliferation in neuroblastoma.

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is upregulated in various tumors, and several studies have demonstrated the role of TPX2 as a prognostic marker in cancer. However, the function of TPX2 in neuroblastoma (NB) has not been completely elucidated. In the present study, the clinical significance and functional role of TPX2 in NB was investigated. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-NB dataset was used. A total of 43 patients with NB were enrolled in the present study as the validation set. After evaluating the prognostic role of TPX2, the combined predictive effect of TPX2 and MYCN proto-oncogene bHLH transcription factor (MYCN) gene amplification was assessed. Double immunofluorescence staining for TPX2 and N-Myc was used to analyze colocalization, and multiple cell function tests were performed by means of in vitro experiments to elucidate the functional role of TPX2 using RNA interference technology in NB cell lines. In both the TARGET-NB set and the validation set, it was found that upregulated of TPX2 was significantly associated with poor overall survival (OS) in patients with NB. The expression of TPX2 was higher in NB patients with MYCN gene amplification, and NB patients with high TPX2 expression and MYCN gene amplification had the poorest OS compared with patients with low TPX2 expression or a single copy of MYCN. In vitro experiments indicated that TPX2 positively regulated cell proliferation and the cell cycle, and promoted cell survival by increasing the resistance to apoptosis. The colocalization of TPX2 with N-Myc in NB cells and tissue was observed. The findings of the present study indicate that TPX2 plays an oncogenic role in NB development and may be a potential prognostic indicator in patients with NB.

[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 C-reactive Protein in the Perioperative Period as a Novel Marker for Oncological Outcome in Patients with Colorectal Cancer Undergoing Curative Resection.

OBJECTIVES: Systemic inflammatory response is strongly associated with poor oncological outcome in colorectal cancer (CRC). Perioperative inflammation caused by surgical stress can lead to the development of postoperative infectious complications (PIC) as well as cancer-related inflammation. We aimed to evaluate the prognostic potential of perioperative systemic inflammation by calculating the time-dependent cumulative C-reactive protein (CRP) levels during the perioperative period. METHODS: We analyzed clinicopathological data from 540 patients with CRC who underwent potentially curative surgery at our institution. The time-dependent aggregated CRP level was denoted "cumulative CRP," which represents the area under the line of time (days) and the CRP levels preoperatively and on postoperative days 1, 3, and 7. RESULTS: Cumulative CRP was significantly higher in patients with CRC undergoing open surgery than in patients undergoing laparoscopic surgery. In multivariate analysis, high cumulative CRP was an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in both the laparoscopic and open surgery groups. Patients with CRC and high cumulative CRP had significantly poorer DFS and OS than those with low cumulative CRP, including those patients without PIC. CONCLUSIONS: Cumulative CRP is an independent predictive marker of OS and DFS in patients with CRC who undergo curative surgery.

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.

Downregulation of trefoil factor-3 expression in the rectum is associated with the development of ulcerative colitis-associated cancer.

Diagnostic markers facilitate more selective screening and treatment strategies for ulcerative colitis (UC)-associated cancer (UCAC). The expression of trefoil factor-3 (TFF3), which is involved in mucosal protection and repair in the gastrointestinal tract, was analyzed and its significance for UCAC was evaluated. A total of 145 patients with UC who underwent proctocolectomies were enrolled, including 15 patients (10.8%) with UCAC. TFF3 expression in the rectal mucosa and in cancer cells was assessed using immunohistochemistry, and the expression in UCAC and sporadic colorectal cancer was compared. Analyzing the mucinous granules of goblet cells located in crypts revealed that the non-cancerous rectal mucosa of patients with UCAC had significantly lower mean TFF3 staining scores compared with patients with UC without UCAC or patients with sporadic cancer. TFF3 staining score was revealed to be an independent predictor of UCAC development. These results indicated that low TFF3 expression in the rectal mucosa was associated with the development of UCAC. Thus, TFF3 expression in the rectal mucosa may be a useful biomarker for monitoring patients with UC.

Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer.

Colony­stimulating­factor­1 (CSF­1) is a hematopoietic growth factor that exerts its effects through the c­fms/CSF­1 receptor (CSF­1R). The CSF­1/CSF­1R axis is thought to be involved in the development of several types of cancer. This study aimed to clarify the clinical and biological significance of the CSF­1/CSF­1R axis in gastric cancer (GC). For this purpose, we evaluated CSF­1 and CSF­1R expression in GC tissues from 148 patients by RT­qPCR and immunohistochemistry. The biological roles of the CSF­1/CSF­1R axis were investigated by measuring the cell proliferation and migration, and anoikis resistance in a human GC cell line following treatment with recombinant human CSF­1 and/or CSF­1R inhibitor. The results revealed that an elevated expression of CSF­1 or CSF­1R significantly correlated with disease progression and with a poor overall survival (OS, P=0.037 and 0.016, respectively) and disease­free survival (DFS, P<0.001 and <0.001, respectively) of patients with GC. Furthermore, a high co­expression of CSF­1 and CSF­1R was an independent prognostic factor for OS (HR, 1.38; 95% CI, 1.02­1.88; P=0.038) and DFS (HR, 1.79; 95% CI, 1.21­2.67; P=0.004), and an independent risk factor for lymph node and peritoneal metastasis. Immunohistochemical analysis revealed an intense CSF­1/CSF­1R expression in the cytoplasm of cancer cells in primary GC tissues. CSF­1 or CSF­1R expression positively correlated with vascular endothelial growth factor A (VEGFA) or Fms related tyrosine kinase 1 (FLT1) expression in GC tissues. Treatment with recombinant human CSF­1 promoted proliferation, migration and anoikis resistance in a GC cell line. These effects were generally blocked by CSF­1R inhibition. On the whole, the findings of this study indicate that the CSF­1/CSF­1R axis may be a clinically useful prognostic and predictive biomarker for lymph node and peritoneal metastasis and a potential therapeutic target in GC.