Prediction of the differences in tumor mutation burden between primary and metastatic lesions by radiogenomics.

Tumor mutational burden (TMB) is gaining attention as a biomarker for responses to immune checkpoint inhibitors in cancer patients. In this study, we evaluated the status of TMB in primary and liver metastatic lesions in patients with colorectal cancer (CRC). In addition, the status of TMB in primary and liver metastatic lesions was inferred by radiogenomics on the basis of computed tomography (CT) images. The study population included 24 CRC patients with liver metastases. DNA was extracted from primary and liver metastatic lesions obtained from the patients and TMB values were evaluated by next-generation sequencing. The TMB value was considered high when it equaled to or exceeded 10/100 Mb. Radiogenomic analysis of TMB was performed by machine learning using CT images and the construction of prediction models. In 7 out of 24 patients (29.2%), the TMB status differed between the primary and liver metastatic lesions. Radiogenomic analysis was performed to predict whether TMB status was high or low. The maximum values for the area under the receiver operating characteristic curve were 0.732 and 0.812 for primary CRC and CRC with liver metastasis, respectively. The sensitivity, specificity, and accuracy of the constructed models for TMB status discordance were 0.857, 0.600, and 0.682, respectively. Our results suggested that accurate inference of the TMB status is possible using radiogenomics. Therefore, radiogenomics could facilitate the diagnosis, treatment, and prognosis of patients with CRC in the clinical setting.

Presence of serum RalA and serum p53 autoantibodies in 1833 patients with various types of cancers.

BACKGROUND: RalA is a member of the Ras superfamily of small GTPases. The Anti-RalA autoantibodies (s-RalA-Abs) act as tumor markers in various types of cancer and are negatively associated with the p53 autoantibodies (s-p53-Abs). This study aimed to evaluate the relationship between s-RalA-Abs and s-p53-Abs in various types of cancer. METHODS: A total of 1833 cancer patients (esophageal cancer, 172; hepatocellular carcinoma, 91; lung cancer, 269; gastric cancer, 317; colon cancer, 262; breast cancer, 364; and prostate cancer, 358) and 73 healthy subjects were enrolled in the study. The levels of s-RalA-Abs and s-p53-Abs were analyzed using enzyme-linked immunosorbent assay, and the positivity rates and relations between the two autoantibodies were evaluated. The cutoff values for s-RalA abs and s-p53 abs were set as mean + 2 standard deviation and the values higher than the cutoff values were defined as positive. RESULTS: The titers in all cancer types were significantly higher than those in the controls (P < 0.01). The positivity rates for s-RalA-Abs ranged between 11.7 and 21.5%, and those for s-p53-Abs ranged between 12 and 28.5%. A combined assay of the two antibodies revealed positivity rates of 20.9 and 44.2%. In Stage 0/I/II tumors, the positivity rates of the combination of the two antibodies ranged between 21.5 and 42.3%. The two autoantibodies were complementary to each other in the prostate and breast cancers, but independent in other carcinomas. CONCLUSION: The combined use of s-RalA-Abs and s-p53-Abs tended to increase the positivity rate in all cancers, including Stage 0/I/II cancers.

Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society.

BACKGROUND: Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). METHODS: Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. RESULTS: In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003). CONCLUSIONS: CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.

Efficacy of thoracotomy and thoracoscopic-assisted esophageal surgery in conversion and salvage surgeries: a retrospective study.

BACKGROUND: The esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient's prognosis. METHODS: Patients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated. RESULTS: A total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy. CONCLUSIONS: In this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy. TRIAL REGISTRATION: This was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

The usefulness of microRNA in urine and saliva as a biomarker of gastroenterological cancer.

MicroRNA (miR) is a type of short non-coding RNA comprising 21-25 nucleotides. While it has been researched widely, its relationship with cancer was clarified recently and it was found to play a significant role in the development and progression of cancer. Furthermore, miR can remain stable for relatively long periods in the blood by being present in exosomes (extracellular microvesicles) or by forming a complex with the Ago2 protein, which gives rise to cancer-specific miR. It is known that miR can indicate the presence and extent of cancer progression. Several reports have proved that miR in urine and saliva is detected in urinary and oral cancer, respectively, and recent studies have also shown it to be present in cases of gastroenterological cancer, showing evidence of it being a biomarker for cancer. To gather further knowledge on this topic, this review aims to summarize the usefulness of urinary and salivary miR as a biomarker for gastroenterological cancer and discuss its existence, stability mechanism, and direction of future research. The findings will be relevant for physicians and oncologists who routinely treat patients with gastric cancers.

[A Study of Laparoscopic Stoma Creation for Patients with Colorectal Cancer].

There are few reports on laparoscopic stoma creation; we report here our experience with laparoscopic stoma creation. PATIENTS AND METHODS: Seven patients who underwent laparoscopic stoma creation between April 2019 and December 2019 were studied and their clinical outcome was evaluated retrospectively. Operation approach: We performed a colostomy in the transverse colon. At first, we insert a 12 mm first port into the site of stoma marking. And more, we insert three 5 mm ports on the opposite side of the first port. We remove the adhesions of the intestinal tract and create a colostomy. RESULT: We changed open method 2 cases out of 7 cases due to extensive adhesion. In laparoscopically, we had an operation time of 97 (42-130) minutes and a blood loss of 5(2-40) mL. We had no postoperative complications or stoma problems. CONCLUSION: Laparoscopic stoma creation was useful due to few postoperative complications and can be rapidly transferred to chemotherapy.

[Intracorporeal Anastomosis in Laparoscopic Colectomy with Blood Flow Confirmation by Fluorescence Angiography].

We verified the significance of intestinal blood flow evaluation by indocyanine green(ICG)fluorescence during intracorporeal anastomosis in laparoscopic colectomy which was performed from July 2019 to December 2019 in our institute. For 11 cases of intracorporeal anastomosis, we examined the patient background, surgical results such as operation time and blood loss, evaluation of intraoperative ICG blood flow, and perioperative complications. In all cases, after the mesentery treatment in the abdominal cavity and before the intestinal incision, the blood flow of the planned anastomosis site was evaluated by ICG fluorescence observation. No cases were required to be changed the anastomosis site. The average operation time was 240 minutes and the average blood loss was 10 mL. There were no perioperative complications such as anastomotic leakage, stenosis, bleeding, nor wound infection. It was suggested that the intraoperative evaluation of ICG blood flow during intracorporeal anastomosis in laparoscopic colectomy may contribute to the suppression of complications such as anastomotic leakage.

Radiogenomics for predicting p53 status, PD-L1 expression, and prognosis with machine learning in pancreatic cancer.

BACKGROUND: Radiogenomics is an emerging field that integrates "Radiomics" and "Genomics". In the current study, we aimed to predict the genetic information of pancreatic tumours in a simple, inexpensive, and non-invasive manner, using cancer imaging analysis and radiogenomics. We focused on p53 mutations, which are highly implicated in pancreatic ductal adenocarcinoma (PDAC), and PD-L1, a biomarker for immune checkpoint inhibitor-based therapies. METHODS: Overall, 107 patients diagnosed with PDAC were retrospectively examined. The relationship between p53 mutations as well as PD-L1 abnormal expression and clinicopathological factors was investigated using immunohistochemistry. Imaging features (IFs) were extracted from CT scans and were used to create prediction models of p53 and PD-L1 status. RESULTS: We found that p53 and PD-L1 are significant independent prognostic factors (P = 0.008, 0.013, respectively). The area under the curve for p53 and PD-L1 predictive models was 0.795 and 0.683, respectively. Radiogenomics-predicted p53 mutations were significantly associated with poor prognosis (P = 0.015), whereas the predicted abnormal expression of PD-L1 was not significant (P = 0.096). CONCLUSIONS: Radiogenomics could predict p53 mutations and in turn the prognosis of PDAC patients. Hence, prediction of genetic information using radiogenomic analysis may aid in the development of precision medicine.

Inducing multiple antibodies to treat squamous cell esophageal carcinoma.

BACKGROUND: The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction. METHODS: Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70. RESULTS: Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis. CONCLUSIONS: The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.

Outcomes of surgical resection for gastric cancer liver metastases: a retrospective analysis.

BACKGROUND: The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients. METHODS: This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016. RESULTS: The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups. CONCLUSION: Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.

[Laparoscopic Partial Colectomy for Transverse Colon Cancer after Open Laparotomy for Gastric Cancer Resection].

We report a case of transverse colon cancer resected by laparoscopic partial colectomy, followed by open gastrectomy. A man in his 70s was diagnosed with transverse colon cancer. He had a history of open gastrectomy for gastric lymphoma; thus, postoperative adhesions were expected in the upper abdomen. We performed a laparoscopic partial colectomy with gentle adhesiotomy, without injury. After preparation of the marginal vessels, blood flow towards the planned anastomotic line was confirmed by infrared observation after venous injection of indocyanine green. However, the initially planned oral anastomotic line did not show a blood supply; therefore, the anastomotic line was altered to a site of sufficient blood flow. In postlaparotomy cases, delicate handling and careful adhesiotomy are necessary in the laparoscopic approach due to the possibility of severe intraoperative injury resulting in conversion to open surgery. Furthermore, blood flow confirmation by fluorescence angiography is recommended in cases in which anatomical alterations might have occurred due to the previous operation.

[Significance of Surgery for Multidisciplinary Treatment Including Neoadjuvant Chemotherapy for Locally Advanced Colorectal Cancer].

Neoadjuvant chemotherapy has been performed for locally advanced colorectal cancer with invasion to other organs or lateral lymph node metastasis in to control local recurrence and distant metastasis. We evaluated the treatment results and the significance of surgery in 53 patients(36 rectal cancer cases and 17 sigmoid colon cancer cases)who underwent surgery after chemotherapy by XELOX plus bevacizumab for 3 months. As pretreatment diagnosis, 42 cases were T4b and 39 cases were lymph node positive. Combined resection was performed in 34 cases including 12 cases of total pelvic exenteration. Pathological diagnosis showed 27 cases of ypT4b and 34 cases of ypN0. Pathological curative resection was performed in 90.4%. Histological effect by chemotherapy was 31 cases in Grade(Gr)1a, 10 cases in Gr 1b, 8 cases in Gr 2, and 4 cases in Gr 3, respectively. The 5-year survival rate was 60.9% in Gr 1a or lower and 100% in Gr 1b or higher. Tumor markers( CEA and CA19-9)were reduced into normal range after neoadjuvant chemotherapy in all 4 patients with Gr 3. Pathological CR could not be predicted from clinical findings after neoadjuvant chemotherapy. It was suggested that neoadjuvant chemotherapy for locally advanced rectal cancer with invasion to other organs or lateral lymph node metastasis is useful for improving the prognosis, surgical resection is indispensable as a multidisciplinary treatment, and that the pathological therapeutic effect leads to prognosis prediction.

Quantitative Assessment of the Blood Perfusion of the Gastric Conduit by Indocyanine Green Imaging.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging has been used to assess the blood perfusion of the gastrointestinal tract in surgery. Especially, it was used to determine the best anastomotic site. However, in previous studies, ICG fluorescence was judged subjectively based on the visual appearance. This study evaluated the usefulness of our novel method to quantitatively assess the blood perfusion of the gastric conduit in esophagectomy based on ICG fluorescence. MATERIALS AND METHODS: Twenty patients who underwent esophagectomy with gastric conduit reconstruction were prospectively investigated. Using a camera in contact with the surface of the stomach, ICG images were quantitatively evaluated using "ROIs", a software program that quantified the fluorescence intensity and created a time-fluorescence intensity curve to assess the blood perfusion three times intraoperatively. RESULTS: No postoperative esophago-gastrostomy leakage developed. However, after preparing the gastric conduit and just before anastomosis, the maximum increase in fluorescence intensity (FImax) significantly decreased (48.8 ± 26.0 and 31.5 ± 14.9 versus 84.9 ± 28.2; P < 0.001 and P < 0.001, respectively), and the time to reach FImax was significantly extended (60 ± 35.4 and 58.3 ± 34.9 versus 18.9 ± 6.5; P < 0.001 and P < 0.002, respectively), in comparison to the control value. Just before anastomosis, 18 cases (90%) showed an identical pattern characterized by an obtuse and low arterial inflow peak and a slow rise of fluorescence intensity over time, indicating a decreased blood flow. CONCLUSIONS: The quantitative analysis of ICG fluorescence imaging could objectively prove a decrease in blood perfusion-which could not be determined macroscopically-in the gastric conduit before esophageal reconstruction. The results from the present and further studies may indicate its clinical value.

Surgical treatment strategy for esophagogastric junction cancers based on the tumor diameter.

BACKGROUND: The number of patients with esophagogastric junction (EGJ) cancers has tended to increase. However, no clear consensus on the optimum treatment policy has yet been reached. METHODS: This study included patients diagnosed with adenocarcinoma of Sievert type II in whom resection was performed in our hospital. We performed a clinicopathological examination, and patients were divided into two groups by the tumor size: L group, tumor size ≥4 cm; and S group, tumor size < 4 cm. The clinical factors, such as nodal dissection and recurrence pattern, were then analyzed. RESULTS: A total of 48 patients were diagnosed with ECJ cancers. The average tumor size was 55.1 mm, and 32 cases (66.7%) had tumors ≥4 cm. Metastasis to the mediastinum was noted in 4 cases (12.5%) in the L group but none in the S group. Recurrence in the upper or middle mediastinum lymph nodes was noted in 3 cases (9.4%) in the L group. The 5-year overall survival rates were 49.7 and 83.9% in the L and S groups, respectively. CONCLUSIONS: As the tumor grows large, it is difficult to accurately judge EGJ on the image, and as a result it is difficult to understand the exact esophageal invasion distance of the tumor. Therefore, lymph node dissection including the upper mediastinum is considered vital, regardless of the degree of esophageal invasion.

[A Case of Concurrent Robotic-Assisted Partial Nephrectomy and Laparoscopic Ileocecal Resection for Synchronous Cancer of the Kidney and Ascending Colon].

We report a case of synchronous cancer of the kidney and ascending colon that was resected concurrently using roboticassisted partialnephrectomy and laparoscopic ileocecalresection. A man in his 70s was diagnosed as having renaland ascending colon cancers. Thus, simultaneous resection was planned. First, robotic partial nephrectomy was performed via a transabdominalapproach by the urologicalsurgeon. After changing the position from semi-lateraldecubitus to supine, severalports were added and laparoscopic ileocecal resection was performed. Robotic and laparoscopic surgery was performed simultaneously, and the benefits of minimally invasive surgery were obtained.

[Results of Neoadjuvant Chemotherapy with S-1 plus CDDP for Gastric Cancer-The Number of Therapeutic Coursers and Therapeutic Effects].

Neoadjuvant chemotherapy(NAC)with S-1 plus CDDP(SP)followed by gastrectomy has been used for the treatment of patients with locally advanced gastric cancer. We examined the number of treatment courses, histologic effects, ypStage, and prognosis to estimate the utility and define the best treatment course of SP NAC. The patients were divided into 1 course(A: 54 cases), 2 courses(B: 50 cases), and incomplete first course(C: 12 cases). The rates of Grade 2 or more in histological effect were 24.1% in group A, 34.0% in B, and 0% in C. Four patients achieved pathological CR(1 case in group A and 3 cases in group B). The pathological response by NAC was more effective in group B than in group A. In down-staging cases by NAC, survival curves were obtained according to ypStage. The 5-year survival rates in R0 cases were 67.0%in the effective therapeutic group and 51.0%in the non-effective group; the results being significantly different. According to the number of therapeutic courses of NAC, the 5-year survival rates were 57.9% in group A, 65.2% in group B, and 20.0% in group C, demonstrating a significantly better prognosis in group B. Although the pathological response appeared in 1 course, it was significant in 2 courses of NAC. The results indicate that the completion of at least 2 courses of NAC are necessary in locally advanced gastric cancer.

[Laparoscopic Gastro-Jejunostomy Using the Overlap Method after Subtotal Gastrectomy for Upper Gastric Cancer].

BACKGROUND: Due to an aging society, patients with gastric cancer are also getting older. Although total gastrectomy should be avoided for elderly patients, laparoscopic subtotal gastrectomy(LSTG)is a technically demanding procedure. Here, we present a safe procedure of gastro-jejunostomy using the overlap method. METHODS: After transection of the stomach using gastroscopy, an entry hole was created at the center of the staple line of the remnant stomach. The jejunum was anastomosed to the dorsal wall of the gastric remnant with a linear stapler, and the entry hole was closed by hand-sewn sutures. Nineteen patients with gastric cancer in the upper third of the stomach underwent LSTG using this technique, and the short-term clinical outcomes were analyzed retrospectively. RESULTS: The median operative time was 221 minutes(143-318), and the median blood loss was 10 mL(3-100). The median postoperative hospital stay was 7 days(6-13), and there were no complications related to anastomosis. CONCLUSIONS: The short-term clinical outcomes of the laparoscopic gastro-jejunostomy using the overlap method after LSTG reveal that this technique is safe and feasible to use for improving patient outcomes.

[Treatment Results and Strategies for Early Gastric Cancer Patients Aged 80 Years or Older-How Should We Deal withNon -Curative ESD Cases ?]

With the aging population, the number ofearly gastric cancer patients aged 80 years or older is increasing. We clarified the outcome ofgastrectomy among early gastric cancer patients aged 80 years or older and examined the significance ofadditional gastrectomy for non-curative ESD cases. 1 ) Surgical outcomes in 90 cases ofearly gastric cancer patients aged 80 years or older with gastrectomy were analyzed. Gastrectomy was performed for patients up to 88 years of age and 84 cases (93.3%)were pStageⅠA. Three years and 5 years survival rates were 83.9% and 60.4%, respectively. The causes ofdeath included other disease in 28 cases, other cancer in 4 cases, and death associated with hospital stay in 1 case. 2 ) There were 28 non-curative ESD cases, including 6 T1a, 9 T1b1, and 13 T1b2. Among them, 8 additional gastrectomies were performed, but none were lymph node metastases and cancer residue at the proper muscle layer was identified in only 1 case. Three years and 5 years survival rates ofthe additional gastrectomy group were 100% and 60%, respectively. Although 2 years survival rate ofthe group without additional gastrectomy was 83.3%, there were no deaths due to gastric cancer. In elderly patients with early gastric cancer, considering the increasing the proportion deaths due to other diseases and the decreased quality of life after gastrectomy, the usefulness of additional gastrectomy for non-curative ESD is limited.

Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and a new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti-inflammation, growth suppression and EMT inhibition. Activation of nuclear factor kappa B (NF-κB), the major transcription factor induced by inflammation, was investigated by immunostaining. We found that localization of NF-κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF-κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT, we examined cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by western blotting. Metformin inhibited cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF-κB localization on ESCC. Further exploration of the marker of treatment efficacy and combination therapy could result in the possibility for novel treatment to use metformin on ESCC.