Cancer Stem Cells of Hepatocellular Carcinoma Are Suppressed by the Voltage-gated Calcium Channel Inhibitor Amlodipine.

BACKGROUND/AIM: The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC. MATERIALS AND METHODS: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis. RESULTS: Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor. CONCLUSION: CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC.

[Identification of ion channel/transporter expression profiles in digestive cancer stem cells for novel targeting therapy].

Recent evidence suggests that the targeting of membrane transporters specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the ion channel expression profiles in digestive CSCs. Cells strongly expressing CSC markers, such as ALDH1A1 and CD44, were separated from the human esophageal squamous cell carcinoma, gastric cancer, and pancreatic cancer cell lines using fluorescence-activated cell sorting, and CSCs were identified based on tumorsphere formation. Messenger RNA levels of CSC markers were higher in CSCs than in non-CSCs. These CSCs also exhibited resistance to anticancer agents. The microarray analysis revealed that the expression of transient receptor potential vanilloid 2 (TRPV2), voltage-gated calcium channels (VGCCs), and voltage-gated potassium channels (VGKCs) were upregulated in esophageal, gastric, and pancreatic CSCs, respectively, compared with non-CSCs. The TRPV2 inhibitor tranilast, VGCCs inhibitors amlodipine and verapamil, and VGKC inhibitor 4-aminopyridine exhibited greater cytotoxicity in CSCs compared with non-CSCs, and their inhibitory effects were also confirmed in a xenograft model in nude mice. Taking these results, phase I/II study to investigate clinical safety and efficacy of neoadjuvant combination chemotherapy of tranilast in advanced esophageal squamous cell carcinoma (TNAC study) is ongoing. These researches identified a role of ion channels in the persistence of CSCs and suggested that their inhibitors may have potential as a therapeutic agent for digestive cancers.

Cancer Stem Cells of Esophageal Adenocarcinoma are Suppressed by Inhibitors of TRPV2 and SLC12A2.

BACKGROUND: The potential of membrane transporters activated in cancer stem cells (CSCs) as new therapeutic targets for cancer is attracting increasing interest. Therefore, the present study examined the expression profiles of ion transport-related molecules in the CSCs of esophageal adenocarcinoma (EAC). METHODS: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from OE33 cells, a human Barrett's EAC cell line, by fluorescence-activated cell sorting. CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were examined by a microarray analysis. RESULTS: Among OE33 cells, ALDH1A1 messenger RNA levels were higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels/transporters, such as transient receptor potential vanilloid 2 (TRPV2) and solute carrier family 12 member 2 (SLC12A2). The cytotoxicities of the TRPV2 inhibitor tranilast and the SLC12A2 inhibitor furosemide were higher at lower concentrations in CSCs than in non-CSCs, and both markedly reduced the number of tumorspheres. The cell population among OE33 cells that highly expressed ALDH1A1 also was significantly decreased by these inhibitors. CONCLUSIONS: Based on the present results, TRPV2 and SLC12A2 are involved in the maintenance of CSCs, and their specific inhibitors, tranilast and furosemide, respectively, have potential as targeted therapeutic agents for EAC.

Effects of TRPV2 on the Expression of PD-L1 and Its Binding Ability to PD-1 in Gastric Cancer.

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) is a member of the TRP superfamily of non-specific cation channels with functionally diverse roles. We herein investigated the effects of TRPV2 on the expression of programmed cell death-ligand 1 (PD-L1) and its binding ability to programmed cell death-1 (PD-1) in gastric cancer (GC). METHODS: Knockdown (KD) experiments were performed on human GC cell lines using TRPV2 small-interfering RNA. The surface expression of PD-L1 and its binding ability to PD-1 were analyzed by flow cytometry. Eighty primary tissue samples were assessed by immunohistochemistry (IHC), and the relationships between IHC results, clinicopathological factors, and patient prognosis were analyzed. The molecular mechanisms underlying the effects of TRPV2 on the intracellular ion environment were also investigated. RESULTS: TRPV2-KD decreased the expression level of PD-L1 in NUGC4 and MKN7 cells, thereby inhibiting its binding to PD-1. A survival analysis revealed that 5-year overall survival rates were significantly lower in the TRPV2 high expression and PD-L1-positive groups. In IHC multivariate analysis of GC patients, high TRPV2 expression was identified as an independent prognostic factor. Furthermore, a positive correlation was observed between the expression of TRPV2 and PD-L1. An immunofluorescence analysis showed that TRPV2-KD decreased the intracellular concentration of calcium ([Ca2+]i). Treatment with ionomycin/PMA (phorbol 12-myristate 13-acetate), which increased [Ca2+]i, upregulated the protein expression of PD-L1 and promoted its binding to PD-1. CONCLUSIONS: The surface expression of PD-L1 and its binding ability to PD-1 in GC were regulated by TRPV2 through [Ca2+]i, indicating the potential of TRPV2 as a biomarker and target of immune checkpoint blockage for GC.

[Clinical Features and Treatment for Cholangiolocellular Carcinoma(CoCC)-Report of Three Cases].

We report 3 cases of cholangiolocellular carcinoma(CoCC)experienced from April 2017 to March 2021 in our hospital. The average age of the cases is 74.3 years old, 2 males and 1 female respectively. Hepatectomy was performed in 2 cases, and transcatheter arterial embolization(TAE)and radiofrequency ablation(RFA)therapy was performed in 1 case because of old age and his wishes as the background liver disease. Chronic hepatitis C was found in 1 case, fatty liver in 1 case, and alcoholic liver disease in 1 case. Two patients who underwent hepatectomy had good long-term prognosis, but another patient who underwent TAE and RFA developed early recurrence at bone and died in 3 months after treatment. Therefore, we consider that the risk of recurrence should be examined and the treatment should be performed accordingly.

[Case of a 5mm Rectal Neuroendocrine Tumor(G1)with Lymph Node Metastasis].

Screening colorectal endoscopy revealed a 5mm rectal neuroendocrine tumor(NET: G1)in a 72-year-old man. Endoscopic mucosal resection(EMR)was performed, and the histopathological examination demonstrated lymphatic and vessel invasion with a possible positive vertical margin. Therefore, we performed laparoscopic low anterior resection, lymphadenectomy, and ileostomy as additional surgical resections. No residual tumor was found in the specimen, but 3 metastatic lymph nodes were identified. The rate of lymph node metastasis in rectal NETs of diameter<10mm is low, and additional surgery can reduce the patient's quality of life affected due to impaired anorectal function. However, in the Japanese guidelines for NET, additional surgery is adopted in cases with high-risk factors for lymph node metastasis. Therefore, it is necessary to select between additional surgery and careful follow-upfor rectal NETs of diameter<10mm with high-risk factors because of possible lymph node metastasis.

[A Case of Laparoscopic Ileocecal Resection for Ascending Colon Cancer with Portosystemic Shunt].

A 72-year-old woman who underwent colorectal endoscopy because of positive fecal occult blood test results was diagnosed with ascending colon cancer.Preoperative CT revealed advanced ascending colon cancer and portosystemic shunt between the ileocecal vein and inferior vena cava.It was necessary to cut the shunt when ileocecal resection was performed. The patient had no symptoms caused by the shunt, and blood examination results showed no liver enzyme abnormalities. Abdominal ultrasound examination revealed no liver cirrhosis and normal blood flow in the portal vein and shunt flow from the ileocecal vein to the inferior vena cava.We assessed that surgery could be safely performed without increasing portal vein pressure.Laparoscopic ileocecal resection was performed by cutting the shunt.Partial jejunum resection was also performed for a mesenteric tumor observed intraoperatively, and pathological findings revealed a lymphangioma.The patient was discharged home on postoperative day 7 without any symptoms, liver enzyme abnormalities, or ascites suggestive of increased portal vein pressure on abdominal ultrasound examination.Colorectal cancer surgery with simultaneous cutting of a portosystemic shunt has rarely been reported.It is necessary to consider the causes of portosystemic shunt and then cut the shunt during surgery when needed.

[Curative Resection of Advanced Rectal Cancer with Direct Invasion of the Prostate and Extra-Regional Lymph Node Metastases after Chemotherapy].

A-69-year-old man presented with an obstructed defecation. He was diagnosed as having advanced lower rectal cancer with direct invasion of the prostate and metastases to regional and para-aortic lymph nodes. Biopsy examination of the tumor showed RAS wild-type expression and negative BRAF V600E mutation. The patient received 13 courses of mFOLFOX6 and panitumumab(Pmab)in combination and 1 course of mFOLFOX6 alone. After the chemotherapy, the size of the primary tumor and lymph node metastases decreased remarkably. 18F-fluorodeoxyglucose-positron emission tomography(18F-FDG- PET)showed no 18F-FDG accumulation in the tumor and lymph nodes. We performed laparoscopic abdominoperineal resection with D3LD2 lymph node dissection and left external iliac lymph node(293-lt)sampling. Pathological examination revealed no residual cancer at the primary tumor location and only a few malignant cells remained in the 293-lt lymph node. The patient has shown no recurrence for 1 year without adjuvant chemotherapy. We conclude that mFOLFOX6 and Pmab in combination is an effective preoperative chemotherapy against advanced RAS wild-type rectal cancer. This strategy may reduce surgical invasion and save the surrounding organs while maintaining curability.

Who needs diverting ileostomy following laparoscopic low anterior resection in rectal cancer patients? Analysis of 417 patients in a single institute.

BACKGROUND: Anastomotic leakage (AL) is one of the most serious complications after low anterior resection (LAR) for rectal cancer, and the significance of diverting stoma to prevent AL is still controversial. The aim of this study is to clarify the potential benefits and safety of diverting ileostomy (DI) following laparoscopic LAR in rectal cancer patients. METHODS: This was a retrospective cohort study of 417 rectal cancer patients who underwent laparoscopic LAR in a single institute. The risk factors for AL and the DI-related morbidity were assessed. RESULTS: DI was performed in 226 patients (54.2%). The incidence rates of symptomatic AL showed no significant difference between patients with and without DI (8.4% vs. 10.0%, p = 0.612). AL requiring a surgical intervention was relatively lower in patients with DI than in those without DI (1.8% vs. 4.7%, p = 0.097). DI construction was an independent risk factor for AL requiring a surgical intervention (OR 3.47, p = 0.041), as was the serum albumin level (p = 0.003), and being male was a relative risk factor (p = 0.058). Focusing on sex, the rate of AL requiring a surgical intervention was significantly different in male (1.7 and 7.9%, p = 0.021) but not in female patients (1.9 and 1.1%, p = 1.000) with and without DI. The DI construction-related morbidity was 9.7%, and no patient required a reoperation. Of 226 patients with DI, 209 (92.5%) underwent stoma closure 118 days (median 30-509 days) after LAR. The stoma closure-related morbidity was 9.1% and 1 patient (0.5%) required a reoperation due to anastomotic leakage. CONCLUSIONS: DI following laparoscopic LAR can decrease the risk of AL, requiring a surgical intervention, especially in male patients with malnutrition. However, due to DI-related morbidity, DI is not recommended in female patients.

Comparison of Feeding Jejunostomy via Gastric Tube Versus Jejunum After Esophageal Cancer Surgery.

BACKGROUND: Jejunostomy is an essential route for nutritional support after esophageal cancer surgery. However, catheter-related complications may occur. This study compared the complications of feeding jejunostomy between gastric tube and jejunum after esophageal cancer surgery. PATIENTS AND METHODS: The records of 215 patients with esophageal cancer who underwent radical esophagectomy with retrosternal gastric tube reconstruction between January 2010 and November 2016 were examined. One hundred and thirty-three patients underwent feeding jejunostomy via gastric tube and 82 patients underwent the procedure via the jejunum, and their records were reviewed for catheter-related complications. RESULTS: Catheter-related complications occurred in five patients in the gastric tube group and 12 in the jejunum group (3.8% vs. 14.6%, p=0.005). Mechanical bowel obstruction requiring surgical therapy occurred in three patients in the jejunum group, but in none in the gastric tube group (p=0.026). CONCLUSION: Feeding jejunostomy reconstruction via gastric tube appears to be a safe and useful procedure.

Oncologic Outcomes of Oral Adjuvant Chemotherapy Regimens in Stage III Colon Cancer: Tegafur-Uracil Plus Leucovorin Versus Capecitabine.

INTRODUCTION: Although several major trials of treatment for stage III colon cancer have been reported, no study has compared oral adjuvant chemotherapy regimens using tegafur-uracil in combination with leucovorin (UFT/LV) and capecitabine (CAPE) alone. This study compared the oncologic outcomes of treatment with these 2 oral regimens. PATIENTS AND METHODS: Records of patients with stage III colon cancer who underwent curative surgery and adjuvant chemotherapy from April 2007 and September 2014 were retrospectively reviewed. RESULTS: A total of 258 patients with stage III colon cancer received oral adjuvant chemotherapy with UFT/LV (n = 157, 61%) and CAPE (n = 101, 39%). The overall rate of completion of scheduled treatment was 78.6%. Significantly fewer patients on UFT/LV completed the regimen compared with those on CAPE (117, 74.5% vs. 86, 85.1%; P < .01). There were no significant differences in oncologic outcome between UFT/LV and CAPE in terms of 3-year overall survival rates (OS; 95.8% vs. 92.4%, P = .45) and 3-year relapse-free survival rates (RFS; 82.7% vs. 79.3%, P = .8). CONCLUSION: The 3-year RFS and OS were similar for both regimens, yielding an excellent outcome. The selection of adjuvant chemotherapeutic regimens must be based on the patient's status as well as considering the incidences of adverse events, medical cost, and administration convenience.

[Surgical Therapy for Locally Recurrent Rectal Cancer].

We examined 40 cases of locally recurrent rectal cancer surgically treated at our hospital. The sites of recurrence were the anastomosis site(16 cases), pelvic lymph nodes(10 cases), pelvis(10 cases), and perineum(5 cases). Intraoperative complications were confirmed in 5% and postoperative complications in 45% of cases. The R0 resection rate was 60.0%, and positive radial margins were confirmed in 35.0% of cases. Second recurrences were confirmed in 60.0% of cases. The 3-year overall survival rate was 68.7%, and the 3-year relapse-free survival rate was 20.3%. Surgery for locally recurrent rectal cancer was performed relatively safely; however, the R1 resection rate and recurrence rate after surgery were high. R0 resection significantly improved the overall survival rate, and it seems that a treatment strategy to raise R0 resection rate is necessary.

Carbonic Anhydrase XII as an Independent Prognostic Factor in Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although recent studies described important roles for carbonic anhydrase (CA) XII in epithelial carcinogenesis and tumor behavior, a consensus has not yet been reached regarding its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance in ESCC. MATERIALS AND METHODS: An immunohistochemical analysis was performed on 70 primary tumor samples obtained from ESCC patients who underwent esophagectomy, and the relationships between the expression of CA XII and various clinicopathological features or prognosis were analyzed. RESULTS: Immunohistochemical staining showed that CA XII was primarily found in the cell membranes of carcinoma cells. Although the expression of CA XII was related to the pT category, it had no prognostic impact. We then examined the expression of CA XII according to the pT category. In pT2-3 ESCC, the 3-year survival rate of patients with the high grade expression of CA XII (29.1 %) was significantly lower than that of patients with the low grade expression of CA XII (70.3 %). Furthermore, a multivariate analysis demonstrated that the expression of CA XII was one of the most important independent prognostic factors following radical esophagectomy in pT2-3 ESCC. CONCLUSION: These results suggest that the expression of CA XII may be a valuable prognostic factor for patients with advanced ESCC. The results of the present study provide an insight into the role of CA XII as a biomarker in ESCC.

Evaluation of the efficacy of peritoneal lavage with distilled water in colorectal cancer surgery: in vitro and in vivo study.

BACKGROUND: Peritoneal lavage with distilled water has been performed during colorectal cancer surgery. This study investigated the cytocidal effects of hypotonic shock in vitro and in vivo in colorectal cancer cells. METHODS: Three human colorectal cancer cell lines, DLD1, HT29, and CACO2, were exposed to distilled water, and morphological changes were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes were assessed using a high-resolution flow cytometer. Re-incubation experiments were performed to investigate the cytocidal effects of distilled water. In the in vivo experiment, cancer cells after hypotonic shock were injected intraperitoneally into mice and the degree of established peritoneal metastasis was subsequently evaluated. The effects of the blockade of Cl(-) channels on these cells during hypotonic shock were also analyzed. RESULTS: Morphological observations revealed a rapid cell swelling followed by cell rupture. Measurements of cell volume changes showed that mild hypotonic shock induced regulatory volume decrease (RVD) while severe hypotonic shock broke cells into fragments. Re-incubation experiments demonstrated the cytocidal effects of hypotonicity. In vivo experiments revealed the absence of peritoneal dissemination in mice in the distilled water group, and its presence in all mice in the control group. The blockade of Cl(-) channels increased cell volume by inhibiting RVD and enhanced cytocidal effects during mild hypotonic shock. CONCLUSIONS: These results clearly support the efficacy of peritoneal lavage with distilled water during colorectal cancer surgery and suggest that regulating of Cl(-) transport may enhance the cytocidal effects of hypotonic shock.

Efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells: an in vivo evaluation.

The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using an in vivo model. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW) (2 mL for 3 days) in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection of DW did not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutes in vitro were then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW.

The K-Cl cotransporter KCC3 as an independent prognostic factor in human esophageal squamous cell carcinoma.

The objectives of the present study were to investigate the role of K-Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with a CN > MT score was lower than that of patients with a CN ≤ MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

[High BMI does not influence short- and long-term outcomes of patients with esophageal cancer treated with esophagectomy].

UNLABELLED: The aim of this study was to clarify the influence of a high body mass index (BMI) on short- and long-term outcomes of patients after esophagectomy for cancer. PATIENTS AND METHODS: A total of 164 patients with a BM ≥ 18.5 who underwent esophagectomy for cancer from July 2008 through March 2013 were enrolled. Patients were divided into 2 groups according to BMI: BMI<5 (normal BMI group) and BM ≥ 25 (high BMI group). Further, the short- and long-term outcomes after esophagectomy were retrospectively analyzed. RESULTS: The median BMI was 21.6. The high BMI group (n=26) had significantly more histological adenocarcinomas than the normal BMI group (p=0.003). Other clinicopathological factors such as the type of surgery performed, R0 resections, and perioperative complications, were not influenced by the BMI. There were no significant differences between the 2 groups in the 3-year disease-free rates and 3-year overall survival rates. CONCLUSIONS: Esophagectomy for patients with a high BMI is acceptable based on the similar short- and long-term outcomes when compared with normal BMI patients.

Prognostic significance of p21 expression in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although p21 is an important component that regulates cell-cycle progression, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated its prognostic significance and correlation with cyclin-D1 (CCND1) expression in ESCC. MATERIALS AND METHODS: The p21 labeling index (LI) was calculated by immunohistochemistry for 69 primary tumor samples obtained from patients with ESCC who had undergone curative esophagectomy, and correlations between p21 LI and various clinicopathological features, prognosis, and CCND1 LI were studied. RESULTS: The p21 LI of these tumors ranged from 2.0% to 57.0% (median=28.4%, mean±SD=27.3% ± 13.0). p21 LI was positively correlated with CCND1 LI. When patients were divided into two groups using a p21 LI cut-off value of 30%, the 5-year survival rate of patients with p21 LI of ≥ 30% was 80.0%, which was significantly higher than that of patients with p21 LI of <30% (55.5%). Furthermore, when patients were divided into four groups according to p21 and CCND1 expression, the 5-year survival rate of patients with p21 LI of <30% and CCND1 LI of ≥ 45% was the lowest (44.4%). Multivariate analysis demonstrated that venous invasion, lymphatic invasion, and p21 LI were independent prognostic factors. CONCLUSION: Our results indicate that p21 LI is correlated with CCND1 LI and can be used as an independent prognostic factor for patients with ESCC following selection of a suitable cut-off value.

[Esophageal carcinosarcoma treated with surgery and chemoradiotherapy-a report of 4 cases].

Esophageal carcinosarcoma is a rare malignant tumor. We report the cases of 4 patients treated with resection and chemoradiotherapy. All patients were men (mean age, 61 years) and presented with dysphagia. Endoscopic examination revealed type 1 tumors in all patients. We planned esophagectomy with extended lymphadenectomy for all patients; however, non-curative resection was performed in 1 patient with extended lymph node metastasis. Curative resection was performed in 3 patients, all of whom showed pT1 wall invasion, and 2 had lymph node metastasis; hence, 1 case was classified as stage I and 2 as stage II. Local recurrence developed in 1 patient at 13 months after curative resection. This patient was treated with chemoradiotherapy and showed a clinical complete response. The patient remains alive without recurrence. The other 2 patients showed no recurrence. Therefore, 3 patients who underwent curative resection survived for more than 5 years. The other patient who underwent non-curative resection died of multiple organ metastasis 111 days after surgery. Because protuberant esophageal carcinosarcoma causes symptoms such as dysphagia, this disease can be diagnosed earlier than esophageal cancer; however, lymph node metastasis at diagnosis is frequently encountered. Surgery with extended lymphadenectomy for esophageal carcinosarcoma results in better prognosis, and chemoradiotherapy is as effective for recurrence as for esophageal cancer.