Satoshi Tsutsumi

Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma

Programmed death‐ligand 1 (PD‐L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD‐L1 also contains a binding site for ZEB1, a transcription factor related to epithelial‐mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD‐L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD‐L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared. ZEB1 and PD‐L1 expression was determined in TE8 cells, which demonstrate the EMT phenotype, following ZEB1 knockdown by siZEB1. TE5, TE6 and TE11 cells with non‐EMT phenotype were also used for studies of TGF‐β1‐dependent EMT induction and ZEB1 and PD‐L1 expression. In cases of high PD‐L1 expression at the invasive front, significantly greater depth of tumor invasion, EMT, and less CD8+ lymphocyte infiltration were observed. High PD‐L1 expression was also associated with worse overall and relapse‐free survival. A correlation was observed between PD‐L1 and ZEB1 expression. In TE8 cells, siZEB1 suppressed PD‐L1 and promoted E‐cadherin mRNA and protein expression. TGF‐β1 induced EMT and surface expression of PD‐L1 in TE5, TE6 and TE11 cell lines. PD‐L1 expression at the ESCC invasive front was related to ZEB1 expression, EMT and poor prognosis. We suggest that a cooperative mechanism bridging between tumor immune avoidance and EMT contributes to tumor malignancy in ESCC.

Prognostic Significance of Postoperative Complications After Curative Resection for Patients With Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to elucidate the impact of postoperative complications on long-term survival after curative resection for esophageal squamous cell carcinoma. Background: The relation between postoperative complications and long-term survival after curative surgery for esophageal squamous cell carcinoma is controversial; thus, this issue should be resolved with a large-scale, well-designed study. Methods: Clinicopathological features and survival of 580 consecutive patients who received curative resection for esophageal squamous cell carcinoma were investigated according to the development of postoperative pulmonary complications and anastomotic leakage. Results: The 5-year survival rates of patients with pStage 0, I, and II disease with postoperative complications (n = 116) were significantly poorer than those of patients without postoperative complications (n = 288) (overall 69.6% vs 46.9%, P < 0.0001; disease-specific; 76.7% vs 58.9%, P < 0.0022), whereas no differences were found in patients with pStage III and IV disease (n = 176). In the univariate and multivariate analyses for disease-specific survival, pT3, pT4, pN positivity, and development of postoperative complications were significant prognostic factors in all patients. Also, when the analysis was limited to the pStage 0, I, and II patients, development of postoperative complications, and pT3, pT4, and pN positivity, were found to be independent poor prognostic factors in multivariate analyses (hazard ratio: 1.56, 95% confidence interval, 1.01–2.41, P = 0.0476). Conclusions: The development of postoperative complications is an independent disease-specific poor prognostic factor after curative resection for patients with less-advanced esophageal squamous cell carcinoma.OBJECTIVE The objective of this study was to elucidate the impact of postoperative complications on long-term survival after curative resection for esophageal squamous cell carcinoma. BACKGROUND The relation between postoperative complications and long-term survival after curative surgery for esophageal squamous cell carcinoma is controversial; thus, this issue should be resolved with a large-scale, well-designed study. METHODS Clinicopathological features and survival of 580 consecutive patients who received curative resection for esophageal squamous cell carcinoma were investigated according to the development of postoperative pulmonary complications and anastomotic leakage. RESULTS The 5-year survival rates of patients with pStage 0, I, and II disease with postoperative complications (n = 116) were significantly poorer than those of patients without postoperative complications (n = 288) (overall 69.6% vs 46.9%, P < 0.0001; disease-specific; 76.7% vs 58.9%, P = 0.0022), whereas no differences were found in patients with pStage III and IV disease (n = 176). In the univariate and multivariate analyses for disease-specific survival, pT3, pT4, pN positivity, and development of postoperative complications were significant prognostic factors in all patients. Also, when the analysis was limited to the pStage 0, I, and II patients, development of postoperative complications, and pT3, pT4, and pN positivity, were found to be independent poor prognostic factors in multivariate analyses (hazard ratio: 1.56, 95% confidence interval, 1.01-2.41, P = 0.0476). CONCLUSIONS The development of postoperative complications is an independent disease-specific poor prognostic factor after curative resection for patients with less-advanced esophageal squamous cell carcinoma.

Clinicopathological Features of Cervical Esophageal Cancer: Retrospective Analysis of 63 Consecutive Patients Who Underwent Surgical Resection

Objective: The objectives of this retrospective study were to elucidate the clinicopathological features and recent surgical results of cervical esophageal cancer. Summary Background Data: Cervical esophageal cancer has been reported to have a dismal prognosis. Accurate knowledge of the clinical characteristics of cervical esophageal cancer is warranted to establish appropriate therapeutic strategies. Methods: The clinicopathological features and treatment results of 63 consecutive patients with cervical esophageal cancer (Ce group) who underwent surgical resection from 1980 to 2013 were analyzed and compared with 977 patients with thoracic or abdominal esophageal cancer (T/A group) who underwent surgical resection during that time. Results: Among the patients who received curative resection, the 5-year overall and disease-specific survival rates of the Ce patients were significantly better than those of the T/A patients (overall: 77.3% vs 46.5%, respectively, P = 0.0067; disease-specific: 81.9% vs 55.8%, respectively, P = 0.0135). Although total pharyngo-laryngo-esophagectomy procedures were less frequently performed in the recent period, the rate of curative surgical procedures was markedly higher in the recent period (2000–1013) than that in the early period (1980–1999) (44.4% vs 88.9%, P = 0.0001). The 5-year overall survival rate in the recent period (71.5%) was significantly better than that in the early period (40.7%, P = 0.0342). Conclusions: Curative resection for cervical esophageal cancer contributes to favorable outcomes compared with other esophageal cancers. Recent surgical results for cervical esophageal cancer have improved, and include an increased rate of curative resection and decreased rate of extensive surgery.

Clinical significance of totally laparoscopic distal gastrectomy: A comparison of short-term outcomes relative to open and laparoscopic-assisted distal gastrectomy

Background: Laparoscopic distal gastrectomy has become an established minimally invasive treatment for gastric cancer since it was first reported in 1994. Materials and Methods: We retrospectively assessed the clinical outcomes of 248 patients who had undergone open distal gastrectomy (ODG), laparoscopic-assisted distal gastrectomy (LADG), and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. Results and Conclusions: TLDG showed superiority in terms of blood loss, reconstruction options, and postoperative recovery compared with ODG and LADG. Especially, the mean operating time in the TLDG group was significantly shorter than that of the LADG group (P=0.003). Book-binding technique used in TLDG was one of the reasons of this result. The only inferior aspect of TLDG was the longer operating time compared with ODG; TLDG had no disadvantages compared with LADG. Although the operating time and long-term outcome remain problems, we suggest that TLDG has the potential to serve as an optimal operative method.

Development of fistula between esophagogastric anastomotic site and cartilage portion of trachea after subtotal esophagectomy for cervical esophageal cancer: a case report

A 65-year-old man with cT3N2M0 stage III cervical esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the retrosternal route after neoadjuvant chemoradiotherapy. The anastomosis was located adjacent to the left side of the trachea, and a circular stapler was used for anastomosis. Postoperative anastomotic leakage occurred, and an esophagotracheal fistula between the esophagogastric anastomotic site and cartilage portion of the trachea was observed on postoperative day 44. The patient underwent division of the fistula, direct suturing of the anastomotic leakage site, left pectoralis major muscle flap placement, and tracheotomy. He was discharged home on postoperative day 120 on an oral diet. All previous reports of tracheobronchial fistula describe the occurrence of the fistula at the membranous portion of the trachea. The formation of a fistula between the esophagogastric anastomotic site and cartilage portion of the trachea is considered a possible complication when a high esophagogastric anastomosis is created.

Blood Flow Assessment with Indocyanine Green Fluorescence Angiography for Pedicled Omental Flap on Cervical Esophagogastric Anastomosis after Esophagectomy

Esophagectomy is an invasive surgical procedure with several serious postoperative complications including anastomotic leak. To reduce the incidence of anastomotic leak, it is necessary to establish more reliable techniques for anastomosis.

High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer

The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E‐cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse‐free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E‐cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E‐cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E‐cadherin expression. In vitro studies suggested that RAS‐MEK‐MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.

Laparoscopic Gastrectomy for Gastric Cancer with Peritoneal Dissemination after Induction Chemotherapy

Gastric cancer with peritoneal dissemination may be diagnosed as unresectable. More recently, as a result of progress in chemotherapy, some patients with peritoneal dissemination have exhibited extended survival. We report on our experience with three patients in whom induction chemotherapy allowed for totally laparoscopic total gastrectomy (TLTG). All three patients were diagnosed as having advanced gastric cancer with peritoneal dissemination using staging laparoscopy. As induction chemotherapy, S-1 combined with cisplatin was administered to two patients and trastuzumab plus capecitabine combined with cisplatin to one patient. TLTG was performed in all patients and there were no postoperative complications. Adjuvant chemotherapy was initiated within 3 weeks after surgery in all three patients. Laparoscopic gastrectomy undertaken after induction chemotherapy was found to be effective and safe; this treatment has the potential to achieve good treatment outcomes in patients with stage IV gastric cancer.