Future prospects for cancer immunotherapy using induced pluripotent stem cell-derived dendritic cells or macrophages.

Cancer immunotherapy is now the first-line treatment for many unresectable cancers. However, it remains far from a complete cure for all patients. Therefore, it is necessary to develop innovative methods for cancer immunotherapy, and immune cell therapy could be an option.

Solitary living worsens the continuation of adjuvant chemotherapy for gastric cancer.

Background: No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy.

Methods: We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020.

Is Prophylactic Splenectomy Necessary for Proximal Advanced Gastric Cancer Invading the Greater Curvature with Clinically Negative Splenic Hilar Lymph Node Metastasis? A Multi-Institutional Cohort Study (YCOG2003).

Background: Prophylactic splenectomy for hilar lymph node (#10) dissection has shown no survival benefit for patients with proximal advanced gastric cancer that does not invade the greater curvature. However, the survival benefit of prophylactic splenectomy for proximal advanced gastric cancer invading the greater curvature side, particularly for clinically negative #10 lymph node metastasis (#10[-]) cases remains controversial.

Methods: This multi-institutional retrospective study enrolled 146 consecutive patients with proximal advanced gastric cancers invading the greater curvature side with clinical #10(-) who underwent R0 total gastrectomy.

Prognostic Factors Affecting Short- and Long-Term Outcomes of Gastrectomy for Gastric Cancer in Older Patients.

Introduction: The benefits of surgery in older patients with gastric cancer are controversial. This single-institution retrospective study in Japan aimed to evaluate the impact of gastrectomy in older patients with gastric cancer.

Methods: A series of 234 patients aged ≥80 years with histologically confirmed gastric cancer had indications for surgical treatment at the Gastroenterological Center, Yokohama City University Medical Center, between April 2002 and December 2018.

Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

Purpose: Few studies have reported the impact of chemoradiotherapy (CRT) on the objective response of patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the factors predicting therapeutic effectiveness and the short- and long-term outcomes in patients with T4b ESCC treated with CRT.

Methods: We included 155 patients with T4b ESCC who underwent CRT at the Department of Surgery, Gastroenterological Center, Yokohama City University, between January 2000 and December 2018.

Feasibility of esophagectomy for esophageal cancer in elderly patients: a case-control study.

Purpose: Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer.

Methods: This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40-64 years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016.

High postoperative neutrophil-lymphocyte ratio and low preoperative lymphocyte-monocyte ratio predict poor prognosis in gastric cancer patients receiving gastrectomy with positive lavage cytology: a retrospective cohort study.

Background: Long-term outcomes in gastric cancer patients with positive lavage cytology (CY1) are generally poor. This multi-institutional retrospective cohort study aims to evaluate the clinical significance of the neutrophil-lymphocyte ratio (NLR) and the lymphocyte-monocyte ratio (LMR) in CY1 gastric cancer patients.

Methods: A total of 121 CY1 gastric cancer patients without other non-curative factors, who underwent macroscopically curative resection, were enrolled in this study.

Prognostic impact of dimensional factors in pT1 gastric cancer.

Background: The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer.

Objectives: This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer.

Methods: We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy.

Real-World Therapeutic Outcomes of S-1 Adjuvant Chemotherapy for pStage II/III Gastric Cancer in the Elderly.

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear.

Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated.

Comparison of Converse Ω Anastomosis and Extracorporeal Anastomosis After Laparoscopic Distal Gastrectomy for Gastric Cancer.

Background: Converse Ω anastomosis is a recently developed technique of delta-shaped anastomosis for intracorporeal gastroduodenostomy to simplify the anastomotic procedures and reduce their potential risks. This study aimed to evaluate the safety and effectiveness of converse Ω anastomosis, comparing it with conventional extracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer.

Patients And Methods: Among 169 gastric cancer patients who underwent LDG with Billroth-I anastomosis anastomosis between April 2013 and March 2018, we selected 100 patients by propensity score matching (50 in the converse Ω anastomosis group and 50 in the extracorporeal anastomosis group).

Systemic Review and Meta-analysis of Impact of Splenectomy for Advanced Gastric Cancer.

Background/aim: Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach.

Role of Conversion Surgery for Unresectable Pancreatic Cancer After Long-Term Chemotherapy.

Background: Unresectable pancreatic cancer (UR-PC) has a poor prognosis. Although conversion surgery has been considered a promising strategy for improving prognosis in UR-PC, the clinical benefit offered to patients with UR-PC remains controversial. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PC.

Impact of intramuscular adipose tissue content on short- and long-term outcomes of hepatectomy for colorectal liver metastasis: a retrospective analysis.

Background: Numerous reports regarding sarcopenia have focused on the quantity of skeletal muscle. In contrast, the impact of the quality of skeletal muscle has not been well investigated.

Methods: A retrospective analysis of 115 patients who underwent initial hepatectomy for colorectal liver metastasis between January 2009 and December 2016 in our hospital was performed.

Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1 Dendritic Cells.

Type I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-α-producing cells by genetically engineered induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) alters the tumor microenvironment and propagates the molecular signature associated with type I IFN.

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Borderline Resectable Pancreatic Ductal Adenocarcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgical Resection.

Background: Increasing evidence suggests that cancer-associated inflammation, as indicated by markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), predicts poor outcomes in pancreatic cancer. In this study, the associations between systemic inflammation markers and survival were examined in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) patients who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection.

Methods: From April 2009 to December 2017, 119 patients diagnosed with BR-PDAC and receiving NACRT followed by radical surgery were included in this retrospective study.

Risk Factors Associated With Early Recurrence of Borderline Resectable Pancreatic Ductal Adenocarcinoma After Neoadjuvant Chemoradiation Therapy and Curative Resection.

Background/aim: To identify risk factors of early recurrence after neoadjuvant chemoradiation therapy (NACRT) and curative pancreatectomy in patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC).

Patients And Methods: Sixty-one patients with BR-PDAC who underwent curative resection after NACRT during July 2009-June 2014 were included. Patients were divided into early recurrence (i.

Feasibility of Laparoscopy-assisted Gastrectomy for Gastric Cancer in Elderly Patients: A Case-Control Study.

Purpose: The present study evaluated the safety and effectiveness of laparoscopic gastrectomy (LG) in elderly gastric cancer patients.

Patients And Methods: This study included 78 gastric cancer patients aged 80 years or above [39 in the LG group and 39 in the open gastrectomy group (matched)]. Patient characteristics, surgical outcomes, survival time, and immunonutritional status were compared.

Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors.

The carcinoembryonic antigen glypican-3 (GPC3) is a good target of anticancer immunotherapy against pediatric solid tumors expressing GPC3. In this non-randomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3-peptide vaccination in patients with pediatric solid tumors. Eighteen patients with pediatric solid tumors expressing GPC3 underwent GPC3-peptide vaccination (intradermal injections every 2 weeks), with the primary endpoint being the safety of GPC3-peptide vaccination and the secondary endpoints being immune response, as measured by interferon (IFN)-γ enzyme-linked immunospot assay and Dextramer staining, and the clinical outcomes of tumor response, progression free survival (PFS), and overall survival (OS).

Cancer immunotherapy-targeted glypican-3 or neoantigens.

Immune checkpoint inhibitors have ushered in a new era in cancer therapy, although other therapies or combinations thereof are still needed for many patients for whom these drugs are ineffective. In this light, we have identified glypican-3 an HLA-24, HLA-A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials showing that glypican-3 peptide vaccines induce specific CTLs in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, and UMIN000006357).

Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma.

We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial.

Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma.

Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface protein overexpressed in hepatocellular carcinoma(HCC), and its overexpression is associated with poor prognosis. The diagnostic potential of GPC3 as a serum marker has been reported. In the present study, we evaluated the usefulness of plasma GPC3 as a predictor for recurrence after surgical resection in stage I HCC patients by newly developed an enzyme-linked immunosorbent assay (ELISA) system.

Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients.

The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial.

Hepatocellular carcinoma cell sensitivity to Vγ9Vδ2 T lymphocyte-mediated killing is increased by zoledronate.

The limited efficacy of vaccines in hepatocellular carcinoma (HCC), due to the low frequency of tumor-infiltrating cytotoxic T lymphocytes (CTLs), indicates the importance of innate immune surveillance, which assists acquired immunity by directly recognizing and eliminating HCC. Innate Vγ9Vδ2 T cells have major histocompatibility complex-unrestricted antitumor activity and are activated by phosphoantigens, which are upregulated in cancer cells by the nitrogen-containing bisphosphonate, zoledronate (Zol). A better understanding of HCC susceptibility to Zol and downstream γδ T cell-mediated killing is essential to optimize γδ T cell-mediated immunotherapy.