Long-term Outcomes of Neoadjuvant Chemotherapy With Docetaxel, Cisplatin and S-1 for Stage III Gastric Cancer.

BACKGROUND/AIM: In the previous phase I/II study, we established neoadjuvant chemotherapy (NAC) using bi-weekly docetaxel, cisplatin, and S-1 (DCS) for clinical stage III gastric cancer. This study aimed to clarify long-term outcomes of this treatment. PATIENTS AND METHODS: Relapse-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method and prognostic factors for RFS and OS were identified by univariate analysis. RESULTS: A total of 47 patients with clinical stage III gastric cancer were enrolled in this study. The 5-year RFS and OS rates were 69.8% and 74.3%, respectively, in all registered patients. Moreover, the 5-year OS and RFS rates in patients receiving R0 gastrectomy were 68.0% and 79.4%, respectively. Neutrophil-lymphocyte ratio (NLR) before NAC ≥2.41, prognostic nutritional index (PNI) before NAC ≤50.4, Glasgow prognostic score before NAC classification 2, NLR after NAC ≥1.43, PNI after NAC <48.0, and Grade 1a/1b pathological response significantly worsened RFS. NLR after NAC ≥1.43, PNI before NAC ≤50.4, NLR after NAC ≥1.43, and body weight loss >5 kg after NAC significantly worsened OS. CONCLUSION: Although bi-weekly DCS therapy as neoadjuvant setting showed acceptable long-term outcomes, poor immune-nutritional status before and after NAC caused worse long-term survival in stage III gastric cancer patients. It is warranted to conduct a well-designed prospective randomized control study to compare long-term outcomes using the bi-weekly DCS regimen between patients with and without immune-nutritional support during peri-NAC.

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. Currently, several institutions are attempting to generate immune cells from induced pluripotent stem cells (iPSCs) for use in cancer immunotherapy. A method for generating dendritic cells (DCs) and macrophages (MPs) from iPSC has been established. iPSC-derived DCs (iPS-DCs) can activate T cells via antigen presentation, and iPSC-derived macrophages (iPS-MPs) attack cancer. Since iPSCs are used as the source, genetic modification is easy, and various immune functions, such as the production of anti-tumour cytokines, can be added. Furthermore, when iPS-DCs and iPS-MPs are immortalized, cost reduction through mass production is theoretically possible. In this review, the achievements of cancer research using iPS-DCs and iPS-MPs are summarized, and the prospects for the future are discussed.

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. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups. RESULTS: The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03). CONCLUSIONS: Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.

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. For 33 of these patients, splenectomy was performed, and the remaining 113 underwent spleen-preservation gastrectomy. Short- and long-term results were compared between the splenectomy and spleen-preservation groups, with the incidence of #10 metastasis in the splenectomy group and recurrence in the spleen-preservation group compared. RESULTS: In the splenectomy group, longer operative time, greater blood loss, more frequent postoperative abdominal infection, and longer hospital stay were observed than in the spleen-preservation group. The two groups exhibited no differences in median relapse-free survival time (31.1 vs 59.8 months; P = 0.684) or median overall survival time (64.9 vs 65.1 months; P = 0.765). The pathologic #10 lymph node metastasis rate was 3% in the splenectomy group, and the #10 lymph node recurrence rate was 2.7% in the spleen-preservation group. CONCLUSIONS: Prophylactic splenectomy showed more frequent postoperative morbidities and a longer hospital stay than spleen preservation, without any long-term survival benefits.

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. Patients who were lost to follow-up (n = 27), had tumors not eligible for surgery (n = 14), and could not achieve R0 resection (n = 7) were excluded from this retrospective study. The remaining 186 patients were included. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were evaluated. RESULTS: The incidence of postoperative complications with Clavien-Dindo grade ≥ II was observed in 61 patients (32.8%). The 5-year relapse-free survival and overall survival (OS) rates were 84.2% and 63.4%, respectively. Multivariate analysis showed that geriatric nutritional risk index (<98) (odds ratio, 1.97; p = 0.047), neutrophil/lymphocyte ratio (>2.36) (odds ratio, 1.94; 95% confidence interval, 1.02-3.67; p = 0.043), and total gastrectomy (TG) (odds ratio, 1.97; p = 0.042) significantly predicted postoperative complications. Moreover, TG (hazard ratio, 1.91; p = 0.036) was an independent prognostic factor of OS. CONCLUSIONS: Poor immunonutritional status and TG led to worse short-term outcomes. Moreover, TG was an independent prognostic factor of OS in older patients with gastric cancer. It is necessary to provide effective perioperative care, including nutritional support, to clarify whether short-term outcomes would be improved.

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. Responders were defined as patients who demonstrated a complete response (CR) or partial response (PR). Multivariate analysis for objective response was performed using a logistic regression model, and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: Among the 155 patients included, 20 and 84 patients demonstrated a CR and PR, respectively, resulting in a response rate of 67.1%. The median overall survival (OS) was 15.2 months, and the 3-year survival rate was 32.1%. High Glasgow prognostic score (GPS) and advanced N-category independently predicted the objective response to CRT. GPS and objective response were independent prognostic factors for OS. There was no significant difference in the long-term survival of responders who received subsequent chemotherapy or salvage surgery. CONCLUSIONS: High GPS and advanced N-category predicted a poor objective response to CRT in patients with T4b ESCC. Therefore, chemotherapeutic regimens with a higher efficacy are required. The indications for salvage surgery for responders should be carefully considered, with care taken to avoid complications. To confirm this, prospective randomized controlled studies are necessary.

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. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. RESULTS: The proportions of comorbid diseases (85.7% vs. 57.1%; P < 0.001), the American Society of Anesthesiologists score (1/2/3; 2.6%/94.8%/2.6% vs. 42.9%/57.1%/0%; P < 0.001), the preoperative systemic inflammation score (SIS) (0/1/2; 20.8%/48.1%/31.2% vs. 38.4%/38.4%/23.2%; P = 0.036), and postoperative complications (Clavien-Dindo grade ≥ III) (33.8% vs. 20.5%; P = 0.041) were significantly higher in the elderly group than those in the non-elderly group. However, long-term overall survival (OS) and relapse-free survival were not significantly different between the groups. On multivariate analysis, SIS (hazard ratio, 3.06; P = 0.037) and severe postoperative complications (hazard ratio, 2.01; P = 0.039) were significantly correlated with OS in the elderly group. CONCLUSIONS: As SIS and severe postoperative complications lead to poor prognosis after R0 esophagectomy in elderly patients, selecting appropriate patients for esophagectomy and preventing severe postoperative complications is essential.

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. The cutoff values of preoperative NLR (pre-NLR), postoperative NLR (post-NLR), preoperative LMR (pre-LMR), and postoperative LMR (post-LMR) were defined by the Contal and O'Quigley method as 2.3, 3.0, 2.5, and 3.2, respectively. A Cox proportional hazard model was used to identify the independent prognostic factors among NLR, LMR, and other clinicopathological factors. RESULTS: There were significant differences in the overall survival (OS) between the two groups: high post-NLR groups vs. low post-NLR group (median survival time, months) (10.9 vs. 22.8, P = 0.006) and high pre-LMR group vs. low pre-LMR group (21.3 vs. 11.0, P = 0.001). The LMR value elevated significantly after gastrectomy (P = 0.020), although not in the NLR value (P = 0.733). On multivariate analysis, high post-NLR (hazard ratio = 1.506; 95% confidence interval = 1.047-2.167; P = 0.027), low pre-LMR (1.773; 1.135-2.769, 0.012), and no postoperative chemotherapy (1.558; 1.053-2.305, 0.027) were found to be independent prognostic factors for adverse OS. CONCLUSIONS: Because a combination of high post-NLR and low pre-LMR may be an adverse prognostic marker in resectable CY1 gastric cancer patients, it is necessary to conduct a prospective trial to confirm a useful perioperative chemotherapeutic regimen for these patients.

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. The cut-off values of each dimensional factor was decided by the ROC curve. RESULTS: Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. CONCLUSIONS: The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

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. RESULTS: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1-100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141-0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. CONCLUSION: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

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). Patients' characteristics, intraoperative outcomes, postoperative complications, and survival time were compared between the 2 groups. RESULTS: Median anastomosis time was significantly longer in the converse Ω group than in the extracorporeal group (40.0 vs. 30.5 min, P=0.005). However, the total procedure time did not differ significantly between the groups. Intraoperative blood loss volume was significantly lower in the converse Ω group than in the extracorporeal anastomosis group (40 vs. 120 mL, P<0.001). There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, or length of hospital stay. The postoperative body mass index and the prognostic nutritional index did not differ between the groups 1 year after surgery. There were no significant differences in overall survival and relapse-free survival between the 2 groups. CONCLUSIONS: Converse Ω anastomosis is feasible and safe. This novel technique can be adopted as a treatment option for reconstruction after LDG in patients with early-stage gastric cancer. Therefore, the risks and benefits of converse Ω anastomosis after LDG should be confirmed in larger cohorts.

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. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen. RESULTS: Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature.

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. Intramuscular adipose tissue content (IMAC) was used to evaluate the quality of skeletal muscle by analysing computed tomography (CT) images at the level of the umbilicus. The impact of poor skeletal muscle quality on short-term and long-term outcomes after hepatectomy for colorectal liver metastasis was analysed. RESULTS: Patients were divided into two groups (high IMAC and normal IMAC) according to their IMAC values, and their backgrounds were compared. There were no significant differences in most factors between the two groups. However, both body mass index (P = 0.030) and the incidence of postoperative complications of Clavien-Dindo grade 3 or worse (P = 0.008) were significantly higher in the high-IMAC group. In multivariate analyses, an operative blood loss > 600 ml (P = 0.006) and high IMAC (P = 0.008) were associated with postoperative complications of Clavien-Dindo grade 3 or worse. Overall survival and recurrence-free survival were significantly lower (P < 0.001 and P = 0.045, respectively) in the high-IMAC group than in the normal IMAC group. In multivariate analyses for poor overall survival, high IMAC was associated with poor overall survival (P < 0.001). CONCLUSIONS: IMAC is a prognostic factor for poor short- and long-term outcomes in patients with colorectal liver metastasis.

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. METHODS: We evaluated patients with UR-PC referred to our department for possible surgical resection between January 2008 and June 2017. Resectability was evaluated using multimodal imaging in patients who underwent chemotherapy for more than 6 months. Conversion surgery was performed only in patients who were judged eligible for R0 resection. RESULTS: In total, 90 patients were evaluated. Among them, only 22 (24.4%) could actually undergo conversion surgery, and the R0 resection rate was 72.7% (16/22). Although Evans grade ≥ IIB was noted in six patients (27.3%), none achieved complete response (CR). The median survival time was significantly longer among patients who underwent conversion surgery than in the unresected patients who underwent chemotherapy (21.3 months vs. 12.6 months; p < 0.001). Multivariate and Kaplan-Meier analyses revealed microvascular invasion to have a significant adverse effect on recurrence-free survival (RFS: 7 months vs. not reached, p = 0.004) and overall survival (OS: 21 months vs. 85 months, p = 0.047). CONCLUSIONS: After long-term chemotherapy, conversion surgery for UR-PC is associated with long-term survival. Microvascular invasion is predictive of poor prognosis in these patients; adjuvant protocols are therefore needed for patients with microvascular invasion.

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. The gene-modified cell actively influences host XCR1+ dendritic cells to enhance CD8+ T cell priming, resulting in CXCR3-dependent and STING-IRF3 pathway-independent systemic tumor control. Administration of IFN-α-iPSC-pMCs in combination with immune checkpoint blockade overcomes resistance to single-treatment modalities and generates long-lasting antitumor immunity. These preclinical data suggest that IFN-α-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade.

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. The associations between the pre- and post-NACRT NLR, PLR, mGPS, and clinicopathological characteristics, as well as their predictive values for survival outcomes, were analyzed. This study was approved by an institutional review board at Yokohama City University (B180600049). RESULTS: On multivariate analysis with a Cox's proportional hazards regression model, post-NACRT NLR ≥3 (p = 0.040; hazard ratio, 2.24; 95% CI 1.28-3.91) and lymph node metastasis (p = 0.002; hazard ratio, 2.33; 95% CI 1.36-3.99) were significantly associated with shorter overall survival. The median survival time was 22.0 months for patients with post-NACRT NLR ≥3 and 45.0 months for patients with post-NACRT NLR <3 (p = 0.028). CONCLUSIONS: The NLR following NACRT might predict survival in BR-PDAC patients. Patients with an elevated post-NACRT NLR or positive lymph node metastasis may be candidates for stronger adjuvant therapies.

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.e., developed recurrence within 1 year after pancreatectomy; n=30) and late/non-recurrence groups (n=31). The patient characteristics, clinicopathological factors of early recurrence, and survival time were retrospectively compared between groups. RESULTS: In the univariate analysis, the maximum standardized uptake value (SUVmax), microvascular invasion, and lymph node metastasis were associated with early recurrence. In the multivariate analysis, the pre-NACRT SUVmax and microvascular invasion in the early recurrence group were significantly different from that in the late/non-recurrence group. A pre-NACRT SUVmax >4.1 was an independent predictor of poor recurrence-free and overall survival. CONCLUSION: SUVmax and microvascular invasion are independent predictors of poor recurrence-free and overall survival after NACRT for BR-PDAC. Although complete pancreatectomy after NACRT was performed, approximately half of the patients had recurrence within 1 year.

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. RESULTS: Mean blood loss was significantly lower in the LG group, although the operation time did not differ. There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, total hospital stay, and the causes of death. The prognostic nutritional index and skeletal muscle index at 1 year were better maintained in the LG group than in the open gastrectomy group. The overall and relapse-free survivals did not differ. CONCLUSIONS: LG may be feasible in elderly patients with gastric cancer. A prospective randomized controlled trial should be conducted to confirm its efficacy.

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). We also describe the current state of personalized cancer immunotherapy based on neoantigens, and assess, based on our own research and experience, the potential of such therapy to elicit cancer regression. Finally, we discuss the future direction of cancer immunotherapy.

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. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination. The secondary endpoints were clinical and biologic outcomes. We demonstrated that the present vaccine induced GPC3 peptide-specific cytotoxic T lymphocytes (CTLs), which were found to infiltrate into the tumor. Moreover, we established GPC3 peptide-specific CTL clones from a biopsy specimen: these cells exhibited GPC3 peptide-specific cytokine secretion and cell cytotoxicity. The plasma GPC3 level tended to decrease temporarily at least once during the follow-up period. The GPC3-specific CTL frequency after vaccination was correlated with overall survival. The degree of skin reactions at the injection site correlated with the GPC3 peptide-specific CTLs. Furthermore, we sequenced the T cell receptors (TCRs) of tumor-infiltrating lymphocyte (TIL) clones, and confirmed the existence of this TCR repertoire in both tumor tissue and PBMCs. In response to these data, we are developing TCR-engineered T cell therapy using TCR sequences obtained from GPC3 peptide-specific CTL clones for improved efficacy in patients with advanced HCC.