Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Laparoscopic sleeve gastrectomy for morbid obesity improves gut microbiota balance, increases colonic mucosal-associated invariant T cells and decreases circulating regulatory T cells.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) for morbid obesity may improve gut microbiota balance and decrease chronic inflammation. This study examines the changes in gut microbiota and immune environment, including mucosal-associated invariant T cells (MAIT cells) and regulatory T cells (Treg cells) caused by LSG. METHODS: Ten morbidly obese patients underwent LSG at our institution between December 2018 and March 2020. Flow cytometry for Th1/Th2/Th17 cells, Treg cells and MAIT cells in peripheral blood and colonic mucosa and 16S rRNA analysis of gut microbiota were performed preoperatively and then 12 months postoperatively. RESULTS: Twelve months after LSG, the median percent total weight loss was 30.3% and the median percent excess weight loss was 66.9%. According to laboratory data, adiponectin increased, leptin decreased, and chronic inflammation improved after LSG. In the gut microbiota, Bacteroidetes and Fusobacteria increased after LSG, and indices of alpha diversity increased after LSG. In colonic mucosa, the frequency of MAIT cells increased after LSG. In peripheral blood, the frequency of Th1 cells and effector Treg cells decreased after LSG. CONCLUSIONS: After LSG for morbid obesity, improvement in chronic inflammation in obesity is suggested by change in the constituent bacterial species, increase in the diversity of gut microbiota, increase in MAIT cells in the colonic mucosa, and decrease in effector Treg cells in the peripheral blood.

Nutritional benefit of remnant gastric preservation in patients with esophageal cancer undergoing radical esophagectomy and ileo-colon interposition.

BACKGROUND: This retrospective study aimed to investigate the short-term surgical outcomes and nutritional status of ileo-colon interposition in patients with esophageal cancer who could not undergo gastric tube reconstruction. METHODS: Sixty-four patients underwent subtotal esophagectomy with reconstruction using ileo-colon interposition for esophageal cancer at the Wakayama Medical University Hospital between January 2001 and July 2020. Using propensity scores to strictly balance the significant variables, we compared treatment outcomes. RESULTS: Before matching, 18 patients had cologastrostomy and 46 patients had colojejunostomy. After matching, we enrolled 34 patients (n = 17 in cologastrostomy group, n = 17 in colojejunostomy group). Median operation time in the cologastrostomy group was significantly shorter than that in the colojejunostomy group (499 min vs. 586 min; P = 0.013). Perforation of the colon graft was observed in three patients (7%) and colon graft necrosis was observed in one patient (2%) in the gastrojejunostomy group. Median body weight change 1 year after surgery in the cologastrostomy group was significantly less than that of the colojejunostomy group (92.9% vs. 88.5%; P = 0.038). Further, median serum total protein level 1 year after surgery in the cologastrostomy group was significantly higher than that of the colojejunostomy group (7.0 g/dL vs. 6.6 g/dL, P = 0.030). CONCLUSIONS: Subtotal esophagectomy with reconstruction using ileo-colon interposition is a safe and feasible procedure for the patients with esophageal cancer in whom gastric tubes cannot be used. Cologastrostomy with preservation of the remnant stomach had benefits in the surgical outcomes and the postoperative nutritional status.

Phase 1 Study of Combined Chemotherapy of Nab-Paclitaxel, S-1, and Oxaliplatin for Gastric Cancer with Peritoneal Metastasis (NSOX Study).

OBJECTIVES: A regimen of S-1 combined with oxaliplatin (SOX) has been widely used as the first-line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric cancer patients with peritoneal metastasis, we added nab-paclitaxel to the established SOX regimen (NSOX). Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. We performed a phase 1 study of this regimen to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in patients with gastric cancer with peritoneal metastasis. METHODS: The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 [level 1] to 80 [level 4] mg/m2 on days 1 and 8) and fixed doses of oxaliplatin (100 mg/m2 on day 1) and S-1 (80 mg/m2/day for 2 weeks). RESULTS: Six patients with gastric cancer with peritoneal metastasis were enrolled. The MTD was determined to be dose level 2, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. No patients experienced DLTs, so the RD was determined to be dose level 1. CONCLUSIONS: The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.

Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune-checkpoint inhibitors.

Immune-related adverse events (irAEs) are often seen during immune-checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow-up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty-six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL-1ß, IL-2, and GM-CSF at baseline, and early decrease of IL-8, G-CSF, and MCP-1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti-PD-1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre-existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.

Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade.

BACKGROUND: Cancer peptide vaccines show only marginal effects against cancers. Immune checkpoint inhibitors (ICIs) show significant curative effects in certain types of cancers, but the response rate is still limited. In this study, we aim to improve cancer peptide vaccination by targeting Ag peptides selectively to a dendritic cell (DC) subset, XCR1-expressing DCs (XCR1+ DCs), with high ability to support CD8+ T-cell responses. METHODS: We have generated a fusion protein, consisting of an Ag peptide presented with MHC class I, and an XCR1 ligand, XCL1, and examined its effects on antitumour immunity in mice. RESULTS: The fusion protein was delivered to XCR1+ DCs in an XCR1-dependent manner. Immunisation with the fusion protein plus an immune adjuvant, polyinosinic:polycytidylic acids (poly(I:C)), more potently induced Ag-specific CD8+ T-cell responses through XCR1 than the Ag peptide plus poly(I:C) or the Ag protein plus poly(I:C). The fusion protein plus poly(I:C) inhibited the tumour growth efficiently in the prophylactic and therapeutic tumour models. Furthermore, the fusion protein plus poly(I:C) showed suppressive effects on tumour growth in synergy with anti-PD-1 Ab. CONCLUSIONS: Cancer Ag targeting to XCR1+ DCs should be a promising procedure as a combination anticancer therapy with immune checkpoint blockade.

Phase I/II Trial of Chemotherapy with Docetaxel, Cisplatin, and S-1 for Unresectable Advanced Squamous Cell Carcinoma of the Esophagus.

Our previous trial with a docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen showed high response rates in metastatic squamous cell carcinoma of the esophagus (SCCE). The observed increased toxicity of the DCF regimen, however, was clinically harmful. S-1, an oral anticancer drug, has been approved as a combination therapy for SCCE, and alternate-day regimen with S-1 has shown lower levels of toxicity. This prospective single-center phase I/II trial examines the efficacy and toxicity of a combination of docetaxel, cisplatin, and an alternate-day regimen of S-1 (modified DCS) for patients with metastatic SCCE. We use a two-stage design. Phase I is undertaken to determine the maximum tolerated dose and the recommended dose. The phase I trial adopts a three-patient cohort with escalating dose study design. In the phase II trial, the primary endpoint is the assessment of the overall response rate (Response Evaluation Criteria in Solid Tumors 1.1). The secondary endpoints are the evaluation of drug-related toxicity (National Cancer Institute Common Toxicity Criteria 4.0), overall survival, and progression-free survival. Fifty patients with metastatic SCCE participate in the phase II section. This study protocol is the first to test the effects of the modified DCS regimen for metastatic SCCE.

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer.

BACKGROUND: We conducted a phase I/Ib, open-label, single-arm trial to assess the safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine in patients with advanced gastric cancer. METHODS: Patients with advanced gastric cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to evaluate the safety, immunological response and schedule. Based on the highest specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the ELISPOT test, cohorts were expanded to define the optimal dosing schedule for OTSGC-A24. RESULTS: In this study, 24 advanced gastric cancer patients with HLA-A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w cohort: 11 and 1w cohort: 10 patients). The most common adverse events were decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common treatment-related adverse event was injection site erythema (25%). No dose-limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated. Positive CTL responses after vaccination were observed in 15 patients (75%) at 4 weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18 patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort (78%). The best radiological was stable disease (40%). Median progression free survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7 months (95% CI 3.8 to 8.6). CONCLUSIONS: OTSGC-A24 combined peptide cancer vaccine was well tolerated. Significant responses in CTL were observed and the recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although no radiological response was observed, a respectable overall survival was achieved, consistent with other immunotherapy agents being investigated in gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01227772 , Date registered: 21 Oct 2010.

Laparoscopic and endoscopic cooperative surgery is a feasible treatment procedure for intraluminal gastric gastrointestinal stromal tumors compared to endoscopic intragastric surgery.

BACKGROUND: Laparoscopic wedge resection of the stomach is an ideal procedure if the gastric gastrointestinal stromal tumors (GISTs) are located in the extraluminal stomach. When the tumor is located in the intraluminal stomach, two minimally invasive surgical procedures involving laparoscopic and endoscopic cooperative surgery (LECS) or endoscopic intragastric surgery (EIGS) are frequently performed. To date, there have been no comparative studies of LECS and EIGS in patients with intraluminal gastric GISTs regarding short-term and long-term outcomes. The aim of this study was to compare the safety and feasibility of LECS and EIGS in patients with intraluminal gastric GISTs. METHODS: This was a single-center retrospective study of 46 consecutive patients with intraluminal gastric GISTs who underwent minimally invasive surgery. LECS (n = 21) was performed between 2013 and 2015 and EIGS (n = 26) was performed between 2001 and 2013. RESULTS: The overall incidence of perioperative complications was significantly higher in the EIGS group than in the LECS group (40 vs 4.8%; P = 0.006). In the EIGS group, three patients with intraoperative gastric mucosal injury were followed-up throughout surgical repair (12%). An esophageal tear was found in one patient during oral removal of tumor (4%). Postoperative gastric hemorrhage occurred in three patients (12%) and superficial surgical site infection was observed in three patients (12%). In the LECS group, anastomotic leakage requiring additional drainage was observed in one patient (4.8%). EIGS had less favorable results regarding median time to resumption of first oral intake (2 vs 1 days; P = 0.005). Two of 46 patients (4.3%), including one patient who underwent LECS and one patient who underwent EIGS developed recurrence. No cause-specific deaths were observed. CONCLUSION: LECS is a feasible and safe procedure for intraluminal gastric GISTs with regard to both short-term surgical and long-term oncological outcomes. Registration number: UMIN000026631.

[In Vivo Antigen Delivery to Dendritic Cells-A Novel Peptide Vaccine for Cancer Therapy].

Tumor-derived peptides can induce antitumor cytotoxic T lymphocyte(CTL)response. However, the effects are limited. We aimed to overcome this limitation by selectively delivering antigen peptides to an XC chemokine receptor 1-expressing dendritic cell subset(XCR1+DC)that is notable for its exceptional ability to generate CTL response. To do that, we designed a vaccine(mXCL1-OVA peptide vaccine)that consisted of a murine XCR1 ligand(XCL1)and an ovalbumin(OVA)-derived MHC class I-restricted antigen. When co-injected with the immune adjuvant polyinosinic-polycytidylic acid(poly[I: C]), mXCL1-OVA peptide vaccine showed much greater antigen-specific cytotoxic T cell(CTL)response than either OVA protein plus poly(I: C)or OVA peptide plus poly(I: C). Furthermore, mXCL1-OVA peptide vaccine plus poly(I: C)showed more prominent antitumor effects against OVA-expressing melanoma(B16-OVA)than other vaccines with regard to growth inhibition. Thus, our results suggest that chemokine-directed antigen delivery to DC subsets with high CTL-inducing ability is a promising method for generating effective antitumor immunity.

Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients.

We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1-20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.

Expression of BRCA1, a factor closely associated with relapse-free survival, in patients who underwent neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil for squamous cell carcinoma of the esophagus.

PURPOSE: The aim of this study was to identify the biomarkers associated with chemotherapeutic efficacy and long-term survival for patients with advanced squamous cell carcinoma of the esophagus (SCCE) who had received neoadjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil (NAC-DCF). METHODS: This study included 45 patients with advanced SCCE who received NAC-DCF between 2008 and 2012. The NAC-DCF was conducted as a phase II study (UMIN000007408). The expressions of excision repair cross-complementing-1 (ERCC1), class III beta-tubulin, breast cancer susceptibility gene I (BRCA1), and thymidylate synthase were investigated simultaneously in the pre-treatment endoscopic tumor biopsy samples. RESULTS: A multivariate logistic regression analysis indicated that pathological responses were significantly associated with tumors with low ERCC1 expression (P = 0.016) and with tumors with high BRCA1 expression (P = 0.030). The multivariate Cox proportional hazard model analysis for relapse-free survival revealed high BRCA1 expression (P = 0.031, hazards ratio 4.39) as the factor associated with survival. CONCLUSIONS: Low ERCC1 expression and high BRCA1 expression in patients with SCCE were associative biomarkers for chemotherapeutic efficacy. High BRCA1 expression was considered the factor associated with survival. These findings may be helpful for tailoring chemotherapy.

The effects of rikkunshito on body weight loss after esophagectomy.

BACKGROUND: After esophagectomy, esophageal cancer patients suffer from malnutrition, anorexia, and dysfunction of digestion and absorption. Rikkunshito, a traditional Japanese herbal medicine, reportedly attenuates gastrointestinal symptoms and appetite loss after gastrointestinal surgery. We evaluated the clinical effect of rikkunshito and its relationship with ghrelin in esophageal cancer patients after esophagectomy. METHODS: This prospective nonrandomized study included 40 patients with esophageal cancer who underwent esophagectomy at Wakayama Medical University Hospital. They were assigned to either the control group (n = 20, April 2011-January 2012) or the rikkunshito group (n = 20, January 2012-August 2012). Patients in the rikkunshito group received 2.5 g of rikkunshito before every meal for 48 wk beginning 4 wk after surgery. During the 48-week treatment, we assessed body weight loss, nutritional parameters, and quality of life (Functional Assessment of Cancer Therapy-Esophageal scale). The primary end point was the rate of body weight loss in two groups after the 48-week treatments. RESULTS: The rate of body weight loss was significantly less in the rikkunshito group than in the control group (P = 0.016). The acyl ghrelin level after the 48-week treatments was significantly higher in the rikkunshito group (131.7% ± 74.5%) than in the control group (75.6% ± 47.5%, P = 0.039). For the Functional Assessment of Cancer Therapy-Esophageal symptom scale, satisfaction of food consumption in the rikkunshito group was significantly better than in the control group at 52 wk postoperatively (P = 0.031). CONCLUSIONS: For esophageal cancer patients after esophagectomy, rikkunshito is useful for improving body weight loss in connection with an increase in plasma acyl ghrelin levels.

[Cancer Immunotherapy Using Human Induced Pluripotent Stem Cell-Derived Dendritic Cells(iPSDCs)Expressing Carcinoembryonic Antigen].

The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture. Additionally, the surface marker expression, cytokine production, and migratory capacity of human iPSDCs were equivalent to those of monocyte-derived DCs(MoDCs). After 3 cycles of stimulation of autologous PBMCs by genetically modified DCs, the 51Cr-release assay was performed. The lymphocytes stimulated by iPSDCs-CEA showed cytotoxic activity against LCL-CEA and CEA652-pulsed LCL, but showed no cytotoxicity against LCL-LacZ. In addition, they showed cytotoxic activity against CEA-positive human cancer cell lines, MKN45 and HT29, but showed no cytotoxicity against CEA-negative human cancer cell line MKN1. In conclusion, CEA-specific CTLs responses could be induced by iPSDCs-CEA. This vaccination strategy may be useful in future clinical applications of cancer vaccines.

Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: in comparison to bone marrow-derived DCs.

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a (51) Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

Is preoperative colonoscopy necessary for patients undergoing gastric cancer surgery?

PURPOSE: The aim of this study was to evaluate the necessity of preoperative colonoscopy (CS) in gastric cancer (GC) patients and to assess the outcomes of different treatments in patients with synchronous GC and colorectal neoplasms (CRN). We also determined the risk factors influencing the comorbidity of colorectal cancer (CRC) in patients with GC. METHODS: This retrospective study included 1891 consecutive GC patients who underwent CS before surgery from January 1, 1999, through June 30, 2012. RESULTS: There was a high prevalence of concurrent CRN (28.4 %) and CRC (3.2 %) in our patients with GC. Sixty-one patients with GC had synchronous CRC. Twenty-three of the 61 tumors were perioperatively treated by endoscopic resection. The other 38 tumors were treated by simultaneous surgery for the GC and CRC. Surgical complications were not found in either the endoscopic or surgical resection group. The multivariate logistic regression analysis indicated that the prevalence of synchronous CRC in patients with GC was significantly associated with the incidence of multiple GCs [P < 0.0001; odds ratio (OR) 15.3], having anemia (P = 0.002; OR 3.0), and having a smoking history (P = 0.021; OR 1.9). CONCLUSIONS: We recommend preoperative CS screening for GC patients. In particular, preoperative CS screening is indispensable for patients with multiple GCs. In addition, simultaneous treatments for patients with synchronous GC and CRN are safe and feasible procedures.

Endoscopic submucosal dissection for gastric tumors in various types of remnant stomach.

BACKGROUND AND STUDY AIMS: The aim of this study was to examine the clinical outcomes of endoscopic submucosal dissection (ESD) for gastric tumors in various types of remnant stomach. PATIENTS AND METHODS: Between January 2002 and March 2013, ESD was performed for 750 gastric tumors. Of these lesions, 49 were in a remnant stomach, and were included in the study. RESULTS: The en bloc resection rate was 100 %. The curative resection rate was 82 %. The rate of perforation was high in patients with gastric conduits (28.6 %). Perforation was significantly more common in patients with lesions located on the suture line (4.9 % vs. 50.0 %; P = 0.0043). CONCLUSION: ESD for gastric tumors in the remnant stomach can be considered feasible and safe in clinical practice. However, the procedure is technically more difficult in patients with a gastric conduit, due to the increased risk of perforation at the suture line.

Atrial fibrillation after esophageal cancer surgery: an analysis of 207 consecutive patients.

PURPOSE: The aim of this study was to identify perioperative risk factors that are associated with postoperative atrial fibrillation (AF) and the outcomes of different pharmacological interventions in esophageal cancer patients who underwent transthoracic esophagectomy. METHODS: This study included 207 patients who underwent a transthoracic esophagectomy for esophageal cancer resection by a single surgeon from January 1, 2004, through December 31, 2010. RESULTS: Postoperative AF occurred in 19 patients (9.2 %), all of whom received antiarrhythmic drug therapy at the early stage. Antiarrhythmic treatment was effective in 12 cases (63.2 %). In this study, landiolol hydrochloride, an ultrashort-acting ß1-selective ß-blocker, was the first-line therapy for postoperative AF. A multivariate logistic regression analysis showed that postoperative AF was significantly associated with the use of an ileo-colon for reconstruction after esophagectomy (P = 0.0023, odds ratios [OR] = 13.6) and with the presence of tachycardia with a heart rate of >100 bpm on postoperative day (POD) 1 (P = 0.0004, OR = 18.4). CONCLUSIONS: Postoperative AF is associated with the use of a colon conduit for reconstruction after esophagectomy and with tachycardia with a heart rate >100 bpm on POD 1. Identifying patients at high risk for postoperative AF will allow for more direct application of pharmacological methods of prophylaxis.

Clinical benefits of thoracoscopic esophagectomy in the prone position for esophageal cancer.

PURPOSES: The clinical benefits of thoracoscopic radical esophagectomy in the prone position compared to conventional open esophagectomy have not been fully documented. METHODS: Forty-six patients with esophageal cancer who underwent MIE in the prone position (MIE-P group) were enrolled, and 46 case-matched controls that underwent open esophagectomy (OE group) were identified using propensity score methods to achieve a valid comparison of outcomes between MIE and open esophagectomy. RESULTS: The duration of systemic inflammatory response syndrome was shorter in the MIE-P group than in OE group (P = 0.005). The time to first walking was earlier in the MIE-P group (P < 0.001). Although the vital capacity ratio (%VC) declined after the operation in both groups, the change ratio of the %VC was 85.3% in the MIE-P group and 69.6% in the OE group (P < 0.001). No mortality occurred in either group. The postoperative morbidity rate was lower in the MIE-P group (13%) than in the OE group (30.4%) (P = 0.020). Two patients (4.3%) in the OE group and one patient in the MIE-P group (2.2%) had pneumonia. CONCLUSIONS: MIE in the prone position was associated with less impairment of the pulmonary function, earlier recovery of activity and lower subsequent morbidity compared to open esophagectomy. Further investigation of the long-term outcomes is, therefore, needed.

New prognostic score for the survival of patients with esophageal squamous cell carcinoma.

PURPOSE: Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS. METHODS: One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP. RESULTS: Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000-9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021-7.112, p = 0.0449). CONCLUSIONS: The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.