Feeding jejunostomy following esophagectomy may increase the occurrence of postoperative small bowel obstruction.

This study aimed to clarify the characteristics and treatment of bowel obstruction associated with feeding jejunostomy in patients who underwent esophagectomy for esophageal cancer. In this single-center retrospective study, 363 patients underwent esophagectomy with mediastinal lymph node dissection for esophageal cancer at the Wakayama Medical University Hospital between January 2014 and June 2021. All patients who underwent esophagectomy routinely underwent feeding jejunostomy or gastrostomy. Feeding jejunostomy was used in the cases of gastric tube reconstruction through the posterior mediastinal route or colon reconstruction, while feeding gastrostomy was used in cases of retrosternal route gastric tube reconstruction. Nasogastric feeding tubes and round ligament technique were not used. Postoperative small bowel obstruction occurred in 19 of 197 cases of posterior mediastinal route reconstruction (9.6%), but in no cases of retrosternal route reconstruction because of the feeding gastrostomy (P < .0001). Of the 19 patients who had bowel obstruction after feeding jejunostomy, 10 patients underwent reoperation (53%) and the remaining 9 patients had conservative treatment (47%). The cumulative incidence of bowel obstruction after feeding jejunostomy was 6.7% at 1 year and 8.7% at 2 years. Feeding jejunostomy following esophagectomy is a risk factor for small bowel obstruction. We recommend feeding gastrostomy inserted from the antrum to the jejunum in the cases of gastric tube reconstruction through the retrosternal route or nasogastric feeding tube in the cases of reconstruction through the posterior mediastinal route.

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.

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.

Tumor RNA transfected DCs derived from iPS cells elicit cytotoxicity against cancer cells induced from colorectal cancer patients in vitro.

Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with in vitro transcriptional RNA (ivtRNA), which was obtained from tumors of three patients with colorectal cancer. We investigated iPSDCs-ivtRNA which were induced by transfecting ivtRNA obtained from tumors of three colorectal cancer patients, and examined its antitumor effect. Moreover, we analyzed neoantigens expressed in colorectal cancer cells and examined whether iPSDCs-ivtRNA induced cytotoxic T lymphocytes (CTLs) against the predicted neoantigens. CTLs activated by iPSDCs-ivtRNA exhibited cytotoxic activity against the tumor spheroids in all three patients with colorectal cancer. Whole-exome sequencing revealed 1251 nonsynonymous mutations and 2155 neoantigens (IC50 < 500 nM) were predicted. For IFN-γ ELISPOT assay, these candidate neoantigens were further prioritised and 12 candidates were synthesized. IFN-γ ELISPOT assay revealed that the CTLs induced by iPSDCs-ivtRNA responded to one of the candidate neoantigens. In vitro CTLs obtained by transfecting tumor-derived RNA into iPSDCs derived from three patients with colorectal cancer showed potent tumor-specific killing effect.

Immune Cells Profiles in the Different Sites of COVID-19-Affected Lung Lobes in a Single Patient.

Whereas the COVID-19 disease pathophysiology is under investigation, it is important to identify the pathways of viral transmission and inflammation from the pre-illness to the disease-onset stages. We analyzed five lung lobes from a patient with COVID-19 who finally died after prolonged lung protective ventilation. Pathological examination revealed moderate inflammation in upper lung lobes and uneven yet severe inflammation and diffuse alveolar damage in lower lung lobes. SARS-CoV-2 was detected at higher levels not in severely, but rather moderately inflamed middle lung lobes, and immunohistochemistry and bulk RNA-sequencing results showed that immune cells were detected at higher levels in lower lung lobes. The mRNA expression of cytokine families varied. We found an increase in keratin 5- or aquaporin 3-expressing basal cells in the severely inflamed lower lung lobes, and the alveolar stromal tissues were filled with them. Thus, this analysis of lung samples from a patient helps to determine the COVID-19 pathophysiology at a specific time point, and the virus localization and inflammatory responses at each site of the lungs provide various important indications.

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.

Venous Invasion Is a Risk Factor for Recurrence of pT1 Gastric Cancer with Lymph Node Metastasis.

BACKGROUND: Postoperative adjuvant therapy for early gastric cancer (EGC) has not been widely studied, and there are differing indications for postoperative adjuvant therapy between Western and Asian countries. Japanese gastric cancer treatment guidelines do not recommend adjuvant chemotherapy for EGC, but it is unclear whether surgery alone is the most appropriate treatment. METHODS: This is a single-center retrospective study of 1001 consecutive patients who underwent radical gastrectomy for pT1 gastric cancer between 1999 and 2013 at the Wakayama Medical University Hospital. RESULTS: Recurrence was observed in 12 patients, nine of whom as the result of hematogenous metastasis. In all patients with pT1 gastric cancer (n = 1001), lymph node metastasis was identified as an independent predictive factor for recurrence (hazard ratio [HR] = 10.910, P = 0.002). In patients with pT1N + gastric cancer, however, the 5-year disease-specific survival (DSS) rate was still high, 90.8%. In patients with pT1N + gastric cancer (n = 97), the presence of venous invasion (pT1N + v +) was identified by univariate and multivariate analyses as an independent risk factor for recurrence (HR = 4.791, P = 0.032). In patients with venous invasion, the 5-year DSS rate was significantly lower than that in those without venous invasion (79.3% vs. 95.2%, P = 0.018). CONCLUSIONS: Long-term prognosis of patients with EGC with lymph node metastasis is good, but venous invasion is associated with a higher risk of recurrence. Selective application of postoperative adjuvant chemotherapy for pT1N + v + gastric cancer may efficiently improve prognosis among patients with EGC.

Pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach for cervical esophageal cancer with right aortic arch: Case report.

We performed pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach and reconstruction of the elongated gastric conduit with microvascular anastomosis for an 83-year-old male patient with esophageal cancer and right aortic arch. For such cases, a surgical approach via the left thoracic cavity is rational, and cases of pharyngolaryngectomy with thoracoscopic esophagectomy require a long reconstruction organ. Also, in cases of right aortic arch, a longer reconstruction route is made to avoid Kommerell's diverticulum. The patient had laryngeal cancer and was diagnosed with cervical esophageal cancer and preoperative computed tomography revealed right aortic arch. There were no complications after surgery, and food intake was good. Pharyngolaryngectomy with thoracoscopic esophagectomy via the left thoracic approach and reconstruction of the elongated gastric conduit with microvascular anastomosis is suggested to be a safe and feasible technique for cases of cervical esophageal cancer with right aortic arch.

ISOlation Procedure vs. conventional procedure during Distal Pancreatectomy (ISOP-DP trial): study protocol for a randomized controlled trial.

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach. METHODS/DESIGN: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival. DISCUSSION: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020.

Short-term Outcomes of Robotic Gastrectomy vs Laparoscopic Gastrectomy for Patients With Gastric Cancer: A Randomized Clinical Trial.

Importance: Robotic gastrectomy (RG) for gastric cancer may be associated with decreased incidence of intra-abdominal infectious complications, including pancreatic fistula, leakage, and abscess. Prospective randomized clinical trials comparing laparoscopic gastrectomy (LG) and RG are thus required. Objective: To compare the short-term surgical outcomes of RG with those of LG for patients with gastric cancer. Design, Setting, and Participants: In this phase 3, prospective superiority randomized clinical trial of RG vs LG regarding reduction of complications, 241 patients with resectable gastric cancer (clinical stages I-III) were enrolled between April 1, 2018, and October 31, 2020. Interventions: LG vs RG. Main Outcomes and Measures: The primary end point was the incidence of postoperative intra-abdominal infectious complications. Secondary end points were incidence of any complications, surgical results, postoperative courses, and oncologic outcomes. The modified intention-to-treat population excluded patients who had been randomized and met the postrandomization exclusion criteria. There was also a per-protocol population for analysis of postoperative complications. Results: This study enrolled 241 patients, with 236 patients in the modified intention-to-treat population (150 men [63.6%]; mean [SD] age, 70.8 [10.7] years). There was no significant difference in the incidence of intra-abdominal infectious complications (per-protocol population: 10 of 117 [8.5%] in the LG group vs 7 of 113 [6.2%] in the RG group). Of 241 patients, 122 were randomly assigned to the LG group, and 119 patients were randomly assigned to the RG group. Two of the 122 patients (1.6%) in the LG group converted from LG to open surgery, and 4 of 119 patients (3.4%) in the RG group converted from RG to open or laparoscopic surgery, with no significant difference. Finally, 117 patients in the LG group completed the procedure, and 113 in the RG group completed the procedure; these populations were defined as the per-protocol population. The overall incidence of postoperative complications of grade II or higher was significantly higher in the LG group (23 [19.7%]) than in the RG group (10 [8.8%]) (P = .02). Even in analysis limited to grade IIIa or higher, the complication rate was still significantly higher in the LG group (19 [16.2%]) than in the RG group (6 [5.3%]) (P = .01). Conclusions and Relevance: This study found no reduction of intra-abdominal infectious complications with RG compared with LG for gastric cancer. Trial Registration: umin.ac.jp/ctr Identifier: UMIN000031536.

Esophagogastrostomy With Fundoplication Versus Double-tract Reconstruction After Laparoscopic Proximal Gastrectomy for Gastric Cancer.

PURPOSE: We investigated that double-tract reconstruction (DTR) may be more beneficial than esophagogastrostomy (EG) with fundoplication in terms of nutritional outcomes, focusing on loss of body weight. MATERIALS AND METHODS: This study included 56 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy, 39 underwent EG. In the 17 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed DTR. RESULTS: There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein, and albumin) at 12 months. However, 8 patients in the EG group had extreme body weight loss (≥20%) within 12 months. Conversely, in the DTR group, no patients had any extreme body weight loss. CONCLUSION: DTR is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.

Advances in immunotherapy for pancreatic ductal adenocarcinoma.

Advances in immunotherapy against advanced cancers can be considered stunning and epoch-making. Meanwhile, efficacy of immune-based therapies, especially immune checkpoint inhibitors, remains insufficient in pancreatic ductal adenocarcinoma, differing from other immunogenic cancers. To date, neither immunotherapies targeting immune system acceleration nor release of immunologic brakes have been able to overcome the robust immune barrier in the pancreatic tumor microenvironment, which is characterized by rich fibrotic stroma and accumulation of immunosuppressive myeloid cells. However, by receiving an immune checkpoint blockade, patients with abundant tumor-infiltrating lymphocytes in pancreatic ductal adenocarcinoma clearly have better prognosis, and patients with mismatch repair deficiency have achieved better outcomes, albeit in a small population of pancreatic ductal adenocarcinoma. We overview recent preclinical and clinical studies that have been concerned with immune-based therapies including cancer vaccine and immune checkpoint inhibitors. By providing a deep insight into the immunosuppressive tumor microenvironment, we suggest the possibility of comprehensive immune intensification that could reverse the tumor microenvironment, making it conducive to cytotoxic T lymphocyte activity for overcoming pancreatic ductal adenocarcinoma.

Safety and feasibility of laparoscopic gastrectomy for remnant gastric cancer compared with open gastrectomy: Single-center experience.

ABSTRACT: The usefulness, safety and oncological validity of laparoscopic gastrectomy (LG) for remnant gastric cancer (RGC) have not been widely reported.A total of 38 patients who underwent gastrectomy for RGC were enrolled at Wakayama Medical University Hospital between April 2008 and December 2018. All consecutive patients were included in this retrospective study; the patients were divided into the open gastrectomy group and the laparoscopic group according to the sequential nature of their operation. Fifteen patients underwent open gastrectomy for RGC (OGR) between April 2008 and December 2013, and 23 patients underwent LG for RGC (LGR) after 2014.In the OGR group, all initial operations were performed by open surgery, whereas in the LGR group, 11 patients (47%) initially underwent laparoscopic surgery and 12 patients (53%) initially underwent open surgery (P = .002), 3 patients of which (25%) converted to open gastrectomy. There was no significant difference in the number of lymph node dissections or in operative time between the 2 groups, but blood loss was significantly lower in the LGR group than that in the OGR group (P = .002). Furthermore, although there was no difference between the 2 groups in C-reactive protein value on postoperative day 1, C-reactive protein value on postoperative day 3 was significantly lower in the LGR group than in the OGR group (P = .012). There were no differences in postoperative complications or long-term outcomes, including recurrence-free survival and overall survival.LGy is suitable in cases in which the initial surgery is performed by laparoscopic surgery. Even if the initial surgery is open surgery, it is oncologically equivalent to open gastrectomy and can be performed safely with less blood loss.

Single-incision laparoscopic antrectomy for type I gastric neuroendocrine tumor: a case report.

BACKGROUND: Type I gastric neuroendocrine tumors (GNETs) originate from hyperplasia of enterochromaffin-like (ECL) cells and are commonly detected in patients with chronic atrophic gastritis, including autoimmune gastritis. Typical treatment for type I GNETs comprises simple surveillance and/or endoscopic resection. For alleviation of hypergastrinemia resulting in ECL cell hypertrophy, antrectomy is a treatment option. Type I GNETs mostly have excellent prognosis, and if a surgical approach is chosen, the procedure must be minimally invasive. One such technique for multiple type I GNETs, minimally invasive single-incision laparoscopic antrectomy (SILA), is reported here for the first time. CASE PRESENTATION: We performed SILA on a 46-year-old woman who developed type I GNETs caused by hypergastrinemia due to autoimmune gastritis. A Lap-Protector was inserted in a 3 cm incision at the umbilicus, and set an EZ Access equipped with two 5 mm trocars and one 12 mm trocar. Antrectomy without lymph node dissection was performed using a 5 mm forward-oblique viewing endoscope, a vessel sealing device, and linear staplers, while reconstruction was by Billroth I reconstruction. Side-to-side anastomosis was performed using a 45 mm linear stapler. The stapler entry hole was sutured intracorporeally using barbed suture material. The operation time was 140 min and blood loss was 5 ml. The patient was discharged ten days after surgery without complications. Serum gastrin level decreased to within the normal range on the day after the operation. One year after surgery, esophagogastroduodenoscopy showed pathological disappearance of all lesions of the remnant stomach. CONCLUSIONS: SILA is a minimally-invasive and tolerable technique for treatment of multiple type I GNETs. In this reported case there was good cohesiveness and effectiveness in normalizing gastrin levels and in elimination of remnant gastric lesions.

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.

Postoperative atrial fibrillation does not impact on overall survival after esophagectomy in patients with thoracic esophageal cancer: results from a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Administration of landiolol hydrochloride was found to be associated with reduced incidence of atrial fibrillation (AF) after esophagectomy for esophageal cancer in our previous randomized controlled trial (RCT). In addition, reduced incidence of AF was associated with reduction of other complications. Meanwhile, the effects of postoperative AF and other complications on long-term survival following esophagectomy are not well understood. MATERIALS AND METHODS: Between March 2014 and January 2016, 100 patients with esophageal cancer were registered in an RCT trial and randomly allocated to receive either administration of landiolol or a placebo. We analyzed data from this RCT to better understand the effect of postoperative AF and severe associated complications on overall survival (OS) after esophagectomy for cancer. We also examined whether prophylactic administration of landiolol hydrochloride directly affects prolonged survival in patients with esophageal cancer. RESULTS: The five-year rates of OS in the patients with and without AF were 60%, and 68.6%, respectively, there was no significant difference (P = 0.328). Five-year rates of OS of the patients with and without severe complications were 64.6%, and 67.5%, respectively (P = 0.995). The five-year rates of OS in the placebo and landiolol groups were 65.8% and 68%, respectively (P = 0.809). In multivariate analysis, high stage (stage III/IV) alone was an independent prognostic factor for esophageal cancer patients following esophagectomy. CONCLUSIONS: New-onset AF and the other severe complications were not associated with poorer long-term survival following esophagectomy. In addition, administration of landiolol hydrochloride after esophagectomy did not contribute to prolonging the OS.

Laparoscopic Limited Resection for Duodenal Gastrointestinal Stromal Tumors.

BACKGROUND: Laparoscopic surgery may be a suitable treatment for gastrointestinal stromal tumors (GISTs) in terms of oncological feasibility and being minimally invasive. Case series of laparoscopic resection for duodenal GISTs have not been reported in detail, so in this report, the detail of laparoscopic surgeries for duodenal GISTs is summarized. METHODS: This is a single-center retrospective case series of six consecutive patients with duodenal GISTs who underwent laparoscopic limited resection of the duodenum between 2003 and 2019. RESULTS: Tumors were located within the first portion in three patients, the second portion in two patients, and the third portion in one patient. Median tumor size was 25 mm. Four patients underwent a laparoscopic and endoscopic full-thickness resection with primary closure, one patient underwent a laparoscopic wedge resection, and one patient underwent a laparoscopic segmental duodenectomy with Roux-en-Y gastrojejunostomy. Median blood loss was minimal (10 ml) with median operative time of 2 h, and there were no conversions to open surgery. There were no intraoperative or postoperative complications. All patients underwent curative resection with negative surgical margins, and none had recurrence of their duodenal GISTs. All patients were alive at the end of the follow-up period of 54 months. CONCLUSION: Laparoscopic limited resection is a feasible, safe, and ideal treatment procedure for duodenal GISTs in terms of short- and long-term surgical outcomes.

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.

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.