Kenta Furukawa

Clinicopathological significance of leucine-rich α2-glycoprotein-1 in sera of patients with pancreatic cancer

Objectives Leucine-rich &agr;2-glycoprotein-1 (LRG-1) is an inflammatory protein. Serum LRG-1 levels can reportedly be used as a cancer biomarker for several types of carcinoma. In the present study, we investigated the clinical usefulness of serum LRG-1 levels as a biomarker of pancreatic cancer. Methods A total of 124 patients with pancreatic cancer, 35 patients with chronic pancreatitis (CP), and 144 healthy volunteers were enrolled in the study. Serum LRG-1 levels were assayed by enzyme-linked immunosorbent assay. Immunohistochemistry was used to examine LRG-1 expression in pancreatic cancer tissues. Results Serum LRG-1 levels were significantly increased in patients with pancreatic cancer compared with CP patients and healthy volunteers. The LRG-1 levels increased with progressive clinical stages of pancreatic cancer. Receiver operator curve analysis showed that a combination of carbohydrate antigen 19-9 and LRG-1 resulted in a higher area under the curve for the diagnosis of pancreatic cancer. Positive staining was observed in all cases of pancreatic cancer, but positive signal was scarcely detected in tissues from CP patients or normal surrounding tissue. Conclusions These results suggest that serum LRG-1 is a promising biomarker for pancreatic cancer.

Signet ring cell carcinoma of the ampulla of vater: Report of a case and a review of the literature

Highlights • Signet ring cell carcinoma in the ampulla of vater is extremely uncommon.• Investigation to confirm the histological origin of signet ring cell carcinoma by immunohistochemical staining might inform the treatment strategy and identify patients with ampullary signet ring cell carcinoma who may have a good prognosis.

Single‐incision totally extraperitoneal inguinal hernia repair is feasible and safe in patients on antithrombotic therapy: A single‐center experience of 92 procedures

The aim of this study was to evaluate the feasibility and safety of SILS for totally extraperitoneal inguinal hernia repair for patients on antithrombotic therapy.

Single-incision totally extraperitoneal inguinal hernia repair is safe and feasible in elderly patients: A single-center experience of 365 procedures

The aim of this study was to evaluate the feasibility and safety of SILS for totally extraperitoneal inguinal hernia repair in elderly patients. A retrospective analysis of 365 patients who underwent of SILS for totally extraperitoneal inguinal hernia repair from January 2012 to November 2015 at Osaka Police Hospital was performed, and the outcomes of patients aged <80 years and those aged ≥80 years were compared. There was a greater proportion of patients with an ASA score ≥3 among those ≥80 years than among those <80 years. The mean operative time for unilateral inguinal hernia was 94 min in patients <80 years and 98 min in patients ≥80 years. The mean operative time for bilateral inguinal hernia was 133 min in patients <80 years and 130 min in patients ≥80. Intraoperative bleeding was minimal in all patients. Conversion to a different operative procedure occurred in 3% (10/322) of patients <80 years and in 5% (2/43) of patients ≥80 years (P = 0.6). The mean postoperative hospital stay was 2.2 days for patients <80 years and 2.2 days for patients ≥80 years. The mean follow‐up period 21 ± 14 months (range, 3–50 months) for patients <80 years and 17 ± 14 months (range, 3–50 months) for patients ≥80 years (P = 0.3). Postoperative complications were seen in 12% (38/322) of patients <80 years and in 14% (6/43) of patients ≥80 years (P = 0.7). A seroma was seen in 9% (28/322) of patients <80 years and in 12% (5/43) of patients ≥80 years (P = 0.6). A wound infection occurred in 2% (8/322) of patients <80 years. These seromas and wound infections were managed conservatively. Pulmonary embolism was seen in one patient <80 years (0.3%). There was no mortality or recurrence in either group. SILS for totally extraperitoneal inguinal hernia repair has good cosmesis and can be performed in elderly patients with acceptable morbidity and mortality.

Liver hilar tuberculous lymphadenitis successfully diagnosed by laparoscopic lymph node biopsy.

Highlights • Tuberculous lymphadenitis should be included among the differential diagnoses of liver hilar lymphadenopathy in patients with a history of tuberculous.• Laparoscopic lymph node biopsy is useful for the diagnosis of undiagnosed lymphadenopathy.• FDG-PET imaging is rarely useful for differentiating cancer from tuberculous lesions.

Safety and feasibility of single-incision laparoscopic cholecystectomy in obese patients

Background Current literature frequently indicates that experienced laparoscopic surgeons can safely perform single-incision laparoscopic cholecystectomy, but there have been few reports evaluating the feasibility and safety of performing single-incision laparoscopic cholecystectomy for obese patients. Therefore, a large single-center database was retrospectively reviewed to evaluate the feasibility and safety of single-incision laparoscopic cholecystectomy for obese patients by comparing the outcomes of normal-weight and obese patients undergoing single-incision laparoscopic cholecystectomy. Methods A retrospective analysis of 608 patients undergoing SILC between May 2009 and May 2015 at Osaka Police Hospital was performed, and the outcomes of obese [body mass index (BMI) ≥ 30 kg/m2] and normal-weight patients (18.5 ≤ BMI < 25 kg/m2) were compared. Results Thirty-eight obese patients (mean BMI 32.5 kg/m2) were compared to 362 normal-weight patients (mean BMI 22.0 kg/m2). The American Society of Anesthesiologists (ASA) scores of the obese patients were significantly higher than those of normal-weight patients. The mean operative times in the normal-weight and the obese groups were 110 min vs. 127 min, respectively (p < 0.05). There were no significant differences in the bleeding volume and the conversion rate to a different operative procedure. Perioperative complications were seen in 6% (23/362) of the patients in the normal-weight group and 8% (3/38) of the patients in the obese group (p = 0.7). The mean postoperative hospital stay was 4.5 days for the normal-weight group and 4.4 days for the obese group (p = 0.8). Conclusions Single-incision laparoscopic cholecystectomy, which offers good cosmetic outcomes, seems feasible and safe in obese patients.

Abstract 732: A practical strategy to pancreatic cancer immunotherapy using resected human tumor lysate vaccines remodeled to express α-gal epitopes

Cancer immunotherapy is a potential treatment for pancreatic ductal adenocarcinoma (PDAC) patients. As the predominant natural Ab found in humans, anti-Gal accounts for approximately 1% of immunoglobulins. The ligand of anti-Gal, “α-gal epitope (Galα1-3Galβ1-4GlcNAc-R),” is a major carbohydrate antigen, expressed by non-primate mammals, New World monkeys. One useful application of anti-Gal abundance is the enhancement of the immunogenicity of tumor-associated antigens (TAAs) that promote effective uptake by antigen-presenting cells (APCs). To develop an effective vaccine-based immunotherapy for PDAC, we hypothesized that resected tumor tissue lysates from patients might be an attractive source of PDAC-associated TAAs vaccination. This study presents a novel immunotherapy expressing α-gal epitopes using freshly obtained human PDAC tumor tissue homogenates from patients. Tumor and normal pancreatic tissue specimens were obtained from 10 patients at the time of surgical exploration for primary PDAC. To synthesize α-gal epitopes on either tumor membranes or normal pancreatic tissue membranes, we employed recombinant α1,3 galactosyltransferase (α1,3GT). PDAC membranes or normal pancreatic tissues were homogenized, and were incubated with UDP-Gal and α1,3GT. α1,3GT KO mice were immunized with pig tissues to produce anti-Gal Ab. The high anti-Gal KO mice were vaccinated by i.p. injection with unprocessed or processed PDAC tumor lysate (α-gal(-) PDAC-ly or α-gal(+) PDAC-ly). The high anti-Gal KO mice were also vaccinated with unprocessed normal or processed normal pancreatic tissue lysate (α-gal(-) N-ly or α-gal(+) N-ly). Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates in Western blot analysis. α-gal(+) PDAC-ly vaccines elicited significant antibody production against multiple TAAs, assessed by ELISPOT (anti-MUC1; α-gal(-) PDAC-ly vs. α-gal(+) PDAC-ly=28.7 vs. 151.8 spots [P=0.0008], anti-mesothelin; α-gal(-) PDAC-ly vs. α-gal(+) PDAC-ly=36.5 vs. 97.2 spots [P=0.029]) and activated multiple tumor-specific T cells, assessed by ELISPOT (MUC1; α-gal(-) PDAC-ly vs. α-gal(+) PDAC-ly=146.0 vs. 828.0 spots [P=0.0009], mesothelin; α-gal(-) PDAC-ly vs. α-gal(+) PDAC-ly= 250.7 vs. 988.0 spots [P=0.021], α-gal(-) N-ly and α-gal(+) N-ly groups did not display significant spots.). To demonstrate in vivo effectiveness, splenocytes from vaccinated KO mice were prepared, and these isolated cells were transferred by i.p. injection into NOD/SCID mice. Then, live PANC1 cells were challenged with s.c. injection. The survival time of NOD/SCID mice received from α-gal(+) PDAC-ly groups was significantly extended (95.0 days) compared with α-gal(-) PDAC-ly groups (45 days, p Citation Format: Masahiro Tanemura, Kenta Furukawa, Eiji Miyoshi, Hidetoshi Eguchi, Hiroaki Nagano, Katsuyoshi Matsunami, Satoshi Nagaoka, Manabu Mikamori, Kentaro Kishi, Hiroki Akamatsu, Masaki Mori, Yuichiro Doki. A practical strategy to pancreatic cancer immunotherapy using resected human tumor lysate vaccines remodeled to express α-gal epitopes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 732.

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

Objectives Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Methods Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Results Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Conclusions Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.

Feasibility and safety of single-incision laparoscopic cholecystectomy in elderly patients: A single institution, retrospective case series

Introduction To evaluate the feasibility and safety of single-incision laparoscopic cholecystectomy (SILC) for uncomplicated gallbladder in elderly patients. Materials and Methods A retrospective analysis of 810 patients undergoing SILC from May 2009 to October 2016 at Osaka Police Hospital was performed, and the outcomes of the patients aged < 80 years and the patients ≥ 80 years were compared. Results The median operative times of patients <80 years and patients ≥80 years were 100 min and 110 min, respectively (p = 0.4). The conversion rates to a different operative procedure (multi-port laparoscopic cholecystectomy or open cholecystectomy) were 3% (22/763) of patients < 80 years and 0% of patients ≥ 80 years (p = 0.6). Perioperative complications were seen in 6% (46/763) of patients < 80 years and 17% (8/47) of patients ≥ 80 years (p < 0.05). Pneumonia was seen in 0% (0/763) of patients < 80 years and 4% (3/47) of patients ≥ 80 years (p < 0.05). There was no mortality in either group. The median postoperative hospital stay was 4 days for patients <80 years and 5 days for patients ≥80 years (p < 0.05). Conclusion SILC for uncomplicated gallbladder could be performed for patients ≥ 80 years with acceptable morbidity and mortality as compared with the previous reports, though the complication rate of patients ≥ 80 years was higher than that of patients < 80 years.

Abstract 1539: Live circulating tumor cells as a predictive biomarker of response to neoadjuvant chemoradiotherapy for resectable pancreatic cancer

The detection of increase in the number of circulating tumor cells (CTCs) during a patient9s clinical course may be a harbinger of forthcoming overt metastasis. To detect live CTCs (l-CTCs) in blood samples of cancer patients (pts), we employed a new genetically modified telomerase-specific replication-selective adenovirous, expressing GFP (TelomeScanF35), containing both type 35 fiber that induce broad infectivity and miR-142-3p target sequence that can prevent a false positive toward blood cells. Recently, we indicated that preoperative chemoradiation therapy comprising gemcitabine and S-1 administration concurrent with full-dose radiation (NACRT) lead to encouraging survival rate in pts with resectable pancreatic cancer. But, NACRT may have disadvantages. NACRT requires several months, potentially delaying surgical resection, and can be waste of time and may result in the pts missing the chance for surgery. We assessed the l-CTCs burden in pts treated with NACRT. This study was approved by the Osaka Police Hospital IRB. Pts with resectable cytologically or histologically proven ductal adenocarcinoma of the pancreas were enrolled. Treatment consisted of an intervenous infusion of Gem 800 mg/m2 on day 1, 8, 22, and 29; and S-1 80 mg/m2 orally on day 1-5, 8-12, 22-26, and 29-33 given concurrently with IMRT to 60 Gy. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction. 7.5 ml of blood samples were obtained from the pts included in this clinical study before NACRT, after 1 month of NACRT, and after 2 months of surgical resection. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 and anti-Cytokeratin Abs. To distinguish cells with mesenchymal origin, cells were labeled with anti-Vimentin Ab. GFP-positive and CD45-negative cells were counted as l-CTC. 16 pts aged 44-78 years (5 males and 11 females) were enrolled. No treatment-related deaths occurred. CA19-9 was reduced to Citation Format: Masahiro Tanemura, Kenta Furukawa, Masaki Wakasugi, Kentaro Kishi, Yasuo Urata, Kiyomi Taniyama, Hiroki Akamatsu. Live circulating tumor cells as a predictive biomarker of response to neoadjuvant chemoradiotherapy for resectable pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1539.