Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus.

BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles.

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.

Correction: Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55.

[This corrects the article DOI: 10.1007/s13340-023-00623-3.].

Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55.

Introduction: To investigate changes in insulin requirements over time in patients who underwent hepatectomy and pancreatectomy with perioperative glycemic control by an artificial pancreas (STG-55). Materials and methods: We included 56 patients (22 hepatectomies and 34 pancreatectomies) who were treated with an artificial pancreas in the perioperative period and investigated the differences in insulin requirements by organ and surgical procedure. Results: The mean intraoperative blood glucose level and total insulin doses were higher in the hepatectomy group than in the pancreatectomy group. The dose of insulin infusion increased in hepatectomy, especially early in surgery, compared to pancreatectomy. In the hepatectomy group, there was a significant correlation between the total intraoperative insulin dose and Pringle time, and in all cases, there was a correlation with surgical time, bleeding volume, preoperative CPR, preoperative TDD, and weight. Conclusions: Perioperative insulin requirements may be mainly dependent on the surgical procedure, invasiveness, and organ. Preoperative prediction of insulin requirements for each surgical procedure contributes to good perioperative glycemic control and improvement of postoperative outcomes.

Comparison between the gonadotropin-releasing hormone antagonist protocol and the gonadotropin-releasing hormone agonist long protocol for controlled ovarian hyperstimulation in the first in vitro fertilization-embryo transfer cycle in an unspecified population of infertile couples.

PURPOSE: We aimed to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist long protocol used in the first in vitro fertilization-embryo transfer (IVF-ET) cycle in an unspecified population of infertile couples. METHODS: Fifty and 34 patients were treated with a GnRH agonist long protocol (agonist group) and GnRH antagonist protocol (antagonist group), respectively, in the first treatment cycle. The primary and secondary outcome measures were cumulative live birth rates after fresh and cryopreserved-thawed ETs and incidence of grades II and III ovarian hyperstimulation syndrome (OHSS), respectively. RESULTS: No significant differences were observed in clinical pregnancy rates (38.0 vs. 32.4%) and live birth rates (22.0 vs. 23.5%), which included both fresh and cryopreserved-thawed ETs, between the 2 groups. However, the incidence of grade III OHSS was significantly lower with the GnRH antagonist protocol than the GnRH agonist long protocol. CONCLUSIONS: Used in the first IVF-ET cycle in an unspecified population of infertile patients, the GnRH antagonist protocol showed the same clinical outcome as the GnRH agonist long protocol.

Hysteroscopic tubal catheterization under laparoscopy for proximal tubal obstruction.

PURPOSE: The purpose of this study was to investigate the fertility outcomes of infertile patients having proximal tubal obstruction treated with hysteroscopic tubal catheterization (HCT) for recanalization under diagnostic laparoscopy. METHODS: From January 2000 to December 2008, diagnostic laparoscopy was used to assess the tubal status of 61 patients with unilateral or bilateral proximal tubal obstruction, as confirmed by hysterosalpingography. Among them, 35 patients with tubal obstruction confirmed by chromopertubation under laparoscopy subsequently underwent HCT. The pregnancy outcomes and success rates of recanalization were investigated. RESULTS: In the 35 patients with confirmed tubal obstruction, HCT was performed in 54 fallopian tubes. The success rate of recanalization was 25.9% (14/54) per tube and 37.1% (13/35) per patient. Of the patients in whom tubal patency was restored, 4 achieved pregnancy, including 1 tubal pregnancy and 1 miscarriage. Among the 61 patients, excluding 14 who underwent in vitro fertilization-embryo transfer (IVF-ET) after laparoscopy, 13 were pregnant (27.7%), 9 gave live births, 1 had tubal pregnancy, and 3 had miscarriages. CONCLUSIONS: HCT under laparoscopy is an option for couples with tubal infertility who do not prefer IVF-ET.

Delayed pneumothorax after laparoscopic ovarian cystectomy.

BACKGROUND: We describe a case that developed a delayed pneumothorax after laparoscopic surgery. CASE: A 40-year-old woman (BMI: 19.1) underwent a laparoscopic ovarian cystectomy. On the first postoperative day, she developed a pneumothorax. The subcutaneous CO2 tracked up through the fascial planes, and ruptured into the pleural space, where delayed pneumothorax developed. CONCLUSION: Gynecologists should be aware of pneumothorax after laparoscopic surgery and should also keep in mind its possible delayed development.

Squamous cell carcinoma arising in an ovarian mature cystic teratoma complicating pregnancy: a case report.

BACKGROUND: The question of whether patients with pure stage I squamous cell carcinoma in a mature cystic teratoma (MCT) should undergo conservative surgery, or postoperative adjuvant treatment remains unresolved. CASE: A 33-year-old woman with a left ovarian cyst underwent laparoscopic cystectomy at 16 weeks of gestation. Histological examination confirmed squamous cell carcinoma arising in an MCT. At 18 weeks of gestation, she underwent left salpingo-oophorectomy, and was diagnosed as having stage Ic malignant transformation of the MCT, and was observed closely without postoperative adjuvant chemotherapy. She delivered a healthy baby at 41 weeks of gestation. No evidence of recurrence was observed 14 months after the initial laparoscopic surgery. CONCLUSION: Although a thorough staging procedure , histopathologic evaluation, and long-term follow-up are indispensable, patients with early stage I squamous cell carcinoma in MCT may safely undergo conservative surgery.

Effects of early endometriosis on IVF-ET outcomes.

There have been very few reports on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with stage I/II endometriosis. The objective of this study was to investigate IVF-ET outcomes in women with early-stage endometriosis. We enrolled 35 women less than 40 years with unexplained infertility who underwent IVF-ET into the study. We compared 18 women with stage I/II endometriosis according to the revised American Society for Reproductive Medicine classification for endometriosis, who underwent 39 IVF-ET cycles (En (+) group) with 17 women without endometriosis who underwent 41 IVF-ET cycles (En (-) group). Higher requirements of total gonadotropin, a lower percentage of high-quality embryos of all fertilized eggs (9.0% vs. 16.3%), a relatively lower pregnancy rate (33.3% vs. 41.5%), and a lower live birth rate (25.6% vs. 34.1%) were observed in the En (+) group. Although no significant effect on IVF-ET outcome was observed, ovarian response may be decreased in women with stage I/II endometriosis. Considering the decreased number of high-quality embryos in the En (+) group, stage I/II endometriosis may have detrimental effects on embryo quality.

Laparoscopic marsupialization of pelvic lymphocele under transvaginal ultrasonographic guidance.

Lymphocyst formation is a common complication of pelvic lymphadenectomy. We treated a 54-year-old woman with lymphocele by laparoscopic marsupialization. She developed hydronephrosis as a result of retroperitoneal lymphocele after total abdominal hysterectomy and pelvic lymphadenectomy for endometrial cancer. Laparoscopic marsupialization under transvaginal ultrasonographic guidance was chosen because conservative therapy including percutaneous or transvaginal drainage ran the risk of bowel perforation. The 6-cm collection was opened and its edges were coagulated electrosurgically and sutured with the surrounding peritoneum. The postoperative course was satisfactory, and hydronephrosis was resolved. This highly effective minimally invasive procedure was beneficial to the patient.

Concurrent chemoradiation for locally advanced squamous cell carcinoma of the vagina: case series and literature review.

BACKGROUND: We reviewed our experience with patients with primary squamous cell carcinoma of the vagina who received concurrent chemoradiation therapy (CCRT). METHODS: We retrospectively analyzed six patients (median age, 60 years) with squamous cell carcinoma of the vagina who underwent CCRT between 2002 and 2005 at the University of the Ryukyus Hospital. Two patients were in International Federation of Obstetricians and Gynecologists (FIGO) stage II, one in stage III, and three in stage IVA. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Tumor size ranged from 3.2 to 7.7 cm. All patients were treated with true pelvic external-beam radiotherapy (EBRT) at 50 Gy. Then two of the six patients underwent intracavitary vaginal brachy-therapy. The remaining four patients received boost EBRT with shrinking fields. Total radiation dose to the vaginal tumor ranged from 60 to 66 Gy. All patients received two or three concomitant cycles of cisplatin during EBRT. RESULTS: All six patients completed their scheduled CCRT, and achieved a clinical complete response. One stage II patient died of disease 24 months after treatment, and the stage III patient had local failure at 12 months. The remaining four patients were free of their disease at 18, 23, 33, and 55 months, respectively. One patient with stage IVA developed a vesicovaginal fistula during CCRT. Nevertheless, CCRT was well tolerated by all six patients, and no grade 3 or 4 late toxicity was observed, as evaluated by the Radiation Therapy Oncology Group (RTOG) scoring system. CONCLUSION: CCRT is effective for primary squamous cell carcinoma of the vagina and should be considered for treatment in patients with high-risk disease having good performance status.