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Background: Although the main manifestation of giant paraesophageal hernia (PEH) is disordered meal passage due to gastric torsion, the contents of the hernia sometimes squeeze the heart and lungs and induce the symptoms of respiratory or heart failure. Furthermore, the quality of life (QOL) of patients with a heavy cardiac load deteriorates. In this study, changes in a heart failure marker and symptoms of cases with a giant PEH from before to after laparoscopic surgery were examined. Methods: Levels of brain natriuretic peptide (BNP) as a heart failure marker were measured before and after radical laparoscopic surgery in cases of type III, IV type of giant PEH. Changes of the symptoms due to heart failure were also investigated. Results: A total of 75 hiatal hernia surgeries were performed in 2012–2019. Of them, 50 had a giant PEH, and 20 (40.0%) had heart failure symptoms such as fatigue and exertional dyspnea. In the giant PEH cases, BNP could be measured before and after surgery to evaluate the presence of heart failure in 23 cases; postoperative BNP levels decreased from the preoperative values in 18 of them. Furthermore, in many cases, chest symptoms also improved. Conclusions: Radical laparoscopic surgery can reduce heart failure due to giant PEH. Therefore, in addition to conventional surgical indication criteria such as vomiting and food loss, increased cardiac load may be added to the new surgical indication criteria.

Background: We have recently standardized upper mediastinal lymph node dissection (UMLND) using a microanatomy-based concept in thoracoscopic esophagectomy in the prone position (TEPP), and introduced robot-assisted minimally invasive esophagectomy (RAMIE) using the same concept as in TEPP while aiming at solo surgery. The purpose of this study was to investigate the outcomes of RAMIE using the microanatomy-based concept in the initial introduction phase. Methods: We have performed more than 500 TEPP procedures as minimally invasive esophagectomy (MIE). After performing about 400 cases of MIE, we established a microanatomy-based standardization of UMLND. In October 2018, we introduced RAMIE, and have performed 75 procedures in 20 months. Two groups were analyzed: a group after microanatomy-based standardization in TEPP (100 cases after completing 400 cases of TEPP) and a RAMIE group (75 cases). Finally, 51 paired cases were matched using a propensity score. Furthermore, the change in postoperative short-term outcome for RAMIE in the initial introduction phase was analyzed. Results: Although there were no significant differences between the two groups in the number of upper mediastinal lymph nodes dissected, there was a significant decrease (P= 0.036) in intraoperative blood loss volume with RAMIE, representing a definite benefit for patients. The thoracoscopic operative time for RAMIE decreased by almost 100 min following less than 50 cases of experience, reaching the same level as that for recent TEPP, but with only one-tenth the operator experience. There were no significant differences in the total postoperative morbidity rate including the recurrent laryngeal nerve palsy rate. Conclusion: RAMIE has been introduced safely and smoothly using the microanatomy-based concept established in TEPP.

Background: Although thoracoscopic esophagectomy in the prone position (TEPP) has become a standard procedure for esophageal cancer surgery, upper mediastinal lymph node dissection (UMLND) on the left side remains an issue. We have recently developed a new standardized approach to left UMLND in TEPP based on the microanatomy of the membranes and layers with the aim of achieving quick and safe surgery. The purpose of this study was to establish and evaluate our new standardized procedure in left UMLND. Patients and methods: Patients were divided into 2 groups: a pre-standardization group (n?=?100) and a post-standardization group (n?=?100). Eventually, 83 paired cases were matched using propensity score matching. In our new standardized procedure, left UMLND was performed while focusing on the visceral sheath, vascular sheath, and the fusion layer between them using a magnified view. Results: The thoracoscopic operative time was significantly shorter (P?<?0.001) in the post-standardization group [n?=?83; 209.0 (176.0–235.0) min] than in the pre-standardization group [n?=?83; 235.5 (202.8–264.5) min]. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the two groups. There was a tendency for the total postoperative morbidity to decrease in the post-standardization group. Furthermore, the left recurrent laryngeal nerve palsy rate was significantly lower in the post-standardization group (18.1% to 8.7%, P?=?0.015). Conclusion: Microanatomy-based standardization contributes to safe and efficient left UMLND.

ABSTRACTCancer-associated fibroblasts (CAFs) are strongly implicated in tumor progression, including in the processes of tumorigenesis, invasion, and metastasis. The targeting of CAFs using various therapeutic approaches is a novel treatment strategy; however, the efficacy of such therapies remains limited. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a novel targeted therapy employing a cell-specific mAb conjugated to a photosensitizer, has been introduced as a new type of phototherapy. In this study, we have developed a novel NIR-PIT technique to target CAFs, by focusing on fibroblast activation protein (FAP), and we evaluate the treatment efficacy in vitroand in vivo. Esophageal carcinoma cells exhibited enhanced activation of fibroblasts, with FAP over-expressed in the cytoplasm and on the cell surface. FAP-IR700-mediated PIT showed induced rapid cell death specifically for those cells in vitroand in vivo, without adverse effects. This novel therapy for CAFs, designed as local control phototherapy, was safe and showed a promising inhibitory effect on FAP+CAFs. PIT targeting CAFs via the specific marker FAP may be a therapeutic option for CAFs in the tumor microenvironment in the future.

Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons’ knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan. Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) > 5 and PGY 1–5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis. A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1–5: 66, PGY > 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY > 5 group compared to the PGY1–5 group (79 [75; 83] % vs. 67 [58; 75] %, p< 0.001). The differences in performance were due to better scores for PGY > 5 group on the sections “equipment,” “patient considerations,” “abdominal access,” “tissue handling,” “hemorrhage and hemostasis,” “tissue approximation,” and “exiting the abdomen.” Overall, the median scores in the “energy sources” and “establishment and physiology of the pneumoperitoneum” subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum. Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

ABSTACTHuman hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required. Iron overload is known to be associated with progression of chronic hepatitis and increased risk of HCC. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Indeed iron depletion therapy including iron chelator needs to be combined with anti-angiogenic drug for its anti-cancer effect. Since sorafenib has an anti-angiogenic effect by its inhibitory targeting VEGFR, we hypothesized that sorafenib could complement the anti-cancer effect of iron depletion. We retrospectively analyzed the relationship between the efficacy of sorafenib and serum iron-related markers in clinical HCC patients. In clinical cases, overall survival was prolonged in total iron binding capacity (TIBC) high- and ferritin low-patients. This result suggested that the low iron-pooled patients, who could have a potential of more angiogenic properties in/around HCC tumors, could be adequate for sorafenib treatment. We determined the effect of sorafenib (Nexavar®) and/or deferasirox (EXJADE®) on cancer cell viability, and on cell signaling of human hepatocarcinoma HepG2 and HLE cells. Both iron depletion by deferasirox and sorafenib revealed insufficient cytotoxic effect by each monotherapy, however, on the basis of increased angiogenesis by iron depletion, the addition of deferasirox enhanced anti-proliferative effect of sorafenib. Deferasirox was confirmed to increase vascular endothelial growth factor (VEGF) secretion into cellular supernatants by ELISA analysis. In in vivo study sorafenib combined with deferasirox also enhanced sorafenib-induced apoptosis. These results suggested that sorafenib combined with deferasirox could be a novel combination chemotherapy for HCC.

Despite the widespread use of surgical energy devices and the potential for rare but serious complications, pilot data from North America suggest that surgeons and surgical trainees have knowledge gaps in their safe use. The purpose of this study was to determine baseline knowledge of general surgeons and surgical trainees regarding the safe use of electrosurgery (ES) across varying levels of experience in Japan. Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of SAGES’ Fundamental Use of Surgical Energy™ curriculum. Sections of the examination included: “principles of ES,” “ES-related adverse events,” “monopolar and bipolar devices,” and “pediatric considerations and interference with implantable devices.” Scores were compared between PGY > 5 and PGY 1–5 participants. A total of 145 general surgeons and surgical trainees of all years after medical school (PGY 1–5: 57, PGY > 5: 88) from ten academic and five community hospitals completed the assessment (mean age 35; 91 % male). The mean score in the entire cohort was 58 ± 12 % (range 23–83 %), with significantly higher scores in the PGY > 5 group compared to the PGY 1–5 group (60 ± 11 vs. 53 ± 12 %, p< 0.01). Among all participants, 92 % were not familiar with best practices when using ES on patients with a pacemaker; 44 % believe that ES uses thermal energy from cautery; 19 % did not know how to manage an operating room fire; 16 % thought that a dispersive electrode should be cut to fit a child; and 27 % believe that insulation failure in minimally invasive surgical instruments is mostly visible under careful inspection. General surgeons and trainees at all levels have knowledge gaps in the safe and effective use of energy devices, regardless of years of experience. There is a need for educational curricula to help address these gaps and contribute to safer surgery.

Anticancer drug discovery has long been hampered by the poor predictivity of the preclinical models. There is a growing realization that the tumor microenvironment is a critical determinant of the response of cancer cells to therapeutic agents. The past 5 years have seen a great deal of progress in our understanding of how the three-dimensional microenvironment modulates the signaling behavior of tumor cells. The present review discusses how three-dimensional in vitrocell culture models can benefit cancer drug discovery through an accurate modeling of the tumor microenvironment, leading to more physiologically relevant experimental outcomes.