ABSTRACT
Telesurgery is expected to improve medical access in areas with limited resources, facilitate the rapid dissemination of new surgical procedures, and advance surgical education. While previously hindered by communication delays and costs, recent advancements in information technology and the emergence of new surgical robots have created an environment conducive to societal implementation. In Japan, the legal framework established in 2019 allows for remote surgical support under the supervision of an actual surgeon. The Japan Surgical Society led a collaborative effort, involving various stakeholders, to conduct social verification experiments using telesurgery, resulting in the development of a Japanese version of the "Telesurgery Guidelines" in June 2022. These guidelines outline requirements for medical teams, communication environments, robotic systems, and security measures for communication lines, as well as responsibility allocation, cost burden, and the handling of adverse events during telesurgery. In addition, they address telementoring and full telesurgery. The guidelines are expected to be revised as needed, based on the utilization of telesurgery, advancements in surgical robots, and improvements in information technology.
Subject(s)
Societies, Medical , Telemedicine , Japan , Humans , Robotic Surgical Procedures/standards , Patient Care Team , Information Technology , Practice Guidelines as Topic , General Surgery/educationABSTRACT
Aim: Possible negative effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods: The National Clinical Database (NCD) is a large-scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30-day mortality, surgical mortality, and postoperative complications (Clavien-Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: In the NCD, postoperative 30-day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30-day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04-1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10-1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08-1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01-1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions: The COVID-19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.
ABSTRACT
Background: The COVID-19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID-19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID-19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID-19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods: We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web-based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity-leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results: The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot-assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre-pandemic period. Conclusions: Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID-19 pandemic.
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Immune checkpoint inhibitor therapy has dramatically improved patient prognosis, and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma (ESCC) in the past decade. Monoclonal antibodies that selectively inhibit programmed cell death-1 (PD-1) activity has now become standard of care in the treatment of ESCC in metastatic settings, and has a high expectation to provide clinical benefit during perioperative period. Further, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody. Well understanding of the existing evidence of immune-based treatments for ESCC, as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant, adjuvant, and metastatic diseases, may provide future prospects of ESCC treatment for better patient outcomes.
Subject(s)
CTLA-4 Antigen , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Immune Checkpoint Inhibitors , Immunotherapy , Neoadjuvant Therapy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/immunology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/immunology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/drug therapy , Neoadjuvant Therapy/methods , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Immunotherapy/methods , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Treatment Outcome , Chemotherapy, Adjuvant/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/immunologyABSTRACT
BACKGROUND: This single-center retrospective study aimed to clarify the clinical and pathologic background of mass-forming intrahepatic cholangiocarcinomas. METHODS: A total of 53 patients with mass-forming intrahepatic cholangiocarcinomas were selected from 2007 to 2021 and analyzed based on several parameters, including the preoperative computed tomography pattern (enhancement in the arterial phase of dynamic contrast-enhanced computed tomography), clinical data, and tumor microenvironment evaluated by immunohistochemistry. The hyperenhancement (n = 13) and hypoenhancement (n = 40) groups were defined using the 50% cutoff of tumors with higher attenuation than the liver parenchyma. RESULTS: The hyperenhancement group was characterized by a better overall survival than the hypoenhancement group (5-year survival: 86% vs 27%, respectively; P < .001) and by a higher infiltration of peritumoral (92% vs 58%; P = .020) and intratumoral CD3-positive T lymphocytes (85% vs 35%; P = .002). Conversely, the hypoenhancement group was characterized by a higher infiltration versus peritumoral CD163-positive tumor-associated macrophages (60% vs 8%; P = .001), peritumoral pentraxin 3-positive tumor-associated macrophages (50% vs 15%; P = .024), and intratumoral α-smooth muscle actin-positive cancer-associated fibroblasts (15% vs 68%; P = .001). A multiple regression analysis was performed to predict overall survival from the microenvironment, and the independent poor predictor factors were low intratumoral CD3-positive T lymphocytes (hazard ratio = 2.75), high peritumoral (hazard ratio = 2.38), and intratumoral CD163-positive tumor-associated macrophages (hazard ratio = 2.81) (all P values < 0.05). CONCLUSION: Compared with hypovascular, hypervascular mass-forming intrahepatic cholangiocarcinomas have better tumor immunity and prognosis.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Tumor Microenvironment , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/pathology , Cholangiocarcinoma/mortality , Male , Retrospective Studies , Female , Tumor Microenvironment/immunology , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/mortality , Middle Aged , Aged , Prognosis , Tomography, X-Ray Computed , Hepatectomy , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/surgery , AdultABSTRACT
BACKGROUND: Although intracorporeal anastomosis (IA) for colon cancer requires longer operative time than extracorporeal anastomosis (EA), its short-term postoperative results, such as early recovery of bowel movement, have been reported to be equal or better. As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum, there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells. However, intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified. AIM: To clarify the effects of bacterial and tumor cell contamination of the intra-abdominal cavity in IA. METHODS: Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020, 75 underwent EA (EA group), and 52 underwent IA (IA group). After propensity score matching, the primary endpoint was 3-year disease-free survival rates, and secondary endpoints were 3-year overall survival rates, type of recurrence, surgical site infection (SSI) incidence, number of days on antibiotics, and postoperative biological responses. RESULTS: Three-year disease-free survival rates did not significantly differ between the IA and EA groups (87.2% and 82.7%, respectively, P = 0.4473). The 3-year overall survival rates also did not significantly differ between the IA and EA groups (94.7% and 94.7%, respectively; P = 0.9891). There was no difference in the type of recurrence between the two groups. In addition, there were no significant differences in SSI incidence or the number of days on antibiotics; however, postoperative biological responses, such as the white blood cell count (10200 vs 8650/mm3, P = 0.0068), C-reactive protein (6.8 vs 4.5 mg/dL, P = 0.0011), and body temperature (37.7 vs 37.5 °C, P = 0.0079), were significantly higher in the IA group. CONCLUSION: IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.
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In the early 1900s, mutation breeding to select varieties with desirable traits using spontaneous mutation was actively conducted around the world, including Japan. In rice, the number of fixed mutations per generation was estimated to be 1.38-2.25. Although this low mutation rate was a major problem for breeding in those days, in the modern era with the development of next-generation sequencing (NGS) technology, it was conversely considered to be an advantage for efficient gene identification. In this paper, we proposed an in silico approach using NGS to compare the whole genome sequence of a spontaneous mutant with that of a closely related strain with a nearly identical genome, to find polymorphisms that differ between them, and to identify the causal gene by predicting the functional variation of the gene caused by the polymorphism. Using this approach, we found four causal genes for the dwarf mutation, the round shape grain mutation and the awnless mutation. Three of these genes were the same as those previously reported, but one was a novel gene involved in awn formation. The novel gene was isolated from Bozu-Aikoku, a mutant of Aikoku with the awnless trait, in which nine polymorphisms were predicted to alter gene function by their whole-genome comparison. Based on the information on gene function and tissue-specific expression patterns of these candidate genes, Os03g0115700/LOC_Os03g02460, annotated as a short-chain dehydrogenase/reductase SDR family protein, is most likely to be involved in the awnless mutation. Indeed, complementation tests by transformation showed that it is involved in awn formation. Thus, this method is an effective way to accelerate genome breeding of various crop species by enabling the identification of useful genes that can be used for crop breeding with minimal effort for NGS analysis.
ABSTRACT
Conferring crops with resistance to multiple diseases is crucial for stable food production. Genetic engineering is an effective means of achieving this. The rice receptor-like cytoplasmic kinase BSR1 mediates microbe-associated molecular pattern-induced immunity. In our previous study, we demonstrated that rice lines overexpressing BSR1 under the control of the maize ubiquitin promoter exhibited broad-spectrum resistance to rice blast, brown spot, leaf blight, and bacterial seedling rot. However, unfavorable phenotypes were observed, such as a decreased seed germination rate and a partial darkening of husked rice. Herein, we present a strategy to address these unfavorable phenotypes using an OsUbi7 constitutive promoter with moderate expression levels and a pathogen-inducible PR1b promoter. Rice lines expressing BSR1 under the influence of both promoters maintained broad-spectrum disease resistance. The seed germination rate and coloration of husked rice were similar to those of the wild-type rice.
ABSTRACT
N6-methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP-seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A-activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer-related signaling pathways was observed relative to TCEAL8-negative cells. Furthermore, among TCEAL8-positive cells, the cells expressing the m6A-modifying enzyme gene METTL3 showed co-activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A-activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.
Subject(s)
Adenosine , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Methyltransferases , Pancreatic Neoplasms , RNA, Messenger , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Signal Transduction/genetics , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Cell Line, Tumor , Receptors, Notch/genetics , Receptors, Notch/metabolism , Gene Expression Profiling/methodsABSTRACT
BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.
Subject(s)
Colorectal Neoplasms , Midkine , Single-Cell Analysis , T-Lymphocytes, Regulatory , Tumor Microenvironment , Female , Humans , Male , Carcinogenesis/genetics , Carcinogenesis/immunology , Cell Communication/immunology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/mortality , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Immune Tolerance , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Transcriptome , Tumor Microenvironment/immunology , Midkine/immunology , Midkine/metabolismABSTRACT
Aim: The aim of this study was to verify the clinical feasibility of tele-proctoring using our ultra-low latency communication system with shared internet access. Methods: Connections between two multiple remote locations at various distances were established through the TELEPRO® tele-proctoring system. The server records the latency between the two locations for tele-proctoring using the annotations. Questionnaires were administered to the surgeons, assistants, and medical staff. Respondents rated the quickness and quality of communication in terms of latency and disturbances in the audio, video, and usefulness of the live telestrations with annotation. Results: Seven hospitals tele-proctored with Sapporo Medical University between January 2021 and September 2022. The median latency of annotation between the two locations ranged from 24.5 to 48.5 ms. No major technological problems occurred, such as streaming interruption, loss of video or audio, poor resolution. The video encoding time was 10 ms, and its decoding time was 0.8 ms. The total latency positively correlated with the distance between two locations (R = 0.55, p < 0.01). The quality of communication regarding latency, disturbance, and surgical education with intraoperative annotative instructions showed similar trends, with perfectly fine being the most common response. No significant differences in surgical quality, educational effect, or social impact were observed between the latency ≥30 and <30 ms groups for whether the size of latency affects surgical education. Conclusion: The feasibility of the tele-proctoring system is expected to be a sustainable approach to help education for young surgeons and surgical supports in rural areas, thereby reducing disparities in health care.
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Aim: Immune checkpoint inhibitors (ICIs) are less effective in mismatch repair (MMR)-proficient (pMMR) colorectal cancers (CRCs) than in MMR-deficient CRCs. Here, we investigated changes in the tumor microenvironment after neoadjuvant chemotherapy (NAC) without radiotherapy in locally advanced rectal cancer (LARC) and the potential of ICIs as therapeutic agents for pMMR CRCs. Methods: This was an ad hoc analysis of a KSCC1301 randomized phase II trial in which patients with untreated resectable LARC were randomly assigned to receive S-1 and oxaliplatin or folinic acid, 5-fluorouracil, and oxaliplatin as NAC. Forty-nine patients were studied in this ad hoc analysis. As a reference cohort, we assessed 25 rectal cancer patients who underwent surgery without NAC outside the randomized trial. Immune checkpoint molecules (ICMs; PD-1, PD-L1, CTLA-4, LAG3), tumor-infiltrating lymphocytes (TILs; CD8, FOXP3), and other related proteins were evaluated by immunohistochemistry. Next-generation sequencing (NGS) using Oncomine™ Comprehensive Assay version 3 was conducted in 23 patients. Results: The expression levels of PD-1, CTLA-4, and LAG3 in the NAC group were significantly higher than in reference patients (p < 0.001). Additionally, the infiltration of CD8+ and FOXP3+ T cells, and the CD8/FOXP3 ratio were significantly higher in the NAC group than in reference patients (p < 0.0001). NGS analysis revealed no specific gene alteration related to TILs or ICMs. Conclusion: We demonstrated changes in the tumor immune microenvironment after NAC in pMMR rectal cancer. NAC was associated with increased expression of ICMs and TILs. Rectal cancer could be susceptible to combined immunotherapy with chemotherapy.
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BACKGROUND: The azygos lobe is a relatively rare anatomical variation, and there have been no reports, until date, of thoracoscopic McKeown esophagectomy for esophageal cancer in a patient with an azygos lobe. The azygos lobe can be diagnosed by chest X-ray or CT, and is usually not associated with any symptoms. However, surgeons should be aware that transthoracic surgical procedures in patients with an azygos lobe could be associated with a high risk of complications. CASE PRESENTATION: An 83-years-old man was brought to our emergency room with fever, severe headache, and difficulty in moving. MRI revealed a brain abscess, which was treated by abscess drainage and systemic antibiotic treatment. Further examinations to determine the cause of the brain abscess revealed esophageal cancer. In addition, CT revealed an azygos lobe in the right thoracic cavity. Although intrathoracic adhesions were anticipated on account of a previous history of bacterial pyothorax, we decided to perform esophagectomy via a thoracoscopic approach. Despite the difficulty in dissecting the intrathoracic adhesions, we were able to obtain the surgical field thoracoscopically. Then, we found the azygos lobe, as diagnosed preoperatively, and the azygos vein was supported by the mesentery draining into the superior vena cava. After dividing the mesentery, we clipped and cut the vessel, and both ends were further ligated. After these procedures, we safely performed esophagectomy with 3-field lymph node dissection. The postoperative course was uneventful, and the patient was discharged on the 21st postoperative day. CONCLUSIONS: Although there was a firm adhesion in the thoracic cavity, preoperative recognition of the azygos lobe could help in preventing intraoperative injury. Especially, esophageal surgeons are required to deal with the azygos lobe safely to avoid serious intraoperative injury.
Subject(s)
Brain Abscess , Esophageal Neoplasms , Male , Humans , Aged, 80 and over , Esophagectomy/methods , Vena Cava, Superior/pathology , Esophageal Neoplasms/pathologyABSTRACT
In patients undergoing haematopoietic stem-cell transplantation (HSCT), the intestinal microbiota plays an important role in prognosis, transplant outcome, and complications such as graft-versus-host disease (GVHD). Our prior research revealed that patients undergoing HSCT substantially differed from healthy controls. In this retrospective study, we showed that administering Clostridium butyricum MIYAIRI 588 (CBM588) as a live biotherapeutic agent is associated with maintaining intestinal microbiota in the early post-HSCT period. Alpha diversity, which reflects species richness, declined considerably in patients who did not receive CBM588, whereas it remained consistent in those who received CBM588. In addition, ß-diversity analysis revealed that CBM588 did not alter the gut microbiota structure at 7-21 days post-HSCT. Patients who developed GVHD showed structural changes in their microbiota from the pre-transplant period, which was noticeable on day 14 before developing GVHD. Enterococcus was significantly prevalent in patients with GVHD after HSCT, and the population of Bacteroides was maintained from the pre-HSCT period through to the post-HSCT period. Patients who received CBM588 exhibited a contrasting trend, with lower relative abundances of both genera Enterococcus and Bacteroides. These results suggest that preoperative treatment with CBM588 could potentially be beneficial in maintaining intestinal microbiota balance.
Subject(s)
Clostridium butyricum , Gastrointestinal Microbiome , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Female , Middle Aged , Adult , Retrospective Studies , Graft vs Host Disease/microbiology , AgedABSTRACT
Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.
Subject(s)
Colorectal Neoplasms , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Transcription Factors , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Mice , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cell Proliferation/genetics , Female , Male , Bromodomain Containing ProteinsABSTRACT
Rice blast fungus (Pyricularia oryzae) is a heterothallic ascomycete that causes the most destructive disease in cultivated rice worldwide. This fungus reproduces sexually and asexually, and its mating type is determined by the MAT1 locus, MAT1-1 or MAT1-2. Interestingly, most rice-infecting field isolates show a loss of female fertility, but the MAT1 locus is highly conserved in female-sterile isolates. In this study, we performed a functional analysis of MAT1 using the CRISPR/Cas9 system in female- and male-fertile isolates and female-sterile (male-fertile) isolates. Consistent with a previous report, MAT1 was essential for sexual reproduction but not for asexual reproduction. Meanwhile, deletion mutants of MAT1-1-1, MAT1-1-2, and MAT1-1-3 exhibited phenotypes different from those of other previously described isolates, suggesting that the function of MAT1-1 genes and/or their target genes in sexual reproduction differs among strains or isolates. The MAT1 genes, excluding MAT1-2-6, retained their functions even in female-sterile isolates, and deletion mutants lead to loss or reduction of male fertility. Although MAT1 deletion did not affect microconidia (spermatia) production, microconidia derived from the mutants could not induce perithecia formation. These results indicated that MAT1 is required for microconidia-mediated male fertility in addition to female fertility in P. oryzae .
Subject(s)
Ascomycota , Genes, Mating Type, Fungal , Genes, Mating Type, Fungal/genetics , Fertility/genetics , Ascomycota/genetics , Reproduction/genetics , Spores, FungalABSTRACT
AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.
ABSTRACT
BACKGROUND & AIMS: Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl-CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood. METHODS: We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC. RESULTS: Patients were divided into ACSL4-positive (n = 72, 20.1%) and ACSL4-negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α-fetoprotein (p = .0180) and more histological liver fibrosis (p = .0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p < .0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer-associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC. CONCLUSION: ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer-associated fibroblasts and anti-tumour immunity.
Subject(s)
Cancer-Associated Fibroblasts , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Retrospective Studies , Prognosis , Coenzyme A Ligases/genetics , Coenzyme A Ligases/metabolism , Tumor MicroenvironmentABSTRACT
Assuring communication redundancy during the interruption and establishing appropriate teaching environments for local surgeons are essential to making robotic telesurgery mainstream. This study analyzes robotic telesurgery with telementoring using standard domestic telecommunication carriers. Can multiple carriers guarantee redundancy with interruptions? Three commercial optical fiber lines connected Hirosaki University and Mutsu General Hospitals, 150 km apart. Using Riverfield, Inc. equipment, Hirosaki had a cockpit, while both Mutsu used both a cockpit and a surgeon's console. Experts provided telementoring evaluating 14 trainees, using objective indices for operation time and errors. Subjective questionnaires addressed image quality and surgical operability. Eighteen participants performed telesurgery using combined lines from two/three telecommunication carriers. Manipulation: over 30 min, lines were cut and restored every three minutes per task. Subjects were to press a switch when noticing image quality or operability changes. Mean time to task completion was 1510 (1186-1960) seconds: local surgeons alone and 1600 (1152-2296) seconds for those under remote instructor supervision, including expert intervention time. There was no significant difference (p = 0.86). The mean error count was 0.92 (0-3) for local surgeons and 0.42 (0-2) with remote instructors. Image quality and operability questionnaires found no significant differences. Results communication companies A, B, and C: the A/B combination incurred 0.17 (0-1) presses of the environment change switch, B/C had 0, and C/A received 0.67 (0-3), showing no significant difference among provider combinations. Combining multiple communication lines guarantees communication redundancy and enables robotic telementoring with enhanced communication security.