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BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.
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BACKGROUND AND AIM: Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions. METHODS: Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single-center, retrospective study. Short- and long-term outcomes were evaluated. RESULTS: Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥ 4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow-up of 40 (interquartile range, 29.5-61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3-year overall and disease-specific survivals were 81% (95% confidence interval, 64%-91%) and 94% (95% confidence interval, 79%-99%), respectively. CONCLUSIONS: Favorable local control and safety of endoscopic submucosal dissection were demonstrated.
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BACKGROUND: To determine the precise frequency of main pancreatic duct (MPD) dilatation within the remnant pancreas at 1 year after pancreatoduodenectomy (PD) and its clinical implications, a prospective multicentre cohort study was performed in patients without MPD dilatation before PD (Registry number; UMIN000029662). METHODS: Between October 2017 and July 2020, patients with MPD diameter <3mm who were planned to undergo PD for periampullary lesions at 21 hospitals were enrolled. The primary endpoints were frequency of MPD dilatation at 1 year after PD, and the relationship between MPD dilatation and pancreatic endo- and exocrine function, nutritional status, and fatty liver. Secondary endpoints were risk factors for MPD dilatation at 1 year after PD and time-course change in MPD diameter. RESULTS: Of 200 registered patients, 161 patients were finally analyzed. Pancreatic fistula was the most frequent complication (n=76; 47.2%). MPD dilatation (MPD>3mm) at 1 year after PD was seen in 35 patients (21.7%). Pancreatic exocrine function, assessed by steatorrhea, was significantly impaired in patients with MPD dilatation. However, endocrine function, nutrition status and fatty liver development were comparable between the two groups. In multivariate analysis, the serum toral protein level≥7.3g/dl was an independent predictor for MPD dilatation at 1 year after PD (OR; 3.12, 95%CI; 1.31-7.15). A mean MPD diameter significantly increased at 6 months after PD and kept plateau thereafter. CONCLUSIONS: MPD dilatation at 1 year after PD was seen in 21.7% of patients and significantly associated with exocrine function impairment but not with endocrine function, nutrition status, or development of fatty liver.
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Aim: Carcinoma of the ampulla of Vater (CAV) shows a favorable prognosis compared to that with the other periampullary tumors, while some cases have a poor prognosis. The aims of the present study are to clarify the clinicopathological factors associated with poor recurrence-free survival (RFS) in patients with CAV after curative resection and to validate the usefulness of adjuvant chemotherapy (AC). Patients: The study design is a multicenter retrospective cohort study. Patients with CAV who underwent pancreaticoduodenectomy between January 2008 and December 2020 at 26 hospitals were analyzed. The 30 clinicopathological factors were evaluated. A propensity score matching (PSM) was used to compare between patients with and without AC. Results: Finally, 460 patients were analyzed. Median duration of follow-up was 47.2 months. Twenty-one prognostic factors associated with poor RFS were identified by univariate analysis. In multivariate analysis, aged ≥71, tumor diameter ≥12 mm, pT2 or higher stage (pT≥2), portal vein invasion (PV+), venous invasion(V+), and node positive disease (pN+) were independent prognostic factors for poor RFS. Out of 80 patients who received AC, 63 patients were assigned to analysis for PSM. The results showed no beneficial effect of AC on RFS. The preoperative factors potentially predicting pT≥2, V+, and/or N+ were at least one of following; (1) CA19-9 > 37 IU/mL, (2) ulcerative or mixed type appearance, (3) except for well-differentiated tumor, or (4) except for intestinal subtype of histology. Conclusions: Aged ≥71, tumor diameter ≥12 mm, pT≥2, PV+, V+, and pN+ were independent prognostic factors for poor RFS in patients with CAV. An additional therapeutic strategy may be desirable in CAV patients at high risk for recurrence.
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Vascular staplers are routinely used in laparoscopic liver resection, which has become a standard procedure in advanced medical facilities. Although previous reports have outlined the benefits of staple line reinforcement (SLR), its application in Glissonean pedicle transection during hepatic resection remains poorly studied. This study investigated surgical SLR as a tool to enhance staple line strength and improve perioperative hemostasis. Here, 10 patients who underwent laparoscopic liver resection using the Tri-StapleTM2.0 Reinforced Reload were included. Patient characteristics, surgical details, and outcomes were assessed. The results demonstrated successful outcomes with no complications related to bile leakage or injuries during staple insertion. Overall, our findings suggest that SLR can be safely utilized in Glissonean pedicle transection during laparoscopic liver resections. Further studies are required to comprehensively evaluate its benefits compared with conventional surgical staplers.
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Laparoscopia , Fígado , Humanos , Projetos Piloto , Resultado do Tratamento , Fígado/cirurgia , Hepatectomia/métodos , Grampeamento Cirúrgico/métodos , Laparoscopia/métodos , SuturasRESUMO
Introduction: Measuring whole-brain networks of the 40 Hz auditory steady state response (ASSR) is a promising approach to describe the after-effects of transcranial direct current stimulation (tDCS). The main objective of this study was to evaluate the effect of tDCS on the brain network of 40 Hz ASSR in healthy adult males using graph theory. The second objective was to identify a population in which tDCS effectively modulates the brain network of 40 Hz ASSR. Methods: This study used a randomized, sham-controlled, double-blinded crossover approach. Twenty-five adult males (20-24 years old) completed two sessions at least 1 month apart. The participants underwent cathodal or sham tDCS of the dorsolateral prefrontal cortex, after which 40 Hz ASSR was measured using magnetoencephalography. After the signal sources were mapped onto the Desikan-Killiany brain atlas, the statistical relationships between localized activities were evaluated in terms of the debiased weighted phase lag index (dbWPLI). Weighted and undirected graphs were constructed for the tDCS and sham conditions based on the dbWPLI. Weighted characteristic path lengths and clustering coefficients were then measured and compared between the tDCS and sham conditions using mixed linear models. Results: The characteristic path length was significantly lower post-tDCS simulation (p = 0.04) than after sham stimulation. This indicates that after tDCS simulation, the whole-brain networks of 40 Hz ASSR show a significant functional integration. Simple linear regression showed a higher characteristic path length at baseline, which was associated with a larger reduction in characteristic path length after tDCS. Hence, a pronounced effect of tDCS is expected for those who have a less functionally integrated network of 40 Hz ASSR. Discussion: Given that the healthy brain is functionally integrated, we conclude that tDCS could effectively normalize less functionally integrated brain networks rather than enhance functional integration.
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BACKGROUND: Texture features reflecting tumour heterogeneity enable us to investigate prognostic factors. The R package ComBat can harmonize the quantitative texture features among several positron emission tomography (PET) scanners. We aimed to identify prognostic factors among harmonized PET radiomic features and clinical information from pancreatic cancer patients who underwent curative surgery. METHODS: Fifty-eight patients underwent preoperative enhanced dynamic computed tomography (CT) scanning and fluorodeoxyglucose PET/CT using four PET scanners. Using LIFEx software, we measured PET radiomic parameters including texture features with higher order and harmonized these PET parameters. For progression-free survival (PFS) and overall survival (OS), we evaluated clinical information, including age, TNM stage, and neural invasion, and the harmonized PET radiomic features based on univariate Cox proportional hazard regression. Next, we analysed the prognostic indices by multivariate Cox proportional hazard regression (1) by using either significant (p < 0.05) or borderline significant (p = 0.05-0.10) indices in the univariate analysis (first multivariate analysis) or (2) by using the selected features with random forest algorithms (second multivariate analysis). Finally, we checked these multivariate results by log-rank test. RESULTS: Regarding the first multivariate analysis for PFS after univariate analysis, age was the significant prognostic factor (p = 0.020), and MTV and GLCM contrast were borderline significant (p = 0.051 and 0.075, respectively). Regarding the first multivariate analysis of OS, neural invasion, Shape sphericity and GLZLM LZLGE were significant (p = 0.019, 0.042 and 0.0076). In the second multivariate analysis, only MTV was significant (p = 0.046) for PFS, whereas GLZLM LZLGE was significant (p = 0.047), and Shape sphericity was borderline significant (p = 0.088) for OS. In the log-rank test, age, MTV and GLCM contrast were borderline significant for PFS (p = 0.08, 0.06 and 0.07, respectively), whereas neural invasion and Shape sphericity were significant (p = 0.03 and 0.04, respectively), and GLZLM LZLGE was borderline significant for OS (p = 0.08). CONCLUSIONS: Other than the clinical factors, MTV and GLCM contrast for PFS and Shape sphericity and GLZLM LZLGE for OS may be prognostic PET parameters. A prospective multicentre study with a larger sample size may be warranted.
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Local recurrence after colorectal liver metastasis (CRLM) resection severely affects survival; however, the required surgical margin width remains controversial. This study investigated the impact of KRAS status on surgical margin width and local recurrence rate (LRR) post-CRLM resection. Overall, 146 resected CRLMs with KRAS status (wild-type KRAS (wtKRAS): 98, KRAS mutant (mKRAS): 48) were included. The LRR for each group, R1 (margin positive) and R0 (margin negative), was analyzed by KRAS status. R0 was further stratified into Ra (margin ≥ 5 mm) and Rb (margin < 5 mm). Patients with local recurrence had significantly worse 5-year overall survival than those without local recurrence (p = 0.0036). The mKRAS LRR was significantly higher than wtKRAS LRR (p = 0.0145). R1 resection resulted in significantly higher LRRs than R0 resection for both wtKRAS and mKRAS (p = 0.0068 and p = 0.0204, respectively), and while no significant difference was observed in the Ra and Rb LRR with wtKRAS, the Rb LRR with mKRAS (33.3%) was significantly higher than Ra LRR (5.9%) (p = 0.0289). Thus, R0 resection is sufficient for CRLM with wtKRAS; however, CRLM with mKRAS requires resection with a margin of at least 5 mm to prevent local recurrence.
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The increasing geriatric population across the world has necessitated the early detection of frailty through the analysis of daily-life behavioral patterns. This paper presents a system for ambient, automatic, and the continuous measurement and analysis of ascent and descent motions and long-term handrail-use behaviors of participants in their homes using an RGB-D camera. The system automatically stores information regarding the environment and three-dimensional skeletal coordinates of the participant only when they appear within the camera's angle of view. Daily stair ascent and descent motions were measured in two houses: one house with two participants in their 20s and two in their 50s, and another with two participants in their 70s. The recorded behaviors were analyzed in terms of the stair ascent/descent speed, handrail grasping points, and frequency determined using the decision tree algorithm. The participants in their 70s exhibited a decreased stair ascent/descent speed compared to other participants; those in their 50s and 70s exhibited increased handrail usage area and frequency. The outcomes of the study indicate the system's ability to accurately detect a decline in physical function through the continuous measurement of daily stair ascent and descent motions.
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Algoritmos , Fragilidade , Idoso , Humanos , Estilo de Vida , Movimento (Física) , TecnologiaRESUMO
Introduction: In rectal surgery, double-stapled anastomosis is one of the most common techniques. However, the crossing of the staple line is considered a weakness of this method and could lead to anastomotic leakage (AL), which is one of the major complications of rectal cancer surgery. Aim: To investigate the usefulness of laparoscopic intracorporeal reinforcement suturing for preventing AL in laparoscopic rectal surgery. Material and methods: A total of 153 patients with rectal cancer underwent laparoscopic rectal resection with anastomosis using the double-stapling technique between January 2015 and December 2018. Patient characteristics, surgical data, and outcomes were recorded and retrospectively analysed. Patients who received intracorporeal reinforcing sutures (n = 72) were compared with those who did not receive the reinforcing sutures (n = 81). Results: AL was observed in 11 (7.2%) cases overall and in only 1 case in the group with intracorporeal reinforcing sutures. There were no associations between clinicopathological factors and the use of reinforcing sutures. Multivariate analysis revealed that a distance from the anal verge of less than 6.5 cm, diabetes mellitus, and the non-use of reinforcing sutures were independent risk factors for AL. Conclusions: Laparoscopic intracorporeal reinforcing sutures reduced the incidence of AL. Therefore, laparoscopic reinforcing sutures for double-stapled anastomoses seem useful for the prevention of AL.
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BACKGROUND: Preoperative evaluation of future remnant liver reserves is important for safe hepatectomy. If the remnant is small, preoperative portal vein embolization (PVE) is useful. Liver volume analysis has been the primary method of preoperative evaluation, although functional examination may be more accurate. We have used the functional evaluation liver using the indocyanine green plasma clearance rate (KICG) and 99mTc-galactosyl human serum albumin single-photon emission computed tomography (99mTc-GSA SPECT) for safe hepatectomy. AIM: To analyze the safety of our institution's system for evaluating the remnant liver reserve. METHODS: We retrospectively reviewed the records of 23 patients who underwent preoperative PVE. Two types of remnant liver KICG were defined as follows: Anatomical volume remnant KICG (a-rem-KICG), determined as the remnant liver anatomical volume rate × KICG; and functional volume remnant KICG (f-rem-KICG), determined as the remnant liver functional volume rate based on 99mTc-GSA SPECT × KICG. If either of the remnant liver KICGs were > 0.05, a hepatectomy was performed. Perioperative factors were analyzed. We defined the marginal group as patients with a-rem-KICG of < 0.05 and a f-rem-KICG of > 0.05 and compared the postoperative outcomes between the marginal and not marginal (both a-rem-KICG and f-rem-KICG > 0.05) groups. RESULTS: All 23 patients underwent planned hepatectomies. Right hepatectomy, right trisectionectomy and left trisectionectomy were in 16, 6 and 1 cases, respectively. The mean of blood loss and operative time were 576 mL and 474 min, respectively. The increased amount of f-rem-KICG was significantly larger than that of a-rem-KICG after PVE (0.034 vs 0.012, P = 0.0273). The not marginal and marginal groups had 17 (73.9%) and 6 (26.1%) patients, respectively. The complications of Clavian-Dindo classification grade II or higher and post-hepatectomy liver failure were observed in six (26.1%) and one (grade A, 4.3%) patient, respectively. The 90-d mortality was zero. The marginal group had no significant difference in postoperative outcomes (prothrombin time/international normalised ratio, total bilirubin, complication, post-hepatectomy liver failure, hospital stay, 90-d, and mortality) compared with the not-marginal group. CONCLUSION: Functional evaluation of the remnant liver enabled safe hepatectomy and may extend the indication for hepatectomy after PVE treatment.
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RNA is spliced concomitantly with transcription and the process is organized by RNA splicing factors, transcriptional regulators, and chromatin regulators. RNA is spliced in close proximity to transcription machinery. Hence, some RNA splicing factors may play a role in transcription. Here, we show that the splicing factor SF3B2 binds to gene regulatory elements and mRNA to modulate transcription and RNA stability in head and neck squamous cell carcinoma cells. High SF3B2 expression leads to poor prognosis in patients with head and neck squamous cell carcinoma and to progression of tumor growth in mice. SF3B2 promotes tumor growth, owing to its involvement in activation of gene expression associated with mitochondrial electron transport and transcription regulatory region DNA binding. SF3B2 is enriched around the promoter element on chromatin and the transcription termination site on RNA. SF3B2 is involved in the regulation of RNA stability. According to the SF3B2-binding profile, SF3B2 regulates RNA polymerase II activity, in addition to regulating RNA splicing. Mechanistically, SF3B2 promotes the binding of structural maintenance of chromosomes 1A and CCCTC-binding factor (CTCF) to the SF3B2-binding genomic regions. SF3B2 also modulates CTCF transcriptional activity. Our findings indicate that SF3B2 has a dual function in both transcription and RNA stability, leading to head and neck squamous cell carcinoma progression.
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According to a report by the Japan Sport Council, more than 1 million injuries occur in the school environment in Japan, which is a significant burden to society in terms of children's physical and psychological well-being as well as the costs of health care. Japanese people are becoming increasingly aware of school safety, but no effective safety education program has yet been established. In this study, we conducted a comprehensive safety education curriculum utilizing photovoice in a needs assessment of school safety and evaluated its use as a tool in student learning processes with regard to injury. The curriculum consists of two parts: (1) classroom lectures (three classes, 45 minutes each) and (2) a photovoice project (four classes, 45 minutes each). In total, 49 students participated in the education program, presenting 23 photovoice pictures. The use of photovoice enabled identification of locations of risk recognized by students and the associated photo R-map assisted students and teachers to deepen their learning about injury. We demonstrated four benefits of applying photovoice to school-based injury prevention education. These findings suggest that our photovoice-based injury prevention education program could positively impact children's research engagement by identifying school needs, and also empower them to affect social change.
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Serviços de Saúde Escolar , Instituições Acadêmicas , Criança , Currículo , Humanos , Aprendizagem , EstudantesRESUMO
As the world's population ages, technology-based support for the elderly is becoming increasingly important. This study analyzes the relationship between natural standing behavior measured in a living space of elderly people and the classes of standing aids, as well as the physical and cognitive abilities contributing to household fall injury prevention. In total, 24 elderly standing behaviors from chairs, sofas, and nursing beds recorded in an RGB-D elderly behavior library were analyzed. The differences in standing behavior were analyzed by focusing on intrinsic and common standing aid characteristics among various seat types, including armrests of chairs or sofas and nursing bed handrails. The standing behaviors were categorized into two types: behaviors while leaning the trunk forward without using an armrest as a standing aid and those without leaning the trunk forward by using an arrest or handrail as a standing aid. The standing behavior clusters were distributed in a two-dimensional map based on the seat type rather than the physical or cognitive abilities. Therefore, to reduce the risk of falling, it would be necessary to implement a seat type that the elderly can unconsciously and naturally use as a standing aid even with impaired physical and cognitive abilities.
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Acidentes por Quedas , Posição Ortostática , Acidentes por Quedas/prevenção & controle , Idoso , Humanos , TroncoRESUMO
BACKGROUND: Preventable injuries are the leading cause of death in children around the world, including in Japan. As children under the age of 5 years spend most of their time at home, home injury prevention is critical for child safety. The purpose of this study was to identify specific, focused, and precise barriers against injury prevention practice. METHODS: We conducted an online survey to examine the barriers faced by parents when taking actions to prevent home injuries. RESULTS: The results revealed common reasons why parents do not or cannot take a recommended action across injury types, and that the magnitude of importance for a specific barrier depends on the type of injury. CONCLUSIONS: Identifying content-specific barriers could help researchers and educators understand parents' needs, discuss what barriers are more important than others by injury type, and develop effective strategies based on the 3Es of injury prevention (enforcement, engineering, and education).
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Sistemas de Proteção para Crianças , Acidentes de Trânsito , Criança , Humanos , Lactente , Japão , Restrição FísicaRESUMO
RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5' and 3' splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.