Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS). Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI ≥70％(RDI 70 group,N=70)or RDI＜70％(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were ＜0.10 in univariate analysis. Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3％ vs. 28.3％,P＜0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7％ vs. 11.3％,P＜0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P＜0.01).Multivariate analysis showed that RDI ≥70％(hazard ratio(HR)=0.55,P=0.025),hypertension grade ≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P＜0.01)were independently associated with improved OS.RDI ≥70％ was not statistically significant in multivariate analysis. Conclusions:Our study revealed the importance of achieving RDI ≥70％ in the first 30 days of treatment to maximize the effects of LEN.

STUDY DESIGN: Retrospective. PURPOSE: This study aims to investigate the accuracy of the oblique fluoroscopic view, based on preoperative computed tomography (CT) images for accurate placement of lumbosacral percutaneous pedicle screws (PPS). OVERVIEW OF LITERATURE: Although PPS misplacement has been reported as one of the main complications in minimally invasive spine surgery, there is no comparative data on the misplacement rate among different fluoroscopic techniques, or comparing such techniques with open procedures. METHODS: We retrospectively selected 230 consecutive patients who underwent posterior spinal fusion with a pedicle screw construct for degenerative lumbar disease, and divided them into 3 groups, those who had undergone: minimally invasive percutaneous procedure using biplane (lateral and anterior-posterior views using a single C-arm) fluoroscope views (group M-1), minimally invasive percutaneous procedure using the oblique fluoroscopic view based on preoperative CT (group M-2), and conventional open procedure using a lateral fluoroscopic view (group O: controls). The relative position of the screw to the pedicle was graded for the pedicle breach as no breach, <2 mm, 2–4 mm, or >4 mm. Inaccuracy was calculated and assessed according to the spinal level, direction and neurological deficit. Inter-group radiation exposure was estimated using fluoroscopy time. RESULTS: Inaccuracy involved an incline toward L5, causing medial or lateral perforation of pedicles in group M-1, but it was distributed relatively equally throughout multiple levels in groups M-2 and controls. The mean fluoroscopy time/case ranged from 1.6 to 3.9 minutes. CONCLUSIONS: Minimally invasive lumbosacral PPS placement using the conventional fluoroscopic technique carries an increased risk of inaccurate screw placement and resultant neurological deficits, compared with that of the open procedure. Inaccuracy tended to be distributed between medial and lateral perforations of the L5 pedicle, as a result of pedicle morphology and the PPS pathway. Oblique fluoroscopic views, based on CT measurement, may allow accurate PPS insertion with a shorter fluoroscopy time.
Fluoroscopy ; Humans ; Pedicle Screws* ; Radiation Exposure ; Retrospective Studies ; Spinal Fusion ; Spine

Objective: The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with MLH1-PHM. Methods: Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. MLH1 methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed. Results: Accordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as “MMR-proficient,” “suspected-LS,” and “met-EC,” respectively. Significantly, “met-EC” had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of “met-EC” were significantly worse than those of “suspected-LS” in all cases. Conclusion In ECs with MMR-D, “met-ECs” were a subgroup with a poorer prognosis than “suspected-LS.” “Met-ECs” would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. METHODS: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. RESULTS: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. CONCLUSION The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

A 50-year-old man was referred to our hospital due to chest pain and loss of consciousness. Diagnosed with cardiac tamponade, he underwent emergency percutaneous pericardial drainage and endotracheal intubation. AAD was not found, although aortic root dissection was suspected from the CT scan and CAG. The MDCT revealed a 16 mm ruptured coronary artery aneurysm connected to the LMT with a CA-PA fistula. Urgently, coronary artery aneurysmectomy, CA-PA fistula repair, and CABG were performed, and the postoperative course was smooth. Surgery reports for ruptured coronary artery aneurysm are rare, so we report the successful surgical case.

BACKGROUND: Internal medicine (IM) doctors in Japan play the role of primary care physicians; however, the shortage of rural physicians continues. This study aims to elucidate the association of age, sex, board certification, type of work, and main clinical work with the retention or migration of IM doctors to rural areas. METHODS: This retrospective cohort study included 82,363 IM doctors in 2010, extracted from the national census data of medical doctors. The explanatory variables were age, sex, type of work, primary clinical work, and changes in board certification status. The outcome was retention or migration to rural areas. The first tertile of population density (PD) of municipalities defined as rural area. After stratifying the baseline ruralities as rural or non-rural areas, the odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. The analyses were also performed after age stratification (<39, 40-59, ≥60 years old). RESULTS: Among the rural areas, women had a significantly higher OR for retention, but obtaining board certification of IM subspecialties had a significantly lower OR. Among the non-rural areas, physicians who answered that their main work was IM without specific subspecialty and general had a significantly higher OR, but obtaining and maintaining board certification for IM subspecialties had a significantly lower OR for migration to rural areas. After age stratification, the higher OR of women for rural retention was significant only among those aged 40-59 years. Those aged under 40 and 40-59 years in the non-rural areas, who answered that their main work was IM without specific subspecialty had a significantly higher OR for migration to rural areas, and those aged 40-59 years in the rural areas who answered the same had a higher OR for rural retention. CONCLUSIONS Obtaining and maintaining board certification of IM subspecialties are possible inhibiting factors for rural work, and IM doctors whose main work involves subspecialties tend to work in non-rural areas. Once rural work begins, more middle-aged female IM doctors continued rural work compared to male doctors.
Middle Aged ; Humans ; Male ; Female ; Retrospective Studies ; East Asian People ; Certification ; Physicians ; Internal Medicine

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION UMIN000030786 .
Asthma ; epidemiology ; etiology ; Cohort Studies ; Dermatitis, Atopic ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; Humans ; Hypersensitivity ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Japan ; Male ; Vaccines, Inactivated ; adverse effects ; Viral Vaccines ; adverse effects