Search

Background Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and seems to be effective. To date, the feasibility of such salvage surgery, particularly anatomical pulmonary resection, has not been fully evaluated. To assess the feasibility of salvage surgery after definitive CRT, we compared clinical outcomes of surgery after definitive CRT to those of surgery after induction CRT. Methods Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. We compared patients with salvage anatomical pulmonary resection after definitive CRT to patients with surgery after induction CRT in terms of perioperative and long-term outcomes. Results Twenty-three patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group) and 36 underwent surgery after induction CRT for cN2-stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bi-lobectomy and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bi-lobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group. Conclusions Salvage anatomical pulmonary resection after definitive CRT for locally advanced lung cancer is feasible with acceptable morbidity and prognosis in highly selected patients.

INTRODUCTION The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1-endometrial endometrioid carcinoma (G1-EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid-based cytological (LBC) samples. METHODS (1) The type and distribution of CD10-positive cells in EGBD and G1-EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double-immunostained with CD31 and CD10 to confirm whether CD10-positive tubular-canalicular material found in (1) was represented by fine threads of endometrial-type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells. RESULTS (1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular-canalicular branching patterns in G1-EEC. (2) The tubular-canalicular material observed in cytological specimens of G1-EEC samples co-expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31-positive signals were found inside the condensed stromal clusters with CD10-positive. (3) Cells surrounding the CD31-positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10-positive fibrous stromal strands also co-expressed αSMA. CONCLUSIONS CD10 is a very useful immunomarker for distinguishing between G1-EEC and the metaplastic changes of EGBD in LBC samples.

There is a significant shortage of surgeons in Japan similar to many other countries. There are 40,267 registered surgeons for Japan Surgical Society, among them 23,723 are board certificated, and 7,246 are certified instructors. A total of 3,207 surgeons are members of The Japanese Associations for Chest Surgery, and 245 (7.6%) are female surgeons. Approximately 8,000 medical students graduate annually with medical license. The number of newly registered residents and surgeons has recently been declining overall in the last two decades, however, the percentage of female physicians entering into surgery has been increasing gradually along with increasing number of female medical students entering the medical schools and colleges. With regard to the issue of gender gap, our country is ranked as low as 121 out of 153 countries according to global gender gap report 2020 by World Economic Forum, dropping down from 110 out of 149 countries from previous report in 2018. As the numbers of female colleagues in our workplace increases, we must consider what we can do to build a better working environment for them that is more inclusive and supports their career. In this review, the brief history of surgery and female surgeons is described as well as current situations of female surgeons today in Japan.

The purpose of this study was to retrospectively investigate risk factors for chest port (port) infections within 30 days of placement (early port infections) in adult oncologic patients.This single-institution, three-center retrospective study identified 1,714 patients (868 males, 846 females; median age 60.0 years old) who underwent port placement between January 2013 and August 2017. All patients received an intravenous antibiotic prior to port placement. The median absolute neutrophil count was 5,260 cells/μL, the median white blood cell (WBC) count was 7,700 cells/μL, and the median serum albumin was 4.00 g/dL at the time of port placement. Double-lumen ports were most commonly implanted (74.85%) more frequently in an outpatient setting (72.69%). Risk factors for early port infections were elucidated using univariate and multivariate proportional subdistribution hazard regression analyses.A total of 20 patients (1.2%) had early port infections; 15 patients (0.9%) had positive blood cultures. The mean time to infection was 20 days (range, 9-30 days). The port-related 30-day mortality rate was 0.2% (4 of 1,714 patients). Most bloodstream infections were attributed to Staphylococcus spp. (n = 11). In multivariate analysis, hematologic malignancy (hazard ratio [HR], 2.61; 95% confidence interval (CI), 1.15-5.92.; P = .02), hypoalbuminemia (albumin3.5 g/dL; HR, 3.52; 95% CI: 1.48-8.36; P = .004), leukopenia (WBC3,500 cells/μL; HR, 3.00; 95% CI: 1.11-8.09; P = .03), and diabetes mellitus (HR, 3.71; 95% CI: 1.57-8.83) remained statistically significant risk factors for early port infection.Hematologic malignancy, hypoalbuminemia, leukopenia, and diabetes mellitus at the time of port placement were independent risk factors for early port infections.

Purpose: A study is presented of the irradiation of cancerous cervical cell line HeLa loaded with a platinum salt, betamethasone and deoxyglucose. The presence of the platinum increases the free-ra...

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8+ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we explored the role of cDC1 in CNS anti-tumor immunity. We determined that cDC1 mediate checkpoint blockade-induced survival benefit and prime neoantigen-specific CD8+ T cells against brain tumors. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor-antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1-equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same subsets, we identified a tumor-specific fluorescent metabolite of 5- aminolevulinic acid, which labels tumor cells during fluorescence-guided glioblastoma resection. Together, these data elucidate the specialized behavior of cDC1 and suggest cDC1 play a significant role in CNS anti-tumor immunity.One Sentence SummaryCNS cDC1 engage in previously undefined behavior to establish immune responses against brain tumors.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI Background Cognitive decline is common among older patients with cardiovascular disease and can decrease their self-management abilities. Therefore, early detection of cognitive decline is clinically important, as it can help guide effective home-based care measures, including education of family members and deployment of healthcare resources. However, the standard instruments for identifying mild cognitive impairment (MCI) are not always feasible in clinical practice. Purpose This study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test (RDST-J), which is a simple screening tool for identifying cognitive decline. Methods This cross-sectional study included patients who were ≥ 65 years old and hospitalised because of cardiovascular disease. Patients with a pre-hospitalisation diagnosis of dementia were excluded. Each patient’s cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment (MoCA-J), which is a standard tool for MCI screening. The RDST-J includes a number transcoding task and a supermarket task, and can be completed in 3 min (range: 0–12 points). The MoCA-J assesses nine domains of cognition and requires 10–15 min to complete (range: 0–30 points). The correlation between the two scores was evaluated using Spearman’s rank correlation coefficient. Receiver operating characteristic (ROC) analysis was also conducted to evaluate whether the RDST-J could identify MCI, which was defined as a MoCA-J score of ≤ 25 points. Results The study included 78 patients (the mean age: 77.2 ± 8.9 years, men: 56.4%). Based on a MoCA-J score of ≤ 25 points, MCI was identified in 73.1% (n = 57) of the patients. The RDST-J and MoCA-J scores were strongly correlated (r = 0.835, p Conclusions The RDST-J is a simple instrument and its score was highly correlated with the standard test for identifying MCI in older patients with cardiovascular disease. Our results suggest that the RDST-J may be useful for routine cognitive assessments in clinical practice. Longitudinal studies are needed to evaluate whether the RDST-J scores respond to changes in cognitive status, as well as whether this tool can be used to predict adverse health outcomes after discharge.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI Background Cardiac rehabilitation (CR) remains underutilised, despite its established clinical benefit. Assessments of personality traits may serve for patient-medical staff communication to promote CR implementation as they are determinants of health-related behavior. However, few studies have explored the potential effects of the Big Five personality traits on CR participation. Purpose This study aimed to examine the association between the Big Five personality traits and CR participation in patients with cardiovascular disease. Methods This longitudinal analysis included patients aged Results A total of 139 patients hospitalised for cardiovascular disease were analysed (the mean age: 67.2 ± 9.8 years, men: 71.9%). Of 49 patients who initiated the outpatient CR after discharge, 26 patients continued CR for three months, and 23 patients dropped out. The results of the logistic regression analysis are shown in Figure 1. After adjusted for age, gender, and heart failure, high conscientiousness was associated with non-participation in CR (odds ratio [OR] 1.35, per 1 point; 95% confidence interval (CI) 1.00-1.87). The primary reason for non-participation among patients with high conscientiousness was a lack of motivation. Conversely, low conscientiousness (OR 0.56; 95% CI 0.35-0.90) and high openness (OR 2.19; 95% CI 1.27-3.78) were predictors of dropout within three months after discharge. Conclusion The results of this study imply that the Big Five assessment serves for the health communication to improve CR participation. In particular, high conscientious was associated with non-participation in CR due to a lack of motivation, and patients with low conscientiousness and high openness tended to dropout.

Funding Acknowledgements Type of funding sources: None. Introduction Long-term care insurance (LTCI) has a key role in the disease management of older patients in Japan. However, clinical benefit of coordinating LTCI service during hospitalization has not been examined in patients with heart failure (HF). Purpose We aimed to examine the association between the coordination of LTCI service and adverse outcome after discharge in Japanese older patients with HF. Methods The inclusion criteria of this retrospective cohort study were patients aged ≥ 65 years hospitalised for HF who used any LTCI services after discharge. In Japan, people aged ≥ 65 who satisfy the eligibility criteria are eligible to receive LTCI services. Questionnaires regarding daily life and activities are used to assess eligibility and create the 7 certification levels: support required 1 or 2, and care levels 1 (least disabled) to 5 (most disabled). In this study, patients were divided into 1) patients without any change in LTCI service during hospitalisation (Group N), 2) patients with coordination of LTCI services during hospitalization (Group C), 3) patients who newly initiated LTCI service after discharge (Group I). The primary outcome was a composite of HF rehospitalisation and all-cause mortality. Survival rate was compared using Kaplan-Meier curve analysis and log-rank test. Multivariate analysis was conducted using Cox proportional-hazards model adjusted for propensity score calculated based on age, gender, brain natriuretic peptide, β-blocker, angiotensin converting enzyme inhibitor /angiotensin II receptor blocker, need of any walking device or assistance at discharge, living alone, LTCI level. Results A total of 135 older patients were included (mean age 84 years, men 46%). During the median follow-up of 580 days, 43 events occurred. The number of patients for each group was as following: Group N, n = 91; Group C, n = 20; Group I, n = 24. The survival rates were significantly different among the three groups (log-rank test p = 0.039 , Figure 1). In Cox proportional-hazards model with Group N as a reference, Group C was associated with reduced risk of the study outcome (hazard ratio 0.22, 95% confidence interval 0.05-0.91, p = 0.036). Group I also showed lower event rate but not statistically significant (hazard ratio 0.81, 95% confidence interval 0.20-0.30, p = 0.756). All the patients in Group C used visiting nurse service, whereas the implementation rates were 12.1% and 37.5% in Group N and Group I, respectively. Implementation rate of visiting rehabilitation was higher in Group C (20.0%) compared to Group N (1.1%) and Group I (4.2). Conclusions Patients with coordination of LTCI service during HF hospitalization showed reduced risk of adverse outcome after discharge, implying the clinical benefits of utilization of LTCI service. Further large-scale studies are needed to examine the optimal utilization of tailor-made LTCI service according to the patient’s condition.

The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping, and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to reevaluate the role of endometrial cytology. LBC samples are easier to screen compared to conventional ones, due to a smaller screening area and an excellent quality of cell preparations. LBC by using peculiar cytoarchitectural features is a useful tool in the cellular diagnosis and follow-up of abnormalities, which, however, remains complementary to histopathology and to the emerging molecular diagnostic cytopathology. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. Herein, we also summarize the process and rationale by which updates were made to the standardized terminology in 2018 and outline the contents of the new Bethesda-style classification (the Yokohama system) for the endometrial cytology.

Objective This study evaluated cellular adequacy in endometrial liquid-based cytology (LBC) specimens. Methods In total, 1267 cases were obtained and the rate of unsatisfactory specimen and diagnostic accuracy for malignancy were assessed. If ≥10 cellular clusters composed of ≤30 endometrial cells were found per specimen, then the sample was provisionally considered adequate. Results The unsatisfactory rate (with fewer than 10 clusters) was 15.4%. Diagnostic accuracy in specimens with ≥10 clusters was significantly higher (90.5% vs 36.4%) than that in specimens with fewer than10 clusters. Moreover, the unsatisfactory rate in patients aged ≥60 years was significantly higher (33.8% vs 13.2%) than that in patients younger than 60 years. Although the unsatisfactory rate was decreased, significant differences were not found between cases with fewer than five clusters (22.6%) and fewer than 10 clusters (33.8%) in patients aged ≥60 years. Diagnostic accuracy in cases with five or more clusters was significantly higher (90.3% vs 0%) than that in cases with fewer than five clusters. Conclusions We propose that ≥10 clusters with ≥30 endometrial cells per cluster could be used as a specimen adequacy criterion for endometrial LBC. If ≥10 clusters cannot be found in patients aged ≥60 years, then the use of the alternative criterion of five or more clusters may yield satisfactory specimen adequacy.

Purpose To compare chest port (port)-related complication rates between right- and left-sided ports placed in adult oncologic patients with a history of right-sided port removal. Materials and Methods A retrospective chart review identified 90 adult oncologic patients with a history of right-sided port removal. Of these, 60 patients had a second port placed on the right side (right-side group), while 30 patients had a second port placed on the left side (left-side group). Median time between first port removal and second port placement was 217 days (range, 0–3808 days). Port-related complications included infection (port-site and/or bloodstream), mechanical, thrombotic, and port-site skin complications. Complication rates between groups were compared. Proportional subdistribution hazard regression (PSHREG) was conducted to determine if laterality of the second port is an independent risk factor for port-related complications. Results The cumulative follow-up period was 34,748 catheter-days (median, 233; range, 9–2162 days). Eleven patients (18.3%) in the right-side group and 2 patients (6.7%) in the left-side group had port-related complications (P = .21), accounting for complication rates of 0.5 and 0.2/1000 catheter-days (P = .24), respectively. No statistical difference was found in the incidence of infection (9/60 vs 1/30, P = .16), mechanical (0/60 vs. 1/30, P = .33), thrombotic (1/60 vs 0/30, P = 1.0), and skin-related (1/60 vs 0/30, P = 1.0) complications between groups. In multivariate PSHREG, laterality of the second port (hazard ratio = 3.09, 95% confidence interval = 0.81–11.76, P = .10) was not a significant risk factor for port-related complications. Conclusions In adult oncologic patients with a history of right-sided port removal, no significant differences in port-related complication rates were observed between right- and left-sided second ports.

OBJECTIVESInduction chemoradiotherapy followed by surgery is the standard treatment for superior sulcus tumours (SSTs). However, the protocols, chemotherapy agents and cycles used as well as the mode and intensity of radiotherapy vary between institutions. Thus, the objective of the study was to investigate the effects of trimodality therapy on the outcomes of patients with SSTs.METHODSSixty patients with SSTs were enrolled between January 1999 and December 2017. Induction therapy consisted primarily of 2 cycles of mitomycin–vindesine–cisplatin or cisplatin–vinorelbine delivered concurrently to the tumour with 40–45 Gy of radiation. Surgery was performed 2–6 weeks after completion of induction therapy.RESULTSFifty-four (90%) patients underwent radical surgical resection. Complete pathological resection was achieved in 44 patients (81%). There was no 30-day mortality. After a median follow-up of 57.0 months, 19 (35%) patients experienced recurrence, and 8 (15%) patients showed brain metastasis. A pathological complete response (PCR) was observed in 12 (22%) patients. The 5-year survival rate for the entire population (n = 54) was 69% (95% confidence interval 55–81%). The survival rate was better for patients who underwent complete resection than for those who underwent incomplete resection (73% vs 51%, P = 0.46). A better survival rate was evident in patients with PCR than in those without PCR (92% vs 62%, P = 0.12).CONCLUSIONSTrimodality therapy for SSTs was efficacious and associated with favourable outcomes, with acceptable morbidity and mortality. PCR in patients with resected SSTs reveals promising long-term survival prospects with the trimodality therapy.

We recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

Since their introduction into clinical practice in the 1950s, ileal conduits have been the most common type of urinary diversion used after radical cystectomy worldwide. Although ileal conduits are technically simpler to construct than other forms of urinary diversion, a variety of complications can occur in the early and late postoperative periods. Early complications include urine leakage, urinary obstruction, postoperative fluid collection (eg, urinoma, hematoma, lymphocele, or abscess), and fistula formation. Late complications include ureteroileal anastomotic stricture, stomal stenosis, conduit stenosis, and urolithiasis. Although not directly related to ileal conduits, ureteroarterial fistula can occur in patients with an ileal conduit. Interventional radiologists can play a pivotal role in diagnosis and management of these complications by performing image-guided minimally invasive procedures. In this article, the authors review the surgical anatomy of an ileal conduit and the underlying pathophysiology of and diagnostic workup for complications related to ileal conduits. The authors also discuss and illustrate current approaches to interventional radiologic management of these complications, with emphasis on a collaborative approach with urologists or endourologists to best preserve patients' renal function and maintain their quality of life. ©RSNA, 2020.

Objective In this study, we aimed to retrospectively investigate and confirm whether atypical nuclear findings in endometrial cytology are useful when assessed by image morphometry in liquid-based cytology (LBC) and compared with microscopic evaluation. Methods In total, 53 cases were selected for this study, including 11 presenting proliferative endometrium, 12 with surface papillary syncytial change with endometrial glandular and stromal breakdown (EGBD-SPSC), 10 endometrioid carcinoma grade 1 (G1-EEC), 10 EEC grade 3 (G3-EEC), and 10 endometrial serous carcinomas (ESC). Nuclear image morphometry for nuclear geometric features (area, grey value, aspect ratio, internuclear distance, nucleolar diameter) was performed using ImageJ computer software. For assessing nucleoli, 3861 nuclei were measured, and for nuclear findings, except for nucleoli, 4036 nuclei were measured in total. Results (a) Compared with G1-EEC, G3-EEC and ESC presented a marked increase in all six parameters (nuclear enlargement, anisonucleosis, nuclear shade, nuclear shape, irregularity of nuclear arrangement, and nucleolar size). (b) EGBD-SPSC presented a marked increase in two parameters (nuclear shade, nuclear shape) when compared with G1/G3-EEC and ESC. (c) Compared with EGBD-SPSC, EEC and ESC demonstrated a marked increase in nucleolar size (≥2.0 μm). (d) ESC presented a marked increase in nucleolar size (≥3.0 μm) when compared with G3-EEC. Conclusions Here we confirmed that atypical nuclear findings evaluated by image morphometry are as useful as microscopic evaluations in endometrial cytology. We believe that the objective evaluation of nucleolar size could contribute to an accurate diagnosis of endometrial-LBC samples.

Encouraging clinical results using immune checkpoint therapies to target the PD-1 axis in a variety of cancer types have paved the way for new immune therapy trials in brain tumor patients. However, the molecular mechanisms that regulate expression of the PD-1 pathway ligands, PD-L1 and PD-L2, remain poorly understood. To address this, we explored the cell-intrinsic mechanisms of constitutive PD-L1 and PD-L2 expression in brain tumors. PD-L1 and PD-L2 expression was assessed by flow cytometry and qRT-PCR in brain tumor cell lines and patient tumor-derived brain tumor-initiating cells (BTICs). Immunologic effects of PD-L2 overexpression were evaluated by IFN-γ ELISPOT. CD274 and PDCD1LG2 cis-regulatory regions were cloned from genomic DNA and assessed in full or by mutating and/or deleting regulatory elements by luciferase assays. Correlations between clinical responses and PD-L1 and PD-L2 expression status were evaluated in TCGA datasets in LGG and GBM patients. We found that a subset of brain tumor cell lines and BTICs expressed high constitutive levels of PD-L1 and PD-L2 and that PD-L2 overexpression inhibited neoantigen specific T cell IFN-γ production. Characterization of novel cis-regulatory regions in CD274 and PDCD1LG2 lead us to identify that GATA2 is sufficient to drive PD-L1 and PD-L2 expression and is necessary for PD-L2 expression. Importantly, in TCGA datasets, PD-L2 correlated with worse clinical outcomes in glioma patients.. By perturbing GATA2 biology, targeted therapies may be useful to decrease inhibitory effects of PD-L2 in the microenvironment.

Sporadic gastrin-producing neuroendocrine tumors (NETs) of the duodenum present with either Zollinger-Ellison syndrome or unspecific syndromes. Ki-67 scoring in cytopathology is an alternative approach for establishing the gastrinoma grade. Although the majority of NETs, including gastrinomas, occur in the duodenum, most research regarding the Ki-67 index is focused on tumors of pancreatic origin. To the best of our knowledge, there is no study on the Ki-67 index for cytological analysis of duodenal gastrinoma. The current report presents two cases of a 56-year-old man and a 66-year-old woman with NET G1 and G2 gastrinoma, respectively, arising in the duodenal bulb. The present report focused on the differences in nuclear pleomorphism and Ki-67 index between these two cases.

Background Although clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed “neoantigens,” represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination. Methods Flow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TILs). Whole-exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite, and top-ranking candidates were screened for reactivity by interferon-gamma enzyme linked immunospot assays. Survival analysis was performed comparing neoantigen vaccination, anti-programmed cell death ligand 1 (αPD-L1), or combination therapy. Results Compared with the GL261 model, CT2A exhibited immunologic features consistent with human GBM including reduced αPD-L1 sensitivity and hypofunctional TILs. Of the 29 CT2A neoantigens screened, we identified neoantigen-specific CD8+ T-cell responses in the intracranial TIL and draining lymph nodes to two H2-Kb restricted (Epb4H471L and Pomgnt1R497L) and one H2-Db restricted neoantigen (Plin2G332R). Survival analysis showed that therapeutic neoantigen vaccination with Epb4H471L, Pomgnt1R497L, and Plin2G332R, in combination with αPD-L1 treatment was superior to αPD-L1 alone. Conclusions We identified endogenous neoantigen specific CD8+ T cells within an αPD-L1 resistant murine GBM and show that neoantigen vaccination significantly augments survival benefit in combination with αPD-L1 treatment. These observations provide important preclinical correlates for GBM immunotherapy trials and support further investigation into the effects of multimodal immunotherapeutic interventions on antiglioma immunity. Key Points 1. Neoantigen vaccines combined with checkpoint blockade may be promising treatments. 2. CT2A tumors exhibit features of human GBM microenvironments. 3. Differential scanning fluorimetry assays may complement in silico neoantigen prediction tools.

Summary Background & aims The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. Subjects/Methods We studied 85,293 Japanese subjects by questionnaire at baseline (age 45–74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. Results After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50–0.99) and 0.66 (0.44–0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39–0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Conclusions Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men.

A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population.A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998.Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72-1.00; P trend0.05), slightly more strongly with distal colon cancer (P trend0.05); but an increased risk of rectal cancer in women (P trend0.05). The westernized pattern showed a significant positive linear trend for colon (P trend0.05) and distal cancer (P trend0.05) in women. There was no apparent association of traditional Japanese dietary pattern on the overall or any specific sites risk of CRC.A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women.

Background It is unknown whether placement of a chest port (port) and a gastrostomy tube (G-tube) in a single session increases the risk of the early device infections in patients with head and neck cancer (HNC) undergoing chemoradiation. Purpose To compare the incidence of early (≤30 days) port and G-tube infections placed in a single session compared to two separate sessions in patients with HNC. Material and Methods Between January 2012 and December 2019, 169 patients with HNC undergoing chemoradiation had a port and a G-tube placed in a single session (single-session group), while 25 had both devices placed in two separate sessions (two-session group) within 30 days of each other. The incidence of early device infections was compared between groups. Logistic regression analysis was conducted to determine if the number of sessions was a variable affecting device infections. Results A total of 6 (3%) early port infections and 13 (6.7%) early G-tube infections were identified. The two groups did not significantly differ in the incidence of early port infections (3.0%, 5/169 and 4.0%, 1/25, p = 0.59) nor early G-tube infections (7.1%, 12/169 and 4.0%, 1/25, p = 1.0). The number of sessions for device placement was not a variable affecting overall device infections in logistic regression analyses (odds ratio: 1.24, 95% confidence interval: 0.20–7.82, p = 0.82) after controlling for potential confounding variables. Conclusions The risk of early device infections in single-session placement appeared to be the same as two-session placement in patients with HNC undergoing chemoradiation.

This study was conducted to investigate the adherence to clinical practice guidelines (CPGs) for Clostridium difficile infection (CDI). A retrospective multicenter observational study was conducted via chart review at four teaching hospitals in Japan from April 2012 through September 2013. CDI was diagnosed based on positive identification of CD toxin by enzyme immunoassay testing. CDI patients were divided into non-severe and severe groups according to the severity criteria of four published guidelines (SHEA/IDSA 2010, ACG 2013, ESCMID 2009, HPA/DH 2008). Three parameters were assessed in association with disease severity: adherence to treatment guidelines, prognosis, and relapse rate. In total, 170 patients were diagnosed with CDI (1.04 cases per 10,000 patient-days). The 30-day all-cause mortality and recurrence rates were 13% and 14%, respectively. CPGs adherence ranged from 52% to 70% in the non-severe group and from 8.5 to 23% in the severe group (P

Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs. The serum-induced differentiation of GICs downregulated the endogenous expression of DPF1 and DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming ability and tumor-forming activity in a mouse xenograft model. Rescue experiments revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have previously reported that d4-family members can function as adaptor proteins between the SWI/SNF complex and NF-κB dimers, this does not significantly contribute to maintaining the stemness properties of GICs. Instead, these proteins were found to link a corepressor complex containing the nuclear receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our results indicate that DPF1 and DPF3a are potential therapeutic targets for glioblastoma.

Background: Rapid on-site evaluation (ROSE) of image-guided fine-needle aspiration (IGFNA) of hepatic lesions is necessary to ensure adequate sample collection and render preliminary diagnosis. We ...

Previously, through a TILLING (Targeting Induced Local Lesions in Genomes) approach applied on barley chloroplast mutator (cpm) seedlings a high frequency of polymorphisms in the rpl23 gene was detected. All the polymorphisms corresponded to five differences already known to exist in nature between the rpl23 gene located in the inverted repeats (IRs) and the rpl23 pseudogene located in the large single copy region (LSC). In this investigation, polymorphisms in the rpl23 gene were verified and besides, a similar situation was found for the pseudogene in cpm seedlings. On the other hand, no polymorphisms were found in any of those loci in 40 wild type barley seedlings. Those facts and the independent occurrence of polymorphisms in the gene and pseudogene in individual seedlings suggest that the detected polymorphisms initially arose from gene conversion between gene and pseudogene. Moreover, an additional recombination process involving small recombinant segments seems to occur between the two gene copies as a consequence of their location in the IRs. These and previous results support the hypothesis that t Instituto de Genética Fil: Lencina, Franco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética "Ewald A. Favret"; Argentina Fil: Landau, Alejandra Mabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética "Ewald A. Favret"; Argentina Fil: Petterson, Maria Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética "Ewald A. Favret"; Argentina Fil: Pacheco, Maria Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética "Ewald A. Favret"; Argentina Fil: Kobayashi, K. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Prina, Alberto Raul. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética "Ewald A. Favret"; Argentina

This study retrospectively evaluated the safety, impact on growth, and clinical outcomes of gastrojejunostomy tubes (GJTs) converted from surgically placed gastrostomy tubes (GTs) in 44 developmentally disabled children (median age: 28 months). The total duration of GJT follow-up was 31,378 device-days (median: 643 device-days). Three major complications (aspiration pneumonia) were identified in 3 patients (6.8%), 63 minor complications in 31 patients (70.5%), and 202 tube maintenance issues (TMIs) in 41 patients (93.2%). A significantly increased average change in weight-for-age z-scores was observed at each 6-month interval that continued past 25 months. Patients above the median rate of TMIs had marginally significant lower z-scores across the study period (P = 0.06), compared with those below the median rate. GJTs were removed in 6 patients (13.6%) because of adequate oral intake at last follow-up. Conversion from GTs to GJTs was a viable option to achieve sustained growth in developmentally disabled children. Frequency of TMIs may negatively impact their growth.

Neoantigens represent promising targets for personalized cancer vaccine strategies. However, the feasibility of this approach in lower mutational burden tumors like glioblastoma (GBM) remains unknown. We have previously reported the use of an immunogenomics pipeline to identify candidate neoantigens in preclinical models of GBM. Here, we report the application of the same immunogenomics pipeline to identify candidate neoantigens and guide screening for neoantigen-specific T cell responses in a patient with GBM treated with a personalized synthetic long peptide vaccine following autologous tumor lysate DC vaccination. Following vaccination, reactivity to three HLA class I- and five HLA class II-restricted candidate neoantigens were detected by IFN-γ ELISPOT in peripheral blood. A similar pattern of reactivity was observed among isolated post-treatment tumor-infiltrating lymphocytes. Genomic analysis of pre- and post-treatment GBM reflected clonal remodeling. These data demonstrate the feasibility and translational potential of a therapeutic neoantigen-based vaccine approach in patients with primary CNS tumors.

Anatomic variations of the pulmonary artery (PA) cause vascular injuries and result in critical mistakes. Here we report the first case of lung cancer with a fissureless left upper lobectomy, an aberrant mediastinal trunk of the lingular and basal segments of the PA. A 65-year-old man was referred to our hospital with a solid mass on the left upper lobe. A fissureless left upper lobectomy was performed due to severe incomplete lobulation. Intraoperative findings showed an extremely rare anatomic variation (left A5+A8+A9b) that arose as a common trunk from the left main PA. To prevent intraoperative injury, it is essential to consider the unexpected mediastinal inferior branch and perform a surgical procedure such as fissureless lobectomy upon encountering incomplete lobulation.