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Metal stents (MS) are recommended for preoperative biliary drainage (PBD) in patients with periampullary cancer, but whether MS are superior in terms of re-intervention and direct cost is debatable. This study aimed to compare the effects of MS and PS on the outcomes of patients with periampullary cancer.For this random-effects meta-analysis, electronic databases were screened for randomized controlled trials (RCTs) published until January 2022. Subgroup analyses were performed basis on the center type and presence of NAC.In this meta-analysis, seven RCTs (440 participants) were included. MS reduced re-interventions (risk ratio [RR] = 0.42, 95% confidence interval [CI] = 0.25-0.72) and direct costs (mean difference = -474 USD, 95% CI = -656 to -292). PBD-related complications (RR = 0.74, 95% CI = 0.32-1.71) and postoperative complications (RR = 0.73, 95% CI = 0.45-1.17) did not differ between MS and PS. Compared PS, MS reduced postoperative complications in high-volume centers (RR = 0.64, 95% CI = 0.49-0.84) and PBD-related complications in patients receiving NAC (RR = 0.29, 95% CI = 0.08-1.08).Metal stents likely reduces re-interventions and direct costs. Further studies are needed to confirm the effects of MS on the outcomes.

Identifying lateral pelvic lymph node (LPN) metastasis in low rectal cancer is crucial before treatment. Several risk factors and prediction models for LPN metastasis have been reported. However, there is no useful tool to accurately predict LPN metastasis. Therefore, we aimed to construct a nomogram for predicting LPN metastasis in rectal cancer.We analyzed the risk factors for potential LPN metastasis by logistic regression analysis in 705 patients who underwent primary resection of low rectal cancer. We included patients at 49 institutes of the Japan Society of Laparoscopic Colorectal Surgery between June 2010 and February 2012. Clinicopathological factors and magnetic resonance imaging findings were evaluated. The nomogram performance was assessed using the c-index and calibration plots, and the nomogram was validated using an external cohort.In the univariable logistic regression analysis, age, sex, carcinoembryonic antigen, tumor location, clinical T stage, tumor size, circumferential resection margin (CRM), extramural vascular invasion (EMVI), and the short and long axes of LPN and perirectal lymph node (PRLN) were nominated as risk factors for potential LPN metastasis. We identified a combination of the short axis of LPN, tumor location, EMVI, and short axis of PRLN as optimal for predicting potential LPN metastasis and developed a nomogram using these factors. This model had a c-index of 0.74 and was moderately calibrated and well-validated.This is the first study to construct a well-validated nomogram for predicting potential LPN metastasis in rectal cancer, and its performance was high.

Acoustic radiation force impulse (ARFI) elastography has been used to diagnose acute pancreatitis (AP). The present study aimed to assess the effectiveness of ARFI elastography in the diagnosis of AP. Studies examining the efficacy of ARFI elastography in AP were selected by searching MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrial.gov. until September 2021. Meta-analyses were performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. Eight case-control studies (994 patients) were included in the meta-analysis. The ARFI-Virtual Touch Quantification value (or ARFI shear wave propagation velocity) of the AP patient group was 0.83 m/s higher (95% confidence interval [CI]: 0.36-1.3) than that in the control group (95% CI: 1.0-1.28). The sensitivity and specificity of ARFI elastography for diagnosing AP were 98.3% (95% CI: 92.6-96.6%) and 95.5% (95% CI: 87.5-98.5%), respectively. The results showed that physicians could use ARFI elastography to accurately diagnose patients with AP. Additional well-designed studies are necessary to validate the efficacy of ARFI elastography in patients with AP.

Few studies have reported the impact of chemoradiotherapy (CRT) on the objective response of patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the factors predicting therapeutic effectiveness and the short- and long-term outcomes in patients with T4b ESCC treated with CRT.We included 155 patients with T4b ESCC who underwent CRT at the Department of Surgery, Gastroenterological Center, Yokohama City University, between January 2000 and December 2018. Responders were defined as patients who demonstrated a complete response (CR) or partial response (PR). Multivariate analysis for objective response was performed using a logistic regression model, and prognostic factors were evaluated by univariate and multivariate analyses.Among the 155 patients included, 20 and 84 patients demonstrated a CR and PR, respectively, resulting in a response rate of 67.1%. The median overall survival (OS) was 15.2 months, and the 3-year survival rate was 32.1%. High Glasgow prognostic score (GPS) and advanced N-category independently predicted the objective response to CRT. GPS and objective response were independent prognostic factors for OS. There was no significant difference in the long-term survival of responders who received subsequent chemotherapy or salvage surgery.High GPS and advanced N-category predicted a poor objective response to CRT in patients with T4b ESCC. Therefore, chemotherapeutic regimens with a higher efficacy are required. The indications for salvage surgery for responders should be carefully considered, with care taken to avoid complications. To confirm this, prospective randomized controlled studies are necessary.

Aberrant activity of the H3K27 modifiers EZH2 and BRD4 is an important oncogenic driver for atypical teratoid/rhabdoid tumor (AT/RT), and each is potentially a possible therapeutic target for treating AT/RT. We, therefore, determined whether targeting distinct histone modifier activities was an effective approach for treating AT/RT. The effects of EZH2 and BRD4 inhibition on histone modification, cell proliferation, and cell invasion were analyzed by immunoblotting, MTS assay, colony formation assay, and cell invasion assay. RNA- and chromatin immunoprecipitation-sequencing were used to determine transcriptional and epigenetic changes in AT/RT cells treated with EZH2 and BRD4 inhibitors. We treated mice bearing human AT/RT xenografts with EZH2 and BRD4 inhibitors. Intracranial tumor growth was monitored by bioluminescence imaging, and the therapeutic response was evaluated by animal survival. AT/RT cells showed elevated levels of H3K27 trimethylation (H3K27me3) and H3K27 acetylation (H3K27ac), with expression of EZH2 and BRD4, and lack of SMARCB1 proteins. Targeted inhibition of EZH2 and BRD4 activities reduced cell proliferation and invasiveness of AT/RT in association with decreasing H3K27me3 and H3K27ac. Differential genomic occupancy of H3K27me3 and H3K27ac regulated specific gene expression in response to EZH2 and BRD4 inhibitions. A combination of EZH2 and BRD4 inhibition increased the therapeutic benefit in vitro and in vivo, outperforming either monotherapy. Overall, histones H3K27me3 and H3K27ac were elevated in AT/RT cells and distributed in distinct chromatin regions to regulate specific gene expression and to promote AT/RT growth. Targeting EZH2 and BRD4 activity is, therefore, a potential combination therapy for AT/RT.

Sarcopenia, as assessed by body composition, can affect morbidity and survival in several gastrointestinal cancer. However, the impact of sarcopenia, referring to both quantity and quality of skeletal muscle, in biliary tract cancer (BTC) is debatable. We aimed to investigate the impact of sarcopenia on morbidity and mortality in patients with BTC.Electronic databases and trial registries were searched through July 2021 to perform random-effects meta-analyses. Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Twenty-nine studies (4443 patients) were included; 28 used computed tomography and one used dual-energy X-ray absorptiometry to assess body composition. Eighteen studies reported the impact of pre-operative sarcopenia on postoperative outcomes; namely, sarcopenia increased postoperative complications (risk ratio = 1.23, 95% confidence interval [CI] = 1.07 to 1.41; IIn sarcopenia, low muscle quantity and quality by body composition conferred an independent risk of morbidity and mortality in patients with BTC. Further studies are needed to confirm these findings and mitigate risk.

Introduction: In Japan, the direct smearing preparation (conventional preparation) has been widely used for cytological examination of the endometrium. Problems with the conventional preparation can be dissolved by liquid-based cytology (LBC) preparation. The Yokohama System is a method for reporting endometrial cytology, but the system lumps cancers together and does not distinguish between histological types. The objective of this study was to clarify morphometrical differences among endometrial endometrioid carcinoma grade 1 (G1), grade 3 (G3), and serous carcinoma (Serous) by image analysis of endometrial LBC. Methods: Using Papanicolaou smears prepared by LBC after sampling with a brush from 32 G1, 16 G3, and 16 Serous patients, image analysis was performed concerning the following 11 items: (1) number of layers of cluster, (2) area of cluster, (3) perimeter of cluster, (4) roundness of cluster, (5) complexity of cluster, (6) area of nucleus, (7) perimeter of nucleus, (8) roundness of nucleus, (9) complexity of nucleus, (10) area of nucleolus, and (11) nucleolus/nucleus (N/N) ratio. The data were statistically compared among G1, G3, and Serous. Results: Significant differences were observed in the number of layers of cluster (G1G3G3, G1>Serous), complexity of cluster (G1Serous), and N/N ratio (G1>G3, G3Conclusion: The number of layers and area of cluster, complexity of cluster, area and complexity of nucleus, area of nucleolus, and N/N ratio were suggested to be useful for the differentiation of histological types among G1, G3, and Serous. Particularly, differences in the number of layers of cluster, size of nucleus, and size of nucleolus among histological types were large and are considered to be potentially effective points of differential diagnosis.

Background. Patients with Parkinson’s disease (PD) receiving levodopa treatment often report motor complications including wearing-off (WO), dyskinesia, and morning akinesia. As motor complications are associated with a decrease in patients’ quality of life (QoL), it is important to identify their occurrence and commence immediate management. This study investigated whether differences in the perception of motor complications exist between patients and their physicians in routine clinical practice. Methods. After an Internet-based screening survey, questionnaires were distributed to physicians and their patients in Japan. The 9-item Wearing-Off Questionnaire (WOQ-9) was used to objectively assess the presence of WO; patients with WOQ-9 scores ≥2 were considered to have WO. McNemar’s test was used to compare physician assessment versus WOQ-9 scores, patient self-awareness versus physician assessment, and patient self-awareness versus WOQ-9, separately. Morning akinesia and dyskinesia were assessed by both physician assessment and patient self-awareness with McNemar’s test. QoL was assessed using the 8-item Parkinson’s Disease Questionnaire (PDQ-8) with the Wilcoxon rank-sum test. Results. A total of 235 patients with PD and their 92 physicians participated in this survey. A significant discordance was observed between the WOQ-9 and physician assessment of WO (67.2% vs 46.0%; p < 0.0001 ). Furthermore, patient self-awareness of WO was 35.3% ( p = 0.0004 , vs physician). Morning akinesia (patient, 58.7%; physician, 48.9%; p = 0.0032 ), dyskinesia (patient, 34.0%; physician, 23.4%; p = 0.0006 ), and bodily discomfort (patient, 25.0; physician, 0.0; p = 0.0102 ) of QoL were underrecognized by physicians. Conclusions. This study investigated differences in the perception of WO between patients with PD and their physicians in routine clinical practice and highlighted that patients have a low awareness of the symptoms of WO compared with physician assessments and WOQ-9. Conversely, morning akinesia, dyskinesia, and bodily discomfort were underrecognized by physicians.

PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration. CONCLUSION DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.

Histone acetylation is a post-translational modification of histones that is catalyzed by histone acetyltransferases (HATs) and plays an essential role in cellular processes. The HAT domain of EP300/CBP has recently emerged as a potential drug target for cancer therapy. Here, we describe the identification of the novel, highly potent, and selective EP300/CBP HAT inhibitor DS-9300. Our optimization efforts using a structure-based drug design approach based on the cocrystal structures of the EP300 HAT domain in complex with compounds

Patients with diffuse midline gliomas that are H3K27 altered (DMG) display a dismal prognosis. However, the molecular mechanisms underlying DMG tumorigenesis remain poorly defined. Here we show that SMARCA4, the catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex, is essential for the proliferation, migration, and invasion of DMG cells and tumor growth in patient-derived DMG xenograft models. SMARCA4 colocalizes with SOX10 at gene regulatory elements to control the expression of genes involved in cell growth and the extracellular matrix (ECM). Moreover, SMARCA4 chromatin binding is reduced upon depletion of SOX10 or H3.3K27M, a mutation occurring in about 60% DMG tumors. Furthermore, the SMARCA4 occupancy at enhancers marked by both SOX10 and H3K27 acetylation is reduced the most upon depleting the H3.3K27M mutation. Taken together, our results support a model in which epigenome reprogramming by H3.3K27M creates a dependence on SMARCA4-mediated chromatin remodeling to drive gene expression and the pathogenesis of H3.3K27M DMG. Significance: DMG is a deadly pediatric glioma currently without effective treatments. We discovered that the chromatin remodeler SMARCA4 is essential for the proliferation of DMG with H3K27M mutation in vitro and in vivo, identifying a potentially novel therapeutic approach to this disease. See related commentary by Beytagh and Weiss, p. 2730. See related article by Panditharatna et al., p. 2880. This article is highlighted in the In This Issue feature, p. 2711

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes.METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias.RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively.CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.

Objective: Recent advances in high-precision mammography and ultrasound screening have led to an increase in the detection of early lesions (ductal carcinoma in situ and small cancers) appearing as microcalcified lesions or microcystic images, and there needs to be an improvement in the accuracy of breast fine-needle aspiration biopsy (FNAB) assessing these lesions. The objective of this study was to investigate whether fractal analysis of Kirsch edge images for the tissue fragment inner structure (FKT) is useful in breast FNAB. FKT measures tissue fragment chromasia of hyperchromatic crowded tissue fragments (HCG), tissue fragment shape unevenness, and tissue fragment inner structure complexity. Study Design Materials: Nineteen epithelial tissue fragments of fibroadenoma (FA) from 7 patients and 52 tissue fragments of invasive breast carcinoma of no special type (IBC-NST) (grade 1–2) from 11 patients were assessed. First, tissue fragments were classified into small (smaller than 60 × 102 μm2), medium, and large (100 × 102 μm2 or larger), and the appearance rate of each size was determined. Second, for FKT, the luminance value of tissue fragment chromasia, the unevenness and fractal value, and the tissue fragment inner structure complexity were determined. In statistical analysis, the Steel-Dwass test, nonlinear discriminant analysis, and receiver operating characteristic analysis were performed, setting the significance level at p < 0.05. Results: “Unevenness of the tissue fragment shape,” “fractal value of the tissue fragment shape,” and “fractal value of the tissue fragment inner structure” were significantly higher in small and large tissue fragments in IBC-NST compared with those in FA. The specificity and sensitivity were the highest (100%) in small tissue fragments in multivariate analysis using 4 variables (“luminance value of tissue fragment chromasia,” “unevenness of tissue fragment shape,” “fractal value of the tissue fragment shape,” and “fractal value of the tissue fragment inner structure”). Conclusion: FKT, which evaluates “tissue fragment darkness,” “tissue fragment shape unevenness,” and “tissue fragment inner structure complexity” focusing on small tissue fragments of HCG in breast FNAB, is useful as a system that assists cytopathological assessment of breast FNAB.

Poly(N-isopropylacrylamide) (PNIPAM) nanogels were prepared by emulsion polymerization using sodium dodecyl sulfate (SDS) and employed as a capping agent in platinum nanoparticle (Pt NP) synthesis by liquid-phase reduction with hydrogen gas. When the PNIPAM nanogels were used without removing SDS, that is, a slight amount of SDS was included in the reaction solution, Pt nanocubes (NCs) were predominantly produced (>80%). The proportion of the resultant Pt NCs was much higher than that obtained using the PNIPAM linear polymer (∼60%). To clarify the effects of the three-dimensional polymer network and SDS, we synthesized Pt NPs using the PNIPAM nanogel without SDS (SDS-free PNIPAM nanogel) and found that Pt NCs are rarely formed, and most NPs obtained have an irregular shape. When only SDS was used as a capping agent, NCs were hardly obtained, but other polyhedral NPs were formed. Furthermore, the use of SDS together with the PNIPAM polymer led to the decrease in the proportion of the Pt NCs compared with that obtained using only the linear polymer. These results indicate that the enhancement of the Pt NC proportion using the PNIPAM nanogel with SDS is attributable to not only the three-dimensional polymer network of the PNIPAM nanogel but also the assist of SDS as a capping agent.

STUDY DESIGN A prospective nutritional intervention study for adult spinal deformity (ASD) patients. OBJECTIVE To investigate how a nutritional intervention affects the incidence of postoperative medical complications and the nutritional status. SUMMARY OF BACKGROUND DATA The medical complication rate in ASD surgery is very high, and one risk factor is malnutrition. Nutritional intervention may improve the patient's nutritional status and reduce risk, but this is unexplored regarding ASD surgery. METHODS Malnourished patients (i.e., a Prognostic Nutritional Index (PNI) score of

Deep digital flexor (DDF) tenotomy and realignment of the distal phalanx (DP) is a therapy used for the treatment of horses with chronic laminitis that, despite the few results described in the literature, presents with promising results. In view of this knowledge gap, this study aimed to describe and compare the clinical and radiographic findings of horses subject to this treatment. To this end, 7 horses with chronic laminitis that underwent tenotomy of the DDF in the metacarpal region and realignment of the DP by means of trimming and shoeing were included in this study. Data were obtained from the moments before and after the procedure. An improvement in clinical and radiographic parameters was observed when comparing the moment before and after the procedure, and it was concluded that this therapy is a viable option for the treatment of horses with chronic laminitis refractory to other therapies. La tenotomía flexora digital profunda (FDP) y el realineamiento de la falange distal (FD) es una terapia utilizada para el tratamiento de caballos con laminitis crónica y a pesar de los pocos resultados descritos en la literatura, es una técnica que presenta resultados prometedores. En vista de este vacío de conocimiento, este estudio tuvo como objetivo describir y comparar los hallazgos clínicos y radiográficos de los caballos que se sometieron a la terapia en cuestión. Para ello, se incluyeron en este estudio 7 caballos con laminitis crónica, a los que se les realizó tenotomía del FDP en la región metacarpiana y realineación de la FD mediante recorte y herrado, se obtuvieron datos del momento previo y posterior al procedimiento. Se observó una mejoría en los parámetros clínicos y radiográficos, al comparar el momento antes y después del procedimiento y se concluyó que esta terapia es una opción viable para el tratamiento de caballos con laminitis crónica refractaria a otras terapias. A tenotomia do flexor digital profundo (FDP) e o realinhamento da falange distal (FD) é uma terapêutica empregada para o tratamento de equinos com laminite crônica e apesar de poucos resultados descritos na literatura, é uma técnica que apresenta resultados promissores. Diante desta lacuna do conhecimento, este trabalho objetivou-se em descrever e comparar os achados clínicos e radiográficos dos equinos que foram submetidos a terapêutica em questão. Para tal, foram incluídos neste estudo 7 equinos apresentando laminite crônica que foram submetidos a tenotomia do FDP na região metacarpiana e realinhamento da FD por meio do casquemento e ferrageamento e foram obtidos dados do momento anterior e do momento posterior ao procedimento. Observou-se melhora dos parâmetros clínicos e dos parâmetros radiográficos quando comparado o momento anterior ao momento posterior ao procedimento e concluiu-se que a esta terapêutica é uma opção viável para o tratamento de equinos com laminite crônica que se apresenta refratária a outras terapias.

Small cell lung cancer (SCLC), accounting for around 13% of all lung cancers, often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. The POU class 2 homeobox 3 (POU2F3) is a master regulator of tuft cell identity and defines the SCLC-P subtype that lacks the neuroendocrine markers. Here, we have identified a previously uncharacterized protein, C11orf53, which is coexpressed with POU2F3 in both SCLC cell lines and patient samples. Mechanistically, C11orf53 directly interacts with POU2F3 and is recruited to chromatin by POU2F3. Depletion of C11orf53 reduced enhancer H3K27ac levels and chromatin accessibility, resulting in a reduction of POU2F3-dependent gene expression. On the basis of the molecular function of C11orf53, we renamed it as “POU Class 2 Homeobox Associating Factor 2” (POU2AF2). In summary, our study has identified a new coactivator of POU2F3 and sheds light on the therapeutic potential of targeting POU2AF2/POU2F3 heterodimer in human SCLC.

For people who are malnourished and unable to consume food by mouth, nasoenteral feeding tubes are commonly used for the administration of liquid food and drugs. Postpyloric placement is when the tip of the feeding tube is placed beyond the pylorus, in the small intestine. Endoscopic-guided placement of postpyloric feeding tubes is the most common approach. Usually, an endoscopist and two or more medical professionals perform this procedure using a guidewire technique. The position of the tube is then confirmed with fluoroscopy or radiography, which requires moving people undergoing the procedure to the radiology department. Alternatively, electromagnetic-guided placement of postpyloric nasoenteral feeding tubes can be performed by a single trained nurse, at the bedside and with less equipment than endoscopic-guided placement. Hence, electromagnetic-guided placement may represent a promising alternative to endoscopic-guided placement, especially in settings where endoscopy and radiographic facilities are unavailable or difficult to access.To assess the efficacy and safety of electromagnetic-guided placement of postpyloric nasoenteral feeding tubes compared to endoscopic-guided placement.We searched the Cochrane Library, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey until February 2021. We screened the reference lists of relevant review articles and current treatment guidelines for further literature. We contacted the study authors for missing data.We included randomised trials comparing electromagnetic-guided placement with endoscopic-guided placement of nasoenteral feeding tubes. We excluded prospective cohort studies, retrospective cohort studies, (nested) case-control studies, cross-sectional studies, and case series or case reports.Two review authors independently assessed the methodological quality of potentially eligible trials and extracted data from the included trials. The primary outcomes were technical success in insertion and aspiration pneumonitis. The secondary outcomes were the time for postpyloric placement of nasoenteral feeding tubes, direct healthcare costs, and adverse events. We performed a random-effects meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. We evaluated the certainty of evidence based on the GRADE approach.We identified four randomised controlled trials with 541 participants which met our inclusion criteria. All trials had methodological limitations, and lack of blinding of participants and investigators was a major source of bias. We had 'some concerns' for the overall risk of bias in all trials. Electromagnetic-guided postpyloric placement of nasoenteral feeding tubes may result in little to no difference in technical success in insertion compared to endoscopic-guided placement (RR 1.09, 95% CI 0.88 to 1.35; IWe found low-certainty evidence that electromagnetic-guided placement at the bedside results in little to no difference in technical success in insertion and aspiration pneumonitis, compared to endoscopic-guided placement. The heterogeneity of the healthcare professionals who performed the procedures and the small sample sizes limited our confidence in the evidence. Future research should be based on large studies with well-defined endpoints to potentially elucidate the differences between these two procedures.

The present study explored preoperative risk factors (predictors) of incisional surgical site infection (I-SSI) in severe or intractable ulcerative colitis (UC). This was a retrospective study of 230 consecutive patients who underwent primary surgery for UC. Patients whose surgical indications were UC with cancer or dysplasia were excluded. SSI was defined as an infection according to the Centers for Disease Control and Prevention Guidelines. Preoperative variables were examined by univariate, receiver operating characteristic curve, and multivariate analyses. We analyzed 208 patients in this study. In a multivariate logistic analysis, C-reactive protein (CRP) ≥ 1.7 mg/dl [odds ratio (OR) 5.35; 95% confidence interval (CI) 1.50–19.06; p = 0.01), albumin ≤ 2.4 g/dl (OR 5.77; 95% CI 1.41–23.57; p = 0.02), and preoperative blood transfusion (OR 3.21; 95% CI 1.04–9.96; p = 0.04) were predictors of I-SSI. Patients with all predictors had a more than 50% incidence of I-SSI, a higher incidence of all severe complications (13.6% vs. 3.2%; p = 0.02), and a longer postoperative hospital stay (19.5 vs. 17.0 days, p = 0.04) than the other patients. CRP ≥ 1.7 mg/dl, albumin ≤ 2.4 g/dl, and transfusion are predictors of I-SSI in severe or intractable UC. Clinician should carefully evaluate the surgical options before these predictors appear.

Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer. This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40–64 years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. The proportions of comorbid diseases (85.7% vs. 57.1%; P

The diagnosis of sarcopenia emphasizes both, the quantity and quality of skeletal muscle. However, the impact of the combination of muscle quantity and quality on long-term survival remains unclear. This study aimed to assess the impact of the combination of skeletal muscle quantity and quality on long-term outcomes in patients with gastric cancer who underwent curative resection. We retrospectively assessed 242 patients aged ≥ 65 ears who underwent curative gastrectomy between 2006 and 2015. The psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) were measured on preoperative computed tomography as skeletal muscle quantity and quality, respectively. The sarcopenia stage was classified by the combination of preoperative skeletal muscle quantity and quality (non-sarcopenia, sarcopenia, and severe sarcopenia). Prognostic factors for the 5-year overall survival (OS), non-cancer-specific survival (non-CSS), and cancer-specific survival (CSS) were evaluated by multivariable Cox regression. The median follow-up period was 63.2 months. The non-sarcopenia, sarcopenia, and severe sarcopenia groups comprised 88, 121, and 33 patients (36.4%, 50.0%, and 13.6%), respectively. The severe sarcopenia group was older, and had a greater depth of invasion, than the non-sarcopenia group. Multivariable analysis revealed severe sarcopenia as an independent predictive indicator of OS (hazard ratio [HR] 4.01; 95% confidence interval [CI] 1.75 to 9.22) and non-CSS (HR 3.27; 95% CI 1.61 to 6.67), but not CSS. The combination of preoperative skeletal muscle quantity and quality was useful for predicting survival, especially death from other diseases, in elderly patients who underwent gastrectomy for gastric cancer.

This study aimed to determine the efficacy and safety of cement augmentation for internally fixed trochanteric fractures through a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases to identify RCTs, published until July 2020 that examined the effects of cement augmentation of internal fixation of trochanteric fractures. The primary outcomes were reoperation and Parker Mobility Score, whereas the secondary outcomes were 1-year mortality rate, EuroQol 5 Dimension, fixation failures, and adverse events. We conducted meta-analyses of the outcome measures using the random-effects models. We evaluated the certainty of evidence based on the Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach. We included three RCTs (326 participants). No significant effect was observed in favor of cement augmentation on all these outcomes. The certainty of evidence for fixation failures was very low and that for the other outcomes was low. The overall risk of bias for each outcome was high or of some concern in all included studies. The effect of cement augmentation of internal fixation of trochanteric fractures was uncertain for the clinical outcomes due to the low certainty of evidence. Further RCTs with a low risk of selection bias may present convincing conclusions on the efficacy and safety of cement augmentation. Level 1

The Surgical Patient Safety System (SURPASS) has been proven to improve patient outcomes. However, few studies have evaluated the details of litigation and its prevention in terms of systemic and diagnostic errors as potentially preventable problems. The present study explored factors associated with accepted claims (surgeon-loss). We retrospectively searched the national Japanese malpractice claims database between 1961 and 2017. Using multivariable logistic regression models, we assessed the association between medical malpractice variables (systemic and diagnostic errors, facility size, time, place, and clinical outcomes) and litigation outcomes (acceptance). We evaluated whether or not the factors associated with litigation could have been prevented with the SURPASS checklist. We identified 339 malpractice claims made against general surgeons. There were 159 (56.3%) accepted claims, and the median compensation paid was 164,381 USD. In multivariable analyses, system (odds ratio, 27.2 95% confidence interval 13.8-53.5) and diagnostic errors (odds ratio 5.3, 95% confidence interval 2.7-10.5) had a significant statistical association with accepted claims. The SURPASS checklist may have prevented 7% and 10% of the accepted claims and systemic errors, respectively. It is unclear what proportion of accepted claims indicated that general surgeon loses should be prevented from performing surgery if the SURPASS checklist were used. In conclusion, systemic and diagnostic errors were associated with accepted claims. Surgical teams should adhere to the SURPASS checklist to enhance patient safety and reduce surgeon risk.

Objective Extracorporeal shock wave lithotripsy (ESWL) has been used to treat pancreatolithiasis in patients with chronic pancreatitis (CP), but the high recurrence rate remains challenging. We therefore evaluated the association between body composition parameters and the prediction of retreatment after ESWL. Methods This study retrospectively evaluated 42 patients with CP who had been treated with ESWL between 2008 and 2019 in a single center. Body composition parameters were measured on pretreatment computed tomography images. Patients who underwent repeat ESWL were classified as the retreatment group. Results There were 13 (31.0%) and 29 (69.0%) patients in the retreatment and non-retreatment groups, respectively. The visceral-to-subcutaneous adipose tissue area ratio (VSR) of the retreatment group was significantly lower than that of the non-retreatment group (p=0.016). When divided by the median VSR, 10 of the 20 patients with a VSR of0.85 underwent retreatment, whereas 3 of the 22 patients with a VSR of ≥0.85 underwent retreatment (p=0.019). According to a multivariate analysis, the VSR (p=0.010) and age (p=0.037) were independent factors associated with retreatment after ESWL. Conclusion This study showed that the VSR can predict the retreatment of patients with CP after ESWL.

Objectives: The present study aimed to identify patients with locally advanced rectal cancer in whom preoperative radiotherapy (RT) can be omitted. Methods: This study was a retrospective multi-institutional study for patients with pathological stage II and III rectal cancer who underwent surgery without preoperative therapy between January 2008 and December 2012. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors of local recurrence (LR). Results: The 5-year cumulative local recurrence rate (LRR) of 815 patients was 11.2%. Independent predictive factors of LR were determined by a multivariate analysis to be a tumor location of

Here, we report our experience with a 5-mm trocar site hernia (TSH) near a stoma. This is the first report describing the relationship between TSH and extraperitoneal colostomy. A 72-year-old man underwent laparoscopic abdominoperineal resection with extraperitoneal sigmoid colostomy and partial hepatectomy for rectal cancer accompanied by synchronous liver metastasis (pT3N1aM1a Stage IVA Union for International Cancer Control [UICC] 8th edition). The surgical procedures were completely performed without morbidity. After 1 year, he presented to our hospital with sudden nausea. Computed tomography (CT) revealed small bowel obstruction due to a 5-mm TSH, 1 cm from the stoma. The patient underwent laparoscopic hernia repair. The incidence of a 5-mm TSH is low. However, an abdominal wall vulnerability caused by the extensive exfoliation of the retroperitoneum due to the construction of the colostomy was observed, and the extraperitoneal colostomy influenced the onset of the 5-mm TSH. When the port and hernia sites are located in close proximity to each other, even a 5-mm trocar site may increase the incidence of TSH.

Introduction Although hepatitis B virus infection is well-described, the additional risk posed by oral bleeding in individuals with chronic hepatitis B virus infection has not been determined. This study aimed to determine the quantity of hepatitis B virus in the saliva of carriers in Japan, as a means of understanding the potential risk for horizontal transmission. Methods Saliva samples from 48 confirmed hepatitis B virus carriers were included in the analysis. Hepatitis B virus concentrations and the presence of occult blood as periodontal disease were evaluated in each sample. Results Hepatitis B surface antigen was identified in 46 of the 48 samples (98%), with hepatitis B virus DNA identified in 19 of the 48 saliva samples (40%). Occult blood was detected in 32 (67%) samples with the prevalence increasing as a function of age (r = 0.413; P = 0.003). There was a significantly positive correlation between hepatitis B virus DNA levels in the serum and saliva specimens (r = 0.895; P Conclusions Occult blood in saliva was detected in most participants. The detection of hepatitis B virus DNA correlated positively with hepatitis B virus in the serum and occult blood in the saliva. Therefore, improved care of periodontal disease among older people is important for preventing horizontal transmission of hepatitis B virus.

ImportanceFor patients with RAS wild-type metastatic colorectal cancer, adding anti–epidermal growth factor receptor (anti-EGFR) or anti–vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined.ObjectiveTo evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer.Design, Setting, and ParticipantsRandomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015–January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022).InterventionsPanitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.Main Outcomes and MeasuresThe primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate.ResultsIn the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%).Conclusions and RelevanceAmong patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population.Trial RegistrationClinicalTrials.gov Identifier: NCT02394795

Background Previous Japanese studies have led to the erroneous conclusion of antioxidant capacity (AOC) intakes of the overall Japanese diet due to limitations in the number and types of food measured, especially in rice and seafood intake. The aims of the study were to construct an AOC database of foods representative of the typical Japanese diet and to clarify the high contributors to AOC intake from the overall diet of the Japanese population. Methods Commonly consumed foods were estimated using 3-day dietary records (DRs) over the four seasons among 55 men and 58 women in Japan. To generate an AOC database suitable for the typical Japanese diet, hydrophilic (H-)/lipophilic (L-) oxygen radical absorbance capacity (ORAC) values of foods in each food group were measured via validated methods using the food intake rankings. Subsequently, we estimated the AOC intake and the AOC characteristics of a typical Japanese diet. Results Of 989 food items consumed by the participants, 189 food items were measured, which covered 78.8% of the total food intake. The most commonly consumed types of antioxidant-containing food were tea, soybean products, coffee, and rice according to H-ORAC, and soybean products, fish and shellfish, vegetables, and algae according to L-ORAC. Conclusions The characteristics of high AOC intake in rice and seafood more appropriately reflected the Japanese-style diet. Further studies are expected to clarify the association between food-derived AOC and its role in preventing or ameliorating lifestyle-related diseases.

Objective The aim of this study was to evaluate the long-term outcomes that were the secondary endpoints of a RCT of multi-port laparoscopic colectomy (MPC) versus SILC in colon cancer surgery. Summary of background data The actual long-term outcomes, such as the 5-year RFS, OS, and recurrence patterns after surgery, have not been evaluated by a RCT. Methods Patients with histologically proven colon carcinoma located in the cecum, ascending, sigmoid or rectosigmoid colon clinically diagnosed as stage 0-III were eligible for this study. Patients were preoperatively randomized and underwent complete mesocolic excision. The 5-year RFS, OS, and recurrence patterns were analyzed (UMIN-CTR 000007220). Results Between March 1, 2012, and March 31, 2015, a total of 200 patients were randomly assigned to either the MPC arm (n = 100) or SILC arm (n = 100). The median follow-up for all patients was 61.0 months. An intention-to-treat analysis showed that the 5-year RFS was 91.0% [95% confidence interval (CI) 85.1%-96.9%] in the MPC arm and 88.0% (95% CI 82.1%-93.9%) in the SILC arm (hazard ratio: 1.37; 95% CI 0.58-3.24; P = 0.479). The 5-year OS was 95.0% (95% CI 91.1%-98.9%) in the MPC arm and 93.0% (87.1%-98.9%) in the SILC arm (hazard ratio: 1.39; 95% CI 0.44-4.39; P = 0.568). There were no significant differences in the recurrence patterns between the 2 arms. Conclusions Even though the results of the 5-year OS and RFS in this trial were exploratory and underpowered, there were no statistically significant differences between the SILC and MPC arms. SILC may be an acceptable treatment option for select patients with colon cancer.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

The diagnosis of strangulated bowel obstruction (SBO) is sometimes difficult. We attempted to create and verify a discriminant formula for use as a diagnostic aid for the early diagnosis of SBO. This retrospective study included 97 patients who underwent an operation for SBO from January 2007 to September 2018. First, a discriminant analysis was performed for 73 patients who underwent an operation from January 2007 to December 2015 in order to obtain a formula. Next, we analyzed 34 patients who underwent an operation from January 2016 to September 2018 to verify the formula. The risk factors for SBO included ascites, signs of preperitoneal irritation, and lactate > 1.16 mmol/L. The discriminant formula is as follows: 1.954 × collection of ascites (1 or 0) + 1.239 × peritoneal irritation sign (1 or 0) + 0.378 × lactate − 2.331 (1: positive, 0: negative). The predictive value was as follows: sensitivity, 87.5%; specificity, 64.7%; and predictive accuracy, 73.5%. In patients who presented within 24 h of the onset, the sensitivity was 92.3%, the specificity was 75.0%, and the predictive accuracy was 85.7%. Our discriminant formula seems useful for the rapid diagnosis of SBO.

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1–100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141–0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.