Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer.</p> <p>Methods</p> <p>Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m²/day was administered on each day of irradiation.</p> <p>Results</p> <p>Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients).</p> <p>Conclusions</p> <p>Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.</p

The risk of newly diagnosed cancer in patients with rheumatoid arthritis by TNF inhibitor use: a nationwide cohort study

Background : Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods : Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results : Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions : The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC17C0069

Balloon Dilatation for Corrosive Esophageal Strictures in Children: Radiologic and Clinical Outcomes

Objective: We retrospectively evaluated the effectiveness of the esophageal balloon dilatation (EBD) in children with a corrosive esophageal stricture. Materials and Methods: The study subjects included 14 patients (M:F = 8:6, age range: 17-85 months) who underwent an EBD due to a corrosive esophageal stricture. The causative agents for the condition were glacial acetic acid (n = 9) and lye (n = 5). Results: A total of 52 EBD sessions were performed in 14 patients (range 1-8 sessions). During the mean 15-month follow-up period (range 1-79 months), 12 patients (86%) underwent additional EBD due to recurrent esophageal stricture. Dysphagia improved after each EBD session and oral feeding was possible between EBD sessions. Long-term success (defined as dysphagia relief for at least 12 months after the last EBD) was achieved in two patients (14%). Temporary success of EBD (defined as dysphagia relief for at least one month after the EBD session) was achieved in 17 out of 52 sessions (33%). A submucosal tear of the esophagus was observed in two (4%) sessions of EBD. Conclusion: Only a limited number of children with corrosive esophageal strictures were considered cured by EBD. However, the outcome of repeated EBD was sufficient to allow the children to eat per os prior to surgical management.Doo EY, 2009, CLIN RADIOL, V64, P265, DOI 10.1016/j.crad.2008.10.001PARK JY, 2009, KOREAN J PEDIAT, V52, P446Hyoung J, 2008, J VASC INTERV RADIOL, V19, P736, DOI 10.1016/j.jvir.2008.01.015Ko HK, 2006, J VASC INTERV RADIOL, V17, P1327, DOI 10.1097/01.RVI.0000232686.29864.0AWeintraub JL, 2006, J VASC INTERV RADIOL, V17, P831, DOI 10.1097/01.RVI.0000217964.55623.19Wilkinson AG, 2004, PEDIATR RADIOL, V34, P414, DOI 10.1007/s00247-004-1164-1Huang YC, 2004, PEDIATR SURG INT, V20, P207, DOI 10.1007/s00383-004-1153-3Lan LCL, 2003, J PEDIATR SURG, V38, P1712, DOI 10.1016/S0022-3468(03)00638-9Fasulakis S, 2003, PEDIATR RADIOL, V33, P682, DOI 10.1007/s00247-003-1011-9Hamza AF, 2003, J PEDIATR SURG, V38, P828Kukkady A, 2002, PEDIATR SURG INT, V18, P486, DOI 10.1007/s00383-002-0798-zYEMING W, 2002, J PEDIATR SURG, V37, P398Jayakrishnan VK, 2001, PEDIATR RADIOL, V31, P98Lisy J, 1998, ACAD RADIOL, V5, P832Yararbai O, 1998, HEPATO-GASTROENTEROL, V45, P59KIM IO, 1993, RADIOLOGY, V189, P741HAN HY, 1993, J KOREAN RADIOL SOC, V29, P1181SONG HY, 1992, RADIOLOGY, V184, P373GUNDOGDU HZ, 1992, J PEDIATR SURG, V27, P767LOVEJOY FH, 1990, NEW ENGL J MED, V323, P668MAYNAR M, 1988, RADIOLOGY, V167, P703DELANGE EE, 1988, RADIOLOGY, V167, P45SATO Y, 1988, AM J ROENTGENOL, V150, P639MCLEAN GK, 1987, RADIOLOGY, V165, P35GOLDTHORN JF, 1984, RADIOLOGY, V153, P655LONDON RL, 1981, GASTROENTEROLOGY, V80, P173MUHLETALER CA, 1980, AM J ROENTGENOL, V134, P1137RAGHEB MI, 1976, SURGERY, V79, P494

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia

IntroductionL-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN.MethodsThe study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias.ResultsThe analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17–1.62) or the complete response rate (OR 0.86; 95% CI = 0.29–2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36–2.78 and OR 1.24; 95% CI, 0.50–3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups.ConclusionThere is no clear rationale for avoiding Asp-TPN in ASNase-treated patients

In vitro ability of Staphylococcus aureus isolates from bacteraemic patients with and without metastatic complications to invade vascular endothelial cells

Invasion of vascular endothelial cells is thought to be a critical step in the development of metastatic infections in patients with Staphylococcus aureus bacteraemia. This study was designed to evaluate the association between the ability to invade endothelial cells and metastatic infection by S. aureus. Patients with metastatic infection were identified among those with community-acquired S. aureus bacteraemia in a tertiary referral hospital. Patients with simple bacteraemia caused by S. aureus over the same period served as the control group. The ability of each clinical isolate to invade endothelial cells was evaluated by counting the number of intracellular organisms 1 h after inoculation onto human umbilical vein endothelial cells in vitro. The cytotoxic activity of intracellular S. aureus was determined 24 h after internalization, and expressed as the percentage of cells killed. The clinical isolates varied in invasiveness and cytotoxicity. The median invasiveness, relative to S. aureus reference strain ATCC 29213, was 145 % in the cases (n=10) [interquartile range (IQR) 103-160] and 153 % (IQR 111-173) in the controls (n=11; P=0.44). The median cytotoxicity was 59.4 % (IQR 47-68) in the cases and 65.2 % (IQR 50-74) in the controls (P=0.44). Differences in the ability of S. aureus to invade and destroy vascular endothelial cells in vitro were not associated with the development of metastatic complications in patients with S. aureus bacteraemia. This implies that the invasiveness and toxicity of S. aureus for endothelial cells may not be major determinants of metastatic infection.The work was supported by grant no. 02-05-026 from the research fund of Seoul National University Bundang Hospital

Diagnostic algorithm for papillary urothelial tumors in the urinary bladder

Papillary urothelial neoplasms with deceptively bland cytology cannot be easily classified. We aimed to design a new algorithm that could differentiate between these neoplasms based on a scoring system. We proposed a new scoring system that enables to reproducibly diagnose non-invasive papillary urothelial tumors. In this system, each lesion was given individual scores from 0 to 3 for mitosis and cellular thickness, from 0 to 2 for cellular atypia, and an additional score for papillary fusion. These scores were combined to form a summed score allowing the tumors to be ranked as follows: 0–1 = UP, 2–4 = low malignant potential (LMP), 5–7 = low-grade transitional cell carcinoma (TCC), and 8–9 = high-grade TCC. In addition to the scoring system, ancillary studies of MIB and p53 indexes with CK20 expression pattern analyses were compared together with clinical parameters. The MIB index was strongly correlated with disease progression. Four of the 22 LMP patients (18.2%) had late recurrences, two of these four (9.1%) had progression to low-grade carcinoma. The MIB index for LMP patients was strongly associated with recurrence (recurrence vs. non-recurrence, 16.5 vs. 8.1, p < 0.001). The proposed scoring system could enhance the reproducibility to distinguish papillary urothelial neoplasms

Drug repurposing using meta-analysis of gene expression in Alzheimer&apos;s disease

IntroductionAlzheimer&apos;s disease and other forms of dementia are disease that bring an increased global burden. However, the medicine developed to date remains limited. The purpose of this study is to predict drug repositioning candidates using a computational method that integrates gene expression profiles on Alzheimer&apos;s disease and compound-induced changes in gene expression levels. MethodsGene expression data on Alzheimer&apos;s disease were obtained from the Gene Expression Omnibus (GEO) and we conducted a meta-analysis of their gene expression levels. The reverse scores of compound-induced gene expressions were computed based on the reversal relationship between disease and drug gene expression profiles. ResultsReversal genes and the candidate compounds were identified by the leave-one-out cross-validation procedure. Additionally, the half-maximal inhibitory concentration (IC50) values and the blood-brain barrier (BBB) permeability of candidate compounds were obtained from ChEMBL and PubChem, respectively. ConclusionNew therapeutic target genes and drug candidates against Alzheimer&apos;s disease were identified by means of drug repositioning.N