Κυριακή 12 Νοεμβρίου 2017

A phase I/II pharmacokinetics/pharmacodynamics study of irinotecan combined with S−1 for recurrent/metastatic breast cancer in patients with selected UGT1A1 genotypes (the JBCRG-M01 study)

Abstract

S-1 and irinotecan combination is attractive for breast cancer refractory to anthracyclines and taxanes. Patients with advanced human epidermal growth factor receptor 2 (HER2)-negative breast cancer previously treated with anthracyclines and taxanes were eligible. Patients with brain metastases and homozygous for UGT1A1 *6 or *28 or compound heterozygous (*6/*28) were excluded. A dose-escalation design was chosen for the phase I portion (level 1: irinotecan 80 mg/m2 days 1–8 and S-1 80 mg/m2 days 1–14 every 3 weeks; level 2: irinotecan 100 mg/m2 and S-1 80 mg/m2). Study objectives included determination of the recommended dose for phase II, response rate, progression-free survival (PFS), and safety. Pharmacokinetics and CD34+ circulating endothelial cells (CECs) as pharmacodynamics were also analyzed. Thirty-seven patients were included. One patient at each level developed dose-limiting toxicities; therefore, level 2 was the recommended dose for phase II. Diarrhea was more common in patients possessing a *6 or *28 allele compared with wild-type homozygous patients (46% and 25%). Among 29 patients treated at level 2, PFS was longer for UGT1A1 wt/*6 and wt/*28 patients than for wt/wt patients (12 vs. 8 months, P = 0.06). PFS was significantly longer in patients with a larger-than-median SN-38 area under the curve (AUC) than in those with a smaller AUC (P = 0.039). There was an association between clinical benefit and reduction in baseline CD34+ CECs by S-1 (P = 0.047). The combination of irinotecan and S-1 is effective and warrants further investigation.

Thumbnail image of graphical abstract

S-1 and irinotecan combination is an attractive option for advanced human epidermal growth factor receptor 2-negative breast cancer refractory to anthracyclines and taxanes. This study determined the recommended dose and safety/efficacy profile of this combination and demonstrated the association between clinical efficacy and pharmacogenomics/pharmacokinetics/pharmacodynamics profile.



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Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study

Abstract

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534–0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (= 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.

Thumbnail image of graphical abstract

PLC and IDC have many different characteristics, but there is not enough difference on the DSS.



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A phase I/II pharmacokinetics/pharmacodynamics study of irinotecan combined with S−1 for recurrent/metastatic breast cancer in patients with selected UGT1A1 genotypes (the JBCRG-M01 study)

Abstract

S-1 and irinotecan combination is attractive for breast cancer refractory to anthracyclines and taxanes. Patients with advanced human epidermal growth factor receptor 2 (HER2)-negative breast cancer previously treated with anthracyclines and taxanes were eligible. Patients with brain metastases and homozygous for UGT1A1 *6 or *28 or compound heterozygous (*6/*28) were excluded. A dose-escalation design was chosen for the phase I portion (level 1: irinotecan 80 mg/m2 days 1–8 and S-1 80 mg/m2 days 1–14 every 3 weeks; level 2: irinotecan 100 mg/m2 and S-1 80 mg/m2). Study objectives included determination of the recommended dose for phase II, response rate, progression-free survival (PFS), and safety. Pharmacokinetics and CD34+ circulating endothelial cells (CECs) as pharmacodynamics were also analyzed. Thirty-seven patients were included. One patient at each level developed dose-limiting toxicities; therefore, level 2 was the recommended dose for phase II. Diarrhea was more common in patients possessing a *6 or *28 allele compared with wild-type homozygous patients (46% and 25%). Among 29 patients treated at level 2, PFS was longer for UGT1A1 wt/*6 and wt/*28 patients than for wt/wt patients (12 vs. 8 months, P = 0.06). PFS was significantly longer in patients with a larger-than-median SN-38 area under the curve (AUC) than in those with a smaller AUC (P = 0.039). There was an association between clinical benefit and reduction in baseline CD34+ CECs by S-1 (P = 0.047). The combination of irinotecan and S-1 is effective and warrants further investigation.

Thumbnail image of graphical abstract

S-1 and irinotecan combination is an attractive option for advanced human epidermal growth factor receptor 2-negative breast cancer refractory to anthracyclines and taxanes. This study determined the recommended dose and safety/efficacy profile of this combination and demonstrated the association between clinical efficacy and pharmacogenomics/pharmacokinetics/pharmacodynamics profile.



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Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study

Abstract

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534–0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (= 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.

Thumbnail image of graphical abstract

PLC and IDC have many different characteristics, but there is not enough difference on the DSS.



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Laparoscopic repair of a right diaphragmatic hernia in a post-partum lady

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Abstract
Traumatic diaphragmatic injuries (TDI) are often challenging to diagnose. Research suggests that no single diagnostic study is sensitive or specific enough to identify such an injury, unless there is established herniation of intrabdominal contents. It is a rare cause of small bowel obstruction, which carries a substantial mortality rate. This report describes a case of a 41-year-old pregnant female who presented with irretractable vomiting and abdominal pain secondary to a delayed presentation of right-sided TDI. The most accepted mechanism regarding TDI is due to sudden elevation in the pleuroperitoneal pressure gradient. This case is unusual given its mechanism of injury during pregnancy and its right-sided location. She underwent laparoscopy which facilitated successful reduction of the hernial and closure of the defect. Postoperatively, she made an excellent recovery and was discharged within a few days. This report aims to increase the awareness amongst surgeons.

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Ultrasound with neurostimulation compared with ultrasound guidance alone for lumbar plexus block: A randomised single blinded equivalence trial

BACKGROUND Ultrasound-guided lumbar plexus blocks usually require confirmatory neurostimulation. A simpler alternative is to inject local anaesthetic inside the posteromedial quadrant of the psoas muscle under ultrasound guidance. OBJECTIVE We hypothesised that both techniques would result in similar total anaesthesia time, defined as the sum of performance and onset time. DESIGN A randomised, observer-blinded, equivalence trial (equivalence margin = 7.4 min). SETTING Ramathibodi Hospital and Maharaj Nakorn Chiang Mai Hospital (Thailand) from 12 May 2016 to 10 January 2017. PATIENTS A total of 110 patients undergoing total hip or knee arthroplasty, who required lumbar plexus block for postoperative analgesia. INTERVENTION In the combined ultrasonography-neurostimulation group, quadriceps-evoked motor response was sought at a current between 0.2 and 0.8 mA prior to local anaesthetic injection (30 ml of lidocaine 1% and levobupivacaine 0.25% with epinephrine 5 μg ml−1 and 5 mg of dexamethasone). In the ultrasound guidance alone group, local anaesthetic was simply injected inside the posteromedial quadrant of the psoas muscle. MAIN OUTCOMES MEASURES We measured the total anaesthesia time, the success rate (at 30 min), the number of needle passes, block-related pain, cumulative opioid consumption (at 24 h) and adverse events (vascular puncture, paraesthesia, local anaesthetic spread to the epidural space). RESULTS Compared with ultrasound guidance alone, combined ultrasonography-neurostimulation resulted in decreased mean (±SD) total anaesthesia time [15.3 (±6.5) vs. 20.1 (±9.0) min; mean difference, −4.8; 95% confidence interval, −8.1 to −1.9; P = 0.005] and mean (±SD) onset time [10.2 (±5.6) vs. 15.5 (±9.0) min; P = 0.004). No inter-group differences were observed in terms of success rate, performance time, number of needle passes, block-related pain, opioid consumption or adverse events. CONCLUSION Although the ultrasonography-neurostimulation technique results in a shorter total anaesthesia time compared with ultrasound guidance alone, this difference falls within our accepted equivalence margin (±7.4 min). TRIAL REGISTRATION www.clinicaltrials in the (Study ID: TCTR20160427003). Correspondence to De Q. Tran, MD, FRCPC, Professor, Department of Anaesthesia, Montreal General Hospital, McGill University, 1650 Ave Cedar, Montreal, QC, Canada H3G-1A4 Tel: +1 514 934 1934x43261; fax: +1 514 934 8249; e-mail: de_tran@hotmail.com © 2017 European Society of Anaesthesiology

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Radiotherapy for Gastric Bleeding from Tumor Invasion of Recurrent Colon Cancer with Liver Metastasis After Resection



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Radiotherapy for Gastric Bleeding from Tumor Invasion of Recurrent Colon Cancer with Liver Metastasis After Resection



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A patient with acquired factor X deficiency and metastatic transitional cell carcinoma of the bladder: is there a link between metastasis and factor deficiency in solid tumors?



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Is Lipidomic the Answer to the Search of a Biomarker for Organ Preservation Protocol in Head and Neck Squamous Cell Carcinoma?

Abstract

In the last decade organ preservation protocols based on chemoradiotherapy (CRT) has been showing the possibility of preserving function without jeopardizing survival for locally advanced head and neck squamous cell carcinoma (HNSCC). Still, only a percentage of the patients will benefit from this approach and, to date, no biomarkers are known to correctly predict these patients. More recently, modern mass spectrometry method has been used to determine metabolic profiles, and lipidomics, in particular, emerged as a new field of study in oncology and other diseases. This study aimed to analyze the lipid profile on saliva from patients undergoing to a prospective, single center, open-label, non-randomized phase II trial for organ preservation on HNSCC. The lipid analysis was performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Multivariate statistical analyses based on principal component analysis and orthogonal partial least square-discriminant analysis were applied to MALDI-TOF-MS data to visualize differences between the lipid profiles and identify potential biomarkers. The results assisted on distinguishing complete responders from non-responders to the treatment protocol. In conclusion, we demonstrated that a group of lipids is differentially abundant in saliva from HNSCC patients submitted to an organ preservation protocol, being able to differentiate responders from non-responders. These results suggest the potential use of lipid biomarkers to identify patients who may benefit from this treatment. Also, we showed that saliva testing might be routinely used in clinical practice, for being a non-invasive alternative to blood testing, besides inexpensive and easy to obtain.



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Is Lipidomic the Answer to the Search of a Biomarker for Organ Preservation Protocol in Head and Neck Squamous Cell Carcinoma?

Abstract

In the last decade organ preservation protocols based on chemoradiotherapy (CRT) has been showing the possibility of preserving function without jeopardizing survival for locally advanced head and neck squamous cell carcinoma (HNSCC). Still, only a percentage of the patients will benefit from this approach and, to date, no biomarkers are known to correctly predict these patients. More recently, modern mass spectrometry method has been used to determine metabolic profiles, and lipidomics, in particular, emerged as a new field of study in oncology and other diseases. This study aimed to analyze the lipid profile on saliva from patients undergoing to a prospective, single center, open-label, non-randomized phase II trial for organ preservation on HNSCC. The lipid analysis was performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Multivariate statistical analyses based on principal component analysis and orthogonal partial least square-discriminant analysis were applied to MALDI-TOF-MS data to visualize differences between the lipid profiles and identify potential biomarkers. The results assisted on distinguishing complete responders from non-responders to the treatment protocol. In conclusion, we demonstrated that a group of lipids is differentially abundant in saliva from HNSCC patients submitted to an organ preservation protocol, being able to differentiate responders from non-responders. These results suggest the potential use of lipid biomarkers to identify patients who may benefit from this treatment. Also, we showed that saliva testing might be routinely used in clinical practice, for being a non-invasive alternative to blood testing, besides inexpensive and easy to obtain.



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Transforaminal intrathecal delivery of nusinersen using cone-beam computed tomography for children with spinal muscular atrophy and extensive surgical instrumentation: early results of technical success and safety

Abstract

Background

Nusinersen, the only treatment approved by the United States Food and Drug Administration for spinal muscular atrophy (SMA), is delivered intrathecally. Many children with SMA have extensive spinal instrumentation and deformities, often precluding the use of standard approaches for gaining intrathecal access. Furthermore the anatomical distortion that often occurs with rotoscoliosis can complicate the use of fluoroscopic guidance. Compared to fluoroscopy, CT affords superior guidance for complex needle placements. This opens up alternatives to the posterior (interlaminar) technique, including transforaminal and caudal approaches.

Objective

This study describes the early results of technical success, complications and radiation dose of intrathecal delivery of nusinersen using cone-beam CT guidance with two-axis fluoroscopic navigational overlay.

Materials and methods

We conducted a retrospective review of 15 consecutive nusinersen injections performed in four children with SMA and extensive spinal hardware precluding standard posterior lumbar puncture techniques. These children were treated using transforaminal thecal access employing cone-beam CT with navigational overlay. We analyzed results including technical success, complications and total fluoroscopy time.

Results

All procedures were technically successful. No major complications and one minor complication were reported; the minor complication was a post-procedural neuropathic headache that was attributed to procedural positioning and was treated successfully with gabapentin. The average procedural fluoroscopy time and air kerma were 1.9 min and 55.8 mGy, respectively.

Conclusion

Cone-beam CT guidance with two-axis navigational overlay is a safe, effective method for gaining transforaminal intrathecal access in children with spinal abnormalities and hardware precluding the use of standard techniques.



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Transforaminal intrathecal delivery of nusinersen using cone-beam computed tomography for children with spinal muscular atrophy and extensive surgical instrumentation: early results of technical success and safety

Abstract

Background

Nusinersen, the only treatment approved by the United States Food and Drug Administration for spinal muscular atrophy (SMA), is delivered intrathecally. Many children with SMA have extensive spinal instrumentation and deformities, often precluding the use of standard approaches for gaining intrathecal access. Furthermore the anatomical distortion that often occurs with rotoscoliosis can complicate the use of fluoroscopic guidance. Compared to fluoroscopy, CT affords superior guidance for complex needle placements. This opens up alternatives to the posterior (interlaminar) technique, including transforaminal and caudal approaches.

Objective

This study describes the early results of technical success, complications and radiation dose of intrathecal delivery of nusinersen using cone-beam CT guidance with two-axis fluoroscopic navigational overlay.

Materials and methods

We conducted a retrospective review of 15 consecutive nusinersen injections performed in four children with SMA and extensive spinal hardware precluding standard posterior lumbar puncture techniques. These children were treated using transforaminal thecal access employing cone-beam CT with navigational overlay. We analyzed results including technical success, complications and total fluoroscopy time.

Results

All procedures were technically successful. No major complications and one minor complication were reported; the minor complication was a post-procedural neuropathic headache that was attributed to procedural positioning and was treated successfully with gabapentin. The average procedural fluoroscopy time and air kerma were 1.9 min and 55.8 mGy, respectively.

Conclusion

Cone-beam CT guidance with two-axis navigational overlay is a safe, effective method for gaining transforaminal intrathecal access in children with spinal abnormalities and hardware precluding the use of standard techniques.



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Diabetes mellitus in a patient with glycogen storage disease type Ia: a case report

Glycogen storage disease type Ia is a genetic disorder that is associated with persistent fasting hypoglycemia and the inability to produce endogenous glucose. The development of diabetes with glycogen storage...

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[Analysis of uterus cervical cancer screening campaign results in Conakry, Guinea].

[Analysis of uterus cervical cancer screening campaign results in Conakry, Guinea].

Bull Cancer. 2017 Nov 07;:

Authors: Leno DWA, Diallo FD, Camara AY, Magassouba M, Komano FD, Traore A, Niamy D, Tolno J, Cissoko O, Bangoura M, Keita N

Abstract
OBJECTIVE: Reduce morbidity and death rates of women with cervical cancer in Guinea.
METHODOLOGY: This was a five-day cross-sectional study carried out in two successive years (2012 and 2013) at the CERFFO-PCG in Conakry. The target population was women aged 25-49. Approximately 500 women for 2012 and 900 women were expected in these cervical screening campaigns by visual methods (IVA and IVL) with immediate treatment of precancerous lesions. After histologic confirmation of the cancer lesions, the management was carried out according to the protocols in force in the country. We performed a simple descriptive analysis and the results expressed as a percentage and on average.
RESULTS: The target population represented 60.4% in 2012 and 76.2% in 2013, of the total number of women received. The incidence rate of high-grade intraepithelial lesions and cancers increased from 2.6% in 2012 to 0.9% in 2013. In 2012, the 57 precancerous lesions were treated with immediate treatment and 10 cases of cancers out of the 16 had a surgical treatment. Also in 2013, all precancerous lesions were treated immediately and 2 cancers out of the 4 benefited from surgery.
CONCLUSION: Our research shows that, with creativity, flexibility, good organization and efficient use of resources, morbidity and death rates of women with cervical cancer in a very resources can be significantly reduced.

PMID: 29126586 [PubMed - as supplied by publisher]



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[Information booklet for related hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

[Information booklet for related hematopoietic stem cell donors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Bull Cancer. 2017 Nov 07;:

Authors: Polomeni A, Tardieu L, Ainaoui M, Andrianne C, Bancillon N, Chapel V, Chevallier N, Evrard S, Fournier I, Gargallo G, Godin S, Issarni D, Le Bars L, Renaud B, Yakoub-Agha I, Wallart A, De Bentzmann N

Abstract
Providing information to living donors is first and foremost a legal obligation as well as an ethical one, not to mention necessary to health care provision. It's been shown that quality of information concerning the procedure's practical aspects, scheduling of clinical tests and examinations, withdrawing stem cells for the donation, post-donation symptoms, and support provided by healthcare teams, directly impacts the donor's quality of experience. Taking this into consideration our group decided it was essential to create an informational support for donors in the form of a booklet to be provided in different hematopoietic stem cell transplant centers across France. In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allergenic hematopoietic stem cell transplantation clinical practices harmonization workshops. As part of these workshops, our group worked collectively to develop a basis of indispensable information to be included in the booklet and presented using clear and accessible language.

PMID: 29126585 [PubMed - as supplied by publisher]



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Is it possible to improve prognostic value of NCCN-IPI in patients with diffuse large B cell lymphoma? The prognostic significance of comorbidities

Abstract

The prognostic value of the International Prognostic Index (IPI) has been re-evaluated in the rituximab-treated diffuse large B cell lymphoma (DLBCL) patients. Accordingly, National Comprehensive Cancer Network-IPI (NCCN-IPI) has been introduced to estimate prognosis of DLBCL patients. However, comorbidities that frequently affect elderly DLBCL patients were not analyzed. The aim of this study was to evaluate the prognostic significance of comorbidities using Charlson Comorbidity Index (CCI) in 962 DLBCL patients. According to CCI, majority of patients (73.6%) did not have any comorbidity, while high CCI (≥ 2) was observed in 71/962 (7.4%) patients, and in 55/426 (12.9%) of the elderly patients aged ≥ 60 years. When the CCI was analyzed in a multivariate model along with the NCCN-IPI parameters, it stood out as a threefold independent risk factor of a lethal outcome. Also, we have developed a novel comorbidity-NCCN-IPI (cNCCN-IPI) by adding additional 3 points if the patient had a CCI ≥ 2. Four risk groups emerged with the following patient distribution in low, low-intermediate, high-intermediate, and high group: 3.4, 34.3, 49.4, and 12.5%, respectively. The prognostic value of the new cNCCN-IPI was 2.1% improved compared to that of the IPI, and 1.3% improved compared to that of the NCCN-IPI (p < 0.05). This difference was more pronounced in elderly patients, in whom the cNCCN-IPI showed a 5.1% better discriminative power compared to that of the IPI, and 3.6% better compared to the NCCN-IPI. The NCCN-IPI enhanced by the CCI and combined with redistributed risk groups is better for differentiating risk categories in unselected DLBCL patients, especially in the elderly.



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Portable abdomen radiography: moving to thickness-based protocols

Abstract

Background

Default pediatric protocols on many digital radiography systems are configured based on patient age. However, age does not adequately characterize patient size, which is the principal determinant of proper imaging technique. Use of default pediatric protocols by inexperienced technologists can result in patient overexposure, inadequate image quality, or repeated examinations.

Objective

To ensure diagnostic image quality at a well-managed patient radiation exposure by transitioning to thickness-based protocols for pediatric portable abdomen radiography.

Materials and methods

We aggregated patient thickness data, milliamperes (mAs), kilovoltage peak (kVp), exposure index (EI), source-to-detector distance, and grid use for all portable abdomen radiographs performed in our pediatric hospital in a database with a combination of automated and manual data collection techniques. We then analyzed the database and used it as the basis to construct thickness-based protocols with consistent image quality across varying patient thicknesses, as determined by the EI.

Results

Retrospective analysis of pediatric portable exams performed at our adult-focused hospitals demonstrated substantial variability in EI relative to our pediatric hospital. Data collection at our pediatric hospital over 4 months accumulated roughly 800 portable abdomen exams, which we used to develop a thickness-based technique chart.

Conclusion

Through automated retrieval of data in our systems' digital radiography exposure logs and recording of patient abdomen thickness, we successfully developed thickness-based techniques for portable abdomen radiography.



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Portable abdomen radiography: moving to thickness-based protocols

Abstract

Background

Default pediatric protocols on many digital radiography systems are configured based on patient age. However, age does not adequately characterize patient size, which is the principal determinant of proper imaging technique. Use of default pediatric protocols by inexperienced technologists can result in patient overexposure, inadequate image quality, or repeated examinations.

Objective

To ensure diagnostic image quality at a well-managed patient radiation exposure by transitioning to thickness-based protocols for pediatric portable abdomen radiography.

Materials and methods

We aggregated patient thickness data, milliamperes (mAs), kilovoltage peak (kVp), exposure index (EI), source-to-detector distance, and grid use for all portable abdomen radiographs performed in our pediatric hospital in a database with a combination of automated and manual data collection techniques. We then analyzed the database and used it as the basis to construct thickness-based protocols with consistent image quality across varying patient thicknesses, as determined by the EI.

Results

Retrospective analysis of pediatric portable exams performed at our adult-focused hospitals demonstrated substantial variability in EI relative to our pediatric hospital. Data collection at our pediatric hospital over 4 months accumulated roughly 800 portable abdomen exams, which we used to develop a thickness-based technique chart.

Conclusion

Through automated retrieval of data in our systems' digital radiography exposure logs and recording of patient abdomen thickness, we successfully developed thickness-based techniques for portable abdomen radiography.



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