This study was conducted to establish the standard method for the contents of biotin in milk formulas. To optimize the method, we compared several conditions for liquid extraction, purification and instrumental measurement using spiked samples and certified reference material (NIST SRM 1849a) as test materials. LC-MS/MS method for biotin was established using $C_{18}$ column and binary gradient 0.1% formic acid/acetonitrile, 0.1% formic acid/water mobile phase is applied for biotin. Product-ion traces at m/z 245.1 ${\rightarrow}$ 227.1, 166.1 are used for quantitative analysis of biotin. The linearity was over $R^2=0.999$ in range of $5{\sim}60{\mu}g/L$. For purification, chloroform was used as a solvent for eliminating lipids in milk formula. The linearity was over 0.999 in range of 5~60 ng/mL. The detection limit and quantification limit were 0.10, 0.31 ng/mL. The accuracy and precision of LC-MS/MS method using CRM were 103%, 2.5% respectively. Optimized methods were applied in sample analysis to verify the reliability. All the tested milk formulas were acceptable contents of biotin compared with component specification and standards for nutrition labeling. The standard operating procedures were prepared for biotin to provide experimental information and to strengthen the management of nutrient in milk formula.
Purpose : This study was undertaken to analyze the efficacy and sphincter preservation rate of platinum based neoadjuvant chemotherapy Plus radiotherapy versus abdominoperineal resection and Postoperative radiotherapy for anal cancer. Materials and Methods : Data of forty-two patients with anal cancer were retrospectively analyzed. Among thirty-eight patients with epidermoid histology, four patients received radiotherapy, and nineteen patients received abdominoperineal resection and adjuvant radiotherapy with or without chemotherapy $(APR+RT{\pm}CT)$, and fifteen patients received neoadjuvant chemotherapy and radiotherapy (CRT). The CRT regimen was composed of three cycles of 5-fluorouracil $(1,000\;mg/m^2\;bolus\;on\;D1\~5)$ and cisplatin $(60\;mg/m^2\;bolus\;on\;D1)$ followed by 50.4 Gy to the tumor bed and regional lymphatics over 5.5 weeks. Both inguinal lymphatics were treated with an identical dose schedule. Residual disease was treated with an additional three cycles of identical adjuvant chemotherapy. An identical dose schedule was used for post-operative radiotherapy. Median follow-up period was eighty-five months. Results : Overall five-year survival rates were $80.3\%$, 88.9 and $79.4\%$ for entire patients, $APR+RT{\pm}CT$ group, and the CRT group, respectively. No significant difference was found between the two groups (p=0.49). Anus preservation rate for the CRT group was $86.7\%$. Age (0=0.0164) and performance status (p=0.0007) were found to be significant prognostic factors by univariate analysis. Age (p=0.0426), performance status (p=0.0008), and inguinal lymph node metastasis (e=0.0093) were statistically significant prognostic factors by multivariate analysis. No case of RTOG grade 3 complication or higher was reported. Conclusion : This and other recent studies have shown that combined chemotherapy plus radiotherapy for anal cancer results in a high rate of anal sphincter preservation as well as local control and survival. Furthermore, neoadjuvant use of chemotherapy with a cisplatin based regimen rather than a concurrent regimen may lead to a decrease in complications.
$\underline{Purpose}$: To evaluate the treatment results and prognostic factors of palliative radiation therapy in the patients with unresectable advanced pancreatic cancer. $\underline{Materials\;&\;Methods$: Thirty-seven evaluable patients with unresectable advanced pancreatic cancer who were treated by palliative radiation therapy for pain relief at the Department of Radiation Oncology, Kangnam St. Mary's hospital, the Catholic University of Korea between March 1984 and February 2005 were analysed retrospectively. There were 22 men and 15 women. Age at diagnosis ranged from 30 to 80 (median 57) years. Twelve patients (32.4%) had liver metastases and 22 patients (59.5%) had lymph node metastases. Radiation therapy was delivered to primary tumor and regional lymph nodes with $1{\sim}2\;cm$ margin, and total dose was $3,240{\sim}5,580\;cGy$ (median 5,040 cGy). Chemotherapy with radiotherapy was delivered in 30 patients (81%) with 5-FU alone (21 patients) or gemcitabine (9 patients). The follow-up period ranged from 1 to 44 months. Survival and prognostic factors were analysed using Kaplan-Meier method and log-rank test respectively. $\underline{Results}$: Overall mean and median survival were 11 and 8 months and 1-year survival rate was 20%. Among 33 patients who were amenable for response evaluation, 7 patients had good response and 22 patients had fair response with overall response rate of 87.9%. Mild to moderate toxicity were observed in 14 patients with nausea, vomiting, and indigestion, but severe toxicity requiring interruption of treatment were not observed. Chemotherapy didn't influence the survival and symptomatic palliation, but the group containing gemcitabine showed a tendency of longer survival (median 12 months) than 5-FU alone group (median 5.5 months) without statistical significance (p>0.05). The significant prognostic factors were Karnofsky performance status and liver metastasis (p<0.05). Age, sex, tumor location, lymph node metastasis, and CA 19-9 level did not show any prognostic significance (p>0.05). $\underline{Conclusion}$: Radiation therapy was effective for symptomatic palliation in the patients with unresectable advanced pancreatic cancer and would play an important part in the survival benefit with gemcitabine or other targeted agents.
Park, Jeong-Hoon;Kim, Woo-Chul;Kim, Hun-Jung;Gwak, Hee-Keun
Radiation Oncology Journal
/
v.27
no.2
/
pp.64-70
/
2009
Purpose: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. Materials and Methods: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/$m^2$). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/$m^2$) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Results: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. Conclusion: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.
Purpose: To obtain regional blood flow and tissue-blood partition coefficient with time-activity curves from ${H_2}^{15}O$ PET, fitting of some parameters in the Kety model is conventionally accomplished by nonlinear least squares (NLS) analysis. However, NLS requires considerable compuation time then is impractical for pixel-by-pixel analysis to generate parametric images of these parameters. In this study, we investigated several fast parameter estimation methods for the parametric image generation and compared their statistical reliability and computational efficiency. Materials and Methods: These methods included linear least squres (LLS), linear weighted least squares (LWLS), linear generalized least squares (GLS), linear generalized weighted least squares (GWLS), weighted Integration (WI), and model-based clustering method (CAKS). ${H_2}^{15}O$ dynamic brain PET with Poisson noise component was simulated using numerical Zubal brain phantom. Error and bias in the estimation of rCBF and partition coefficient, and computation time in various noise environments was estimated and compared. In audition, parametric images from ${H_2}^{15}O$ dynamic brain PET data peformed on 16 healthy volunteers under various physiological conditions was compared to examine the utility of these methods for real human data. Results: These fast algorithms produced parametric images with similar image qualify and statistical reliability. When CAKS and LLS methods were used combinedly, computation time was significantly reduced and less than 30 seconds for $128{\times}128{\times}46$ images on Pentium III processor. Conclusion: Parametric images of rCBF and partition coefficient with good statistical properties can be generated with short computation time which is acceptable in clinical situation.
Purpose: To assess the utility of magnetic resonance(MR) cerebral blood volume (CBV) map in the evaluation of brain tumors. Materials and Methods: We performed perfusion MR imaing preoperatively in the consecutive IS patients with intracranial masses(3 meningiomas, 2 glioblastoma multiformes, 3 low grade gliomas, 1 lymphoma, 1 germinoma, 1 neurocytoma, 1 metastasis, 2 abscesses, 1 radionecrosis). The average age of the patients was 42 years (22yr -68yr), composed of 10 males and S females. All MR images were obtained at l.ST imager(Signa, CE Medical Systems, Milwaukee, Wisconsin). The regional CBV map was obtained on the theoretical basis of susceptibility difference induced by first pass circulation of contrast media. (contrast media: IScc of gadopentate dimeglumine, about 2ml/sec by hand, starting at 10 second after first baseline scan). For each patient, a total of 480 images (6 slices, 80 images/slice in 160 sec) were obtained by using gradient echo(CE) single shot echo-planar image(EPI) sequence (TR 2000ms, TE SOms, flip angle $90^{\circ}$, FOV $240{\times}240mm,{\;}matrix{\;}128{\times}128$, slice-thick/gap S/2.S). After data collection, the raw data were transferred to CE workstation and rCBV maps were generated from the numerical integration of ${\Delta}R2^{*} on a voxel by voxel basis, with home made software (${\Delta}R2^{*}=-ln (S/SO)/TE). For easy visual interpretation, relative RCB color coding with reference to the normal white matter was applied and color rCBV maps were obtained. The findings of perfusion MR image were retrospectively correlated with Cd-enhanced images with focus on the degree and extent of perfusion and contrast enhancement. Results: Two cases of glioblastoma multiforme with rim enhancement on Cd-enhanced Tl weighted image showed increased perfusion in the peripheral rim and decreased perfusion in the central necrosis portion. The low grade gliomas appeared as a low perfusion area with poorly defined margin. In 2 cases of brain abscess, the degree of perfusion was similar to that of the normal white matter in the peripheral enhancing rim and was low in the central portion. All meningiomas showed diffuse homogeneous increased perfusion of moderate or high degree. One each of lymphoma and germinoma showed homogenously decreased perfusion with well defined margin. The central neurocytoma showed multifocal increased perfusion areas of moderate or high degree. A few nodules of the multiple metastasis showed increased perfusion of moderate degree. One radionecrosis revealed multiple foci of increased perfusion within the area of decreased perfusion. Conclusion: The rCBV map appears to correlate well with the perfusion state of brain tumor, and may be helpful in discrimination between low grade and high grade gliomas. The further study is needed to clarify the role of perfusion MR image in the evaluation of brain tumor.
Purpose: Functional MR imaging is the method of demonstrating changes in regional cerebral blood flow produced by sensory, motor, and any other tasks. Functional MR of visual cortex is performed as a patient stares a photic stimulation, so adaptable photic stimulation is necessary. The purpose of this study is to evaluate whether the size of photic stimulator can affect the degree of visual cortex activation. Materials and Methods: Functional MR imaging was performed in 5 volunteers with normal visual acuity. Photic stimulator was made by 39 light-emitting diodes on a plate, operating at 8Hz. The sizes of photic stimulator were full field, half field and focal central field. The MR imager was Siemens 1.5-T Magnetom Vision system, using standard head coil. Functional MRI utilized EPI sequence (TR/TE= 1.0/51. Omsec, matrix $No.=98{\times}128$, slice thickness=8mm) with 3sets of 6 imaging during stimulation and 6 imaging during rest, all 36 scannings were obtained. Activation images were obtained using postprocessing software(statistical analysis by Z-score), and these images were combined with T-1 weighted anatomical images. The activated signals were quantified by numbering the activated pixels, and activation a index was obtained by dividing the pixel number of each stimulator size with the sum of the pixel number of 3 study using 3 kinds of stimulators. The correlation between the activation index and the stimulator size was analysed. Results: Mean increase of signal intensities on the activation area using full field photic stimulator was about 9.6%. The activation index was greatest on full field, second on half field and smallest on focal central field in 4. The index of half field was greater than that of full field in 1. The ranges of activation index were full field 43-73%(mean 55%), half field 22-40 %(mean 32%), and focal central field 5-24%(mean 13%). Conclusion: The degree of visual cortex activation increases with the size of photic stimulator.
Purpose: The aim of this study was to evaluate the normal values of regional cerebral blood flow (rCBF) and cerebrovascular reserve (CVR) in normal children to aged volunteers using Tc-99m HMPAO, Materials and Methods: Thirty four right-handed normal volunteers (20 males, 14 females, mean age $40.3{\pm}24.9$ years, range 4 to 82 years) were underwent rost/acetazolamide (ACZ) brain SPECT using Tc-99m HMPAO and the sequential injection and subtraction method. rCBF was estimated on the basis of a semiquantitative approach by means of right/left ratio, region/cerebellum and region to whole brain ratios in (rental, parietal, temporal, and occipital lobes, basal ganglia, thalami, and cerebellum. CVR was measured by means of % perfusion increase calculated as % mean count change compared to rest rCBF in each regions. Results: Mean values of right to left ratios range from 1.004 to 1.018, rCBF was highest in cerebellum and lowest in basal ganglia and thalami. Frontal and temporal rCBF decreased while occipital and thalamic rCBF increased according to age. No sexual difference of rCBF was noted. Mean CVR was $29.9{\pm}12.9%$. Mean CVR significantly increased to late teens, and declined thereafter. After 6th decade, CVR in both frontal lobes, left parietal lobe and right basal ganglia decreased significantly with advancing age. There was no sexual difference of CVR. Conclusion: Quantitative assessment of CVR was possible by ACZ Tc-99m HMPAO brain SPECT. It revealed that rCBF and CVR changed according to age in normal Korean volunteers. There was no sexual difference.
Purpose: To assess the quantitative accuracy and the clinical utility of 3D volumetric PET imaging with FDG in brain studies, 24 patients with various neurological disorders were studied. Materials and Methods: Each patient was injected with 370 MBq of 2-[$^{18}F$]fluoro-2-deoxy-D-glucose. After a 30 min uptake period, the patients were imaged for 30 min in 2 dimensional acquisition (2D) and subsequently for 10 min in 3 dimensional acquisition imaging (3D) using a GE $Advance^{TM}$ PET system, The scatter corrected 3D (3D SC) and non scatter-corrected 3D images were compared with 2D images by applying ROIs on gray and white matter, lesion and contralateral normal areas. Measured and calculated attenuation correction methods for emission images were compared to get the maximum advantage of high sensitivity of 3D acquisition. Results: When normalized to the contrast of 2D images, the contrasts of gray to white matter were $0.75{\pm}0.13$ (3D) and $0.95{\pm}0.12$ (3D SC). The contrasts of normal area to lesion were $0.83{\pm}0.05$ (3D) and $0.96{\pm}0.05$ (3D SC). Three nuclear medicine physicians judged 3D SC images to be superior to the 2D with regards to resolution and noise. Regional counts of calculated attenuation correction was not significantly different to that of measured attenuation correction. Conclusion: 3D PET images with the scatter correction in FDG brain studies provide quantitatively and qualitatively similar images to 2D and can be utilized in a routine clinical setting to reduce scanning time and patient motion artifacts.
Purpose : Since February 1991 a Prospective study for non-small cell lung cancer patients who underwent radical resection and had a risk factor of positive resection margin or regional lymph node metastasis has been conducted to evaluate the effect of MVP chemotherapy and radiotherapy on the pattern of failure, disease free and overall survival. and tolerance of combined treatment. Materials and Methods: Twenty nine patients were registered to this study until Sep. 1993; of these 26 received planned therapy Within 3 weeks after radical resection, two cycles of MVP(Mitomycin C $6mg/m^2,$ Vinblastin $6mg/m^2,$ Cisplatin $60mg/m^2$) chemotherapy was given with 4 weeks intervals. Radiotherapy (5040cGy tumor bed dose and 900cGy boost to high risk area) was started 3 to 4 weeks after chemotherapy. Results: One and two year overall survival rates were $76.5\%\;and\;58.6\%$ respectively. Locoregional failure developed in 6 patients$(23.1\%)$ and distant failure in 9 patients$(34.6\%)$ Number of involved lymph nodes, resection margin positivity showed some correlation with failure pattern but T-stage and N-stage showed no statistical significance. The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70 days showed lower incidence of distant metastasis. Postoperative combined therapy were well tolerated without definite increase of complication rate, and compliance rate in this study was $90\%$. Conclusion: 1) MVP chemotherapy showed no effect on locoregional recurrence, but appeared to decrease the distant metastasis rate and 2) combined treatments were well tolerated in all patients. 3) The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70days showed lower incidence of distant metastasis. 4) Addition of chemotherapy to radiotherapy failed to increase the overall or disease free survival.
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