An emerging analytical tool for highly sensitive quantitative analysis based on liquid chromatography-multiple-reaction monitoring cubed (MRM3) / 中国药科大学学报

@#Liquid chromatography-multiple-reaction monitoring (LC-MRM) has been widely recognized as the golden standard for multiple components-targeted quantitative analysis of complicated matrices,with extensive applications for analysis in such fields as chemical drugs, traditional Chinese medicines and foods.Unfortunately, when facing the task of quantitatively analyzing trace chemical components in complex matrices, MRM suffers dramatically from the background noise or matrix interference, leading to undesirable sensitivity and selectivity in terms of the lower limits of quantification (LOQ) and detection (LOD).In recent years, MRM cubed (MRM3), also known as MS3 scan, has received much attention because of its unique ability to significantly improve detection selectivity and sensitivity attributing to the successive ion filtering function, enabling LC-MRM3 as an emerging analytical tool.In this review,our attention is devoted to: 1) the illustration of the principle for MRM3; 2) parameter settings; and 3) the application progress of LC-MRM3 in such fields as the pursuit of biomarkers, pharmaceutical analysis, forensic analysis, toxicological analysis, food chemistry, and environmental analysis, aiming to provide a promising analytical tool of LC-MRM3 advantageous in the quantification analysis of trace chemical components in complex matrices.

Analysis of blood components of Yougui Yin in normal rats and rats with kidney deficiency caused by adenine based on UPLC-MS technology / 中国中药杂志

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.

Comparison of post-operative complications in modified radical mastectomy patients with full suction and compression bandage versus half suction and non-compression bandage

Background: Modified radical mastectomy still remains the most common surgical procedure employed in definitive management of breast cancer. Post mastectomy problems include skin flap necrosis, prolonged axillary drainage, seroma formation, wound gaping etc., among all seroma is commonest. Drainage usage and dressing applied after this procedure is debatable due to varying recommendations.Methods: A prospective randomized control trial was conducted on 84 FNAC/TRUECUT biopsy proven cases of early and locally advanced breast cancer patients admitted in surgery department, GSVM Medical College, Kanpur over a period of two years. Aiming to compare full suction drainage and compression dressing (n=42) (group 1) with half suction drainage and non-compression dressing (n=34) (group 2), in terms of post-operative morbidities like skin flap necrosis, prolonged axillary drainage, seroma formation, wound gaping and length of hospital stay. Romsons 16 number Romovac drains were used for suction and 2 elastic 6” crape bandage were used for compression.Results: During follow-up there was significant lower incidence of seroma formation in group 1 patients compared to group 2 patients (p<0.0019). Full compression dressing patients have increased incidence of superficial skin necrosis compared to non-compression dressing patients (p<0.022). Patients with half suction drainage and non-compression dressing has early drain removal than patients with full suction drainage and compression dressing (p<0.05), the length of hospital stay was less in group 2 compared to group 1.Conclusions: There is markedly lesser incidence of post-operative seroma formation along with reduced morbidity in the form of patients discomfort and flap necrosis in post MRM patients with full suction drainage and compression dressing, but it requires a greater hospital stay and has slightly higher risk of superficial skin necrosis which can be easily managed with topical ointments, compared to patients with half suction drainage and non-compression dressing.

Effects of Juglone on Serum Biomarkers Related to Brain Tissue Injury in Rats / 中国药房

OBJECTIVE：To investigate th e effects of juglone on brain tissu e of rats and its relationship with the biomarkers related to brain tissue injury. METHODS ：Totally 40 rats were divided into blank group ，juglone high-dose ，medium-dose and low-dose groups （34.832，17.416，8.708 mg/kg），with 10 rats in each group. They were given medicine intragastrically once a day ， for consecutive 4 weeks.After last administration ，the general behavior ，brain index and brain tissue morphology were investigated. UPLC-MRM-MS method was used to determine the serum contents of L-dopa（L-Dopa），L-tyrosine（L-Tyr）and L-tryptophan（L-Trp） in rats. The chromatographic condition included Waters Acquity UPLC BEH C 18 column，mobile phase consisted of ammonium acetate aqueous solution-acetonitrile ，gradient elution ，at the flow rate of 0.3 mL/min，sample size of 5 μL，column temperature of 30 ℃；MS condition include electrospray ion source ，in positive ion mode ，capillary voltage of 3 500 V，desolvent gas flow of 650 L/h，desolvent temperature of 350 ℃，ion source temperature of 110 ℃. RESULTS ：Compared with blank group ，the rats in each dose group showed the behavior of tiredness and weakness of limbs. The brain tissue morphology showed pathological changes ， which contained blood vessel congestion in the cerebral and cerebellar cortex ，partial cell nucleus pyknosis in the pyramidal cell layer，deep staining of nuclei ，irregular shape and unclear boundary and other pathological changes ；the brain index of juglone high-dose group increased significantly （P＜0.05）. The established UPLC-MRM-MS method showed good specificity and the range of L-Dopa，L-Tyr and L-Trp were 31.25-32 000，31.25-32 000，15.625-16 000 ng/mL（r＝0.999 1-0.999 9），respectively. The limits of detection were 6.250，5.625，3.125 ng/mL，respectively. The limits of quantitation were 15.625，18.75，10.00 ng/mL，respectively. RSDs of precision ，accuracy and stability （24 h）tests were all Matrix effects were 95.1％-100.1％ （RSD are not more than 3.25％，n＝3）. Compared with blank group，the contents of L-Dopa were increased significantly injuglone medium-dose and high-dose groups （P＜0.01）. The contents of L-Tyr were increased significantly in juglone lowdose，medium-dose and high-dose gro ups，while the contents of L-Trp were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Juglone has an effect on the general behavior，brain index and brain tissue morphology of rats. It may affect the brain function of rats by increasing the contents of L-Dopa and L-Tyr in serum and decreasing the contents of L-Trp.

A validated LC-ESI-MS/MS method for the quantification of Selegiline HCl in bulk and pharmaceutical formulation

Selegiline HCl is an irreversible MAO-B inhibitor used to reduce symptoms in early-stage Parkinson’s disease. It isused as an adjunct to drugs, such as L Dopamine (L-DOPA). The present study is designed to develop and validatea rapid, sensitive, and straightforward separation method with Electrospray ionization and triple quadrupole massanalyzer for the quantification of Selegiline HCl in bulk and pharmaceutical formulation. Zorbax C18 column (50 mm× 4.6 mm i.d, 5 µ particle size) was used for the separation of analyte and internal standard. The samples were elutedusing 0.1% Formic acid in water and Methanol (40:60%v/v) which is delivered at 0.5 ml/minute flow rate, with achromatographic runtime of 5 minutes. The eluents were monitored using a tandem mass spectrometer equipped withan electrospray ionization in positive mode and a triple quadrupole mass analyzer. The detection was carried out inmultiple reaction-monitoring mode by quantifying the m/z 188.05→91.10 ion transition pair; with collision energy−29.0 V for Selegiline HCl. Linearity was achieved over the concentration range 3.5–6.5 ng/ml for the developedmethod. The limit of detection and limit of quantification were found to be 0.2 and 0.5 ng/ml, respectively. Thecorrelation coefficient (r2) value was ≥0.9985 for Selegiline HCl. This method offers a sensitive quantification ofSelegiline HCl in the pharmaceutical formulation.

Simultaneous quantification of 26 bile acids in Calculus Bovis Sativus and Calculus Bovis by HPLC-MS/MS / 中草药

Objective To develop an HPLC-MS/MS method for the simultaneous determination of 26 bile acids in Calculus Bovis Sativus (CBS) and Calculus Bovis (CB). Methods Chromatographic separation was performed on a Symmetry C18 column (150 mm × 2.1 mm, 3.5 μm) with linear gradient elution of water (0.1% formic acid + 10 mmol/L ammonium acetate) and methanol (0.1% formic acid + 10 mmol/L ammonium acetate) at a flow rate of 0.15 mL/min, and the injection volume was 10 μL. Switching electrospray ion source polarity in negative mode. The ion spray voltage was set at - 4 500 V, the turbo spray temperature was maintained at 350 ℃, and multiple-reaction monitoring (MRM) was employed. Results The 26 bile aicds showed good linearity within the linear ranges (r ≥ 0.991 4). The average recoveries of the bile acids ranged from 98.2% to 102.3%. The precisions (RSD) for the investigated components were less than 0.95%. There are some differences in variety and chemical components between CBS and CB. Conclusion The proposed method is reliable and has high sensitivity and good specificity, which allows the determination of various bile acids in CB.

A study on the outcome of tympanoplasty with various graft materials

Background: Chronic Suppurative Otitis Media (CSOM) is one of the most common causes of preventable hearing loss especially in developing countries CSOM is a disease condition characterized by persistent perforation of tympanic membrane with recurrent or persistent mucopurulent Otorrhoea Aim: This study was undertaken to review the outcomes (hearing improvement) achieved by using various graft materials like temporalis fascia (TF), tragal cartilage (TC), Conchal cartilage (CC), autologous sculpted incus (I), autologous cortical bone (BG) in tympanoplasty surgery Material and methods: This study comprised of 14 males and 16 females patients with age ranging from 12 years to 55 years They were selected for surgery after adequate history taking, clinical, otoscopic and microscopic examination Type 1 tympanoplasty was done in 19 patients, Type 3 tympanoplasty + Modified Radical Mastoidectomy (MRM) was done in 11 patients by using various graft materials The results were evaluated in the form of rate of graft success, hearing gain, and the pre and post-operative Air Bone gap Results: Out of 30 patients, in 20 TF graft patients AB gap improvement seen in 14 patients, 5 patients did not show any change and 1 patient did not come for follow up In 2 TC graft patients, both showed improvement in AB gap In 1 patient where CC graft was used showed improvement in AB gap In 6 patients I graft was used, 2 patients showed improvement, 2 patients did not show any change, 1 patient did not come for follow up and in 1 patient AB gap worsened In 1 patient BG was used and no change in AB gap was seen Out of 30 cases graft uptake was seen in 25 cases and graft rejection was seen in 3 cases and 2 patients did not come for follow up Graft rejection was documented in one case where TF was used, one case where incus graft was used and in another case where BG was used Harinarayana N, Srikanth M A study on the outcome of tympanoplasty with various graft materials IAIM, 2018; 5(12): 77- 82 Page 78 Conclusion: Post-operative hearing gain obtained was found to be better in patients operated upon with tubotympanic disease than those operated upon with atticoantral disease The post-operative hearing improvement depends not only on the graft material used and the type of tympanoplasty but also on the pre-operative status of the ossicular chain

Determination of ten mycotoxins in food by HPLC-MS/MS / 国际药学研究杂志

Objective: To establish sample preparation and high performance liquid chromatography combined with electro- spray ionization tandem mass spectrometry(HPLC-MS/MS)methods for simultaneous determination of 10 mycotoxins in food. Meth- ods: This work established sample preparation method for mycotoxins in food using accelerated solvent extraction and solid phase ex- traction for solid food,using gel permeation chromatography for liquid food. Furthermore,it simultaneously identified and quantified 10 mycotoxins(aflatoxin M1,aflatoxin B1,aflatoxin B2,aflatoxin G1,aflatoxin G2,neosolaniol,deoxynivalenol,nivalenol,3- acetyldeoxynivalenol,15-acetyldeoxynivalenol)in food using HPLC-MS/MS. Separation and quantification were performed in both pos- itive and negative modes under multiple reaction monitoring(MRM)in a single run. Results: The results indicated as follows:high correlation coefficients(r≥0.999)of ten mycotoxins were obtained within their respective linear ranges and the detection limits for them ranged from 0.006 to 1 μg/L. The average recoveries were between 61.99% and 103.97%,with a relative standard deviation (RSD)varying from 0.76% to 10.63%. Conclusion: This method is rapid,accurate and highly sensitive for quantitative analysis and quality monitoring of mycotoxins in solid and liquid food.

Rapid Determination of 17 Chemicals Illegally Added into Anti-rheumatic TCM Patches by UPLC-MS/MS / 中国药房

OBJECTIVE:To establish a rapid determination method for 9 kinds of glucocorticoid and 8 kinds of non-steroidal anti-inflammatory drugs illegally added into anti-rheumatic TCM patches. METHODS:UPLC-MS/MS method was adopted. The samples were separated on Acquity UPLC? BEN C18 column with methanol-water(90:10,V/V)as mobile phase at flow rate 0.4 mL/min. The column temperature was set at 30℃,and sample size was 1μL. The ionization mode was electrospray ion source(ESI):spray needle voltage of 5500 V,ion source spray GS1,GS2 pressure of 50,50 psi,ion source temperature of 500 ℃,scanning range of m/z 50-500. The multiple reaction monitoring(MRM)combined with information-dependent acquisition (IDA) and en-hanced product ion scanning(EPI)was used to rapid qualitative analysis. RESULTS:The detection limits for 17 kinds of chemical components were not more than 0.400 μg/mL. RSDs for precision,repeatability,stability tests were not more than 4.93%,7.69%, 9.57%,respectively. Diclofenac sodium was detected in the sample. CONCLUSIONS:The method is selective and sensitive. It is suitable for qualitative analysis of chemicals illegally added into anti-rheumatism TCM patches.

Quality of life assessment after modified radical mastectomy in early breast cancer

Background: Modified radical mastectomy performed for CA breast is a life modifying surgery for most women. It creates a profound impact on the quality of life enjoyed by the women. The magnitude of change in quality may pave the way for more conservative surgery in the future. Aim: To assess the quality of life in patients undergoing modified radical mastectomy for early breast cancer. Materials and methods: This was a prospective study consisting of 50 patients who underwent modified radical mastectomy in our institution from 2013-2015 for early breast cancer. Quality of life was assessed 6 months after surgery using a translated version of a customized questionnaire, which was based on the Royal College of surgeons’ questionnaire. Results: In our study, the most common age group was found to be between 51-60 years (24). Most patients (30) had poor quality of life with 19 patients having an average quality of life. 23 patients with poor quality of life were from the lower socioeconomic class. 47 patients (94%) did not have any restriction of daily activities. Most of the patients (49) had mild pain and discomfort. Among the patients experiencing mild pain 59% (29 patients) had poor quality of life. Severe psychological impairment was present in 30 of our study population and was associated with poor quality of life in 29 cases (97%). 34 patients in the study population were not satisfied with their body image and was associated with poor quality of life in 30 (88%) of the cases. 27 patients in the study group were not satisfied with their sexual life and it was associated with poor quality of life in 23 (85%) of the patients. Conclusion: From this study we have concluded that the quality of life is poor in majority of the patients undergoing modified radical mastectomy for early breast cancer with most of the patients S. Maniselvi, T. Babu Antony, Ponmuthu, Deepak David Chellappa. Quality of life assessment after modified radical mastectomy in early breast cancer. IAIM, 2017; 4(12): 52-58. Page 53 having psychological impairment, unsatisfied body image perception, unsatisfied sexual life and mild pain. In addition to these factors socioeconomic status of the patient also affects the quality of life in these patients

Thoracic epidural versus general anaesthesia for MRM surgeries.

Background: General anaesthesia is still the preferred technique amongst many practitioners for oncologic breast surgeries. However the TEA technique has a lot of advantages over the conventional GA technique. Objective: We attempted to evaluate the two techniques of anaesthesia for MRM surgeries. Materials and method: Sixty ASA I-II patients undergoing MRM were randomly assigned to two study groups of 30 patients each. In the TEA group( group T), an epidural catheter was inserted at T7-T8 level, and 8-10 ml of 0.5% bupivacaine was titrated and administered.GA (group G) was induced with 2mg/kg of propofol and was maintained with Isoflurane ,intermittent inj. Vecuronium and 70% N2O in oxygen. The authors evaluated the adequacy of anesthesia, surgical condition, post anesthetic recovery, post anesthetic analgesia and patients’ satisfaction. Results: The intra operative haemodynamics was comparable in between the two groups. The incidence of nausea and vomiting was significantly lower in the TEA group ( 16.5% in group T and 39.6% in group G , P = 0.02).The mean immediate VAS score was also lower in TEA group ( group T =2.4 , group G =5.8,P = 0.001).Aldrete recovery score was 9/10 in 1st hr in a significant proportion in the TEA group (89.1% in group T v/s 59.4% in group G , P = 0.003).Patient satisfaction was significantly higher. The surgeons were however satisfied with both the methods. Conclusion: Use of thoracic epidural technique as a sole anaesthetic technique for MRM surgeries provides adequate operating conditions, better side effect profile, better pain management and patient satisfaction.

Identification of 17 Memory-enhancing Drugs Illegally Added in Traditional Chinese Medicines and Health Foods by LC-MS/MS / 中国药师

Objective:To develop an LC-MS/ MS method for the analysis of 17 memory-enhancing drugs illegally added in tradi-tional Chinese medicines(TCM)and health foods. Methods:The method involved liquid chromatography-tandem mass spectrometry (LC-MS/ MS),and the separation was conducted on an Eclipse XDB C18 column(100 mm × 3. 0 mm,1. 8 μm). The 17 memory-en-hancing drugs illegally added in traditional Chinese medicines and health foods were analyzed by LC-MS/ MS with electrospray ioniza-tion(ESI)and multiple reactions monitoring(MRM). Results:A fast LC-MS/ MS method for the simultaneous screening of 17 illegal-ly added chemical components was described with the LOD below 10 ng·ml - 1 . Conclusion:The method is selective and sensitive in the detection of memory-enhancing drugs illegally added in traditional Chinese medicines and health foods.

Determination of allantoin in Dioscoreae Rhizoma by LC-MS/MS / 中草药

Objective: To establish an HPLC-MS/MS method for determination of allantoin in Dioscoreae Rhizoma. Methods: Determination of LC system used Agilent Eclipse Plus C18 (100 mm × 4.6 mm, 3.5 μm) column and acetonitrile-water (90:10) as mobile phase in linear gradient condition. The flow rate was 0.3 mL/min. The mass spectrometer was operated under the negative ion mode with ESI source. MRM (precursor ion of m/z 156.9 and product ion of m/z 96.7) was used to qualify allantoin. Results: The linear range of the component was 0.12-6.0 μg/mL, r=0.998 5; The average recovery was 101%, and the RSD was 3.2%. Conclusion: The method is sensitive, reliable, and accurate, and can be applied in the quality control of Dioscoreae Rhizoma.

Rapid determination of 13 components illegally added in slimming functional products by UPLC-MS/MS method / 中草药

Objective: To develop a UPLC-MS/MS method for determination of the illegal addition of 13 components in slimming products. Methods: Samples were extracted with methanol by ultrasonic processing, separated by quick UPLC, and detected by quadrupole mass spectrometry with "MRM" mode. Results: The method for the rapid determination of the 13 components illegally added in slimming products was established, and the determination limits of quantification was below 2 ng. Conclusion: The method is specific, sensitive, simple, and fast for the rapid determination of the components illegally added in slimming products.

The Path to Clinical Proteomics Research: Integration of Proteomics, Genomics, Clinical Laboratory and Regulatory Science / 대한진단검사의학회지

Better biomarkers are urgently needed to cancer detection, diagnosis, and prognosis. While the genomics community is making significant advances in understanding the molecular basis of disease, proteomics will delineate the functional units of a cell, proteins and their intricate interaction network and signaling pathways for the underlying disease. Great progress has been made to characterize thousands of proteins qualitatively and quantitatively in complex biological systems by utilizing multi-dimensional sample fractionation strategies, mass spectrometry and protein microarrays. Comparative/quantitative analysis of high-quality clinical biospecimen (e.g., tissue and biofluids) of human cancer proteome landscape has the potential to reveal protein/peptide biomarkers responsible for this disease by means of their altered levels of expression, post-translational modifications as well as different forms of protein variants. Despite technological advances in proteomics, major hurdles still exist in every step of the biomarker development pipeline. The National Cancer Institute's Clinical Proteomic Technologies for Cancer initiative (NCI-CPTC) has taken a critical step to close the gap between biomarker discovery and qualification by introducing a pre-clinical "verification" stage in the pipeline, partnering with clinical laboratory organizations to develop and implement common standards, and developing regulatory science documents with the US Food and Drug Administration to educate the proteomics community on analytical evaluation requirements for multiplex assays in order to ensure the safety and effectiveness of these tests for their intended use.

Significance of trilineage myelodysplasia in de novo acute myeloid leukemia / 대한임상병리학회지

BACKGROUND: The findings of dysplastic features in haemopoietic cells in de novo acute myeloid leukemia(AML) is defined as AML with trilineage myelodysplasia(AML/TMDS). These cases have been reported accounting for 10-5% of de novo AML. The rate of complete remission(CR) in AML/TMDS to conventional chemotherapy is poor and relapse occur much earlier than in patients without dysplastic features. TMDS features are also observed during remission and termed this de novo AML with myelodysplastic remission marrow(AML/MRM). Recent report described that TMDS during remission was more closely related to prognosis than dysplastic features at diagnosis. We investigated the incidence of AML/TMDS and AML/MRM and evaluated the impending role of dysplasia in prognosis. METHOD: Ninety-ive patients with de novo AML from March 1994 to December 1998 were enrolled according to the FAB classifiction. To determine AML/TMDS and AML/MRM, we used Brito-abapulle's criteria and Kazuhiro's criteria. Prognosis was aalysed by the means of disease free survival(DFS) and overall survival(OS). RESULTS: Nine(9.5%) patients had AML/TMDS and it was 7.7%, 17.2%, 50% of patients with M2, M4 and M6. CR rate was 44.4% for TMDS patients compared to 76.7% for patients without TMDS(p<0.05). AML/TMDS also showed significantly shorter DFS and OS. The incidence of AML/MRM was higher in the group of AML/TMDS(44.4%) compared to AML without TMDS(8.1%) but was not related to prognosis. CONCLUSION: We concluded that the presence of TMDS in de novo AML exerts a negative effect on the ability to achieve CR and in the prognosis. But the MRM has no significance to predict poor prognosis and early relapse.

Significance of trilineage myelodysplasia in de novo acute myeloid leukemia / 대한임상병리학회지

BACKGROUND: The findings of dysplastic features in haemopoietic cells in de novo acute myeloid leukemia(AML) is defined as AML with trilineage myelodysplasia(AML/TMDS). These cases have been reported accounting for 10-5% of de novo AML. The rate of complete remission(CR) in AML/TMDS to conventional chemotherapy is poor and relapse occur much earlier than in patients without dysplastic features. TMDS features are also observed during remission and termed this de novo AML with myelodysplastic remission marrow(AML/MRM). Recent report described that TMDS during remission was more closely related to prognosis than dysplastic features at diagnosis. We investigated the incidence of AML/TMDS and AML/MRM and evaluated the impending role of dysplasia in prognosis. METHOD: Ninety-ive patients with de novo AML from March 1994 to December 1998 were enrolled according to the FAB classifiction. To determine AML/TMDS and AML/MRM, we used Brito-abapulle's criteria and Kazuhiro's criteria. Prognosis was aalysed by the means of disease free survival(DFS) and overall survival(OS). RESULTS: Nine(9.5%) patients had AML/TMDS and it was 7.7%, 17.2%, 50% of patients with M2, M4 and M6. CR rate was 44.4% for TMDS patients compared to 76.7% for patients without TMDS(p<0.05). AML/TMDS also showed significantly shorter DFS and OS. The incidence of AML/MRM was higher in the group of AML/TMDS(44.4%) compared to AML without TMDS(8.1%) but was not related to prognosis. CONCLUSION: We concluded that the presence of TMDS in de novo AML exerts a negative effect on the ability to achieve CR and in the prognosis. But the MRM has no significance to predict poor prognosis and early relapse.

Patterns of Locoregional and Systemic Failure after a Mastectomy in Breast Cancer and Risk Factors Predicting Failure

PURPOSE: In spite of improved local control and adjuvant therapy in breast cancer, many patients after a modified radical mastectomy suffer from locoregional or systemic failure. The purpose of this study was to assess both the patterns of failure following a mastectomy and the predictive factors affecting the risks of locoregional or systemic failure. METHODS: The study population consisted of 195 patients who developed locoregional or systemic failure from among 1,187 patients treated by using a modified radical mastectomy between July 1989 and October 1998 at the Asan Medical Center's Breast Clinic. The median follow-up time following the mastectomy was 41 months (range; 1-119 months). RESULTS: Isolated locoregional recurrence (LRR) developed in 46 patients (24%), LRR with distant metastasis in 43 (22%), and only distant metastasis in 106 (54%). The sites of LRR were as follows: the chest wall, 52%; the ipsilateral supraclaviclar node, 22%; and the axillary node, 15%; etc. The first sites of distant metastasis were as follows: bone, 46%; lung, 38%; liver, 12%; brain, 6%; and pleura, 6%; etc. Local or systemic failure appeared within the first 3 years following the mastectomy in 75-82% of the patients, and within 5 years in 95-98%. Multivariate analysis showed that increasing initial tumor size, increasing number of involved nodes, negative progesterone receptor, and increasing histologic grade were significant factors for increased risks of LLR or distant metastasis. CONCLUSION: Half of the locoregional recurrences following a mastectomy are isolated. T-stage, nodal status, progesterone receptor, and histo logic grade may help to identify patients at risk for locoregional or systemic failure after a mastectomy.