Prognostic predictive value of detecting minimal residual disease in acute myeloid leukemia after 2 courses of hypomethylating agents combined with low-dose induction chemotherapy / 白血病·淋巴瘤

Objective:To explore the prognostic predictive value of detecting minimal residual disease (MRD) after 2 courses of hypomethylating agents (HMA) combined with low-dose induction chemotherapy in patients with acute myeloid leukemia (AML).Methods:The data of 43 newly diagnosed AML patients treated by HMA combined with low-dose induction chemotherapy in Jingjiang People's Hospital of Jiangsu Province from January 2016 to January 2021 were retrospectively analyzed, and the bone marrow MRD levels were detected by multiparametric 10-color flow cytometry (MFC) after 1 course and 2 courses of chemotherapy. Patients were divided into three groups according to MRD levels: the group with negative MRD after 1 course of induction chemotherapy (MRD-1 group), the group with negative MRD after 2 courses of induction chemotherapy (MRD-2 group), and the group without negative MRD after 2 courses of induction chemotherapy (MRD+ group). Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves of all patients and each group, and log-rank test was performed to compare them; the influencing factors for OS were analyzed using univariate and multivariate Cox proportional hazards models.Results:Among the 43 patients, 17 patients (39.5%) were in the MRD-1 group, 14 patients (32.6%) were in the MRD-2 group, and 12 patients (27.9%) were in the MRD+ group. There were no statistical differences among the 3 groups in gender, age, hemoglobin level at initial diagnosis, white blood cell count, platelet count, lactate dehydrogenase level, disease subtype, WT1 expression, karyotype, and genetic risk stratification (all P > 0.05). The median follow-up was 15 months (1-67 months). Survival analysis showed a median OS time of 21 months (95% CI 15 months -not reached) in 43 patients and a median PFS time of 12 months (95% CI 9-18 months) in 29 patients included in the PFS analysis; PFS and OS in the MRD-1 and MRD-2 groups were better than those in the MRD+ group (all P < 0.01), and the differences in PFS and OS between the MRD-1 and MRD-2 groups were not statistically significant (both P > 0.05); the median PFS time was 5 months (95% CI 2 months-not reached) in the MRD+ group, the median PFS time was 15 months (95% CI 7 months-not reached) in the MRD-1 group, and the median PFS time was 18 months (95% CI 11 months-not reached) in the MRD-2 group; the median OS time in the MRD+ group was 9 months (95% CI 7 months-not reached), the median OS time was not reached in the MRD-1 group, and the median OS time was 38 months (95% CI 38 months-not reached) in the MRD-2 group. Multivariate Cox regression analysis showed that age ( HR = 1.080, 95% CI 1.004-1.160, P = 0.038), MRD status (MRD-1 vs. MRD+: HR = 0.125, 95% CI 0.031-0.507, P = 0.004; MRD-2 vs. MRD+: HR = 0.146, 95% CI 0.037-0.577, P = 0.006) were independent influencing factors for OS in AML patients. Conclusions:The survival is good in AML patients with MRD negative conversion after both 1 course and 2 courses of HMA combined with low-dose induction chemotherapy, and both are better than that in patients with positive MRD after 2 courses of chemotherapy.

Active surveillance and response evaluation strategy after neoadjuvant therapy for esophageal cancer / 中华放射肿瘤学杂志

A considerable proportion of esophageal carcinoma patients could achieve pathological complete response (pCR) after neoadjuvant therapy, for whom accurate response evaluation and active surveillance rather than surgery-aiming to avoid the complications, mortality and reduced quality of life after surgery-has become a research hotspot. To detect residual disease and predict pCR accurately by appropriate method(s) is the key of active surveillance strategy. In this article, we elaborated the active surveillance strategy of esophageal cancer and characteristics of different evaluation methods in terms of radiology, pathology and combined detection.

Cost-effectiveness analysis of Ado-trastuzumab emtansine for the treatment of residual invasive HER2-positive breast cancer

ABSTRACT Objective Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancer cases. Ado-trastuzumab emtansine (T-DM1) is approved to treat residual HER2-positive breast cancer after neoadjuvant therapy. The aim of this study was to determine the quality-adjusted time with symptoms or toxicity and without symptoms or toxicity (Q-TWiST) of T-DM1 compared to trastuzumab for residual invasive HER2-positive breast cancer. Methods The authors developed an analytical model extracting individual patient data and estimated invasive disease-free survival and overall survival over a 30-year time horizon. Only direct costs from adjuvant treatment were considered as well as relapse treatment from Brazilian and American payer perspectives. Heart events were considered for utility and cost analysis. Results The 30-year projection utilizing the Weibull method estimated a mean invasive disease-free survival of 16.4 years for T-DM1 and 10.4 for Trastuzumab, in addition to a mean overall survival of 18.1 and 15.4 years, respectively. We determined a Q-TWiST gain of 3,812 years for the T-DM1 arm when compared to trastuzumab and an Incremental cost-effectiveness ratio per Q-TWiST of US$ 11,467.65 in the United States and US$ 3,332.73 in Brazil. Conclusion Ado-trastuzumab emtansine is cost-effective from both Brazilian and American perspectives.

Analysis of therapeutic effect and influencing factors of radiofrequency ablation for colorectal cancer liver metastases / 中华放射学杂志

Objective:To explore the efficacy and influencing factors of radiofrequency ablation (RFA) in the treatment of colorectal cancer liver metastases (CRLM).Methods:The clinical and imaging data of 281 patients (477 intrahepatic metastatic tumors) who received percutaneous RFA treatment in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from December 2009 to December 2020 were retrospectively analyzed. Factors that may affect the efficacy of RFA were recorded, including carcinoembryonic antigen (CEA), differentiation, extrahepatic metastasis, tumor location and size, complications and other information. Patients were followed up through hospital admissions, telephone, etc. The primary endpoints were overall survival (OS) and local tumor progression-free survival (LTPFS). Univariate and multivariate logistic regression models were used to identify predictors of residual tumor. Univariate and multivariate Cox proportional hazards regression were used to identify the influencing factors of LTPFS and OS. The median LTPFS and OS were estimated by the Kaplan-Meier curve and compared by the log-rank test.Results:After RFA, 68 (14.3%) tumor residues were observed. Multivariate logistic regression showed that the risk factors for residual tumor were size ≥20 mm, high-risk and perivascular location, and minimal ablative margin<5 mm. During the follow-up period, the main complication rate was 4.3% (12/281) and the fatality rate was 31.3% (88/281). At the same time, local tumor progression was found in 167 (35.0%) lesions post-RFA. The median time of LTPFS and OS estimated by the Kaplan Meier method were 35.0 (95%CI 26.53-43.48) and 44.0 (95%CI 29.70-58.30) months, respectively. The cumulative proportion of LTPFS and OS were 37.2% and 40.4% respectively in the 5th year. Multivariate Cox proportional hazard regression showed that CEA≥30 ng/ml, tumor size ≥20 mm, and minimal ablative margin<5 mm were risk factors for LTPFS; extrahepatic metastasis, tumor burden>30 mm, and lesion with minimal ablative margin<5 mm were independent risk factors for OS; re-intervention was an independent protective factor for OS.Conclusions:Adequate ablative margin and less tumor burden were beneficial to local tumor control and long-term survival of patients in the RFA treatment; the existence of extrahepatic metastasis was an important risk factor for OS, and re-interventional therapy was beneficial to extend OS.

Detección por citometría de flujo de la enfermedad mínima residual en las leucemias agudas / Detection of the minimal residual disease by flow cytometry in patients with acute leukemia

Introducción: La enfermedad mínima residual es la permanencia de células leucémicas residuales en niveles subclínicos luego de la remisión de la enfermedad. Esta condición incrementa el riesgo de recaída y mortalidad. Objetivo: Caracterizar factores clínicos y moleculares de pacientes con leucemias agudas y enfermedad mínima residual detectada por citometría de flujo en una institución de alta complejidad de la ciudad de Medellín, Colombia durante los años 2015 - 2017. Metodología: Este es un estudio descriptivo retrospectivo, que incluyó pacientes con leucemia diagnosticada por citometría de flujo. Se realizó un muestreo no probabilístico de casos consecutivos. La información recolectada fue digitada en una base de datos en Excel, y el análisis se realizó a través del programa IBM SPSS Versión 24, empleando según la naturaleza de cada variable frecuencias absolutas y relativas, promedio y desviación estándar o mediana y rangos intercuartílicos según su distribución. Resultados: Se incluyó un total de 60 pacientes con predominio del sexo masculino 63,3 por ciento (38). El diagnóstico más frecuente fue la leucemia linfoide 78,3 por ciento (47). Del total de pacientes incluidos, 36,6 por ciento (22) fue positivo para enfermedad mínima residual; 28,3 por ciento recibió trasplante de médula ósea y el 10 por ciento (6) presentó compromiso de líquido cefalorraquídeo. En la segunda citometría en pacientes con enfermedad mínima residual, 90,9 por ciento (20) expresaba CD45+. El 31,8 por ciento (7) de los pacientes con enfermedad mínima residual presentó recaída. Conclusión: La enfermedad mínima residual es una condición frecuente en pacientes con leucemias agudas que requiere seguimiento y constituye un factor pronóstico relevante(AU)

Introduction: The minimal residual disease is the permanence of residual leukemic cells at subclinical levels after remission of the disease. This condition increases the risk of relapse and mortality. Objective: To characterize the clinical and molecular factors of patients with acute leukemias and minimal residual disease detected by flow cytometry in a highly complex institution in the city of Medellín, Colombia during the years 2015 - 2017. Methodology: This is a retrospective descriptive observational study, which included patients with leukemia diagnosed by flow cytometry. A non-probabilistic sampling of consecutive cases was carried out. The information collected was entered into a database in Excel, and the analysis was carried out through the IBM SPSS Version 24 program, using absolute and relative frequencies, average and standard deviation or median and interquartile ranges, according to the nature of each variable and its distribution. Results: 60 patients were included in which male sex predominated with 63.3 percent (38). The most frequent diagnosis was lymphoid leukemia with 78.3 percent (47). Of the total patients included, 36.6 percent (22) were positive for minimal residual disease; 28.3 percent received a bone marrow transplant and 10 percent (6) had a cerebrospinal fluid compromise. In the second cytometry of the patients with minimal residual disease, 90.9 percent (20) expressed CD45 +. 31.8 percent (7) of the patients with minimal residual disease relapsed. Conclusion: Minimal residual disease is a frequent pathology in patients with acute leukemias that requires follow-up and constitutes a relevant prognostic factor(AU)

Tratamiento de la leucemia mieloblástica aguda con translocación (8; 21) en Hospital Base Valdivia: ejemplificado en un caso clínico / Management and follow-up of acute myeloblastic leukemia with translocation (8; 21): report of one case

We describe the management and follow-up of a 20-year-old male with acute myeloblastic leukemia with translocation (8; 21) [t (8; 21)]. A quantitative polymerase chain reaction for t(8; 21) in bone marrow was performed at diagnosis and after three consolidations with high doses of cytarabine. Currently, the management of this type of leukemias has been oriented towards the early detection of relapse. The concept of minimal or measurable residual disease, as the burden of leukemia cells that persist undetected, is an important tool in the therapeutic decision and follow-up of these patients.

Comparison of I-131 Biokinetics after Recombinant Human TSH Stimulation and Thyroid Hormone Withdrawal Measured by External Detector in Patients with Differentiated Thyroid Cancer / 전남의대학술지

The aim of this study was to compare radioactive iodine (I-131) biokinetics after recombinant human TSH stimulation (rhTSH) and thyroid hormone withdrawal (THW) in patients with differentiated thyroid cancer (DTC). External effective dose rates were measured using external detectors and imaged quantitatively at the time of discharge from the isolation wards. We retrospectively analyzed 32 patients who had been diagnosed with DTC, papillary or follicular, and underwent remnant ablation after either rhTSH stimulation (n=22) or THW (n=10). The uptake of I-131 by remnant thyroid tissue was measured from 20.0 cm, 100.0 cm and 200.0 cm distances using a handheld external detector. The remnant thyroid tissue measured by the whole body images two to five days from administration was 10.7+26.0% (range 0.5 to 60.0%). The values measured at 20 cm were best correlated to the thyroid residual uptake measured by SPECT/CT. The half-lives of I-131washout (T1/2) in rhTSH group measured by external detector were shorter than those of THW group. T1/2 becomes longer when it was measured over longer distances. They were 10.9, 12.3 and 13.1 hours at distances of 20, 100, and 200 cm in rhTSH group, respectively. The TWH group showed 12.8, 14.9 and 17.7 hours, respectively. We conclude that I-131 biokinetics can be measured by external detector after high dose I-131 therapy for DTC. It showed that washout of I-131 was faster after rhTSH stimulation than THW, and slower in patients with distant metastasis than those without metastasis.

Clinical significance of next-generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia / 白血病·淋巴瘤

Objective@#To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR).@*Methods@#The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring.@*Results@#There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ2 = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2 = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ2 = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05).@*Conclusions@#Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.

Clinical significance of next‐generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia / 白血病·淋巴瘤

Objective To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR). Methods The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring. Results There were 39 males (57.4% ) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%;χ 2＝ 9.249, P＝ 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2＝ 9.249, P＝ 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ 2 ＝ 4.122, P＝ 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05). Conclusions Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.

Impact of diverse shapes of prostatic apex on positive apical margin rate and biochemical recurrence following laparoscopic radical prostatectomy / 中华外科杂志

Objective@#To explore the effects of various forms of prostatic apex on positive apical margin rate (PAM) and biochemical recurrence (BCR) after laparoscopic radical prostatectomy.@*Methods@#A retrospective analysis of 309 patients (aging (65±6) years) who were experienced laparoscopic radical prostatectomy from January 2010 to December 2016 at the Department of Urology, First Affiliated Hospital of Fujian Medical University. According to the relationship between prostate apex and membrane urethra at the mid-sagittal plane of preoperative MRI, all patients were classified into 4 categories. There were 31 patients for type 1, apex covering both anterior and posterior aspects of membranous urethra, 139 patients for type 2, apex covering anterior side of membranous urethra, 63 patients for type 3, apex covering posterior aspect of membranous urethra, 76 patients for type 4, apex not covering membranous urethra. PAM and BCR after operation were compared between this four groups respectively. The χ2 test was used to compare PAM among the 4 types. Logistic regression analysis were undertaken to analyze the factors affecting PAM. Cox′s proportional hazards regression model was undertaken to identify the variables influencing BCR.@*Results@#There was no significant difference in the 4 groups concerning age, body mass index, prostate volume, preoperative prostate-specific antigen (PSA) value, postoperative Gleason score and pathological stage (P>0.05).The median follow-up time was 32 months (ranged from 12 to 60 months).The data showed that the apical type 3 patients has the highest PAM. There was statistical difference among the 4 groups in PAM (χ2=15.592, P=0.001). Preoperative level of PSA (OR=20.356, 95% CI: 2.440 to 169.810, P=0.005), postoperative Gleason score (OR=4.113, 95% CI: 1.911 to 8.849, P=0.001), pathological stage (OR=3.422, 95% CI: 1.600 to 7.319, P=0.002) and apical type 3 (OR=6.134, 95% CI: 2.196 to 17.132, P=0.001) were independent relactive factors of PAM. Preoperative level of PSA (HR=1.362, 95% CI: 1.006 to 1.843, P=0.045), postoperative Gleason score (HR=1.920, 95% CI: 1.384 to 2.665, P=0.001), pathological stage (HR=1.476, 95% CI: 1.098 to 1.983, P=0.010), PAM (HR=3.497, 95% CI: 2.407 to 5.081, P=0.001)and apical type 3 (HR=1.828, 95% CI: 1.266 to 2.639, P=0.001) were independent prognosis factors of BCR.@*Conclusion@#Prostate apical type 3 could be a significant independent predictor of PAM, and an independent prognosis factor for BCR.

Relationship between various histological status of margins of LEEP and residual HSIL or worse at hysterectomy following conization / 中华妇产科杂志

Objective To investigate the relationship between various loop electrosurgical excision procedure (LEEP) margin status and residual high grade squamous intraepithelial lesion (HSIL) or worse at hysterectomy following conization. Methods The relevant clinicopathological data were collected in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2014 to Dec. 2015, including 947 cases who underwent hysterectomy within 6 months of LEEP. The residual HSIL or worse at hysterectomy were analyzed among the groups. (1) Clear margins, involved margins, and without 1 mm negative margins. (2) Only one positive margin, two positive margins and three positive margins. (3) A positive margin of internal ostium of cervix, of external ostium of cervix and of the basement. Results (1) The histological evaluation of the uterine specimens showed residual HSIL or worse in 234 cases (24.7％, 234/947). The proportion of residual lesions was 7.3％ (21/286) in population with clear margins, 33.2％ (211/635) with involved margins, 7.7％ (2/26) without 1 mm negative margins, respectively. The positive margins group had significant difference at the aspect of residual rate in contrast to the negative margins group and the without 1 mm negative margins group (P<0.01). Further studies conclusively showed that the proportion of residual lesions was very similar between the negative margins group and the without 1 mm negative margins group (P>0.05). (2) The involved margins were interpretable in 621 cases. This was detected in 25.3％(111/438) patients with only one positive margin, 47.4％(74/156) with two positive margins and 77.8％(21/27) among three positive margins, respectively (P<0.01). (3) Furthermore, there were 418 cases only one positive margin was definite, and the proportion of residual lesions was 31.0％(62/200) in population with a positive margin of internal ostium of cervix, 18.2％(31/170) of external ostium of cervix and 33.3％(16/48) of the basement. The residual rates were higher in the endocervical and basal margin groups than that in the ectocervical margin group, and the differences were significant (P<0.05). Conclusions The risk of residual HSIL or worse is significantly greater with involved margins at hysterectomy following LEEP. Both the positive endocervical and basal margin are excellent predictors of residual diseases, while the without 1 mm negative margin may be not. Clinicians should avoid treating it as positive margin and prevent overtreatment.

Enfermedad Mínima Residual en leucemia: rompiendo el paradigma de remisión completa / Residual minimal disease: breaking the paradigm of complete remission

Las malignidades hematológicas constituyen un grupo heterogéneo de condiciones. La enfermedad mínima residual (EMR) hace referencia a la presencia de enfermedad maligna hematológica, en pacientes que se encuentran en remisión según análisis convencionales. La EMR ha mostrado tener importancia pronóstica en condiciones como: leucemia mieloide aguda, leucemia mieloide crónica, mieloma múltiple, y en leucemia linfoide aguda y crónica. La detección ultrasensible de este estado podría permitir una mejor estratificación del riesgo y de igual forma abrir oportunidades para intervenciones terapéuticas tempranas. En el siguiente artículo se realiza una breve revisión acerca de la importancia pronóstica de la EMR en diferentes malignidades hematológicas(AU)

Hematological malignancies constitute a heterogeneous group of conditions. Residual minimal disease (RMS) refers to the presence of haematological malignancy in patients who are in remission if conventional pathological analyzes are used. RMS has been shown to have prognostic significance in conditions such as: acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, and acute and chronic lymphoblastic leukemia. Ultrasensitive detection of this condition could allow a better risk stratification and open opportunities for early therapeutic interventions. In the following article there will be a brief review about the prognostic importance of RMS in different hematologic malignancies(AU)

Detection and clinical application of minimal residual disease in multiple myeloma / 国际肿瘤学杂志

Minimal residual disease (MRD) is a very important prognostic factor in multiple myeloma (MM).The major types of MRD tests include cell-based test (multi-parameter flow cytometry) and molecular tests (including PCR and gene sequencing),and the various techniques have inherent advantages and limitations.In clinical application,MRD negative can significantly prolong progression-free survival and overall survival of patients who receive hematopoietic stem cell transplantation and conventional che-motherapy.Moreover,the MRD status is of great significance to the selection of treatment options.

The value of P16 immunohistochemical detection in judge residue of patients with conization in high grade intraepithelial neoplasia / 重庆医学

Objective To investigate the feasibility of P16 immunohistochemistry combined with routine pathology in judging the residual lesion of high grade cervical intraepithelial neoplasia.Methods Patients with cervical conization for high grade cervical intrapithelial neoplasia in this hospital from January 2014 to May 2016 were chose and divided into P16 immunohistochemical detection combined with pathological diagnosis group and pathological evaluation group according to patient's motivation.Patients with residual margins were treated in accordance with the clinical guidelines and TCT was followed up for 6 months after no margin.Then sensitivity and accuracy of two group were analyzed by gold standard of follow-up results.Results 104 patients in P16 immunohistochemical detection combined with pathological diagnosis group were negative in TCT test after 6 month of following up after surgery.However,at the time of 6 months follow-up after surgery,7 patients of 112 patients have been diagnosed with positive by TCT in pathological evaluation group.The Sensitivity and accuracy in P16 immunohistochemical detection combined with pathological diagnosis group were 100％ which were higher than pathological evaluation group.Conclusion P16 immunohistochemical detection combined with conventional pathology can accurately diagnose the cervical cutting edge of conization.

The value of minimal residual disease with acute myeloid leukemia in prognostic evaluation and its correlation with cell morphology and genetics / 中国医师杂志

Objective To explore the value of minimal residual disease with acute myeloid leukemia in prognostic evaluation and its correlation with cell morphology and genetics.Methods A total of 105 patients with acute myeloid leukemia (AML) (non M3) was used as the research subjects to evaluate the correlation between the level of minimal residual disease (MRD) and the degree of cellular morphological remission,and cytogenetics.According to the different levels of MRD,78 patients of cell morphology complete remission (CR) were grouped to evaluate the one-year recurrence rate after the first chemotherapy treatment.Results The correlation was evaluated between MRD level and morphological remission in 105 patients with AML after initial chemotherapy.In the degree of cellular morphological remission cell evaluation showed 78 (74.29％) cases of CR,27 (25.71％) cases of partial remission (PR) or non remission (NR).Among 78 cases of CR,MRD negative rate was 66.67％ (52/78),MRD was 33.33％ (26/78);and 27 cases of NR or PR,MRD was 100％ (27/27).The correlation between MRD level and cytogenetic evaluation,cytogenetic prognosis group and prognosis of middle group and poor prognosis group,and the negative rate of MRD were 66.67％,45.90％,and 35.29％,without significant difference (P ＞ 0.05).Seventy eight patients with CR were divided into two groups according to the level of MRD to evaluate the recurrence rate of the 1 year,the recurrence rate of the positive group was significantly higher than that of the negative group (P ＜ 0.05).Conclusions With the development of hematology,the meaning of CR deeply,using flow cytometry method to detect the MRD,MRD positive cells relapse earlier than the traditional morphology,it has important clinical significance for guiding treatment and early prediction of recurrence of CR AML.

Prognostic value of dynamic monitoring of RUNX1-RUNX1T1 transcript in pediatric acute myeloid leukemia / 中华血液学杂志

Objective@#To investigate the prognostic value of dynamic monitoring of RUNX1-RUNX1T1 transcript in pediatric patients with t (8;21) acute myeloid leukemia (AML) .@*Methods@#The clinical features and RUNX1-RUNX1T1 transcript levels of 55 pediatric t (8;21) AML patients, newly diagnosed from Jan. 2010 to Apr. 2016, were analyzed retrospectively. The relationship between the minimal residual disease (MRD) and prognosis was analysed by dynamic monitoring of RUNX1-RUNX1T1 transcript levels using real-time quantitative PCR (RQ-PCR) technology.@*Results@#The RUNX1-RUNX1T1 transcript levels in bone marrow cells at diagnosis was not related to relapse. After one course of induction therapy, patients with a more than 2 Log reduction of RUNX1-RUNX1T1 transcript levels (>2 Log) had lower 5 years cumulative incidence of relapse (CIR) [ (24.3±8.4) % vs (52.6±9.7) %, χ2=9.046, P=0.003], relapse-free survival (RFS) [ (71.6±12.7) % vs (48.1±13.2) %, χ2=5.814, P=0.016], and better overall survival (OS) [ (76.9±12.5) % vs (48.9±14.7) %, χ2=6.346, P=0.012], compared to patients with a less than 2 Log reduction (a<2 Log) . Multivariate Cox survival analysis suggested that a>2 Log reduction in RUNX1-RUNX1T1 transcript levels after a course of induction therapy was an independent prognostic factor for RFS (HR=0.263, 95%CI 0.081-0.851, P=0.026) and OS (HR=0.214, 95% CI 0.057-0.808, P=0.023) . During consolidation therapy and follow-up period, molecular relapse of 16 cases and hematologic relapse of 13 cases were identified by continuous dynamic monitoring of RUNX1-RUNX1T1 transcript levels, with a median interval of 4.0 (1.5-5.8) months from the molecular relapse to hematologic relapse. 2 cases of molecular relapse who received timely allogeneic hematopoietic stem cell transplantation did not experience hematologic relapse.@*Conclusion@#Dynamic monitoring RUNX1-RUNX1T1 transcript levels by RQ-PCR technique can subdivide patients into relatively low and high risk group, early screen patients at high risk of relapse and provide a scientific basis for precision stratification and risk-adapted therapy for pediatric t (8;21) AML children.

Effect of minimal residual disease monitoring by multiparameter flow cytometry pre-conditioning on prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR1-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR1-AML.@*Methods@#Between April 2012 and March 2015, consecutive 186 patients with CR1-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive.@*Results@#①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR1-AML.@*Conclusion@#MRD positive pre-conditioning was the only negative impact factor for patients with CR1-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR1-AML after allo-HSCT.

Clinical outcome and high risk factor for residual lesion analysis of HSIL half a year after loop electrosurgical excision procedure: a clinical study of 1502 cases / 中华妇产科杂志

Objective To analyze clinical outcome of high-grade squamous intraepithelial lesion (HSIL) half a year after loop electrosurgical excision procedure (LEEP) and explore the high risk factor of residual cervical HSIL.Methods The retrospective study was carried out on 1 502 patients who underwent LEEP,with HSIL in the LEEP histopathology from January 2011 to December 2013 at Obstetrics and Gynecology Hospital of Fudan University to confer the difference between residual group and non-residual group after 6 months of the leep conization.Patients were followed with ThinPrep cytologic test (TCT),high risk HPV (HR-HPV) test,colposcopy guided biopsy (CBD) and endocervical curettage (ECC).The high risks of residual cervical HSIL was analyzed.Results Among 1 502 cases,48 (3.20％,48/1 502) cases suffered HSIL residual disease.Forty cases were diagnosed by CBD,4 cases were diagnosed by ECC.The other 4 cases were both positive in CBD and ECC.Residul rate were different among different age groups.The residual rate was higher in the age ≥50 years old compared to the age below 50 [9.70％ (16/165),2.39％ (32/1 337);x2=25.33,P＜0.01].For post-LEEP specimens,both circumference (2.5,2.8 cm;Z=-3.17,P＜0.01) and width [0.6,0.6 cm;Z=-2.88,P＜0.01) were less in HSIL lesion residual group than those in non-residual group,though length showed no obvious difference [1.5,1.5 cm;Z=-1.55,P＞0.05).The residual rate of leep positive margin was obviously higher than that in the negative margin group [6.77％ (18/266) vs 2.43％(30/1 236);x2=13.30,P＜0.01].Different positive margin had diverse residual rate,as positive endocervical margin was 16.07％ (9/56),positive margin undetermined was 7.29％ (7/96) and positive ectocervical margin was 3.33％ (4/120).Both positive endocervical margin and positive margin undetermined had a higher residual rate than residual rate (x2=26.99,P＜0.01;x2=4.24,P＜0.05).Abnormal cytology showed higher residual rate than the non-residual with significant difference [6.00％ (6/100) vs 1.29％ (14/1 083),x2=9.50,P＜0.01].In terms of the post-LEEP HR-HPV test follow-up,HR-HPV positive's residual rate was higher than that in the negative group [2.91％ (6/206) vs 0.96％ (7/727)],while there was no statistical significance (x2=3.10,P＞0.05).Multivariate logistic analysis showed that abnormal cytology in 6 month's follow-up post-LEEP conization was an independent risk factor on residual lesion (OR=3.75,P＜0.05).Conclusions Patient with age ≥50 years old and positive endocervical margin are high risk factors for the residual HSIL lesion after LEEP conization,especially for abnormal cytology during follow up is independent risk factor for residual lesion.Colposcopy directed biopsy and (or) ECC still play an indispendsable role in finding the HSIL residual lesion.

Minimal residual disease detection in multiple myeloma: current status, challenges and strategies / 白血病·淋巴瘤

Long time clinical results have showed that multiple myeloma (MM) patients who achieved complete remission (CR) had heterogeneous prognosis. Some patients who achieved CR relapsed in a short time, even died within 2 years after initial therapy, while other patients acquired long-term survival. With the emergence of minimal residual disease (MRD) assessment, rigorous personal therapy monitoring and accurate prognostic evaluation could be realized. MRD can monitor inside the bone marrow by multi-parameter flow cytometry, allele-specific oligonucleotide-based quantitative polymerase chain reaction and next-generation sequencing, as well as the external conditions of the bone marrow by sensitive imaging techniques. This article focuses on clinical benefit, characteristics of different monitoring methods and future direction of MRD in MM.

Perioperative changes in serum CA125 levels: a prognostic factor for disease-specific survival in patients with ovarian cancer / 부인종양

OBJECTIVE: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival. METHODS: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models. RESULTS: A postoperative decline in serum CA125 level of ≥80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR(50%–79%)=0.52 [95% CI: 0.28–0.96] and HR(≥80%)=0.26 [95% CI: 0.13–0.54] vs. the serum CA125 decline of <50% [p<0.001]). CONCLUSION: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons’ estimation of residual tumor volume.