Clinicopathological characteristics and prognosis of IgA nephropathy patients with gross hematuria / 中华全科医师杂志

Objective:To investigate the clinicopathological features and prognosis of IgA nephropathy (IgAN) patients with gross hematuria.Methods:The clinical and pathological data of 490 primary IgAN patients admitted in the Affiliated Hospital of Qingdao University from January 2010 to June 2019 were analyzed. Patients were divided into gross hematuria group and non-gross hematuria group. The clinical and pathological features and prognosis were compared between the two groups. All patients were diagnosed by kidney biopsy, and followed up until June 30, 2020. Kaplan-Meier survival curve was used to examine the renal survival,and Cox regression model was used to analyze the risk factors affecting renal survival in two groups.Results:Among 490 patients there were 111 patients (22.7%) in the gross hematuria group and 379 patients (77.3%) in the non-gross hematuria group. Age, hypertension, 24-h urine protein, serum creatinine, blood uric acid, blood triglycerides, total blood cholesterol level, mesangial cell hyperplasia (M1), the proportion of renal tubular atrophy or renal interstitial fibrosis (T1/2) in gross hematuria group were lower than those in non-gross hematuria group ( P<0.05), while the estimated glomerular filtration rate (eGFR) in gross hematuria group was higher than those in non-gross hematuria group ( P<0.05). Four hundred and twenty six patients (86.9%) were followed up for at least 6 months, including 93 patients in gross hematuria group and 333 patients in non-gross hematuria group. There was no statistically significant difference in treatment method between the two groups ( P>0.05). The incidence of end-point events in non-gross hematuria group was higher than that in gross hematuria group [18.6%(62/333) vs. 6.5%(6/93), χ2=8.023, P<0.05]. Kaplan-Meier survival analysis showed that the cumulative renal survival rate of the gross hematuria group was higher than that of the non gross hematuria group (χ2=11.44, P<0.001). Multivariate Cox regression analysis showed that urine protein>1 g/24 h, eGFR<60 ml·min -1·(1.73 m 2) -1, hypertension, hyperuricemia and the elevated serum IgA/C3 were risk factors for renal survival [ HR(95% CI)=3.457(1.137-10.514),2.736(1.073-6.977),2.720(1.144-6.465),2.789(1.102-7.060),1.070(1.009-1.135), all P<0.05]. Conclusions:IgAN patients with gross hematuria has less severe kidney damage and higher cumulative renal survival rate than non-gross hematuria patients. Urinary protein>1.0 g/d, hypertension, hyperuricemia and the elevated serum IgA/C3 are risk factors for adverse end-point events, to which timely attention and corresponding treatment should be given.

Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma / 中华病理学杂志

Objective@#To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas.@*Methods@#One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis.@*Results@#One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients′ age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8).@*Conclusion@#EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens / 中华病理学杂志

Objective@#To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).@*Methods@#Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis.@*Results@#The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis.@*Conclusions@#Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

Progress of molecular pathogenesis of extranodal natural killer/T-cell lymphoma / 白血病·淋巴瘤

Extranodal nature killer/T cell lymphoma (ENKTCL) is a highly aggressive non-Hodgkin lymphoma (NHL) with a high mortality. ENKTCL is epidemic in Asia and Latin America, especially in China, Japan and South Korea. EBV has been proved to be associated closely with ENKTCL; however, specific molecular mechanism which can explain how the neoplasm develops is still unclear. Chinese population seems to be more susceptible to this lymphoma and Chinese scientists have made great contributions to the pathogenesis and the treatments of ENKTCL. This review mainly introduces the recent progress of molecular pathogenesis of ENKTCL.

Prognostic analysis of BCL-2/MYC double- hit in diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of BCL-2/MYC double-hit on prognosis in diffuse large B-cell lymphoma（DLBCL）.</p><p><b>METHODS</b>A retrospective study was conducted to investigate clinical and pathological data of 111 patients with DLBCL. CD10, BCL-6, MUM-1, BCL-2 protein expressions were examined by immune-histochemical methods, and abnormal BCL-2 and MYC genes were analyzed by FISH for patients with sufficient pathological data. SAS 8.2 was adopted to perform Chi- square test, COX's proportional Hazard Model, Life table survival analyses.</p><p><b>RESULTS</b>Of 111 patients, male 77 cases, female 34 cases, the median age was 55（14-85）years, CD10, BCL-6, MUM-1, BCL-2 positive rates were 15.7%（16/102）, 58.8%（60/102）, 33.0%（34/103）, 74.8（77/103）respectively, the abnormal rate of BCL-2 gene was 43.1%（25/58, 24 cases with multiple copies, 1 case with translocation）, and the abnormal rate of MYC gene was 20.4%（10/49, 10 cases with multiple copies）. Coexistence of BCL-2 and MYC genes abnormalities accounted for 13.0%（6/46）. According to the classification of Hans model, GCB subgroup accounted for 41.2%（42/102）, and non-GCB subgroup 58.8%（60/102）, the median survival time was 24 months, 3-year and 5-year overall survival rates were 48.5% and 39.7% respectively. Overall survival rates of normal and abnormal BCL-2 gene were 34.2%，22.8%, respectively with no statistical significance（P=0.770）. Overall survival rates of normal and abnormal MYC gene were 35.9% and 22.2% ，with no statistical significance（P=0.650）. Overall survival rate of double-hit was 0, far worse than that of single abnormal gene（P=0.034）, which implied double-hit of BCL-2 and MYC gene abnormality to be adverse prognostic factors. BCL-6 protein express could be classified as benign prognostic factors, while ECOG score≥2, escalated IPI index as adverse prognostic factors, and further COX risk model regression analysis indicated that ECOG score, IPI grading and treatment methods were independently adverse factors affecting prognosis. Comprehensive therapy based on chemotherapy could improve outcome.</p><p><b>CONCLUSION</b>BCL-2/MYC genes double-hit was the factor for the adverse outcome in DLBCL patients. However, ECOG score, IPI risk grading and treatment methods were the independent factors affecting prognosis.</p>

Clinical significance of expression of matrix metalloproteinase 13 in breast cancer / 国际外科学杂志

Objective To find out the correlation between MMP-13 and clinicopathological parameters of breast cancer and identify clinical significance of MMP-13 overexpression on overall survival of breast cancer.Methods Immunohistochemistry was performed on paraffin-embedded tissue microarray containing 159 tissue dots from breast cancer patients.The intensity and the extent of IHC were scored by pathologists blind to clinicopathological parameters of the specimens.Different expression profiles of MMP-13 in breat cancer tissues and paraneoplastic tissues,and correlation between MMP-13 and breast cancer clinicopathological parameters were analyzed for statistical significance respectively.The impact of MMP-13 overexpression on overall survival of breast cancer.Results MMP13 expression were significantly higher in breast cancer tissues(54.4％) than in their corresponding paraneoplastic tissues(27.5％)(P =0.003).Expression of MMP-13 in breast cancer positively correlated with lymphma node metastasis(r =0.257,P =0.006),clinical TNM classification (r =0.310,P =0.001),HER2 expression (r =0.192,P =0.041).However,no significant correlation were oberserved between MMP-13 expression and tumor size,MMP-13 expression and tumor grade,MMP-13 expression and ER expression,MMP-13 expression and PR expression respectively.Conclusions Overexpress of MMP-13 is more common in breast cancer tissues than in their corresponding paraneoplastic tissues,and is an independent prognosis indicator of breast cancer.

Advances on etiology and pathogenesis of angioimmunoblastic T-cell lymphoma / 白血病·淋巴瘤

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma entity originating from follicular helper T (TFH) cell with peculiar clinical and pathological features.Today,it is still difficult to realize its etiology and pathogenesis clearly. This review presents the latest updated progresses on etiology and pathogenesis of AITL.

Comparison of RapidArc plans and fixed field intensity modulated radiotherapy planning in cervical cancer radiotherapy / 中华放射医学与防护杂志

Objective To explore the advantages and disadvantages between the RapidArc plans and fixed-field IMRT plan (IMRT).Methods Ten cases of cervical cancer,aged 55 (36-70),who were to receive post-operative radiotherapy were selected randomly.Single arc (Arc 1),two arcs (Arc 2),and three arc (Arc 3) RapidArc plans and fixed-field IMRT plan were designed respectively in the Eclipse 8.6 planning system.The designing,treatment time,target area,and dose distribution of organs at risk by these 4 planning techniques were compared.Results The values of average planned treatment time by the Arc 1,Arc 2,and Arc 3 ten cases was 98,155,185,and 46 min,respectively.The values of average treatment time in the Varian IX accelerator were 2.15,3.32,4.48,and 6.95 min,respectively.The average mean doses were (48.99±1.08),(49.40±0.51) ,(49.51±0.62) ,and (48.65±0.92) Gy,respectively.The values of homogeneity index (HI) of target were 1.11±0.07,1.07±0.02,1.06±0.02,and 1.12±0.05,respectively.The values of eonformal index (CI) of target were 0.73±0.13,0.87±0.06,0.87±0.06,and 0.79±0.06,respectively.The doses at rectum,bladder,and small intestine calculated by IMRT plan were the lowest,and the doses at the femoral neck calculated by these 4 plans were similar.Conclusions The RapidArc plan is superior in dose distribution at target,HI,CI,and treatment time to IMRT,but IMRT plan is superior to RapidArc in planned dose calculation time and protection of organs at risk.However,in general,the RapidArc plan is better in clinical application than IMRT plan.

Clinical-pathological study of diffuse large B-cell lymphoma treated with R-CHOP regimen / 白血病·淋巴瘤

Objective To investigate the effect of chemotherapy regimen of rituxmab combined with CHOP (R-CHOP) on the survival of patients with diffuse large B cell lymphoma (DLBCL). Methods One hundred and fifty-six cases of DLBCL diagnosed according to the WHO 2008 classification were collected from the haematopathological laboratory, the department of pathology, and Beijing University Health Science Center. Standard two-step method of immunohistochemical staining with Envision was used to assess the expression of CD10, MUM-1, bcl-6, and bcl-2. The different classification models were made according to the immuaohistochemical staining results. Hans algorithm classifies the patients into two subgroups originating from germinal center B cell-like cell (GCB) and non-germinal center B cell-like cell (non-GCB), and Muris model were classfied the DLBCL patients into the good-survival groupl and the poor-survival group2. Thirty patients with treatment of R-CHOP were set as study group and the other 126 patients without Retuxmab were defied as control group. The data were analyzed with X2 test, log-linear model and Life Table survival analysis by the SAS 8.2 statistical package. Results The 3-year survival rate of the study group was 78.3 %, but was 53.4 % in the control group. The over-all survival of the study group was obviously better than the control group with the significant difference (P <0.05). Hans algorithm showed no implication of survival for any group. The survival of different groups in Muris model has no difference in study group but was obvious in control group. The expression of bcl-2 protein has no association with survival in study group but acted as a worse implication of survival in control group. Conclusion R-CHOP chemotherapy regimen could improve the remission rate and over-all survival of DLBCL. Rituxmab could weaken the effect of bcl-2 expression in the prognosis, and the implication of survival by Muris model has diminished.

Expression of ALK-1, TIA-1 and granzyma B in primary systematic anaplastic large cell lymphoma and their significances on clinical outcome / 白血病·淋巴瘤

Objective To study the expressions of anaplastic lymphoma kinase (ALK-1) and cytotoxic proteins in primary systemic anaplastic large cell lymphoma (S-ALCL) and their relationship with clinical outcome. Methods 51 S-ALCL cases were collected from Lymphoma Lab of Peking University Health Science Centre & Peking Children's Hospital. The morphologic characteristics were studied under routine microscope, and essential immunohistochemical stainings were performed and reviewed to confirm the diagnosis of S-ALCL. Immunohistochemical stainings for ALK-1 and cytotoxic proteins (TIA-1 & granzyme B) were performed using standard SP method. Patients related clinical data including follow-up materials were collected. Results Survival time of 44 cases with completely clinical follow up materials ranged from 0.5～66months. 36 out of 51 cases(37 %) was positive for ALK-1 protein. While 20 cases out of 47 S-ALCL cases ( 42.55 % ) positive for granzyme B and 22 out of 28 cases (81.48 %) were positive for TIA-1. The prognosis of patients with ALK-1 protein positive and granzyme B negative expression was better, but TIA-1 expression might have nothing to do with clinical outcome (P＞0.05). In addition, multivariate analysis confirmed that ALK-1 protein expression, granzyme B protein expression and Ann-Arbor stage system were possible for prognosis(P＜0.05), Conclusion Expression of ALK-1 and granzyme B protein expression may serve as two independent prognostic predictors in S-ALCL patients.