Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Nivolumab-associated pulmonary toxicities： a retrospective study based on FARES database from 2016 to 2019 / 上海预防医学

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC025： 3.99， ROR025： 17.25）， pneumonitis （IC025： 3.34， ROR025： 10.64） and bronchial fistula （IC025： 2.94， ROR025： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC025： 0.50， ROR025： 1.44）， pneumonia （IC025： 0.08， ROR025： 1.07） and pneumonitis （IC025： 3.34， ROR025： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.

Flipped classroom teaching:Practice and evaluation / 上海预防医学

Objective To evaluate the feasibility and effectiveness of flipped classroom teaching in medical research design class with more than 50 undergraduate. Methods Using randomized parallel-control study, two classes were chosen for this study:flipped classroom teaching group (i.e.FC group) and traditional teaching group (i.e.control group).Except for different teaching modes, all the other conditions of these two groups remained the same, including learning materials, network reference materials and teaching equipment. Results The FC group had 52 students and the control group had 69 students.After teaching, the final test score on study design in FC group was 11.53 higher (95%CI:4.75-18.32, t=3.37, P=0.001).However, there was no statistically significant difference between the test scores of other medical statistic teaching units (t=0.223, P=0.824). Conclusion FC teaching can be used in large class (more than 50 students) in medical undergraduate education.For flipped classroom teaching with large number of students, teachers should strengthen the arrangement of students′ self-study before class, organize effective team discussion, and make full use of new technologies to support teaching.

Detection of tin in human urine by atomic fluorescence spectrophotometry / 中国职业医学

OBJECTIVE: To establish a method for determination of urinary tin by atomic fluorescence spectrophotometry.METHODS: The graphite digestion instrument was used to digest 2. 50 m L urinary sample with 1. 50 m L concentrated nitric acid,hydrochloric acid( volume fraction 4. 00%) was added to a total constant volume of 10. 00 m L. After 2. 50 m L of thiocarbamide-ascorbic acid( mass concentration 100 g / L) was added,hydrochloric acid( volume fraction 4. 00%) was added to a total constant volume of 25. 00 m L( equivalent to urinary sample was diluted 10 times),1. 00 m L of the sample was collected and detected by atomic fluorescence spectrophotometry. RESULTS: The good linear relationship was shown in the range of 4. 00-200. 00 μg / L with a correlation coefficient of 0. 999 5. The limit of detection was 0. 20 μg / L. The recovery rates ranged from 100. 20% to 100. 84%. The within-run relative standard deviation( RSD) and between-run RSD were 0. 11%-2. 01% and 1. 37%-5. 58%,respectively. The samples can be stored for 7 days under the temperature of4 ℃. CONCLUSION: This method has the advantages of high sensitivity,precision and convenient operation,which is suitable for the daily determination of urinary tin in human.

Significance of interleukin-1beta expression and microvascular density in invasive micropapillary carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of interleukin-1beta (IL-1beta) expression and microvascular density (MVD) in invasive micropapillary carcinoma (IMPC) of breast.</p><p><b>METHODS</b>Immunohistochemical study for IL-1beta and CD34 was performed on 100 cases of IMPC and 97 cases of invasive ductal carcinoma (IDC). The relationship between IL-1beta expression, MVD and various pathologic parameters (estrogen and progesterone receptor status, Ki-67 proliferative index, histologic grade and lymph node metastasis) in IMPC was analyzed.</p><p><b>RESULTS</b>There was no significant difference in expression of IL-1beta between IMPC and IDC (P = 0.924). The expression of IL-1beta positively correlated with proliferative index (P = 0.023), histologic grade (P = 0.038) and lymph node metastasis (P = 0.008), and negatively correlated with estrogen receptor expression (P = 0.035). The MVD in IMPC was significantly higher than that in IDC (66.4 versus 60.0, P = 0.003). The mean MVD in node-positive IMPC was higher than that in node-negative IMPC (68.8 versus 54.4, P = 0.001). In IMPC, the MVD in histologic grade II and III tumors was much higher than that in histologic grade I tumors (68.3 versus 59.9, P = 0.025). It had no relationship with hormonal receptor status and proliferative index.</p><p><b>CONCLUSION</b>Overexpression of IL-1beta and high microvessel density may have important roles in tumor cell proliferation and lymph node metastasis in IMPC.</p>

Evaluation of efficacy of stereoscopic location and whole serial sections of margin status in breast conservation therapy specimens / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of different methods in pathologic assessment of margin status in breast conservation therapy specimens.</p><p><b>METHODS</b>Assessment of margin status in breast conservation therapy specimens by stereoscopic location and whole serial sections (SLWS) and selective margin sections (SMS) was compared. The margin status was evaluated with intraoperative frozen sections either by SLWS (145 cases) or SMS (79 cases). On the other hand, with formalin-fixed specimens, the margin status of 84 cases was assessed by SLWS and that of another 226 cases by SMS. Follow-up data of all patients were analyzed.</p><p><b>RESULTS</b>The rate of detection of positive margin by SLWS (24.1%, 35/145) was significantly higher than that by SMS (6.3%, 5/79) during frozen section setting. Similarly, the rate of detection of positive margin by SLWS (34.5%, 29/84) was also higher than that by SMS (12.0%, 27/226) when applied in formalin-fixed specimens. The duration of follow-up ranged from 2 to 46 months. None of the patients with margin status assessed by SLWS developed local recurrence. This was in contrast to 3 cases with tumor recurrence (6 months, 15 months and 28 months after the operation respectively) in SMS group.</p><p><b>CONCLUSIONS</b>Assessment of margin status by SLWS in breast conservation therapy specimens can reduce the chance of missing underlying minute foci of margin involvement and help to localize the exact site of positive margin. It thus reduces the overall risk of local recurrence and the need of a second operation.</p>

Diagnosis and prognosis study of breast carcinoma with micropapillary component / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the diagnostic criteria, clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma (IMPC) of breast.</p><p><b>METHODS</b>All cases of breast carcinoma diagnosed during the period from 1989 to 2001 were retrospectively reviewed. One hundred examples with IMPC component, according to the 2003 World Health Organization classification of breast tumors, were identified. The clinicopathologic features and follow-up data of these cases were analyzed.</p><p><b>RESULTS</b>Amongst the 100 cases of IMPC studied, 69% (69/100) had evidence of lymphovascular invasion. The incidence of regional lymph node metastasis was 84.8% (84/99). Follow-up information was available in 98 patients (mean of follow-up duration = 60.1 months). Eleven patients (11.2%) had local recurrence within a mean of 26.4 months after the operation, while 38 patients (38.8%) had distant metastases within a mean of 36.0 months. Thirty-six patients (36.7%) died of the disease. The overall 5-year survival rate was 59% and the 10-year survival rate was 48%. Univariate and multivariate analysis showed that the prognosis of patients was adversely affected by the presence of lymphovascular invasion and family history of breast cancer. On the other hand, tamoxifen therapy and adjuvant chemotherapy improved survival.</p><p><b>CONCLUSIONS</b>Breast carcinoma with IMPC component is associated with poor prognosis, despites the relative proportion of this architectural pattern. The overall prognosis is related to the presence of lymphovascular invasion and family history of breast cancer. Hormonal therapy and individualized chemotherapy can improve the survival rate.</p>

Clinical analysis of 31 patients with fungemia / 中国感染与化疗杂志

Objective To investigate the epiderniology of fungemia and provide evidence for clinical therapy.Methods A retro- spective survey was done with the 31 cases of fungemia in our hospital from August 2004 to November 2005.Results More than 80% of the patients suffered from two and more underlying diseases.Over a half of infections developed following placement of catheters.And 83.9% of the patients had a history of antimicrobial agents use before blood culture.The pathogens of 24 (77.4%) cases were associated with Candida spp.Only 3 strains were C.albicans.The mortality rate of candidemia was 45.8%.Different Candida species had different resistance rates to antifungal agents.Conclusions Fungemia patients often have serious underlying diseases.Most fungemia cases were candidemia caused by non-C.albicans.Some fungal pathogens are re- sistant to fluconazole and itraconazole.

Relationship between lymph node metastasis and pathologic features of invasive micropapillary carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between lymph node metastasis and pathologic features of invasive micropapillary carcinoma (IMPC) of the breast.</p><p><b>METHODS</b>Histopathologic features and status of lymph node metastasis of fifty-one cases of IMPC were studied by microscopic examination, immunohistochemical staining (VEGF-C and VEGFR-3) and analysis of lymphatic vessel density.</p><p><b>RESULTS</b>(1) The number of positive lymph nodes in histologic grade II/III IMPCs was significantly higher (mean 12.5) than that in histologic grade I tumors (mean 4.0). (2) The incidence of nodal metastases in IMPCs with lymphocyte infiltration (+)/(++) was significantly higher (27/28, 96.4%) than that in tumors with no or minimal lymphocyte infiltration (-)/(+/-) (14/23, 60.9%), and the number of positive nodes was also higher (mean 14.4) in tumors with lymphocyte infiltration compared with those without (mean 4.6). (3) In IMPCs with histologic grade II/III, the expression of VEGF-C was significantly higher than that of histologic grade I tumors (P = 0.03). VEGF-C expression was in positive correlation with lymph node metastasis (P = 0.006) and lymphatic vessel density (P = 0.009). Lymph node metastasis was also correlated with lymphatic vessel density (P = 0.007). (4) The percentage of IMPC component in the tumor did not correlate with nodal metastasis. The metastatic foci in lymph node were all IMPC or mainly IMPC. (5) Fourteen of twenty-eight cases (14/28, 50%) of IMPC containing ductal carcinoma in-situ (DCIS) were DCIS of micropapillary type.</p><p><b>CONCLUSIONS</b>The histologic grade, lymphatic vessel density and lymphocyte infiltration are key histological features that are correlated with lymph node metastasis of IMPC. The expression of VEGF-C and VEGFR-3 may play an important role in the development of lymph node metastasis of IMPC. Micropapillary type DCIS may be the early stage of IMPC.</p>

Distribution and susceptibility of pathogens isolated from postoperative infections in liver transplantation recipients / 中国感染与化疗杂志

Objective To investigate the epidemiology of bacterial infections after liver transplantation and anaIyze the antimi- crobial susceptibility of major pathogens to provide reference for clinical therapy.Methods A retrospective survey was conduc ted in 174 patients who underwent liver transplantation during 2001 and 2004.Identification and susceptibility of pathogens were assayed by Microscan Walkaway 40 Automatic System.Results Infection was identified in 59.8% of the 174 patients after liver transplantation.A total of 218 non-duplicate strains were isolated.Most infections were caused by single pathogen.The infection was frequently identified in respiratory tract,biliary tract,blood stream or intra-abdominal cavity.The top 5 patho- gens were Acinetobacter baumannii,Staphylococcus aureus,Pseudomonas aeruginosa,Stenotrophomonas maltophilia and Escherichia coli.Gram-negative bacilli were usually resistant to multiple antimicrobial agents,but less resistant to piperacillin- tazobactam or imipenem.Most of S.aureus isolates were methicillin-resistant,which were susceptible to vancomyein.Conclu- sions Pathogens of postoperative infections in liver transplantation recipients are mostly multi-drug resistant.The microbiologi- cal surveillance is important for guiding clinical therapy.