The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

China guideline for the screening and early detection of prostate cancer (2022, Beijing) / 中华肿瘤杂志

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

Placental site nodule: a clinicopathological study of 20 cases / 临床与实验病理学杂志

Purpose To investigate the clinical manifesta-tions and morphologic features of placental site nodules (PSNs), and its clinical significance. Methods Twenty patients diag-nosed as PSNs were collected, then a retrospective analysis was conducted, and the characteristics of clinical data and follow-up results were analyzed,including of clinical manifestations, ultra-sonographic evaluation, morphologic and immunohistochemical features. Results The age of patients ranged from 25 to 41 years (32. 48 ± 4. 77 years in average). Three fifths of patients had pregnancy history for at least two times and the interval time to the last pregnancy ranged from 5 to 37 months (15. 33 ± 8. 05 months on average). 15 (75% ) patients went to the hospital because of abnormal vaginal bleeding. In our study, most of the samples showed a membrane-like structure without definite nod-ule. Microscopically, single or multiple, well-circumscribed and oval small nodules were found in endometrial tissue. In most ca- ses, the hyalinization was generally uniform in the center of the nodules, more or less intermediate trophoblasts appeared on the edge of the nodules. Immunohistochemically, the strong diffuse expressed CK (AE1/AE3), CAM5. 2, EMA, GATA-3, Cyclin E and p63 were detected in most of all cases, and PLAP showed strong focal expression, α-inhibin and hPL showed faint focal expression, Ki-67 staining for proliferative index was less than 4% . Conclusion PSN is a benign lesion of the intermediate trophoblast at the chorionic leave. Some diseases including hya-linized decidua, epithelioid trophoblastic tumor, and squamous cell carcinoma with hyalinization need to be identified. Some im-munohistochemical markers may be certain helpful in distinguis-hing as necessary.

Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.</p><p><b>METHODS</b>Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of α = 0.05.</p><p><b>RESULTS</b>Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age ≤45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 × upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not.</p><p><b>CONCLUSIONS</b>Five risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.</p>

Famitinib in metastatic renal cell carcinoma: a single center study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).</p><p><b>METHODS</b>The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent.</p><p><b>RESULTS</b>A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg, 20 mg and 30 mg, respectively. Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD). Progressive disease was found in 3 (12.5%) patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% CI 7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% CI 8.7-57.3) months. The adverse drug reactions mainly included hypertension (54.1%), hand-foot skin reactions (45.8%), diarrhea (33.3%), mucositis (29.2%), neutropenia (45.8%), thrombocytopenia (29.2%), hyperlipidemia (41.7%) and proteinuria (41.7%). The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%.</p><p><b>CONCLUSIONS</b>Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.</p>

Value of CK20 immunocytochemistry as an adjuvant to urine liquid-based cytology in detection of urothelial carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of cytokeratin 20 (CK20) immunocytochemical (ICC) detection in the urine liquid-based cytological specimens in diagnosis of urothelial carcinoma (UC).</p><p><b>METHODS</b>The study consisted of prospective and retrospective groups. In the prospective group, voided urine samples were collected from patients with a variety of urological conditions and healthy individuals. Urine cytological diagnosis and CK20 ICC were performed on the collected specimens. In the retrospective group, archived urine slides with cytological diagnoses of atypical urothelial cells (AUC), suspicious carcinoma (SuCA) and carcinoma (CA) were selected. Then they were re-stained immunocytochemically with monoclonal antibody against CK20 after decolorization. Histological diagnosis and clinical follow-up result were used as the gold standard for analysis.</p><p><b>RESULTS</b>There were 136 cases in the prospective group, including 89 cases of UC, 19 cases of other urogenital malignancies, 12 cases of benign lesions and 16 cases of normal control. The sensitivity of CK20 ICC in detection of UC was 75.3%, significantly higher than that of LBC (48.3%, P < 0.001). The positive rate of CK20 was 64.7% (22/34) in G1 UC, 73.3% (22/30) in G2 UC, and 91.3% (21/23) in G3 UC (P < 0.001). The specificity of CK20 ICC was 91.5%, the same as that of LBC. There were 163 cases in retrospective group, including 119 cases of UC, 17 cases of other urogenital malignancies and 27 cases of benign lesions. The cytological diagnoses of them were 68 cases of CA, 47 cases of SuCA and 48 cases of AUC. The positive rates of CK20 ICC in UC and non-UC (other urogenital malignancies and benign lesions) cases were 90.8% and 15.9%, respectively, with a statistically very significant difference (P < 0.001). The LBC of all the 119 cases of UC included 62 (52.1%) cases of CA, 35 (29.4%) cases of SuCA and 22 (18.5%) cases of AUC. The positive rates of CK20 in the LBC-diagnosed CA, SuCA and AUC were 96.8%, 97.1% and 63.6%, respectively. The LBC of all the 44 non-UC cases included 6 (13.6%) cases of CA, 12 (27.3%) cases of SuCA and 26 (59.1%) cases of AUC, and the positive rates of CK20 in the LBC-diagnosed CA, SuCA and AUC were 33.3%, 33.3% and 3.8%, respectively. The differences of UC and non-UC cases between the corresponding categories of LBC were significant (P < 0.0001, respectively).</p><p><b>CONCLUSION</b>CK20 immunocytochemistry as an auxiliary method to urine liquid-based cytology can increase the sensitivity in detection of urothelial carcinomas.</p>

Sorafenib in combination with interferon-α-2b for the treatment of metastatic renal cell carcinoma: pre-liminary results / 中华泌尿外科杂志

Objective To explore the efficacy and tolerability of sorafenib in combination with interferon-α-2b for Chinese patients with metastatic renal cell carcinoma. Methods Seventeen pa-tients with unreseetable metastatic renal cell carcinoma were enrolled and received sorafenib in combi-nation with interferon-α-2b. Sorafenib was continuously given at the dose of 400 mg twice per day, in-terferon-α-2b 300 MIU subscutaneously once per day for 5 d each week, until disease progression or intolerable toxieities occurred. Tumor responses were evaluated every two months by response evalua-tion criteria in solid tumor. Results The median treatment duration was 120(51-442)d. All 17 pa-tients were evaluable for efficacy and safety. Five patients achieved partial responses (PR), 1 uncon-firmed PR,9 stable diseases. Two patients had progressed diseases. The overall response rate was 29%(5/17)with the disease control rate of 88%(15/17). Due to short-time follow up, the median progression free and overall survival time were not yet available. The common side effects included: fever 82%(14/17), diarrhea 82%(14/17), hand-foot syndrome 71%(12/17), asthenia 65%(11/17), rash 53%(9/17), alopecia 41% (7/17), mucosities 41% (7/17), hypertension 29% (5/17), anorexia 24% (4/17), hoarseness 24% (4/17), myalgia 24 % (4/17), nausea/vomiting 12 % (2/17) and headach/ dizzle 12%(2/17). Eleven (65%) out of 17 patients developed neutropenia, 5(29%) thrombocytope-nia and 5 (29%)anemia. Four(24%) out of 17 patients had abnormally elevated ALT/AST. Conclu-sion Sorafenib in combination with interferon-α-2b for metastatic renal cell carcinoma improves re-sponse rate with manageable toxicity.

Long-term outcome of testicular seminoma in 294 patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the correlation of long-term survival with the treatment strategies in patients with testicular seminoma.</p><p><b>METHODS</b>Clinical data of 294 patients with testicular seminoma treated in our hospital between 1959 and 2004 were collected and analyzed. The median age of the patients was 37 years (range 13 - 70 years). Among them, 260 were in stage I disease, 16 in stage II, and 18 in stage III. The patients were treated by surgical resection plus chemotherapy and/or radiotherapy. The survival rate was calculated using Kaplan-Meier method and log-rank test using SPSS 13.0 software.</p><p><b>RESULTS</b>The overall 5-, 10-, 20- and 30-year survival rates in this series were 92.1%, 91.8%, 85.5% and 71.4%, respectively. The major prognostic factor was found to be clinical stage. The patients with adjuvant chemotherapy after orchiectomy had better 10-year survival than the patients without (97.5% vs. 79.2%, P = 0.001). For stage II/III patients, the patients with chemotherapy and the patients with chemotherapy plus radiotherapy had a similar progression-free survival (PFS) and overall survival (OS) (P > 0.05).</p><p><b>CONCLUSION</b>Testicular seminoma is sensitive to chemotherapy and radiotherapy, and a good cure rate can still be achieved in the relapsed patients with a salvage treatment. Therefore, wide excision and long-term chemotherapy should be avoided in order to maintain the quality of life in those patients.</p>

Autophagy in fibrotic and postoperative remnant liver in rat / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver.</p><p><b>METHODS</b>Male Wistar rats were randomly divided into three groups: control group; fibrosis group, which received the solution of CCl4 in oil twice a week for 5 weeks; and hepatectomy group, which underwent 70% hepatectomy. Liver tissues and plasma were harvested 18 hours after the surgery. The rats' general conditions and plasma liver function were observed. Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope. Qualitative analysis of autophagosome was made base on the data from transmission electron microscope.</p><p><b>RESULTS</b>Compared with the control group, plasma total protein and albumin level significantly decreased in the fibrosis group (P < 0.01). Proliferating cell nuclear antigen (PCNA) index was 85%-95% in the fibrosis group. Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group (P < 0.01), while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group (-95%, P < 0.01; -19%, P < 0.05, respectively). PCNA index was 20%-30% in the hepatectomy group.</p><p><b>CONCLUSIONS</b>Autophagy is weakened after fibrosis and hepatectomy, although it differs between these two processes. Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.</p>

A pharmacodynamic study of intervals of Mitomycin C treatment on human bladder cancer cell line in vitro / 肿瘤研究与临床

Objective To study the relationship between the intervals of Mitomycin C treatment and cytotoxicity, apoptosis and drug resistance for bladder cancer cells.Methods The bladder transitional cell cancer line BIU-87 was treated for two hours every time for five times with intervals of 24, 48, 72 and 96 hours respectively.Cytotoxicity was measured by MTT.p53,bcl-2,Bax and p170 expression were analyzed by Western blot.Results The IC_(50)(?g/ml)were 4.41,0.71,2.83,4.51and 6.16 with treatment intervals of 24, 48, 72 and 96 hours respectively, p53 and bcl-2 were significantly down-regulated and bcl-2/Bax was re- duced at 24 hour treatment interval but not changed at 48,72 and 96 hour intervals,p170 was not detected at 24 hour treatment interval but increasingly expressed at 48,72 and 96 hours intervals.Conclusion The in- terval of Mitomycin C treatment is closely related with cytotoxieity and apoptosis and drug resistance of blad- der cancer cells.The intervals of intravesical instillations may play an important role in the effect of chemotherapy.

The current research status of genetics of sporadic clear renal cell carcinoma / 肿瘤研究与临床

The mechanism of the development of sporadic renal cell carcinomas is complicated,which is different from that of hereditary renal-cell carcinoma.Genetics abnormality such as loss of 3p,VHLgene mutations may help differentiate pathological subtype of renal cell carcinoma and some gene markers may be useful predictors for prognosis.The current status of genetic study in renal cell carcinomas is reviewed in this article.