[Diagnostic value of multiparametric MRI-based models in the assessment of extra-prostatic extension of prostate cancer].

Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.

[Value of clear cell likelihood score in differentiation between renal oncocytoma and clear cell renal cell carcinoma].

Objective: To evaluate the value of clear cell likelihood score (ccLS) in identifying renal oncocytoma (RO) and clear cell renal cell carcinoma (ccRCC). Methods: Retrospective data of pathologically confirmed 43 RO patients [24 men and 19 women, aged 22-77 (54±14) years] between February 2008 and September 2021 and 43 ccRCC patients [30 men and 13 women, aged 29-78 (56±12) years] between May and July 2021 were consecutively included in the department of radiology, Chinese PLA General Hospital. Two radiologists used ccLS to assess each case independently, and disagreements were resolved by consensus. The ability of ccLS to identify RO and ccRCC was examined by the receiver operating characteristic (ROC) curve which identified the best optimal diagnostic cut-off values, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Results: The mean tumor diameter was 3.8 cm in RO patients and 3.7 cm in ccRCC patients. Central scar and segmental enhancement inversion (SEI) were more frequently observed in the RO group compared to the ccRCC group [53.5% (23∶43) versus 11.6% (5∶43) and 41.9% (18∶43) versus 7.0% (3∶43), respectively], with statistical differences (P<0.001). The ccLS scores in the RO group ranged from 1 to 4, while 79.0% of the cases were 3. The ccLS scores in the ccRCC group ranged from 2 to 5, while 72% of the cases were 4. The scores of the two groups were statistically different (P<0.001). The ccLS showed the best performance when the threshold was 4 according to the ROC curve. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of ccLS for distinguishing RO from ccRCC were 83.7%, 90.7%, 87.2%, 90.0%, and 84.8%, respectively, and the area under the ROC curve value was 0.879. Conclusion: The ccLS has credible sensitivity and specificity in differentiating renal oncocytoma from clear cell carcinoma, which may be helpful for the preoperative diagnosis.

Risk factors for oxaliplatin-induced peripheral neuropathy: a systematic review and meta-analysis.

OBJECTIVE: Oxaliplatin-induced neuropathy is a significant complication of cancer therapy. We aimed at investigating the risk factors of oxaliplatin-induced neuropathy (OIPN) and providing evidence to enhance its prevention. MATERIALS AND METHODS: PubMed, Medline, Web of Science, Embase, China Knowledge Resource Integrated Database, and the Wanfang Database were searched comprehensively for observational studies investigating the prevalence and risk factors of OIPN from inception to November 30, 2021. The Newcastle-Ottawa Scale was used by two independent reviewers to assess methodological quality. When applicable, we used meta-analysis to determine mean differences and odds ratios for continuous and nominal scaled data. RESULTS: We included 20 studies involving 10,900 participants for analysis. Factors associated with OIPN risk identified by meta-analysis were age, gender, diabetes, anemia, hypomagnesaemia, alcohol consumption, body mass index, body surface area, cumulative oxaliplatin dose and the number of chemotherapy cycles. Factors not associated with OIPN risk included smoking history and chemotherapy regimen. CONCLUSIONS: This meta-analysis identified multiple variables associated with OIPN. The recognition of modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.

[Predictive value of left ventricular ejection fraction for the occurrence of postoperative myocardial infarction after coronary endarterectomy in patients with diffuse coronary artery disease].

Objective: To investigate the predictive value of ejection fraction for the postoperative myocardial infarction after coronary endarterectomy (CE) in patients with diffuse coronary artery disease (DCAD). Methods: Patients who underwent cardiac artery bypass graft (CABG) surgery and CE in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2020 were enrolled in this prospective observational study. Baseline features including age, sex and echocardiography parameters were obtained. Left ventricular ejection fraction(EF) was measured by echocardiography. The patients were divided into postoperative myocardial infarction (PMI) group and non-PMI group according to PMI occurrence. Linear regression analysis, logistic regression model, and receiver operating characteristic(ROC) curve were used to analyze the correlation between left ventricular ejection fraction and PMI and the influencing factors. Results: A total of 120 patients were enrolled in the study. There were 32 patients (27%) in the PMI group (male 27(84%), age (62±8)), inferior myocardial infarction occurred in 24 (75%) patients. There were 88 patients (73%) in the non-PMI group (male 70(80%), age (62±8)). EF (55% (49%, 64%) vs. 62% (55%, 67%), P=0.01) was significantly lower in the PMI group than in the non-PMI group. Perioperative TNI, IABP use and length of hospitalization were significantly higher in the PMI group than in the non-PMI group. Multivariate logistic regression showed that lower EF was an independent risk factor of PMI (OR=0.93, 95%CI: 0.89-0.98, P=0.01) after adjusting age, sex and body mass index. ROC curve analysis showed that EF<60% could sufficiently predict the occurrence of PMI (AUC= 0.67, sensitivity 64%, specificity 69%, P=0.01). Linear regression analysis showed that left ventricular end-diastolic diameter (OR=-0.52, 95%CI:-1.13-0.60, P<0.001), graft flow in left anterior descending (OR=-0.20, 95%CI:-0.15-0.01, P=0.02) and history of diabetes (OR=-0.28, 95%CI:-8.25-1.85, P=0.002) were negatively correlated with preoperative EF value. Conclusion: Lower preoperative EF is an independent risk factor for PMI after CABG and CE in DCAD patients, closely related to the left ventricular end-diastolic diameter, graft flow in left anterior descending artery and diabetes mellitus.

[Clinicopathological features of malignant mixed mesodermal tumor: analysis of 50 cases].

Objective: To investigate the clinicpathological, immunohistochemical and molecular genetic features of malignant mixed mesodermal tumor (MMMT) in the female reproductive system. Methods: To analyze its histopathological characteristics, we performed a retrospective review of the MMMT cases diagnosed at PLA General Hospital, Beijing, China during 2005-2019 using its surgical and pathological databases. EnVision immunohistochemical staining was used to detect the expression of ER, PR, p16, p53 and MMR proteins. Results: Fifty cases were conformed to the diagnosis, including 29 cases originated in the uterus, 16 cases in ovary, 4 cases of synchronous occurrence in uterus and ovary, 1 case in cervix. The tumor was histologically composed of two components, namely carcinoma and sarcoma ones, with clear borderline or blend mutually. The proportion of cancer component in the whole tumor ranged from 5%-90%. The proportion of carcinoma was more than 50% in 76% of the cases, and less than 50% in 24% of cases, including 2 cases with<10% of carcinoma. In the cases of primary uterine MMMT, the main carcinoma type was high grade endometrioid carcinoma (55%, 16/29). In ovarian MMMT, the main carcinoma type was serous carcinoma (12/16), while that of cervical MMMT was squamous cell carcinoma. The others were clear cell carcinoma or the undifferentiated carcinoma. There was one carcinoma type in most cases, only 7 cases had two carcinoma types. Homologous sarcomas, including stromal sarcoma, leiomyosarcoma and high-grade spindle cell sarcomas, were more commonly found in uterine MMMT (72.4%, 21/29). While heterogenic sarcomas, including chondrosarcoma, osteosarcoma and rhabdomyosarcoma, were more commonly noted in ovarian MMMT (12/16) than MMMT of other sites. There were 10 cases that consisted of two types of sarcomas. The synchronous MMMT of uterus and ovary had similar morphology and the types of carcinoma and sarcoma. The tumor cells that spread or metastasized to lymph node, omentum, intestinal wall or skin were all carcinoma cells, and were morphologically consistent with the original tumors. Immunohistochemically, ER and PR were both negative (23/25 in uterine, 8/10 in ovarian tumors). p16 was strongly positive (11/11 in uterine tumors, and 6/6 in ovarian tumors), with similar expression patterns in the carcinoma and sarcoma components. p53 showed mutant-type staining (64%, 21/33) and expressed synchronously in carcinoma and sarcoma components. p53 mutation was found in 35% cases of endometrial carcinoma and 46.7% cases of non-endometrial carcinoma. p53 mutation was also found in only 31.8% cases of heterogenic sarcomas, but in 50% of non-heterogenic sarcomas. Twenty-eight cases (28/33, 85%) presented intact mismatch repair proteins, while 5 cases (5/33, 15%) presented deficient mismatch repair proteins. Conclusions: MMMT in female reproductive system is a rare high-grade biphasic tumor with complex and diverse morphology. The immunohistochemical features are characterized by negative ER/PR and strongly positive p16, mostly mutant p53 and proficient mismatch repair proteins. The patients with a high FIGO stage have worse prognosis.

[Comparison of the clinicopathological features between adenoid basal cell carcinoma and adenoid cystic carcinoma of the cervix].

Objective: To compare the clinical and histopathological characteristics of cervical adenoid basal cell carcinoma and adenoid cystic carcinoma for improving the diagnosis accuracy and differential diagnosis of these tumors. Methods: A retrospective study was conducted on 9 cases of cervical adenoid basal cell carcinoma and 3 cases of adenoid cystic carcinoma which were diagnosed and consulted at the First Medical Center of PLA General Hospital from March 2009 to April 2019. Detailed clinical data were reviewed. All pathological sections and immunohistochemical results were reviewed and the clinicopathological characteristics were analyzed. Follow-up information by telephone was collected and relevant literature was consulted. Results: Both tumors were more commonly found in postmenopausal women (the age of onset ranged 43-74 years). Adenoid basal cell carcinoma was often clinical asymptomatic. Most of them presented as abnormal smears of the cervix during physical examination, and there was no definite mass in colposcopy.Adenoid cystic carcinoma was mostly presented with abnormal vaginal bleeding. A mass was seen in colposcopy.Histologically, the two tumors were characterized by nest-like growth of the tumors, consisting of basal-like tumor cells, and often surrounded by palisade structures. The two lesions might coexist, or be mixed with squamous cell carcinoma or high-grade squamous intraepithelial lesions. The difference was that adenoid basal cell carcinoma was mostly located at the junction of cervical squamous epithelium and columnar epithelium and beneath the overlying epithelium, the tumor cells were arranged in nests, with squamous differentiation in the center of the nests, or in double-layer adenoid arrangement. The cell morphology was bland with occasional mitoses, and the stromal reaction was not obvious. And adenoid cystic carcinoma cells in the nest arranged like a sieve, the homogenous red-stained and blue-stained secretions were observed in the sieve holes, with obvious cell atypia, frequent mitoses, and obvious stromal reaction.In one case of adenoid cystic carcinoma, sarcomatoid area presented around the nests.Both of them were positive in clinical HPV test. Among the 9 cases of adenoid basal cell carcinoma, 3 were tested for HPV and 5 were tested for p16, and all showed positive expression. Among the 3 cases of adenoid cystic carcinoma, 2 were tested for HPV and 3 were tested for p16, both of which showed positive expression. Telephone follow-up was conducted by June 2019(follow-up time ranged 2-37 months). No recurrence or metastasis occurred in 7 of the 9 cases of adenoid basal cell carcinoma, while 1 case had a ground-glass nodule in lung and another had recurrence of vaginal stump 32 months after the surgery.One case of adenoid cystic carcinoma developed lung metastasis 8 months after surgery and died 2 years after surgery; another case was followed up for 6 months, which showed no recurrence or metastasis; the third case was lost to follow-up. Conclusions: Both adenoid cystic carcinoma and adenoid basal cell carcinoma of the cervix are the tumors originating from cervical reserve cells and are associated with high-risk HPV infection. Due to the differences in clinical treatment and prognosis, careful histological evaluation and immunohistochemical analysis should be carried out to make accurate pathological diagnosis.

[Expression of ARID1A in ovarian seromucinous neoplasms and its clinicopathological significance].

Objective: To investigate the clinical, pathological and immunohistochemical features of seromucinous neoplasms, including seromucinous cystadenoma, borderline tumour and seromucinous carcinomas of the ovary. Methods: A retrospective review of the seromucinous neoplasms collected between June 2006 and December 2018 was conducted at the First Medical Center of PLA General Hospital. EnVision immunohistochemical staining was used to detect the expression of CK7, PAX8, ER, PR, WT1, p16, p53 and Baf250a which was encoded by the ARID1A gene. Results: A total of 75 ovarian seromucinous neoplasms were included. There were 30 cases of benign seromucinous cystadenoma, whose patients aged 12 to 83 years (mean, 36 years). The tumor histologically composed of endocervical-type mucinous epithelium and serous-type cells, each of which accounted for more than 10%. Among the 34 cases of seromucinous borderline tumour including 7 cases with concurrent endometriosis, the patients aged 21 to 72 years (mean, 39 years). Characteristic histologic features were broad papilla structure and an admixture of cell types, predominant endocervical-like mucinous cells (non-intestinal, no goblet cells), eosinophilic cells and others such as clear cells, hobnail cells, ciliated cells, and endometrioid cells. The larger papillae tended to have oedematous stroma containing neutrophils. In the 11 cases of seromucinous carcinomas including 2 cases with concurrent endometriosis, patients aged 26 to 61 years (mean, 40 years). Seromucinous carcinomas exhibited a predominant papillary architecture with smaller components of confluent glandular, microglandular and solid structure, expansive stromal invasion pattern, and sometimes locally destructive infiltration. An admixture of epithelial cell types was in seromucinous carcinomas, as well as borderline tumour. Immunohistochemically, the tumours were positive for CK7, PAX8, p16, estrogen receptor and progesterone receptor (positive in 10% to 80% of the cases). They were negative for WT1, while p53 staining showed a "wild-type" pattern. The Ki-67 positive rate was 20% to 60%. Loss of ARID1A-encoded protein Baf250a staining was observed in 6 (30%) of the 20 seromucinous borderline tumors, and 2 of the 11 seromucinous carcinomas. According to FIGO 2014 staging system, there were 4 cases of ⅠA, 3 cases of ⅡA and 4 cases of ⅢC. Follow-up information was available in 9 patients of seromucinous carcinomas, and 2 lost to follow-up. Eight were alive (follow-up for 6 to 108 months), including 2 patients with relapse, but 1 patient who initially presented with a stage ⅢC tumor died of disease 60 months after the cancer diagnosis. Thirty-four patients of borderline tumour were all alive at the end of follow-up, including 1 with relapse. Conclusions: Seromucinous neoplasms have characteristic histopathological and immunopathological features. Both borderline tumors and carcinomas have complex structures and cellular components. ARID1A as a tumor-suppressor gene plays a role in the oncogenesis of ovarian seromucinous neoplasms. The loss of staining with ARID1A-encoded Baf250a and wild-type p53 in seromucinous neoplasms together support that seromucinous neoplasms could be type Ⅰ tumor of dualistic model of epithelial ovarian cancer, with favourable prognosis.

[Clinicopathological analysis of cervical basaloid squamous cell carcinoma].

Objective: To investigate the clinical and histopathological features of cervical basal squamous cell carcinoma (BSCC). Methods: A retrospective analysis of 10 cases of cervical BSCC was carried out. The clinical data and all the pathological sections were reviewed, the related immunohistochemical results were statistically analyzed, the clinicopathological features were analyzed, and then followed the prognosis. Results: (1) Clinical features: the median onset age of BSCC in cervix was 51 years old (ranged 35-69 years old), 5 of them were postmenopausal women. Vaginal bleeding was often seen in clinic (7 cases). Of the 10 cervical BSCC patients, 5 tested HPV types. All of them were HPV positive, including 2 cases of HPV 16 positive and 1 case of high-risk HPV positive. At the time of colposcopy, 3 cases showed exogenous nodular mass, 3 cases showed endogenous infiltrating mass, and 4 cases had unclear type of mass.(2)Treatment: of the 10 patients, 8 underwent hysterectomy+bilateral adnexal excision+pelvic lymphadenectomy, of which 6 underwent radiotherapy or chemotherapy after operation.Radiotherapy and chemotherapy were performed only in 2 cases. (3) Pathological features: histologically, the tumor cells were nests and stripe like growth, which were composed of basal like tumor cells. The cells had obvious heteromorphosis, less cytoplasm, deep dyed nuclei and common nuclear mitosis, and there were often palisade like structures around the cell nests, and some cells in the center of the cell nests were found to have acne like necrosis. It could be mixed with normal squamous cell carcinoma and squamous epithelial lesion. Among the 10 patients, 6 had immunohistochemical results. BSCC mainly expressed p16 and squamous cell markers such as p63, cytokeratin (CK) 5/6 and p40 protein, the positive expression rates were 3/3, 3/3, 2/2 and 3/3, respectively. A few expressed CK7 protein, and the positive expression rate was 1/3. (4) Prognosis: follow-up time ranged from 1 week to 64 months, and 2 cases were lost to follow-up. Among the 8 follow-up patients, 3 had iliac bone, lung or skin metastasis, and 5 had no recurrence or metastasis during the follow-up period. Conclusions: BSCC of cervix is a rare malignant tumor of cervix associated with high-risk HPV infection, p16 is more positive. The treatment is similar to that of normal cervical squamous cell carcinoma. Surgical resection and radiotherapy and chemotherapy are the most effective methods according to the clinical stage. At present, the disease is considered to be highly aggressive and the poor prognosis.

[Clinicopathologic characterisitics of pancreatic acinar cell carcinomas].

Objective: To investigate clinical, pathological and immunohistochemical features of pancreatic acinar cell carcinoma. Methods: A retrospective review of surgical and pathological databases between 2011 and 2016 at PLA General Hospital was collected and 14 cases of acinar cell carcinoma (ACC) of the pancreas were identified. EnVision immunohistochemistry was used to detect the expression of Trypsin, bcl-10 and cytokeratin(CK) proteins. Results: The patients included nine cases of pure ACC, 3 cases of mixed acinar ductal carcinoma, 1 case of mixed acinar-neuroendocrine carcinoma and acinar-ductal-neuroendocrine carcinoma, respectively. Tumors involved different anatomic locations of the pancreas, including eight involving the head of pancreas, four in the body and tail, one in the uncinate process and one in a heterotopic pancreas. Two patients had lymph node and liver metastases before surgery. Microscopically, the tumor was hypercellular with less fibroblastic proliferation and tumor cells arranged in acinar or solid pattern. The well differentiated tumor cells showed eosinophilic, granular cytoplasm with single prominent nucleoli, while the poorly differentiated tumor cells tended to grow in solid sheets. Immunohistochemically, the tumor cells were positive for pan-cytokeratin (14/14), Trypsin (12/14) and bcl-10 (11/14). Stains for CK7 and CK19 were negative (11/14 and 3/4). According to the pTNM staging, there were 7 cases at stageⅠ, 3 at stage ⅡA, 3 at stage Ⅲ and 1 at stage Ⅳ. With average postoperative follow-up of 6-58 months, the median disease-free survival time was 16 months. Conclusions: Pancreatic acinar cell carcinoma is a rare and relatively indolent malignant tumor with characteristic histopathological and immunohistochemical features. Accurate pathological diagnosis plays an important role in patients' treatment and evaluation of prognosis.

Human papillomavirus type 16 E6 gene variations in Chinese population.

OBJECTIVE: To identify genetic variants in the E6 gene of HPV 16 and to examine the association between these variants and cervical cancer development. METHODS: Cervical samples were collected from 72 patients with cervical cancer and 72 age-matched control subjects, all from Hubei Province, China. HPV 16 sequence was detected with E6 gene-specific polymerase chain reaction, and variants were identified by DNA sequencing. RESULTS: HPV 16 was detected in 81% of the patients and 43% of control subjects, respectively. The rank orders of incidence of HPV 16 prototype and E6 variants were as follows: D25E (62%), the prototype (17%), E113D (9%), L83V (6%) in case subjects; the prototype (71%), D25E (23%), L83V/E113D (7%) in control subjects. The odds ratio of HPV 16 E6 variant was higher than that of prototype (RR=11.73, 95% CI=4.18-32.94, P=0.0001). CONCLUSION: The D25 E variant is the most prevalent E6 genomic variant in Hubei, China. The presence of HPV 16 E6 variant in cervical intraepithelial neoplasia (CIN) lesions may serve as a useful predictor of clinical outcome of the disease.

Risk factors for cervical cancer in China: a case-control study.

OBJECTIVES: To determine the prevalence of human papillomavirus types and investigate the risk factors for cervical cancer in Hubei, China. METHODS: We conducted a case-control study to investigate risk factors. RESULTS: HPV DNA was detected in 94.55% of patients with cervical carcinoma, and 23.64% of control subjects. The most common HPV type in cervical cancer was HPV type 16 (81.82%), followed by HPV 58 (6.36%). HPV infected patients have a higher risk of developing cervical carcinoma, which is 75.79 times more than non-infected people. The other risks were age at first intercourse (p = 0.017) and number of live births (p = 0.032). A history of previous cytologic screening was associated with a substantial reduction in risk (p = 0.001). CONCLUSIONS: The three principal reasons that Hubei has a high rate of women developing cervical carcinoma are HPV infection, age at first sexual intercourse and number of live births. Cervical cytology screening provides efficacious protection.