Peritumoural MRI radiomics signature of brain metastases can predict epidermal growth factor receptor mutation status in lung adenocarcinoma.

AIM: To investigate whether magnetic resonance imaging (MRI) radiomics features of brain metastases (BMs) can predict epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. MATERIALS AND METHODS: Between June 2014 and December 2022, 58 histopathologically confirmed lung adenocarcinoma patients (27 with EGFR wild-type, 31 with EGFR mutation) who underwent gadobenate dimeglumine-enhanced brain MRI were recruited retrospectively. A total of 123 metastatic brain lesions were allocated randomly into the training cohort (n=86) and test cohort (n=37) at a ratio of 7:3. Radiomics models based on multi-sequence MRI images in different regions such as volume of interest (VOI)enhancing tumour, VOIwholetumour, VOIperitumour 1mm, VOIperitumour 3mm, and VOIperitumour 5mm were built. The optimal radiomics model was integrated into the clinical or radiological indicators to construct a fusion model through multivariable logistic regression analysis. RESULTS: The optimal radiomics model based on the VOIperitumour 1mm, a combination of nine features selected from the fluid-attenuated inversion recovery (FLAIR) sequence, yielded areas under the curves (AUCs) of >0.75 in the training and test cohorts. The prediction of the fusion model with integration of clinical factors (age) and radiomics score (the optimal radiomics model) was not better than that of the optimal radiomics model alone in the test cohort (AUC: 0.808 and 0.785, respectively, p=0.525). CONCLUSION: The FLAIR radiomics model based on VOIperitumour 1mm as an effective biomarker helps predict EGFR mutation status in lung adenocarcinoma patients with BMs and then assists clinicians in selecting optimal treatment strategies.

[Anti-inflammatory mechanism of Balanophora involucrata: a network pharmacology and molecular docking-based analysis and verification in lipopolysaccharide-induced RAW264.7 cells].

OBJECTIVE: To investigate the main chemical constituents of Balanophora involucrata and the mechanism of its antiinflammatory effect based on network pharmacology and molecular docking technology. METHODS: Literature reports, Materia Medica, GeneCards and other databases were searched for anti-inflammatory compounds and their targets. String database and Cytoscape 3.7.2 software were used to obtain the protein-protein interaction (PPI) network and the drug-active ingredienttargets network and for GO and KEGG enrichment analyses. Molecular docking was performed using Auto Dock Tools 1.5.6. In an inflammatory RAW264.7 cell model induced by lipopolysaccharide (LPS), the effect of 25, 50, 100, 200 µg/mL Balanophora involucrata extract was tested on the production of inflammatory cytokines and phosphorylation level of PI3K and Akt using ELISA and Western blotting. RESULTS: A total of 318 common targets of drugs and diseases were identified, and the core targets were Src, HSP90AA1 and PIK3CA, involving cancer, PI3K/Akt, MAPK and other signaling pathways as shown by KEGG analysis. Molecular docking showed that both the main active constituents of Balanophora involucrata could spontaneously bind to the core targets. In the inflammatory cell model, treatment with Balanophora involucrata extract significantly inhibited the production of IL-1ß at the concentrations of 100 and 200 µg/mL, reduced IL-6 and TNF-α expressions at the concentrations of 50, 100, and 200 µg/mL, and lowered phosphorylation levels of PI3K and Akt proteins at the concentrations of 25, 50, 100, and 200 µg/mL (all P < 0.05). CONCLUSIONS: The anti-inflammatory mechanism of Balanophora involucrata involves multiple targets and multiple pathways, and its effect is mediated possibly by reducing IL-1ß, IL-6 and TNF-α production and inhibiting phosphorylation levels of PI3K and Akt proteins to suppress the activation of the PI3K/Akt signaling pathway.

[Ovarian Sertoli-Leydig cell tumors: DICER1 hotspot mutations and associated clinicopathological features].

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age (P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

[Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis].

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

[Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features].

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion: BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.

[Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma].

Objective: To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement. Methods: Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed. Results: All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year. Conclusion: BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.

[Clinicopathologic analysis of primary carcinoid of the ovary].

Objective: To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors. Methods: A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017. Results: The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival. Conclusions: Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.

[Impacts of different methods in laryngeal mask airway positioning on the airway management of elderly patients with general anesthesia].

Objective: By observing the clinical effect of ultrasound, fiberoptic bronchoscopy and traditional standard in positioning the general anesthesia of laryngeal mask ventilation in elderly patients, the superiority of laryngeal mask positioning with visualization technique of ultrasound and fiberoptic bronchoscope on airway management in elderly patients with general anesthesia was analyzed. Methods: One hundred and twenty cases of elderly patients with general anesthesia of laryngeal mask ventilation from the People's Hospital of Yuyao city from October 2016 to October 2017 were selected and randomly divided into 3 groups(n=40)according to American Society of Anesthesiologists (ASA) grading criteria Ⅰ-Ⅲ. Group A: traditional standard positioning laryngeal mask group. Group B: fiberoptic bronchoscope positioning laryngeal mask group. Group C: ultrasound positioning laryngeal mask group. The general information of sex ratio of male and female, mass, and height, and operation type, operation duration, anaesthesia duration, and modified Mallampati grade were observed and compared among the three groups. The number of successful laryngeal mask ventilation after laryngeal mask placement in 3 groups was observed, the laryngeal mask placement time (T(0)) and the normal ventilation time after adjustment (T(1)) in each group were recorded, and the first success rate of laryngeal mask placement, the success rate after adjusting the positioning, and the success rate of re-placement were calculated. Moreover, the mean peak airway pressure at 5 min after operation, the minimum intrathecal injection gas for minimum ventilation (V(min)), the minimum laryngeal mask intravesical pressure (ICP(min)), and the lowest air pressure for oral and pharyngeal leakage (OLP(min)) were recorded. The airway seal pressure (OLP(60)) and the volume of gas injection (V(60)) when the intravesical pressure was 60 cmH(2)O (1 cmH(2)O=0.098 kPa) were used to record the incidence of postoperative laryngeal mask bleeding, cough, nausea and vomiting, and the incidence of pharyngalgia, odynophagia, hoarseness and other related complications after 24 hours of the operation. Results: There was no significant difference in general information, airway evaluation and anesthesia operation among the three groups (all P>0.05). The incidence of intraoperative laryngeal mask bleeding in group B and C was 7.9% and 2.6% respectively, the incidence of odynophagia at 24 hours after operation was 5.3% and 0 respectively, and the incidence of pharyngalgia and hoarseness was 18.4% and 7.9% respectively, less than that in group A (24.2%, 12.1% and 36.3%). The difference was statistically significant (χ(2)=8.900, 6.880, 9.000, P<0.05). The success rate of adjustment and positioning after the placement of laryngeal mask was 84.2% and 94.7% respectively in group B and C, higher than that in group A of 72.7%, and the difference was statistically significant (χ(2)=6.500, P<0.05). The lowest laryngeal mask intralaryngeal pressure for ventilation in group B and C was (35.39±4.67) cmH(2)O and (32.61±3.22) cmH(2)O, lower than that in group A of (39.30 ± 5.93) cmH(2)O, the intralaryngeal pressure was 60 cmH(2)O, and the airway seal pressure was (25.82±4.48) cmH(2)O and (28.34±6.99) cmH(2)O, higher than that in group A of (22.45±4.98) cmH(2)O, which was significantly different (F=18.200, 9.720, P<0.05). Conclusions: In elderly patients with general anesthesia, it is feasible to manage the airway by ultrasound or fiberoptic bronchoscopy with laryngeal mask. Ultrasound positioning laryngeal mask improves the accuracy of the intraoperative ventilation, and reduces the incidence of postoperative airway related complications.

[Clinicopathologic study of infiltrating epitheliosis of the breast].

Objective: To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods: Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer. Results: The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc. Conclusions: Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.

[Values of JAZF1 gene rearrangement detected by fluorescence in-situ hybridization in diagnosis of endometrial stromal tumours].

Objective: To investigate the role of JAZF1 gene rearrangement in the diagnosis and differential diagnosis of endometrial stromal sarcomas by fluorescence in situ hybridization (FISH). Methods: JAZF1 gene rearrangement was analyzed by FISH in 129 cases of ESS diagnosed from January 2008 to December 2016 including 105 cases of low-grade endometrial stromal sarcoma (LG-ESS), 21 cases of high-grade endometrial stromal sarcoma (HG-ESS) and 3 cases of undifferentiated uterine sarcoma (UUS). Sixteen cases of the related tumours in uterus were also collected as control group. The results were compared with our previous studies of JAZF1/JJAZ1 fusion gene in ESS by RT-PCR. Results: Detection of JAZF1 gene rearrangement by FISH was successfully analyzed in 144 cases. JAZF1 gene alteration was detected in 63 cases, all of which were LG-ESS, with an overall positivity of 60.6% (63/104), while no JAZF1 gene rearrangement was found in all other cases. JAZF1 gene rearrangement was present in LG-ESS with classic histology (69.3%, 52/75), smooth muscle differentiation (2/10), sex cord-like differentiation (4/5), fibromyxoid change (1/5), clear cell change (0/1), skeletal muscle differentiation (0/1), and schwannoma-like palisading pattern (0/1). The different components in all the cases of LG-ESS with variant histology had the clonal origin, with or without JAZF1 gene alteration. Compared to the results of JAZF1/JJAZ1 fusion gene by RT-PCR, the positive rate of JAZF1 gene rearrangement in LG-ESS by FISH (61.9%, 26/42) was significantly higher than that of RT-PCR (30.0%, 12/40; P<0.01). Conclusions: JAZF1 gene rearrangement is present only in LG-ESS, but not in HG-ESS, UUS or other related tumours in uterus. The frequency of JAZF1 gene rearrangement varies between classic LG-ESS and different morphologic variants. It is frequently, but not consistently, present in classic LG-ESS and less often positive in variant cases. The results of JAZF1 gene alterations in LG-ESS with different morphologic variants support the contention that the endometrial stromal and their variant morphologic components have the same clonal origin. Detection of JAZF1 gene rearrangement by FISH is very useful for the diagnosis and differential diagnosis of ESS.

[Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma].

Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions: AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma].

Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. Results: The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, P<0.05 for HER2; and 4 months vs 10 months, P<0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2; and 13 months vs 43 months, P<0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion: HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

[Expression of DNA mismatch repair protein in endometrial carcinomas and its correlation with clinicopathologic features].

OBJECTIVE: To study the expression of mismatch repair protein in a series of endometrial carcinomas and its correlation with clinicopathologic features. METHODS: The clinical data of 150 consecutive cases of endometrial carcinoma were collected during the period from December, 2014 to August, 2015 in Fudan University Cancer Center. Morphologic features including tumor infiltrating lymphocytes (TIL), peritumoral lymphocytes and tumor heterogeneity were reviewed. Immunohistochemistry for expression of mismatch repair proteins was performed. The correlation with clinicopathologic features was analyzed. RESULTS: Loss of mismatch repair protein expression was observed in 43 cases (28.7%), including loss of MLH1/PMS2 in 27 cases (18%), loss of MSH2/MSH6 in 7 cases (4.7%), loss of MSH6 in 6 cases (4%) and loss of PMS2 in 3 cases (2%). There were 23.3% and 27.1% of mismatch repair protein-deficient endometrial carcinomas in women under and above 50 years of age, respectively, which was not statistically significant. Amongst the 12 cases with family history of tumors, 4 of the 6 mismatch repair protein-deficient cases were under 50 years of age, which was higher than that in the 6 cases with mismatch repair protein expression (P=0.014). The mismatch repair protein-deficient group showed significantly more prominent TIL and peritumoral lymphocytes than protein-expression group (P=0.033 and <0.001). Moreover, there were also significant differences in depth of myometrial invasion and occurrence of synchronous malignancy (2 cases of ovarian clear cell carcinoma and 1 case of colonic carcinoma) between the two groups (P=0.039 and 0.022). However, there were no significant differences in lymph node metastasis, tumor heterogeneity, lower uterine segment involvement and tumor stage between the two groups. CONCLUSIONS: Prominent TIL and peritumoral lymphocytes characteristically occur in mismatch repair protein-deficient endometrial carcinomas. Patient age does not significantly correlate with the loss of mismatch repair protein expression, but individuals under 50 years of age are more likely to have no expression if there is family history of tumors.

[Endometrial stromal sarcoma: morphologic features and detection of JAZF1-SUZ12 and YWHAE FAM22 fusion genes].

OBJECTIVE: To study the morphologic features, immunophenotype and significance of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in endometrial stromal sarcoma (ESS). METHODS: Fifty-three cases of ESS were retrieved and the pathologic features were reviewed. Immunohistochemical study for estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon were carried out using tissue microarray technology. Reverse transcription-polymerase chain reaction (RT-PCR) was applied for detection of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in 47 cases of ESS and 12 cases of other spindle cell neoplasia in uterus (including 2 cases of undifferentiated sarcoma, 3 cases of leiomyosarcoma, 3 cases of leiomyoma, 4 cases of adenosarcoma and 2 cases of uterine tumor resembling ovarian sex cord tumor). RESULTS: The 53 cases of ESS studied included 43 cases of low-grade ESS and 10 cases of high-grade ESS. As for low-grade ESS, in addition to the classic morphologic features, smooth muscle differentiation was present in 7 cases (16.3%), sex cord-like differentiation in 2 cases (4.7%), rhabdoid differentiation in 1 case (2.3%), clear cell changes in 1 case (2.3%) and schwannoma-like palisading pattern in 1 case (2.3%). As for high-grade ESS, sex cord-like differentiation (1 case), mucinous microcystic changes (1 case) and focal clear cell changes (1 case) were also observed. The expression rate of estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon was 86.0%, 81.4%, 74.4%, 2.3%, 23.3%, 23.3% and 4.7% in low-grade ESS, respectively, and was 1/10, 6/10, 6/10, 7/10, 1/10, 1/10 and 0 in high-grade ESS, respectively. RNA extraction was successful in 47 cases of ESS, including 39 cases of low-grade ESS and 8 cases of high-grade ESS. The positive rate of JAZF1-SUZ12 fusion gene was 30.8% (12/39) in low-grade ESS. The positive rate of YWHAE-FAM22 fusion gene was 12.5% (1/8) in high-grade ESS. The 14 control cases were all negative for JAZF1-SUZ12 and YWHAE-FAM22 fusion genes. CONCLUSIONS: As uncommon pathologic pattern may occur in both low-grade ESS and high-grade ESS, detection of JAZF1-SUZ1 and YWHAE-FAM22 fusion genes by RT-PCR would be helpful in diagnosis and differential diagnosis of ESS, especially for those tumors which lack typical morphologic features.

Mutations in WT1 in boys with sporadic isolated steroid-resistant nephrotic syndrome.

Mutations in the Wilms' tumor gene, WT1, can lead to syndromic steroid-resistant nephrotic syndrome and isolated steroid-resistant nephrotic syndrome. WT1 mutations have been identified in the majority of children with Denys-Drash or Frasier syndrome. WT1 mutations have not previously been identified in boys with sporadic isolated steroid-resistant nephrotic syndrome, but, recently, four boys with isolated nephrotic syndrome were identified to have WT1 mutations. However, whether boys with sporadic isolated steroid-resistant nephrotic syndrome should be routinely subjected to mutation analysis of WT1 has not been established. We examined 35 boys with sporadic isolated steroid-resistant nephrotic syndrome for mutations in WT1. Mutation analysis of all 10 exons of WT1 was performed by polymerase chain reaction and direct sequencing. Karyotype analysis or Y chromosome identification was performed for all patients. A Y chromosome or a 46, XY karyotype was demonstrated for all 35 patients. No causative WT1 mutation was identified in any of the patients. The WT1 mutation, IVS4+14T>C, which is not predicted to affect splicing, was identified in one patient who achieved complete remission after 8 weeks of oral prednisone treatment, indicating that IVS4+14T>C is not a causative mutation. Five WT1 polymorphisms were also identified in some patients and controls. Our results suggest that mutation analysis of WT1 should not be routinely performed for genetically defined boys with sporadic isolated steroid-resistant nephrotic syndrome.

Retrospective analysis of early outcomes after a single-armed suture technique for microsurgical intussusception vasoepididymostomy.

Longitudinal intussusception microsurgical vasoepididymostomy (LIVE) increases the patency rate in men with epididymal obstructive azoospermia (EOA). Here, we retrospectively analyzed the early outcomes of our modified single-armed suture technique for LIVE in men with EOA. From February 2012 to November 2013, 51 men received the modified technique and 39 men provided at least one post-operative semen sample. The mean age was 31.4 years old for the men and 29.2 years old for their female partners. The mean duration of obstruction was 34.3 months. Patency was noted in 24 (61.5%) men and pregnancy was reported in 15 (38.5%) female partners. Motile spermatozoa in the epididymal fluid were observed intraoperatively in 14 (58.3%) patent men and 3 (20%) non-patent men, respectively (p < 0.05). In the patent cohort, the mean ages of the pregnant and non-pregnant female partners were 26.5 and 32.7 years old, respectively (p < 0.05). Our modified technique resulted in favorable patency and pregnancy rates in this study. Sperm motility in epididymal fluid and female partner age were important factors associated with the patency and pregnancy rates.

Gas purification by nonthermal plasma: a case study of ethylene.

The destruction of ethylene in a dielectric barrier discharge plasma is investigated by the combination of kinetic modeling and experiments, as a case study for plasma-based gas purification. The influence of the specific energy deposition on the removal efficiency and the selectivity toward CO and CO2 is studied for different concentrations of ethylene. The model allows the identification of the destruction pathway in dry and humid air. The latter is found to be mainly initiated by metastable N2 molecules, but the further destruction steps are dominated by O atoms and OH radicals. Upon increasing air humidity, the removal efficiency drops by ± 15% (from 85% to 70%), but the selectivity toward CO and CO2 stays more or less constant at 60% and 22%, respectively. Beside CO and CO2, we also identified acetylene, formaldehyde, and water as byproducts of the destruction process, with concentrations of 1606 ppm, 15033 ppm, and 185 ppm in humid air (with 20% RH), respectively. Finally, we investigated the byproducts generated by the humid air discharge itself, which are the greenhouse gases O3, N2O, and the toxic gas NO2.

Laparoscopic excision of a large prostatic utricle revealed by haematuria: 1-year follow-up.

Prostatic utricles revealed by the presentation of haematuria are very rare. Only limited experience with laparoscopic surgery of prostatic utricle has been reported to date. Herein we report a 20-year-old male with frequently terminal haematuria and oligozoospermia who underwent successful laparoscopic excision of a large prostatic utricle. Haematuria disappeared and semen quality improved during 1-year follow-up.