[Primary mucinous gland lesions of fallopian tube: a clinicopathological analysis of fourteen cases].

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.

[Clinicopathological analysis of primary gastric (gastrointestinal)-type mucoglandular lesion of endometrium].

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.

[Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix].

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Association between depression subtypes and response to repeated-dose intravenous ketamine.

OBJECTIVE: About half or more of treatment-resistant depressed patients do not respond to ketamine, and few clinical predictors to gauge the most likely antidepressant response have been proposed. We explored whether depression subtypes are associated with response to ketamine. METHOD: Ninety-seven participants with depression were administered six repeated-dose intravenous ketamine and assessed for depression (Montgomery-Åsberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAMA), and suicidal ideation (Beck Scale for Suicidal Ideation, SSI) at baseline, 24 h after each infusion, and 2 weeks after the whole treatment. Participants were classified by melancholic/anxious subtype. Individuals who met criteria for neither or both subtypes were classified separately, resulting in four mutually exclusive groups. RESULTS: Patients with melancholic or melancholic-anxious features were less likely to respond (e.g., day 13, melancholic-anxious vs. anxious, OR 0.138, 95% CI 0.032-0.584, P = 0.007) or remit (e.g., day 26, melancholic vs. no subtype, OR 0.182, 95% CI 0.035-0.960, P = 0.045) and took longer to achieve response/remission than those with anxious or no subtype features. Faster HAMA score reductions were observed in patients with anxious or melancholic-anxious features, and faster SSI score reductions were observed among those with melancholic-anxious features. CONCLUSION: Our study shows promising results for ketamine as a novel antidepressant preferentially for the treatment of non-melancholic or anxious depression.

[Combining relative alpha variability and electroencephalogram reactivity to predict the prognosis of hypoxic-ischemic encephalopathy in adult patients].

Objective: To evaluate the role of combining relative alpha variability and electroencephalogram (EEG) reactivity to predict the prognosis of hypoxic-ischemic encephalopathy(HIE) in adult patients. Methods: A total of 28 adult patients with HIE admitted to general intensive care unit at Xiangya Hospital in Central South University were enrolled in this observational study from January2016 to April 2017. These patients with body temperature over 35℃ after 72-hour admission could be continuously monitored at least 12 hours byEEG.At the same time,each patient was assessed for EEG reactivity.Then we analyzed the correlation between EEG reactivity, relative alpha variability and clinical prognosis. Results: EEG reactivity was elicited in 15/28 patients, among whom 12 patients had a good outcome. While in the other 13 patients, EEG reactivity was not elicited, among whom only 3 patients had a good outcome. As to the results ofrelative alpha variability,11/13 patients with degree 3-4were of good prognosis; while only 3/15 patients with degree 1-2 were of good prognosis. Glasgow coma scale(GCS), EEG reactivity, and relative alpha variability were correlated with clinical outcome(χ(2)=5.073,9.073,-3.626, respectively,all P<0.05). The sensitivity of GCS, EEG reactivity, and relative alpha variability to predict the poor prognosis were 69.2%, 76.9%, 84.6%, respectively. The specificity were 73.3%, 80.0%, 73.3%, respectively. The consistency rates were 71.4%, 78.6%, 78.6%, respectively. The positive predictive values were 69.2%, 76.9%, 73.3%, respectively. The negative predictive values were 73.3%, 80.0%, 84.6%, respectively. More importantly, the accuracy of the relative alpha variability combined with EEG reactivity for the prediction of poor prognosis was much higher with the positive predictive value of 90.0%,the specificity of 93.3%, the sensitivity of 69.2%, the consistency rate of 82.1%,and the negative predictive values of 77.8%. Conclusions: The combination of relative alpha variability and EEG reactivityis reliable to predict clinical outcome of patients with HIE.

[Relationship between various histological status of margins of LEEP and residual HSIL or worse at hysterectomy following conization].

Objective: To investigate the relationship between various loop electrosurgical excision procedure (LEEP) margin status and residual high grade squamous intraepithelial lesion (HSIL) or worse at hysterectomy following conization. Methods: The relevant clinicopathological data were collected in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2014 to Dec. 2015, including 947 cases who underwent hysterectomy within 6 months of LEEP. The residual HSIL or worse at hysterectomy were analyzed among the groups. (1) Clear margins, involved margins, and without 1 mm negative margins. (2) Only one positive margin, two positive margins and three positive margins. (3) A positive margin of internal ostium of cervix, of external ostium of cervix and of the basement. Results: (1) The histological evaluation of the uterine specimens showed residual HSIL or worse in 234 cases (24.7%, 234/947). The proportion of residual lesions was 7.3% (21/286) in population with clear margins, 33.2% (211/635) with involved margins, 7.7% (2/26) without 1 mm negative margins, respectively. The positive margins group had significant difference at the aspect of residual rate in contrast to the negative margins group and the without 1 mm negative margins group (P<0.01). Further studies conclusively showed that the proportion of residual lesions was very similar between the negative margins group and the without 1 mm negative margins group (P>0.05). (2) The involved margins were interpretable in 621 cases. This was detected in 25.3% (111/438) patients with only one positive margin, 47.4% (74/156) with two positive margins and 77.8% (21/27) among three positive margins, respectively (P<0.01). (3) Furthermore, there were 418 cases only one positive margin was definite, and the proportion of residual lesions was 31.0% (62/200) in population with a positive margin of internal ostium of cervix, 18.2% (31/170) of external ostium of cervix and 33.3% (16/48) of the basement. The residual rates were higher in the endocervical and basal margin groups than that in the ectocervical margin group, and the differences were significant (P<0.05). Conclusions: The risk of residual HSIL or worse is significantly greater with involved margins at hysterectomy following LEEP. Both the positive endocervical and basal margin are excellent predictors of residual diseases, while the without 1 mm negative margin may be not. Clinicians should avoid treating it as positive margin and prevent overtreatment.

[The mediating role of psychological resilience to childhood abuse and binge eating among middle school students].

To explore the mediating role of psychological resilience to childhood abuse and binge eating. This study assessed the childhood abuse, binge eating and psychological resilience of 3 453 middle school students in Harbin city, Heilongjiang Province. SPSS PROCESS macro program, combined with Bootstrap method, was employed to explore the mediating effect of psychological resilience. The incidence of middle school students experiencing at least one type of abuse in their childhood was 81.3% (2 807/3 453). Childhood abuse, psychological resilience and binge eating were all significantly different in terms of gender, household registration and whether they were only child (all P values<0.05). There was a significant positive correlation between childhood abuse and binge eating. Psychological resilience was negatively associated with childhood abuse and binge eating. Childhood abuse could not only directly predict the binge eating behavior of adolescents, but also could indirectly affect it via psychological resilience.

[Clinical characteristics of human adenovirus type 7 pneumonia and genetic characteristics of human adenovirus type 7].

Objective: To better understand the clinical features of human adenovirus type 7 (hAdV7) pneumonia and to identify whether there is a variation in the genome of the strain (CHN/BeiJing/2018) isolated during the small-scale epidemic. Method: Forty-two patients were diagnosed with hAdV7 pneumonia between October 27th, 2017 and February 28th, 2018. They were all males with an average age of (21±2) years. Demographic and clinical data were reviewed and analyzed in detail. The nucleic acid of the epidemic strain was extracted from a bronchoalveolar lavage fluid sample. Whole genome sequencing (WGS) was then performed and sequences were compared with other hAdV7 strains distributed globally. Phylogenetic tree analysis was conducted based on whole genome sequences of the epidemic strain. Results: Thirty-eight cases with hAdV7 pneumonia presented with influenza-like symptoms (90.5%) at the onset and 36 cases developed fever (85.7%), followed by cough (97.6%), expectoration (90.5%) and chest pain (28.6%). Five cases presented with tonsillitis(11.9%) and 4 had transient hemoptysis (9.5%), while 3 patients reported dyspnea (7.1%). Moist rales were only heard in 3 patients (7.1%). Notably elevated creatine kinase (CK) concentrations were observed in 8 patients (19.1%), but all returned to normal after treatment. Four cases developed hypoxemia (9.5%), but none of them progressed to respiratory failure or acute respiratory distress syndrome (ARDS). Chest CT imaging showed bilateral patchy parenchymal opacities with a random distribution with or without consolidation. Ten patients were co-infected with influenza virus (23.8%), while 32 patients developed atypical pneumonia (76.2%). Genomic analysis revealed that the strain isolated during this epidemic was 99% similar to the known hAdV7 strains (19BOVLB/Volgograd/Rus/2014 and 0901HZ/ShX/CHN/2009). Phylogenetic tree analysis suggested that the strain was closely related to the hAdV7 strain isolated in Jingmen China in 2012. Conclusions: Cases with hAdV7 pneumonia were generally mild. Symptomatic treatment was sufficient for a favorable prognosis. A good genome stability of the hAdV7 strain was observed, indicating that hAdV7 could remain stable for a long period and cause continuing sporadic cases and clusters.

Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients.

Using approved methods, circulating tumor cells (CTCs) are only isolated from blood in 30%-50% of metastatic colorectal cancer (mCRC) patients. We previously validated a technique to isolate circulating tumor cells (CTCs) in a cohort of mCRC patients by combining immunomagnetic enrichment of EpCAM+/CD45- cells with qRT-PCR amplification of CK20 and survivin expression. Here, we examined the prognostic utility of CTC epithelial-mesenchymal transition (EMT) and stem cell gene expression. An 8 ml blood sample was collected from 78 consecutive mCRC patients before treatment with investigational and standard chemotherapeutics. The mRNA expression of EMT (PI3Kα, Akt-2, Twist1) and stem cell (ALDH1) markers was measured. Associations between CTC gene expression and progression-free survival (PFS) and overall survival (OS) were determined using Cox regression models. Among patients without CK20 or survivin-expressing CTCs (n=17), 55% had expression of ALDH1, PI3Kα and/or Akt-2. Patients with positive CTC Akt-2 expression had a significantly shorter median PFS (3.0 versus 4.0 months) compared with those without CTC Akt-2 expression in univariable (hazard ratio (HR)=1.61; log-rank P=0.034) and multivariable analyses (HR=1.70; adjusted P=0.041). In univariable analysis, CTC ALDH1 expression was associated with shorter OS (10.0 versus 38.6 months; HR=2.04, P=0.021). Patients with CTCs expressing ALDH1, PI3Kα and/or Akt-2 had a significantly inferior PFS (3.0 versus 7.7 months; HR=1.88, P=0.015) and OS (10.0 versus 26.8+ months; HR=2.25, P=0.050) in univariable, but not multivariable, analysis. CONCLUSIONS: CTC Akt-2 expression may serve as a clinically useful prognostic marker in mCRC patients and warrants further evaluation in prospective trials.

A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials.

The Hippo pathway is involved in colorectal cancer (CRC) development and progression. The Hippo regulator Rassf1a is also involved in the Ras signaling cascade. In this work, we tested single nucleotide polymorphisms within Hippo components and their association with outcome in CRC patients treated with cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab within the FIRE-3 trial and 67 Ras WT patients treated either with first-line mFOLFOX6 or SOX plus Cetuximab). In these two populations, Rassf1a rs2236947 was associated with overall survival (OS), as patients with a CC genotype had significantly longer OS compared with those with CA or AA genotypes. This association was stronger in patients with left-side CRC (hazard ratio (HR): 1.79 (1.01-3.14); P=0.044 and HR: 2.83 (1.14-7.03); P=0.025, for Fire 3 and JACCRO cohorts, respectively). Rassf1a rs2236947 is a promising biomarker for patients treated with cetuximab plus chemotherapy.

Prognostic impact of FOXF1 polymorphisms in gastric cancer patients.

A recent genome-wide association study identified seven single-nucleotide polymorphisms (SNPs) in region 16q24, near the Forkhead box-F1 (FOXF1) gene, which confer susceptibility to esophageal adenocarcinoma. We examined whether these SNPs are associated with clinical outcomes in gastric cancer (GC) patients in Japan and the United States. A total of 362 patients were included in this study: 151 Japanese GC patients treated with first-line S1 plus CDDP (training cohort) and 211 GC patients from Los Angeles County (LAC; validation cohort). Genomic DNA was isolated from whole blood or tumor tissue and analyzed by PCR-based direct DNA sequencing. Cox proportional hazard regression analyses were used to assess relationships between FOXF1 SNPs and progression-free survival (PFS) and overall survival (OS). FOXF1 rs3950627 was significantly associated with survival in both the training and validation cohorts. Japanese patients with the C/C genotype had a longer PFS (median 8.2 vs 5.3 months, hazard ratio (HR) 1.44, P=0.037) and OS (median 16.4 vs 12.2 months, HR 1.44, P=0.043) compared to patients with any A allele. Similarly, LAC patients with the C/C genotype had improved OS (3.9 vs 2.3 years, HR 1.5, P=0.022). Subgroup analyses showed these associations were specific to male patients and primary tumor subsite. Our findings suggest that FOXF1 rs3950627 might be a promising prognostic marker in GC patients.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. METHODS: Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. CONCLUSIONS: This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. METHODS: The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. RESULTS: Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. CONCLUSIONS: Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.

[Synchronous mucinous metaplasia and neoplasia of the female genital tract].

Objective: To describe the clinicopathological features of synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT). Methods: The sample consisted of 7 cases of SMMN-FGT recorded from November 2014 to September 2017 at Obstetrics and Gynecology Hospital, Fudan University.PAP method was used in immunohistochemistry.Clinical histories were retrieved and pathological slides were reviewed. Results: The patients were 37 to 70 years old(mean 54 years old). All patients showed endometrial mucinous lesions associated with cervical lesions. Three cases were an admixture of minimal deviation adenocarcinoma(MDA) and gastrictype adenocarcinoma(GAS). Three cases were an admixture of lobular endocervical glandular hyperplasia (LEGH), atypical LEGH and focal gastrictype adenocarcinoma in situ, one of which had early invasive gastrictype adenocarcinoma.Endometrium showed a structure of LEGH in one patient with focal simple gastric mucinous metaplasia in her cervix. Gastric mucinous differentiation was found in unilateral fallopian tube in 6 patients. Ovarian mucinous lesions were found in 3 patients. p16 was negative staining in 6 cases and positive in 1 case. CK7 was diffusely positive in all lesions. CK20 and CDX2 were negative or only focally positive.The expression of MUC6 was strongly positive staining or focal staining. p53 in GAS and GAS in situ had mutant expression, but wild expression in MDA region. Patients were followed up for 2 to 34 months and no recurrence was found. Conclusions: SMMN-FGT is a series of rare mucinous lesions involving multiple areas of the female genital tract, including benign or malignant lesions with gastric differentiation. It is not related to infection with high-risk human papilloma virus. When cervical gastrictype lesions are found, SMMN-FGT should be considered and should be differentiated from metastatic mucinous adenocarcinoma.

[Ovarian clear cell borderline tumour: a clinicopathologic analysis].

Objective: To investigate the clinical and pathological characteristics and prognosis of ovarian clear cell borderline tumor. Methods: A total of 12 cases of ovarian clear cell borderline tumors recorded were collected from May 2011 to December 2017 at Obstetrics and Gynecology Hospital, Fudan University.Clinical histories were retrieved and pathological slides were reviewed. Results: The age of the patients ranged from 35 to 65 years with a mean age of 52 years. Seven cases were associated with cystic endometriosis of the ovary. All tumors consisted of irregular and crowded glands or cysts embedded in a fibromatous stroma. The cysts and glands were lined by mild to moderate atypical cells.CK7 and HNF-1ß were expressed in all cases, and Naspin A was expressed in 11 cases. ARID1A expression was absent in 5 cases and p53 showed wild-type expression. None of the cases developed recurrence during follow-up ranging from 7 to 79 months. Conclusions: Ovarian clear cell borderline tumor may be associated with endometriosis and tumor suppressor gene ARIDA. The tumor has a good prognosis without recurrence and progression to carcinoma.

[Feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug â ¢].

Objective: To investigate the feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug Ⅲ (AVP Ⅲ). Methods: A retrospective analysis was performed in 5 patients with anastomotic leakage after aortic surgery, who underwent transcatheter closure in our hospital from January to June 2017 using AVP Ⅲ. Surgeries were performed in 3 cases of Standford type A dissection, 1 case of ascending aortic aneurysm and 1 case of persistent truncus.There were 3 males,and age was (43.8±13.1) years old. Anastomotic leakages located at the ascending aorta in 4 patients, and the other one located between the aortic arch and the stent-graft.Three of them had aorta-right atrium fistula and patients suffered from progressive heart failure. False aneurysm between aorta and pulmonary artery was formed in 1 patient, and patent aortic false lumenwas found in the other patient. All the AVP Ⅲ were deployed based on a femoral arteriosus loop. Patients were followed up after transcatheter closure to observe the clinical results. Results: Six AVP Ⅲ were successfully implanted in the 5 patients. Trivial residual shunt was seen in 1 patient after closure. The patients were followed up 6 (1, 6) months. The cardiac function improved from NYHA class Ⅱ-Ⅳ to class Ⅰ-Ⅱ after the procedure in 3 congestive heart failure patients.The right atrium systolic pressure was significantly reduced after the procedure((8.7±1.8) mmHg (1 mmHg=0.133 kPa) vs. (24.3±2.3) mmHg, P=0.03). The diameter of the false aneurysm reduced in 1 patient after the procedure. Complete thrombosis formation of the thoracic false lumen was observed in 1 patient. Conclusion: Transcatheter closure of anastomotic leakage after aortic surgery using AVP Ⅲ is feasible and effective according to our primary experience.

[Effect of emergency thoracic endovascular aortic repair in patients with acute traumatic thoracic aortic injury].

Objective: To investigate the effect of emergency thoracic endovascular aortic repair (TEVAR) in patients with acute traumatic thoracic aortic injury. Method: From January 2014 to December 2016, a total of 35 patients with acute traumatic thoracic aortic injuries were treated with emergency TEVAR in our hospital, their clinical data were analyzed retrospectively in this study. Results: The patients were 42 (34, 55) years old,and there were 31 males.All cases were diagnosed by emergency aorta computed tomography angiography (CTA),and 5 cases were diagnosed as aortic transaction, 13 cases were diagnosed as aortic pseudoaneurysm, 7 cases were diagnosed as aortic dissection, and 10 cases were diagnosed as aortic intramural hematoma combined hemothorax.The concomitant injuries included cerebral contusion (3 cases, 8.6%), pulmonary contusion with rib fracture (31 cases, 88.5%), long bone fracture (7 cases, 22.5%), contusion of viscera or internal organs (3 cases, 8.6%).Emergency TEVAR were performed with vascular suture system preset under local anesthesia after diagnosis,and combined injury was treated in related departments.CTA was repeated after 1, 3 and 6 months and yearly thereafter. One patient died before transferring to catheter room,and 34 (97.1%) patients underwent TEVAR procedure successfully.Time from door to operating room was (88.6±26.6) minutes,and the procedure time was (52.0±9.4) minutes. A total of 69 Perclose Proglide vascular suture system were used,and 2 cases underwent surgical suture because of hematoma and pseudoaneurysm formation in femoral arteries.The involved length of thoracic aorta was (44.5±7.4)mm. A total of 46 stent-grafts were implanted, the length of stent-graft was (164.3±15.2)mm,and the proximal oversize rate was (22.3±8.6)%. The follow-up time was 24 (12,24) months, and there were no procedure related complication such as endoleak and paraplegia. Complete aortic remodeling was observed in 14 cases. Fully thrombolization at stent segments were observed in 7 cases. Fully thrombalization of pseudoaneurysms were observed in 13 cases. One patient complained mild left upper limb weakness due to left subclavian artery occlusion. Conclusion: Emergency TEVAR is safe and effective procedure for the treatment of patients with acute traumatic thoracic aortic injury.

Impact of genetic variations in the MAPK signaling pathway on outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI and bevacizumab: data from FIRE-3 and TRIBE trials.

BACKGROUND: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev). PATIENTS AND METHODS: A total of 567 patients with KRAS wild-type mCRC in the randomized phase III FIRE-3 and TRIBE trials treated with first-line FOLFIRI/bev (discovery and validation cohorts) or FOLFIRI and cetuximab (cet) (control cohort) were included in this study. Five single-nucleotide polymorphisms in the MAPK signaling pathway were analyzed. RESULTS: AA genotype carriers of the MKNK1 rs8602 single-nucleotide polymorphism treated with FOLFIRI/bev in the discovery cohort (FIRE-3) had a shorter progression-free survival (PFS) than those harboring any C (7.9 versus 10.3 months, Hazard ratio (HR) 1.73, P = 0.038). This association could be confirmed in the validation cohort (TRIBE) in multivariable analysis (PFS 9.0 versus 11.0 months, HR 3.04, P = 0.029). Furthermore, AA carriers in the validation cohort had a decreased overall response rate (25% versus 66%, P = 0.049). Conversely, AA genotype carriers in the control group receiving FOLFIRI/cet did not show a shorter PFS. By combining both FOLFIRI/bev cohorts the worse outcome among AA carriers became more significant (PFS 9.0 versus 10.5 months) in univariable (HR 1.74, P = 0.015) and multivariable analysis (HR 1.76, P = 0.022). Accordingly, AA carriers did also exhibit an inferior overall response rate compared with those harboring any C (36% versus 65%, P = 0.005). CONCLUSION: MKNK1 polymorphism rs8602 might serve as a predictive marker in KRAS wild-type mCRC patients treated with FOLFIRI/bev in the first-line setting. Additionally, MKNK1 might be a promising target for drug development.

Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.

Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.