Oncofertility outcomes after fertility-sparing treatment of bilateral serous borderline ovarian tumors: results of a large retrospective study.

STUDY QUESTION: What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery? SUMMARY ANSWER: Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates. WHAT IS KNOWN ALREADY: Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures. LIMITATIONS, REASONS FOR CAUTION: As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred. WIDER IMPLICATIONS OF THE FINDINGS: The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Retrospective analysis of seven cases of pancreatic mixed adenoneuroendocrine carcinoma from a high-volume center and review of the literature.

BACKGROUNDS: The clinicopathologic features and biological behaviors of pancreatic mixed adenoneuroendocrine carcinoma (pMANEC) and its impacts on survival are poorly known. METHODS: We retrospectively reviewed seven pMANEC cases from a single institution from September 2010 to January 2017 along with twenty-one previously reported cases from the literature. Survival and prognostic analyses were conducted using Kaplan-Meier estimates and Cox regression, respectively. RESULTS: Seven pMANEC cases were identified during the study interval. Among the six patients who underwent operations, five reached R0 resections, one experienced postoperative pancreatic fistula, and two suffered other complications. The median progression-free survival (PFS) and disease-specific survival (DSS) were 7.5 months (2 to 36 months) and 15 months (6 to 36 months), respectively. A total analysis of twenty-eight pMANEC cases showed that patients were mostly older (median age, 59.5 years) and male (64.3%). The two most common symptoms were abdominal pain (53.6%) and obstructive jaundice (35.7%). The majority of pMANECs were non-functional (89.3%) and located in the pancreatic head (64.3%). The median diameter of pMANEC was 3.0 cm, with a wide range (0.5 to 19.0 cm). Lymph node metastasis (P = 0.015) was associated with decreased DSS, while age (P = 0.414), sex (P = 0.125), tumor size (P = 0.392), location (P = 0.913), functional status (P = 0.313), CA19-9 level (P = 0.608), and liver metastasis (P = 0.935) did not show significant prognoses on DSS. CONCLUSIONS: We reported seven pMANEC cases and outlined their clinical behaviors and prognoses with a review of twenty-one cases from the literature. Lymph node metastasis was found to be a negative prognostic factor of DSS based on the present study.

Safety and fertility outcomes after the conservative treatment of endometrioid borderline ovarian tumours.

BACKGROUND: Because of the rarity of endometrioid borderline ovarian tumours (EBOTs), there is a paucity of data concerning the natural history and prognosis of this condition. Thus, the objective of our study was to establish the feasibility of fertility preservation in young women with EBOTs, as well as their oncological and reproductive outcomes. METHODS: Consecutive patients with EBOTs, treated at a tertiary referral centre during a span of 22 years, were retrospectively analysed. Recurrence-free interval, as well as its association with the type of surgery and with other clinical and pathological features, was assessed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: Of the 59 patients studied, the median follow-up time was 30 months (range, 6-177 months). Nine (15.3%) patients developed 13 recurrences 6-137 months after the initial surgeries, including three patients (5.1%; n = 3/59) who developed six invasive recurrences 8, 18 and 68 months after their initial surgeries. Conservative surgery showed a tendency towards a high recurrence rate (17.2% versus 13.3%); however, this difference was not significant (p = 0.45). The 5-year recurrence-free survival rate was significantly higher in the oophorectomy group than in the cystectomy group (p = 0.001). Cox regression analysis showed that none of the variables assessed were associated with an increased hazard ratio for recurrence, except for a younger age at diagnosis (p = 0.021). Of 20 patients who attempted to conceive, three pregnancies among two patients (10.0%) resulted in two live births. CONCLUSIONS: Conservative surgery with unilateral adnexectomy can be proposed for young women with EBOTs with fertility desire; however, the reproductive result is not satisfactory. In addition, careful evaluations of the endometria should be offered during the initial surgery and follow-up period. TRIAL REGISTRATION: Retrospectively registered.

Clinicopathological Features of Intraductal Pancreatic Neuroendocrine Tumors.

Objective To evaluate the clinical and pathologic characteristics of intraductal pancreatic neuroendocrine tumors (PanNETs). Methods Four cases of intraductal PanNETs were studied by light microscopy and immunohistochemistry with the analysis of morphologic features and review of relevant literatures. Results Two female patients and two male patients aged 41- 58 years were enrolled in this study. The chief complaint was abdominal pain in two patients,vomiting in one patient,and jaundice in the last patient. Imaging examination showed intraductal neoplasm with diagnosis as intraductal papillary mucinous neoplasm (IPMN) in case 1; space-occupying lesions were found in the head of pancreas in the other three cases with pancreatic ductal ectasia and distal pancreatic atrophy. Grossly the masses were located in pancreatic main duct and invaded into surrounding pancreatic parachyma. Microscopically the tumors arranged with solid pattern,with some trabecular structures in the last two cases. Small duct and ductules were seen in intraductal PanNETs. The immunohistochemical expression showed that SYN and CgA were positive in neoplastic cells and negative in small duct and ductules.Conclusions Intraductal PanNETs are rare conditions. The clinical symptoms and imaging findings are similar to IPMN or pancreatic carcinoma. The tumors are located within pancreatic duct partly and can invade the pancreatic parenchyma. Microscopically the neuroendocrine tumors mix with small duct and forms ductulo-insular structure,which should be differentiated with mixed ductal endocrine carcinoma. The grade and prognosis are similar to those of classical neuroendocrine tumors.

Effects of miR-125a-5p on Cell Proliferation,Apoptosis and Cell Cycle of Pancreatic Cancer Cells.

Objective To investigate the effects of miR-125a-5p on cell proliferation,apoptosis and cell cycle of pancreatic cancer cells.Methods The expression level of miR-125a-5p in pancreatic cancer was determined using quantitative real-time polymerase chain reaction analysis in 4 pairs of pancreatic cancer tissues and matched adjacent normal tissues samples. The expression of miR-125a-5p was downregulated in pancreatic cancer cell lines by transfection with miR-125a-5p inhibitor. Cell counting kit-8 assays was conducted to detect the growth ability of pancreatic cancer cell lines. Flow cytometry was applied to detect the cell cycle and apopotosis. Soft agar colony formation test was employed to assess the role of miR-125a-5p in process of malignant transformation.Results MiR-125a-5p was significantly highly expressed in pancreatic ductal adenocarcinoma tissues than adjacent normal tissues(P<0.05). After the expression level of miR-125a-5p in Panc-1 and MIA PaCa-2 was downregulated,the growth ability was suppressed(P<0.05),early apopotosis rate was promoted by 13.6% and 11.0% respectively(P<0.05),the amount of colony formation was reduced by 27.3% and 27.8%,respectively(P<0.05),and the percentage of S stage of Panc-1 was reduced by 11.8% (P<0.05).Conclusions The expression of miR-125a-5p is high in pancreatic ductal adenocarcinoma tissues. After the expression level of miR-125a-5p is downregulated,the growth ability,colony formation,and cell cycle of Panc-1 and MIA PaCa-2 are suppressed,and the early apopotosis rate will be promoted. Therefore,miR-125a-5p may play an oncogenic role in pancreatic ductal adenocarcinoma.

Gliomatosis peritonei: a series of eight cases and review of the literature.

BACKGROUND: Gliomatosis peritonei (GP) is a rare condition characterized by mature glial tissue implants widespread in the peritoneum. The GP is often associated with ovarian teratoma. However, little is known about the characteristics and prognosis of GP. The purpose of this study was to describe the features, treatment, and prognosis of GP. Additionally, we review previously reported cases of GP, summarizing the presently known data. METHODS: From January 2000 to January 2016, cases of ovarian teratoma and GP treated at Peking Union Medical College Hospital were reviewed. We assessed the pathology, treatments, and outcomes along with prognostic information. Additionally, the literature regarding this clinical condition was also reviewed. RESULTS: Eight patients met the inclusion criteria. Patients had a median age of 20 (range, 15-25) years. GP was diagnosed as the primary tumor in 6 patients and at a secondary surgery in two patients. The primary ovarian tumor consisted of immature teratoma (n = 7) and mature teratoma (n = 1). Grades of immature ovarian teratoma were 2, grade 1; 3, grade 2; and 2, grade 3. Tumors mean had a size of 20.4 (range, 11-30) cm. The median follow-up time was 60.5 (range, 3-144) months. All cases had conservative surgery and seven of them had macroscopic residual disease postoperatively. During the study period, the eight patients remained alive and asymptomatic. Three patients in the study experienced spontaneous pregnancy. After reviewing the existing literature, a total of 14 patients with nodal gliomatosis were present and 10 of them were alive. According to the literature review, five articles reported more than five cases. Of a total of 67 patients, 60 of them remained alive. CONCLUSION: The prognosis of immature ovarian teratoma with GP is favorable. Complete resection of GP is often difficult. Residual peritoneal disease in GP can be asymptomatic and quiescent over a long period. A more conservative surgical approach may be carried out in patients with massive peritoneal spread after the presence of metastatic immature elements is excluded. Owing to the risk of recurrence and malignant transformation of GP, a long-term follow-up is necessary for patients with residual peritoneal disease.

Clinicopathological features of primary gastric neuroendocrine neoplasms: A single-center analysis.

OBJECTIVE: To assess the clinical characteristics, diagnosis and therapeutic modalities for gastric neuroendocrine neoplasms (GNENs) among the Chinese population in a single institution. METHODS: A total of 57 patients with histologically confirmed GNENs, who were diagnosed between 1995 and 2015 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinical, imaging and histopathologic characteristics as well as the treatments of GNENs were collected and analyzed. RESULTS: Patients with GNENs mostly presented with non-specific symptoms. Gastric body was the most common site of involvement. The choice of imaging modality, such as endoscopy and computed tomography depended on the tumor subtype. Chromogranin A (CgA) and synaptophysin were indispensable immunohistochemical markers for diagnosis. Significant inter-group differences in the positivity rate of CD56 were observed among the three grades (G1, G2 and G3). Therapeutic modalities included endoscopic intervention, surgical resection and pharmacotherapy, which were largely guided by the tumor subtype and the presence or absence of distant metastasis or tumor recurrence. CONCLUSIONS: Routine endoscopic examination is recommended for the early diagnosis of GNENs. Histopathological examination can make the definite diagnosis of GNENs and clarify the nature of gastric polyps. A multidisciplinary approach is important in the management of patients with GNENs.

Lipopolysaccharide challenge induces long pentraxin 3 expression in mice independently from acute lung injury.

OBJECTIVE: To determine whether the onset of acute lung injury (ALI) induces the up-regulation of pentraxin 3 (PTX3) expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-induced ALI. METHODS: Wild-type C57BL/6 mice (12-14 weeks old) were randomly divided into 3 groups. Mice in the group 1 (n=12) and group 2 (n=12) were instilled with lipopolysaccharide via intratracheal or intraperitoneal routes, respectively. Mice in the group 3 (n=8) were taken as blank controls. Pulmonary morphological and functional alterations were measured to determine the presence of experimental ALI. PTX3 expression in the lung was quantified at both protein and mRNA levels. PTX3 protein concentration in blood and bronchoalveolar lavage fluid was measured to evaluate its ability to diagnose sepsis-induced ALI by computing area under receiver operator characteristic curve (AUROCC). RESULTS: ALI was commonly confirmed in the group 1 but never in the other groups. PTX3 expression was up-regulated indiscriminately among lipopolysaccharide-challenged mice. PTX3 protein concentration in the biofluid was unable to diagnose sepsis-induced ALI evidenced by its small AUROCC. PTX3 concentration in bronchoalveolar lavage fluid did not correlate with that in serum. CONCLUSIONS: Lipopolysaccharide challenges induced PTX3 expression in mice regardless of the presence of ALI. PTX3 may act as an indicator of inflammatory response instead of organ injury per se.

Lipocalin-2 test in distinguishing acute lung injury cases from septic mice without acute lung injury.

OBJECTIVE: To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury (ALI) in mice. METHODS: Lipopolysaccharide (LPS, 10 mg/kg) injection or cecal ligation and puncture (CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups (n=10 in each group): group A (intraperitoneal LPS injection), group B (intravenous LPS injection via tail vein), group C (CLP with 25% of the cecum ligated), group D (CLP with 75% of the cecum ligated), and the control group (6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin (IL)-6 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves (ROC) and computing area under curve (AUC). RESULTS: In both group B and group D, most of the main features of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI (group A+group C), lipocalin-2 protein expression in septic mice with ALI (group B+group D) was significantly up-regulated in BALF (P<0.01) and in serum (P<0.01), and mRNA expression boosted in lung tissues (all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former (BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio (13.000) and the lowest negative likelihood ratio (0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum (Spearman r=0.8803, P<0.0001). CONCLUSIONS: Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.

Application of the BIOMED-2 standardized primer system for the diagnosis of primary gastric B-cell non-Hodgkin's lymphoma.

Primary gastric B-cell non-Hodgkin's lymphoma (B-NHL) has a similar morphocytological presentation to severe chronic gastritis, which complicates the pathological diagnosis of this disease. To investigate the practicality and utility of the BIOMED-2 standardized primer system for the diagnosis of primary gastric B-NHL from endoscopic biopsy specimens, we selected 65 cases of archived paraffin-embedded primary gastric B-NHL specimens as well as 27 cases of severe chronic gastritis samples to serve as a negative control group. The positivity rates of immunoglobulin heavy chain (IgH) gene rearrangements detected by the BIOMED-2 standardized primer system for the two groups were 86.4% and 12.0%, respectively, which are significantly different (p < 0.05). Importantly, the combined detection of the five groups of the IgH primer system increased the detection rate of B-NHL. These findings indicate that the BIOMED-2 standardized primer system is suitable for formalin-fixed and paraffin-embedded (FFPE) specimens and is valuable as a secondary diagnostic tool for primary gastric B-NHL as well as the differential diagnosis of severe chronic gastritis.

[MiR-150-5p inhibits the proliferation and promoted apoptosis of pancreatic cancer cells].

OBJECTIVE: To investigate the role of miR-150-5p in cell proliferation and apoptosis in human pancreatic cancer cell lines. METHODS: The expression of miR-150-5p in pancreatic cancer was detected by real time qPCR analysis in 11 pairs of pancreatic cancer tissue and matched adjacent normal tissue samples and in 4 pancreatic cancer cell lines. PANC-1, MIA PaCa-2,BxPC-3 and AsPC-1 cells were transfected with chemically synthesized MiR-150-5p mimics, and CCK-8 assays was then performed to assess cellular functions. To fully understand the mechanisms by which miR-150-5p exerted its function, cell cycle analysis was performed on MIA PaCa-2 and PANC-1 cells 48 hours after transfection, by incubating with propidium iodide (PI)and subsequently analyzed by fluorescence-activated cell sorting (FACS) . Apoptosis assay was performed on MIA PaCa-2 and PANC-1 cell lines 24 hours after transfection using the Annexin V-FITC Apoptosis Detection Kit I (BD Biosciences) and analyzed by FACS. RESULTS: The expression of miR-150-5p was consistently lower in the pancreatic cancer tissues than in normal tissues, and the miR-150-5p was also down-regulated in pancreatic cancer cell lines (P < 0.05) . MiR-150-5p mimics transfection significantly raised the expression level of miR-150-5p mRNA in PANC-1 and MIA PaCa-2 (P < 0.01) . The CCK-8 proliferation assay showed that cell growth was reduced in 4 pancreatic cancer cell lines (AsPC-1, BxPC-3,MIA PaCa-2, PANC-1) of miR-150-5p transfected cells compared with NC-transfected cells. The inhibition rates were 50.7%, 48.6%, 30.8% and 42.3%, respectively (P < 0.01). The apoptotic rate was increased in cells transfected with miR-150-5p mimics (P < 0.01) . The cell cycle analysis in MIA PaCa-2 indicated that miR-150-5p treatment induced cell cycle arrest in G1 phase with a significant increase in the percentage of cells in G1 phase (P < 0.01), and a reduction of the S-phase cell population in MIA PaCa-2 and PANC-1 (P < 0.01). CONCLUSIONS: MiR-150-5p is down-regulated in pancreatic cancer. Over-expression of miR-150-5p inhibits cell proliferation, blocked the cell cycle, but promotes cell apoptosis in pancreatic cancer cells.

[Target prediction and verification of miR-27a in pancreatic cancer].

OBJECTIVE: To predict and verify the target gene of miR-27a in pancreatic cancer by combining the result of comparative proteome analysis. METHODS: The bioinformatics softwares of TargetScan,PicTar and miRanda were used to predict the possible target genes of miR-27a. Based on the results of comparative proteomics analysis, possible candidates of the target genes were selected. Expression vector of target gene 3'UTR was constructed, and then target gene was verified by dual-luciferase reporter assay system. The PANC-1 and BxPC-3 pancreatic cancer cells were treated with miR-27a mimics or negative control for 48 h. Western blot analysis was used to verify alterations of protein expression of the genes. RESULTS: PSMA1 was selected as the candidate target gene of miR-27a by bioinformatics prediction and comparative proteome analysis. Dual-luciferase reporter assay showed that miR-27a decreased luciferase activity in cells co-transfected with pmirGLO-PSMA1-WT, compared to the negative control, although significant difference of luciferase activity was not observed in cells co-transfected with pmirGLO-PSMA1-MUT between the two groups. The protein level of PSMA1 was down-regulated in pancreatic cancer cells transfected with miR-27a mimics in comparison with pancreatic cancer cells transfected with negative control. CONCLUSION: PSMA1 is the direct target gene of miR-27a in pancreatic cancer.

[Significance of chemokine receptor CXCR3 expression in breast cancer].

OBJECTIVE: To investigate the expression of CXCR3 and its association with clinicopathologic features in breast carcinoma. METHODS: The expression level of CXCR3 in 18 samples of breast cancer and corresponding normal tissues was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis. Immunohistochemistry was carried out to examine the expression of CXCR3 in 80 breast cancers, 20 fibroadenomas and 15 normal breast tissues. RESULTS: (1) RT-PCR and real-time RT-PCR analysis showed a higher level of CXCR3 in breast cancer tissues than that in the corresponding normal breast tissues (P < 0.05). (2) Immunohistochemistry analysis showed that the positive rate of CXCR3 in breast cancer tissues was significantly higher than that in fibroadenomas and the normal breast tissues (P < 0.05). The expression level of CXCR3 in the lymph node-positive group was higher than that in the lymph node-negative group (P < 0.05). The expression of CXCR3 was positively correlated with the number of lymph nodes involved by metastasis, tumor size and pTNM tumor stage (P < 0.05). CONCLUSIONS: Chemokine receptor CXCR3 was up-regulated in breast cancer, and was associated with the progression of breast cancer. CXCR3 might be a novel molecular marker to predict lymph node metastasis and prognosis of breast cancer.