Targeting ENPP1 depletion may be a promising therapeutic strategy for treating oral squamous cell carcinoma via cytotoxic autophagy-related apoptosis.

ENPP1 depletion closely related with modulation immunotherapy of several types of cancer. However, the role of ENPP1 correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, effects of ENPP1 on OSCC cells in vitro were examined by cell proliferation assay, transwell chamber assay, flow cytometry analysis and shRNA technique. Cellular key proteins related to cell autophagy and apoptosis were evaluated by Western blot and immunofluorescent staining. Moreover, functions of ENPP1 on OSCC process were observed in nude mouse model. We reported that overexpression of ENPP1 promote the growth of OSCC cell xenografts in nude mouse model. In contrast, ENPP1 downregulation significantly inhibits OSCC cancer growth and induces apoptosis both in vitro and in vivo, which are preceded by cytotoxic autophagy. ENPP1downregulation induces a robust accumulation of autophagosomes, increases LC3B-II and decreases SQSTM1/p62 in ENPP1-shRNA-treated cells and xenografts. Mechanistic studies show that ENPP1 downregulation increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ENPP1 downregulation-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates it's effects. Collectively, these data uncover that ENPP1 downregulation induces autophagic cell death in OSCC cancer, which may provide a potential therapeutic target for the treatment of OSCC.

The tumoral microbiome of pancreatic intraductal papillary mucinous neoplasm: A single-center retrospective cohort study.

BACKGROUND AND AIM: Pancreatic intraductal papillary mucinous neoplasm (IPMN) is one of the most common precancerous lesions of pancreatic carcinoma. Studies have found that the tumoral microbiome has an important influence on pancreatic carcinoma. However, the tumoral microbiome of IPMNs has rarely been explored. METHODS: Tumoral microbiome gene sequencing was carried out using 16 specimens of IPMN and 45 specimens of IPMN with associated invasive carcinoma (IPMN-IC) by 2bRAD sequencing for microbiome. The profile of the tumoral microbiome was summarized. Associations of the tumoral microbiome with disease grade, histological subtype, and prognosis were analyzed. RESULTS: A total of 598 species of microbes were identified, comprising 228 genera, 109 families, 60 orders, 29 classes, 14 phyla, and 2 kingdoms. The genus Pseudomonas was detected more frequently and had higher relative abundance in IPMN-ICs; Alcaligenes faecalis was detected with higher relative abundance in IPMNs. Bifidobacterium pseudolongum had a higher relative abundance in the IPMN-IC group, regardless of histological subtype. Moreover, among patients with IPMN-ICs, those with a high relative abundance of B. pseudolongum had better overall survival than those with a low relative abundance. Patients who were positive for Staphylococcus aureus or Mycolicibacillus koreensis had shorter survival. The presence of S. aureus was an independent risk factor for poor prognosis. CONCLUSIONS: There are enriching tumoral microbes in IPMN. The tumoral microbiome of IPMN is different from that of IPMN-IC.

Clinical characteristics and oncological outcomes of recurrent adult granulosa cell tumor of ovary: A retrospective study of seventy patients.

INTRODUCTION: This study aimed to describe the clinicopathological characteristics of recurrent adult granulosa cell tumor and identify the risk factors for recurrence. MATERIAL AND METHODS: Seventy recurrent adult granulosa cell tumor patients treated in Peking Union Medical College Hospital between 2000 and 2020 were retrospectively reviewed. The primary outcomes were progression-free survival after first recurrence (PFS-R), overall survival after first recurrence (OS-R) and recurrence frequency. The Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard analysis, and the Prentice, Williams and Peterson counting process (PWP-CP) model were adopted. RESULTS: There were 70 patients included in the study, and recurrence occurred twice in more than 71% of patients, and 49.9% of patients relapsed ≥ three times. The recurrence pattern in over half of the patients at first recurrence was multifocal and distant disease, and abdominal or pelvic mass and liver metastasis were the most common. The 5-year PFS-R was 29.3%, and the 10-year PFS-R was 11.3%; the 5-year OS-R was 94.9%, and the 10-year OS-R was 87.9%. Kaplan-Meier analysis demonstrated that patients with distant recurrence and PFS1 (PFS when first recurrence occurred) ≤60 months had worse PFS-R (p = 0.017, 0.018), and patients with PFS-R ≤ 34 months had worse OS-R (p = 0.023). It demonstrated that PFS1 ≤ 60 months (hazard ratio, HR 1.9, 95% confidence interval [CI]: 1.1-3.4, p = 0.028) was an independent risk factor for PFS-R, and local lesion at recurrence (HR 0.488, 95% CI: 0.3-0.9, p = 0.027) was an independent protective factor for PFS-R. In addition, it demonstrated that PFS-R ≤ 33 months (HR 5.5, 95% CI: 1.2-25.3, p = 0.028) was an independent risk factor for OS-R. The PWP-CP analysis showed that laparoscopic operation (at each operation) could significantly increase recurrence times (p = 0.002, HR = 3.4), and no existence of gross residual lesion (R0) at each recurrence operation could significantly decrease recurrence frequency (p < 0.001, HR <0.001). CONCLUSIONS: The recurrence pattern in patients with recurrent adult granulosa cell tumor was characterized as late and repeated, multifocal, and distant relapse. It has been demonstrated that PFS1 ≤ 60 months and distant lesion at recurrence are independent risk factors for PFS-R, and PFS-R ≤ 33 months is an independent risk factor for OS-R. The PWP-CP model showed that the transabdominal approach and surgery reaching R0 could significantly decrease the recurrence frequency.

Oncological and reproductive outcomes after fertility-sparing surgery in patients with seromucinous borderline ovarian tumor: Results of a large retrospective study.

OBJECTIVE: To evaluate the oncological and reproductive outcomes in patients with seromucinous borderline ovarian tumors (SMBOT) treated with fertility-sparing surgery (FSS). METHODS: We retrospectively reviewed the medical records of patients with SMBOT who underwent surgery between 2000 and 2019. A centralized histological review was performed and recurrence rates were compared between different surgical procedures. RESULTS: A total of 105 patients fulfilled the inclusion criteria, of whom 65 underwent FSS and 40 were treated with radical surgery (RS). Fourteen patients had recurrent disease after a median follow-up time of 59.6 months (range: 22.1-256.8 months). All but one relapsed with SMBOT. There was no significant difference in disease-free survival (DFS) between the two groups (P = 0.141). Multivariate analysis showed that only bilateral involvement was associated with increased recurrence (P = 0.008). In the subgroup of patients treated with conservative surgery, there was no significant difference in DFS with regard to surgical procedures (ovarian cystectomy vs salpingo-oophorectomy, P = 0.487). Of the 12 patients in the FSS group who developed recurrence, 11 underwent a second round of FSS and all remained alive with no evidence of disease at the end of follow-up. Of 20 patients desiring pregnancy, 16 patients were successful and resulted in 17 term deliveries. CONCLUSIONS: FSS is feasible for young patients who wish to preserve their fertility. Patients initially treated with ovarian cystectomy may be managed by close surveillance if post-operative imaging are negative. Repeat FSS remains a valuable alternative for young patients with recurrent SMBOT after thorough communication.

Alternative Lengthening of Telomeres Phenotype Predicts Progression Risk in Noninsulinomas in a Chinese Cohort.

INTRODUCTION: Recent studies have suggested that alternative lengthening of telomeres (ALT) is associated with metastasis and poor survival in pancreatic neuroendocrine tumors (PanNETs). This study evaluated whether this association is applicable to Chinese patients as well as the potential somatic mutations associated with ALT. METHODS: We assessed the prevalence of ALT by performing telomere-specific fluorescence in situ hybridization and analyzed DAXX/ATRX expression using immunohistochemistry in 112 Chinese patients with PanNETs to evaluate the association between ALT and clinical outcomes. A subset of the noninsulinoma samples (28/60) was subjected to Sanger sequencing and targeted sequencing. RESULTS: The ALT-positive phenotype was identified in 23.2% (26/112) of the samples. The clinicopathologic factors significantly associated with progression in the noninsulinoma (n = 60) cohort were the female sex (p = 0.006), Ki-67 index (p < 0.001), World Health Organization grade (p = 0.031), and ALT positivity (p = 0.013). Patients with ALT-positive PanNETs had significantly shorter progression-free survival than those with ALT-negative PanNETs in the entire cohort (p < 0.001), noninsulinoma subgroup (p = 0.01), and G2 subgroup (p = 0.001). ALT-positive samples frequently harbored somatic mutations in DAXX, ATRX, MEN1, SETBP1, PRKDC, and GNAS. CONCLUSIONS: We confirmed that ALT positivity is an effective risk predictor, especially in the noninsulinoma and G2 subgroups. ALT is also related to somatic mutations in MEN1, SETBP1, PRKDC, and GNAS, in addition to DAXX and ATRX.

Oncological and Reproductive Outcomes of Cystectomy Compared with Unilateral Salpingo-Oophorectomy as Fertility-Sparing Surgery in Patients with Apparent Early Stage Pure Immature Ovarian Teratomas.

PURPOSE: To compare the oncological and reproductive outcomes of patients with apparent early stage pure ovarian immature teratomas (IMTs) treated with unilateral salpingo-oophorectomy (USO) or cystectomy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with apparent early stage pure ovarian IMTs who received fertility-sparing surgery (FSS) between 1984 and 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving USO and cystectomy. Reproductive outcomes and menstrual histories were assessed by telephone interview. RESULTS: A total of 124 patients were included, of whom 83 underwent USO and 41 underwent cystectomy. After a median follow-up of 70.6 months (range: 6.2-410.6 months), eight patients suffered recurrences (5 in the USO group and 3 in the cystectomy group). The median times to recurrence were 5.0 and 5.1 months in the USO and cystectomy groups, respectively (P = 0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P = 0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates. CONCLUSIONS: A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy with adjuvant chemotherapy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option.

The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma.

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochemistry. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A positive correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 months, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 months, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-molecule Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.

Whole-genome sequencing reveals distinct genetic bases for insulinomas and non-functional pancreatic neuroendocrine tumours: leading to a new classification system.

OBJECTIVE: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs. DESIGN: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed. RESULTS: PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period. CONCLUSION: These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.

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.

Diagnosis and management of growing teratoma syndrome after ovarian immature teratoma: A single center experience.

OBJECTIVES: To evaluate the diagnostic, surgical, and oncological outcomes of patients with growing teratoma syndrome (GTS). METHODS: Patients diagnosed with ovarian immature teratoma (IMT) between 1980 and 2018 at Peking Union Medical College Hospital (PUMCH) were evaluated for the development of GTS. Their clinical characteristics, surgical and pathological data, and oncological outcomes were collected. RESULTS: Between 1980 and 2018, 175 cases of IMT were referred to PUMCH. Thirty-five patients subsequently developed GTS with a crude rate of approximately 20%. The median interval between the initial diagnosis of IMT and the first occurrence of GTS was 18.5 months (range, 6-78 months). Residual disease (P < 0.001) and gliomatosis peritonei (GP) at initial surgery (P = 0.023) were independent risk factors for GTS development. Fertility-sparing surgery for GTS was performed in 27 patients and four patients achieved five singleton pregnancies. The median follow-up time was 73 months (range, 11-401 months). Eleven patients developed at least one recurrence. Residual disease after GTS surgery was associated with GTS recurrence (P = 0.001). By the end of follow-up, 27 patients were alive without disease and the other eight patients were alive with disease. CONCLUSION: The presence of residual disease and GP at initial surgery are risk factors for GTS. Complete surgical resection is the cornerstone for treatment of GTS. The presence of residual disease after surgery for GTS is a risk factor for GTS recurrence. Fertility-sparing surgery should be performed because spontaneous pregnancy is possible. The overall prognosis of GTS is excellent.

Role of staging surgery and adjuvant chemotherapy in adult patients with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery.

OBJECTIVE: The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging surgery followed by platinum-based chemotherapy. However, the role of complete staging surgery and adjuvant chemotherapy remains controversial. The aim of this study was to investigate the role of complete staging surgery and adjuvant chemotherapy in patients with early-stage pure immature teratoma after fertility-sparing surgery. METHODS: Patients with stage I pure immature teratoma who underwent fertility-sparing surgery between January 1986 and June 2018 were reviewed retrospectively. Fertility-sparing surgery was defined as preservation of the uterus and at least one adnexa. The inclusion criteria were age >18 years, stage I disease (confined to one ovary), and diagnosis of pure immature teratoma. Patients with distant metastasis or mixed ovarian germ cell tumor were excluded. Complete staging surgery was defined as peritoneal cytology examination, peritoneal biopsy, omentectomy, or omental biopsy with or without lymph node dissection. Patients designated with stage I disease without complete staging surgery were categorized as stage X. Disease-free survival was defined as the interval from the date of surgery to the date of recurrence or censoring. Disease-free survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 75 patients were included in the analysis, with a median age of 26 years (range 18-40): 26 (34.7%) patients had received complete staging surgery; 51 (68%) patients received postoperative adjuvant chemotherapy while 24 (32%) underwent surgery alone; and 4 patients (5.3%) had recurrent disease during a median follow-up time of 80.2 months (range 13.7-261). The recurrence rates in the chemotherapy group and surveillance groups were 3.9% and 8.3%, respectively (p=0.46). All patients were successfully salvaged, except for one death. Tumor relapse occurred in patients with all grades of immature teratoma (G1: 1/35; G2: 2/25; G3: 1/15). Univariate analysis revealed that complete staging surgery, adjuvant chemotherapy, and tumor grade were not associated with 5 year disease-free survival (p=0.69, p=0.46, p=0.7, respectively). The 5 year disease-free survival rate was 94.6% and the overall survival rate was 98.7%. CONCLUSION: Adult patients with stage I pure immature teratoma had 98.7% overall survival and recurrence rates were low after fertility-sparing surgery.

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.

Analysis of oncologic and reproductive outcomes after fertility-sparing surgery in apparent stage I adult ovarian granulosa cell tumors.

OBJECTIVE: We evaluated the oncological and reproductive outcomes after fertility-sparing surgery (FSS) in patients with a stage I adult ovarian granulosa cell tumor (AGCT). METHODS: The medical records of patients aged <50 years with a stage I AGCT who underwent surgery between January 1983 and April 2017 were reviewed. Fertility-sparing surgery was defined as the preservation of the uterus and at least one adnexa. Outcomes were compared between groups who underwent FSS or radical surgery. Patients who had undergone FSS were contacted to gather reproductive outcomes and menstrual histories. RESULTS: A total of 113 patients who met the inclusion criteria were included: 61 had FSS while 52 underwent radical surgery. After a median follow-up of 99.2 months (range 20.2-394.3 months), 30 patients had recurrent disease (17 in the FSS group and 13 in the radical surgery group). Multivariate analysis showed no difference in disease-free survival between the groups who underwent FSS or radical surgery (P = 0.550). In patients who underwent FSS, incomplete staging was significantly associated with the risk of recurrence (P = 0.024). Of the 22 patients desiring pregnancy, 19 achieved 20 singleton pregnancies. The pregnancy rate was 86.4% and the live birth rate was 95%. CONCLUSIONS: FSS is an acceptable option for young patients who wish to preserve their fertility. Secondary surgical staging is an important treatment in patients with an unstaged AGCT. Reproductive outcomes are promising. Radical surgery might be delayed until recurrence, provided they are willing to undergo a prolonged follow-up.

Intravascular Fibrolipoma of the Femoral Vein.

Lipoma of the lower leg vein is rare, and the histopathological variant, fibrolipoma, is even rarer. Here, we report an intravascular fibrolipoma located at the junction of the deep femoral vein and the femoral vein in a 50-year-old male patient. Tumor resection and venous reconstruction with a prosthetic graft were performed. Eight months later, the patient was asymptomatic and did not exhibit swelling. To our knowledge, this is the first case report of an intravascular fibrolipoma in the literature. Lower vein venography, computed tomography venography, ultrasonography, and histologic images are presented, along with a description of the procedures employed for tumor resection and venous reconstruction.

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.

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.

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.

High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: The cytokine interleukin-22 (IL-22) and its receptor are present in the tumor microenvironment. Their function in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. The goal of the present study was to measure the expression of IL-22 and IL-22R in PDAC and assess their relationship with clinicopathological features and prognosis. METHODS: The expression of IL-22 and IL-22R was evaluated by immunohistochemistry in PDAC tissues from 57 patients and by Western blotting in six tumors and adjacent nontumor tissues. A statistical analysis was conducted to assess the relationship between levels of expression, clinicopathological factors, and overall survival. In addition, the relationship between the expression of IL-22 and IL-22R and invasion was assessed by Western blotting and transwell assay with the PDAC cell lines PANC1 and BxPC3. RESULTS: Positive IL-22 staining was detected in PDAC tissues and adjacent nontumor tissues. Positive IL-22R staining was detected in PDAC cells. High expression of IL-22 and IL-22R correlated significantly with lymph node involvement. IL-22 increased the phosphorylation of signal transducer and activator of transcription3, the expression of matrix metalloproteinase 9, and the invasion in PANC1 and BxPC3 cells in vitro while silencing of IL-22R RNA caused opposite effects. Most importantly, overall survival was significantly poorer in patients with high expression of IL-22 and IL-22R than in those with low expression. CONCLUSIONS: These findings reveal the positive role of IL-22 and IL-22R in invasion and metastasis in human PDAC. IL-22 and IL-22R may be suitable independent prognostic markers in PDAC.