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Introduction: Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV., Methods: From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological, and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported., Results: Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio [HR] 0.305, p = 0.003) and multivariate analyses (HR 0.221, p = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage, and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809., Conclusions: Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Ovarian mucinous carcinoma is a disease that requires unique treatment. But for a long time, guidelines for ovarian serous carcinoma have been used for the treatment of ovarian mucinous carcinoma. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with ovarian mucinous adenocarcinoma., Methods: In this study, patients initially diagnosed with ovarian mucinous adenocarcinoma from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into the training group and the validation group at a ratio of 7:3. Independent risk factors for OS and CSS were determined by multivariate Cox regression analysis, and nomograms were constructed and validated., Results: In this study, 1309 patients with ovarian mucinous adenocarcinoma were finally screened and randomly divided into 917 cases in the training group and 392 cases in the validation group according to a 7:3 ratio. Multivariate Cox regression analysis showed that the independent risk factors of OS were age, race, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. Independent risk factors of CSS were age, race, marital, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. According to the above results, the nomograms of OS and CSS in ovarian mucinous adenocarcinoma were constructed. In the training group, the C-index of the OS nomogram was 0.845 (95% CI: 0.821-0.869) and the C-index of the CSS nomogram was 0.862 (95%CI: 0.838-0.886). In the validation group, the C-index of the OS nomogram was 0.843 (95% CI: 0.810-0.876) and the C-index of the CSS nomogram was 0.841 (95%CI: 0.806-0.876). The calibration curve showed the consistency between the predicted results and the actual results, indicating the high accuracy of the nomogram., Conclusion: The nomogram provides 3-year and 5-year OS and CSS predictions for patients with ovarian mucinous adenocarcinoma, which helps clinicians predict the prognosis of patients and formulate appropriate treatment plans., (© 2022. The Author(s).)

Background: Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs)., Methods: A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs., Results: Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p <  0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01-1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78-17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19-9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19-9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79)., Conclusions: Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs., (© 2021. The Author(s).)

Ovarian cancers include several disease subtypes and patients often present with advanced metastatic disease and a poor prognosis. New biomarkers for early diagnosis and targeted therapy are, therefore, urgently required. This study uses antibodies produced locally in tumor-draining lymph nodes (ASC probes) of individual ovarian cancer patients to screen two separate protein microarray platforms and identify cognate tumor antigens. The resulting antigen profiles were unique for each individual cancer patient and were used to generate a 50-antigen custom microarray. Serum from a separate cohort of ovarian cancer patients encompassing four disease subtypes was screened on the custom array and we identified 28.8% of all ovarian cancers, with a higher sensitivity for mucinous (50.0%) and serous (40.0%) subtypes. Combining local and circulating antibodies with high-density protein microarrays can identify novel, patient-specific tumor-associated antigens that may have diagnostic, prognostic or therapeutic uses in ovarian cancer.

Background: Mucinous colorectal adenocarcinoma (MAC) has a higher incidence of local extension, leading to lower overall resection rates. Few studies have investigated the outcomes of laparoscopic surgery for MACs to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for mucinous adenocarcinoma (MAC). Methods: This study analyzed short-term and long-term outcomes between laparoscopic and open surgery for MACs from 2008 to 2018. Multivariate analyses were used to define prognostic factors of overall survival (OS) and disease-free survival (DFS). Results: Patients in the laparoscopy (LAP) group had significantly less blood loss, fewer days to first flatus and to diet, and shorter length of hospital stay. The 3-year and 5-year DFS rates for all stages combined were 65.7% and 62.5% in the LAP group compared with 60.5% and 57.6% in the open (OPEN) surgery group ( P  = .521). The 3-year and 5-year OS rates for all stages combined were 72.3% and 67.3% in the LAP group compared with 72.6% and 67.8% in the OPEN group ( P  = .934). OS and DFS in stage II, stage III, and pathological T4 (pT4) stage patients who underwent laparoscopic surgery did not differ from patients who underwent open surgery. Multivariate analysis showed that stage pT4, pN2, and carcinoembryonic antigen (CEA) were significant predictors of OS. Independent factors, including intraoperative blood transfusion, stage pT4, pN2, CEA, and CA19-9, carbohydrate antigen 19-9, have a great effect on DFS. Conclusions: Laparoscopic surgery is a safe and feasible option for mucinous colorectal AC, which provides faster postoperative recovery and less intraoperative blood loss.

Background: Chronic inflammation is a hallmark of colorectal mucinous adenocarcinoma (CMA). Albumin-to-fibrinogen ratio (AFR) and fibrinogen-to-pre-albumin ratio (FPR) were independent prognostic factors for many kinds of solid malignancies. However, the association between the inflammatory scores and progression of metastatic CMA remains unknown., Methods: Peripheral blood neutrophil count and circulating fibrinogen, albumin, and pre-albumin levels were detected, and neutrophil-to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio(NPAR), AFR, and FPR were calculated in 42 metastatic MCA patients. Kaplan-Meier curve, Cox regression, time-dependent receiver operating characteristic curve (tdROC) were selected to investigate the prognostic utility of them in the patients., Results: Metastatic CMA patients commonly occurred in middle-younger patients (80.95%). NPAR (adjusted hazard ratio (HR)=2.405, 95% confidence interval (CI)=1.195-4.842) and FPR (p log-rank =0.007, adjusted HR=2.364, 95% CI=1.203-4.645) were significantly associated with poor progression-free survival in these patients. The prognostic prediction area under tdROC (AUROC) of FPR was significantly higher than that of NPAR(0.703 versus 0.537). Moreover, the patients with a high CA19-9-FPR score showed worse outcomes than those with the low score (p log-rank <0.001, adjusted HR=7.273, 95% CI=2.721-19.435 for the score 1 versus 0). The prediction AUROC, sensitivity, and specificity of the score were 0.892 (0.788-0.996), 76.32%, and 100.00%, respectively, and its predicted efficacy was better than that of the single biomarkers., Conclusion: The combined CA19-9-FPR score is an economical, simple, effective, and independent prognostic factor for metastatic MCA., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Upfront surgery is the standard treatment for resectable invasive intraductal papillary mucinous carcinoma; however, recurrence is common. Therefore, we investigated the recurrence, surgical outcome, and preoperative prognostic factors for recurrence in patients with resectable invasive intraductal papillary mucinous carcinoma., Methods: We analyzed 111 patients who underwent upfront surgery for resectable invasive intraductal papillary mucinous carcinoma between 2000 and 2017 and evaluated the relationship among clinicopathologic factors, recurrence, and outcomes., Results: The 5-year recurrence-free survival and disease-specific survival rates were 61% and 74%, respectively. The median time to recurrence was 1.1 years. In multivariate analysis, carbohydrate antigen 19-9 ≥83 U/mL (hazard ratio: 2.8 and 3.1), tumor size ≥2.2 cm (hazard ratio: 3.5 and 4.7), and pathologic tubular adenocarcinoma grade 2 (hazard ratio: 3.1 and 5.2) were risk factors for a shorter recurrence-free survival and disease-specific survival, respectively. Lymph node metastasis (hazard ratio: 3.9) was also a risk factor for a shorter disease-specific survival. When examining outcomes according to preoperatively measurable factors (carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm), the 5-year recurrence rates in patients with none (n = 47), 1 (n = 46), and both (n = 18) risk factors were 17%, 48%, and 78%, respectively. Five-year disease-specific survival rates in patients with none, 1, and both preoperative risk factors were 95%, 69%, and 31%, respectively., Conclusion: Carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm were independent preoperative risk factors for poor outcomes in patients with resectable invasive intraductal papillary mucinous carcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. We evaluated the levels of family members relative to the internal control miR-103a in ovarian cancer and control blood specimens collected from American and Hong Kong Chinese institutions, as well as from a laying hen spontaneous ovarian cancer model. The levels of miR-200a, miR-200b and miR-200c were significantly elevated in all human cancer versus all control blood samples. Further analyses showed significantly higher miR-200 levels in Chinese control (except miR-429) and cancer (except miR-200a and miR141) samples than their respective American counterparts. Subtype-specific analysis showed that miR-200b had an overall elevated level in serous cancer compared with controls, whereas miR-429 was significantly elevated in clear cell and endometrioid cancer versus controls. MiR-429 was also significantly elevated in cancer versus control in laying hen plasma samples, consistent with the fact that endometrioid tumor is the prevalent type in this species. A neural network model consisting of miR-200a/200b/429/141 showed an area under the curve (AUC) value of 0.904 for American ovarian cancer prediction, whereas a model consisting of miR-200b/200c/429/141 showed an AUC value of 0.901 for Chinese women. Hence, miR-200 is informative as blood biomarkers for both human and laying hen ovarian cancer.

The purpose of the present study was to evaluate the diagnostic role of CRP in ovarian cancer and to assess whether CRP can be combined with tumor markers to enhance the diagnostic efficacy toward ovarian cancer. Area under the curve, sensitivity, and specificity were calculated to access the diagnostic ability of each singly and combined as markers for ovarian cancer. The CRP cut-off value was then calculated to evaluate the diagnostic efficacy of CRP for ovarian cancer. Our results showed that values for all markers were significantly higher in the cancer group than in the control group. Receiver operating characteristic curve results showed that CA125 had the highest diagnostic efficacy for ovarian cancer, while the sensitivity for CRP was higher than for CA125, and the specificity for CRP was equal to that of CA125. The combination of CRP, CA125, and HE4, however, provided the strongest diagnostic capability. Furthermore, the diagnostic cut-off value for CRP with regard to ovarian cancer was 9.8 mg/L, and high levels of CRP were correlated with stage and tumor size of ovarian cancer. Our study indicated that CRP is valuable in the diagnosis of ovarian cancer, and that combining CRP with CA125 and HE4 improved the diagnostic efficacy with respect to ovarian cancer.

Background: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC)., Patients and Methods: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies. The result was validated in 14 patients (five IPMNs, three IPMCs and six PDACs)., Results: The scoring system utilizing the expression levels of 13 genes showed high diagnostic yield (sensitivity=94.0%, specificity=92.0% and area under the curve=0.94), which was confirmed in the validation set. Furthermore, its diagnostic yield was not reduced even in early-stage pancreatic malignancies (sensitivity=85.0%, specificity=93.0% and area under the curve=0.88)., Conclusion: We developed a blood-based gene expression scoring system for cancer screening in patients with BD-IPMNs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This study aimed to evaluate the predictive value of hematological inflammation-based indexes in the treatment response to neoadjuvant chemoradiotherapy (NCRT) in rectal mucinous adenocarcinomas (MACs)., Methods: Patients with rectal MACs undergoing NCRT and curative resection were included. Inflammation-based indexes such as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated. Receiver operator characteristics analysis was used to determine the optimal cutoff points. Multivariable logistic analysis identified predictors of good response to NCRT. A nomogram was developed and validated internally., Results: A total of 100 patients met the inclusion criteria, with 32 patients developing good response (tumor regression grade, TRG 0 + 1) to NCRT. Lower pre-treatment SII, NLR, and PLR levels were associated with a higher probability of good response to NCRT (P = 0.025, P < 0.001, P = 0.003, respectively), and a higher pre-treatment PNI level was associated with a higher probability of good response to NCRT (P = 0.005). Logistic regression analysis demonstrated that tumor size (< 3 cm, OR = 5.489, P = 0.025), pre-treatment NLR level (< 3.05, OR = 4.025, P = 0.028), pre-treatment PLR level (< 145.98, OR = 4.337, P = 0.038), and pre-treatment PNI level (≥ 41.32, OR = 3.477, P = 0.039) were independent predictors of good response to NCRT. A nomogram was developed with a C-index of 0.827., Conclusion: Hematological inflammation-based indexes, in terms of pre-treatment NLR, PLR, and PNI levels, can help in predicting the treatment response to NCRT for rectal MACs.

Aim: The aim of this study was to identify whether metabolite biomarker candidates for pancreatic cancer (PC) could aid detection of intraductal papillary mucinous neoplasms (IPMN), recognized as high-risk factors for PC. Materials & methods: The 12 metabolite biomarker candidates, which were found to be useful to detect PC in our previous study, were evaluated for plasma samples from patients with PC (n = 44) or IPMN (n = 24) or healthy volunteers (n = 46). Results: Regarding the performance of individual biomarkers of PC and PC high-risk IPMN, lysine exhibited the best performance (sensitivity: 67.8%; specificity: 86.9%). The multiple logistic regression analysis-based detection model displayed high sensitivity and specificity values of 92.5 and 90.6%, respectively. Conclusion: Metabolite biomarker candidates for PC are useful for detecting high-risk IPMN, which can progress to PC.

Objective: The aim of the study was to clarify the diagnostic impact of measuring serum anti-p53 antibody (S-p53Ab) in predicting the histological grades of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas., Methods: We compared the measured values and positive prevalence of S-p53Ab across the different histological grades of 111 resected IPMN cases. We also evaluated the TP53 alterations using immunohistochemistry and next-generation sequencing., Results: Serum anti-p53 antibody were detected in 6 of 111 cases, all of their histological grades were high-grade dysplasia (HGD) and invasive carcinoma (INV). Positive prevalence of S-p53Ab was higher in cases with INV (4/35 cases, 11.4%) than those with HGD (2/38 cases, 5.3%), whereas S-p53Abs were undetectable in cases with low-grade dysplasia. Measured S-p53Ab values were not correlated with either carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9). In 4 of 6 S-p53Ab-positive cases, the TP53 alterations-somatic pathogenic mutations or aberrant immunoreactivity-were identified in their IPMN lesions. A combination assay of S-p53Ab, CEA, and CA 19-9 revealed a 38.4% sensitivity and 81.6% specificity for predicting HGD/INV., Conclusions: Serum anti-p53 antibody can serve as a surrogate marker for TP53 alterations and help predict the presence of HGD/INV in cases with IPMN, in combination with CEA and CA 19-9.

Objective: Ovarian cancer is one of the leading causes of cancer deaths in women. Ovarian cancer is diagnosed at the late stages and generally relapses within 12-14 months of cytoreductive surgery. This is attributed to lack of precise molecular detection methodologies to detect and track the disease. Epigenetic alteration such as aberrant promoter hypermethylation is an important early event that occurs during cancer development and progression. This study focuses on development of a minimally invasive methylation marker that could be used for detection and prognosis of ovarian cancer patients., Methods: Aberrant promoter hypermethylation of RASSF1a and BRCA1 was assessed in circulating DNA of 72 EOC patients using methylation-specific PCR. The findings were correlated with various clinicopathological parameters. Statistical analysis was done using the Fisher exact test and chi-square test., Results: The aberrant methylation patterns of RASSF1a and BRCA1 was identified to be present in the cancerous samples. A total of 31.9 % and 56.9% methylation was observed for RASSF1a and BRCA1 respectively. A striking 50% methylation of BRCA1 was identified in the benign sample cohort, which marks the significance of assessing the hypermethylation pattern to detect cancer at its early stages. Methylation of the two tumor suppressor genes was evident across various stages and grades of ovarian tumors suggesting that this could also help as a prognostic marker., Conclusion: The results of the current study hold significance since the hypermethylation patterns can be identified in the cell-free circulating tumor DNA from a small volume of blood plasma and is a simple and minimally-invasive method. Assessment of hypermethylation patterns of a panel of TSG along with the existing screening markers could aid in better diagnosis and management of the disease. It could also aid in designing specifically tailored treatment strategies to fight the disease.

Objectives: We sought to determine if interleukin (IL)-1β and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone., Methods: Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003-2016) was analyzed for PGE2 and IL-1β (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined., Results: Levels of IL-1β were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0-2671] vs 5.9 [0-797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20-15,180] vs. 140 [10-14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN., Conclusions: Cyst fluid PGE2, IL-1β, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.

Background: Epithelial ovarian cancer is the second most common gynecological cancer. Human Epididymis Protein 4 is a novel biomarker for ovarian cancer. This study aims to explore the role of HE4 in monitoring recurrence and prognostication of ovarian cancer by predicting overall survival (OS) and progression-free survival (PFS)., Materials and Methods: In total, 149 patients with ovarian carcinoma were enrolled in the study. Baseline and post-treatment 3 monthly biomarker levels were recorded. For analysis, patients were divided into primary debulking surgery (PDS) and interval debulking surgery (IDS) groups. Statistical analysis was done using SPSS 24., Results: Median age of patients at diagnosis was 45 (19-75) years. Recurrence was seen in 68.5% (n = 102) patients. The sensitivity of serum HE4 in detecting recurrence was 85.3% (95%CI: 76.95%-91.5%) and specificity was 91.5% (95%CI: 89.5%-98.2%). A >80% decline in HE4 levels during treatment indicated a better PFS, which was statistically significant in both groups (P = 0.04 in PDS and P = <0.001 in IDS group). Multivariate analysis suggested that OS was influenced by optimal cytoreduction in both groups of patients and stage in the IDS group. On the contrary, PFS was influenced by stage and response in HE4 levels in both groups., Conclusion: HE4 levels have similar sensitivity but more specificity when compared with CA125 in diagnosing recurrent ovarian cancer. A >80% decline in HE4 levels during treatment predicts better PFS and can help in prognostication., Competing Interests: None

Early detection of ovarian cancer has the potential to impact mortality. A multimodal screening strategy where rising CA125 values over time, analyzed with the risk of ovarian cancer algorithm (ROCA), triggers transvaginal sonography and possible surgery has high sensitivity and specificity, but still fails to detect the 20% of early-stage cases that do not express CA125. Use of multiple biomarkers could detect cases missed by CA125. We have studied the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) compared with CA125 alone. We used PRoBE design principles to select preclinical longitudinal specimens from 75 women (50 screen-positive, 25 screen-negative) who developed invasive epithelial ovarian cancer (3-5 serial specimens each) and 547 corresponding healthy controls (1-10 serial specimens each) from the ovarian cancer screening trial, UKCTOCS, in a blinded fashion. We measured the multi-marker concentrations in ultra-low serum volumes (16 μL) utilizing multiplexed bead-based immunoassays with low detection limits, high inter- and intra-assay precision, negligible cross-reactivity, and good correlation with standard immunoassays. While, at least one of the complementary biomarkers rose with CA125 in 44% (22/50) of screen-positive cases, there was no advantage in lead time over CA125. Therefore, we developed single-marker longitudinal algorithms (ROCA-like) to determine the presence of a change point to distinguish between the cases and controls. Using these algorithms, at 98% specificity, HE4 and CA72-4 identified 16% (4/25) of screen-negative cases, while MMP-7 identified none. Taken together, HE4 and CA72-4 show promise as complementary biomarkers to CA125 for longitudinal screening., (©2019 American Association for Cancer Research.)

Background: Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction. This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as well as non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum human epididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancers and comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benign ovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125 levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses was calculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levels significantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Using benign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off value for diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6% vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivity to detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125 (92.61% vs. 63.41%). Conclusion: Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer from benign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinous epithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may provide higher accuracy for detecting epithelial ovarian cancer particularly in the early stages., (Creative Commons Attribution License)

Background: IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix glycoprotein-may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN., Methods: Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade., Results: 164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade., Conclusion: Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Accurate preoperative prediction for malignant IPMN is still challenging. The aim of this study was to investigate the validity of neutrophil-to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant intraductal papillary mucinous neoplasm (IPMN)., Methods: The medical records of 60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed., Results: NLR tended to be higher in malignant IPMN (median: 2.23) than in benign IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN (median: 16 mm) than in benign IPMN (median: 8 mm; p < .01). The optimal cutoff values for the NLR and MNH were 3.60 and 11 mm, respectively. The sensitivity and specificity of NLR ≥3.60 for predicting malignant IPMN were 40% and 93%, and those of MNH ≥11 mm were 73% and 77%, respectively. Univariate analysis revealed that NLR ≥3.60 (p < .01) and MNH ≥11 mm (p < .01) were significant predictive factors. On multivariate analysis, enhanced solid component was identified as an independent factor, but NLR ≥3.60 and MNH ≥11 mm were not., Conclusions: NLR and MNH are suboptimal tests in predicting malignant IPMN; however, they can be useful to assist in clinical decision-making.

Background and Objectives: The Sendai consensus guidelines (SCG) and Fukuoka consensus guidelines (FCG) have been examined for their roles in predicting advanced neoplasia (AN) in pancreatic cystic neoplasm (PCN) patients with mixed results. We aim to evaluate the utilities of both guidelines in a Chinese cohort with preoperatively diagnosed mucinous PCNs., Methods: One hundred ninety-seven patients who underwent resections from 2008 to 2015 in Zhong Shan Hospital, Fudan University for suspected PCNs were retrospectively reviewed. Receiver operating characteristic (ROC) curves were calculated and compared to measure diagnostic value., Results: Fifty-five patients were diagnosed with AN pathologically. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the SCG high-risk (SCG HR ) criteria were 87.3%, 28.2%, 32.0%, 85.1%, and 44.7%, respectively, and for the FCG high-risk (FCG HR ) criteria, they were 40.0%, 95.8%, 78.6%, 80.5%, and 80.2%, respectively. ROC curve comparison analyses showed that the FCG HR were superior to the SCG HR (P = 0.02). The performance of the FCG HR was enhanced with CA19-9 incorporated (P = 0.004)., Conclusions: The FCG were superior to the SCG in this retrospective analysis, which could be further improved by the incorporation of CA19-9. However, the practical safety remains uncertain because of missed invasive carcinoma cases., (© 2017 Wiley Periodicals, Inc.)

Background: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers., Methods: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction., Results: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022)., Conclusions: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (P trend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all P heterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all P heterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer., (© 2017 UICC.)

Background: To evaluate whether pretreatment carcinoembryonic antigen and carbohydrate antigen (CA)19-9 are useful predictors of survival in patients with stage IV rectal cancer who have undergone curative resection., Methods: In this retrospective study, data on 73 patients who had undergone curative resection of stage IV rectal cancer were reviewed. Associations between various clinicopathological factors and survival outcomes were analyzed., Results: According to univariate analysis, elevated pretreatment CA19-9 (p = 0.0028), R1 resection (p = 0.0318), and mucinous or poorly differentiated adenocarcinoma (p = 0.0228) were significantly associated with poor overall survival (OS), and lymph node metastasis (p = 0.0211) was significantly associated with poor disease-free survival (DFS). Multivariate analyses showed that elevated pretreatment serum CA19-9 concentration (hazard ratios [HR] 3.33; 95% CI 1.24-9.42; p = 0.0174) was an independent predictor for OS and lymph node metastasis (HR 2.26; 95% CI 1.15-4.82; p = 0.0164) was an independent predictor for DFS. Among 55 patients with recurrences after curative resection, the rate of complete resection of recurrences was significantly higher in patients with normal pretreatment CA19-9 than in those with elevated CA19-9 (p = 0.049). Post-recurrence survival was significantly worse in patients with elevated pretreatment CA19-9 than in those with normal CA19-9 (p = 0.0196)., Conclusions: Pretreatment CA19-9 is good predictor of survival after curative resection of stage IV rectal cancer., (© 2017 S. Karger AG, Basel.)

Purpose: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery., Methods: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves., Results: Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients., Conclusions: Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.

Objective: To evaluate the value of three tumor markers serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19.9) in the diagnosis and postoperative evaluation of ovarian cancer by detecting these three markers., Patients and Methods: A total of 187 patients were studied and included in the ovarian cancer group, benign pelvic mass group, and the normal control group. The levels of serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 199 (CA19.9) were detected, respectively, and their effects on the diagnosis, evaluation, pathology typing and staging of ovarian cancer were measured., Results: The sensitivity of the detection of ovarian cancer by GOLPH3 combined with CA125 and CA19.9 was higher than that by a single marker (p<0.05). The level of serum GOLPH3 in patients with serous and endometrioid carcinoma was significantly higher than that in patients with mucinous carcinoma, clear-cell carcinoma and germ cell tumor (p<0.05). There was no significant statistical difference in serum GOLPH3 level between patients with ovarian malignancies at stage III-IV and those at stage I-II (p>0.05). The levels of serum GOLPH3, CA125 and CA19.9 in patients with ovarian malignancies after surgery were significantly lower than those before surgery (p<0.05)., Conclusions: The combined detection by GOLPH3, CA125, and CA19.9 may improve the diagnosis rate of ovarian epithelial cancer. GOLPH3, as a new ovarian cancer tumor marker used in clinical diagnosis, is expected to become an important indicator for the early diagnosis of ovarian cancer and the determination of clinical surgery efficacy.

Objective: To investigate the clinicopathological features and risk factors in patients with mucinous borderline ovarian tumors (MBOT). Methods: From 1999 to 2006, 66 MBOT patients in our hospital with more than ten-year follow-up were enrolled retrospectively. They were re-classified according to the literature. The clinicopathological features of different subgroups, including age, preoperative serum tumor markers, surgical methods, pathological features, surgical pathology staging, as well as the risk factors of recurrence and survival were analyzed. Results: Median age was 39 years in 66 patients. Before the surgery, 33.3% (20/60) patients had elevated CA125 and 51.7% (30/58) had elevated CA199. The accurate rate for fast frozen pathology of resected specimen was 73.4%. 21 patients underwent conservative surgery and 45 patients underwent extensive surgery. 57 patients underwent comprehensive operation and 43 cases (75.4%) resulted in stage Ⅰ. 48 of the 66 patients (72.7%) had intestinal-type tumors (IMBT) and 18 patients (27.3%) had endocervical-like tumors (EMBT). The median follow-up was 150 months. Eight recurrences (12.1%) were identified. The mean time between surgery to the initial recurrence was 26.4 months (13 to 50 months). Recurrence rate of IMBT was higher than that of EMBT (14.6% versus 5.6%) with no significance ( P >0.05). All patients with pseudomyxoma had disease recurrence. Recurrence rate of stage Ⅲ patients was significantly higher than that of stage Ⅰ patients (33.3% versus 9.3%, P <0.05). During the follow-up period, tumor-related death occurred in 2 cases with a 10-year survival rate of 95.4%. Kaplan-Meier method and Log Rank analysis showed that clinical staging and peritonealmyxoma were adverse prognostic factors ( P <0.05). Although the recurrence rate of patients undergoing conservative surgery was higher than that of patients with extensive surgery (23.8% versus 6.7%, P =0.047), the overall survival was almost the same between these two groups ( P >0.05). Conclusions: MBOT patients have relatively good prognosis. IMBT are more common than EMBT subtypes, but recurrence rate and patient survival were almost the same between these two groups. Patients with pseudomyxoma was more likely to have disease recurrence. Patients who underwent conservative surgery resulted in higher recurrence rate but did not affect the overall survival of patient. Pseudomyxoma and clinical staging were adverse prognostic factors in MBOT patients.

Objectives: Circulating epithelial cells (CECs) are identified in the blood of patients with intraductal papillary mucinous neoplasms (IPMNs) despite the absence of malignancy. We assessed the blood of patients undergoing resection for IPMN or other benign pancreatic lesions for CECs., Methods: Peripheral blood was collected from 26 patients prior to pancreatic resection and filtered by the ISET (Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and duodenal homeobox protein 1), a pancreas marker., Results: Nineteen patients underwent resection of an IPMN without associated malignancy. Eleven patients (58%) had cytokeratin-positive CECs. Circulating epithelial cells were significantly more likely to be found in patients with IPMNs with high-grade dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin-positive CECs also had separate populations of cytokeratin-positive, Pdx1-positive CECs, suggesting a pancreatic source. Dual-staining CECs were more frequently found in patients with high-grade dysplasia (P = 0.04). Patients with IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood compared with those without IPMNs (P = 0.01)., Conclusions: Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.

Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples ( n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples ( n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups ( p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

Backround: The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection., Methods: Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured., Results: A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant., Conclusion: Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Importance: Invasive intraductal papillary mucinous carcinoma has aggressive malignant behavior, including lymph node metastasis. It is important to identify factors associated with invasive intraductal papillary mucinous carcinoma to determine operative procedures, but they remain unclear., Objective: To identify the specific factors associated with invasive intraductal papillary mucinous neoplasms for branch duct, main duct, and mixed type carcinomas., Design, Setting, and Participants: Retrospective cohort study of 286 consecutive patients who underwent surgical resection for intraductal papillary mucinous neoplasm from July 1999 to December 2015 at a tertiary institute. We compared clinical features between 96 patients (33.6%) with invasive intraductal papillary mucinous carcinoma and 190 patients (66.4%) with noninvasive intraductal papillary mucinous neoplasm for each morphological type., Main Outcomes and Measures: Factors associated with invasive intraductal papillary mucinous carcinoma. Mural nodule size was measured by endoscopic ultrasonography., Results: Of the 286 patients included in the cohort, the median (range) age was 71 (28-86) years, and 162 (56.6%) were male. High mural nodule size was independently associated with invasive intraductal papillary mucinous carcinoma in all types (branch duct: odds ratio [OR], 1.992; 95% CI, 1.177-3.367; P = .01; main duct: OR, 1.443; 95% CI, 1.094-1.905; P = .01; and mixed: OR, 1.178; 95% CI, 1.057-1.312; P = .04). The cutoff values for intraductal papillary mucinous neoplasms, determined by a receiver operating characteristic, were 9 mm for branch duct and 6 mm for mixed and main duct carcinoma. A high carcinoembryonic antigen level in the pancreatic juice was independently associated with mixed (OR, 1.002; 95% CI, 1.000-1.003; P = .01) and main duct (OR, 1.002; 95% CI, 1.000-1.003; P = .048) carcinomas, and the cutoff values were determined to be 150 and 300 ng/mL, respectively (to convert to micrograms per liter, multiply by 1). In addition, both being female and having an elevated serum carbohydrate antigen 19-9 level were also found to be independently associated with mixed type invasive intraductal papillary mucinous carcinoma, and using any 2 among 4 identified factors yielded the highest accuracy (79.0%) for mixed type carcinomas. For all types, the accuracy for these factors was 86.0% for differentiating between invasive and noninvasive intraductal papillary mucinous neoplasms, which was superior to the accuracies using the "high-risk stigmata" factors or "worrisome features" suggested by the international consensus guideline in 2012 (66.1% and 39.9%, respectively)., Conclusions and Relevance: The measurement of mural nodule size in all types of carcinomas and carcinoembryonic antigen level in the pancreatic juice in mixed and main duct carcinomas might play important roles in predicting invasive intraductal papillary mucinous carcinoma, but further large studies are needed to confirm these results.

There are no suitable screening modalities for ovarian carcinomas (OC) and repeated imaging and CA-125 levels are often needed to triage equivocal ovarian masses. Definitive diagnosis of malignancy, however, can only be established by histologic confirmation. Thus, the ability to detect OC at early stages is low, and most cases are diagnosed as advanced disease. Since tumor cells expose phosphatidylserine (PS) on their plasma membrane, we predicted that tumors might secrete PS-positive exosomes into the bloodstream that could be a surrogate biomarker for cancer. To address this, we developed a highly stringent ELISA that detects picogram quantities of PS in patient plasma. Blinded plasma from 34 suspect ovarian cancer patients and 10 healthy subjects were analyzed for the presence of PS-expressing vesicles. The nonparametric Wilcoxon rank sum test showed the malignant group had significantly higher PS values than the benign group (median 0.237 vs. -0.027, p=0.0001) and the malignant and benign groups had significantly higher PS values than the healthy group (median 0.237 vs -0.158, p<0.0001 and -0.027 vs -0.158, p=0.0002, respectively). ROC analysis of the predictive accuracy of PS-expressing exosomes/vesicles in predicting malignant against normal, benign against normal and malignant against benign revealed AUCs of 1.0, 0.95 and 0.911, respectively. This study provides proof-of-concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.

Objective: To investigates the diagnostic value of combined detection serum CCL18, CXCL1 antigen, C1D, TM4SF1, FXR1, TIZ IgG autoantibody by suspension array for ovarian cancer. Methods: Suspension array was used to detect CCL18, CXCL1 antigen, C1D, TM4SF1, FXR1, TIZ IgG autoantibody in 120 cases of healthy women, 204 cases of patients with benign pelvic tumors, 119 cases of pelvic malignant tumor patients, and 40 cases with breast cancer, lung cancer oroliver cancer, respectively. Constructed diagnosis model of combined detection six biomarkers for diagnosis of ovarian malignant tumor. Constructed diagnosis model of combined detection autoantibodies to diagnose epithelial ovarian cancer. Analysed the value of detecting six biomarkers for diagnosis of ovarian malignant tumor and detecting autoantibodies for diagnosis of epithelial ovarian cancer. Analysed diagnostic value of detecting six biomarkers to diagnose stage Ⅰ and Ⅱepithelial ovarian cancer. Compared diagnostic value of detecting six biomarkers in diagnosis of tissue types and pathologic grading with that of CA(125). Results: Model of combined detecting six biomarkers to diagnose ovarian malignant tumor was logit ( P ) =-11.151+0.008×C1D+0.011×TM4SF1+0.011×TIZ-0.008×FXR1+0.021×CCL18+0.200×CXCL1. Model of combined detection autoantibodies to diagnose epithelial ovarian cancer was logit ( P ) =-5.137+0.013×C1D+0.014×TM4SF1+0.060×TIZ-0.060×FXR1. Sensitivity and specificity of detecting six biomarker to diagnose ovarian malignant tumor was 90.6% and 98.7%. Sensitivity and specificity of detecting autoantibodies to diagnose epithelial ovarian cancer was 75.8% and 96.7%. Combined detection for six biomarkers to diagnose serous and mucinous ovarian cancer was statistically no better than those of CA(125) ( P =0.196 and P =0.602, respectively); there was significantly difference in diagnosis of ovarian cancer ( P =0.023), and there was no significantly difference in diagnosis of different pathological grading ( P =0.089 and P =0.169, respectively). Conclusions: Constructing diagnosis model of combined detection six biomarker to diagnose ovarian malignant tumor and constructed diagnosis model of combined detectionautoantibodies to diagnose epithelial ovarian cancer. Combined detection six biomarkers to diagnose serous and mucinous ovarian tumors is better than that of CA(125).

Objective: To elucidate the clinicopathologic characteristics, immunophenotype and differential diagnosis of ovarian seromucinous carcinoma. Methods: The clinical and pathological characteristics of 7 cases of ovarian seromucinous carcinoma were analyzed. Immunohistochemical study of selected markers was performed employing the EnVision method. Literature of ovarian seromucinous carcinoma were also reviewed. Results: The age of the 7 ovarian seromucinous carcinoma patients ranged from 27 to 70 years of age (mean=48 years). Two patients had bilateral ovarian tumors. The complaint of most patients was abdominal distention. The serum concentration of CA125 and/or CA19-9 was elevated in most patients.Four patients were found to have ascites during surgery, of whom 2 were also found to have malignant cells in their ascites or peritoneal washings. The maximum dimension of these tumors ranged from 6.0 to 15.0 cm (mean=9.3 cm). Grossly, 6 of 9 tumors were predominantly cystic with protrusions of papillae from the inside wall of the cysts. Among these 6 tumors, 2 had brown viscous material in the cyst. The other 3 tumors were predominantly solid. Microscopically, all 9 tumors contained endocervical-like mucinous cells and other Mullerian cells. The tumor cells had intermediate or severe atypia. A lot of acute inflammatory cells especially neutrophil polymorphs could be seen in the stroma and lumens of all the 9 tumors, which is an apparent feature for ovarian seromucinous tumors. Architecturally, the tumors mainly exhibited complex papillary architectures, compactly back-to-back glandular lumensforming cribriform, labyrinthine formations, or solid growth pattern, with immunophenotype of Mullerian tumors. Mucin stain was performed in 1 tumor with AB positive, PAS positive and D-PAS positive, highlighting intracytoplasmicmucin secretions. Follow-up (3-86 months with a mean of 21 month) data revealed that except 1 patient dying of the tumor at 81 months after surgery, the other 6 patients all survived the malignancy. Conclusions: Seromucinous carcinoma of the ovary possesses relatively special clinicopathologic features, with some morphological and immunophenotypical overlap with endometrioid carcinoma and low grade serous carcinoma of the ovary. It is necessary to thoroughly investigate the pathogenesis and molecular changes involved in the type of tumor to determine whether it is a convincingly distinctive category of ovarian carcinoma.

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

Objectives: The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary., Methods: This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed., Results: One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%., Conclusions: Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) are the most frequent cystic pancreatic tumors. Little is known about their molecular alterations, but mutations in GNAS have been reported to promote IPMN formation. A tumor-derived fraction of circulating cell-free DNA (cfDNA), isolated from blood samples, contains many of the same mutations as the primary tumor, and could be a tool for noninvasive disease monitoring. We found that the total amount of cfDNA can discriminate between individuals without pancreatic lesions (controls) and patients with Fukuoka-negative branch-duct IPMN or pancreatic cancer. Furthermore, we detected GNAS mutations in cfDNA from patients with IPMN, but not in patients with serous cystadenoma or controls. Analyses of cfDNA might therefore be used in the diagnosis of patients with IPMN or in monitoring disease progression., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Premalignant lesions for many cancers have been identified, and efforts are currently directed toward identification of antigens expressed on these lesions that would provide suitable targets for vaccines for cancer prevention. Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts of which a subset has the potential to progress to cancer. Currently, there are no validated predictive markers for progression to malignancy. We hypothesized that the presence or absence of immune surveillance of these lesions would be one such factor. Here we show that the tumor antigen MUC1, which is abnormally expressed on pancreatic cancer and is a target for cancer immunosurveillance, is also abnormally expressed on premalignant IPMN. We show that some IPMN patients make MUC1-specific IgG. Moreover, we show evidence of CD4 and CD8 T cell infiltration into IPMN areas of high dysplasia suggesting an ongoing immune response within the lesions. We also found, however, increased levels of circulating myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in some IPMN patients as well as evidence of T cell exhaustion. Further studies correlating immunosurveillance or immunosuppression with IPMN progression to malignancy will help define the immune response as a biomarker of risk, leading potentially to a vaccine to boost spontaneous immunity and prevent progression to cancer.

Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

Purpose of Investigation: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous ovarian cancer (MOC)., Materials and Methods: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC., Results: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125., Conclusions: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.

Background: CA125 is very helpful in treatment monitoring and detection of epithelial ovarian cancer (EOC) recurrence. However there is controversy as to its accuracy and optimal usage. What is the impact of the CA125 levels before primary surgery treatment to the survival of patients? This study aimed to detect any association of preoperative serum levels with prognosis and survival in EOC patients., Materials and Methods: Our cohort comprised EOC patients in Dr. Sardjito Hospital, Yogyakarta, Indonesia, who complied with follow up. To explore the effect of preoperative CA125 levels and other variables on survival Cox's regression models were applied., Results: A total of 90 cases of EOC who had surgery were available for follow up. The level of CA125 poroved to be a prognostic factor for overall survival of EOC patients, with an adjusted HR of 4.10 (p = 0.03). Adjuvant chemotherapy was another prognostic factor, 1 - 2 cycles having an adjusted HR of 0.17 (p = 0.04) and 3 - 8 cycles HR 0.39 (p = 0.06). Other factors such as age of patients adjusted HR 1.54 (p = 0.32), moderate differentiation (adjusted HR 1.61, p = 0.51) poor differentiation (adjusted HR 3.41, p = 0.15), and stage of disease (adjusted HR 1.98, p = 0.27) were statistically not significant. However, this might have been because the power of the study was low., Conclusions: Preoperative level of CA125 is a prognostic factor for overall survival in EOC patients. The best cut-off for prognostic classification of CA125 serum level is 70 U/ml.

Introduction: Determining the dignity of intraductal papillary mucinous neoplasms (IPMNs) by imaging procedures is challenging. Various CT-based criteria were evaluated., Patients and Methods: Preoperative CT scans from 47 patients with IPMN were analyzed. Predefined criteria of malignancy were compared between patients with benign (bIPMN; n = 28) and malignant (mIPMN; n = 19) tumors, and a summation score was determined., Results: Preoperative carbohydrate-antigen 19-9 levels were higher in patients with mIPMN (p = 0.013). The diameter of the main pancreatic duct was greater in patients with mIPMN (p < 0.0001). More patients with mIPMN showed bile duct obstruction (p = 0.0076), solid tumor components (p = 0.0076), contrast enhancement in cystic walls (p = 0.0086), peripancreatic lymph nodes (p = 0.0076), and abrupt diameter changes of the main pancreatic duct (p = 0.0008). The CT density of the cysts was higher in mIPMN (p = 0.0063). The diagnostic accuracy of the summation score (sensitivity: 0.84, specificity: 0.96) was greater when compared to each individual CT parameter., Conclusions: The prevalence and extent of various CT-based abnormalities are greater in patients with mIPMN, but the wide overlap limits the diagnostic value of each individual parameter. A simple summation score largely enhances the diagnostic accuracy., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate the utility of tumor markers and complete blood count to increase the diagnostic accuracy to detect malignant cases that are intraoperatively reported as mucinous borderline ovarian tumors (BOT)., Study Design: Patients who underwent laparotomy at our gynecologic oncology clinic between 2007 and 2015 for evaluation of an adnexal mass with an intraoperative frozen section report of mucinous BOT were retrospectively analyzed. Patients were grouped according to the final pathological diagnoses (malignant, borderline and benign), and were compared in terms of tumor marker levels and complete blood count parameters. Significant parameters were evaluated together with frozen section results, and were assessed for diagnostic accuracy., Results: A total of 63 patients were included in the study. Of these, 41 patients had borderline, 11 patients had benign, and 11 patients had malignant mucinous ovarian tumors. Patient age, menopausal status, hemoglobin, platelet and lymphocyte counts were similar among the groups (p>0.05). On the other hand, white blood cell, neutrophil counts and neutrophil/lymphocyte ratio (NLR) were significantly higher in malignant cases (p<0.05). Similarly, CA125 and CA19-9 were significantly higher in malignant group (p<0.05). When evaluated with the frozen section results, CA19-9 and NLR had the highest sensitivity to detect mucinous cancers (81 and 78 percent, respectively)., Conclusions: In patients who have an intraoperative frozen section diagnosis of borderline mucinous ovarian tumors, CA19-9, NLR and CA125 were significant predictors of malignancy. In light of larger future studies, we believe that integrating these parameters into routine clinical practice may decrease the rate of under diagnosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose of Investigation: To correlate serum CA125 at relapse with survival in ovarian cancer patients who achieved a complete response after primary cytoreduction and paclitaxel- and platinum-based chemotherapy., Materials and Methods: The study was conducted in 104 patients., Results: The 25%, 50%, and 75% quantiles of CA125 levels at relapse were 46, 118, and 190 U/ml. By log-rank test, survival after recurrence was related to consolidation treatment (p = 0.046), platinum-free interval (PFI) (p < 0.000005), number of recurrence sites (p = 0.03), treatment at recurrence (p = 0.002), and serum CA125 taking 118 U/ml as cut-off (p = 0.013). On multivariate analysis, consolidation treatment (p = 0.007), PFI (p = 0.0001), treatment at recurrence (p = 0.01), and serum CA125 taking 118 U/ml as cut-off (p = 0.04) were independent prognostic variables for survival., Conclusions: Serum CA125 at relapse was an independent prognostic variable. Patients with serum CA125 > 118 U/m had 1.943 higher risk of death than those with lower antigen value.

Background: MicroRNAs (miRs) have been implicated in the etiology of various human cancers. The aim of this study was to investigate the association of the expression of three members--miR 200a, miR 200b, and miR 200c belonging to the miR-200 family with clinicopathological characteristics and their impact on the progression of epithelial ovarian cancer (EOC)., Materials and Methods: Total RNA from serum was isolated by Trizol method, polyadenylated, and reverse transcribed into cDNA. Expression levels of miR-200a, miR-200b, and miR-200c were detected by using miRNA qRT-PCR. We measured miR expression in 70 serum samples of EOC patients with matched controls using U6 snRNA as a reference. Levels of miR expression was compared with distinct clinicopathological features., Results: Expression of miR-200a was found to be greater than six-fold (p = 0.01), miR-200b and miR-200c greater than three-fold (p = 0.01) in comparison with matched normal controls. Association of miRNA expression with clinicopathological factors and progression was statistically evaluated. The expression levels of miR-200a and miR-200c were found to be significantly associated with disease progression (p = 0.04 and p < 0.001, respectively). miR-200a overexpression was found be associated with tumor histology and stage. Patients with lymph node metastasis showed significant elevation of miR-200c (p = 0.006). The AUC in ROC curve also indicated that serum levels of miR-200a and miR-200c might be worthwhile as a diagnostic tool in the near future., Conclusion: Our findings suggest that miR-200a, miR-200b, and miR-200c overexpressions are associated with the aggressive tumor progression and be recognized as reliable markers to predict the prognosis and survival in EOC patients.

Background: The immune system is important in epithelial ovarian cancer (EOC). Interleukin-6 is associated with chemoresistance and an immune-suppressive tumor microenvironment. We investigated whether a combination of chemotherapeutics, blockade of interleukin 6 (IL-6) receptor (IL-6R; tocilizumab), and immune enhancer interferon-α (Peg-Intron) is feasible, safe, and able to enhance immunity in patients with recurrent EOC., Patients and Methods: In this dose-escalation study, patients received tocilizumab 1, 2, 4, or 8 mg/kg i.v., q4 weeks during the first three cycles of carboplatin (AUC5) plus doxorubicin [pegylated liposomal doxorubicin (PLD) 30 mg/m(2) or doxorubicin 50 mg/m(2) i.v., day 1, q4 weeks, for six cycles]. At the highest tocilizumab dose (8 mg/kg), Peg-Intron (1 µg/kg s.c.) was added. Peripheral blood mononuclear cells were collected for immunomonitoring at baseline, after three and six cycles. Dose-limiting toxicity (DLT), CA-125, and radiologic response were evaluated., Results: In the 23 patients enrolled, no DLT was established. The most frequent grade 3/4 adverse events (CTCAE v4.03) were neutropenia (23%), febrile neutropenia (19%), and ileus (19%). No treatment-related deaths occurred. Using CT evaluation, 11 of 21 assessable patients responded, 6 had stable disease and 3 progressive disease. Patients receiving highest dose tocilizumab showed a functional blockade of IL-6R with increased levels of serum IL-6 (P = 0.02) and soluble IL-6R (P = 0.008). Consequently, immune cells displayed decreased levels of pSTAT3, myeloid cells produced more IL-12 and IL-1β while T cells were more activated and secreted higher amounts of effector cytokines interferon-γ and tumor necrosis factor-α. An increase in sIL-6R was potentially associated with a survival benefit (P = 0.03)., Conclusions: Functional IL-6R blocking is feasible and safe in EOC patients treated with carboplatin/(pegylated liposomal)doxorubicin, using 8 mg/kg tocilizumab. This combination is recommended for phase II evaluation based on immune parameters., Clinical Trial Register: NCT01637532., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Little is known about the prognostic significance of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) concentrations for predicting malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) of pancreas., Method: The study cohort consisted of 367 patients with surgical biopsy proven IPMN at Seoul National University Hospital. Preoperative serum tumor markers were evaluated and compared with other clinical variables., Results: Malignant pathology (high grade dysplasia [HGD] and invasive IPMN) was identified in 117 (31.9%) patients. Elevated serum CA19-9 was more frequent in patients with malignant (34.2%, P < 0.001; invasive IPMN vs. HGD 47.9% vs. 11.4%, P < 0.001) and main duct type (40.0%, P = 0.003) IPMN. Multivariate analysis showed main pancreatic duct (MPD) >5 mm (P < 0.001), mural nodules (P < 0.001), and elevated serum CA19-9 (P < 0.001) were independent predictors of malignancy. The sensitivity, specificity and accuracy were 34.2%, 92.4%, and 73.8%, respectively, for elevated serum CA19-9; 63.3%, 78.0%, and 73.3%, for MPD >5 mm; and 59.0%, 86.4%, and 77.7%, for mural nodules., Conclusion: Serum CA19-9 is significantly higher in patients with malignant IPMN, especially in patients with invasive and main duct type IPMN. The diagnostic power of serum CA19-9 in predicting malignancy is comparable to that of MPD >5 mm and mural nodules., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse., Methods: CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively., Results: We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse., Discussion: Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Background/objectives: Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N-glycan profile and to investigate its clinical utility in patients with IPMNs., Methods: We measured serum N-glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N-glycan changes and clinical parameters., Results: Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve = 0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60-486.4] and the presence of enhancing solid components (OR, 35.8; 95% CI, 5.39-409.6) were significant risk factors for invasive IPMNs., Conclusions: We performed a comprehensive evaluation of the changes in serum N-glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)