Concordance of BRCA mutation detection in tumor versus blood, and frequency of bi-allelic loss of BRCA in tumors from patients in the phase III SOLO2 trial.

OBJECTIVE: Maintenance olaparib provided a progression-free survival benefit in the phase III SOLO2 trial (NCT01874353) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (BRCAm). However, questions remain regarding tumor versus germline BRCA testing and the impact of heterozygous versus bi-allelic loss of BRCA1 or BRCA2 in the tumor. METHODS: Blood and tumor samples were analyzed. A concordance analysis of germline BRCAm status (BRACAnalysis® CLIA test) and tumor BRCAm status (myChoice® CDx test) was conducted (Myriad Genetic Laboratories, Inc.). Bi-allelic loss of BRCA1 and BRCA2 and a genomic instability score (GIS) (myChoice® CDx test) were also determined. RESULTS: 289 of 295 enrolled patients had a germline BRCAm confirmed centrally and tumor BRCAm status was evaluable in 241 patients. There was 98% and 100% concordance between tumor and germline testing for BRCA1m and BRCA2m, respectively, with discordance found in four cases. Of 210 tumor samples evaluable for BRCA zygosity, 100% of germline BRCA1-mutated tumors (n = 144) and 98% of germline BRCA2-mutated tumors (n = 66) had bi-allelic loss of BRCA. One patient with a heterozygous BRCA2m had a GIS of 53, was progression free for 911 days and remained on olaparib at data cut-off. CONCLUSIONS: Very high concordance was demonstrated between tumor and germline BRCA testing, supporting wider implementation of tumor BRCA testing in ovarian cancer. Near 100% rates of bi-allelic loss of BRCA in platinum-sensitive relapsed ovarian tumors suggest routine testing for BRCA zygosity is not required in this population and reflects BRCA loss being a driver of tumorigenesis.

Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer.

OBJECTIVES: Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell-free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients. METHODS: The status of THBS1 methylation was detected by quantitative methylation-specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve. RESULTS: Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non-atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001). CONCLUSION: Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.

A Possible Definition of Oligometastasis in Pancreatic Cancer and Associated Survival Outcomes.

BACKGROUND: Oligometastatic cancer (OM) is possibly associated with relatively better survival outcomes. We attempted to identify cases in line with this OM concept. PATIENTS AND METHODS: A total of 130 cases with unresectable metastatic pancreatic cancer underwent non-curative surgery from April 2001 to December 2019. Sites of metastasis, clinicopathological information, and surgical outcomes were collected to formulate a better definition of OM. RESULTS: OM criteria were defined as having metastasis to a single organ, few countable lesions and low serum cancer antigen 19-9 level. The median overall survival after non-curative surgery of OM cases was 13.0 months and was significantly better than that of non-OM cases (8.4 months, p=0.003). CONCLUSION: We propose single-organ metastasis of limited tumor volume (H1 or P1/2 by the Japanese Society of Cancer of the Colon and Rectum classification) and low serum cancer antigen 19-9 level (<2,000 U/ml) as new criteria for defining OM pancreatic cancer.

Effect of Preoperative Immunonutrition on Postoperative Major Morbidity after Cytoreductive Surgery and HIPEC in Patients with Peritoneal Metastasis.

The effect of preoperative immunonutrition intake on postoperative major complications in patients following cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) was assessed. The accuracy of C-Reactive Protein (CRP) for detecting postoperative complications was also analyzed. Patients treated within a peritoneal carcinomatosis program in which a complete or optimal cytoreduction was achieved were retrospectively analyzed. They were divided into two groups based on whether preoperative immunonutrition (IMN) or not (non-IMN) were administered. Clinical and surgical variables and postoperative complications were gathered. Predictive values of major morbidity of CRP during the first 3 postoperative days (POD) were also evaluated. A total of 107 patients were included, 48 belonging to the IMN group and 59 to the non-IMN group. In multivariate analysis immunonutrition (OR 0.247; 95%CI 0.071-0.859; p = 0.028), and the number of visceral resections (OR 1.947; 95%CI 1.086-3.488; p = 0.025) emerged as independent factors associated with postoperative major morbidity. CRP values above 103 mg/L yielded a negative predictive value of 84%. Preoperative intake of immunonutrition was associated with a decrease of postoperative major morbidity and might be recommended to patients with peritoneal carcinomatosis following CRS. Measuring CRP levels during the 3 first postoperative days is useful to rule out major morbidity.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs. cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: A retrospective cohort study.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefits in patients with intraperitoneal malignant lesions, but there is no study specific to intrahepatic cholangiocarcinoma (ICC). PURPOSE: To compare the prognosis of patients with advanced ICC undergoing CRS + HIPEC compared with CRS alone. METHODS: This study was a retrospective cohort study of patients with advanced ICC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between 01/2014 and 12/2018. The patients were divided into either CRS + HIPEC or CRS group based on the treatment they received. Overall survival (OS), complications, hospital stay, biochemical indicators, tumor markers, and number of HIPEC were examined. RESULTS: There were 51 and 61 patients in the CRS + HIPEC and CRS groups, respectively. There were no differences between the groups regarding preoperative CA19-9 levels (421 ± 381 vs. 523 ± 543 U/mL, P = 0.208). The hospital stay was longer in the CRS + HIPEC group (22.2 ± 10.0 vs. 18.6 ± 7.6 days, P = 0.033). The occurrence of overall complications was similar in the two groups (37.2% vs. 34.4%, P = 0.756). The postoperative CA19-9 levels were lower in the CRS + HIPEC group compared with the CRS group (196 ± 320 vs. 337 ± 396 U/mL, P = 0.044). The median OS was longer in the CRS + HIPEC group than in the CRS group (25.53 vs. 11.17 months, P < 0.001). Compared with the CRS group, the CRS + HIPEC group showed a higher occurrence of leukopenia (7.8% vs. 0, P = 0.040) but a lower occurrence of total bilirubin elevation (15.7% vs. 37.7%, P = 0.032). CONCLUSION: CRS + HIPEC could be a treatment option for patients with advanced ICC, with improved OS and similar complications and adverse events compared with CRS alone.

Development and validation a simple model for identify malignant ascites.

The differential diagnosis of benign ascites and malignant ascites is incredibly challenging for clinicians. This research aimed to develop a user-friendly predictive model to discriminate malignant ascites from non-malignant ascites through easy-to-obtain clinical parameters. All patients with new-onset ascites fluid were recruited from January 2014 to December 2018. The medical records of 317 patients with ascites for various reasons in Renmin Hospital of Wuhan University were collected and reviewed retrospectively. Thirty-six parameters were included and selected using univariate logistic regression, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses to establish a mathematical model for differential diagnosis, and its diagnostic performance was validated in the other groups. Age, cholesterol, hypersensitivity C-reactive protein (hs-CRP) in serum, ascitic fluid adenosine deaminase (AF ADA), ascitic fluid lactate dehydrogenase (AF LDH) involvement in a 5-marker model. With a cut-off level of 0.83, the sensitivity, specificity, accuracy, and area under the ROC of the model for identifying malignant ascites in the development dataset were 84.7%, 88.8%, 87.6%, and 0.874 (95% confidence interval [CI], 0.822-0.926), respectively, and 80.9%, 82.6%, 81.5%, and 0.863 (95% CI,0.817-0.913) in the validation dataset, respectively. The diagnostic model has a similar high diagnostic performance in both the development and validation datasets. The mathematical diagnostic model based on the five markers is a user-friendly method to differentiate malignant ascites from benign ascites with high efficiency.

Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid.

Tumor-derived cell-free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC-LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC-PM). This study evaluated the presence of tumor-derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC-PM and in the plasma of 100 patients with isolated CRC-LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor-derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC-LM and 20% of CRC-PM patients and in peritoneal fluid in all CRC-PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC-PM plasma than in CRC-LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC-PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor-derived cfDNA in plasma is a poor biomarker to monitor CRC-PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC-PM treatment decisions.

Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients.

OBJECTIVE: The role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC. METHODS: From a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs). RESULTS: The median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8-43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8-8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7-10.2, months), CC-2 (5.6, 95%CI: 3.0-8.2, months) and CC-3 (6.5, 95%CI: 5.2-7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%. CONCLUSIONS: Only complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.

Occurrence of seromucinous borderline tumours in the peritoneal lesions after bilateral salpingo-oophorectomy.

A 65-year-old woman with a previous history of bilateral salpingo-oophorectomy had peritoneal cysts, increasing in size over 15 years and an increasing cancer antigen 19-9 (CA 19-9) level. The size of the cysts eventually reached 86 mm and 70 mm. As malignant transformation of endometriosis was suspected, we performed peritoneal cystectomy and hysterectomy. Histopathology revealed seromucinous borderline tumours (SMBTs) derived from endometriosis. One month after surgery, her CA 19-9 level had decreased. It is rare for SMBT to occur after bilateral salpingo-oophorectomy; surgical management is the best treatment at present.

Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases. PATIENTS AND METHODS: We recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression. RESULTS: ctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (< 0.25%) in both the pre- and postoperative settings (median 4.8 vs. 19.3 months, p < 0.001, and 9.2 vs.15.0 months, p = 0.049, respectively; log-rank test). On multivariate analysis, high-grade histology [hazard ratio (HR) 3.42, p = 0.001], incomplete resection (HR 2.35, p = 0.010), and high preoperative MSVAF (HR 3.04, p = 0.001) were associated with worse PFS. Patients with new postoperative alterations in the context of preoperative alteration(s) also had a significantly shorter PFS compared with other groups (HR 4.28, p < 0.001). CONCLUSIONS: High levels of perioperative ctDNA and new postoperative ctDNA alterations in the context of preoperative alterations predict worse outcomes in patients undergoing resection for peritoneal metastases. This may highlight a role for longitudinal ctDNA surveillance in this population.

Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases.

Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.

Efficacy of ascitic fluid cell block for diagnosing primary ovarian, peritoneal, and tubal cancer in patients with peritoneal carcinomatosis with ascites.

OBJECTIVE: To compare the efficacy of ascitic fluid cell block (ACB) with that of core needle biopsy (CNB) or the CA125/CEA ratio in diagnosing primary tubo-ovarian cancer in female patients with peritoneal carcinomatosis (PC) with ascites. METHODS: This retrospective study examined female patients with PC with ascites who had available results for ACB, peritoneal tumor CNB, and the CA125/CEA ratio. Several measures of the accuracy of ACB and the CA125/CEA ratio were calculated and compared, with CNB as the reference standard. RESULTS: Of 81 patients with available results, 57 were clinically diagnosed with primary tubo-ovarian cancer. Overall, 52, 47, and 64 patients were diagnosed via CNB, ACB, and CA125/CEA ratio > 25, respectively. CNB and ACB identified the cancer origin in 91.4% and 82.7% cases, respectively. The concordance ratio of the immunohistochemical findings between ACB and CNB was 93.6%. Two patients with inconclusive CNB results were diagnosed with primary tubo-ovarian cancer via ACB. The sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio were 86.5%, 93.1%, 95.7%, 79.4%, and 12.5, respectively, for ACB and 94.2%, 48.3%, 76.6%, 82.4%, and 1.82, respectively, for CA125/CEA ratio > 25. CONCLUSIONS: ACB is not inferior to CNB in diagnosing primary tubo-ovarian cancer; the two methods complement each other. ACB can substitute CNB in diagnosing primary tubo-ovarian cancer in selected PC patients. ACB is superior to a CA125/CEA ratio of >25 in diagnosing primary tubo-ovarian cancer. ACB is effective, reliable, and convenient for diagnosing primary tubo-ovarian cancer in PC patients with ascites.

Prognostic value of serum HE4 in patients with advanced ovarian, fallopian tube, and peritoneal carcinoma.

PURPOSE: In this study, the prognostic value of serum HE4 was investigated in patients with advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: Serum HE4 and CA125 levels were measured in both patients and controls, and the response of treatment and the detection of recurrence were evaluated by serum HE4 and CA125 levels in the patients. RESULTS: The results showed that the levels of serum HE4 and CA125 were significantly higher in advanced patients than those seen in benign disease controls (p < 0.001). Compared with CA125, HE4 had higher specificity, but lower sensitivity. Furthermore, serum HE4 was closely associated with the response of treatment and recurrence, the effective response rate for therapy treatment showed by HE4 was higher than CA125, and a serum HE4 level was correlated with a sensitivity of 82.8% and a specificity of 99%, a positive predictive value (PPV) of 97.7%, and a negative predictive value (NPV) of 77.9% to show the presence of recurrence; the accuracy of HE4 for recurrence prediction after treatment was 88.6%. CONCLUSIONS: Our study indicated that serum HE4 levels are effective for diagnosis, evaluating the response of treatment and predicting recurrence in patients with advanced ovarian, fallopian tube, and peritoneal carcinoma.

Different variables predict the outcome of patients with synchronous versus metachronous metastases of colorectal cancer.

PURPOSE: Timing of metastasis is a controversial prognostic factor for patients with metastatic colorectal cancer (mCRC), as well as the performance of the common prognostic variables within patients with synchronous (SMs) or metachronous metastases (MMs). The aim of the current study is to evaluate outcome by the timing of metastases and to explore different tumor characteristics associated with SMs and MMs. METHODS: Data were collected from the clinical records of patients with mCRC, which were referred to the Department of Oncology of the Ospedale Civile di Sanremo from 2006 to 2011. A comparison of the characteristics of tumors of patients, overall and by the timing of metastases, and a Cox regression analysis have been performed to select the most relevant prognostic factors. Finally, the characteristics of the variables associated with the outcome were analyzed through a logistic regression. RESULTS: Two hundreds fifteen patients with SMs and two hundreds ten with MMs were included. Patients with SMs reported a poor prognosis (18.5 versus 62.8 months; p value < 0.001). Among patients with SMs there was a significant difference in overall survival between patients with a CEA-positive or negative disease, while no difference was present among patients with MMs. After multivariate analysis, only within the SMs group the occurrence of liver metastases was related to a CEA-positive disease. CONCLUSIONS: Within the cohort of SMs high CEA levels, occurrence of liver metastases and right-sided colon tumors were associated with a very poor prognosis, whereas no relationship was detectable in the group of patients with MMs.

Pre-operative serum CA125, peritoneal cancer index and intra-operative mapping score as predictors of surgical results in primary epithelial ovarian cancer.

OBJECTIVE: Prediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer and their predictive value for post-operative outcome. METHODS: A total of 70 patients with primary epithelial ovarian cancer, who underwent primary cytoreductive surgery at Charité, Berlin between January 2013 and February 2014 were included. In all patients, pre-operative CA125 values, intra-operative peritoneal cancer index, and intra-operative mapping of ovarian cancer were determined. RESULTS: Using a receiver operating characteristic analysis, cut-off values for CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer score could be defined. Patients with pre-operative serum CA125 >600 U/mL had a three times higher risk for residual tumor after primary cytoreductive surgery (p=0.037). A peritoneal cancer index score >20 indicated a nine times increased risk for residual tumor (p=0.003). More than six affected abdominopelvic fields on the intra-operative mapping of ovarian cancer was associated with a 25 times higher risk of residual tumor after primary cytoreductive surgery (p≤0.05). The combination of all three values predicted residual tumor in up to 90% of patients. CONCLUSION: We found that pre-operative CA125 >600 U/mL, peritoneal cancer index >20, and intra-operative mapping of ovarian cancer score >6 could be used as predictors of complete tumor resection. The combination of all these three values predicted the incomplete resection of disease in up to 90% of patients even in experienced centers.

The neutrophil/lymphocyte ratio as a predictor of peritoneal metastasis during staging laparoscopy for advanced gastric cancer: a retrospective cohort analysis.

BACKGROUND: The use of staging laparoscopy (SL) has become widespread in patients with advanced gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the presence of peritoneal metastasis during staging laparoscopy in patients with advanced GC. METHODS: This retrospective analysis was performed in 35 patients with advanced GC who underwent SL at Kanazawa Medical University Hospital between January 2009 and December 2017. Clinicopathological characteristics were examined and multivariate analyses were performed to identify preoperative laboratory parameters that were independently associated with the presence of peritoneal metastasis or cytological malignancy (P/CY positive) during SL. RESULTS: A P/CY-positive result was confirmed during SL in 16 patients (45.7%). Patients with type 4 or diffuse type 3 tumors showed a significantly higher P/CY-positive rate than those with other tumor types (58.3% vs. 18.2%, P = 0.02). In the univariate analysis for preoperative laboratory parameters, NLR (P < 0.0001) and total protein (P = 0.03) and albumin (P = 0.04) levels were significantly correlated with a P/CY-positive result. On multivariate analysis, NLR was significantly correlated with a P/CY-positive result (P = 0.0002). In patients with type 4 or diffuse type 3 tumors, a high NLR (> 3.5) was associated with a significantly higher P/CY-positive rate than a low NLR (≤ 3.5) (83.3% vs. 33.3%, P = 0.01). Moreover, in patients without type 4 or diffuse type 3 tumors, the P/CY-positive rates were 100% and 0% in patients with NLR > 3.5 and NLR ≤ 3.5, respectively. CONCLUSIONS: The preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis during SL. Regardless of tumor type, patients with a high NLR could be reasonable candidates for SL. On the other hand, non-diffuse type tumor accompanied by a low NLR may not need to undergo SL.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

AIM: In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). PATIENTS AND METHODS: A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. RESULTS: Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the log-rank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. CONCLUSION: Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.

Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is a rare, but fatal disease with few treatment options. The diagnosis and treatment response are challenging in MM. Therefore, the search for novel diagnostic and prognostic biomarkers is ongoing. The aim of our study was to investigate matrix metalloproteinase 9 (MMP9) as a potential serum biomarker of treatment response and survival in MM. We also investigated the influence of genetic polymorphisms on MMP9 serum levels. METHODS: We included 110 patients with MM that have been previously genotyped for common MMP9 polymorphisms. Serum samples were collected before treatment, at the end of chemotherapy, and at the time of progression. MMP9 serum levels were measured using enzyme-linked immunosorbent assay kits. The role of serum MMP9 and MMP9 polymorphisms in treatment response was determined using the nonparametric tests and logistic or Cox regression. RESULTS: Median serum MMP9 was 706.7 (499.6-1224.9) ng/ml before treatment, 440.5 (255.9-685.2) ng/ml after chemotherapy, and 502.8 (307.2-851.4) ng/ml at disease progression. After chemotherapy, 87 (79.8%) patients had lower serum MMP9, with the median change of -286.3 (-607.3 to -70.2) ng/ml (P < 0.001). At disease progression, 47 (65.3%) patients had lower serum MMP9 compared to pretreatment values, with the median change of -163.7 (-466.6 to 108.6) ng/ml (P = 0.001). Patients with higher performance status had higher serum MMP9 before treatment (P = 0.010). Among investigated polymorphisms, only rs17576 was associated with serum MMP9 levels before treatment (P = 0.041). CONCLUSION: Median serum MMP9 levels differed significantly before and after treatment of MM, but failed to reach significance as a standalone biomarker. The contribution of MMP9 serum levels and MMP9 polymorphisms to a composite diagnostic and prognostic biomarker should be further tested.

The Value of COX-2, NF-κB, and Blood Routine Indexes in the Prognosis of Malignant Peritoneal Mesothelioma.

BACKGROUND/AIMS: To investigate differences in blood routine indexes and the expression of cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) in malignant peritoneal mesothelioma (MPeM) and their relationship with clinical prognosis. METHODS: We investigated changes in blood routine indexes between the MPeM patients and healthy subjects and detected the expression of COX-2 and NF-κB in peritoneal tissues by a streptavidin-peroxidase immunohistochemistry method. Potential prognostic factors were analyzed including age, gender, white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), COX-2, and NF-κB. Cox regression model analysis established independent factors for the survival prognosis of the patients. RESULTS: Compared with the control group, AMC, MXD%, ANC, neutrophilic granulocyte percentage (NEUT%), APC, NLR, MLR, and PLR were markedly increased (p < 0.05) in the MPeM group. The positivity rates for COX-2 and NF-κB expression were 59.4 and 44.9%, respectively. Single factor analyses indicated that PLR, NLR, MLR, COX-2, and NF-κB were factors that affected the overall survival of MPeM patients, but multivariate analyses identified MLR and COX-2 as independent prognostic factors. CONCLUSIONS: High blood levels of MLR and COX-2 are adverse prognostic factors for patients with MPeM.