Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood,bone marrow and peritoneal lavage of pancreatic carcinoma patients

AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas. METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pan- creatic benign surgical diseases (n = 15, control group) were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR. RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 (40%) of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancerpatients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis. CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocar- cinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.

Outcome Results of Treatment with Selective Internal Radiation Therapy (SIRT) in Patients with Hepatocellular Carcinoma: A Single Center Experience

Background: Hepatocellular carcinoma (HCC) has a poor prognosis. Selective internal radiation therapy (SIRT) with microspheres is a treatment option for HCC. This study aimed to assess safety and survival (OS) in patients with HCC treated with SIRT, to stratify patients with tumor vascularization and analyze the impact of sequential sorafenib treatment. Methods: Thirty-nine patients who received SIRT for HCC between 2010 and 2013 at our center were included in this retrospective analysis. Tumor vascularization was assessed using a combination of MRI, MAA-scintigraphy and angiography. Tumor vascularization was correlated with survival. Subgroups are treated with two commercially available 90Y-labeled products SIR-Spheres (n = 16) and TheraSpheres (n = 23) and sequential therapy with sorafenib compared to SIRT only was analyzed. Results: Adverse events occurred in 49% of patients with only four grade 3 and no grade 4 event. Median survival for all patients was 12.5 months (95% CI: 8.7 - 16.3). No significant differences were detectable between Thera Spheres or SIR Spheres. Survival was shorter in patients with low tumor vascularization score (OS: 3.8 months (95% CI 0 - 15.0), p = 0.043). Survival was longer with sorafenib upon progression after SIRT (n=16) with an OS of 17.4 months (95% CI: 12.1 – 22.7) compared to no sorafenib (n = 13;9.1 months;95% CI: 3.0 - 15.1) or progression upon sorafenib before SIRT (n = 10;8.6 months;95% CI: 5.5 - 11.7). Conclusions: SIRT is safe in HCC patients. Tumor vascularization by radiography and scintigraphy may predict survival benefit. Sorafenib is active after SIRT and significantly prolongs survival.

Incidence trends and survival prediction of hepatoblastoma in children:a population-based study

Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level.Methods:Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance,Epi-demiology,and End Results(SEER)database between 2004 and 2015 were examined.Joinpoint regression analyses were applied to assess incidence trends in annual percentage change(APC).Multivariable Cox regression was used to identify factors associated with overall survival(OS).A nomogram was constructed to predict OS in individual cases based on independent predictors.Concordance index(C-index)and calibration curves were used to evaluate predic-tive performance.Results:Between 2004 and 2015,hepatoblastoma incidence increased significantly(APC,2.2%;95%confidence interval[CI]0.5%to 3.8%,P<0.05).In particular,this increase was observed among 2-to 4-year-old patients,males,and African-Americans.The 5-and 10-year OS rates were 81.5%and 81.0%,respectively.Age of 2 to 4 years,Afri-can-American ethnicity,and no surgery were independent predictors for short OS.Distant disease at presentation was found not to be an independent factor of survival.The nomogram had a C-index of 0.79(95%CI 0.74-0.84)with appropriate calibration curve fitting.Conclusions:We constructed a nomogram that integrates common factors associated with survival for hepatoblas-toma patients.It provides accurate prognostic prediction for children with hepatoblastoma.

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score:is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)?

Background:Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)is not always reliable with currently available scores,particularly in patients with primary liver tumor.This study aims to(I)to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and(II)to create a score predicting 90-day mortality preoperatively.Methods:Thirteen high-volume centers participated in this retrospective multicentric study.A risk analysis based on patient characteristics,underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score.A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index(CCI),the age-adjusted CCI(aCCI),the ALPPS risk score before Stage 1(ALPPS-RS1)and Stage 2(ALPPS-RS2).The model was internally validated applying bootstrapping.Results:A total of 451 patients were included.Mortality was 14.4%.The CAPRA score is calculated based on the following formula:(0.1×age)−(2×BSA)+1(in the presence of primary liver tumor)+1(in the presence of severe cardiovascular disease)+2(in the presence of moderate or severe diabetes)+2(in the presence of renal disease)+2(if classic ALPPS is planned).The predictive ability was 0.837 for the CAPRA score,0.443 for CCI,0.519 for aCCI,0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2.After 1,000 cycles of bootstrapping the C statistic was 0.793.The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70.Conclusions:Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure.By assessing the patient’s preoperative condition in relation to ALPPS,the CAPRA score has a very good ability to predict postoperative mortality.

Prospective study to evaluate the prognostic value of different nutritional assessment scores in liver surgery: NURIMAS Liver (DRKS00006340)

Background:Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection.It is important to identify malnourished patients and take preventive therapeutic action before surgery.However,there is no evidence regarding which existing nutritional assessment score(NAS)is best suited to predict outcomes of liver surgery.Methods:All patients scheduled for elective liver resection at the surgical department of the University Hospital of Heidelberg and the Municipal Hospital of Karlsruhe were screened for eligibility.Twelve NASs were calculated before operation,and patients were categorised according to each score as being either at risk or not at risk for malnutrition.The association of malnutrition according to each score and occurrence of at least one major complication was the primary endpoint,which was achieved using a multivariate logistic regression analysis including established risk factors in liver surgery as covariates.Results:The population consisted of 182 patients.The percentage of patients deemed malnourished by the NAS varied among the different scores,with the lowest being 2.20%(Mini Nutritional Assessment)and the highest 52.20%(Nutritional Risk Classification).Forty patients(22.0%)had a major complication.None of the scores were significantly associated with major complications.Conclusions:None of the twelve investigated NAS defined a state of malnutrition that was independently associated with postoperative complications.Other means of measuring malnutrition in liver surgery should be investigated prospectively.

Editorial on“Uncommon indications for associating liver partition and portal vein ligation for staged hepatectomy:a systematic review”

Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS),an innovative procedure in liver surgery,capacitated resection of previously unresectable liver tumors.Originally ALPPS was predominantly applied in patients suffering from extensive colorectal liver metastases(CRLM)with good results(1).ALPPS is thought to exploit liver’s ability to regenerate upon mechanical injury,while safeguarding against liver failure by temporarily leaving a deportalized and detached portion of the liver afflicted with disease.The non-tumorous tissue of the diseased portion is entrusted to support liver function during the regeneration process,thus preventing overexertion of the hepatocytes in the remnant that would otherwise cause their demise.