Purpose To describe the clinical characteristics and outcomes of patients with dual-phenotype hepatocellular carcinoma (DPHCC) and investigate the use of radiomics to establish an image-based signature for preoperative differential diagnosis. Methods This study included 50 patients with a postoperative pathological diagnosis of DPHCC (observation group) and 50 patients with CK7- and CK19-negative HCC (control group) who attended our hospital between January 2015 and December 2018. All patients underwent Gd-EOB-DTPA-enhanced MRI within 1 month before surgery. Arterial phase (AP), portal venous phase (PVP), delayed phase (DP) and hepatobiliary phase (HBP) images were transferred into a radiomics platform. Volumes of interest covered the whole tumor. The dimensionality of the radiomics features were reduced using LASSO. Four classifiers, including multi-layer perceptron (MLP), support vector machines (SVM), logistic regression (LR) and K-nearest neighbor (KNN) were used to distinguish DPHCC from CK7- and CK19-negative HCC. Kaplan-Meier survival analysis was used to assess 1-year disease-free survival (DFS) and overall survival (OS) in the observation and control groups. Results The best preoperative diagnostic power for DPHCC will likely be derived from a combination of different phases and classifiers. The sensitivity, specificity and accuracy of LR in PVP (0.740, 0.780, 0.766), DP (0.893, 0.700, 0.798), HBP (0.800, 0.720, 0.756) and MLP in PVP (0.880, 0.720, 0.798) were better performance. The 1-year DFS and OS of the patients in the observation group were 69% and 78%, respectively. The 1-year DFS and OS of the patients in the control group were 83% and 85%, respectively. Kaplan-Meier survival analysis showed no statistical difference in DFS and OS between groups (P = 0.231 and 0.326), but DFS and OS were numerically lower in patients with DPHCC. Conclusion The radiomics features extracted from Gd-EOB-DTPA-enhanced MR images can be used to diagnose preoperative DPHCC. DPHCC is more likely to recur and cause death than HCC, suggesting that active postoperative management of patients with DPHCC is required.
Dr. Tarek Haykal et al. (145:1795-1809, 2019) reported a meta-analysis of aspirin for the primary prevention of cancer in individuals without known cancer. The authors found that aspirin use was not associated with significant reduction in cancer mortality or incidence, but with higher rates of bleeding. The findings of this study added some evidence to the clinical practice. However, several issues might have compromised the strength of the evidence of this systematic review. If the investigators could have further clarified the inclusion and exclusion criteria, included all eligible studies, extracted data more meticulously, and performed more necessary sensitivity analyses to confirm the robustness of their findings, the strength of evidence of this meta-analysis would have been stronger.
Purpose To determine the association between lymphovascular invasion (LVI) and upper tract urothelial carcinoma (UTUC) among patients who underwent radical nephroureterectomy (RNU). Materials and methods From 2003 and 2018, retrospective data of 453 patients treated for UTUC with open, laparoscopic, or robotic RNU were collected. Pathological specimens were assessed for LVI through hematoxylin and eosin staining. According to presence of LVI, patients were stratified into two groups and compared for perioperative characteristics. Kaplan-Meier analysis was used to assess progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Uni- and multivariate Cox regression models were used to find significance of LVI to survival. Results LVI was present in 132 (29.1%) of patients and was associated with higher age and lower preoperative GFR. Pathological outcomes included significantly higher tumor grade, higher rates of lymph node invasion and more positive surgical margins. During median 23.2 months follow-up (mean 37.1 months), 59.2% (n = 268) of total patients had tumor recurrence, with highest incidences in lymph nodes (51.5%). 5-year PFS, CSS, and OS were estimated at 35.4%, 94.6%, and 91.1% in LVI-negative patients and 17.2%, 75.1%, and 70.8% in LVI-positive patients, respectively (all p < 0.001). Multivariate analysis showed LVI to be an independent predictor of PFS (HR = 1.480; p = 0.018). Conclusion LVI is an independent predictor of adverse PFS and is associated with poor CSS and OS in patients undergoing RNU for UTUC. These results may guide clinicians in selecting patients for adjuvant chemotherapy. Future prospective trials are necessary to further validate our results.
Purpose The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. Methods We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. Results For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. Conclusions Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.
Purpose We examined whether multi-disciplinary stepped psychosocial care for cancer patients improves quality of care from the patient perspective. Methods In a university hospital, wards were randomly allocated to either stepped or standard care. Stepped care comprised screening for distress, consultation between doctor and patient, and the provision of psychosocial services. Quality of care was measured with the Quality of Care from the Patient Perspective questionnaire. The analysis employed mixed-effects multivariate regression, adjusting for age and gender. Results Thirteen wards were randomized, and 1012 patients participated (n = 570 in stepped care and n = 442 in standard care). Patients who were highly distressed at baseline had 2.3 times the odds of saying they had had the possibility to converse in private with doctors and/or psychologists/social workers when they were in stepped care compared to standard care, 1.3 times the odds of reporting having experienced shared decision-making, 1.1 times the odds of experiencing their doctors as empathic and personal, and 0.6 times the odds of experiencing the care at the ward to be patient oriented. There was no evidence for an effect of stepped care on perceived quality of care in patients with moderate or low distress. Conclusions Stepped care can improve some aspects of perceived quality of care in highly distressed patients.
Purpose Molecular mechanisms of response to hypomethylating agents in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) still remain largely unknown. Therefore, the effects of 5-Azacytidine (Aza) on clonal architecture and DNA methylation were investigated in this study. Methods Using next-generation sequencing (NGS), 30 myeloid leukemia-associated genes were analyzed in 15 MDS/CMML patients with excellent response to Aza. Effects on methylation levels were analyzed by quantitative methylation analysis using pyrosequencing for the global methylation marker LINE-1 in patients and myeloid cell lines. Various myeloid cell lines and a healthy cohort were screened for methylation levels in 23 genes. Selected targets were verified on the MDS/CMML cohort. Results The study presented here showed a stable variant allele frequency and stable global methylation levels in responding patients. A significant demethylation of EZH2 and NOTCH1 was revealed in patients with Aza response. Conclusions A response to Aza is not associated with eradication of malignant clones, but rather with a stabilization of the clonal architecture. We suggest changes in CpG methylation levels of EZH2 and NOTCH1 as potential targets of epigenetic response to Aza treatment which may also serve as useful biomarkers after clinical evaluation.
Purpose The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown. Methods We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC. Results The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS. Conclusion Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.
Background Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients. Patients and methods The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000-2003 (pre-SBRT); (2) 2004-2007 (interim); and (3) 2007-2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed. Results A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000-2003 is compared to 2004-2007 (HR 0.92, 95% CI 0.85-1.01) or 2008-2014 (HR 0.93, 95% CI 0.86-1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000-2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000-2003 vs. > 2007: 0.74, 95% CI 0.58-0.94). On an additive scale, treatment x period interaction revealed an RERI for 2000-2003 vs. > 2007 of - 1.18 (95% CI - 1.8, - 0.55). Conclusions Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery.
Background Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics. Methods We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH). Results In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs. Conclusions In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.
Background The purpose of this study was to explore the demographics, multimodality therapeutic outcomes*** and prognostic factors in sinonasal rhabdomyosarcoma (SNRMS). Methods We conducted a retrospective analysis of 40 patients who underwent treatment of SNRMS from March 2007 to March 2018. The Kaplan-Meier method and the log-rank test were used to assess survival rates. The Cox regression model was used for multivariate survival analysis. Results In total, 25 males and 15 females were included in the study; the median age was 33 years (range, 2-67 years). All patients underwent surgical resection, and surgery prior to or after adjuvant therapy (chemotherapy and radiotherapy) was performed in 91.4% of the patients. The overall 1-, 3- and 5-year survival rates were 77.0%, 46.5% and 46.5%, respectively, during a mean follow-up time of 27.9 (range, 2-128) months in all patients. The log-rank test showed Intergroup Rhabdomyosarcoma Study (IRS) group and infiltration of the skull base influenced overall survival (p = 0.001; p = 0.022). Advanced IRS stage, lymph node metastasis and tumor size >= 5 cm were also associated with an unfavorable outcome on overall survival (p = 0.01; p = 0.035; p = 0.02). The results of multivariate regression analysis showed patients with IRS group I were associated with better prognosis outcome on overall survival. Conclusion Patients with SNRMS have poor 5-year overall survival, and IRS group is the independent prognostic factor for overall survival.
Purpose To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Methods This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. Results 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). Conclusions CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.
Purpose N2 lymph-node metastases occur in approximately 6-17% of the patients with T1-2 non-small cell lung cancer (NSCLC). However, the clinical characteristics of N2 patients are not fully understood. Methods This retrospective, multi-center analysis included T1 NSCLC patients receiving surgical resection during a period from Jan 2nd, 2014 to Dec 27th, 2017. The diagnosis was pathologically verified in all cases. Univariate and multivariate logistic regression analyses were conducted to analyze the factors that are associated with pN2 lymph-node metastases. Results A total of 10,885 patients (48.4% men; 84.7% adenocarcinoma) were included in the analysis. The mean age was 59.0 +/- 9.9 years. The mean tumor size was 1.8 +/- 0.8 cm. Of the patients, 3260 (29.9%) were smokers or ex-smokers. Lymph-node metastases were verified in 1808 (16.6%) patients, and 1167 (10.7%) patients had N2 lymph-node metastases. The multivariate analyses indicated that larger tumor size, lower differentiation, CEA level >= 5 ng/mL, vascular invasion (+), and pleural involvement (+) were associated with higher percentages of N2 lymph-node metastases (p < 0.001 for all). Conclusions This study demonstrated the significant association between N2 lymph-node metastases and tumor size and differentiation, CEA levels, and status of vascular invasion and pleural involvement.
Purpose This study aims to examine the health-related quality of life in patients with hepatocellular carcinoma. Methods 181 patients attending a tertiary center outpatient clinic were interviewed and completed the short form 36 (SF36) questionnaire. The SF36 was used to assess health-related QoL. Cross-sectional analyses by group (age, gender, clinical scores, systemic, and local interventions) as well sequel questionnaires were conducted. Results Participants included were 79% (143/181) men [mean age at first SF36: 63.8 (+/- 12.3; 18.4-85.8) years]. Barcelona Clinic Liver Cancer (BCLC) stadium C was associated with significantly lower SF36 total scores, and elevated initial alpha-fetoprotein (AFP) concentrations were associated with lower SF36 functional and mental health sum scores throughout the course of the third questionnaire. Patients treated with sorafenib had within the sub-dimension scores a significantly lower result for role limitations due to physical health compared to patients without sorafenib treatment. Patients who underwent a transarterial chemoembolization (TACE) had within the sub-dimension scores a significantly higher result for control of pain compared to patients without TACE. Kaplan-Meier analysis revealed significant survival benefits for patients who underwent any intervention at the first SF36 (mean survival in years 4.3 vs. 1.6; P < 0.01) as well as for patients who underwent hepatic resection (mean survival in years 6.3 vs. 2.7; P < 0.0001). Conclusion Advanced tumor stages marked by BCLC stadium C and elevated initial AFP concentrations were associated with lower SF36 total scores and functional sum scores, respectively. During the course of sorafenib treatment, the sub-dimensional score for role limitations due to physical health decreased significantly, whereas TACE performance was associated with a significant improvement of the control of body pain.
Background Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer. Materials and methods We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay). Results The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity. Conclusion These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.