Validation for models for tumor recurrence after liver transplantation in hepatectomy patients.

Purpose: Early recurrence of hepatocellular carcinoma (HCC) remains a challenging issue after hepatic resection (HR) because of the associated poor prognosis. Models for tumor recurrence after liver transplantation (MoRAL) have been designed to predict tumor recurrence in HCC patients in the liver transplantation setting. This study aimed to validate the predictability of MoRAL for HCC recurrence or patient death and to evaluate the predictors of early HCC recurrence in hepatectomy patients with treatment-naïve solitary HCC. Methods: This study included 443 patients with HCC recurrence after HR from January 2005 to December 2011. Patients were stratified into early recurrence (n = 312) and late recurrence (n = 131) groups according to the development of recurrence either within or more than 2 years after hepatectomy. Results: The median levels of alpha-fetoprotein and protein induced by vitamin K absence-II and the median MoRAL score were significantly higher in the early recurrence group than in the late recurrence group. Regarding pathologic characteristics, the median tumor size, prevalence of tumor grade 3 or 4, microvascular invasion, presence of tumor necrosis, and macrovascular invasion in the early recurrence group were greater than those in the late recurrence group. Multivariate analysis showed that tumor grade 3 or 4, microvascular invasion, and high preoperative MoRAL score were predisposing factors for early HCC recurrence after HR. Conclusion: The MoRAL score can be used to predict early recurrence in patients with HCC who undergo curative HR. Using this model, other treatments could be considered for patients with early recurrence predicted after HR.

New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma.

BACKGROUND: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. METHODS: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients' sera and plasmas, along with IL-6, TNF-α, SAA1, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. RESULTS: Glucose concentrations showed statistically significant (p < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. CONCLUSION: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB.

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study.

BACKGROUND: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. OBJECTIVE: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). RESULTS AND LIMITATIONS: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. CONCLUSIONS: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. PATIENT SUMMARY: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.

The luminance ratio of autofluorescence in a xenograft mouse model is stable through tumor growth stages.

The aim of this research was to investigate the value of autofluorescence imaging of oral cancer across different stages of tumor growth, to assist in detecting tumors. A xenograft mouse model was created with human oral squamous cell carcinoma cell line HSC-3 being subcutaneously inoculated into nude mice. Tumor imaging was performed with an autofluorescence imaging method (Illumiscan®) using the luminance ratio, which was defined as the luminance of the tumor site over the luminance of normal skin tissue normalized to a value of 1.0. This luminance ratio was continuously observed postinoculation. Tumor and normal skin tissues were harvested, and differences in the concentrations of flavin adenine dinucleotide and nicotinamide adenine dinucleotide were examined. The luminance ratio of the tumor sites was 0.85 ± 0.05, and there was no significant change in the ratio over time, even if the tumor proliferated and expanded. Furthermore, flavin adenine dinucleotide and nicotinamide adenine dinucleotide were significantly lower in tumor tissue than in normal skin tissue. A luminance ratio under 0.90 indicates a high possibility of tumor, irrespective of the tumor growth stage. However, this cutoff value was determined using a xenograft mouse model and therefore requires further validation before being used in clinical diagnosis.

The Role of 18F-FDG PET/CT in Evaluating Elevated Levels of Tumor Markers in Breast Cancer.

OBJECTIVE: Our aim was to assess the diagnostic performance of integrated positron emission tomography/computed tomography (PET/CT) in the follow-up of breast cancer patients, who underwent a PET/CT scan due to a suspicion of recurrence based on elevated levels of serum tumor markers. METHODS: Seventy-seven consecutive patients were included in this study. PET/CT scan results were compared with the final diagnoses that were obtained from histopathological sampling or a minimum 6 months of radiological follow-up. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the diagnostic accuracy of PET/CT for detecting recurrence were calculated. RESULTS: All 77 patients had increased serum cancer antigen 15-3 levels while 37 had increased serum carcinoembryonic antigen levels. According to PET/CT scan results, 59 of 77 patients (PET/CT positive) had local recurrence and/or distant metastasis while there was no pathological finding in 18 patients (PET/CT negative). In a follow-up of minimum 6 months, tumor recurrence was confirmed in 58 of "PET/CT positive" patients while no tumor recurrence was detected in 16 of "PET/CT negative" patients. According to these results the sensitivity, specificity, PPV, NPV and the diagnostic accuracy of PET/CT for detecting recurrence on a per-person basis were calculated as 98%, 88%, 96%, 94% and 96%, respectively. CONCLUSION: In case of elevated levels of serum tumor markers, PET/CT has a high diagnostic accuracy in detecting tumor recurrence in patients with breast cancer, and it is an effective modality that can be used in addition to conventional imaging techniques.

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study.

BACKGROUND: Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. METHODS: A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis. RESULTS: Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35-15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47-16.55). CONCLUSION: An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker of ovarian cancer: A pilot study.

OBJECTIVE: To compare accuracy of serum human epididymis protein 4 (HE4) levels with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer. METHODS: The study population included 94 Korean women, including 32 patients with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed according to the manufacturer's instructions. Serum CA-125 levels were determined using a Modular analytics E170 module. RESULTS: The median serum CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than those with other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM; P < 0.05 in both). An additional comparison revealed that the patients with endometriosis had greater median serum CA-125 levels than those with other benign ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum HE4 levels were similar among the two benign ovarian tumor groups, with no statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49). The receiver operating characteristics curve analysis for the benign ovarian tumor and ovarian cancer patients showed that HE4 showed a greater area under the curve with borderline significance when compared with CA-125 in both groups (0.93 vs. 0.85). CONCLUSION: Serum HE4 levels may not only allow for the detection of ovarian cancer, but also allow for better differentiation of cases of ovarian cancer versus other benign ovarian tumors compared with serum CA-125.

Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker of ovarian cancer: A pilot study

OBJECTIVE: To compare accuracy of serum human epididymis protein 4 (HE4) levels with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer. METHODS: The study population included 94 Korean women, including 32 patients with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed according to the manufacturer's instructions. Serum CA-125 levels were determined using a Modular analytics E170 module. RESULTS: The median serum CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than those with other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM; P < 0.05 in both). An additional comparison revealed that the patients with endometriosis had greater median serum CA-125 levels than those with other benign ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum HE4 levels were similar among the two benign ovarian tumor groups, with no statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49). The receiver operating characteristics curve analysis for the benign ovarian tumor and ovarian cancer patients showed that HE4 showed a greater area under the curve with borderline significance when compared with CA-125 in both groups (0.93 vs. 0.85). CONCLUSION: Serum HE4 levels may not only allow for the detection of ovarian cancer, but also allow for better differentiation of cases of ovarian cancer versus other benign ovarian tumors compared with serum CA-125.