Shir-Hwa Ueng

Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes

Purpose: We herein examine whether macrophage inflammatory protein-3α (MIP-3α) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions. Experimental Design: The study population comprises 275 NPC patients and 250 controls. MIP-3α levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. EBV DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3α on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. Results: MIP-3α was overexpressed in NPC tumor cells. Serum MIP-3α levels were significantly higher in untreated patients, recurrent patients and patients with distant metastases versus non-NPC controls, patients with complete remission, and long-term disease-free patients. In the prospective cohort, serum MIP-3α levels were significantly higher in untreated NPC patients with advanced tumor-node-metastasis stage versus early stage and also correlated with EBV DNA load. Measurement of MIP-3α, EBV DNA, and viral capsid antigen IgA levels in serial serum/plasma samples from treated patients at 6-month intervals revealed a high association between MIP-3α level, EBV DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3α serum levels over 65 pg/mL had worse prognoses for overall survival and distant metastasis-free survival in univariate and multivariate analysis. Additionally, cell functional assays showed that MIP-3α contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3α knockdown. Conclusions: MIP-3α may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.

Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in dense breasts compared to mammography alone: interobserver blind-reading analysis

AbstractPurposeTo analyse the accuracy of dual-energy contrast-enhanced spectral mammography in dense breasts in comparison with contrast-enhanced subtracted mammography (CESM) and conventional mammography (Mx).Materials and methodsCESM cases of dense breasts with histological proof were evaluated in the present study. Four radiologists with varying experience in mammography interpretation blindly read Mx first, followed by CESM. The diagnostic profiles, consistency and learning curve were analysed statistically.ResultsOne hundred lesions (28 benign and 72 breast malignancies) in 89 females were analysed. Use of CESM improved the cancer diagnosis by 21.2xa0% in sensitivity (71.5xa0% to 92.7xa0%), by 16.1xa0% in specificity (51.8xa0% to 67.9xa0%) and by 19.8xa0% in accuracy (65.9xa0% to 85.8xa0%) compared with Mx. The interobserver diagnostic consistency was markedly higher using CESM than using Mx alone (0.6235 vs. 0.3869 using the kappa ratio). The probability of a correct prediction was elevated from 80xa0% to 90xa0% after 75 consecutive case readings.ConclusionCESM provided additional information with consistent improvement of the cancer diagnosis in dense breasts compared to Mx alone. The prediction of the diagnosis could be improved by the interpretation of a significant number of cases in the presence of 6xa0% benign contrast enhancement in this study.Key Points• DE-CESM improves the cancer diagnosis in dense breasts compared with mammography.n • DE-CESM shows greater consistency than mammography alone by interobserver blind reading.n • Diagnostic improvement of DE-CESM is independent of the mammographic reading experience.

The 30-bp Deletion of Epstein-Barr Virus Latent Membrane Protein-1 Gene Has No Effect in Nasopharyngeal Carcinoma†

Objective: The specific 30‐bp deletion of the Epstein‐Barr virus (EBV)‐derived latent membrane protein‐1 gene has been suggested to be associated with the pathogenesis of nasopharyngeal carcinoma (NPC) and a more aggressive phenotype of some EBV‐associated malignancies.

Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis

ObjectiveTo assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications.MethodsTwo hundred and fifty-six DE-CESMs were reviewed from 2012–2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology.ResultsOf the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9xa0%) cancers, three (11.55xa0%) atypia and three (11.55xa0%) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75xa0% vs. 50xa0%). Overall, the diagnostic sensitivity of enhancement was 90.9xa0%, with 83.78xa0% specificity, 76.92xa0% positive predictive value, 93.94xa0% negative predictive value and 86.4xa0% accuracy. Performance was good (AUCu2009=u20090.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05xa0cm on a Bland-Altman plot.ConclusionsDE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology.Key Points• DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications.• The enhanced cancer size closely correlates to microscopy by Bland-Altman plot.• DE-CESM could be considered for evaluation of suspicious malignant microcalcifications.

A hepatoid carcinoma of the ovary.

A rare case of primary hepatoid carcinoma of the ovary in a 64-year-old Taiwanese woman, who had high serum levels of afetoprotein (AFP) and CA-125, is reported. Histologically, the tumor resembled hepatocellular carcinoma by its architectural and cytological features. To date, no more than 10 cases have been reported in the literature. Clinically, our case was allocated as an ovarian carcinoma Stage IIIc. Poor prognosis was expected from reviewing the previous reports. However, the patient in our case had a relatively successful 5-year survival through proper chemotherapy and radiotherapy.

Expression of ROR1 has prognostic significance in triple negative breast cancer

Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4xa0%) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; Pxa0=xa00.00015), distant metastasis-free survival (DMFS; Pxa0=xa00.00013) and overall survival (OS; Pxa0=xa00.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3xa0%) with medullary features showed longer OS (Pxa0=xa00.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness.

MRI findings of cancers preoperatively diagnosed as pure DCIS at core needle biopsy.

Background Under-estimation of invasion components occur occasionally at core needle diagnosed ductal carcinoma in situ (DCIS) that may change the prognosis or treatment planning. Purpose To determine whether enhanced magnetic resonance imaging (MRI) features of biopsy-proven ductal cancers in situ help predict the under-estimation of invasive breast cancers. Material and Methods After a retrospective review of the enhanced MRI features on preoperative proven breast ductal cancers in situ by biopsy, tumor morphology (mass and non-mass), enhancing curve patterns, and non-mass enhanced appearances were compared between pure ductal cancers in situ and invasive ductal cancers (IDCs) after surgery. A statistical analysis was performed, and P values <0.05 were deemed significant. Results Twenty-five breast cancers from 24 women were analyzed. Eleven DCIS remained as DCISs, and 14 were upgraded to IDC after surgery. Eight of 14 IDCs (57%) and one of 11 DCISs (9%) presented as mass lesions; otherwise six (43%) IDCs and 10 (91%) DCISs were non-mass lesions (P = 0.013). Among the non-mass cancers, six of 10 DCISs (60%) were focally enhanced and six of 6 IDCs (100%) were segmentally enhanced. The overall cancer sizes measured on enhanced MRI were moderately correlated with histopathology, with a Spearmans rank correlation coefficient of 0.656 (P = 0.001). The mean diameter of the IDCs was larger than that of the pure DCISs on enhanced MRI (2.69 ± 1.42 cm for IDC and 1.62 ± 1.03 cm for DCIS; P = 0.048). The cut-off size was optimally selected at 1.95 cm with a 64% sensitivity and a 77% specificity, using a receiver-operating characteristic curve. The enhancement curves, with washout or persistent rising, were statistically insignificant (P = 0.085 and 0.93, respectively). Conclusion Enhanced MRI provided informative morphology and size features that might help to predict the underestimation of invasiveness in preoperative biopsy-proven DCIS.

Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer.

BackgroundPancreatic adenocarcinoma (PCA) is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors.MethodsWe retrospectively reviewed the medical files of 688 patients (422 men and 266 women) who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection.ResultsA carbohydrate antigen 19–9 (CA 19–9) level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl), radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival.ConclusionsBesides traditional imaging studies, preoperative CA 19–9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well-differentiated tumors predict the favorable prognosis of PCA patients after resection.

Primary angiosarcoma of the spleen in a child with long-term survival

Primary angiosarcoma of the spleen is a very rare and aggressive neoplasm with poor prognosis. Splenic angiosarcoma rarely occurs in the pediatric group (18xa0years or younger). Survival duration for pediatric patients is very limited. We report a 7-year-old boy with splenic angiosarcoma presented with left upper quadrant abdominal pain and a palpable abdominal mass. Hematogram revealed anemia. Abdominal ultrasound revealed a heterogeneous mass about 12xa0cm in diameter in the left upper abdomen. Abdominal computed tomography demonstrated a huge heterogeneous mass with some cystic components closely attached to the spleen. Splenectomy was performed. Histological examination of the surgical specimen showed that this tumor had typical feature of angiosarcoma including vasoformative architecture, highly pleomorphic tumor cells with irregular, hyperchromatic and prominent nucleoli, and some mitosis. The postoperative course was uneventful. The patient was disease free at 16xa0years after surgery. This is the longest reported duration of survival in a patient with splenic angiosarcoma.

A novel role of the tumor size in pancreatic cancer as an ancillary factor for predicting resectability

BACKGROUNDnPancreatic adenocarcinoma (PCA) is a devastating disease. Only surgery can provide effective treatment. The resectability of pancreatic cancer is mainly determined by image studies. However, half of the patients deemed as operable, radiologically, are found to be inoperable during surgery. Previously, we have showed that both CA 19-9 and tumor size could predict PCA resectability, independently. Here, we aimed to determine the cut-off value for tumor size permitting PCA resectability by receiver operating characteristic (ROC) curve analysis.nnnMATERIALS AND METHODSnWe retrospectively reviewed 372 patients undergoing surgery for histopathologically proven PCA. We compared tumor sizes of patients in resectable and unresectable groups and analyzed them by the ROC curve.nnnRESULTSnThe tumor size in unresectable groups is significantly larger than that in the resectable group. The area under the ROC curve was 0.73 (95% confidence interval [CI], 0.665-0.789), which represented a good correlation between the tumor size and pancreatic cancer resectability. The PCA patients with a tumor diameter of > 4.8 cm had a 5.043-fold higher chance of unresectability than did those with a tumor diameter < 4.8 cm (odds ratio, 5.043; 95% CI, 3.221-7.894).nnnCONCLUSIONSnA tumor diameter > 4.8 cm is a potential ancillary parameter for determining the resectability of PCA in addition to traditional image studies. Diagnosis laparoscopy may be indicated for radiologically resectable PCA patients with tumor size > 4.8 cm to prevent unnecessary laparotomy.