Adult Patient With Neuroblastoma Presenting as Acute Leukemia.

Neuroblastoma (NB) is the most common extra-cranial cancer of early childhood and rarely occurs in adults. The clinical symptoms of NB can be diverse. We discuss a rare case of an adult NB presenting as acute leukemia. A 45-year-old woman presented with persistent hip pain, weight loss, anemia, and incidental fever for several months. Imaging studies showed diffuse bone marrow (BM) uptake and hypermetabolic lesions involving the left adrenal gland, bilateral axillary nodes, and left lateral aspect of the abdomen. Her 24-hour urine catecholamines were within the normal range. On the peripheral blood film, blast-like cells were noted, occupying approximately 2% of leukocytes. The BM imprints showed infiltration of blast-like cells with convoluted nuclei and scant cytoplasm in more than 85% of the total nucleated cells. Acute leukemia was initially suspected based on morphology. Blast-like cells were negative for myeloperoxidase, combined esterase, periodic acid-Schiff, CD45RB, CD68, and CD138. In a further study, these cells were positive for CD56, synaptophysin (SYN), and CD99 with negativity for desmin, myogenin, NKX-2.2, CD31, cytokeratin (AE1/AE3), Melan-A, ERG, S-100, and SALL4. Morphologically similar neoplastic cells in axillary node biopsy were positive for CD56, chromogranin A, SYN, and neurofilament, but negative for GFAP, CD246, and vimentin. Based on laboratory, pathological, and imaging studies, metastatic NB with BM and multifocal involvement was diagnosed. The differential diagnosis of metastatic small blue round cell tumors should be considered for adult patients with circulating blast-like cells, and an accurate diagnosis would enable the patient to receive appropriate and timely treatment.

Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUVmax of FDG-PET scan in esophageal squamous cell carcinoma.

We appraised Warburg effect through analysis of mitochondrial DNA (mtDNA) copy number and maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan and their alterations in esophageal squamous cell carcinoma (ESCC). Later T-status and longer longitudinal tumor length were associated with lower mtDNAESCC copy number (p < .05) but higher SUVmax-ESCC (p < .05), respectively. Lower mtDNAESCC copy number correlated with higher SUVmax-ESCC, reciprocally (p < .05). ESCCs expressing mutant p53 protein had lower mtDNAESCC copy number (p = .056) but higher SUVmax-ESCC (p = .046). We conclude that mutant p53 protein may be involved in the Warburg effect of ESCC.

The Impact of First Complete Remission by PET-CT and Time to Next Treatment on Survival of Follicular Lymphoma Patients.

We retrospectively analyzed the impact of initial positron emission tomography and computed tomography (PET-CT) complete remission (CR) and time to next treatment (TTNT) on patient outcome in follicular lymphoma. Between 2002 and 2014, 150 patients could be evaluated for treatment response and long-term outcome. The CR after first line treatment with either rituximab-cyclophosphamide, oncovin, and prednisolone (R-COP) or rituximab-cyclophosphamide, doxorubicin, oncovin, and prednisolone (R-CHOP) was 89% and partial response (PR) was 7%. The 5- and 10-year survival rates were 86.0% and 62.6%, respectively. In five years, 11% of patients had died of lymphoma and 3% from other causes. Forty-seven patients (31%) underwent a second line of treatment comprising 19 (40%) with a TTNT shorter than 24 months and 28 (60%) longer than 24 months. There was no difference in overall survival (OS) between R-COP (86%) and R-CHOP (77%) at 5 years, but there were more next treatment events in the R-COP compared with the R-CHOP group on longer follow-up (60% versus 35% at 8 years). For PET-CT response, there was a significant OS difference between initial CR and PR patients (88% versus 70%, p < 0.01), and a longer TTNT was seen in initial CR patients. Patients with a TTNT longer than 24 months had better OS compared with patients with a shorter TTNT (93% versus 54% at 5 years, p < 0.01). In conclusion, patients with initial PET-CT CR and TTNT longer than 24 months had better OS compared with those achieving only PR and shorter TTNT. PET-CT CR should be considered the treatment goal during initial treatment, and more aggressive treatment should be considered for patients with a TTNT of less than 24 months.

A Microchip Electrophoresis Device Integrated with the Top-bottom Antiparallel Electrodes of Indium Tin Oxide to Detect Inorganic Ions by Contact Conductivity.

A microchip electrophoresis (ME) device with off-channel contact conductivity detection (C2D) was constructed using top-bottom antiparallel indium tin oxide (ITO) electrodes and a cross-type microchannel. The 500-m wide top-bottom antiparallel decouplers were found to effectively decrease the interference of the electrophoretic current. The cross-type microchannel was formed by bonding the patterned negative photoresist microstructures and the two top-bottom opposed ITO-deposited glass substrates. Five seconds of 150 V/cm injection field and the 100 V/cm separation field equipped with the C2D of AC 200 mV excitation voltage provided adequate ME operational parameters to obtain the K+ and Na+ peaks separation. The ME devices obtained good coefficients in a range of 11000 µM for the K+ and Na+ detection. The calculated limit of detection was 1 µM. This design for off-channel and top-bottom antiparallel electrodes shows that C2D ME devices have great potential for the measurement of inorganic ions.

An electrooxidative technique to fast fabricate copper phosphate electrodes capable of integrating high performance liquid chromatography for the label-free detection of fish freshness.

A simple and fast one-step electrooxidative method has been developed to monolithically produce a copper phosphate (Cu3(PO4)2) compound on a disposable copper tape, which can be integrated with high performance liquid chromatography (HPLC) for the estimation of fish freshness. The Cu3(PO4)2 compound of flake-like nanostructures was formed by applying a first anodic peak potential at the copper tape for 10 min in a 1 M sodium dihydrogen phosphate (NaH2PO4) (pH 5.0) solution. The Cu3(PO4)2 electrodes can detect the oxidative reaction of histidine and histamine in 20 mM NaH2PO4 solutions with pH 5.0-8.5. When integrating the electrodes with a flow injection system, the linear range and the calculated detection limit of histamine were respectively 2.5-250 ppm and 0.15 ppm. The electrodes integrated to HPLC can specifically detect the histamine concentrations in fish samples in the pH 7.5 NaH2PO4 solution, achieving an accuracy rate of 95.3% and a recovery rate of 101.1%.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy.

BACKGROUND: The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. METHODS: Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3-5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. RESULTS: Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3-5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all's P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3-5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all's P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. CONCLUSIONS: Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion.

Radical Lymph Node Dissection in Primary Esophagectomy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Subtotal esophagectomy with radical lymph node dissection (RLND) remains an effective therapeutic strategy for localized esophageal squamous cell carcinoma (ESCC). However, controversy exists regarding the extent to which RLND should be performed. We reappraised the prognostic impact and accurate nodal staging of RLND in ESCC. METHODS: The data from 101 ESCC patients (mean age, 57.5 years; 93 men) who underwent primary subtotal esophagectomy were retrospectively collected. Candidate variables, including the number of total dissected lymph nodes (TDLN [subgrouped into TDLN less than 13, TDLN 13 to 40, and TDLN more than 40]), were evaluated to determine their prognostic impacts and hazard ratio (HR). RESULTS: Fewer TDLN (p < 0.001; HR 9.011, 2.449, and 1.000 for TDLN less than 13, TDLN 13 to 40, and TDLN more than 40, respectively), tumor length exceeding 3.5 cm (p < 0.001; HR 3.321), resection margin invasion (p < 0.001; HR 14.493), and positive nodal status (p = 0.002; HR 2.730) were independent predictors of a poor prognosis. Considering the 54 node-negative patients, more TDLN correlated with improved survival (p = 0.001). Risk analysis demonstrated that one fewer TDLN could contribute to an increased HR of 1.047 (p = 0.014). However, RLND involving more TDLN appeared to lose the prognostic impact for the 47 node-positive patients (p = 0.072). Furthermore, the number of positive dissected lymph nodes remained at approximately 4 if the number of TDLN exceeded 20. CONCLUSIONS: For N-negative or N-positive ESCC patients undergoing primary surgical resection, the number of TDLN influenced their prognosis or nodal staging accuracy, respectively. At least 20 TDLN were necessary for N-positive patients.

Active targeted drug delivery for microbes using nano-carriers.

Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nanocarriers utilized targeting ligands on their surface called 'active target' provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced.

Fermented broth in tyrosinase- and melanogenesis inhibition.

Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed.

Nasopharyngeal alveolar rhabdomyosarcoma expressing CD56: a mimicker of extranodal natural killer/T-cell lymphoma.

Alveolar rhabdomyosarcoma (ARMS) is remarkably rare in adults older than 45 years. Histologically, the tumor is composed of blue round cells with frequent expression of CD56 in addition to myogenic markers. Recent studies of ARMS have shown two specific recurrent translocations: PAX3-FKHR [t(2;13)(q35;q14)] or PAX7-FKHR [t(1;13)(p36;q14)]. Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) occurs most frequently in the upper aerodigestive tract with a male preference in East Asia and Central and South Americas with neoplastic cells frequently expressing CD56. We report a 53-year-old Taiwanese man presenting with a nasopharyngeal mass, cervical lymphadenopathy, and multiple bone metastases. Histologically, the nasopharyngeal biopsy revealed diffuse sheets of small blue round tumor cells without obvious alveolar pattern, angioinvasion or tumor necrosis. An initial erroneous diagnosis of ENKTL was made due to CD56 expression using fresh tumor tissue with flow cytometric analysis and the patient was treated accordingly. Retrospective study showed that the tumor cells expressed CD56, desmin, and myogenin. Fluorescence in situ hybridization revealed that the tumor cells were positive for FKHR gene rearrangement, confirming the diagnosis of ARMS. Our case illustrates that a diagnosis of ENKTL based solely on CD56 expression can be misleading for a nasopharyngeal small blue round cell tumor. ARMS should be included as a differential diagnosis, and a correct diagnosis can be reached only after a high index of suspicion and a thorough histological examination with the aid of ancillary studies.

The prognostic value of circumferential resection margin in esophageal squamous cell carcinoma after concurrent chemoradiation therapy and surgery.

BACKGROUND: Despite the significant advances in surgical techniques and multimodality treatments for esophageal cancer, the overall survival remains unsatisfactory. During the past years, efforts were made to determine the prognostic factors that would help in identifying patients suitable for surgery or guiding adjuvant therapy. Positive circumferential resection margins (CRMs) in esophageal cancer have been previously linked with poor prognosis, but their impact on survival remains controversial in patients treated by a multimodality protocol. The aim of our study was to examine the significance of tumor involvement of CRM in patients with esophageal squamous cell carcinoma after concurrent chemoradiation therapy followed by esophagectomy. METHODS: Between 2000 and 2010, 94 esophageal squamous cell carcinoma patients who received preoperative concurrent chemoradiation therapy followed by surgery were enrolled in our study. We focused on the CRM, which was defined microscopically as clear (negative) or involved (positive). Univariate and multivariate survival analyses were performed with overall survival as the endpoint. RESULTS: Our cohort was predominantly male (94.7%) with a median age of 57 years. All of them received concurrent chemoradiation therapy followed by esophagectomy. Overall, 17 patients (18.1%) had positive CRM. Kaplan-Meier survival analysis demonstrated that the 5-year overall survival of patients with clear and involved CRM is 60.1% and 11.8%, respectively (log rank p < 0.001). Multivariate analysis with the Cox proportional hazard model demonstrated that CRM involvement is a significant prognostic factor for overall survival (p < 0.001). CONCLUSION: In patients with esophageal squamous cell carcinoma who underwent trimodality treatment, CRM involvement is a significant risk factor predicting survival. Additional effort is required to achieve a clear CRM in esophageal cancer treatment.

Bispectral analysis and genetic algorithm for congestive heart failure recognition based on heart rate variability.

This paper proposes a congestive heart failure (CHF) recognition method that includes features calculated from the bispectrum of heart rate variability (HRV) diagrams and a genetic algorithm (GA) for feature selection. The roles of the bispectrum-related features and the GA feature selector are investigated. Features calculated from the subband regions of the HRV bispectrum are added into a feature set containing only regular time-domain and frequency-domain features. A support vector machine (SVM) is employed as the classifier. A feature selector based on genetic algorithm proceeds to select the most effective features for the classifier. The results confirm the effectiveness of including bispectrum-related features for promoting the discrimination power of the classifier. When compared with the other two methods in the literature, the proposed method (without GA) outperforms both of them with a high accuracy of 96.38%. More than 3.14% surpluses in accuracies are observed. The application of GA as a feature selector further elevates the recognition accuracy from 96.38% to 98.79%. When compared to the Isler and Kuntalp's impressive results recently published in the literature that also uses GA for feature selection, the proposed method (with GA) outperforms them with more than 2.4% surpass in the recognition accuracy. These results confirm the significance of recruiting bispectrum-related features in a CHF classification system. Moreover, the application of GA as feature selector can further improve the performance of the classifier.

Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma.

INTRODUCTION: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a very rare subtype of non-small-cell lung cancer. Most cases are reported in Southeast Asia and are associated with Epstein-Barr virus infections. Because of its rare incidence, the optimal treatment and the results of long-term follow-up are not well understood. This study is an attempt to discover the multimodality treatment results of the primary pulmonary LELC. METHODS: This retrospective study enrolled 21 patients with primary pulmonary LELC treated at 2 hospitals with a multimodality approach, including surgery, chemotherapy, radiotherapy, and targeted therapy. RESULTS: The median follow-up time is 5.9 years and the median survival is 6.4 years. The median overall survival for patients with stage III and with stage IV disease is 3.4 years. In early-stage primary pulmonary LELC, surgery and adjuvant chemotherapy provided good treatment outcome. Advanced primary pulmonary LELC is relatively more chemosensitive and radiosensitive. CONCLUSION: Patients with primary pulmonary LELC showed better prognosis than those with other types of non-small-cell lung cancer and achieved longer survival under multimodality treatment. This disease character is similar to that of nasopharyngeal carcinoma. Accurate pathologic diagnosis is recommended before the treatment. For advanced diseases, platinum-based doublet chemotherapy can be considered the first-line treatment. Radiation dose should consider tumor location, and 5000 to 7000 cGy is frequently applied for pulmonary LELC.

Conditional mutual information-based feature selection for congestive heart failure recognition using heart rate variability.

Feature selection plays an important role in pattern recognition systems. In this study, we explored the problem of selecting effective heart rate variability (HRV) features for recognizing congestive heart failure (CHF) based on mutual information (MI). The MI-based greedy feature selection approach proposed by Battiti was adopted in the study. The mutual information conditioned by the first-selected feature was used as a criterion for feature selection. The uniform distribution assumption was used to reduce the computational load. And, a logarithmic exponent weighting was added to model the relative importance of the MI with respect to the number of the already-selected features. The CHF recognition system contained a feature extractor that generated four categories, totally 50, features from the input HRV sequences. The proposed feature selector, termed UCMIFS, proceeded to select the most effective features for the succeeding support vector machine (SVM) classifier. Prior to feature selection, the 50 features produced a high accuracy of 96.38%, which confirmed the representativeness of the original feature set. The performance of the UCMIFS selector was demonstrated to be superior to the other MI-based feature selectors including MIFS-U, CMIFS, and mRMR. When compared to the other outstanding selectors published in the literature, the proposed UCMIFS outperformed them with as high as 97.59% accuracy in recognizing CHF using only 15 features. The results demonstrated the advantage of using the recruited features in characterizing HRV sequences for CHF recognition. The UCMIFS selector further improved the efficiency of the recognition system with substantially lowered feature dimensions and elevated recognition rate.

Histopathologic correlation of hepatocellular carcinoma after transcatheter arterial chemoembolization with polyvinyl alcohol particle of various sizes.

AIM: Transcatheter arterial chemoembolization (TACE) is one of major treatment for unresectable hepatocellular carcinomas (HCC) and has been used as a neoadjuvant treatment before surgery. This study was to describe the histopathologic features of HCC after TACE with variously sized polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Seventeen patients undergoing TACE with PVA followed by surgery for HCC were analyzed. The PVA particles used in TACE were categorized into two groups in respects of particle sizes: the group I, 47-90 µm (n=8) and the group II, >90-250 µm (n=9). The histopathologic features of the resected HCC were characterized with the emphasis on the number of thrombosed vessels and minimal diameter of arterioles/capillaries containing polyvinyl alcohol particles. The clinical results after TACE were also addressed. RESULTS: Histopathologic examinations showed that the median minimal diameters of arterioles containing PVA particles were 0.035 mm in group I and 0.06 mm in group II (p=0.0078). We observed the PVA particle in the sinusoidal spaces of non-tumourous liver in only one patient. However, no sinusoidal infarction was demonstrated in either group. Mean tumour necrosis rate was 67% vs. 61% for the group I and II, respectively. CONCLUSIONS: The smaller PVA particles can reach and occlude more distal arteriolar capillaries, but rarely leak into non-tumourous hepatic sinusoidal spaces. Slightly better tumour necrosis rate after TACE can be achieved.

Multiscale sample entropy based on discrete wavelet transform for clinical heart rate variability recognition.

Traditional multiscale method uses coarse grained average (CGA) to evaluate sample entropy (SE) parameters in different scales for signal characterization. In this study, we propose to use discrete wavelet transform (DWT) to decompose hear rate variability signals into multiscale sequences for the calculation of SE features for the recognition of congestive heart failure (CHF) and atrial fibrillation (AF) from normal sinus rhythm (NSR). The support vector machine (SVM) is used as the classifier and the capability of the features are justified with leave-one-out cross-validation method. The results demonstrate that the system using multiscale SE features calculated from both CGA and DWT with five dyadic scales outperforms that based on tradition multiscale method using CGA and 20 scales. Compared to the 5-scale CGA method, the proposed 5-scale DWT method achieved 6.7% and 0.77% increases in the recognition rates for CHF and AF, respectively, and resulted in an 8.35% raise in the overall recognition accuracy.

Underperformance of gallium-67 scan is greater in relapse than in initial staging, compared with FDG PET.

PURPOSE: The purpose of this study is to evaluate the performance of gallium-67 scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and recurrence detection by comparing the 2 imaging studies in the same patient. MATERIALS AND METHODS: A total of 42 patients from the period between July 2002 and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG PET scans and also underwent corresponding GS performed within 7 days of FDG PET, for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed in these 42 patients, 27 were for staging, and 19 for restaging after recurrence. RESULTS: In all these studies, FDG PET detected 230 lesion sites, whereas GS detected 85 lesion sites. All of the lesions detected by GS were noted on FDG PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the 27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68 lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110 lesions, whereas GS detected only 17 (15.5%). CONCLUSIONS: FDG PET is superior to GS in staging and detecting all types of lymphoma. The difference is notably more significant in recurrence detection.

Rab5A is associated with axillary lymph node metastasis in breast cancer patients.

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade (P = 0.004), more lymphovascular invasion (P = 0.027), more axillary lymph node (LN) metastasis (P = 0.008), and a higher number of axillary LN metastases (P = 0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients.