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.

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.

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.

Epigenetic therapy using the histone deacetylase inhibitor for increasing therapeutic gain in oral cancer: prevention of radiation-induced oral mucositis and inhibition of chemical-induced oral carcinogenesis.

In addition to genetic changes, epigenetic aberrations also play important roles in radiation- and chemical-induced disorders and carcinogenesis. The present study investigated whether epigenetic therapy with a histone deacetylase (HDAC) inhibitor has dual benefits for radiation-induced oral mucositis and chemical-induced oral carcinogenesis, which should be treated at the same time. The HDAC inhibitor phenylbutyrate was first tested to determine if it influences DNA damage repair and survival in irradiated normal cells in vitro by investigating the patterns and dynamics of phospho-gammaH2AX foci, Rad51 foci and phospho-gammaH2AX/Rad51 colocalization and using the comet and clonogenic assays. Oral mucositis or carcinogenesis was induced in hamsters using radiation or 7,12-dimethylbenz[a]anthracene (DMBA) irritation to the cheek pouch. The ability of phenylbutyrate formed in proper carriers to prevent radiation-induced oral mucositis and inhibit chemical-induced oral carcinogenesis was assessed. The treated or untreated irradiated or DMBA-irritated oral tissues or mucosal epithelia were subjected to the studies of histology, immunohistochemistry, gene expression, comet assay, HDAC activity or oxidative stress. We found that phenylbutyrate promoted DNA repair and survival in normal cells after radiation. Compared with blank or vehicle-treated hamsters, the irradiated mucosa treated with phenylbutyrate had significantly lower oxidative stress and tumor necrosis factor-alpha expression and less severe oral mucositis of a shorter duration. A reduction of the oral tumor incidence, burden and progression by phenylbutyrate correlated with the suppression of oncomiRs and Rad51 overexpression, the upregulation of differentiation markers and the decrease of intracellular HDAC activity and oxidative stress during DMBA-induced oral carcinogenesis. Thus, epigenetic therapy using the HDAC inhibitor as an adjuvant to radiotherapy for chemical-induced oral cancer may provide a promising strategy combining the prevention of radiation-induced oral mucositis and the inhibition of oral carcinogenesis.

Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary lesions.

PURPOSE: Management of papillary lesions of the breast identified during preoperative tissue diagnosis remains controversial. This study was designed to analyze the clinical factors associated with under-diagnosis of malignancy in breast papillary lesions. METHODS: Patients with a preoperative tissue diagnosis of benign or atypical papillary lesions, who received surgical excision between 1991 and 2005, were identified. Age of diagnosis, family history of breast cancer, presentation of nipple discharge, palpable mass, mammogram grading, size of lesion, and final pathological diagnosis were analyzed. Tissue sections were reviewed to confirm the diagnosis of malignancy and reasons of discrepancy. RESULTS: A total of 205 women with 228 papillary lesions were studied. The median age was 42 (range, 12-83) years. Malignancies were diagnosed after surgery in 21 cases (9.2%). Patients aged 45 years or older and atypical lesions according to fine needle aspiration cytology (FNAC) or core needle biopsy (CNB) were associated with higher risk for postoperative malignant diagnosis with P values of 0.0008 and < 0.0001, respectively. Pathology review of 19 lesions with malignancy revealed that reasons for preoperative nonmalignant diagnosis were borderline lesions in nine (47.3%), sampling problem in six (31.5%), interpretation error in three (15.7%) and uninterpretable sample in one (5.2%). CONCLUSIONS: In this cohort, 9.21% of preoperative nonmalignant papillary lesions were converted to malignant diagnosis after surgery. Atypical lesions and patients aged 45 years or older were significant factors associated with such conversion. Surgical excision should be considered for papillary lesions of breast, especially for patients with the identified risk factors.

CT-guided needle biopsy: value of on-site cytopathologic evaluation of core specimen touch preparations.

PURPOSE: To examine the diagnostic effect of immediate on-site cytopathologic evaluation of tissue core touch preparations in computed tomographic (CT)-guided coaxial needle biopsy. MATERIALS AND METHODS: The authors reviewed the records of 430 patients and included 413 patients with 432 biopsies (210 in the lungs, 222 in other locations). Each time the guiding needle was moved to a new location in the lesion for tissue core procurement with the cutting needle, it represented a new session. Core specimen touch preparations were obtained and immediately evaluated on-site for specimen adequacy and preliminary diagnosis. New sessions were considered and/or executed in the case of inconclusive cytopathologic readings. Each final diagnosis was reached according to the pathology report showing "positive for malignancy," "negative but with a specific diagnosis," or "unclear" for further surgical resection specimen or radiologic follow-up. RESULTS: The accuracy of on-site cytopathologic examination of touch preparations was 80.6% for the first session and increased to 85.9% and 86.3%, respectively, for the second and third sessions. The corresponding accuracies for biopsy were 88.2%, 93.8%, and 94.9%. The overall accuracy was 97.1% for lesions in the lungs and 92.8% for lesions at other sites. More biopsy sessions were deemed necessary in lesions measuring 2 cm or smaller (P = .0045). During CT-guided lung biopsy, 10 patients (4.8%) had major complications that necessitated chest tube insertion. CONCLUSIONS: The diagnostic accuracy of CT-guided needle biopsy can be increased through repeated sessions with immediate on-site cytologic evaluation, especially for lesions of 2 cm or smaller and those from nonpulmonary sites.

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.

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.

Thoracic chordoma: an unusual presentation of the spinal tumor.

Chordoma is an uncommon malignant bone tumor that originates from the remnants of the embryonic notochord. In most of the reported cases, chordomas occur at the skull base or in the sacrococcygeal spine but rarely in the thoracic spine. In this report, we describe a case of a large thoracic chordoma with posterior mediastinal extension in a 25-year-old woman who presented with left-hand anhydrosis. The imaging studies, pathology findings, and recent advances in treatment are discussed.

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%.

Clinicopathologic analysis of acute myeloid leukemia in a single institution: biphenotypic acute myeloid leukemia may not be an aggressive subtype.

BACKGROUND: Most acute leukemias are classified as lymphoid or myeloid lineages by standard microscopic morphology, cytochemistry and a panel of immunologic markers. The World Health Organization classification of acute leukemia incorporates morphologic, cytogenetic, immunologic and clinical features to define the entities that are biologically homogeneous and that have clinical relevance. The purpose of this study was to determine the clinicopathologic characteristics of acute myeloid leukemia (AML) in Taiwan. METHODS: Archival tissues from 70AML patients during the period of 1995 to 2003 were retrieved. Histologic subtype was classified, defined by World Health Organization classification. Clinical data, including age, gender, treatment and outcome, were scrutinized. RESULTS: There were 37 males and 33 females. The median age at onset of disease was 49 years (range, 2-78 years), which was younger in biphenotypic AML (23.5 years) and older in multilineage dysplasia-related AML (61 years). There were 9 cases (13%) with recurrent cytogenetic abnormality, 7 (10%) multilineage dysplasia-related, 7 (10%) therapy-related, 39 (56%) not other categorized and 8 (11%) of ambiguous lineage. The 2- and 5-year overall survival rates of AML were 26.5% and 20.6%, respectively. Histologic subtype was a significant parameter to determine survival (p < 0.05). The median survivals of therapyrelated, multilineage dysplasia-related and biphenotypic AML were 2 months, 9 months and 30.5 months, respectively. CONCLUSION: This was a clinicopathologic study of AML in Taiwan. Histologic subtype plays a significant prognostic role. Multilineage dysplasia- and therapy-related AML have worse prognosis. Biphenotypic AML may not be an aggressive subtype.

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.

Clinicopathological analysis of malignant lymphoma in Taiwan, defined according to the World Health Organization classification.

We report the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan, defined according to the WHO classification. Data including age and gender of the patients, clinical staging and disease courses were collected for 598 cases of malignant lymphomas. The results showed that the epidemiological characteristics of malignant lymphomas in Taiwan are similar to those in other Asian countries except for a lower incidence rate of T/NK cell lymphoma.

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.

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.

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.