Search

This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months) than those with the other types of EGFR mutations (4.08 months; hazard ratio [HR]: 0.26, P=0.038) and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025). Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043). Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR and/or PIK3CA mutations implies that targeted drugs may provide a feasible CCC treatment in the future. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) play essential roles in promoting cholangiocarcinoma (CCA) cell survival by mediating paracrine crosstalk between tumor and cancer-associated fibroblasts (CAFs), indicating the potential of PDGFR as a target for CCA treatment. Clinical trials evaluating PDGFR inhibitors for CCA treatment have shown limited efficacy. Furthermore, little is known about the role of PDGF/PDGFR expression and the mechanism underlying PDGFR inhibitors in CCA related to Opisthorchis viverrini (OV). Therefore, we examined the effect of PDGFR inhibitors in OV-related CCA cells and investigated the molecular mechanism involved. We found that the PDGF and PDGFR mRNAs were overexpressed in CCA tissues compared to resection margins. Notably, PDGFR-α showed high expression in CCA cells, while PDGFR-β was predominantly expressed in CAFs. The selective inhibitor CP-673451 induced CCA cell death by suppressing the PI3K/Akt/Nrf2 pathway, leading to a decreased expression of Nrf2-targeted antioxidant genes. Consequently, this led to an increase in ROS levels and the promotion of CCA apoptosis. CP-673451 is a promising PDGFR-targeted drug for CCA and supports the further clinical investigation of CP-673451 for CCA treatment, particularly in the context of OV-related cases.

Introduction: Bile duct cancer (cholangiocarcinoma, CCA) has a poor prognosis for patients, and despite recent advances in targeted therapies for other cancer types, it is still treated with standard chemotherapy. Anaplastic lymphoma kinase (ALK) has been shown to be a primary driver of disease progression in lung cancer, and ALK inhibitors are effective therapeutics in aberrant ALK-expressing tumors. Aberrant ALK expression has been documented in CCA, but the use of ALK inhibitors has not been investigated. Using CCA cell lines and close-to-patient primary cholangiocarcinoma cells, we investigated the potential for ALK inhibitors in CCA., Methods: ALK, cMET, and ROS1 expression was determined in CCA patient tissue by immunohistochemistry and digital droplet polymerase chain reaction, and that in cell lines was determined by immunoblot and immunofluorescence. The effect on cell viability and mechanism of action of ALK, cMet, and ROS1 inhibitors was determined in CCA cell lines. To determine whether ceritinib could affect primary CCA cells, tissue was taken from four patients with biliary tract cancer, without ALK rearrangement, mutation, or overexpression, and grown in three-dimensional tumor growth assays in the presence or absence of humanized mesenchymal cells., Results: ALK and cMet but not ROS were both upregulated in CCA tissues and cell lines. Cell survival was inhibited by crizotinib, a c-met/ALK/ROS inhibitor. To determine the mechanism of this effect, we tested c-Met-specific and ALK/ROS-specific inhibitors, capmatinib and ceritinib, respectively. Whereas capmatinib did not affect cell survival, ceritinib dose-dependently inhibited survival in all cell lines, with IC 50 ranging from 1 to 9 µM and co-treatments with gemcitabine and cisplatin further sensitized cells, with IC 50 ranging from IC 50 0.60 to 2.32 µM. Ceritinib did not inhibit cMet phosphorylation but did inhibit ALK phosphorylation. ALK was not mutated in any of these cell lines. Only ceritinib inhibited 3D growth of all four patient samples below mean peak serum concentration, in the presence and absence of mesenchymal cells, whereas crizotinib and capmatinib failed to do this. Ceritinib appeared to exert its effect more through autophagy than apoptosis., Discussion: These results indicate that ceritinib or other ALK/ROS inhibitors could be therapeutically useful in cholangiocarcinoma even in the absence of aberrant ALK/ROS1 expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Myint, Sueca-Comes, Collier, Balasubramanian, Venkatraman, Gordan, Zaitoun, Mukherjee, Arora, Larbcharoensub, Suriyonplengsaeng, Wongprasert, Janvilisri, Gomez, Grabowska, Tohtong, Bates and Yacqub-Usman.)

Background: Nasopharyngeal carcinoma (NPC) is a type of cancers that develops in the nasopharynx, the very upper part of the throat behind the nose. NPC is typically diagnosed in later stages of the disease and has a high rate of recurrence due to the location of the tumor growth site. In this study, we compared the gene expression profiles of NPC tissues from patients with and without recurrence to identify potential molecular biomarkers of NPC recurrence., Methods: Microarrays were used to analyze the expression of genes in 15 NPC tissues taken at the time of diagnosis and at the site of recurrence following therapeutic treatment. Pathway enrichment analysis was used to examine the biological interactions between the major differentially expressed genes. The target identified was then validated using immunohistochemistry on 86 NPC tissue samples., Results: Our data showed that the Wnt signaling pathway was enhanced in NPC tissues with recurrence. FZD10, a component of the Wnt signaling pathway, was significantly expressed in NPC tissues, and was significantly associated with NPC recurrence., Conclusion: Our study provides new insights into the pathogenesis of NPC and identifies FZD10 as a potential molecular biomarker for NPC recurrence. FZD10 may be a promising candidate for NPC recurrence and a potential therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tulalamba, Ngernsombat, Larbcharoensub and Janvilisri.)

Objective:  Salivary gland diseases and their pathologies may affect the glandular structure including collagen, a major stromal component, in response to tissue damage or diseases. This study aimed to examine the changes in collagens in different salivary gland diseases using polarized picrosirius red staining., Materials and Methods:  The submandibular gland samples diagnosed as sialadenitis, chronic sclerosing sialadenitis, pleomorphic adenoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma were stained with picrosirius red, Masson's trichrome, and anticollagen I staining. The quantity of collagens was examined and reported as a percentage of positive picrosirius red area. The maturity of collagens was studied with polarized light microscope and reported as a percentage of orange-red and yellow-green polarized collagens, representing the mature and immature collagens, respectively., Statistical Analysis:  The % positive areas for picrosirius red representing the collagen amount among salivary gland diseases were analyzed by one-way analysis of variance with Tukey's test. The % orange-red and % yellow-green polarized areas representing the collagen maturity were analyzed by Kruskal-Wallis test and Mann-Whitney U test., Results:  The malignant tumors, adenoid cystic carcinoma (29.92) and mucoepidermoid carcinoma (26.59), had higher significant percentage of positive picrosirius red area, compared with the benign tumor (14.56), chronic sclerosing sialadenitis (10.61), and sialadenitis (7.22) ( p  < 0.05). The percentages of orange-red polarized areas are 48.07, 39.6, 62.67, 83.75, and 76.05 in sialadenitis, chronic sclerosing sialadenitis, pleomorphic adenoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma, respectively. This percentage tended to increase in the benign and malignant lesions with statistical difference, compared with the inflammatory lesions ( p  < 0.05). There was no statistical difference in the percentages of yellow-green polarized areas among various salivary gland diseases. In addition, the results of Masson's trichrome and anticollagen I staining are corresponding to that of picrosirius red among various salivary gland diseases., Conclusions:  Polarized picrosirius red demonstrated the most amounts of collagen in the malignant lesion, and represented the different maturity of collagens in each lesion group. Studying the amounts and maturity of collagen with picrosirius red for extracellular matrix alteration in salivary gland diseases along with routine hematoxylin and eosin, Masson's trichrome, and immunohistochemistry may provide a better understanding in different salivary gland pathologies., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Purpose: This article aims to review and assess the post-operative management and treatment outcomes of papillary thyroid microcarcinoma (PTMC) in risk-stratified patients., Methods: We retrospectively analyzed the data of PTMC patients who underwent thyroid surgery with or without radioactive iodine treatment (RAI) in a single center between January 2011 and December 2017. Demographic and clinicopathologic data were collected. Risk stratification according to the 2015 American Thyroid Association guideline was applied., Results: Three hundred forty PTMC patients were included. Post-operative RAI was performed in 216/340 (63.53%) patients. In the non-RAI scenario, there were 122 low-risk and two intermediate-risk patients. In total, 261 (76.77%), 57 (16.76%), and 22 (6.47%) patients were classified as low, intermediate, and high risk, respectively. With a median follow-up time of 36 months (interquartile range: 23, 52), we found unfavorable outcomes (evidenced by imaging or out-of-range serum tumor marker levels: high thyroglobulin [Tg] or rising Tg antibody [TgAb] levels) in 8/340 (2.35%) patients, all of which received RAI. PTMC patients with unfavorable outcomes were stratified as low risk (4/261 [1.53%]), intermediate risk (1/57 [1.75%]), or high risk (3/22 [13.64%]). One death occurred in a patient with initial distant metastasis in the high-risk group. Initial high-risk stratification and initial stimulated Tg (of at least 10 ng/mL) were demonstrated as independent predictors for PTMC unfavorable outcomes (persistent or recurrent disease). Five patients with unfavorable outcomes (four with persistent disease and one with recurrent disease) had abnormal Tg or TgAb values despite unremarkable imaging findings. Moreover, 79/124 (63.71%) patients in the non-RAI scenario were only followed up with neck ultrasound., Conclusions: In general, at least 98% of low-risk and intermediate-risk PTMC patients showed favorable outcomes without persistent or recurrent disease, defined by either imaging or serum tumor markers. Nevertheless, aggressive disease could occur in few PTMC patients. Decisions on post-operative management and follow-up may be guided by initial high-risk stratification and initial stimulated Tg levels (≥10 ng/mL) as independent predictors for PTMC unfavorable outcomes. Monitoring using both imaging and serum tumor markers is crucial and should be implemented for patients with PTMC., (© 2022. The Author(s).)

Background: Members of the Wnt signaling pathway have been shown to play a role in nasopharyngeal carcinoma (NPC) progression., Aim: The purpose of this study was to investigate WNT8B protein expression in NPC patients using tissue microarray (TMA) analysis and to evaluate its correlation with patient survival and clinical parameters., Methods: A total of 82 NPC cases, together with six normal nasopharyngeal tissue samples, were targeted to construct the TMA blocks. The WNT8B protein expression was evaluated by immunohistochemistry and its correlation to the clinicopathological features was investigated., Results: Sixty-two of 82 (75.6%) cases exhibited high WNT8B protein expression while 20/82 (24.4%) cases appeared to have low WNT8B expression. The univariate analysis revealed that systemic metastasis was associated with patient 5-year survival. The multivariate Cox proportional hazard regression analysis showed that WNT8B expression and systemic metastasis were significantly associated with the survival of NPC patients. Furthermore, there was no correlation found between the WNT8B protein expression and other clinicopathological parameters., Conclusion: Our results suggest that the expression of WNT8B is associated with NPC patients' survival and could serve as an independent prognostic factor for NPC patients.

Kikuchi-Fujimoto disease (KFD) is an extremely rare disease, and although it is reported to have a worldwide distribution, young Asian women are most likely to be affected. Although this disease is generally benign and self-limiting, distinguishing it from other diseases that cause lymphadenopathy (e.g., leukemia, lymphoma, and infectious diseases) is challenging. A lymph node biopsy is a definitive diagnostic technique for KFD and only requires skillful pathologists. There are no specific symptoms or laboratory tests for KFD, and more than 50% of KFD patients have suffered from being misdiagnosed with lymphoma, which leads to improper treatment. In this study, lymph node tissue samples from KFD patients were used to reveal their exomes and transcriptomes using a high-throughput nucleotide sequencer. Fourteen single nucleotide polymorphisms (SNPs) were identified as candidate KFD markers and were compared with a healthy lymph node exome dataset. The mutation of these genes caused disruptive impact in the proteins. Several SNPs associated with KFD involve genes related to human cancers, olfaction, and osteoblast differentiation. According to the transcriptome data, there were 238 up-regulated and 1,519 down-regulated genes. RANBP2-like and ribosomal protein L13 were the most up-regulated and down-regulated genes in KFD patients, respectively. The altered gene expression involved in the human immune system, chromatin remodeling, and gene transcription. A comparison of KFD and healthy datasets of exomes and transcriptomes may allow further insights into the KFD phenotype. The results may also facilitate future KFD diagnosis and treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells., Materials and Methods: ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments., Results: CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib., Conclusion: Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.

X-linked hyper IgM (X-HIGM) syndrome is a combined immunodeficiency disease caused by mutations in the CD40LG gene, leading to a defect in immunoglobulin (Ig) class switching recombination and effector T-cell responses. X-HIGM patients usually present in early life with pyogenic bacterial and opportunistic infections. Herein, we report a previously healthy 13-year-old Thai boy who first presented with cutaneous and meningoencephalitis cryptococcosis. Whole-exome sequencing revealed that he was hemizygous for a missense c.514T>C (p.Tyr172His) in CD40LG, confirming a diagnosis of X-HIGM. This report demonstrates that X-HIGM could have an age of onset in teens and systemic cryptococcosis could be its presenting symptoms.

Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy in Asia. Infection by human papilloma virus (HPV) has been recognized as an etiological risk for HNSCC, especially oropharyngeal region. While the association between HPV and HNSCC has been well evaluated in Western countries, only a few investigated the HPV-associated HNSCC in Southeast Asia. This study evaluated the prevalence, the characteristics, and the impact of HPV on the treatment outcomes in Thai HNSCC patients., Methods: Non-nasopharyngeal HNSCC patients treated at Ramathibodi Hospital during 2007-2013 were identified through the cancer registry database. Baseline patient, treatment data and survivals were retrospectively reviewed. The formalin-fixed paraffin-embedded (FFPE) tissue sections were retrieved for p16 analysis. The HPV status was determined by p16 immunohistochemistry. The survival outcomes were analyzed in cases which p16 status was confirmed., Results: Total of 200 FFPE tissues of HNSCC patients was evaluated for p16 expression. Positive p16 status was observed in 24 cases (12%); majority of p16-positive were men (20:4 cases). The oropharynx (37.9%) was the most common site found in p16-positive while oral cavity (3.2%) was the least common site. Interestingly, 66.7% of p16-positive were former/current smokers, and 70.8% of this subgroup was categorized as clinical AJCC stage III-IV. The p16-positive HNSCC was significantly superior in 5-year overall survival [5-yrs OS 63% vs. 40%, p=0.03], 5-year disease-free survival [5-yrs DFS 61% vs. 36%, p=0.03] and in 5-year locoregional relapse-free survival [5-yrs LRFS 93% vs. 68%, p=0.018] when compared with p16-negative., Conclusions: In comparison to the results from the Western countries, the prevalence of HPV-related HNSCC in Thai patients was less, and differences in some characteristics were observed. Nevertheless, improvement in OS, DFS and LRFS were observed in p16-positive patients. Our analyses suggested that p16 status is also a strong prognostic marker for HNSCC patients in Thailand.

Background: No predictive biomarker of immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) has been well established. The impact of programmed death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocytes (TILs), and p16 status in HNSCC is unclear and may vary according to ethnicity., Methods: HNSCC patients treated between 2007 and 2013 were reviewed. Archival tissues were retrieved for PD-L1, CD8+ TILs, and p16 analyses. PD-L1 expression was evaluated by using the validated SP142 assay on the VENTANA platform. CD8+ TILs were defined by using semiquantitative scoring., Results: A total of 203 patients were analyzed. PD-L1 expression was observed in 80% of patients and was significantly associated with older age (P < 0.001). A high CD8+ TIL score (≥ 6) was significantly associated with never-smoking (P = 0.020), oral cavity cancer (P < 0.001), and stage M0 at presentation (P = 0.025). The p16 status was positive in 12% of patients. Patients with a high TIL score had a significantly longer OS (P = 0.032). Patients with PD-L1 expression of 1-49% and ≥ 50% were associated with a significantly shorter OS compared with those with PD-L1 < 1% (P = 0.027 and P = 0.011, respectively). Multivariate analysis showed that PD-L1 ≥ 50% was significantly associated with a poor OS. (HR 2.98 [95% CI 1.2-7.39]; P = 0.019.) CONCLUSIONS: A high prevalence of PD-L1 expression was observed in HNSCC using the validated SP142 assay. PD-L1 expression was associated with older age, while highly PD-L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L1 untreated HNSCC patients.

Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients., Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated., Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival., Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.

Objectives: Vascular pythiosis is a life-threatening infection caused by the oomycete Pythium insidiosum. This article reports the clinical presentation, serodiagnosis, pathology, and outcomes seen at the authors' institution., Methods: The cases of patients with proven vascular pythiosis at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand from January 2006 to December 2016 were analyzed retrospectively., Results: Thirteen patients were analyzed, eight of whom had underlying thalassemias. Of the remaining five patients, one had aplastic anemia, one had myelodysplasia, one had acute leukemia, one had cirrhosis, and one had alcoholism. Neutropenic patients showed a rapid clinical deterioration. Atypical presentations including carotid arteritis, aneurysm, brain abscess, and stroke occurred in the non-thalassemic patients. Serology yielded positive results in all cases, with a rapid turnaround time. Serology has the advantage of providing a presurgical diagnosis, which allows prompt surgery and clinical cure to be achieved. Pathology revealed a neutrophilic response in the acute phase and a later shift to granuloma. Immunotherapy in combination with itraconazole and terbinafine was given. The amputation rate was 77%, and disease-free surgical margins were achieved in five cases (38%). The mortality rate was 31%., Conclusions: This study highlights new aspects of pythiosis, such as the unusual host, clinical presentation, serology as a marker for rapid diagnosis, histopathology, and outcomes. Early recognition of the disease with prompt multimodality treatment may improve survival., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Myoepithelial carcinoma is an uncommon malignant tumor of the lacrimal gland, composed of neoplastic myoepithelial cells with an infiltrative growth. The present study describes a unique case of progressive proptosis and blindness of the right eye in a 68-year-old woman following total tumor removal for lacrimal pleomorphic adenoma. Clinical study, surgical exploration, and pathology revealed lacrimal myoepithelial carcinoma ex recurrent pleomorphic adenoma, T2N0M0. In addition, 18 cases of lacrimal myoepithelial tumor that have been previously described in the literature are reviewed. The application of clinical, radiological, histopathologic, and immunohistochemical investigations may help to reach the definite diagnosis. Criteria for malignancy of lacrimal myoepithelial tumor should be the same as salivary myoepithelial tumor diagnosis, until long-term outcome data for a larger number of patients with lacrimal myoepithelial carcinoma become available.

Objective: To evaluate the clinicopathologic findings and treatment outcome in laryngectomized patients with laryngeal cancer and hypopharyngeal cancer. Materials and Methods: The authors retrospectively reviewed the medical records of 212 patients who had been newly diagnosed and treated with laryngectomy between January 2000 and December 2010. The age, gender, clinical manifestations, associated predisposing condition, tumor WHO grade, AJCC tumor stage, maximum tumor size, anatomical involvement, type of surgery, postoperative sequelae, treatment and therapeutic outcome were analyzed. Results: The present study included laryngeal cancer (n = 155) and hypopharyngeal cancer (n = 57). The patients’ age ranged from 38 to 84 years, with the mean age of 62.08±9.67 years. The common clinical presentations were hoarseness (73.6%), cervical lymphadenopathy (35.8%), sorethroat (22.2%), and odynophagia (14.6%). The laryngeal cancer commonly involves true vocal cord (86.5%), anterior commissure (65.8%), false vocal cord (56.8%), laryngeal ventricle (53.5%), subglottis (47.1%), and paraglotic space (35.5%), respectively. Fifty-three percent of cases had stage IV cancer. The most common postoperative surgical sequela was hypothyroidism (77.8%). The overall 5-year survivals for laryngeal cancer and hypopharyngeal cancer were 55% and 9%, respectively. The 5-year survival for node-negative cases was 61.8% versus 17% for node-positive cases (p< 0.001). AJCC stage of laryngeal cancer and hypopharyngeal cancer was a significant predictor of 5-year survival (p< 0.001 and p = 0.004, respectively). Conclusions: The advanced AJCC stage, advanced T stage, advanced N stage, extracapsular tumor spread, and tumor invasion of false vocal cord, epiglottis, preepiglottic space, paraglottic space, thyroid cartilage, cricothyroid membrane were found to significantly augment the decrease of 5-year survival in laryngeal cancer. Only advanced AJCC stage was significantly associated with 5-year survival rate in hypopharyngeal cancer., (Creative Commons Attribution License)

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sister Mary Joseph nodule is an uncommon metastatic intra-abdominal malignancy involving the umbilicus. The present study describes a rare case of desmoplastic small round cell tumor (DSRCT), histological grade 3, high grade, Gilly classification 4, stage IV, in an 18-year-old Thai man presenting with the Sister Mary Joseph nodule, ascites and pleural effusion. The histopathological examination of the umbilical mass revealed the presence of malignant small round cells associated with prominent stromal desmoplasia. Immunohistochemical stains showed positive reactivity to cytokeratin, desmin, neuron-specific enolase, Wilms' tumor 1, CD56, CD99 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)/INI1 in the small round cells. Fine needle aspirations of the ascitic fluid and pleural effusion were performed, and immunocytochemistry revealed a metastatic DSRCT. The patient received a VDC/IE regimen of chemotherapy, comprising vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide; however, the patient developed systemic metastasis and succumbed to the disease 6 months later.

Sialoblastoma is a rare salivary gland tumor that recapitulates the primitive salivary gland anlage. The authors herein report a case of sialoblastoma of a minor salivary gland, clinically presenting with progressive enlargement of a mass in the cheek of a 1-year-old female infant. Histopathologically, the mass consisted of tight clusters of basaloid cells and partially formed ductal and pseudo-ductal spaces separated by thin fibrous bands. Immunohistchemical studies demonstrated the presence of cytokeratin AE1/AE3, p63, CD99, α-fetoprotein (AFP) and Hep Par-1 expression in a considerable number of tumor cells. The clinical and pathological characteristics are presented and relevant literature is reviewed. Early complete surgical excision is recommended for the treatment of sialoblastoma. Radiation may be considered in cases with incomplete resection of the tumor. Chemotherapy may play a vital role in extensive, metastatic, or relapsed cases, or in cases with inadequate excision. The follow-up treatment should be frequent and prolonged. To the best of our knowledge, this is the first reported case of sialoblastoma of the cheek with immunoreactivity for AFP and Hep Par-1, which may be associated with the embryonic origin of the tumor. AFP may be a useful marker of tumor response in patient with sialoblastoma.

Polymorphous low-grade adenocarcinoma is an uncommon malignant tumor derived from the terminal duct cells of the salivary glands. The present study described a rare case of polymorphous low-grade adenocarcinoma, T2N0M0 stage 2, in a 65-year-old man, who presented with a sore throat and painful dysphagia. Computed tomography revealed an infiltrative heterogenous enhancing mass involving the left aryepiglottic fold. He underwent a tumor removal with frozen section for evaluating the surgical margin. Subsequent supraglottic laryngectomy was performed. Polymorphous low-grade adenocarcinoma was diagnosed histologically, characterized by cytologic uniformly, morphologic diversity and an infiltrative growth pattern. Epiglottic cartilaginous invasion by the tumor is demonstrated. Clinical, radiological, endoscopic and pathological features with briefly reviewed relevant literatures are discussed. This is the first reported description in the literature, to the best of our knowledge, of an epiglottic polymorphous low-grade adenocarcinoma receiving successful supraglottic laryngectomy with 7 year disease free survival.

Background: Preoperative combined chemoradiation treatment (CRT) is now accepted as the treatment of choice due to its benefits of decreasing the primary tumor volume and enhancing the sphincter preservation surgery. Determining whether a patient is responding to therapy is crucial for rectal cancer patients who may benefit from prompt treatment modifications., Objective: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response., Material and Method: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed., Results: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during-CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%]., Conclusion: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients.

Pythiosis is an emerging and life-threatening infectious disease of humans and animals living in tropical and subtropical countries and is caused by the fungus-like organism Pythium insidiosum. Antifungals are ineffective against this pathogen. Most patients undergo surgical removal of the infected organ, and many die from advanced infections. Early and accurate diagnosis leads to prompt management and promotes better prognosis for affected patients. Immunohistochemical assays (IHCs) have been developed using rabbit antibodies raised against P. insidiosum crude extract, i.e., culture filtrate antigen (CFA), for the histodiagnosis of pythiosis, but cross-reactivity with pathogenic fungi compromises the diagnostic performance of the IHC. Therefore, there is a need to improve detection specificity. Recently, the elicitin protein, ELI025, was identified in P. insidiosum, but it was not identified in other human pathogens, including true fungi. The ELI025-encoding gene was successfully cloned and expressed as a recombinant protein in Escherichia coli. This study aims to develop a new IHC using the rabbit anti-ELI025 antibody (anti-ELI) and to compare its performance with the previously reported anti-CFA-based IHC. Thirty-eight P. insidiosum histological sections stained positive by anti-ELI-based and anti-CFA-based IHCs indicating 100% detection sensitivity for the two assays. The anti-ELI antibody stained negative for all 49 negative-control sections indicating 100% detection specificity. In contrast, the anti-CFA antibody stained positive for one of the 49 negative controls (a slide prepared from Fusarium-infected tissue) indicating 98% detection specificity. In conclusion, the anti-ELI based IHC is sensitive and specific for the histodiagnosis of pythiosis and is an improvement over the anti-CFA-based assay., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Dermatofibrosarcoma protuberans (DFSP) is a superficial cutaneous tumor of low malignant potential characterized by a high rate of local recurrence. The histopathological appearance shows uniform spindle neoplastic cells arranged in a predominantly storiform pattern, typically with positive staining for cluster of differentiation (CD)34 and vimentin on immunohistochemistry. A minority of cases of DFSP have areas of sarcomatous transformation. Wide surgical excision is the cornerstone of treatment for DFSP. The objective of the present study was to determine the clinicopathological features of DFSP. Pathological records were searched for cases of DFSP in the database of the Department of Pathology, Faculty of Medicine Ramathibodi Hospital (Mahidol University, Bangkok, Thailand) between 1994 and 2013. The results showed 68 cases with DFSP. The mean age at diagnosis was 40 years (range, 3-86 years). Among this group of patients, 26 cases (38.2%) experienced local recurrence and 6 (8.8%) exhibited sarcomatous transformation of DFSP. The factors that predict the recurrence of DFSP are an incorrect first pathological diagnosis and an inadequate surgical margin. The factors that predict the sarcomatous transformation of DFSP are a larger tumor size and an incorrect first pathological diagnosis. In patients who have tumors with spindle cells arranged in a storiform pattern, CD34 immunohistochemical staining provides the definitive diagnosis. Exact histopathological categorization is important to select the appropriate treatment and predict the clinical outcome.

Background: The complex anatomy of the pancreaticobiliary duct was crucial in management of pancreatic and biliary tract disease., Materials and Methods: Fresh specimens of pancreas, common bile duct (CBD), and duodenum were obtained en bloc from autopsies of 160 patients., Results: Ninety-three male and 67 female patients were included. The length of the pancreas ranged from 9.8-20 cm (mean, 16.20 +/- 1.70 cm). The intrapancreatic portion of the CBD showed patterns of three types: most common (85.30%) was type A, in which the anterior surface of the common bile duct was totally covered, while its posterior surface was partially covered, by the pancreatic parenchyma. On dissection of the accessory duct of Santorini, the accessory duct was traceable to the duodenal wall in 67.6%. The anatomy of the Wirsung-choledochus confluence was grouped into five different types. The common channel was found in 75.60% and its length varied from just a common junction (so-called "V-type" anatomy) to 15 mm (Y-type-b). Separate papillae (so-called "II-type") were found in 15.3% of specimens., Conclusions: Several important points regarding the anatomy of the pancreaticobiliary junction and pancreatic ductal system were illustrated in this study.

We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity., (© 2015 by the Society for Experimental Biology and Medicine.)

Objective: The objective of this study was to analyze the clinicopathologic data of salivary gland tumors in Bangkok, Thailand., Method and Materials: Cases diagnosed with salivary gland tumors were retrieved from a dental school and a medical school in Bangkok, Thailand. Clinicopathologic data were recorded and analyzed with respect to gender, age, site, and histologic type., Results: Of the 411,851 cases, 1,047 salivary gland tumors (0.2%) were found. The male to female ratio was 1:1.2. The age of patients ranged from 1 to 88 years with an average age of 47.1 years. 721 cases were benign tumors (68.8%) while 326 cases (31.2%) were malignant tumors. The parotid gland was the most common site (62.7%), followed by the submandibular gland (18.8%), and the intraoral minor salivary glands (18.0%). Among the intraoral minor salivary glands, palate was the most common site (49.2%). The most common benign and malignant tumors were pleomorphic adenoma and mucoepidermoid carcinoma., Conclusions: Salivary gland tumors are rare. Compared with Western countries, the prevalence of polymorphous low-grade adenocarcinoma (PLGA) in Southeast Asia is low. Data from this study may be helpful for dentists in making differential diagnoses.

Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches.