Publications by authors named "Hung-Chang Wu"

18 Publications

  • Page 1 of 1

Optimal Lymph Node Yield for Survival Prediction in Rectal Cancer Patients After Neoadjuvant Therapy.

Cancer Manag Res 2021 24;13:8037-8047. Epub 2021 Oct 24.

Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Purpose: A lymph node (LN) yield ≥12 is required to for accurate determination of nodal status for colorectal cancer but cannot always be achieved after neoadjuvant therapy. This study aims to determine the difference in LN yield from rectal cancer patients treated with and without neoadjuvant therapy and the effects of specific LN yields on survival.

Patients And Methods: The study cohort included a total of 4344 rectal cancer patients treated between January 2007 and December 2015, 2260 (52.03%) of whom received neoadjuvant therapy. Data were retrieved from the Taiwan nationwide cancer registry database. The minimum acceptable LN yield below 12 was investigated using the maximum area under the ROC curve.

Results: The median LN yield was 12 (8-17) for patients who received neoadjuvant therapy and 17 (13-24) for those who did not. The recommended LN yield ≥12 was achieved in 82.73% of patients without and 57.96% of those with neoadjuvant therapy ( < 0.0001). Patients with LN yield ≥12 had a higher OS probability than did those with LN <12 (OR, 1.33; 95% CI, 1.06-1.66; = 0.0124). However, the predictive accuracy for survival was greater for LN yield ≥10 (AUC, 0.7767) than cut-offs of 12, 8, or 6, especially in patients with pathologically-negative nodes (AUC, 0.7660).

Conclusion: Neoadjuvant therapy significantly reduces the LN yield in subsequent surgery. A lower yield (LN ≥ 10) may be adequate for nodal evaluation in rectal cancer patients after neoadjuvant therapy.
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http://dx.doi.org/10.2147/CMAR.S328666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554321PMC
October 2021

Adjuvant Radiotherapy Significantly Increases Neck Control and Survival in Early Oral Cancer Patients with Solitary Nodal Involvement: A National Cancer Registry Database Analysis.

Cancers (Basel) 2021 Jul 26;13(15). Epub 2021 Jul 26.

Department of Radiation Oncology, Chi Mei Medical Center, Tainan 71069, Taiwan.

We assessed the role of adjuvant radiotherapy on neck control and survival in patients with early oral cancer with solitary nodal involvement. We identified pT1-2N1 oral cancer patients with or without adjuvant radiotherapy from the 2007-2015 Taiwan Cancer Registry database. The effect of adjuvant radiotherapy on 5-year neck control, overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method, log-rank tests, and Cox regression analysis. Of 701 patients identified, 505 (72.0%) received adjuvant radiotherapy and 196 (28.0%) had surgery alone. Patients receiving adjuvant radiotherapy were more likely to be aged <65 years, pT2 stage, poorly graded and without comorbid conditions (all, < 0.05). The 5-year OS and DFS differed significantly by receipt of adjuvant radiotherapy. Multivariable analysis showed adjuvant radiotherapy significantly associated with better 5-year OS (adjusted hazard ratio (aHR), 0.72; 95% confidence interval (CI), 0.54-0.97; = 0.0288) and DFS (aHR, 0.64; 95% CI, 0.48-0.84; = 0.0016). Stratified analysis indicated the greatest survival advantage for both 5-year OS and DFS in those with pT2 classification ( = 0.0097; 0.0009), and non-tongue disease ( = 0.0195; 0.0158). Moreover, adjuvant radiotherapy significantly protected against neck recurrence (aHR, 0.30; 95% CI, 0.18-0.51; < 0.0001). Thus, adjuvant radiotherapy is associated with improved neck control and survival in these early oral cancer patients.
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http://dx.doi.org/10.3390/cancers13153742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345217PMC
July 2021

Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer.

Aging (Albany NY) 2021 07 5;13(13):17337-17348. Epub 2021 Jul 5.

Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan.

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, = 0.002) and gastrointestinal (46.9% vs. 14.3%, = 0.027) toxicities and death (12.5% vs. 0.0%, = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.
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http://dx.doi.org/10.18632/aging.203223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312439PMC
July 2021

Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study.

Sci Rep 2021 01 15;11(1):1614. Epub 2021 Jan 15.

Department of Hematology and Oncology, Chi Mei Medical Center, No. 901 Zhonghua Rd., Yung Kang District, Tainan City, 701, Taiwan, ROC.

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P < 0.001). Uni- and multivariate analyses also showed that radiotherapy increased survival after adjusting for confounders (adjusted HR 0.57; 95% CI 0.51-0.63). Further stratified analysis according to the timing of radiotherapy relative to sorafenib treatment revealed that patients who underwent radiotherapy after sorafenib had greater 1-year survival than did those undergoing radiotherapy within sorafenib use or sorafenib alone (adjusted HR 0.39; 95% CI 0.27-0.54). Combined treatment with sorafenib and radiotherapy results in greater HCC patient survival and should be considered an option for treating this challenging disease.
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http://dx.doi.org/10.1038/s41598-021-81176-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810734PMC
January 2021

Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer.

Pharmaceutics 2020 Aug 16;12(8). Epub 2020 Aug 16.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, Taiwan.

Pancreatic cancer is one of the highest causes of mortality throughout the world; thus, it requires an effective treatment strategy. Some chemotherapeutic agents used in the clinics or under clinical trials are hydrophobic and have poor aqueous solubility; consequently, they also have minimal systemic bioavailability. Nanoparticle-based drug delivery tactics have the potential for overcoming these limitations and enhancing their therapeutic efficacy. Herein, a glutathione (GSH)-sensitive micelle (PAH-SS-PLGA) was synthesized for the combined delivery of alpha-tocopheryl succinate (TOS) and curcumin to improve its therapeutic efficacy. The chemical structures of PAH-SS-PLGA were analyzed using Proton Nuclear Magnetic Resonance (H-NMR) and Fourier Transform Infrared (FTIR) spectroscopy, whereas the particle size, zeta potential, and surface morphology were observed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release results revealed that more TOS and curcumin were released in the presence of GSH (5 mM) than the physiological pH value. Fluorescence microscopy images revealed that nanoformulated curcumin/rhodamine was uptaken by PAN02 pancreatic cancer cells. In vitro cytotoxicity assays showed higher cytotoxicity for nanoformulated TOS and/or curcumin than free TOS and/or curcumin. In addition, higher cytotoxicity was observed for combination drugs than free drugs alone. Most interestingly, at all tested concentrations of nanoformulated drugs (PAH-SS-PLGA, TOS, and curcumin), the calculated combination index (CI) value was less than one, which shows that TOS and curcumin have a synergistic effect on cellular proliferation inhibition. Overall, synthesized co-polymers are the best carriers for combination drugs, TOS, and curcumin, because they enhance the therapeutic efficacy and improve pancreatic cancer treatments.
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http://dx.doi.org/10.3390/pharmaceutics12080778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464675PMC
August 2020

Comparison of stereotactic body radiation therapy with and without sorafenib as treatment for hepatocellular carcinoma with portal vein tumor thrombosis.

Medicine (Baltimore) 2020 Mar;99(13):e19660

Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.

Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for unresectable hepatocellular carcinoma (HCC) patients. However, the treatment outcomes for patients with portal vein tumor thrombosis (PVTT) remain poor. In this study, we evaluate the efficacy of SBRT with and or without sorafenib for advanced HCC with PVTT.Fifty four HCC patients with PVTT treated with SBRT using the Cyberknife system was retrospectively analyzed between January 2009 and June 2016. Of these, sorafenib combined with SBRT was administered to 18 patients and SBRT alone was administered to 36 patients. SBRT was designed to target the liver tumor and tumor thrombosis, with a radiation dose of 36 to 45 Gy (median 40 Gy) given in 3 to 5 fractions.The mean follow-up period for SBRT with sorafenib and SBRT alone was 13.22 ± 10.07 months and 15.33 ± 22.01 months, respectively. The response rate was comparable in both groups. Complete response and partial response rates were 77.77% for SBRT with sorafenib and 75.00% without sorafenib (P = .43). The median progression-free survival rate was 6 months (2-11 months) versus 3 months (2-5.6 months) (P = .24) and the 1- and 2-year progression-free survival rates were 25.7% and 15.2% versus 11.1% and 8.3% (P = .1225). The median, 1- and 2-year overall survival rates (OSR) were 12.5 months, 55.6% and 17.7% versus 7 months (5-13.5 months), 33.3% and 11.1% (P = .28), for SBRT with sorafenib versus SBRT alone groups, respectively.The result of our study shows that SBRT with sorafenib administered group resulted in a higher median, progression-free, and OSR for HCC patients with PVTT. However, the trends did not attain statistical significance. A large-scale randomized study is needed to assess the benefits of SBRT with sorafenib administration for patient with PVTT.
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http://dx.doi.org/10.1097/MD.0000000000019660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220154PMC
March 2020

ALK+ Anaplastic Large Cell Lymphoma of Null Cell Phenotype with Leukemic Transformation and Leukemoid Reaction

Turk J Haematol 2019 Nov 9;36(4):289-290. Epub 2019 Jul 9.

Chi-Mei Medical Centre, Department of Hemato-Oncology, Tainan, Taiwan

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http://dx.doi.org/10.4274/tjh.galenos.2019.2019.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863027PMC
November 2019

The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status, as a potent accompanist in combined therapeutic regimens.

J Exp Clin Cancer Res 2019 Jul 1;38(1):282. Epub 2019 Jul 1.

Institute of Clinical Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan.

Background: Lung cancer is the most common cause of cancer-related mortality worldwide despite diagnostic improvements and the development of targeted therapies, notably including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling has been shown to contribute to tumorigenesis, tumor progression, and resistance to therapy in most human cancer types, including lung cancer. Here, we explored the therapeutic effects of co-inhibition of PI3K and mTOR in non-small-cell lung cancer (NSCLC) cells with different EGFR status.

Methods: The antiproliferative activity of a dual PI3K/mTOR inhibitor BEZ235 was examined by the WST-1 assay and the soft agar colony-formation assay in 2 normal cell lines and 12 NSCLC cell lines: 6 expressing wild-type EGFR and 6 expressing EGFR with activating mutations, including exon 19 deletions, and L858R and T790 M point mutations. The combination indexes of BEZ235 with cisplatin or an EGFR-TKI, BIBW2992 (afatinib), were calculated. The mechanisms triggered by BEZ235 were explored by western blotting analysis. The anti-tumor effect of BEZ235 alone or combined with cisplatin or BIBW2992 were also studied in vivo.

Results: BEZ235 suppressed tumor growth in vitro and in vivo by inducing cell-cycle arrest at G1 phase, but without causing cell death. It also reduced the expression of cyclin D1/D3 by regulating both its transcription and protein stability. Moreover, BEZ235 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells by enhancing or prolonging DNA damage and BIBW2992-induced apoptosis in EGFR-TKI-resistant NSCLC cells containing a second TKI-resistant EGFR mutant.

Conclusions: The dual PI3K/mTOR inhibition by BEZ235 is an effective antitumor strategy for enhancing the efficacy of chemotherapy or targeted therapy, even as a monotherapy, to restrict tumor growth in lung cancer treatment.
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http://dx.doi.org/10.1186/s13046-019-1282-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604380PMC
July 2019

Comparative effectiveness of antifungal agents in patients with hematopoietic stem cell transplantation: a systematic review and network meta-analysis.

Infect Drug Resist 2019 15;12:1311-1324. Epub 2019 May 15.

Division of Hematology-Oncology, Department of Internal medicine, Chi Mei Medical Center, Tainan City, Taiwan.

The aim of this study was to use a network meta-analysis to evaluate the relative efficacy of various agents at preventing invasive fungal infections (IFIs). In this way, suitable prophylactic regimens may be selected for patients with hematopoietic stem cell transplantation (HSCT). We conducted a systematic review of randomized controlled trials comparing the prophylactic effects of two antifungal agents or an antifungal agent and a placebo administered to patients with HSCT. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry. Sixteen two-arm studies were identified. Compared with placebo, all six antifungal agents (amphotericin B, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole) presented with greater efficacy at controlling proven IFIs. OR ranged from 0.08 to 0.29. Voriconazole (surface under the cumulative ranking curve [SUCRA]=71.6%), posaconazole (SUCRA=68.9%), and itraconazole (SUCRA=64.7%) were the three top-ranking drugs for preventing proven IFIs. Itraconazole ranked highest (SUCRA=83.1%) and had the greatest efficacy at preventing invasive candidiasis. Posaconazole and micafungin were the two top-ranking drugs (SUCRA=81.3% and 78.4%, respectively) at preventing invasive aspergillosis. Micafungin and voriconazole were the drugs of choice because they lowered mortality more than the other agents (SUCRA=74.6% and 61.1%, respectively). This study is the first network meta-analysis to explore the prophylactic effects of antifungal agents in patients with HSCT. Voriconazole was the best choice for the prevention of proven IFIs in HSCT patients.
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http://dx.doi.org/10.2147/IDR.S203579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526929PMC
May 2019

Accuracy of a Staging System for Prognosis of 5-Year Survival of Patients With Nasopharyngeal Carcinoma Who Underwent Chemoradiotherapy.

JAMA Otolaryngol Head Neck Surg 2017 11;143(11):1086-1091

Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan.

Importance: Concurrent chemoradiotherapy delivers a high level of tumor control and survival benefits for patients with nasopharyngeal carcinoma (NPC). However, many uncertainties still exist regarding the outcomes of chemoradiotherapy, making a more precise survival prognostic system necessary.

Objective: To introduce a new staging system that combines tumor and clinical characteristics to improve the accuracy of prognosis for patients with NPC.

Design, Setting, And Participants: This cohort study enrolled 207 patients with newly diagnosed NPC who underwent concurrent chemoradiotherapy between January 1, 2007, and December 31, 2014, at Chi-Mei Medical Center in Tainan, Taiwan. Data on these patients were collected from the cancer registry database of the Chi-Mei Medical Center. Patients who had a history of cancer or were unable to complete a full course of radiotherapy were excluded. Follow-up was completed on September 30, 2016, and the data analysis was performed from January 1, 2017, to February 28, 2017.

Main Outcomes And Measures: The risk factors associated with 5-year disease-specific survival were incorporated into the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer TNM staging system to construct a new prognostic staging system. The χ2 test for linear trend, the Akaike information criterion, and the C statistic were used to evaluate the monotonicity and discriminatory ability of the new prognostic staging system and the AJCC TNM staging system.

Results: Of the 207 patients enrolled in the study, 157 (75.8%) were men, and the mean (SD) age was 48 (11) years. Multivariate analysis identified advanced clinical T stage (adjusted hazard ratio [aHR], 3.20; 95% CI, 1.58-6.48), poor performance status (aHR, 2.62; 95% CI, 1.30-5.28), and cumulative cisplatin dose lower than 100 mg/m2 (aHR, 2.28; 95% CI, 1.10-4.74) as independent prognostic factors. The β coefficients from the Cox proportional hazards regression model were used to develop an integer-based, weighted point system; advanced clinical T stage, poor performance, and cumulative cisplatin dose lower than 100 mg/m2 were each assigned a score of 1. The sum of these risk scores was stratified into new stage I (score of 0), new stage II (score of 1), new stage III (score of 2), and new stage IV (score of 3). Compared with the AJCC TNM staging system, the new prognostic staging category had better monotonicity with a higher χ2 value (17.8 vs 25.6) for linear trend, better discriminatory ability with a smaller Akaike information criterion (367 vs 360), and a greater C statistic (0.702 vs 0.740) for 5-year disease-specific survival.

Conclusions And Relevance: The new prognostic staging system has a better accuracy of prognosis of survival than the routinely used AJCC TNM staging system and thus is more useful in identifying high-risk patients for more intense treatment and care.
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http://dx.doi.org/10.1001/jamaoto.2017.1562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710352PMC
November 2017

Acute transformation of chronic-type adult T-cell leukemia/lymphoma presenting with seizures.

Kaohsiung J Med Sci 2015 Nov 2;31(11):603-4. Epub 2015 Nov 2.

Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.kjms.2015.09.009DOI Listing
November 2015

Adiponectin is down-regulated in bone marrow interstitial fluid in hematological malignancy.

Int J Hematol 2015 Sep 27;102(3):312-7. Epub 2015 Jun 27.

Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan.

Adipokines play a role in carcinogenesis in a variety of malignancies. These findings were established with regard to serum adipokines and malignancies. However, the expression of adipokines in bone marrow fluid remains unclear, and an investigation of the correlation between bone marrow adipokines and hematological malignancy is needed. The present study was designed to detect adipokine concentrations, including adiponectin, leptin and resistin, in bone marrow interstitial fluid from patients with hematological malignancy and controlled counterparts. The correlations between adipokines, body mass index, clinical parameters, and hematological malignancy were assessed. A total of 80 bone marrow samples were assessed for values of adipokines, adiponectin, leptin and resistin. Patients with hematological malignancy had lower levels of adiponectin. Adiponectin from leukemia bone marrow expressed significantly low values. The adiponectin levels were inversely correlated with body mass index. In conclusion, adiponectin was decreased in bone marrow from patients with leukemia and negatively correlated with body mass index.
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http://dx.doi.org/10.1007/s12185-015-1831-zDOI Listing
September 2015

Bcl-6 expression and lactate dehydrogenase level predict prognosis of primary gastric diffuse large B-cell lymphoma.

J Formos Med Assoc 2013 Jul 11;112(7):382-9. Epub 2012 Oct 11.

Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.

Background/purpose: The gastrointestinal tract is the most common site of primary extranodal non-Hodgkin lymphoma, and the prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) differ in various studies.

Methods: We retrospectively searched for PG-DLBCL in a single institution, performed immunohistochemical analysis, classified tumor phenotype (Hans and Muris algorithms), reviewed medical records, and analyzed the clinical and immunophenotypic variables using Cox proportional hazard regression model.

Results: A total of 46 cases were identified including 25 males and 21 females with a median age of 63.5; 18 (39%) were at stage I and 28 (61%) at stage II. Seven (15%) patients underwent surgery as initial treatment including total (n = 3, 7%) and subtotal (n = 4, 9%) gastrectomy. Thirty-three patients (72%) received frontline chemotherapy treatment including ten with additional rituximab (MabThera) injection, and two (6%) of these patients developed perforation after chemotherapy. Four patients passed away shortly after diagnosis and the remaining three were lost to follow-up. The overall 2- and 5- year survival rates were 55% and 50%, respectively. The expression of various differentiation markers was CD10 (25%), bcl-2 (50%), bcl-6 (84%), and MUM1 (64%). Half of the cases studied (22/44) were classified as germinal center B-cell (GCB) phenotype and the remaining half as non-GCB according to Hans algorithm; 66% and 34% cases belonged to groups 1 and 2, respectively, according to Muris algorithm. Univariate analysis showed the expression of bcl-6 by the tumor cells as a favorable factor, while elevated serum lactate dehydrogenase (LDH) level, bcl-2 expression, and Muris group 2 were associated with poorer outcome. Multivariate analysis revealed that the two prognostic factors were bcl-6 expression and elevated LDH level, with hazard ratios of 0.09 (p = 0.002) and 3.72 (p = 0.024), respectively.

Conclusion: In this retrospective study with heterogeneous treatment modality, we identified bcl-6 expression and elevated LDH level as two prognostic factors for PG-DLBCL.
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http://dx.doi.org/10.1016/j.jfma.2012.07.031DOI Listing
July 2013

Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance.

J Biomed Sci 2013 Jun 27;20:43. Epub 2013 Jun 27.

Institute of Clinical Medicine College of Medicine, National Cheng Kung University, 7th Floor, No.35 Xiaodong Rd., Tainan City 701, Taiwan.

Background: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting.

Results: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants.

Conclusions: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.
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http://dx.doi.org/10.1186/1423-0127-20-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710269PMC
June 2013

CD4 and CD8 double-negative adult T-cell leukemia/lymphoma with monomorphic cells expressing CD99: a diagnostic challenge in a country non-endemic for human T-cell leukemia virus.

Pathol Int 2013 Feb;63(2):132-7

Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus type I (HTLV-I). The neoplastic cells are highly pleomorphic and are usually CD4+ and CD8- phenotypically. We reported the case of a 46-year-old woman presenting with fever, abdominal distention, lymphadenopathy, leukocytosis and hypercalcemia. Nodal biopsy showed diffuse infiltration by monomorphic small to medium-sized atypical lymphocytes expressing CD3, CD25, CD30 and CD99, but not CD1a, CD4, CD8, CD34, terminal deoxynucleotidyl transferase or ALK. An initial diagnosis of T-lymphoblastic leukemia/lymphoma was made based on cytomorphology, CD4 and CD8 double negativity, and the expression of CD99. The diagnosis was later revised to ATLL based on the positive serology study for anti-HTLV I/II antibody and confirmation by the clonal integration of HTLV-I proviral DNA into the tumor tissues by Southern blotting analysis. The patient had a stage IVB disease and died of septic shock after 2 courses of chemotherapy 3 months after diagnosis. Immunohistochemical staining for CD99 in archival ATLL tissues showed a positive rate of 67% (4 of 6 tumors). Our case showed that ATLL with atypical morphology and immunophenotype in HTLV non-endemic areas might pose a diagnostic challenge and CD99 expression is frequent in ATLL.
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http://dx.doi.org/10.1111/pin.12040DOI Listing
February 2013

Intracranial hemorrhage in adult patients with hematological malignancies.

BMC Med 2012 Aug 29;10:97. Epub 2012 Aug 29.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: Clinical characteristics and outcomes of intracranial hemorrhage (ICH) among adult patients with various hematological malignancies are limited.

Methods: A total of 2,574 adult patients diagnosed with hematological malignancies admitted to a single university hospital were enrolled into this study between 2001 and 2010. The clinical characteristics, image reports and outcomes were retrospectively analyzed.

Results: A total of 72 patients (48 men and 24 women) with a median age of 56 (range 18 to 86) had an ICH. The overall ICH incidence was 2.8% among adult patients with hematological malignancies. The incidence of ICH was higher in acute myeloid leukemia (AML) patients than in patients with other hematological malignancies (6.3% vs 1.1%, P = 0.001). ICH was more common among patients with central nervous system (CNS) involvement of lymphoma than among patients with CNS involved acute leukemia (P <0.001). Sites of ICH occurrence included the cerebral cortex (60 patients, 83%), basal ganglia (13 patients, 18%), cerebellum (10 patients, 14%), and brainstem (5 patients, 7%). A total of 33 patients (46%) had multifocal hemorrhages. In all, 56 patients (77%) had intraparenchymal hemorrhage, 22 patients (31%) had subdural hemorrhage, 15 patients (21%) had subarachnoid hemorrhage (SAH), and 3 patients (4%) had epidural hemorrhage. A total of 22 patients had 2 or more types of ICH. In all, 46 (64%) patients died of ICH within 30 days of diagnosis, irrespective of the type of hematological malignancy. Multivariate analysis revealed three independent prognostic factors: prolonged prothrombin time (P = 0.008), SAH (P = 0.021), and multifocal cerebral hemorrhage (P = 0.026).

Conclusions: The incidence of ICH in patients with AML is higher than patients with other hematological malignancies. But in those with intracranial malignant disease, patients with CNS involved lymphoma were more prone to ICH than patients with CNS involved acute leukemia. Mortality was similar regardless of the type of hematological malignancy. Neuroimaging studies of the location and type of ICH could assist with prognosis prediction for patients with hematological malignancies.
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http://dx.doi.org/10.1186/1741-7015-10-97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482556PMC
August 2012
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