Biomedical subjects

Mei-Hua Tsou

Publications and source records attributed to Mei-Hua Tsou.

15 recordsLinked to original sources

PubMed2007

Effects of paclitaxel and doxorubicin in histocultures of hepatocelular carcinomas.

Cancer has been the leading cause of death in Taiwan over the past two decades and liver cancer is the leading cause of all cancer deaths in Taiwan with a trend of increase in incidence. Therapeutic options and efficacy for liver cancer have been limited and the 5-year survival rate is less than 7% in the Unite States. The study was conducted to establish a histoculture system of human hepatocellular carcinomas (HCC) for biological and pharmacological studies and to determine the efficacy of anticancer drugs with the established HCC histocultures. Patient HCC tissues freshly obtained after surgeries were prepared and histocultured. The histocultured HCC were treated with doxorubicin and paclitaxel of various concentrations for 96-h. Upon drug treatments, the activity of tumor cell proliferation and extent of cell death induction were measured and changes of the alpha-fetoprotein levels in the culture medium were determined. We demonstrated that human HCC can be successfully cultured in a 3-dimensional histoculture system and used for pharmacological studies. Doxorubicin and paclitaxel showed concentration-dependent activities in anti-proliferation and cell death induction against the human HCC. Inhibitory effects of both drugs on alpha-fetoprotein production of the cultured HCC were in agreement with their anti-proliferative effects. Exposure time-dependent antitumoral effects of paclitaxel treatments at 3-, 24-, and 96-h against the histocultured HCC PLC/PRF/5 xenograft tumors were also observed. In conclusion, we have demonstrated a histoculture system for patient HCC and it can be utilized in selection of active drugs prior to treatments in patients and in evaluation of new agents against HCC, for which therapeutic agents are in desperate needs worldwide.

Antineoplastic Agents↗

PubMed2006

Genomic prediction of locoregional recurrence after mastectomy in breast cancer.

PURPOSE: This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy. PATIENTS AND METHODS: A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence. RESULTS: Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control. CONCLUSION: Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression-based predictive index can be used to select patients for PMRT.

Adult↗

PubMed2006

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy.

PURPOSE: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Adult↗

PubMed2006

Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients.

PURPOSE: To develop clinical prediction models for local regional recurrence (LRR) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status. METHODS AND MATERIALS: Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratified by lymph node involvement (<4 vs. >or =4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients). RESULTS: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival. CONCLUSION: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.

Adult↗

PubMed2006

Nasopharyngeal biopsy imprint cytology: a retrospective analysis of 191 cases.

Patients with nasopharyngeal carcinoma (NPC) are common in Taiwan. To provide efficient management to patients, the surgeons often perform cytological imprints immediately after biopsies of lesions suspicious for NPC. The results of cytological assessment of imprints usually are reported within 30 min after biopsies. The patients with positive cytological results can then be arranged for further examinations during the same visit. We reviewed 191 imprints and corresponding biopsies from 187 patients during 1997-2004 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The cytological diagnoses were categorized into four groups: negative (62 cases), suspicious (8 cases), positive (116 cases), and inadequate specimen (5 cases). There were 18 false-negative and 1 false-positive diagnoses. All suspicious cases were positive histologically. Our results showed a sensitivity of 87.2% and a specificity of 97.8%. The accuracy was 89.8%. Therefore, nasopharyngeal imprint cytology is a sensitive and specific method for rapid diagnosis of nasopharyngeal cancer at an outpatient setting.

Biopsy↗

PubMed2006

A unique pancreatic tumor with exclusive hepatocytic differentiation.

Only 7 cases of pancreatic tumor with hepatocytic differentiation have been reported in the literature, including 6 cases of hepatoid carcinoma and one case of hepatoid adenoma. Diagnosis of hepatoid carcinoma depends on recognition of characteristic histological features, supported by other evidence linked to hepatic lineage including alpha-fetoprotein production, positive immunoreactivity to liver synthesized proteins, and in situ hybridization detection of albumin mRNA. In addition, a synchronous focus of carcinoma arising in pancreatic ducts, islet cells, or acinar cells is essential. We report a unique case of pancreatic tumor with exclusive hepatocytic differentiation. In this tumor, we were unable to find a synchronous focus of carcinoma arising in pancreatic ducts, islet cells, or acinar cells, ruling out the possibility of its being hepatoid carcinoma. Long term follow-up can help to determine whether this tumor is benign or malignant. The patterns of reticulin staining and immunohistochemical staining are suggestive of malignancy, but mitotic activity is low and nuclear pleomorphism is minimal.

Adult↗

PubMed2005

Interpretation of magnetic resonance imaging for locally advanced rectal carcinoma after preoperative chemoradiation therapy.

PURPOSE: Neoadjuvant concomitant chemoradiotherapy has been used in cases of locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. Preoperative staging is essential for planning and providing optimal therapy. The purpose of this study is to determine the accuracy of staging with magnetic resonance imaging and to define any factors that interfere in interpretation of images obtained after preoperative chemoradiation therapy. METHODS: Thirty-six patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed six to eight weeks later by radical surgery. Preoperative magnetic resonance images were reinterpreted by one radiologist and the results compared with histopathologic staging. RESULTS: T-level downstaging occurred in 10 of 36 patients (28 percent), and N-level downstaging occurred in 29 of 36 patients (80 percent) after completion of chemoradiation therapy. Pathologic complete remission after chemoradiotherapy occurred in five patients (12 percent). Of the 36 patients, 17 (47 percent) were overstaged and 2 (6 percent) were understaged in T-level, whereas 10 patients (28 percent) were overstaged and 3 patients (8 percent) were understaged in N-level. The accuracy of magnetic resonance imaging for determining depth of wall invasion was 47 percent, with 64 percent accuracy for nodal staging. CONCLUSIONS: Magnetic resonance imaging is commonly used in staging of pelvic malignancies because of its fine resolution, but chemoradiotherapy may decrease its accuracy. Thickening of the rectal wall after radiation by marked fibrosis, and peritumoral infiltration of inflammatory cells and vascular proliferation may contribute to overestimation of stage. By contrast, pathologic residual cancer beneath normal mural structure after chemoradiation therapy may result in understaging of rectal cancer.

Adult↗

PubMed2005

Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study.

OBJECTIVE: The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer. METHOD: A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months. RESULTS: All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively. CONCLUSION: Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.

Adult↗

PubMed2005

Clinicopathological analysis of T-cell lymphoma in Taiwan according to WHO classification: high incidence of enteropathy-type intestinal T-cell lymphoma.

OBJECTIVES: The clinicopathological characteristics of malignant lymphomas vary according to geography, especially for the T-cell lymphoma (TCL). The aim of this study is to demonstrate the incidence and clinicopathological characteristics of TCL in Taiwan according to WHO classification. METHODS: Archival tissue from 600 malignant lymphomas during the period of 1995-2002 was retrieved, there were 74 cases diagnosed with TCL. Hematoxylin and eosin slides stained and other special studies were reviewed. All cases were reclassified according to the WHO classification. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. RESULTS: There were 52 males and 22 females with male predilectation. The incidence of TCL in malignant lymphoma was 12.3%. The most prevalent histologic subtype was peripheral T-cell lymphoma (PTCL), followed by nasal T-cell/Natural killer- (T-/NK-) cell lymphoma, T-lymphoblastic lymphoma (LBL), anaplastic large cell lymphoma, and enteropathy-type intestinal lymphoma (ETCL). Clinically, 39 cases (49%) had higher clinical stage (III/IV). Overall 2-year and 5-year survival rate was 51.4% and 34.7%, respectively. It was noteworthy that ETCL had high incidence rate (8.1%) and high mortality. There was significant difference in survival rates in respect of clinical stages and histological subtypes. CONCLUSIONS: TCL is relatively less frequent in Taiwan, compared to other countries in Asian and western countries. The most common histological subtypes are PTCL, unspecified and T-/NK-cell lymphoma. Five-year survival rate is 34.7%. ETCL has higher incidence rate in Taiwan. The clinical stage and histological subtypes are prognostic parameters in determining the survival rates.

Female↗

PubMed2005

Xanthogranulomatous appendicitis.

Xanthogranulomatous inflammation is an uncommon, though well-recognized entity that has been described in various organs but mostly commonly in the kidney and gallbladder. There have been few reports of its occurrence in the appendix. We report a 39-year-old man who presented with fever, right lower quadrant abdominal pain and mass. Abdominal computed tomography (CT) revealed diffuse wall thickening over the terminal ileum and cecum with involvement of the mesentery. CT-guided biopsy showed colitis with infiltration of lymphocytes, neutrophils and eosinophils. The patient's illness responded to intravenous antibiotics, but relapsed after switching to oral antibiotics. After the second course of intravenous antibiotics was given without resolution of symptoms, exploratory laparotomy was performed. Although operative findings favored colitis of the cecum, cancer of the cecum could not be completely ruled out. Right hemicolectomy was done and pathology confirmed the diagnosis of xanthogranulomatous appendicitis. This case illustrates that xanthogranulomatous appendicitis may mimic a locally advanced cancer, has a benign course, and can be cured by surgical resection.

Adult↗

PubMed2004

Integrated modeling of clinical and gene expression information for personalized prediction of disease outcomes.

We describe a comprehensive modeling approach to combining genomic and clinical data for personalized prediction in disease outcome studies. This integrated clinicogenomic modeling framework is based on statistical classification tree models that evaluate the contributions of multiple forms of data, both clinical and genomic, to define interactions of multiple risk factors that associate with the clinical outcome and derive predictions customized to the individual patient level. Gene expression data from DNA microarrays is represented by multiple, summary measures that we term metagenes; each metagene characterizes the dominant common expression pattern within a cluster of genes. A case study of primary breast cancer recurrence demonstrates that models using multiple metagenes combined with traditional clinical risk factors improve prediction accuracy at the individual patient level, delivering predictions more accurate than those made by using a single genomic predictor or clinical data alone. The analysis also highlights issues of communicating uncertainty in prediction and identifies combinations of clinical and genomic risk factors playing predictive roles. Implicated metagenes identify gene subsets with the potential to aid biological interpretation. This framework will extend to incorporate any form of data, including emerging forms of genomic data, and provides a platform for development of models for personalized prognosis.

Bayes Theorem↗

PubMed2004

Chromosomal comparative genomic hybridization abnormalities in early- and late-onset human breast cancers: correlation with disease progression and TP53 mutations.

Nearly 30% of the breast cancer patients in the Taiwanese community have their diseases diagnosed before the age of 40. Their 5-year survival rate is poorer than that of their late-onset breast cancer counterparts. Genomic abnormalities between these two breast cancer age groups were compared using comparative genomic hybridization (CGH) analyses. The sample set was made up of 44 early-onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and 8p. These were very similar for the two age groups, as well as for Taiwanese women and other ethnic populations. In contrast, several less common lesions, such as gains on 16p and 8p and losses on 11q and 9p, were significantly different between the early- and late-onset breast tumors. In addition, more profound chromosomal changes were consistently associated with the more advanced-stage tumors, and less expression of the estrogen and the progesterone receptors, and of HER-2/neu. About 19% of the breast cancers examined carried a TP53 mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and these were distributed randomly along the tested gene fragments without apparent clustering, as has been shown in certain other ethnic or regional studies. On average, patients carrying these TP53 mutations had 9.5 CGH lesions per case, compared to only 2.8 changes in samples that had no TP53 mutation. Our results indicate that certain genomic lesions, especially 11q loss, may play a role in early-onset breast tumor formation, and that combined use of genomic patterns and molecular targets may provide a useful tool for diagnostic, therapeutic, and prognostic purposes.

Adult↗

PubMed2004

Early gastric MALT lymphoma.

The endoscopic findings of mucosa-associated lymphoid tissue (MALT) lymphoma were classified into exophytic and infiltrative types by Palmer and Seifert. Normal-appearing gastric MALT lymphoma is quite uncommon, and only one case had been reported in the literature. Here we report the case of a 49-year-old woman who underwent esophagogastroduodenoscopy for health screening. Endoscopy revealed indistinct follicular gastritis mucosal change and a duodenal ulcer scar, and random biopsy was taken from her stomach to check for the presence of Helicobacter pylori (H. pylori). Biopsy revealed chronic gastritis with H. pylori, and atypical lymphoid infiltration highly suggestive of MALT lymphoma. Polymerase chain reaction study using primers specific for immunoglobulin heavy chain gene showed a clonal B cell lymphoproliferation consistent with MALT lymphoma. Treatment with amoxicillin, clarithromycin, and omeprazole for H. pylori rendered complete resolution of the disease. In conclusion, follicular gastritis may be a high-risk condition that gives rise to MALT lymphoma, and further investigation is indicated.

Female↗

PubMed2002

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy.

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.

Adult↗

PubMed2002

Primary pulmonary paraganglioma.

We describe a 46-year-old man with a mass in the lower lobe of the right lung. The tumor was initially suspected to be a poorly differentiated adenocarcinoma after endobronchial biopsy. Subsequently, a right lower lobectomy was performed, and a paraganglioma was diagnosed histologically. Using whole-body CT scan and metaiodobenzylguanidine (MIBG) scintigraphy, we excluded the involvement of other organs. No evidence of recurrence or metastasis was found during the follow-up period of 3 years. Primary pulmonary paragangliomas are very uncommon tumors. Literature relevant to this disease entity is discussed.

3-Iodobenzylguanidine↗