Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma.

In an effort to identify the functional alleles associated with hepatocellular carcinoma (HCC), we investigated 152 genes found in the 4q21-25 region that exhibited loss of heterozygosity (LOH). A total of 2,293 pairs of primers were designed for 1,449 exonic and upstream promoter regions to amplify and sequence 76.8-114 Mb on human chromosome 4. Based on the results from analyzing 12 HCC patients and 12 healthy human controls, we discovered 1,574 sequence variations. Among the 99 variants associated with HCC (p < 0.05), four are from the Dickkopf 2 (DKK2) gene: three in the promoter region (g.-967A>T, g.-923C>A, and g.-441T>G) and one in the 5'UTR (c.550T>C). To verify the results, we expanded the subject cohort to 47 HCC cases and 88 healthy controls for conducting haplotype analysis. Eight haplotypes were detected in the non-tumor liver tissue samples, but one major haplotype (TAGC) was found in the tumor tissue samples. Using a reporter assay, this HCC-associated allele registered the lowest level of promoter activity among all the tested haplotype sequences. Retention of this allele in LOH was associated with reduced DKK2 transcription in the HCC tumor tissues. In HuH-7 cells, DKK2 functioned in the Wnt/ß-catenin signaling pathway, as an antagonist of Wnt3a, in a dose-dependent manner that inhibited Wnt3a-induced cell proliferation. Taken together, the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/ß-catenin signaling, contributing to HCC oncogenesis. Thus our study reveals a new mechanism through which a tumor suppressor gene in a LOH region loses its function by allelic selection.

An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients.

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.

Primary Intestinal Diffuse Large B-cell Lymphoma in Taiwan Showed a Relative Higher Rate of Perforation and EBV Association.

We retrospectively investigated 59 surgically resected primary intestinal diffuse large B-cell lymphomas (PI-DLBCL) including 31 males and 28 females with a median age of 66. Eleven (19%) tumors were perforated at presentation; 8 (14%) were multicentric. Ileum (n=24; 43%) and ileocecum (n=17; 30%) were most frequently involved. Twenty-one (36%) patients did not receive chemotherapy or radiotherapy including 6 with perforation and died in 0.2 to 7 months. The 1-, 2-, and 5-year overall survival rates were 68.4%, 56.5%, and 50.0%, respectively. Seven (12%) of 59 cases were positive for Epstein-Barr virus (EBV) by in situ hybridization. IGH, BCL2, BCL6, and MYC foci were rearranged in 22%, 3%, 17%, and 7% cases, respectively, with 14% exhibiting gain/amplification at the MYC locus. Perforation (P=0.009), high ECOG PS (≥2) (P=0.018), and no adjuvant chemotherapy (P<0.001) were poor prognostic factors but not immunophenotype including co-expression of bcl-2 and myc, EBV status, or chromosomal aberrations. Perforation and chemotherapy remained significant by multivariate analysis. PI-DLBCL in Taiwan carried a relatively higher rate of perforation, lower frequency of germinal center B-cell phenotype, and higher EBV association as compared with studies from other geographic areas. Furthermore, perforation was a poor prognostic factor.

Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma.

BACKGROUND: Renal cell carcinoma, a common malignant tumor arising from the kidney, occurs in 3.62 and 1.95 cases per one hundred thousand people among men and women, respectively, in Taiwan each year. Approximately 80% of cases are classified as clear-cell renal cell carcinoma. Inactivation of the von Hippel-Lindau tumor suppressor gene has been implicated in the tumorigenic pathway of renal cell carcinoma. Two single nucleotide polymorphisms, rs779805 and rs1642742, located in the promoter and 3' untranslated regions of the von Hippel-Lindau gene are informative and implicated in the occurrence of renal cell carcinoma worldwide. The aim of this study is to clarify whether these polymorphisms are associated with renal cell carcinoma in Taiwanese. Genomic DNA was isolated from normal and tumor tissues of 19 renal cell carcinoma patients. The samples were screened for allelic polymorphisms by restriction fragment length polymorphism with BsaJ I and Acc I digestion. Reconfirmation was carried out by direct sequencing. RESULTS: Consistent with Knudson's two-hit theory, AA to AG somatic mutations were observed in rs779805. In addition, loss of heterozygosity in both rs779805 and rs1642742 was demonstrated in 10 out of 15 RCC patients aged 50 or over. The G allele or AG heterozygote frequencies at these two loci were much higher in patient germline DNA when compared with the control group. After adjusting for age, the frequency of the G allele in both loci was much higher for late onset renal cell carcinoma in the Taiwanese population. CONCLUSIONS: Our current results confirmed that the existence of G allele in both rs779805 and rs1642742 in the von Hippel-Lindau tumor suppressor gene is of importance in renal cell carcinoma tumorigenesis. However, more comprehensive and detailed research is needed to address the clinical relevance. Larger sample size is required to determine the exact power of correlation between these two genetic polymorphisms and renal cell carcinoma.

Validating a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer.

PURPOSE: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. RESULTS: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. CONCLUSIONS: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

Mycobacterium abscessus granulomatous prostatitis.

Infectious granulomatous prostatitis is uncommon, and most cases of granulomatous prostatitis are classified as nonspecific granulomatous prostatitis. From 2007 to 2009, 5 patients experienced poor wound healing after radical prostatectomy for prostate cancer at a specialist cancer center. Mycobacterium abscessus was cultured from the debridement specimens, and acid-fast-positive bacilli were identified histologically within the prostates. All 180 radical prostatectomy specimens from May 2007 to June 2009 were reviewed, and 7 additional cases with morphologies suspicious of M. abscessus granulomatous prostatitis (MAGP) were identified. The characteristic morphologic feature of MAGP was suppurative necrotizing granulomatous inflammation extensively (10% to 80% of the gland; mean, 39%) involving the prostate. The centers of MAGP were large areas of neutrophilic abscess and necrotic debris, which were surrounded by histiocytes, lymphocytes, plasma cells, scattered multinucleated giant cells, and eosinophils. In the adjacent areas, there was a lobular extension of mixed inflammatory infiltrates into dilated and ruptured ducts. Involvement of extraprostatic soft tissue and seminal vesicles/vas deferens was found in 9 and 4 cases, respectively. Acid-fast-positive bacilli were identified in 5 radical prostatectomies. Eleven patients had fresh tissue specimens stored at -150°C, and M. abscessus was cultured from 8 prostates. Random amplified polymorphic DNA-polymerase chain reaction showed the same clone for all isolates. After prostatectomy, 8 patients experienced prolonged wound healing, with urethrorectal fistula formation in 1 patient and a pelvic abscess in another. It is critical for pathologists to recognize MAGP and to distinguish it from the more common nonspecific granulomatous prostatitis and other granulomatous lesions within the prostate.

NK-cell lineage predicts poor survival in primary intestinal NK-cell and T-cell lymphomas.

Most primary intestinal natural killer (NK)-cell and T-cell lymphomas (PINKTL) in the Northern Europe are enteropathy-associated T-cell lymphomas, a complication of celiac disease, which is rare in the East. Primary intestinal NK-cell lymphoma is extremely rare and is poorly characterized. We investigated 30 cases of PINKTL from Taiwan with male: female at 2:1, median age at 55.5, 80% with jejunal/ileal involvement, 77% with perforation, 27% with multicentric tumors, and 67% at stage IE. All 7 cases tested for serum IgA anti-tissue transglutaminase were negative. Only 3 (10%) tumors showed enteropathy. Six (20%) were NK-cell lymphoma and 24 (80%) were T-cell lymphoma. The tumor cells in 21/30 (70%) cases were small to medium sized, which correlated with the coexpression of both CD8 and CD56. All tumors expressed at least 1 cytotoxic marker. All 6 NK-cell lymphomas were negative for betaF1, diffusely positive for Epstein-Barr virus-encoded mRNA (EBER), and polyclonal for T-cell receptor gene rearrangement. Five (22%) of the 24 T-cell tumors expressed betaF1, 8 (35%) of the 23 tumors were positive for EBER, and 20 (95%) of the 21 tumors were clonal for T-cell receptor. The overall 1-year survival was 36%. Univariate regression analysis showed that NK-cell lineage, multicentricity, and perforation were associated with poor prognosis. NK-cell lineage (P=0.037) was a poor prognostic factor by multivariate Cox proportional hazard regression analysis. PINKTL in Taiwan is predominantly not enteropathic with a high frequency of perforation, small to medium tumor cell size and cytotoxic phenotype. Primary intestinal NK-cell lymphoma carries a very poor prognosis, and is probably a distinct entity.

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

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

Study of prostate cancer pathologic features in Chinese populations.

OBJECTIVES: To report the pathologic features of prostate cancer and its clinical outcome in the Chinese population in Taiwan. METHODS: A total of 139 radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen Cancer Center from 1993 to 2001 were reviewed. RESULTS: The median patient age was 69 years. The histologic type was acinar adenocarcinoma in 137, mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median tumor number in each prostate gland was 2. The main tumor location was distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%). The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in 48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19 (13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P = 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012), seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001) were all significant factors for disease progression on univariate analysis. On multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin status (P = 0.02) remained significant. CONCLUSIONS: The patients with prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center were older and had greater PSA levels, a more advanced stage, higher grade tumors, and high positive surgical margin rates. Increased public awareness and implementing a PSA screening program in Taiwan are of crucial importance.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.