[Show abstract][Hide abstract] ABSTRACT: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).
PLoS ONE 01/2014; 9(8):e103822. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoscopic examination shows that serrated neoplasias (SNs), such as serrated adenomas and sessile serrated adenomas, exhibit different mucosal crypt patterns. However, it remains unclear whether advanced serrated polyps with different mucosal crypt patterns have different clinicopathological or molecular features.
We classified the mucosal crypt patterns of 86 SNs into three types (hyperplastic, adenomatous, and mixed pattern) and evaluated their clinicopathological and molecular features.
We found significant differences in the proliferative activity status between SNs with mixed/adenomatous patterns and those with the hyperplastic patterns. SNs with the hyperplastic pattern were frequently located in the proximal colon and had a macroscopically superficial appearance, whereas SNs with the adenomatous pattern were often located in the distal colon and had a protruding appearance. Furthermore, a significant difference was observed in the frequency of the CpG island methylator phenotype (CIMP), involving the methylation of two or more CIMP-related genes (MINT1, MINT2, MINT31, p16, and MLH1), between SNs with the hyperplastic pattern and those with the mixed/adenomatous patterns (18/32 (56%) vs. 8/28 (29%) or 7/26 (27%); P=0.0309 or P=0.0249, respectively). Moreover, the prevalence of KRAS mutations was significantly higher in SNs with the adenomatous pattern than in those with the hyperplastic pattern (7/26 (27%) vs. 1/32 (3%); P=0.0173). In comparison with other patterns, the mixed pattern was detected more frequently in mixed serrated polyps (MSPs), which contain separate histological components. Some MSPs exhibited concordant molecular alterations among the different histological components.
The clinicopathological and molecular features of SNs correlated strongly with their mucosal crypt patterns, which were observed using chromoendoscopy.
The American Journal of Gastroenterology 03/2011; 106(7):1351-8. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 67-year-old man visited our hospital with a history of continuous hematochezia leading to hemorrhagic shock. An abdominal computed tomography scan revealed a large mass in the ascending colon invading the duodenum and pancreatic head as well as extravasation of blood from the gastroduodenal artery (GDA) into the colon. Colonoscopy revealed an irregular ulcerative lesion and stenosis in the ascending colon. Therefore, right hemicolectomy combined with pylorus-preserving pancreaticoduodenectomy was performed. Histologically, the tumor was classified as a moderately differentiated adenocarcinoma. Moreover, cancer cells were mainly located in the colon but had also invaded the duodenum and pancreas and involved the GDA. Immunohistochemically, the tumor cells were positive for cytokeratin (CK)20 and carcinoembryonic antigen (CEA) but not for CK7 and carbohydrate antigen (CA)19-9. The patient died 23 d after the surgery because he had another episode of arterial bleeding from the anastomosis site. Although En bloc resection of the tumor with pancreaticoduodenectomy and colectomy performed for locally advanced colon cancer can ensure long-term survival, patients undergoing these procedures should be carefully monitored, particularly when the tumor involves the main artery.
World journal of gastrointestinal pathophysiology. 02/2011; 2(1):15-8.
[Show abstract][Hide abstract] ABSTRACT: The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.
We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.
Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.
Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.
PLoS ONE 01/2011; 6(11):e27889. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of micropapillary carcinoma (MPC) of the transverse colon. A 56-year-old woman was admitted to our hospital
with hematochezia. A lower gastrointestinal examination revealed an irregular ulcerative tumor of approximately 60 mm diameter
with marginal elevation in the transverse colon. Abdominal computed tomography showed multiple swollen lymph nodes. A histological
examination of the resected specimen revealed that cancer cells had invaded the subserosa. Microscopically, small papillary
cells proliferated with lacuna spaces and the cribriform glandular configuration was observed. Immunohistochemically, the
basal surface of the neoplastic cell clusters was diffusely positive for MUC1. No primary tumor was observed except for the
colon. Therefore, this tumor was diagnosed as a primary MPC of the colon. Since a colorectal MPC was first reported in 2005,
seven case reports and three pathological reviews have been presented in the English literature. MPC has an aggressive behavior
with a high incidence of lymphovascular invasion and nodal metastases. We should take intensive chemotherapy for colorectal
MPC into account, even if surgical resection is curative.
Clinical Journal of Gastroenterology 01/2011; 4(2):99-103.
[Show abstract][Hide abstract] ABSTRACT: To assess the cost-effectiveness of chemotherapy for patients with non-resectable pancreatic cancer, we compared two regimens containing either gemcitabine (GEM) or S-1.
We developed a decision tree that showed the clinical processes of non-resectable pancreatic cancer patients. We calculated the probabilities of endpoint and life months gained (LMG) based on previously reported articles. To estimate the costs, we analyzed medical records of 44 inpatients with non-resectable pancreatic cancer treated with GEM(n=34)or S-1(n=10). Sensitivity analysis was used to check the robustness of the results.
In the GEM group and S-1 group, costs were 1,636,393 and 985,042 yen, and LMG was 6. 0 and 9. 0 months, respectively. Thus, the cost-effectiveness ratio(CER)was calculated to be 272,732 and 109,449 yen/LMG, respectively, and the incremental cost effectiveness ratio (ICER) was -217,117 yen/LMG. The sensitivity analysis showed that the result was definitely robust.
Our findings suggest that the markedly cost-effective S-1 regimen could prolong LMG with less cost than the GEM regimen.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2010; 37(4):659-64.
[Show abstract][Hide abstract] ABSTRACT: Esophageal squamous cell carcinoma (ESCC) exhibits abnormalities in epidermal growth factor receptor (EGFR) gene. To identify a prognostic marker, the overexpression of EGFR protein, mutations in EGFR and p53 mutations were analyzed in pretreatment biopsy specimens removed from T3-4 and/or M1 LYM ESCC patients who received chemoradiotherapy. A silent mutation comprised of a single nucleotide polymorphism (SNP) at codon 787 of exon 20 of the EGFR gene was found in 19 patients (33%). In multivariate analysis, a significant difference was seen in the overall survival (odds ratio; 2.347, 95% confidence interval; 1.183-4.656, p = 0.015) between patients with and without the EGFR heterozygous genotype. Among the 57 eligible patients, 3-year survival rates was 21%, while in patients with EGFR heterozygous genotype the rate were 0%. However, neither overexpression of EGFR nor p53 mutations was associated with the overall survival. These results suggest that the EGFR SNP at codon 787 of exon 20 determined in pretreatment biopsy specimens may be a clinically useful biomarker for predicting the prognosis of ESCC patients.
Frontiers in Bioscience 01/2010; 15:65-72. · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking and alcohol consumption are well-known risk factors for esophageal squamous cell carcinoma (ESCC), which has a very poor prognosis. Successful screening strategies for precursor lesions that can be targets for early detection and treatment are required to prevent ESCC.
This is a prospectively cross-sectional study. To clarify whether daily smoking and/or alcohol consumption are risk factors for dysplasia, which is the initial lesion leading to ESCC. Lugol chromoendoscopy was performed in 1,345 eligible individuals. Six hundred ninety individuals had daily smoking and/or alcohol consumption; 655 individuals did not smoke and drink alcohol. The effects of smoking and alcohol consumption among high-grade dysplasia (HGD), low-grade dysplasia (LGD), and controls without dysplasia were evaluated using multiple logistic regression analysis.
Among 1,345 individuals, 17 HGD and 23 LGD lesions were confirmed histologically. The prevalence of both smoking and drinking consumption was significantly higher in HGD than in LGD individuals (age and sex adjusted odds ratio; 113.0, 95% confidence interval; 6.26), whereas no significant difference was seen in both consumption between LGD individuals and controls (odds ratio; 1.29, 95% confidence interval; 0.33-6.37). Approximately 70% of HGD individuals, but only 13% of LGD individuals, both smoked and consumed alcohol.
Daily cigarette and alcohol consumption were not the risk factors for LGD, however, consumption of both were high-risk factors for HGD. We suggest that documenting the difference of risk factors for LGD and HGD can assist in the development of effective screening, early detection, and prevention strategies for ESCC.
Journal of clinical gastroenterology 10/2009; 44(3):173-9. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epigenetic changes have been proposed as mediators of the field defect in colorectal carcinogenesis, which has implications for risk assessment and cancer prevention. As a test of this hypothesis, we evaluated the methylation status of eight genes (MINT1, 2, 31, MLH1, p16, p14, MGMT, and ESR1), as well as BRAF and KRAS mutations, in 57 multiple colorectal neoplasias (M-CRN) and compared these to 69 solitary colorectal cancers (S-CRC). There were no significant differences in methylation between M-CRNs and S-CRCs except for p14 and MGMT that was significantly higher in M-CRNs than S-CRCs (16.1% versus 9.3%; 26.5% versus 17.3%, respectively; P < 0.05). We found significant (P < 0.05) correlations for MINT1 (r = 0.8), p16 (r = 0.8), MLH1 (r = 0.9), and MGMT (r = 0.6) methylation between tumors pairs of the same site (proximal/proximal and distal/distal). KRAS showed no concordance in mutations. BRAF mutation showed concordance in proximal site pairs but was discordant in different site pairs. Histologically, eight of 10 paired cancers with similar locations were concordant for a cribriform glandular configuration. We conclude that synchronous colorectal tumors of the same site are highly concordant for methylation of multiple genes, BRAF mutations, and a cribriform glandular configuration, all consistent with a patient-specific predisposition to particular subtypes of colorectal cancers. Screening for and secondary prevention of colon cancer should take this fact into account.
Cancer Prevention Research 09/2009; 2(9):814-22. · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present a case of membranous nephropathy (MN) associated with esophageal squamous cell carcinoma (ESCC) with a high serum level of squamous cell carcinoma antigen (SCC). ESCC reached complete response (CR) for radiotherapy, with a partial remission of the proteinuria and decreased serum SCC levels. Six months after radiotherapy, the ESCC recurred, and the patient was treated with endoscopic mucosal resection (EMR), achieving a pathologic CR and disappearance of proteinuria and normalized serum SCC levels. The correlation of proteinuria and the serum level of SCC indicates that SCC could be a pathogenic antigen, responsible for the pathogenesis of MN in this patient.
Internal Medicine 02/2009; 48(1):65-9. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microvessel density (MVD) is an excellent predictive biomarker regarding tumor stage and survival in esophageal squamous cell carcinomas (ESCCs). However, it is obscure when tissues initiate angiogenesis in the malignant transformation of human esophageal squamous epithelium. To investigate the onset of angiogenesis in the multistep progressive process of ESCCs, immunohistochemical staining for CD31, CD105, and vascular endothelial growth factor receptor 2 (VEGFR-2) was performed in normal epithelium, Lugol-unstained lesions with non-dysplastic epithelium (LULs-NDE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) samples. There were significant differences in the mean MVD for CD31 and CD105 between LULs-NDE and LGD (p less than 0.001, p less than 0.001), and between LGD and HGD (p less than 0.001, p=0.006), respectively. Furthermore, a significant difference in MVD for CD105 was seen in normal controls and LULs-NDE (p=0.002), while thick vessels (less than 10m m) stained with anti-CD105 were not present in normal controls and LULs-NDE despite the presence of these thickened vessels in dysplasia. Our results suggest that CD105 is an efficient marker protein to determine MVD, suggesting that the angiogenic switch occurs at the earliest stage of dysplastic transformation in ESCC.
Frontiers in Bioscience 02/2009; 14:3872-8. · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aberrant promoter hypermethylation and associated gene silencing are epigenetic hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation can affect the sensitivity of cancers to antineoplastic agents by altering expression of genes critical to drug response. To study this issue, we used bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in human cancer cell lines from the National Cancer Institute (NCI) drug-screening panel (NCI-60 panel). The frequency of aberrant hypermethylation of these islands ranged from 2% to 81% in NCI-60 cancer cells, and provided a database that can be analyzed for the sensitivity to approximately 30,000 drugs tested in this panel. By correlating drug activity with DNA methylation, we identified a list of methylation markers that predict sensitivity to chemotherapeutic drugs. Among them, hypermethylation of the p53 homologue p73 and associated gene silencing was strongly correlated with sensitivity to alkylating agents. We used small interfering RNA to down-regulate p73 expression in multiple cell lines, including the resistant cell lines TK10 (renal cancer) and SKMEL28 (melanoma). Down-regulating p73 substantially increased sensitivity to commonly used alkylating agents, including cisplatin, indicating that epigenetic silencing of p73 directly modulates drug sensitivity. Our results confirm that epigenetic profiles are useful in identifying molecular mediators for cancer drug sensitivity (pharmaco-epigenomics).
Cancer Research 01/2008; 67(23):11335-43. · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease.
Proceedings of the National Academy of Sciences 12/2007; 104(47):18654-9. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interleukin (IL)-1 gene polymorphisms are associated with development of gastric atrophy and with increased risk of gastric carcinoma. A -31C to T base transition in the promoter region of this gene is involved in carcinogenic changes within the stomach, especially in Helicobacter pylori infected individuals. We examined association between IL-1 locus polymorphisms and risk of esophageal, gastric and colorectal carcinomas in Japanese patients with H. pylori infection. IL-1B and IL-1RN polymorphisms were analyzed in 136 controls, 75 patients with esophageal carcinoma, 186 patients with gastric carcinoma, 69 patients with colorectal carcinoma, and 18 patients with ulcerative colitis (UC). For IL-1B-511 and -31 polymorphisms were determined by fluorescence-based polymerase chain reaction single-strand conformation polymorphism analysis. For IL-1 receptor antagonist gene (IL-1RN), penta-allelic variable number of tandem repeats (VNTR) was determined by PCR-standard agarose gel electrophoresis. For gastric carcinoma, IL-1B-511 heterozygotes (OR, 0.48; 95% CI, 0.3-0.9; p=0.0115) and T carriers (OR, 0.52; 95% CI, 0.3-1.0; p=0.0185) had a significantly reduced risk of carcinoma. For colorectal carcinoma, IL-1B-511 heterozygotes (OR, 0.34; 95% CI, 0.2-0.7; p=0.0028) and T carriers (OR, 0.43; 95% CI, 0.2-0.9; p=0.0015) had a significantly low risk of carcinoma. No significant difference was observed in the frequencies of IL-1B-31C/T and IL-1RN genotypes between controls and the esophageal carcinoma patients. Our results shows that IL-1B-511C/T and T carrier state may indicate less risk for gastric and colorectal carcinoma in the Japanese population.
[Show abstract][Hide abstract] ABSTRACT: Gene silencing associated with promoter methylation can inactivate tumor suppressor genes (TSG) in cancer. We identified RIL, a LIM domain gene mapping to 5q31, a region frequently deleted in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), as methylated in 55 of 79 (70%) of cancer cell lines tested. In a variety of primary tumors, we found RIL methylation in 55 of 92 (60%) cases, with highest methylation in AML and colon cancer, and in 30 of 83 (36%) MDS samples, whereas normal tissues showed either absence or substantially lower levels of methylation, which correlates with age. RIL is ubiquitously expressed but silenced in methylated cancers and could be reactivated by the hypomethylating agent 5-aza-2'-deoxycytidine. Restoring RIL expression in colon cancer cells by stable transfection resulted in reduced cell growth and clonogenicity and an approximately 2.0-fold increase in apoptosis following UV exposure. In MDS, RIL methylation is a marker of adverse prognosis independent of chromosome 5 and 7 deletions. Our data suggest that RIL is a good candidate TSG silenced by hypermethylation in cancer.
Cancer Research 04/2007; 67(5):1997-2005. · 8.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously reported that a high degree of age-related methylation was found in both the dysplastic and nondysplastic mucosa of patients with ulcerative colitis (UC). Whether this translates into hypermethylation in UC-associated cancers (UC-Cs) is not known.
We evaluated the methylation status of 11 genes (MINT1, 2, 31, hMLH1, p16, p14, MGMT, HPP1, SFRP1, ERalpha, and LINE-1) in 48 UC-Cs, 21 UC-associated dysplasias, and 69 sporadic colorectal cancers (S-CRCs) using a quantitative bisulfite pyrosequencing analysis.
Methylation levels in UC-Cs were lower than S-CRCs for all the genes except MGMT. A methylation index based on the average of Z-scores, for type C (cancer-specific genes: MINT1, MINT2, MINT31, hMLH1, p16, and p14) was -.97 in UC-Cs and .92 in S-CRCs (P = .009). That of type A (age-related genes: HPP1, SFRP1, and ERalpha) was -1.97 in UC-Cs and 1.24 in S-CRCs (P < .001). We observed a significant difference in the incidence of CpG island methylator phenotype between UC-Cs and S-CRCs (8 of 48 [17%] and 26 of 69 [38%]; P = .022). UC-associated dysplasias had significantly higher methylation of type A gene than UC-Cs (Z-score: .07 and -1.97, respectively; P < .001). By contrast, global DNA methylation measured using a LINE-1 assay was significantly higher in UC-Cs than in S-CRCs (58.2% vs 51.0%, P < .001).
DNA methylation alterations are uncommon in UC cancers. Given that both genetic and epigenetic changes are common in UC mucosa and dysplasias, we speculate that the genetic changes lead to a more aggressive clinical course than epigenetic changes.
[Show abstract][Hide abstract] ABSTRACT: Mutations of the p53 gene are detected frequently in oesophageal dysplasia and cancer. It is unclear whether Lugol-unstained lesions (LULs) with non-dysplastic epithelium (NDE) are precursors of oesophageal squamous cell carcinoma (ESCC). To study the genetic alterations of NDE in the multistep process of oesophageal carcinogenesis, we determined the relationship between p53 mutations and LULs-NDE. Videoendoscopy with Lugol staining was performed prospectively in 542 oesophageal cancer-free subjects. Lugol-unstained lesions were detected in 103 subjects (19%). A total of 255 samples, including 152 LULs (NDE, 137; dysplasia, 15) and 103 paired samples of normal staining epithelium, were obtained from 103 subjects. After extraction of DNA and polymerase chain reaction analysis, direct sequencing method was applied to detect mutations of the p53 gene. The p53 mutation was detected in five of 137 samples with LULs-NDE (4%) and in five of 15 samples with dysplasia (33%). A hotspot mutation was found in 20% of LULs-NDE with p53 mutation and in 40% of dysplasia with p53 mutation. In contrast, no p53 mutations were found in 103 paired NDE samples with normal Lugol staining. In biopsy samples from oesophageal cancer-free individuals, the p53 missense mutations containing a hotspot mutation were found in NDE, which was identified as an LUL. These findings suggest that some LULs-NDE may represent the earliest state of oesophageal squamous cell carcinoma in Japanese individuals.
British Journal of Cancer 03/2007; 96(3):492-8. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epigenetic processes such as DNA methylation and histone modifications are now recognized as critical events for regulation of gene expression in mammalian cells and affect gene function without a change in coding sequence. Neoplastic cells often show profound epigenetic alterations that contribute to tumorigenesis by altering expression of critical genes. In colorectal tumorigenesis, detailed analysis led to a hypothesis on a critical role for epigenetic changes in age-related cancer susceptibility and separately identified a distinct phenotype termed the CpG island methylator phenotype. CpG island methylator phenotype-positive colorectal cancers have significant associations with female sex, older age, proximal location, mucinous histology, KRAS and BRAF mutations, wild-type p53, and microsatellite instability. Histone modifications that affect chromatin structures are also closely implicated in tumor suppressor gene inactivation and DNA methylation and histone modifications seem to form reinforcing networks for stable gene silencing. Much of the excitement in this field relates to the possibility of therapeutic reversal of epigenetic changes by chromatin-modifying drugs. In CpG island methylator phenotype-positive colorectal cancers, DNA methylation inhibitors restore key silenced pathways in vivo (eg, mismatch repair defects), and hypomethylation can largely abolish tumorigenesis in a mouse model. Drugs that inhibit DNA methylation and histone deacetylation are in use in the clinic and should be tested in colorectal malignancy.
The Cancer Journal 01/2007; 13(1):49-55. · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively investigated long-term toxicity after concurrent chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC).
Concurrent chemoradiotherapy was performed in 110 patients with T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil 400 mg/m(2) per 24 h on days 1 to 5 and 8 to 12, combined with 2-h infusion of cisplatin 40 mg/m(2) on days 1 and 8. Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was administered concomitantly with chemotherapy. A course schedule with a 3-week treatment and a 2-week break was applied twice, with a total radiation dose of 60 Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema was adopted.
A total of 81 patients were recruited in patients with stage I to IVA. Of 34 patients with complete response, 1 patient died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in 3 patients, 1 patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients; pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and 1 patient, respectively.
Definitive chemoradiotherapy for ESCC is effective with substantial toxicities. Further investigation is warranted to minimize the normal tissue toxicities.
Journal of Gastroenterology 06/2006; 41(5):425-32. · 3.79 Impact Factor