Search PubMed⌕ Search

Biomedical subjects

Morito Monden

Publications and source records attributed to Morito Monden.

At least 91 records · Page 5Linked to original sources
PubMed2005

[Successful treatment of combined intraarterial (5-fluorouracil and adriamycin and cisplatin) infusion chemotherapy for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis--two case reports].

Hepatic arterial infusion chemotherapy has been often selected as a therapeutic option for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis. We successfully treated and obtained CR in the 2 cases of far advanced hepatocellular carcinoma with intraarterial infusion chemotherapy (FAP). Case 1 was a 71-year-old male who had advanced hepatocellular carcinoma with intrahepatic metastasis (IM3) which was recurrent after two surgeries. He received hepatic arterial infusion chemotherapy (FAP: 5-fluorouracil 500 mg/day: continuous infusion, day 1-5, adriamycin 10 mg/day, day 1, CDDP 10 mg/day, day 1). After 10 courses, abdominal CT revealed that the viable lesions had completely disappeared (CR). This patient is still alive with no recurrence after 21 months from the beginning of this treatment. Case 2 was a 74-year-old male who had advanced hepatocellular carcinoma with portal vein thrombi (Vp4) and intrahepatic metastasis (IM3). He received FAP arterial infusion chemotherapy with the same protocol as case 1. After 8 courses of this therapy, CT revealed that these lesions had disappeared (CR). This patient is still alive with no recurrence after 9 months from the beginning of this treatment. For 15 patients with advanced hepatocellular carcinoma using a same protocol, the response rate of this therapy was 33.3% (CR & PR). These findings suggested that combined arterial infusion chemotherapy of FAP may be feasible and a promising modality for the advanced HCC with intrahepatic metastases and/or portal vein thrombosis.

Aged↗
PubMed2005

Quantitative tissue blood flow evaluation of pancreatic tumor: comparison between xenon CT technique and perfusion CT technique based on deconvolution analysis.

PURPOSE: There has been one report that tissue blood flow (TBF) quantification with xenon CT was effective in predicting the therapeutic response to an anticancer drug in pancreatic cancer. The purpose of this study was to evaluate the correlation between the TBF of pancreatic tumors calculated with xenon CT and those with perfusion CT, in order to evaluate whether perfusion CT could replace xenon CT. MATERIALS AND METHODS: Nine patients with pathologically proved pancreatic tumors who underwent both xenon CT and perfusion CT were included. RESULTS: Quantitative TBF of pancreatic tumors measured by perfusion CT ranged from 22.1 to 196.2 ml/min/100 g (mean+/-SD, 52.6+/-54.8 ml/min/100 g). In contrast, those obtained by xenon CT ranged from 10.3 to 173.6 ml/min/100 g (mean+/-SD, 47.4+/-49.4 ml/min/100 g). There was a good linear correlation between xenon CT and perfusion CT (y=0.8537x+2.48, R2=0.895: p<0.05). CONCLUSION: The TBF of pancreatic tumors measured by xenon CT and perfusion CT techniques showed a close linear correlation. We can expect that perfusion CT based on the deconvolution algorithm may replace xenon CT to predict the effect of pancreatic tumor treatment with anticancer drugs.

Adenocarcinoma↗
PubMed2004

Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.

PURPOSE: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. RESULTS: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. CONCLUSION: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.

Adult↗
PubMed2004

Preoperative intraperitoneal chemotherapy for patients with serosa-infiltrating gastric cancer.

BACKGROUND AND OBJECTIVES: Serosa-infiltrating gastric cancer poses a high risk for peritoneal recurrence. This study examined the feasibility and efficacy of preoperative intraperitoneal (i.p.) chemotherapy for such cancer. METHODS: Patients with serosa-infiltrating tumors, diagnosed by conventional examinations as well as by staging laparoscopy, were enrolled in this study. Those with unresectable T4 tumors, visible peritoneal metastasis or distant organ metastasis were excluded. Twenty-five eligible patients received preoperative i.p. chemotherapy, which consisted of i.p. injection of 20 mg of mitomycin C on day 1 and 10 mg of cisplatin for 5 days, followed by surgery. RESULTS: Of the 25 patients, 24 underwent gastrectomy with lymph node dissection and 1 underwent palliative gastrojejunostomy. The curability of the surgery was curability A in 6, B in 16, and C in 3. Preoperative T stages (T3 in 21 and T4 in 4) were downstaged postoperatively (T1 in 1, T2 in 10, T3 in 11, and T4 in 3). The 1- and 2-year overall survival was 83.3 and 51.3%, respectively. The median survival time was 24.4 months. The toxicity of the preoperative treatment was tolerable and no serious postoperative complication was seen. CONCLUSIONS: Preoperative i.p. chemotherapy seems to be a safe and effective therapy for serosa-infiltrating gastric cancer. Randomized clinical trials comparing preoperative i.p. chemotherapy followed by surgery and surgery alone are needed.

Adenocarcinoma↗
PubMed2004

NY-ESO-1 expression and immunogenicity in esophageal cancer.

PURPOSE: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patients have not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients. EXPERIMENTAL DESIGN: One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzyme-linked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed. RESULTS: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with tumors that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients. CONCLUSIONS: The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.

Antibodies↗
PubMed2004

Molecular prediction of response to 5-fluorouracil and interferon-alpha combination chemotherapy in advanced hepatocellular carcinoma.

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) is very poor, particularly in patients with tumors that have invaded the major branches of the portal vein. Combination chemotherapy with intra-arterial 5-fluorouracil and subcutaneous interferon-alpha has shown promising results for such advanced HCC, but it is important to develop the ability to accurately predict chemotherapeutic responses. EXPERIMENTAL DESIGN: We analyzed the expression of 3,080 genes using a polymerase chain reaction-based array in 20 HCC patients who were treated with combination chemotherapy after reduction surgery. After unsupervised analyses, a supervised classification method for predicting chemotherapeutic responses was constructed. To minimize the number of predictive genes, we used a random permutation test to select only significant (P < 0.01) genes. A leave-one-out cross-validation confirmed the gene selection. We also prepared an additional 11 cases for validation of predictive performance. RESULTS: Hierarchical clustering analysis and principal component analysis with all 3,080 genes revealed distinct gene expression patterns in responders (those with complete response or partial response) and nonresponders (those with stable disease or progressive disease) to the combination chemotherapy. Using a weighted-voting classification method with either all genes or only significant genes as assessed by permutation testing, the objective responses to treatment were correctly predicted in 17 of 20 cases (accuracy, 85%; positive predictive value, 100%; negative predictive value, 80%). Moreover, patients in the validation dataset could be classified into two distinct prognostic groups using 63 predictive genes. CONCLUSIONS: Molecular analysis of 63 genes can predict the response of patients with advanced HCC and major portal vein tumor thrombi to combination chemotherapy with 5-fluorouracil and interferon-alpha.

Adult↗
PubMed2004

Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. EXPERIMENTAL DESIGN: VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. RESULTS: Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups. CONCLUSION: This study demonstrated the prognostic significance of VCP expression in ESCC.

Adenosine Triphosphatases↗
PubMed2004

Constrained clusters of gene expression profiles with pathological features.

MOTIVATION: Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features. RESULTS: We present the novel technique of 'itemset constrained clustering' (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as 'tumor' and 'man', or 'except tumor' and 'normal liver function'. In contrast, the k-means method overlooked these clusters.

Algorithms↗
PubMed2004

Biologically different subgroups of invasive ductal carcinoma of the pancreas: Dpc4 status according to the ratio of intraductal carcinoma components.

PURPOSE: Among invasive ductal carcinomas of the pancreas (IDCP), there is a morphologically characteristic subgroup accompanied by abundant intraductal carcinoma components (ICCs). With the aim of determining whether ICC-rich IDCP are biologically different from ICC-poor IDCP, the expression status of Dpc4 protein was analyzed. EXPERIMENTAL DESIGN: A total of 43 IDCP was subdivided into two groups: (a). ICC-rich IDCP (ICCs area occupies >or=10% of the entire tumorous area); and (b). ICC-poor IDCP (with <10% of ICCs area). A total of 10 invasive carcinomas derived from intraductal papillary-mucinous neoplasms (ICs from IPMNs) were also analyzed. Each invasive and intraductal carcinoma area was then evaluated for Dpc4 protein status by immunohistochemistry. RESULTS: In a total of 43 IDCP, there were 23 ICC-rich IDCP and 20 ICC-poor IDCP. Dpc4-positive immunostaining was observed in the invasive carcinoma component of ICC-rich IDCP, ICC-poor IDCP, and ICs from IPMN in 18 of 23 (78%), 4 of 20 (20%), and 7 of 10 (70%) cases, respectively. In the intraductal component, positive staining for Dpc4 was found in 20 of 23 (87%), 3 of 7 (41%), and 8 of 10 (80%) cases, respectively. Dpc4 expression was found in both the invasive and ICC components of ICC-rich IDCP, similar to that found in IC derived from IPMN, whereas the expression of Dpc4 was largely diminished in ICC-poor IDCP. CONCLUSIONS: Morphologically distinct subgroups of invasive ductal carcinomas of the pancreas, namely ICC-rich IDCP and ICC-poor IDCP, are also biologically distinguishable as revealed by the differential expression of Dpc4.

Adenocarcinoma↗
PubMed2004

Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma.

PURPOSE: Akt is a serine/threonine kinase that plays a central role in tumorigenesis. Among the members of Akt family, Akt2 is associated with the development of human cancers. The present study was designed to clarify the prognostic significance of Akt2 and activated Akt expression in pancreatic ductal adenocarcinoma (PDAC). In addition, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and the proliferation activity of tumor cells detected by Ki-67 immunohistochemistry were examined. EXPERIMENTAL DESIGN: Immunohistochemical analysis was performed on paraffin-embedded specimens from 65 patients with PDAC; 36 males and 29 females with ages ranging from 48 to 79 years (median, 66 years) of age. Expression levels of Akt2, phosphorylated Akt (p-Akt), and phosphorylated ERK 1/2 (p-ERK 1/2) were categorized as either weaker (low intensity) or equal to stronger (high intensity) compared with those in the endothelial cells of the same specimens. For Ki-67 immunohistochemistry, cases were divided into two groups: level 1, Ki-67 labeling index (LI), <20%; level 2, Ki-67 LI, > or = 20%. RESULTS: Twenty-six (42.6%), 28 (45.9%), 39 (63.9%), and 46 (75.4%) of the tumors showed high intensity of Akt2, p-Akt, and p-ERK 1/2 expression, and Ki-67 LI level 2, respectively. A significant positive correlation was observed between Akt2 and p-Akt expression (P < 0.01). Multivariate analysis revealed that p-Akt expression, Ki-67 LI, and histological differentiation are independent prognosticators for PDAC. CONCLUSIONS: p-Akt expression is a significant prognostic indicator for PDAC. Inhibition of Akt is a possible molecular approach for treatment of PDAC.

Adenocarcinoma↗
PubMed2004

NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors.

NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific humoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in 1 mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only 1 breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-gamma enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.

Adenoviridae↗
PubMed2004

Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system.

HOX genes are well known as master control genes in embryonic morphogenesis. We hypothesized that HOX genes give cells spatial information to maintain tissue- or organ-specificity in adult body and that the deregulated expression of HOX genes results in tumor development. We established a comprehensive analysis system to quantify expression of 39 human HOX genes based on the real-time reverse transcription PCR (RT-PCR) method. Analysis of 39 HOX genes of 20 normal adult organs by this system revealed that 5' HOX genes were expressed in organs in the caudal parts of the body, and that the more caudal regions the more numbers of HOX genes were expressed. It was also found that the expression patterns of HOX genes were more similar in the adjacent genes on the same cluster rather than in those belonging to the same paralogs. Compared with normal thyroid tissues, thyroid cancer cell lines showed the altered expression of some HOX genes, especially Abd-B homeobox family genes. Our results showed that HOX genes were organ-specifically expressed in adult body and that the deregulated expressions of Abd-B family genes were implicated in thyroid tumor development.

Actins↗
PubMed2004

Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.

PURPOSE: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci. RESULTS: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively). CONCLUSIONS: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.

Adenoma↗
PubMed2004

Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.

Angiopoietin-1↗
PubMed2004

Application of molecular diagnosis for detection of peritoneal micrometastasis and evaluation of preoperative chemotherapy in advanced gastric carcinoma.

BACKGROUND: In advanced gastric cancer, peritoneal recurrence is the main cause of death after curative surgical resection. The aim of this report was to describe a novel approach for quantitative genetic diagnosis using peritoneal lavage for the identification of patients at high risk for peritoneal recurrence and for evaluation of the clinical response to intraperitoneal chemotherapy in advanced gastric cancer. METHODS: Nineteen patients with advanced gastric cancer who underwent staging laparoscopy and intraperitoneal chemotherapy before surgical resection or systemic chemotherapy between June 1999 and September 2001 were enrolled in this study. All peritoneal lavage specimens, collected at both staging laparoscopy and gastrectomy, were subjected to real-time quantitative genetic diagnosis. RESULTS: The reverse transcriptase polymerase chain reaction (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately negative survived except for one, and all but one patient whose values increased during treatment died of recurrence. CONCLUSIONS: Quantitative evaluation of genetic changes can provide accurate, useful information on the effects of preoperative intra-abdominal chemotherapy and overall prognosis for patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed2004

Interstitial pneumonia induced by combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma.

Previously we reported combined chemo-immunotherapy, using interferon (IFN)-alpha and 5-fluorouracil (5-FU) for patients with advanced hepatocellular carcinoma (HCC), and this regimen improved the prognosis. Recently, we experienced an HCC patient who died of severe interstitial pneumonia during the combined IFN-alpha and 5-FU therapy. This is the first report of the occurrence of interstitial pneumonia during combined IFN-alpha and 5-FU treatment. A 60-year-old-man was admitted to Osaka University Hospital to receive systemic chemo-immunotherapy for recurrent HCC. In the second week of the chemo-immunotherapy, he showed a decreased level of consciousness, and respiratory insufficiency. Emergency roentgenogram revealed diffuse infiltration in both lungs. Respiratory dysfunction due to interstitial pneumonia was suspected, and steroid pulse therapy was started. However, the patient showed respiratory failure, and he died 32 days after the start of the therapy. Autopsy findings showed atelectasis in the bilateral lungs, which showed elastic hard solidity and a dark red color; esophageal varices were also shown, and there was cirrhosis with a large tumor in the liver. Microscopically, the alveolar wall showed marked fibrous thickness and moderate inflammatory change, which is consistent with acute interstitial pneumonia, and the acute pulmonary change was suspected to have been the cause of death. The association of IFN with the development of interstitial pneumonia has been reported. However, the prognosis of IFN-induced interstitial pneumonia has mostly been favorable when the medication was discontinued. It has been postulated that interstitial pneumonia induced by the combination of IFN and 5-FU may be therapy-resistant. The combination of IFN-alpha and 5-FU is a useful therapy for patients with advanced HCC, such as that with portal vein invasion or multiple metastatic foci. Thus, interstitial pneumonia in these patients should be carefully managed.

Antineoplastic Combined Chemotherapy Protocols↗