[A resected case of huge advanced hepatocellular carcinoma(BCC)treated with intra-arterial infusion chemotherapy combined with interferon-alpha].

A58-year-old man with upper abdominal pain had a duodenal perforation and a huge hepatocellular carcinoma (BCC). Atumor embolism in the main portal vein was also seen. Extended right lobectomy against a huge tumor in right lobe and ethanol injection to a tumor in the lateral segment were performed. In addition, fluorouracil arterial infusion and interferon therapy(FAIT)were carried out. He has been for 4 years and 6 months without recurrence. Although prognosis of patients with a huge BCC is miserable even if curative hepatic resection is performed, it may be possible for adjuvant FAIT to suppress the recurrence after hepatic resection for huge BCC.

Authentication of the traditional medicinal plant Eleutherococcus senticosus by DNA and chemical analyses.

Shigoka (SGK), the rhizome of Eleutherococcus senticosus, is a traditional medicine used as a tonic in northeastern Asia and far eastern Russia. We analyzed the nuclear ribosomal DNA internal transcribed spacer (ITS) sequence of the medicine available on the Japanese and Chinese markets and found that at least 3 species were used as the source plant of the commercial SGKs and that only 70% of all samples was made from the correct species. Furthermore, we performed the quantitative determination of 3 marker compounds, eleutheroside B (EB), syringaresinol diglucoside (Syr), and isofraxidin (Iso) by ultraperformance liquid chromatography (UPLC)/mass spectrometry (MS). We found that EB and Iso are specific to the correct source plant of SGK. Of them, EB is thought to be the best marker compound for quality assurance of the SGK from the viewpoint of its pharmacological activity.

Authentication and chemical study of isodonis herba and isodonis extracts.

Isodonis Herba is used as a Japanese dietary supplement and folk medicine. The extract of the herb (Isodonis extract) is also used as a food additive whose major compound is enmein (1). Here we compared internal transcribed spacer sequences of nuclear ribosomal DNA from Isodonis Herba available on the Japanese and Chinese crude drug markets, and found that the former derived from Isodon japonicus and Isodon trichocarpus, while the latter derived from distinct species such as Isodon eriocalyx. The liquid chromatography/mass spectrometry profiles of Isodonis Herba were classified into four chemotypes (A to D) according to the ratio of the major constituents. Types B and C contained 1 and oridonin (2) as major components, respectively. An intermediate (or mixed) form of types B and C in various ratios was designed type A. Type D contained eriocalyxin B (3) as its major component. Japanese herba were types A-C, while Chinese herba were types C and D. The commercial Isodonis extract products tested were classified as type D, suggesting that they originated from Chinese Herba. Understanding the relationship between extract constituents and DNA profiles is important for the official specification of dietary supplements and food additives of plant origin.

Therapeutic outcomes of continuous hyperthermic peritoneal perfusion against advanced gastric cancer with peritoneal carcinomatosis.

BACKGROUND/AIMS: To clarify the efficacy of therapeutic continuous hyperthermic peritoneal perfusion in peritoneal carcinomatosis of gastric cancer. METHODOLOGY: The subjects of this study were 73 advanced gastric cancer patients who underwent palliative surgery between 1992 and 1999. Therapeutic continuous hyperthermic peritoneal perfusion (T-CHPP) was performed in 21 patients, who had macroscopic peritoneal carcinomatosis or positive lavage cytology, were under 65 years old, had no concomitant disease, and gave informed consent. Fifty-two patients who did not meet the inclusion criteria formed the control group. After reconstruction of the alimentary tract, T-CHPP was carried out for 40 min with 300 mg of Cisplatin, 30 mg of mitomycin C, and 300 mg of etoposide in 5-6 L of physiological saline maintained at 42 degrees C to 43 degrees C. RESULTS: The survival of patients who had CY1, P1, P2, P3 was not affected by T-CHPP. Univariate analysis revealed that the degree of peritoneal carcinomatosis and adjuvant chemotherapy were prognostic factors. Furthermore, ill-defined macroscopic appearance and P3 independently affected prognosis, according to multivariate analysis. Patients treated by T-CHPP had higher incidences of respiratory failure (76.2% vs. 17.3%; p < 0.0001) and renal failure (14.3% vs. 0%; p < 0.0054) than those undergoing T-CHPP. CONCLUSIONS: As T-CHPP had no efficacy, a new therapeutic strategy such as chemosensitivity assessment or a well-structured randomized controlled trial is necessary to obtain good therapeutic results with T-CHPP.

Predicting 5-fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: three-gene expression model predicts clinical response.

We identified genes related to 5-fluorouracil (5-FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5-FU sensitivity of liver metastases. Eighty-one candidate genes involved in 5-FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5-FU-related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real-time quantitative RT-PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5-FU-based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG-1 and OPRT) had significantly different expression profiles in 5-FU-nonresponding and responding tumors (p < 0.05). A "Response Index" system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5-FU-based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our "Response Index" system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5-FU-based chemotherapy against liver metastases from colorectal cancer.

Usefulness of prophylactic transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection.

To improve the prognosis after hepatectomy for HCC, repeated postoperative transcatheter arterial infusions of anticancer drugs and lipiodol (TAI) were given. TAI may be effective as an adjuvant therapy for prevention of residual liver recurrence after hepatectomy, probably by suppression of the development of intrahepatic micrometastases rather than of multicentric carcinogenesis.

Therapeutic strategy for scirrhous type gastric cancer.

BACKGROUND/AIMS: As no appropriate therapeutic strategy has yet been established in scirrhous type gastric cancer, we retrospectively analyzed the therapeutic outcomes in patients with this type of cancer. METHODOLOGY: A total of 183 patients with scirrhous type gastric cancer were enrolled in the study. 127 of them underwent resection; 61 potentially curative gastrectomy; 66 palliative resection; and 56 had no surgery. RESULTS: Univariate analysis revealed that the number of metastatic lymph nodes and the depth of invasion influenced prognosis in curatively resected cases, whereas no factor did so after palliative resection. Multivariate analysis showed that prognosis was affected independently by peritoneal metastasis and non-regional lymph node metastasis in all resected cases, but by the number of metastatic lymph nodes in curatively resected cases. There was no significant difference in survival between patients undergoing and those not undergoing palliative gastrectomy. Prophylactic (6) and therapeutic CHPP (12) had no efficacy on peritoneal metastasis. Furthermore, left upper abdominal evisceration (LUAE) (9) did not improve long-term results in curatively resected cases. CONCLUSIONS: In scirrhous type gastric cancer, gastrectomy including extended lymph node dissection is justified only in patients with limited lymph node metastasis, and palliative gastrectomy should be not performed because it has no efficacy on survival.

Adjuvant hepatic arterial infusion chemotherapy after curative resection for Dukes C colorectal cancer: a pilot study.

BACKGROUND/AIMS: The aim of this study was to evaluate the effect and the toxicity of prophylactic adjuvant hepatic arterial infusion chemotherapy (HAIC) on liver metastases and on overall survival of Dukes C colorectal cancer patients. METHODOLOGY: Ninety patients in whom Dukes C colorectal cancer was diagnosed and were treated with curative resection between 1993 and 1997 underwent HAIC. The HAIC regimen consisted of a 24-hour continuous infusion of 1500 mg of 5-fluorouracil, administered once a week for 8 weeks, utilizing a portable infusion drug delivery system to ambulatory patients. Patients to whom 7 g or more of 5-fluorouracil could be given were included in the HAIC group, which resulted in 70 of the 90 patients being in this group. The HAIC group overall survival and liver recurrence rates were compared with those of 62 non-treated cases of Dukes C, which formed the non-HAIC control group. RESULTS: There were no serious toxic effects in this study. Significant differences were seen in the cumulative overall 5-year survival (HAIC group, 84.1%; non-HAIC group, 65.2%; p=0.0369). The cumulative 5-year liver metastasis-free rate was 92.7% in the HAIC group and 78.6% in the non-HAIC group (p=0.0649). In cases of distal lymph node metastasis, a risk factor for liver metastasis, the cumulative 5-year liver metastasis-free rate in the HAIC group (91.7%) was significantly higher than that in the non-HAIC group (58.6%; p=0.0268). CONCLUSIONS: HAIC effectively prevents metachronous liver metastasis, especially in patients with pre-existing distal lymph node metastases, and improves the prognosis of advanced colorectal cancer.

Digalactosyldiacylglycerol is a major glycolipid in floral organs of Petunia hybrida.

In higher plants, glycolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are major components of chloroplast membranes in leaves. A recent study identified an isoform of MGDG synthase that is expressed specifically in floral organs, suggesting a novel function for glycolipids in flowers. To elucidate the localization and developmental changes of glycolipids and their biosynthetic activities in flowers, we carried out a series of analytical studies with Petunia hybrida. The results showed that the biosynthetic activities of galactolipid synthesis, particularly for DGDG, increased during flower development. Among the floral organs, the pistil had the highest galactolipid synthetic activity. Its specific activity for incorporation of UDP-galactose to yield galactolipids was estimated to be more than twice that of leaves, which are the major site of galactolipid synthesis in plant tissues. Analysis of lipid contents of pistils revealed that they contained higher amounts of galactolipids than other floral organs. Moreover, DGDG was more abundant than MGDG in both pistils and petals. These results show that DGDG is a major glycolipid in floral organs and that DGDG biosynthetic activity is highly upregulated in the pistils and petals of Petunia flowers.

[Efficacy of circadian chronotherapy via hepatic arterial infusion].

For hepatectomy after neoadjuvant chemotherapy (NAC), we applied circadian chronotherapy via the hepatic artery for multiple bilobar liver metastases from colorectal cancer. Four patients underwent chronotherapy and 16 patients underwent flat infusion therapy (5 day q 2 weeks, 4 or more courses). We used 2 drugs, (5-fluorouracil (5-FU) and l-leucovorin (l-LV)), and partially added cisplatin (CDDP) in the flat infusion group. The result was a higher response rate (75% vs 37.5%) and lower toxicity (0% vs 31.3%) in the chronotherapy group. Hepatectomy was performed on 12 of the 20 patients. The 5 responders to NAC showed better overall survival (p < 0.05) and lower remnant liver recurrence (p = 0.052) than the 7 non-responders. We therefore conclude that chronotherapy via the hepatic artery prior to hepatectomy may improve the survival of patients with multiple bilobar liver metastases.

[Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer].

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.

Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer.

BACKGROUND: Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. METHODS: From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42 degrees C to 43 degrees C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. RESULTS: When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. CONCLUSIONS: P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP.

Two types of ferrochelatase in photosynthetic and nonphotosynthetic tissues of cucumber: their difference in phylogeny, gene expression, and localization.

Ferrochelatase catalyzes the insertion of Fe(2+) into protoporphyrin IX to generate protoheme. In higher plants, there is evidence for two isoforms of this enzyme that fulfill different roles. Here, we describe the isolation of a second ferrochelatase cDNA from cucumber (CsFeC2) that was less similar to a previously isolated isoform (CsFeC1) than it was to some ferrochelatases from other higher plants. In in vitro import experiments, the two cucumber isoforms showed characteristics similar to their respective ferrochelatase counterparts of Arabidopsis thaliana. The C-terminal region of CsFeC2 but not CsFeC1 contained a conserved motif found in light-harvesting chlorophyll proteins, and CsFeC2 belonged to a phylogenetic group of plant ferrochelatases containing this conserved motif. We demonstrate that CsFeC2 was localized predominantly in thylakoid membranes as an intrinsic protein, and forming complexes probably with the C-terminal conserved motif, but a minor portion was also detected in envelope membranes. CsFeC2 mRNA was detected in all tissues and was light-responsive in cotyledons, whereas CsFeC1 mRNA was detected in nonphotosynthetic tissues and was not light-responsive. Interestingly, tissue-, light-, and cycloheximide-dependent expressions of the two isoforms of ferrochelatase were similar to those of two glutamyl-tRNA reductase isoforms involved in the early step of tetrapyrrole biosynthesis, suggesting the existence of distinctly controlled tetrapyrrole biosynthetic pathways in photosynthetic and nonphotosynthetic tissues.