Narihide Goseki

Antitumor effect of methionine-depleting total parenteral nutrition with doxorubicin administration on yoshida sarcoma-bearing rats

Methionine‐depleting total parenteral nutrition (methionine‐depleting TPN), which infuses an amino acid solution devoid of L‐methionine and L‐cysteine as the sole protein source, showed enhancement of the effect of several anti‐cancer agents. In this study, the combined effect of the methionine‐depleting TPN with the administration of doxorubicin was examined in Yoshida sarcoma (YS)‐bearing rats with regard to effects on the primary tumor growth, the extension of metastasis, and the host animals life span.

Synergistic Effect of Methionine‐depleting Total Parenteral Nutrition with 5‐Fluorouracil on Human Gastric Cancer: A Randomized, Prospective Clinical Trial

Methionine‐depleting total parenteral nutrition (Met‐depleting TPN), infusing AO‐90 amino acid solution (lacking both L‐methionine and L‐cysteine) as a sole nitrogen source, showed synergistic effects with 5‐fluorouracil (5‐FU) in tumor‐bearing rats and in clinical trials with gastrointestinal tract cancers. In this study, the effect of Met‐depleting TPN with 5‐FU upon thymidylate synthase (TS) activity was examined, and the histological effect of this treatment on human gastric cancer was evaluated. Fourteen preoperative advanced gastric cancer patients were divided randomly into two groups. Seven cases were given Met‐depleting TPN for 7 days before surgery with continuous intravenous administration of 5‐FU (500 mg/body per day; total 4.0 g/body) (AO‐90 group). The other 7 received conventional L‐methionine‐containing TPN with 5‐FU (control group). All patients underwent gastrectomy without complications due to these treatments. Resected materials were examined for TS kinetics, and the anti‐cancer effect was also assessed histopathologically. The specimens in the AO‐90 group showed marked degeneration of cancer, while almost no effect was seen in the control group. The free TS activity of carcinoma tissue in the AO‐90 group was decreased and the TS inhibition rate was increased in comparison with the control group (P= 0.0165 and P= 0.0243, respectively). Met‐depleting TPN appears to play a role as a biomodulator of 5‐FU in human gastric cancer.

Endoscopic resection of early-stage esophageal cancer

SummaryEarly-stage esophageal cancerous lesions in four clinical cases were endoscopically resected via a newly developed procedure, endoscopic esophageal mucosal resection using a transparent tube (EMRT). In the complete resection of cancer-bearing mucosa, more than half of the circumferential mucosal resections did not involve major complications such as perforation or massive bleeding. Large ulcers artificially induced by this procedure disappeared within 3 weeks, exhibiting no stenotic changes. Resected specimens contributed well to microscopic examination for histological classification and determination of the depth of cancer invasion and possible vascular involvement. No signs of recurrence were observed during the 15-month follow-up period. We conclude that EMRT is a safe and minimally invasive local treatment for early-stage esophageal cancer that also provides specimens that are suitable for accurate histopathological diagnosis.

Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas

To identify differentially expressed genes in hepatocarcinogenesis, we performed differential display analysis using surgically resected hepatocellular carcinoma (HCC) and adjacent non-tumorous liver tissues. We identified four cDNA fragments upregulated in HCC samples, encoding antisecretory factor-1 (AF), gp96, DAD1 and CDC34. Northern blot analysis demonstrated that these mRNAs were expressed preferentially in HCCs compared with adjacent non-tumorous liver tissues or normal liver tissues from non-HCC patients. The expression of these mRNAs was increased along with the histological grading of HCC tissues. These mRNA levels were also high in three human HCC cell lines (HuH-7, HepG2 and HLF), irrespective of the growth state. We also demonstrate that sodium butyrate, an inducer of differentiation, downregulated the expression of AF and gp96 mRNAs, supporting in part our pathological observation. Immunohistochemical analysis revealed that gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei of HCC cells, respectively. Overexpression of these genes could be an important manifestation of HCC phenotypes and should provide clues to understand the molecular basis of hepatocellular carcinogenesis.

Nourishment of hepatocellular carcinoma cells through the portal blood flow with and without transcatheter arterial embolization

Background. Although transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) is very effective, local recurrence is not so rare. The reason is thought to be related to portal blood flow. The changes in the nourishing vessels in HCC after TAE were examined from the viewpoint of cell kinetics with direct reference to intracellular transportation of biochemical substrates, namely 5 bromo‐2′‐deoxyuridine (BrdU), an analogue of thymidine.

GIANT EPIPHRENIC DIVERTICULUM WITH ACHALASIA OCCURRING 20 YEARS AFTER HELLER'S OPERATION

We report a case of giant epiphrenic diverticulum in a 43-year-old woman who underwent Hellers myotomy because of achalasia 20 years earlier. She complained of heartburn and dysphagia from March of 1991 and was hospitalized in our institution. An upper gastrointestinal X-ray examination with contrast medium revealed a large hemispheric lesion (7.8×4.8cm) occupying the right posterior wall of the lower thoracic and abdominal esophagus. Manometry revealed a motility disorder and high pressure of the lower esophageal sphincter due to achalasia. Therefore she was diagnosed as having a giant diverticulum with achalasia after Hellers operation. She underwent transhiatal esophagectomy and reconstruction with placement of a gastric tube on June 4, 1992. Pathology results on the resected specimen revealed a false diverticulum. She has been doing well for 4 years since the operation.It has been said that a complication of incomplete long myotomy causes pulsion diverticulum, but we could not find a case of epiphrenic diverticulum after myotomy for achalasia reported in the literature in the last 10 years.

Endoscopic resection of carcinoma in situ of the esophagus accompanied by esophageal varices

SummaryA case of carcinoma in situ of the esophagus accompanied by esophageal varices was treated by endoscopic mucosal resection using a transparent tube (EMRT) following eradication of the varices via injection sclerotherapy (EIS). Intravariceal injection sclerotherapy was performed for esophageal varices, and after eradication of the varices had been achieved, half of the circumferential esophageal mucosal resection of the cancer lesion was carried out. No serious complication such as perforation or mass bleeding was observed. Cancer-involved mucosa was completely resected and all specimens contributed well to accurate histopathological study, being diagnosed as intraepithelial squamous-cell carcinoma. The artificial ulcer recovered completely, showing no stenotic changes. Our conclusion from this experience is that EIS + EMRT is a valuable and minimally invasive treatment for patients exhibiting this disease, providing an accurate histopathological diagnosis.

Anti-tumor effect of L-methionine-deprived total parenteral nutrition with 5-fluorouracil administration on Yoshida sarcoma-bearing rats.

L-methionine-deprived total parenteral nutrition (methionine-deprived TPN), infusing amino acid solution devoid of L-methionine and L-cysteine by the method of TPN as an only protein source, showed enhancement of the effect of several anti-cancer agents. In this study the combined effect of the methionine-deprived TPN with administration of 5-fluorouracil (5-FU) was examined in Yoshida Sarcoma (YS)-bearing rats, from aspects of effects on the tumor metastasis and the host animals life span, in the following four groups treated with: methionine-deprived TPN with administration of 5-FU, methionine-deprived TPN without administration of 5-FU, L-methionine-contained TPN plus 5-FU, and L-methionine-contained TPN without 5-FU. In the first experiment, TPN was continued for 8 days in the four groups, and the anti-cancer effect of methionine-deprived TPN and administration of 5-FU based on both the growth of the primary tumor at the implanted site and the tumor metastasis was studied from the view point of pathologic findings of animals killed immediately after these treatments. In experiment 2 the survival period was examined after these treatments for 10 days with subsequent oral feeding until death. The results were as follows: proliferation of YS, transplanted subcutaneously, was markedly suppressed; particularly hematogenous metastasis, characteristic in YS, was prominently blunted then obtained an apparent longer survival period in rats treated with the methionine-deprived TPN with administration of 5-FU.

Esophageal varices evaluated by endoscopic ultrasonography: observation of collateral circulation during non-shunting operations

SummaryTo clarify the inflow and outflow vessels of esophagogastric varices, we investigated the collateral circulation using endoscopic ultrasonography (EUS; Olympus GF-UM2, 7.5 MHz, radial type) during non-shunting operations in 16 cases of portal hypertension. The main inflow vessels were the left gastric veins and the short gastric veins. The paraesophageal vessels coalescent with esophageal varices were distributed up to 7 cm from the esophagogastric junction. It was possible to devascularize these inflow vessels from the transabdominal approach, and it was also easy to evaluate the complete devascularization by the intraoperative EUS. The main outflow vein seemed to be the azygos arch from the investigation of cross-sectional areas of the azygos system. EUS is very useful in evaluating portal hypertension and in determining the indications and the efficacy of the treatment.

Selection of the treatment for esophagogastric varices. Analyses of collateral structures by endoscopic ultrasonography.

SummaryIn 57 cases with portal hypertensive disease, we investigated the intramural and extramural structure of the stomach and the esophagus by endoscopic ultrasonography (EUS). Variously developed intra- and extramural vascular structures had a relationship to the endoscopic variceal form, and communicating (inflow) vessels to varices were found in 28 of the 43 primary cases treated (65%). We then classified the esophagogastric varices into three types according to the vascular structure, such as the esophageal type, esophagogastric type, and solitary gastric type. Based on the analysis of these collateral structures, we selected the treatment as follows. In the esophageal type, which has a few inflow vessels, it is easy to eliminate the varices by obturating the inflow vessels by endoscopic injection sclerotherapy (EIS). In the esophagogastric type, which has many enlarged inflow vessels, the Hassab operation is effective in devascularizing the extramural inflow vessels, and the combination of EIS is necessary to sclerose the intramural varices. In the solitary gastric type, which is a part of the downward portosystemic shunt, the Hassab operation is recommended to prevent rupture of the varices for the subtype with intramural running vessels, but conservative therapy is enough for the subtype without.