Hand-assisted laparoscopic splenectomy for a huge splenic cyst: operative technique and case report.

We report the case of a huge splenic cyst that was successfully treated by hand-assisted laparoscopic splenectomy. A 17-year-old girl with a chief complaint of left-sided abdominal pain was admitted to our department for investigation of a splenic tumor. Ultrasonography, computed tomography, and magnetic resonance imaging revealed a huge cystic lesion in the spleen measuring approximately 10 cm in diameter. Hand-assisted laparoscopic splenectomy was safely performed to diagnose and treat the splenic tumor. The histologic diagnosis was an epithelial cyst of the spleen with no atypical cells in the cyst wall. Hand-assisted laparoscopic splenectomy may be a good method of managing a huge splenic cyst that becomes symptomatic and potentially life-threatening through enlargement, rupture, and secondary infection.

The usefulness of laparoscopy-assisted distal gastrectomy in comparison with that of open distal gastrectomy for early gastric cancer.

BACKGROUND: The technique of laparoscopy-assisted distal gastrectomy (LADG) was developed for early gastric cancer, but its feasibility and the associated clinical outcome remain unclear. METHODS: We reviewed 24 patients who underwent LADG (LADG group) and 35 patients who underwent traditional open distal gastrectomy (ODG group) for early gastric cancer in our hospital, and compared the clinical data of the two groups. RESULTS: The clinical and pathological backgrounds of the patients in the two groups were similar. The duration of surgery was not significantly different between the two groups, but the blood loss in the LADG group was significantly less than that in the ODG group. The number of removed lymph nodes was not significantly different between the two groups. The times to the first passing of flatus, first walking, and the restarting of oral intake; the length of hospital stay; and the duration of epidural analgesia were significantly shorter in the LADG group. The morbidity rate in the LADG group was lower than that in the ODG group. CONCLUSIONS: LADG is a safe and minimally invasive surgical technique, after which we can expect a faster recovery.

[Evaluation of chemosensitivity testing by CD-DST, and TS and DPD activity in cases of colorectal liver].

We evaluated the usefulness of the following three in vitro assays in cases of resected colorectal liver metastases. Chemosensitivity by collagen gel droplet drug sensitivity test (CD-DST) was very low in all cases, suggesting this method is not predictive for this disease. In contrast, thymidylate synthetase (TS) activity and dihydropyrimidine dehydrogenase (DPD) activity in tumor tissue were high in many patients with recurrent disease. Thus, these enzyme activities are promising for assessment of clinical outcome following hepatic resection of colorectal liver metastases. Further analyses with large numbers of cases are needed to determine the significance of these in vitro studies.

[Significant role of cisplatin and 5-FU combination chemotherapy for first-line intensive treatment for advanced esophageal cancer].

We evaluated the efficacy of first-line chemotherapy consisting of cisplatin and 5-fluorouracil combination therapy (in the following, FP) in intensive treatment for esophageal cancer. This first-line chemotherapy was administered to 18 patients with squamous cell carcinoma. Three patients had T2 tumor, 10 had T3 and 5 had T4. Lymph node metastasis was detected in 10 patients and not detected in 8 patients. Five patients had distant metastasis. Ten patients showed a partial response and the response rate was 55.6%. Of these 10 patients, 5 were followed with surgery, 3 of whom survived without recurrence of the disease. Five patients were treated by FP, radiation therapy or combination of FP and radiation. Of these 5 patients, 2 showed a complete response. On the other hand, 8 nonresponders died from progressive disease, despite following intensive treatment. These results suggest that first-line chemotherapy by FP, which requires following intensive treatment, improves the overall long-term survival of advanced esophageal cancer patient.

[Usefulness of hepatic arterial infusion chemotherapy for liver metastasis in gastric cancer].

UNLABELLED: We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs. RESULTS: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion. CONCLUSION: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.

Determination of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione, a novel metabolite of L-histidine, in tissue extracts from sunlight-irradiated rat by capillary electrophoresis.

Exposure of the skin to sunlight results in an increase in the content of epidermal urocanic acid, a key metabolite of L-histidine, and some portions of the metabolite penetrate into the body fluid. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of glutathione and urocanic acid, was proposed to be an origin of a urinary compound, S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). Various catabolites of Cys(CIE) were also isolated from human urine previously. However, no direct evidence to show the existence of GS(CIE) as a biological material had been found. By using capillary electrophoresis, the glutathione adduct has now been found in the extracts of rat tissues from the kidney, liver, skin and blood when the rat was kept under conditions of sunlight irradiation after the fur on the dorsal skin had been clipped. On the other hand, no or a trace of GS(CIE) was determined in rat tissue extracts when the animal was kept indoor in usual manner. The glutathione adduct was isolated from the kidney extract of the sunlight-irradiated rat using ion-exchangers and high-voltage paper electrophoresis, and determined by fast-atom-bombardment mass spectrometry. These results indicate that GS(CIE) formation actually occurs in the body and that the formation is accelerated by exposing the rat to sunlight irradiation. From these findings, we propose an alternative pathway of histidine metabolism which is initiated by the adduction of urocanic acid to glutathione to form GS(CIE) and terminates with the formation of the urinary compounds via Cys(CIE).

[Evaluation of hepatic resection following hepatic arterial infusion chemotherapy for colorectal liver metastases].

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.

[Malignant islet cell tumor of the pancreas with multiple liver metastases effectively treated by transcatheter arterial embolization with degradable starch microspheres--a case report].

A 57-year-old woman underwent distal pancreatectomy for malignant islet cell tumor of the pancreas in 1991. One year later, multiple liver metastases appeared. Although three transcatheter arterial embolizations (TAE) with spongel and nine ethanol injections were performed over seven years, the tumors were growing gradually. Therefore, TAE with degradable starch microspheres (DSM) was selected. Under angiography, TAE of the left hepatic artery was done using 900 mg of DSM following injection of Farumorubicin (20 mg), Lipiodol (3 ml) and cisplatin (90 mg). The tumors in the embolized hepatic area were remarkably decreased in size, and satisfactory local control was obtained. Thereafter, TAE with DSM was carried out twice, and she is still living with outpatient treatment. Thus, it is suggested that TAE with DSM could be a promising, alternative therapeutic modality for liver metastases from malignant islet cell tumor of the pancreas.

The usefulness, indications, and complications of laparoscopy-assisted colectomy in comparison with those of open colectomy for colorectal carcinoma.

The technique of laparoscopy-assisted colectomy (LAC) was developed for benign and malignant diseases of the colon and rectum; however, its feasibility and the associated clinical outcome remain unclear. We reviewed 45 patients who underwent LAC (LAC group) and 62 patients who underwent traditional open surgery (Open group) for colorectal carcinoma in our hospital, and compared the clinical data between the two groups in an effort to determine whether LAC is really minimally invasive and if it enhances the quality of life. So that the backgrounds of the patients in both groups were almost the same, we only compared data of patients with colorectal carcinoma of stages 0, I, and II. The duration of surgery in the Open group was significantly shorter for all procedures except sigmoid resection, but the blood loss was not significantly different between any of the procedures except for right colectomy. The time to the first passing of flatus and restarting oral intake, length of hospital stay, and duration of epidural analgesia were significantly shorter in the LAC group. The morbidity and mortality rates in the LAC group were almost the same as those in the Open group at 29.5% and 3.3% versus 22.6% and 1.6%, respectively. However, five major complications of LAC for advanced colorectal carcinomas might be prevented by performing an open procedure. In conclusion, LAC is a safe and minimally invasive surgical technique following which we can expect a faster recovery; however, patients with advanced colorectal carcinomas must be carefully selected for this operation.

Inhibitory effects in vitro of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-glutathione, a proposed metabolite of L-histidine, on gamma-glutamyltransferase activity.

A transfer of the gamma-glutamyl moiety of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (I), an adduct of glutathione and L-histidine metabolite urocanic acid, has been investigated by using gamma-glutamyltransferase preparation from bovine kidney. When an equimolar mixture of two diastereomers of compound I in a phosphate buffer was allowed to react with glycylglycine in the presence of the transferase, two diastereomers of N-[S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl]glycine (II) were formed in the same yield with each other and this was accompanied by a formation of gamma-glutamylglycylglycine. Kinetics of compound I with the transferase indicated high affinity between the two materials, while the maximal reaction velocity of the gamma-glutamyl transfer was low. Effects of compound I in vitro on the transfer of gamma-glutamyl moiety of gamma-glutamyl-p-nitroanilide to glycylglycine with the transferase were also studied, and the results indicated that the transfer was suppressed by compound I based on its competitive and non-competitive inhibitions. These results suggest that little variation in reactivities of two diastereomers of compound I as the substrate is given by the difference in stereomerism of their asymmetric carbon atoms and that inhibitory effects of compound I on the catalytic action of the transferase is of sufficient physiological importance to decrease the degradation of natural gamma-glutamyl compounds, such as glutathione and its analogs.

Determination of chiral catabolites from S-[2-carboxyl-1-(1H-imidazol-4-yl)ethyl]glutathione, a proposed metabolite of L-histidine, by capillary electrophoresis].

A new method for simultaneous determination of two diastereomers in each of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (I) and N-¿S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl¿glycine (II) was developed by electrophoresis using a neutral coated capillary with a separation buffer, pH 6.00, containing 80 mM hydroxypropyl-beta-cyclodextrin at a field strength of 500 V cm-1 at 20 degrees C. This method was applied to establishment of a catabolic pathway from S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (III) to compound I. Incubation of either of compound II diastereomers as an enzyme substrate with rat kidney homogenate in a phosphate buffer, pH 7.4, resulted in a formation of compound I only having correspondent configurations on asymmetric carbon atoms of its molecule with those of the substrate, i.e., no occurrence of isomerization in the catabolism. Additionally, little difference in action as the substrate between two diastereomers of compound II was found. When an equimolar mixture of two diastereomers of compound III was allowed to react with the homogenate in the presence of glycylglycine, two diastereomers of compound II were formed in the same yield with each other and then these were catabolized gradually to both isomers of compound I. These results suggest that compound II is a metabolic intermediate for the formation of compound I from compound III, and that little variation in reactivities of two diastereomers of compound III as well as compound II with enzymes is given by the difference in stereoisomerism of asymmetric carbon atoms on their molecules.

[Analysis of 18 breast cancer patients with hypercalcemia].

A total of 91 breast cancer patients died of advanced and recurrent breast cancer at the Osaka Teishin Hospital from 1986 to 1996. There were 18 cases (19.8%) among them showing hypercalcemia (serum corrected Ca > or = 11.0 mg/dl). These 18 cases were analyzed to determine the incidence of hypercalcemia and to find a more effective treatment. All these patients had multiple bone metastases during their clinical course, and six patients (33.3%) had pathologic bone fracture just before the occurrence of hypercalcemia. Their common symptoms were general fatigue, gastrointestinal symptoms, renal dysfunction or neurological symptoms. There was no definitive correlation between clinical signs and serum calcium values. Among various therapies, the use of pamidronate disodium (Aredia) in combination with hydration, steroid and calcitonin was found to be the most effective treatment for hypercalcemia. The survival time from the diagnosis of hypercalcemia in the patients undergoing treatment with Aredia was significantly better than without it (p < 0.01). This suggests that Aredia should be effective and useful for advanced breast cancer patients with hypercalcemia.

Appraisal of combination treatment for hepatocellular carcinoma: long-term follow-up and lipiodol-percutaneous ethanol injection therapy.

Since 1988, 124 patients with hepatocellular carcinoma were treated in our departments. Among them, 31 cases treated by surgical resection and 30 cases administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte, France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-, and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy group. The follow-up results at less than 4 years after the procedures revealed that the survival rate with the combination therapy was slightly better than that with the surgical treatment. However, in the subsequent 4 years, the survival rate of the combination therapy group decreased rapidly. The reasons for this deterioration were local recurrence and/or new primary lesions of hepatocellular carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the ethanol so that the location of the injected ethanol could be easily confirmed. The effectiveness of L-PEIT was thus confirmed by computed tomography, performed on the following day. Defective Lipiodol accumulation in the tumor and/ or neighboring tissues was able to be corrected by additional ethanol injections. With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore, a better prognosis is expected.

Isolation and characterization of N-acetyl-S-[2-carboxy-1-(1 H-imidazol-4-yl) ethyl]-L-cysteine, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1 H-imidazol-4-yl) ethyl]-L-cysteine.

N-Acetyl-S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (I), a new imidazole compound with a sulfur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving 1H-NMR spectrometry, mass spectrometry and high-voltage paper electrophoresis as well as chemical synthesis. Approximately five milligrams of crystals of the compound were obtained from 450 litres of the urine. Compound I was synthesized by the addition of N-acetyl-L-cysteine to urocanic acid. The compound was also formed by incubation of S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (II) with acetyl-CoA in the use of rat kidney or liver homogenate as an enzyme source in a Tris buffer at pH 7.4. Rat brain and spleen homogenates were the less or no effective preparations as the enzyme source. On the other hand, little N-acetylation of a diastereomer of compound II occurred in enzymatic reactions with rat tissue homogenates. Compound I was degraded to compound II by rat kidney or liver homogenate. These results suggest that compound I is a new N-acetylated metabolite of compound II, a compound previously found in human urine, and that the acetylating enzyme recognizes stereoisomerism of asymmetric carbon atoms on the molecule of compound II. These findings support an alternative pathway of L-histidine catabolism initiated by the adduction of glutathione and/or cysteine to urocanic acid, the first catabolite of histidine.

[Intra-arterial infusion chemotherapy for liver metastases from breast cancer].

Twelve patients with liver metastases of breast cancer were treated with hepatic arterial infusion chemotherapy using 20-30 mg/body of epi-adriamycin (epi-ADM) every 2 weeks and continuous infusion of 250 mg/body/day of 5-fluorouracil (5-FU). All patients were followed by systemic chemo-endocrine therapy with oral administration of 600-1,200 mg/day of me droxyprogesterone acetate (MPA) alone or with 600-800 mg/day of 5'-deoxy-5-flurouridine (5'-DFUR). The response rate was 41.7% (5/12 cases). Duration of response was 2-28 months (mean 10 months). At one year, the survival rate was 46.8% (Kaplan-Meier method). As for side effects, gastrointestinal disturbance, bone marrow depression and alopecia were mild. These results suggest that hepatic arterial infusion therapy in combination with MPA is safe and effective for controlling liver metastases of breast cancer.

[A comparison of intra-arterial chemoembolization and infusion chemotherapy for liver metastases of breast cancer].

Seventeen patients with liver metastases of breast cancer were treated with a combination of intra-arterial chemotherapy and endocrine therapy at our hospital from 1986 to 1994. Of 17 patients, 9 were treated with transarterial chemoembolization through hepatic artery using 40-50 mg/body of 4'epi-adriamycin (epi-ADM) and lipiodol, and the other 8 were treated with hepatic infusion chemotherapy using 20-30 mg/body of epi-ADM every 2 weeks. All patients were followed by endocrine therapy with oral administration of 800-1,200 mg/day of medroxyprogesterone acetate (MPA). The results were as follows: 1) The comparison of response rate between the two groups was not substantially changed (44.4% x 4/9 in TAE group and 50.0% x 4/8 in Reservoir group). 2) Duration of response was 4-45 months (mean 25 months) in TAE group and 3-15+ alpha months (mean 8.7 months) in Reservoir group. But in the latter group, 3 patients are now under treatment. 3) At one year, the survival rates were 44.4 percent in TAE group and 50.0 percent in Reservoir group. We conclude that combination of intra-arterial chemotherapy and endocrine therapy is a useful treatment modality for controlling liver metastases of breast cancer.

A method for determination of total glutathione and total cysteine as S-carboxymethyl derivatives by using an amino acid analyzer, and its application to samples from rat liver, kidney and blood after intraperitoneal administration of 2-(4-carboxy-D-gluco-tetrahydroxybutyl)thiazolidine-4-carboxylic acid.

The effects of intraperitoneal administration of 2-(4-carboxy-D-gluco-tetrahydroxybutyl)thiazolidine-4-carboxylic acid (CGUA), a cysteine derivative conjugated with glucuronic acid, on total glutathione and total cysteine contents in rat tissues were investigated. Total glutathione (GSH and GSSG) and total cysteine (cysteine and cystine) were determined by a new method consisting of preparation of S-carboxymethylglutathione (CMSG) and S-carboxymethylcysteine (CMC), respectively, and subsequent analyses with an amino acid analyzer. CGUA was determined by a coloration method employing an acidic ninhydrin reagent. Total cysteine contents in liver, kidney and plasma rapidly increased to 2.3, 2.7 and 6.5 times the levels of the controls, respectively, after CGUA administration at a dose of 5 mmol/kg of body weight. Total glutathione content did not change significantly in the liver or blood except for the kidney with a significant increase during the first 1-h period after administration. CGUA content increased markedly in these tissues, especially in the kidney, and 30% of administered CGUA was excreted in urine within 2h. These results indicate that CGUA is converted into cysteine in vivo, suggesting the usefulness of this compound for protection of the kidney and the liver.

Difference in rates of the reaction of various mammalian oxyhemoglobins with phenylhydrazine.

Second order rate constants for the initial reaction of 12 mammalian oxyhemoglobins (Hb) with equimolar phenylhydrazine (PHZ), a compound inducing Heinz body hemolytic anemia, were determined by recording continuous changes in absorbance with time at 577 nm. The rate constants were varied in a range from 43 m-1.s-1 with pig Hb to 255 m-1.s-1 with dog Hb. On the other hand, isosbestic points at 526 and 587 nm were common to all the reaction processes. The aerobic reaction of Hb with PHZ resulted in denaturation of hemoprotein, and final reaction products were determined to be beta-meso-phenylbiliverdin IX alpha and N-phenylprotoporphyrin IX. These results suggest that the reactivity of PHZ to Hb is influenced by the globin molecule, and the oxidative cleavage of the porphyrin ring causes the denaturation of hemoprotein.

Increase in cystathionine content in rat liver mitochondria after D,L-propargylglycine administration.

Intraperitoneal administration of D,L-propargylglycine to rats resulted in an increase in the cystathionine content of whole liver and liver mitochondria. Cystathionine in mitochondria was identified by amino acid analysis, thin layer chromatography, high-voltage paper electrophoresis and liquid chromatography-mass spectrometry. The cystathionine content of whole liver was 5.37 ± 1.59µmol per g of fresh liver at 14 h after the administration of 50 mg of D,L-propargylglycine per kg of body weight, while 0.07 ± 0.02µmol of cystathionine per g of fresh liver was detected in the control rats. The cystathionine content of liver mitochondria from both groups of rats was 9.40 ± 1.20 and 0.19 ± 0.04 nmol of cystathionine per mg of protein, respectively. The mitochondrial cystathionine increased dose-dependently with the increase of D,L-propargylglycine administered. The increase was proportional to the time after the administration up to 12 h, and then decreased. The increase of cystathionine in the liver mitochondria was linearly proportional to that in the whole liver. These results suggest that cystathionine in liver mitochondria is in an equilibrium with that in the cytosol.