Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition.

We encountered six cases of total parenteral nutrition (TPN)-associated lactic acidosis during the 6-y period of 1988-1993. The patients were characterized by severe disease of the digestive organs, minimal food intake before surgery, and postoperative TPN with no food intake and with no vitamin supplements. Within 4 wk of TPN, they developed hypotension (< or = 80/60 mmHg), Kussmaul's respiration, and clouding of consciousness, as well as abdominal pain not directly related to the underlying disease. Routine laboratory examinations revealed no acute aggravation in hepatic, renal, or pancreatic functions. Arterial blood gas analysis showed pH < or = 7.134 and base excess < or = -17.5 mmol/L. Additional laboratory examinations revealed serum lactate > or = 10.9 mmol/L, serum pyruvate > or = 159 mumol/L, and lactate/pyruvate ratio > or = 0.029. None of the patients responded to sodium bicarbonate or other conventional emergency treatments for shock and lactic acidosis. After the first case, we suspected that thiamine deficiency might be responsible for this pathologic condition, Serum thiamine was proved to be < or = 196 nmol/L in 5 patients. Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients. This article includes a review of 11 relevant reports published from 1982-1992 and a discussion of the biochemical mechanism of onset of thiamine deficiency-associated lactic acidosis. We emphasize the needs (1) to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; (2) to monitor the patients routinely measuring serum thiamine concentration and erythrocyte transketolase activity during TPN; and (3) to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.

[A case of advanced gastric cancer with liver metastasis with no recurrence and long survival].

A 61-year-old male was admitted after detecting gastric lesion by gastrography in a medical health examination. The patient was diagnosed as Borrmann 2 advanced gastric cancer with remarkable intraperitoneal lymph node metastasis and liver tumor of lateral segment. Relative non-curative gastrectomy was performed with combined partial hepatectomy. The liver tumor measured 1.5 x 1.5 cm and was intraoperatively diagnosed as metastasis of gastric cancer. Mitomycin C 26 mg was given intravenously on the day of operation and 5-fluorouracil (5-FU) 150 mg/day orally since postoperative 14th day as adjuvant chemotherapy. The administration of 5-FU was continued for 5 years. As a result of such combination therapy, the patient still has had no recurrence 8 years following operation.

The technical problems shoot for the production of anti low molecular weight hapten antibody.

Four kinds of small molecular weight haptens, Desmosine, Adriamycin, 4'-carboxycotinine and 5'-Fluorouracil were used as the immunizing antigens to obtain rabbits polyclonal antisera. All of these haptenes were conjugated to Bovine Serum Albumin (BSA) using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDCl) reagent. The functional amino or/and carboxyl group in hapten molecules was utilized for conjugation with BSA by EDCl reagent. The hapten conjugated with BSA was mixed with Freund's Complete or Incomplete Adjuvant, and immunized to rabbits abdominal subcutaneous regions. More than 3 times immunized rabbit's antisera were evaluated the titer, and the specificity was investigated by ELISA method. The specific antisera against desmosine and adriamycin were produced. Anti-desmosine antibodies had no cross-reaction to molecular structure resemble pyridinoline. Anti-adriamycin antibodies reacted well to adriamycin and it could distinguish the differences of -epi type of adriamycin. The ELISA assay systems used here had such sensitivity. However the specificity possessing antisera against 4'-carboxycotinine and 5-Fluorouracil could not produce even though the antisera titers were elevated. The reasons why and what kinds of problems were there are discussed in this paper. For the production of the specific affinity possessing antisera, the length and distance between the carrier protein and the hapten and the shape of the functional groups were the important factors for production of the specific antisera which recognize free form hapten molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical evaluation of operative and non-operative treatment in hepatocellular carcinoma with main portal vein tumor thrombus].

It has been well recognized that results of treatment in hepatocellular carcinoma with main portal vein tumor thrombus (Vp 3 HCC) are very poor. But we tried aggressive transcatheter treatment (one shot or continuous hepatic arterial infusion, TAE) and hepatectomy with postoperative TAE in 52 cases by Vp3 HCC in recent 10 years. Analysis of the results disclosed that PR or CR cases were observed only in the series of continuous hepatic arterial infusion therapy. And cumulative survival rate was the best in the series of hepatectomy (50% survival interval is 18 months). We concluded that hepatectomy and resection of the tumor thrombus with postoperative TAE is the best treatment in Vp3 HCC.

[Combined therapy with 5-FU and levamisole].

Levamisole, which had been used as an insecticide for more than 20 years, was reported to have anticancer effects as an immunopotentiator. Among many clinical trials with this agent, Moertel and his colleagues reported excellent results in Dukes-C colon cancer patients treated with 5-FU and levamisole in 1990. In this paper, results of our animal experiments would be reported in conjunction with the review of the recent clinical trials.

Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa).

A randomized, controlled trial of adjuvant immunochemotherapy with PSK (Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK group received PSK orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow-up time for this study was four years (range, three to five years). The disease-free survival curve and the survival curve of the PSK group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival, P = 0.013; survival, P = 0.013). These results indicate that adjuvant immunochemotherapy with PSK was beneficial for curatively resected colorectal cancer.

[Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum].

To evaluate of adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer, randomized controlled study by 35 institutions in Kanagawa prefecture was conducted. From March 1985 till February 1987, 462 patients were assigned one of two different regimens. 448 patients (97.0%) of them satisfied the eligibility criteria. Control group received mitomycin C intravenously on the day and the day after the operations respectively followed by 5-FU orally over for 6 months. PSK group received in addition to mitomycin C and 5-FU as in control group, PSK orally for over 3 years. By February 1989, follow up studies of the patients after their operations had been carried out for two years to four years. The disease free curve and the survival curve of PSK group were higher than those of control group, differences between the two groups were statistically significant (Disease free curve: P = 0.0096, survival curve: p = 0.0391). From these results, adjuvant immunochemotherapy with PSK was considered beneficial for curatively resected colorectal cancer.

Copper deficiency in an infant on prolonged total parenteral nutrition.

An infant with the megacystis microcolon intestinal hypoperistalsis syndrome, required total parenteral nutrition due to ineffective gastrointestinal function, and developed copper deficiency after a prolonged course in total parenteral nutrition in conjunction with a chronic draining jejunostomy. She responded promptly to copper supplementation.

[High-dose combination chemotherapy with autologous bone marrow transplantation in breast carcinoma].

Twelve patients with breast carcinoma were treated with high-dose combination chemotherapy supported by autologous bone marrow transplantation (ABMT). Seven of them had advanced metastatic disease and received 12 cours of A treatment, response rate (CR +PR) was 71.5% (CR: 1, PR: 4, NC: 2 and PD: 0) and it should be noted that all 4 patients who had received adriamycin 150 mg+5-fluorouracil 1,500 mg divided in two consecutive days or equivalent high-dose of other chemotherapeutic regimen responded (CR: 1 and PR: 3). To the therapy Five other patients received ABMT-supported adjuvant chemotherapy because of high risk of recurrence. One of them died of unrelated cause and other 4 are free of disease at 11, 14, 17 and 17 months following this treatment. A major toxicity was of myelosuppression and nadirs of neutrophils were 100-1,800 on days 9-19 (median: 400 on day 12), neutrophils recovered rather rapidly to levels of greater than or equal to 1,000, greater than or equal to 1,500 and greater than or equal to 2,000 by day 15, 16 and 17, respectively. High-dose combination chemotherapy with ABMT seemed quite effective in advanced breast carcinoma and a similar approach in adjuvant setting has also been suggested.