Preoperative short-term radiation therapy (25 Gy, 2.5 Gy twice daily) for primary resectable rectal cancer (phase II).

To evaluate the feasibility, effectiveness, and long-term bowel function of preoperative hyperfractionated accelerated radiotherapy in primary resectable rectal cancer. A total of 184 consecutive patients (median age 65 years, male : female=2 : 1) with clinical T3Nx rectal adenocarcinoma received preoperative pelvic radiation therapy with single fractions of 2.5 Gy twice daily (interval 6 h between fractions) to a total dose of 25 Gy within 1 week. Surgery was conducted the following week. Postoperative histology revealed UICC stage I in 33%, stage II in 26%, stage III in 34%, and stage IV in 7% of the patients. Median follow-up was 43 months (53 months for surviving patients). The actuarial 4-year-local-recurrence rate was 2.1%, overall recurrence 23%. Disease-specific and disease-free survivals at 4 years (excluding stage IV) were 82 and 69%, respectively. Overall survival for 4 years was 68%. Postoperative mortality was 0.5% (one patient), early anastomotic leakage occurred in 11.4%, and anastomotic stenosis requiring treatment in 6%, of 132 patients with primary anastomosis. Seven of 184 patients (3.8%) died of abdominal complications, all within the first year. Bowel function was satisfactory after more than 5 years. Local control in primarily resectable rectal cancer after 10 x 2.5 Gy is excellent, warranting further evaluation of this treatment.

Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro.

LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell.

[Results of molecular diagnosis in 30 Austrian families with familial adenomatous polyposis]. / Ergebnisse der molekularen Diagnostik bei 30 österreichischen Familien mit familiär adenomatöser Polyposis.

Familial adenomatous polyposis is a dominantly inherited precancerous condition of the colorectum. The isolation of the responsible gene has facilitated the search for mutation in affected individuals and risk estimation for family members. The aim of our study was the assessment of the disease by molecular biological methods in order to estimate the risk for family members. Blood probes from 30 non-related Austrian families (44 persons affected, 61 at risk) were examined for detection of a defect in the adenomatous polyposis gene by means of the protein truncation test and, if necessary, by linkage analysis. The protein truncation test led to successful identification of the defect gene in 66.7% (20/30 families). In 3 families, the presymptomatic difference between mutation carriers and healthy subjects could only be assessed by linkage analysis. Genetic diagnosis enabled us to detect the disease before the onset of clinical symptoms in 16 persons at risk, 37 could be identified as genetically healthy. In 8 persons at risk out of 5/30 families we were unable to identify a defect gene by the methods used until now. In conclusion, we have succeeded in establishing genetic diagnosis of familial adenomatous polyposis using the protein truncation test in Austria. Our method of genetic risk estimation is an important step in Austria towards earlier diagnosis and well-timed therapy management, and helps to exclude persons at risk who are genetically healthy from the laborious screening program.

Genetic analysis of multiple synchronous lesions of the colon adenoma-carcinoma sequence.

The colorectal adenoma-carcinoma sequence represents a well-known paradigm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence is well investigated, studies about tumours of different dignity co-existent in the same patient are seldom. In order to address the distribution of genetic alterations in different lesions of the same patient, we coincidently investigated carcinomas, adenomas and aberrant crypt foci in patients with sporadic colon cancer. By utilizing polymerase chain reaction, single-strand conformation polymorphism, heteroduplex-analysis, restriction fragment length polymorphism, protein truncation test and sequencing techniques we looked for mutations and microsatellite instability of APC, H-ras, K-ras, p53, DCC and the DNA repair genes hMLH1/hMSH2. In accordance with the suggested adenoma-carcinoma sequence of the colon, four patients reflected the progressive accumulation of genetic defects in synchronously appearing tumours during carcinogenesis. However, two patients with non-hereditary malignomas presented different genetic instabilities in different but synchronously appearing tumours suggesting non-clonal growth under almost identical conditions of the environment. Thus, sporadically manifesting multiple lesions of the colon were not necessarily driven by similar genetic mechanisms. Premalignant lesions may transform into malignant tumours starting from different types of genetic instability, which indicates independent and simultaneous tumorigenesis within the same organ.

Combined restorative proctocolectomy and pancreaticoduodenectomy for familial adenomatous polyposis.

This is a case report on FAP in a 41-year-old woman in which preoperative examination showed a giant tubulovillous adenoma of the descending duodenum surrounding the papilla of Vater, in addition to pancolon adenomatous polyposis, and isolated adenomas in the gastric antrum and corpus. As it was impossible to remove the giant villous adenoma in the duodenum endoscopically, prophylactic surgical treatment was chosen consisting of restorative proctocolectomy and additional pancreaticoduodenectomy. Flat tubulovillous adenomas in the gastric corpus were successfully removed by total snare biopsies before operation. FAP coli patients treated by prophylactic surgery are now known to be at risk of developing adenomas anywhere in the intestine and many affected patients later die from upper gastrointestinal tumors. In this single case report, the simultaneous occurrence of FAP coli and giant villous adenoma of the duodenum indicates the frequent outcome of this genetic alteration requiring lifelong surveillance. This rare case report includes a short survey of the relevant literature.

Abdominosacral resection of recurrent rectal cancer in the sacrum.

PURPOSE: Resection of the sacrum is the only curative therapy of isolated sacral recurrence after primarily resected rectal cancer. The aim of the study was to assess whether there is a benefit in terms of overall survival, morbidity, and mortality when sacrum resection is performed more radically and in cooperation between colorectal and orthopedic surgeons. Possible prognostic factors were also assessed. METHODS: Twelve consecutive patients who underwent interdisciplinary partial sacral resection were included in a retrospective cohort study. Furthermore, overall survival rate and survival time were calculated. RESULTS: Histologic examination showed tumor-free resection margins in all cases. Extended resection was necessary in seven patients, including total pelvic exenteration in two. No perioperative death occurred and no patient required early reoperation. Complications were observed in 42 percent of patients, mainly caused by poor wound healing. All patients experienced relief from pain. One-year and three-year overall survival rates were 50 and 17 percent, respectively. The overall mean survival time was 21.7 months. Patients who died of recurrent disease within one year either underwent former resection for locoregional recurrence, had extensive local recurrent tumors affecting pelvic visceral structures, or retrospectively suffered from metastatic sacral tumor manifestation. CONCLUSION: The mortality and morbidity rates observed in the present study seem to justify partial sacral resection as a means to achieve palliation of perineosacral pain in spite of rare overall long-term survival.

[Management of severe infection complicating aortofemoral grafts]. / Management der tiefen Infektion als Komplikation nach Bifurkationsprothese.

OBJECTIVE: Infection of the retroperitoneum after implantation of an abdomino-femoral aortic graft remains one of the main problems in vascular surgery. On basis of a critical review of own experiences we evaluated the management of this difficult clinical situation. PATIENTS: From 1970-1996 1500 aortofemoral graft operations (aneurysmal disease: 512, aortoiliacal occlusive disease: 988) were performed. Abdominal infection occurred in 12 patients (0.8%) (12 men, median age 60.5 [48-80] years). RESULTS: The median interval between operation and infection was 17.7 (0.5-108) months. The port of infection was in 50% the groin, 25% suffered from abdominal infection, in 3 cases it was not to identify. Clinical manifestation of infection was aortoduodenal fistula in 2 patients, false aneurysms in 2 cases, and a paraprosthetic abscess in another 4 patients. Operative therapy comprised (partial) removal of infected material in 10 patients with consecutive extraanatomical reconstruction in 8 of these. Mortality of graft infection was 50%. Causes of death were untreatable sepsis in 4 patients, another 2 died from hemorrhagic shock. 3 out of 6 surviving patients finally lost their limbs following multiple vascular procedures. CONCLUSION: Adequate surgical therapy of infected aortofemoral grafts remains an unsolved problem. Lack of knowledge of suitable parameters for the best treatment leaves the outcome of prosthetic infection unpredictable. Removal of the infected graft with extraanatomic reconstruction seems to be the standard of surgical treatment, which is recommended in these cases.

Survival of normal colonic epithelial cells from both rats and humans is prolonged by coculture with rat embryo colonic fibroblasts.

Primary cultures of normal colonic epithelial cells from both humans (HCEC) and rats (RCEC) have been established using coculture with colon fibroblasts isolated from rat term embryos. While no other factors we have analyzed had any effect on the survival of epithelial cells, which is normally 3-4 days, coculture with viable fibroblasts extended this period to at least 2 weeks. The effects depended on early passages and low seeding densities of the fibroblasts and on direct cell-cell contact. We have obtained cultures of epithelial cells expressing keratin, laminin, and uvomorulin, displaying a polygonal, epithelial morphology and forming microvilli. DNA synthesis as measured by BrdU uptake into DNA varied widely between colonies of the same culture depending on cell morphology: flat colonies of RCECs contained 5.7% +/- 0.56% BrdU-positive cells, while the proportion in dense three-dimensional colonies reached 50.3% +/- 2.6%. In HCECs the growth fraction was lower, but showed the same distribution between classes of colonies. In the presence of rat embryonic colon fibroblasts, growth factors exerted survival activity on colonic epithelial cells. Consecutive addition of insulin and epidermal growth factor/fibroblast growth factor (EGF/FGF) increased colony number (15.0 +/- 1.0 and 23.0 +/- 2.0 colonies/well respectively; p < or = 0.05 increased above control) and size (1022 +/- 155 and 1207 +/- 158 cells/colony respectively; p < or = 0.05 increased above control) compared to serum-free control medium and basic MEM without growth factors. BrdU labeling index was not increased, however: EGF/FGF actually decreased BrdU labeling from 33.2% +/- 3.9% in controls to 21.3% +/- 3.8% in the EGF/FGF group (p < or = 0.05) owing to the high proportion of flat colonies consisting of resting cells. The newly established culture model can now be used to investigate growth control mechanisms in colonic mucosa and the effects of toxic and/or tumor-promoting substances on these mechanisms.

Ophthalmic and genetic screening in pedigrees with familial adenomatous polyposis.

PURPOSE: To study the possible association between ophthalmic findings, genetic status, and clinical course of the disease in Austrian pedigrees with familial adenomatous polyposis (FAP). METHODS: Thirty-nine members of 16 consecutive FAP families with 20 affected patients and 19 relatives with a 50% a priori risk to develop the disease were examined ophthalmologically. The intestinal status of all persons was established by colonoscopy. Direct or indirect molecular genetic analysis, or both, was possible in eight of the 16 FAP families. RESULTS: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was discovered in 15 (75%) of the 20 persons affected by familial adenomatous polyposis. Five (25%) of the patients with an established FAP were CHRPE-negative. Four of the 19 at-risk individuals were CHRPE-positive. According to DNA analysis, five of the 19 at-risk relatives had a high risk to develop a manifest disease. The ophthalmoscopic tests were in complete agreement with the molecular risk estimation. Furthermore, the combined results of endoscopy and ophthalmoscopy suggested a relationship between a positive CHRPE status and the severity of FAP. CONCLUSIONS: Ophthalmic examinations facilitate predictive diagnosis in FAP patients and first-degree relatives, permitting a noninvasive, highly reliable risk assessment. When present, CHRPE lesions are a reliable clinical marker for FAP in CHRPE-positive families. In CHRPE negative families, negative ophthalmic examinations are of no predictive value. The CHRPE status can add information about the location of the genetic mutation. The combination of an ophthalmic examination with DNA analysis and endoscopy improves the risk assessment of FAP carriers.

Microsatellite instability analysis: a multicenter study for reliability and quality control.

The molecular biology section of the Hereditary Non-Polyposis Colorectal Cancer study group-Germany, instituted a multicenter study to test the reliability and quality of microsatellite instability (MSI) analysis. Eight laboratories compared MSI analyses performed on 10 matched pairs of normal and tumor DNA from patients with colorectal carcinomas. A variety of techniques were applied to the detection of microsatellite changes: (a) silver and ethidium bromide staining of polyacrylamide gels; (b) radioactive labeling; and (c) automated fluorescence detection. The identification of highly unstable tumors and tumors without MSI was achieved in high concordance. However, the interpretation of the band patterns resulted in divergent classifications at several microsatellite marker loci for a large fraction of this tumor/normal panel. The data on more than 30 primers per case suggest that the enlargement of the microsatellite panel to more than 10 loci does not influence the results. In this study, cases with MSI in less than 10% of loci were classified as microsatellite stable, whereas MSI was diagnosed in cases with more than 40% of all markers unstable. We propose that a panel of five microsatellite loci consisting of repeats with different lengths should be analyzed in an initial analysis. When less than two marker loci display shifts in the microsatellite bands from tumor DNA, the panel should be enlarged to include an additional set of five marker loci. The number of marker loci analyzed as well as the number of unstable marker loci found should always be identified. These criteria should result in reports of MSI that are more comparable between studies.

Family history as a marker of risk for colorectal cancer: Austrian experience.

A family history of colorectal cancer is a known risk factor for the disease. As a result of different study designs from different populations, the strength of this association varies in the literature. We intended to define the incidence and the risk predictors in first-degree relatives of patients with colorectal cancer in the Austrian population. A family history was obtained from first-degree relatives of 100 consecutive patients with sporadic colorectal cancer. Life-table methods were used to compare the observed and expected incidence of colorectal cancer and the influence of differences in risk for first-degree family members. The calculated lifetime risk for colorectal cancer in Austria is 1:16. Individuals with a positive family history had a 4.6-fold risk (p

Screening by genomic linkage studies and mutation analysis of hereditary adenomatous polyposis coli: usefulness for clinical practice.

A heterogeneous group of patients suffering from adenomatous polyposis coli (APC) were evaluated by clinical and genetic investigations for the first time in Austria. The patients belonged to eight unrelated APC families. In six families several family members were affected with APC, and linkage analysis with highly informative markers was used to estimate the risk of single individuals in these families to develop APC. All index patients were also tested for the most frequent mutation in the APC gene (mutation cluster region, exon 15). Clinical investigations included ophthalmologic tests for congenital hypertrophy of retinal pigment epithelium and colonoscopy. According to DNA analysis, 5 of 19 at-risk individuals had to be considered to be at high risk of having inherited the disease. Four of them underwent proctocolectomy, one patient at risk is under colonoscopic surveillance. The predictive value of indirect genotype analyses reached 83.3%; direct mutation analyses allowed risk estimation in 50% of cases. Ophthalmologic investigation was informative in 75% of the families. Direct and indirect genotyping using a panel of highly polymorphic, closely linked microsatellite markers is a valuable, rapid, reliable method for establishing a presymptomatic diagnosis of APC, especially in families in which more than one affected individual is available for analysis. With regard to the onset of APC and extracolonic manifestations, the variability of APC demands clinical investigations in addition to the molecular tests for all patients and their first-degree relatives.

The importance of the effect of underlying disease on rejection outcomes following orthotopic liver transplantation.

Despite major advances in immunopharmacology, virtually all patients receive the same center-specific immunosuppressive regimen following orthotopic liver transplantation (OLT). The present analysis was performed on the hypothesis that the original disease representing the indication for OLT leads to a different initial immunological situation of the patient. The type of original disease might therefore be a predisposing factor for acute rejection episodes and influence graft and patient survival. From January 1988 to July 1994, 34 patients received OLT at our institution for end-stage primary biliary cirrhosis (group 1) and 66 patients for end-stage alcoholic cirrhosis (group 2). Overall survivals at 1 and 5 years in group 1 versus group 2 were 67% versus 80% and 50% versus 68%, respectively (P<0.04). Retransplantation was performed in 21% of patients from group 1 and in 6% from group 2. The estimated risk for freedom from acute rejection amounts to 38% in group 1 compared with 59% in group 2 (P<0.02). Multivariate regression analysis of potential risk factors identified only the underlying disease as independent predictor. Analysis of cumulative rates of clinically relevant rejection episodes stratified by group revealed 0.29 and 0.05 episodes per patient at one month and 0.80 and 0.06 at six months (P<0.009) respectively. In our clinical experience it was possible to confirm the hypothesis that the underlying disease is the reason for a significantly different incidence of acute rejection episodes and that it subsequently influences graft and patient survival. This approach to an individually adapted immunosuppressive therapy should be taken into consideration and other appropriate parameters investigated.

Vegetable oil as an MR contrast agent for rectal applications.

The purpose of this study was to evaluate the feasibility of pure vegetable oil as an MR contrast agent for rectal applications. The hypothesis was that vegetable oil highlights the lumen of the rectum after rectal application as a positive contrast medium and offers additional contrast qualities using fat suppression techniques. Eleven MRI examinations were performed on 11 subjects (five healthy volunteers, all males, mean age 35 yr; and six patients, three males, three females, mean age 49 yr). Peanut oil, 200 ml, was applied rectally. In addition, 0.1 mmol/kg GD-DTPA was administered intravenously to the six patients only. Conventional T1-weighted SE sequences and T1-weighted SE images with fat suppression were obtained. Criteria for image evaluation were: overall image quality; uniformity of contrast distribution; chemical shift artifact; and delineation of the rectal wall. Side effects were assessed. There were no complaints reported by the 11 subjects. The image quality was sufficient in all studies. In all five of the volunteers and five of the six patients, the distribution of oil was uniform. Chemical shift artifacts did not deteriorate image quality. After rectal application of vegetable oil, the delineation of the rectal wall was sufficient with and without fat suppression techniques. Vegetable oil highlights the lumen of the rectum in MRI studies and offers additional contrast qualities with fat suppression techniques, acting as a positive as well as a negative contrast agent, depending on the chosen sequence.

Intersphincteric resection for low rectal tumours.

An abdominoperineal operation is described that extends rectal resection for low tumours into the intersphincteric plane with removal of the internal sphincter. Bowel continuity is restored by coloanal anastomosis. Of 38 patients who underwent surgery since 1984, 34 had low rectal cancer and four carcinoid or large villous adenoma. There was no mortality. Four patients developed local recurrence during a median observation period of 3 years. Continence was satisfactory in all patients. The median daily number of bowel movements during the first months after colostomy closure was 9 but decreased to 3 after 1 year and 1 after 2 years. Anal manometry demonstrated a significant reduction of mean resting pressure from 91.8 to 35.1 cmH2O with no recovery after 2 years (P < 0.0001). Squeeze pressure showed only a transient decrease.

Five of six protein kinase C isoenzymes present in normal mucosa show reduced protein levels during tumor development in the human colon.

Protein kinase C (PKC) isoenzyme patterns were analyzed from human colonic epithelial cells of normal, premalignant and malignant origin. PKCs alpha, beta and zeta were found predominantly in the cytosol and the subtypes delta, epsilon and neta almost exclusively in the particulate fraction. Of the isoenzymes found beta, epsilon and neta were low in abundance and could only be detected after partial purification of cellular fractions on DE52-cellulose. Only PKC beta was similar in abundance in normal mucosa, premalignant and malignant colonic epithelial cells, while all other isoenzymes were decreased in abundance in tumor cells. The loss of PKC protein in tumor cells correlated with a loss in enzyme activity, as has been described before by other groups, especially affecting the Ca(2+)-dependent isoenzymes. On the other hand, activation of PKC by phorbol ester treatment in vivo was only possible in carcinoma cells (4/4) and a subset of adenomas (3/7). Normal human colonic epithelial cells did not respond to TPA treatment with either stimulation of PKC activity or translocation of cytosolic enzymes to the particulate fraction. Instead, TPA treatment resulted in a rapid loss of protein for the isoenzymes alpha, delta and to a lesser degree also beta. We assume that this reflects qualitative differences in response between normal and tumor cells, that may be due to the differences in isoenzyme distribution.

[Vascular surgery and smoking--a retrospective multivariant analysis]. / Gefässchirurgie und Rauchen--eine retrospektive multivariante Analyse.

In a retrospective study of 2,988 patients operated because of chronic occlusive arterial disease preoperative smoking habits were related to the patency rates of arterial reconstructions of carotid arteries, infrarenal aorta, iliac vessels, of the lower extremity, and to overall survival rates: 1) 75.2% of the patients were smokers, 24.8% were nonsmokers (NS). 2) Smokers needed the first vascular procedure about 7 years earlier than NS (62.4 +/- 10.3 vs. 69.9 +/- 9.9 years of age; p = 0.001). 3) A significant difference between the 2 groups could be found regarding the location of occlusion (p = 0.000): 20.7% of all occlusions of infrarenal aorta and iliac vessels occurred in smokers (8.8% NS), whereas NS showed a higher percentage of carotid artery stenosis (20.5 vs. 11.9% in smokers). 4) Postoperative morbidity and mortality did not differ between the 2 groups. There was no difference regarding primary patency rates and preoperative smoking habits. 5) The late patency rates of reconstruction of the legs were 72.4 and 52.9% for smokers 1 and 5 years after operation, which was significantly higher than in NS (65.5 and 46%). 6) The overall number of reoperations was higher in smokers than in NS (p = 0.001). 7) Smokers received significantly less often a further anticoagulant treatment than NS (40 vs. 47%; p < or = 0.05). 8) Preoperative smoking habits influenced the overall survival rate in a statistically significant manner with disadvantage for smokers (74.5 vs. 79.9 years; p = 0.000).

[Diabetes mellitus and vascular surgery: a retrospective, multivariate analysis]. / Diabetes mellitus und Gefässchirurgie: eine retrospektive, multivariate Analyse.

The influence of diabetes mellitus on the outcome of arterial reconstructions was evaluated. 25.7% of 2,735 patients (average age: 63.7 years), who underwent arterial reconstruction for arterial occlusive disease, suffered from a diabetes mellitus in need of treatment. The sex ratio within the diabetic patients was 2:1 (male:female). Regardless other influencing factors insulin-depending diabetic patients (average age: 64.6 years) were operated in average 1 year earlier than non-diabetics (average age: 65.5 years). No significant differences were found for perioperative complications. Overall, diabetic patients live significantly shorter than non-diabetics (average age: 72.8 vs. 75.8 years). Concerning the survival after the operation a stronger influence can be seen (8.3 vs. 4.4 years). The lower extremity was found to be the main localization for this negative observation on survival of patients (femoro-popliteal: 8.3 vs. 3.5 years; femoro-crural: 7.7 vs. 3.8 years). No statistical significant differences between diabetics and non-diabetics were found concerning patency rates of a reconstruction of the carotid, the aortic or the iliac arteries. There was a slight tendency pointing to a worse patency in diabetics undergoing reconstruction of the femoro-popliteal level (diabetics: 77%/1, 63%/3, 38%/5 years; non-diabetics: 80%/1, 67%/3, 58%/5 years), but this tendency did not reach statistical significance. A similar result was seen in patients with femoro-crural reconstructions (diabetics: 67%/1, 51%/3, 43%/5 years; non-diabetics: 68%/1, 56%/3, 49%/5 years). We were forced to perform a major amputation significantly more often in diabetics than in non-diabetics (13% vs. 7% after 1 year).(ABSTRACT TRUNCATED AT 250 WORDS)

[Determinants of pouch function after continence-preserving proctocolectomy]. / Determinanten der Pouchfunktion nach kontinenzerhaltender Proktokolektomie.

A prospective study was undertaken in 17 patients undergoing restorative proctocolectomy for ulcerative colitis (13 patients) or familial adenomatous polyposis (4 patients) to determine relationship between pre- and postoperative anal sphincter function, pouch characteristics and functional results. Postoperatively all manometric parameters were significantly reduced and remained so permanently. Only squeeze pressure rose to normal values again. The most important factor for a favourable functional outcome was pouch volume. A capacious reservoir was associated with a low stool frequency, low risk of incontinence and general success of the operation, as assessed subjectively. Perianal soreness with considerable skin problems occurred frequently when resting and squeeze pressures were markedly reduced postoperatively.

Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes?

Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease-stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8-85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages.