Search

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

A second primary malignancy (SPM) is frequently reported in patients with a gastrointestinal neuroendocrine tumour (NET). The majority of SPM are located in the gastrointestinal tract, but malignancies at other sites are described as well. This phenomenon might just be coincidental due to high incidence rates of asymptomatic NET lesions in patients who are operated or who undergo autopsy for another primary malignancy. However, other theories have been developed since the observed incidences rates seem to be double as high as expected. Some authors suggest a common genetic predisposition, while others report tumourigenic properties of various neuroendocrine peptides, including secretin, gastrin and cholecystokinin. This review is illustrated by a case report of a patient in whom the radiological diagnosis of a diffuse liver metastasized adenocarcinoma of the rectum changed dramatically after positron emission tomography and explorative laparoscopy to a curable adenocarcinoma of the rectum with a simultaneous well-differentiated neuroendocrine carcinoma.

The purpose of this study was to confirm the reported incidence of hyperprolactinemia in colorectal cancer and to find further evidence for an ectopic prolactin production by the tumor.Thirty two consecutive patients with an adenocarcinoma of the colon (n = 17) or the rectum (n = 15) were included. Preoperative serum prolactin concentrations were determined and correlated with CEA concentrations and tumor stages. To exclude an ectopic production by the colon cancer, prolactin concentrations were determined during the operation, in the peripheral blood and in the efferent venous drainage area of the tumor. After resection, immunohistochemical staining for prolactin was made in all resected tumors.In all except two patients with a rectal cancer, preoperative plasma prolactin concentrations were normal. Peroperative serum concentrations of prolactin were high in all patients. No significant gradient was found between the peripheral venous concentration and the local venous concentration in the drainage area of the tumor. Immunohistochemical staining for prolactin was positive in only one rectal cancer. Finally, no correlation was found between plasma prolactin concentrations and tumor stages or CEA concentrations.Our results do not support the hypothesis of an ectopic prolactin production by colon adenocarcinoma. Only in a subgroup of rectal cancers, an ectopic prolactin production remains probable. At present, prolactin cannot be recommended as a tumor marker in colorectal cancer.

Pressure pain over the abdominal aorta is a clinical sign of undetermined significance. Ultrasonographic criteria were used to define and further evaluate this variety of epigastric tenderness. The incidence of aortic pressure pain, aortic characteristics, and gastrointestinal symptoms were scored in 250 consecutive patients. The incidence was approximately 7%. All the patients with aortic pressure pain had gastrointestinal symptoms, with a significantly higher mean symptom score. The occurrence of pressure pain was independent of any of the examined aortic characteristics, age, or body mass index. We further compared the incidence of aortic pressure pain between 25 patients with irritable bowel syndrome and 25 patients without apparent functional gastrointestinal disease. It was present in approximately 50% of the patients with irritable bowel syndrome. We found pressure pain over the abdominal aorta to be associated with significant gastrointestinal discomfort. A causal relationship is possible but not proven. Aortic pressure pain can be provoked in a significant subgroup of patients with the irritable bowel syndrome.

We report a rare variant of Peutz-Jeghers syndrome identified by the presence of nasal polyposis and extreme anemia. Multiple hamartomatous polyps were found throughout the upper and lower gastrointestinal tract. We conducted a combined surgical-endoscopic approach to prevent the development of a short-bowel syndrome. The polyps removed by snare and surgical polypectomy showed features typical of harmartomas. Three colonic polyps and two nasal polyps showed histological evidence of adenomatous change. This adenomatous change seems to fit into the pathogenic sequence of hamartoma-adenoma.

We report a case of cholangitis, liver abscess, and common bile duct stones in a patient with a benign stricture at a choledochojejunal anastomosis, 3 yr after a complicated duodenohemipancreatectomy. Because surgical reintervention seemed inappropriate, a percutaneous transhepatic balloon dilation was performed after temporary internal-external biliary drainage. Extracorporeal shockwave lithotripsy (ESWL) was successfully applied to fragment all common bile duct stones, with subsequent spontaneous evacuation of all stone fragments through the dilated bilioenteric anastomosis. Only one similar case report has been published before (1), though with a different sequence of therapeutic modalities. Moreover, according to our literature review, this is the first report of ESWL of common bile duct stones by means of the Dornier Compact Lithotriptor (Dornier, Germany) with electromagnetic shockwave source.

Severe depression is characterized by anorexia and weight loss, symptoms that could endanger the patient's nutritional state. In order to investigate the nutritional state of depressed patients we determined the following in 113 healthy controls and depressed inpatients: (1) anthropometric variables such as body weight, ideal body weight (IBW), percentage of IBW, mean arm circumference, triceps skinfold thickness and arm muscle circumference, and (2) biochemical parameters such as albumin (Alb), prealbumin (Prealb), and transferrin (Tf). We were unable to detect any differences in the anthropometric parameters between healthy controls, minor and major depressed patients. Depressed patients exhibited significantly lower Alb and Tf levels than healthy controls. The drop in both plasma proteins was highly sensitive (72%) and specific (92%) for melancholia. These results may point towards the existence of a disorder in protein homeostasis or protein malnutrition without a marasmic component.

The diagnostic value of serum amylase determination for pancreatic disease has been questioned due to its lack of specificity. Several methods have been developed to separate the tissue-unspecific salivary fractions from the tissue-specific pancreatic fractions. Agarose or cellulose acetate gel electrophoresis are most suitable for clinical practice. The isoamylase patterns were studied by agarose electrophoresis in 55 patients with known pancreatic diseases (acute pancreatitis, pancreatic pseudocysts, exocrine pancreatic insufficiency and pancreatic carcinoma). Increased P-type isoamylase seems to be more sensitive than total amylase in diagnosing acute pancreatitis, while identification of the minor isoamylase P3 is more specific and could have a prognostic value. Detection of low P-type isoamylase levels is an easy method to diagnose exocrine pancreatic insufficiency. Furthermore, a group of patients with pancreatic disease (Pa), was compared with a group of patients with biliary disease without clinical evidence of pancreatic involvement (Bi), and patients with abdominal pain, without evidence of biliary or pancreatic disease (Ab). More than half of the Bi patients presented with abnormal P isoenzyme patterns, whereas 72% of the Ab patients had a normal pattern. Only P3 could distinguish between the Bi and Ab group. This might point to pancreatic involvement in patients presenting with biliary disease, only detected by isoamylase analysis.

In the treatment of polyps of the colon, clips — introduced via the colonofiberscope — have two uses

Methods have been worked out for digestion of RNA with pancreatic ribonuclease and for fractionation of the products. In appropriate conditions the hydrolysis seemed to proceed strictly according to the known specificity of the enzyme. The resulting oligonucleotides of general formula (purine nucleotide) n pyrimidine nucleotide were separated on the basis of chain length by chromatography on DEAE-cellulose in the presence of 7 M -urea. Other factors, however, influenced the separation as well. The methodology was worked out by means of yeast RNA and some of these results are presented. The distribution of purines in the bacteriophage MS2 RNA reveals a striking pattern of alternating excess ( n = 0, 2, 4, 6, 8) and deficit ( n = 1, 3, 5, 7) over the amount calculated on the basis of a random distribution. A similar rhythm is present in yeast RNA. The estimated number of the various tracts per MS2 RNA molecule are reported. There occur three octanucleotides, three nonanucleotides and two decanucleotides ( n respectively 7, 8 and 9). The minimum molecular weight, based on the decanucleotide content, amounts to 1·06 × 10 6 , which is in complete agreement with the physical value. The implications of the results, especially the rhythmic distribution, for the genetic code are discussed. It may be concluded that the sequence of triplets is not random, but subject to a higher degree of order.

In order to assess the relationship between obesity and serum lipids, a homogenous group of adult men and premenopausal women is assessed for body mass index, body fat distribution reflected by the waist/hip ratio (WHR), serum lipid parameters and apolipoproteins. Body fat distribution is distinguished in an abdominal and gluteal-femoral type using a cut-off point of 1.00 for the ratio of waist-to-hips girth for men. In women the cut-off value is considered as 0.80 but was also evaluated when considered as 0.85. In the next step tertiles for WHR are created to show a graded relationship between WHR and lipoprotein fraction. The results indicate that WHR is an important determinant for most atherosclerosis-related lipids and apoproteins: in both men (P less than 0.05) and women (P less than 0.005) WHR is significantly correlated with apolipoprotein B. Using multiple regression analysis, in women WHR seems to be the most important dependent variable, where body mass index is not significantly contributing to the explained variance. In men, however, besides WHR age is the most significant variable, although age distribution is similar in men and women. Using tertiles of WHR, we show a clear graded relationship with most lipids and lipoproteins; this gives additionally an argument to confirm that in women WHR = 0.80 is the most accurate cut-off value for abdominal obesity. This study demonstrates that both obese men and women with an abdominal fat mass distribution show a lipid and apoprotein profile that is less favorable than that seen in gluteal-femoral obese subjects insofar as the risk of coronary artery disease is concerned.

According to recent studies, vitamin D deficiency may contribute to the osteoporosis observed in elderly subjects, with reduced intestinal calcium absorption and secondary hyperparathyroidism. Vitamin D deficiency is often present in elderly people, due to inadequate diet and confinement at home. The administration of either oral vitamin D in doses of 4,000 IU per day, or six-monthly intramuscular injections of ergocalciferol 600,000 IU, combined with a daily intake of at least 1 g of calcium brings back to normal both 25 OH D concentrations and parathyroid hormone levels. When pursued for one year, these treatments also maintain the formation of cortical bone, as shown by the metacarpal index. As for the concentration of 25 OH D, it seems that 60 to 75 nmol/l are necessary to restore calcium homeostasis. The dietary habits of elderly people are such that a supplement of medicinal calcium is required. Finally, we regard the parenteral form of ergocalciferol as being preferable to the oral form at that age for better compliance with treatment.

Calcium and phosphorus metabolism was studied in 101 institutionalized subjects over 70 years of age (mean: 82.5 years). The study was performed in serum and urine; it included parathyroid hormone and calcidiol (250HD3) assays and radiological examination of bones with determination of Meunier's index and metacarpal cortical index. Calcidiol concentrations did not vary with age but were higher in people who left the institution and in men. In contrast, there was a significant age-group related increase of parathyroid hormone concentrations. This increase was accompanied by an increase of parathyroid hormone activity, as shown by a parallel fall in phosphorus reabsorption rate. These findings are in agreement with current pathogenetic theories on senile osteoporosis. Invalid subjects had higher urinary calcium and serum parathyroid hormone levels and a lower cortical index. Paradoxically, there was less vertebral collapse as evaluated by Meunier's index, which may suggest that very old patients develop progressive cortical bone hyperresorption entirely independent of sequelae from their former trabecular osteoporosis.

A group of patients with only moderately active chronic hepatitis has been studied. The follow-up was long (mean 87 months). All patients except one were treated with prednisone and/or azathioprine. Of the hepatitis B virus positive patients two-thirds developed cirrhosis between the second and fifth year of evolution, while in the hepatitis B negative group this occurred in less than one-third. The transition to cirrhosis was clinically silent. The patients were all allowed to do their normal work except in the terminal stages of cirrhosis. Five patients died of causes related to the disease: three patients with cirrhosis and hepatocellular carcinoma, one with gallbladder carcinoma, and one from bleeding varices. The high incidence of tumour, especially liver-cell carcinoma, may be due to a cumulative effect of the presence of hepatitis B virus, cirrhotic transformation, and immuno-suppression. The other patients are currently in apparently good health.

The effects of cisapride, a nondopaminolytic motility-enhancing agent, were studied in 56 patients with chronic functional dyspepsia; all had symptoms suggestive of delayed gastric emptying. The patients received 4 mg or 8 mg of cisapride or placebo orally three times daily for two successive three-week periods according to a randomized, double-blind, crossover study design. Although there was a high placebo response (55% showed good or excellent results), the global response to treatment was significantly (P = 0.024) in favor of cisapride (75% had good or excellent results). The drug was particularly superior to placebo (P = 0.03) in the improvement of a cluster of symptoms typical of postprandial discomfort, including early satiety and nausea. Side effects were minimal.

Each isoplithio peak, obtained by chromatography of a pancreatic ribonuclease digest of RNA, contains up to 2n+1 different compounds of general formula (purine nucleotide)n pyrimidine nucleotide. Methods have been worked out for the quantitative separation of respectively the mono-, di- and trinucleotide fractions by chromatography on DEAE-Sephadex columns. Complete resolution was achieved, except that rechromatography on paper was necessary to separate the positional isomers GpApCp and GpApUp from ApGpCp and ApGpUp, respectively. The quantitative distribution of two mononucleotides, four dinucleotides and eight trinucleotides in yeast RNA and in MS2 RNA is reported. The two types of RNA show certain similarities. The results of the MS2 RNA digests have been recalculated as absolute numbers of tracts per molecule and compared to a random distribution. There is a small excess of Cp and ApCp. Among the trinucleotides ApApCp is exceptionally abundant, whereas only half the expected amount of ApGpUp is found. This may mean that the former is a frequently occurring code word, and the latter only rarely or not at all.