Whole-body MR imaging versus sequential multimodal diagnostic algorithm for staging patients with rectal cancer: cost analysis.

PURPOSE: To compare the direct costs of two diagnostic algorithms for pretherapeutic TNM staging of rectal cancer. MATERIALS AND METHODS: In a study including 33 patients (mean age: 62.5 years), the direct fixed and variable costs of a sequential multimodal algorithm (rectoscopy, endoscopic and abdominal ultrasound, chest X-ray, thoracic/abdominal CT in the case of positive findings in abdominal ultrasound or chest X-ray) were compared to those of a novel algorithm of rectoscopy followed by MRI using a whole-body scanner. MRI included T 2w sequences of the rectum, 3D T 1w sequences of the liver and chest after bolus injection of gadoxetic acid, and delayed phases of the liver. The personnel work times, material items, and work processes were tracked to the nearest minute by interviewing those responsible for the process (surgeon, gastroenterologist, two radiologists). The costs of labor and materials were determined from personnel reimbursement data and hospital accounting records. Fixed costs were determined from vendor pricing. RESULTS: The mean MRI time was 55 min. CT was performed in 19/33 patients (57%) causing an additional day of hospitalization (costs 374 euro). The costs for equipment and material were higher for MRI compared to sequential algorithm (equipment 116 vs. 30 euro; material 159 vs. 60 euro per patient). The personnel costs were markedly lower for MRI (436 vs. 732 euro per patient). Altogether, the absolute cost advantage of MRI was 31.3% (711 vs. 1035 euro for sequential algorithm). CONCLUSION: Substantial savings are achievable with the use of whole-body MRI for the preoperative TNM staging of patients with rectal cancer.

Optimised surgery (so-called TME surgery) and high-resolution MRI in the planning of treatment of rectal carcinoma.

BACKGROUND: Since November 1998, we have applied the concept of total mesorectal excision (TME) to rectal carcinoma together with a standardised pathological quality assessment. Participation in the European MERCURY study [The MERCURY Study Group Radiology (in press), 2006] required us to establish the indication for neoadjuvant radiochemotherapy on the basis of an magnetic resonance imaging (MRI) scan. The aim of the present retrospective study is to evaluate the quality of the surgery, the efficacy of the MRI and the oncological outcomes achieved. MATERIALS AND METHODS: Between November 2001 and October 2005, 68 out of 109 patients with carcinoma of the rectum were submitted to radical surgery in curative intent and 23/68 (34%) were given neoadjuvant therapy. In an interdisciplinary study group, each patient was evaluated pre-operatively and post-operatively using standardised MRI and histopathological methods. RESULTS: The quality of surgery was established on the basis of the pathological examination of the surgical specimen. The rates of incomplete mesorectal excision, intra-operative tumour cell dissemination and positive circumferential margins were all low at 4%, 7% and 3%, respectively. The effectiveness of MRI proved to be greatest in predicting the tumour status at the circumferential resection margin: in the admittedly limited number of patients it proved possible to correctly predict the tumour status for every patient. The assessment of the anatomic extent of the primary tumour and of the regional lymph node metastasis according to the TNM system, in contrast, was considerably less successful at 73% and 75%, and 37% and 57%, respectively. CONCLUSION: By applying the TME concept and MRI-based therapy planning, excellent results can be achieved and, at the same time, the number of patients requiring neoadjuvant treatment is considerably reduced.

On the role of gastrin-releasing peptide in meal-stimulated exocrine pancreatic secretion.

The contribution of gastrin-releasing peptide (GRP) in the physiologic pancreatic response to a meal is unknown. We therefore investigated whether immunoneutralization of GRP could influence the exocrine pancreatic response to a meal as well as plasma concentrations of the peptide hormones neurotensin (NT) and cholecystokinin (CCK). Modified Herrera fistulas were implanted in five mongrel dogs. After a standard meal, we analyzed plasma NT, CCK, and GRP, and protein and enzyme (amylase, lipase, trypsin) content of exocrine pancreatic juice. An unspecific rabbit immunoglobulin solution was administered intravenously as a control. This experiment was repeated with a specific anti-GRP-immunoglobulin. The i.v. administration of the anti-GRP-antibody significantly inhibited meal-stimulated pancreatic secretion. Integrated protein output decreased from 58.4 to 36.8 g/180 min (p < 0.05), as did amylase (2,102 to 1,145 KU/180 min; p < 0.05), lipase (2,258 to 1,172 KU/180 min; p < 0.05), and trypsin (5,321 to 4,990 U/180 min). Postprandially released NT decreased from 8,271 to 5,825 pmol/180 min (p < 0.05). In contrast, integrated amounts of CCK remained relatively stable with 473 to 611 pmol/180 min. The neuropeptide GRP is one of the biologically important regulatory factors influencing meal-stimulated pancreatic secretion, as well as the postprandial plasma level of the peptide hormone NT in the dog. These mentioned effects of postprandially released GRP seem not to be mediated by CCK in an endocrine manner.

[Unusual diagnosis in recurrent arthritis, erythema nodosum and arrhythmia]. / Ungewöhnliche Diagnose bei rezidivierender Arthritis, Erythema nodosum und Herzrhythmusstörungen.

HISTORY AND ADMISSION FINDINGS: A 42-year-old woman, with recurrent arthritis of the large joints and erythema nodosum for 7 years, was admitted because of recent onset of bouts of rapid heart rate. A 2/6 systolic murmur at Erb's point was the only contributory finding on physical examination. INVESTIGATIONS: The transaminases and gamma-GT were elevated, as were total cholesterol, LDL fraction, IgM, total protein, gamma-globulin and IgM. Antimitochondrial antibodies, especially anti-M2, were positive, while rheumatoid factor and C-reactive protein were negative. ANA, ANCA and antibodies against double-strand DNA were not demonstrated. ENA screening was negative. Abdominal computed tomography showed discrete intrahepatic cholestasis. Liver biopsy revealed chronic destructive cholangitis, i.e. the early stage of primary biliary cirrhosis. TREATMENT AND COURSE: On treatment with ursodeoxycholic acid (10 mg/kg daily) the patient has remained free of symptoms for 3 years and laboratory tests no longer showed evidence of impaired liver function. CONCLUSION: Primary biliary cirrhosis should be included in the differential diagnosis of recurrent arthritis and erythema nodosum, as early treatment with ursodeoxycholic acid can favourably influence its course.

Etiology and age have only a limited influence on the course of acute pancreatitis.

In a retrospective study of 602 patients with a first attack of acute pancreatitis, it was investigated whether the etiology of the disease and age of the patient are negative factors. There was no significant difference concerning hospital stay, respiratory and renal insufficiency, indication for surgery, or mortality rate among the different etiological groups. However, pancreatic pseudocysts developed significantly more frequently in alcoholics than in patients with other etiologies (p < 0.001 to p = 0.007). There was also no difference concerning hospital stay and respiratory insufficiency among the age groups. The increased incidence of renal insufficiency probably is related to physiological alteration with age, but the indication for dialysis did not increase. Pancreatic pseudocysts were more frequent in patients between 31 and 40 years of age, which was also the peak age group of alcoholics. Indication for surgery was the same for all age subgroups. The increase in mortality rate with age was weakly significant (p = 0.049). For the etiological subgroups, an increase in mortality with age was found only for biliary pancreatitis patients (p = 0.003). It is concluded that etiology and age of the patient have only limited influences on the course of acute pancreatitis.

Morbidity and mortality in 602 patients with acute pancreatitis seen between the years 1980-1994.

The course of a first attack of acute pancreatitis was evaluated in a retrospective study of 602 patients, who were admitted between 01.01.1980 and 30.09.1993 to the Centers of Internal Medicine and Surgery of the University of Göttingen (n = 417) and from 16.11.1986 to 30.06.1994 to the Municipal Hospital of Lüneburg (n = 185). Etiology was biliary tract disease in 227 (37.7%), alcohol abuse in 177 (29.4%), unknown in 133 (22.1%), and other causes in 65 (10.8%) patients. Mean hospital stay was 27.9 +/- 24 days (x +/- SD), median 23 days. Pancreatic pseudocysts developed in 14.3% of the patients, and surgical treatment was necessary in 11.1%. Within the first 48 hours, respiratory insufficiency was observed in 63.2% of the 204 patients undergoing arterial blood gas analysis while renal impairment occurred in 32.6% of 602 patients. Artificial ventilation was indicated in 12.5%, and dialysis in 7% of the patients. Mortality rate was 6.1%, correlating significantly with respiratory and renal impairment and procedures in connection with these complications and also with transfers from other hospitals.

[Individual therapeutic procedure in metastatic carcinoid of the small intestine]. / Individuelles therapeutisches Vorgehen beim metastasierten Dünndarmkarzinoid.

Actually, the therapeutic goal in a metastasized carcinoid tumor is rather symptomatic than curative. Here we report the case of a 53 year old woman with a hepatic and pulmonal metastasized carcinoid tumor of the small intestine. We will discuss current therapeutic options and the approach to the individual patient. After treatment with the standard therapeutics Octreotide and Interferon alpha we could achieve a remarkable and persistent remission by applying the rather unusual drug Dacarbacine in this patient. This is an example for the frequently occurring clinical situation in the treatment of patients with rare tumors requiring the application of individually modified therapeutic regimens. Furthermore, the potency of Dacarbacine in the treatment of carcinoid tumors seems to be underestimated up to now.

Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP): both are necessary for diagnosing or excluding chronic pancreatitis.

Results of the SPT and the ERCP staged for their severity were compared in 202 patients. The correlation between both investigations was significant (p < 0.001); however, ERCP showed significantly more severe changes (p = 0.04). Furthermore, we found that 129 (64%) patients had parallel SPT and ERCP results, matching in all four gradings of severity. Forty-three (21%) patients had abnormal results for both SPT and ERCP, but the severity gradings did not parallel. Finally, 30 (15%) patients showed totally nonparallel results, a normal SPT and abnormal ERCP, or vice versa. Abnormal ERCP but normal SPT results were found in 23 of these 30 patients (group 1), and normal ERCP but abnormal SPT results in the seven remaining cases (group 2). In the first group, more patients had a history of acute pancreatitis compared to the second group (19 vs. one, p < 0.005). Based on medical history, laboratory and functional test results, and other morphological tests, chronic pancreatitis was diagnosed in two of 23 patients in group 1 and in all seven patients in group 2. Follow-up interviews (86 +/- 54 months) were possible in 20 of the remaining 21 patients in group 1 and showed definite chronic pancreatitis in one and probable chronic pancreatitis in another two of them, whereas in the other 17 patients no symptoms of acute pancreatitis or abdominal pain suggestive of chronic pancreatitis had occurred. In conclusion, both SPT and ERCP should be used to complement each other when chronic pancreatitis is suspected. ERCP seems to over-diagnose the disease since duct changes may only reflect scars after severe acute pancreatitis, or old age, and are not necessarily a sign of chronic pancreatitis. SPT seems to diagnose chronic pancreatitis with more reliability.

Effect of a platelet-activating factor antagonist on pancreas perfusion after 24 h of ischemia.

Platelet-activating factor (PAF) is a strong mediator of inflammation that is present in many mammalian tissues and cell types. In the pancreas, PAF can be synthesized in acinar cells after stimulation with secretagogues. The present study uses a perfused porcine pancreas model to investigate the role of PAF in pancreatic ischemia and the effect of the PAF antagonist bepafant on pancreas preservation. Pancreata were preserved with or without bepafant, stored for 24 h at 4 degrees C, and then reperfused at 37 degrees C in a perfusion chamber. Reperfusions were significantly improved by the addition of bepafant. This was indicated by a significantly increased arteriovenous volume flow (16.54 +/- 1.88 ml/min versus controls 8.54 +/- 1.31 ml/min; p = 0.0068; bepafant, n = 7; controls, n = 12) and a reduced vascular resistance (p = 0.0068; bepafant, 1.95 +/- 0.22 mm Hg * min/ml versus controls 4.08 +/- 0.56 mm Hg * min/ml). Radioimmunological quantification of PAF in pancreatic tissue revealed that PAF levels remain unchanged during storage in a cold protective solution at 4 degrees C but increase significantly during surgical pancreas preparation under general anesthesia (from 142.1 +/- 21.2 to 368.8 +/- 52.5 pg/g; n = 15; p = 0.0007). The present study shows that bepafant improves pancreas preservation after cold ischemia. The beneficial effect might be explained by antagonizing inflammatory and vasoconstrictory responses to PAF synthesized during surgical pancreas preparation.

Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and clonidine.

A 69-yr-old man with known carcinoid syndrome treated with octreotide and interferon-alpha 2b developed diarrhea, with six to eight watery to semiliquid stools per day. Diminished stool frequency and increased stool consistency were obtained by treatment with the 5-hydroxytryptamine-3 receptor antagonists ondansetron and tropisetron. Successful alleviation of the diarrhea was also observed with the alpha 2-receptor agonist clonidine. These observations indicate that these classes of drugs should be evaluated in a controlled trial in patients with carcinoid-associated diarrhea.

[Pancreatic function and quality of life after resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized comparative study after duodenum preserving resection of the head of the pancreas versus Whipple's operation]. / Pankreasfunktion und Lebensqualität nach Pankreaskopfresektion bei der chronischen Pankreatitis. Eine prospektive, randomisierte Vergleichsstudie nach duodenumerhaltender Pankreaskopfresektion versus Whipple'scher Operation.

Given an indication for surgery in patients with chronic pancreatitis, such as distal common bile duct obstruction, duodenal stenosis, or dilated pancreatic duct with stones and congestion, the surgeon must decide the type of operation to perform. A duodenopancreatectomy, the Whipple procedure, is widely considered to be the gold standard. It is highly effective in relieving pain and eliminating the structural abnormalities noted above. Duodenum-preserving resection of the head of the pancreas (DPRHP) seems to be an attractive alternative to pancreaticoduodenectomy (PD) in the treatment of chronic pancreatitis. In a clinical prospective randomized trial the efficiency of both operative methods was investigated. Between 7/1987 and 12/1993 43 patients were randomly assigned to undergo either a Whipple procedure (n = 21) or DPRHP (n = 22). Data on postoperative course, mortality, and postoperative morbidity were compiled. As concerns long-term results, postoperative hormonal status (insulin, neurotensin, cholecystokinin, gastrin) was checked, basal and stimulated with a standardized meal, using standard hormonal assay kits. All patients with PD survived, whereas one with DPRHP died from peritonitis. Patients with DPRHP had a significant more rapid convalescence (16.5 vs. 21.7 days). The range for postoperative follow-up is from 36 months to 5.5 years. In the DPRHP group 18 patients are in good condition. Two had diabetes and one developed carcinoma. In the PD group one died from hepatic coma, 14 are in good condition and 6 developed diabetes. All gained body weight with an average of 6.4 vs. 4.9 kg, DPRHP vs. PD. A difference between DPRHP and PD was obvious for the postoperative hormonal status. Results are satisfactory in both groups. For patients with DPRHP however, we see a quicker convalescence and a significant benefit as concerns postoperative hormonal status.

Treatment of metastasized midgut carcinoids with dacarbazine.

Seven patients with metastasized midgut carcinoids were treated with intravenous infusion of dacarbazine [dimethyltriazenoimidazole carboxamide (DTIC)] (650 mg/m2) every 4 wk. After 2 wk, white blood cell counts decreased transiently in three patients. No other DTIC-associated side effects occurred. Biochemical markers of disease activity decreased significantly in four patients for 4-20 months (mean duration, 12 months). Size of hepatic metastases was reduced or remained unchanged in six patients for 6-20 months (mean duration, 10 months). Clinical symptoms such as cutaneous flush, diarrhea, abdominal pain, constipation, night sweat, or weight loss improved in six of seven patients. We conclude that DTIC represents a useful therapeutic option in the treatment of advanced and metastasized carcinoid tumors.

Gastrin-releasing peptide and CCK after intraduodenal inhibition of proteases in dogs.

The intraduodenal application of a potent protease inhibitor (camostate, 600 mg) causes a significant increase in basal pancreatic secretion in the manner of a negative-feedback mechanism. The integrated protein secretion during the entire study period was 9.9 +/- 1.8 g in 120 min. The iv application of anti-GRP immunoglobulin caused a significant reduction to 5.0 +/- g in 120 min. No significant changes in the plasma concentrations of GRP and CCK were detectable. The increased secretion occurring after the administration of the protease inhibitor could be mediated by neural GRP-dependent mechanisms. These may also be relevant for CCK-dependent factors, which are only briefly mentioned.

Detection of the human glucagon-like peptide 1(7-36) amide receptor on insulinoma-derived cell membranes.

125I-glucagon-like peptide 1(7-36)amide was covalently cross-linked to a specific binding protein in human insulinoma cell membranes. A single radiolabeled band at M(r) 63,000 was identified by SDS-PAGE after solubilization of the ligand-binding protein complex. The molecular weight of this apparent GLP-1 receptor in human endocrine pancreatic tissue was of identical size as the GLP-1 receptor on rat insulinoma-derived RINm5F cell membranes. The radiolabeled band was undetectable when 1 microM of unlabeled GLP-1(7-36)amide or of the GLP-1 antagonist exendin(9-39)amide was included in the binding assay. Utilizing isolated poly-A+ RNA from the human insulinoma and a 1,500 bp Eco-RI fragment of the cDNA coding for the rat GLP-1(7-36)amide receptor for Northern blot analysis, a main hybridization signal at about 7 kb was found by Northern blotting. Our data provide the first direct evidence of the existence of GLP-1 receptors in human endocrine pancreatic tissue.

Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group.

BACKGROUND: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. METHODS: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. RESULTS: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups. CONCLUSIONS: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

The effect of different solutions for organ preservation on immediate postischemic pancreatic function in vitro.

The present study compares the effect of organ preservation with Euro-Collins solution, cardioplegic histidine-tryptophan-ketoglutarate solution, and University of Wisconsin solution on immediate pancreatic function after cold storage at 4 degrees C for 24 hr. Postischemic organ quality of a porcine pancreas preparation was tested by quantification of physiological and biomedical parameters in a one-line reperfusion system. During reperfusion with a constant arterial pressure the arteriovenous flow rate was significantly higher for HTK (5.7 +/- 0.91 ml/min, n = 8; P < 0.05 vs. EC) and UW (7.4 +/- 0.81 ml/min, n = 8; P < 0.05 vs. EC) than for EC (3.0 +/- 0.26 ml/min, n = 6). The lowest lactate content in the reperfusate was found after HTK protection (HTK, 64.0 +/- 7.2 mumol/50 ml, n = 8; versus EC, 114.2 +/- 1.7 mumol/50 ml, n = 6, P < 0.001; versus UW, 148.0 +/- 28.6 mumol/50 ml, n = 8, P < 0.05). Amylase in the venous effluent was significantly lower (P < 0.05) for HTK or UW protection than for EC (HTK, 189 +/- 72.6 U/ml; UW, 188 +/- 39.4 U/ml; EC, 416 +/- 71.7 U/ml). Oxygen consumption during reperfusion was significantly higher for HTK (2.15 +/- 0.22 microliters/g/min, P < 0.001) and UW (1.80 +/- 0.52 microliters/g/min, P < 0.05) than for EC (0.47 +/- 0.13 microliters/g/min). We conclude that immediate postischemic organ quality and pancreatic function after protection with HTK is not inferior to preservation with UW.

Effect of camostate administration for two weeks on experimental pancreatitis in mice and rats.

The present study investigates the effect of oral pretreatment with the protease inhibitor camostate on the outcome of pancreatitis in three experimental models. In pancreatitis induced by overstimulation with cholecystokinin (CCK) in rats, pancreatic enzymes and the histological degree of pancreatitis were quantified; in pancreatitis induced by a choline-deficient ethionine-supplemented (CDE) diet in mice, the effect on survival was monitored; and in bile-induced pancreatitis in rats, the effect on survival, pancreatic enzymes, and histology was studied. Feeding of camostate (200 mg/kg/day) for 2 weeks worsened the histological degree of pancreatitis induced by overstimulation with CCK or by injection of taurocholate. The concentration of amylase in the pancreas and in serum was significantly lower after pretreatment with camostate, both in cerulein-induced pancreatitis and in bile-induced pancreatitis, while the concentration of trypsin in the pancreas was significantly increased in the camostate-treated animals. Pretreatment with camostate significantly lowered survival. In pancreatitis induced by a CDE diet, 3 of 20 mice survived the observation period, while 9 of 20 control animals survived (p < 0.05). In taurocholate-induced pancreatitis, 5 of 29 rats were alive after 3 days versus 18 of 30 animals in the control group (p < 0.001). CCK levels were not elevated in camostate-treated rats, when pancreatitis was induced 24 h after finishing camostate feeding. It is concluded that camostate induced pancreatic hypertrophy and increased concentration of proteolytic enzymes aggravate experimental panceatitis and that this is not mediated by increased CCK levels.