Background: The effectiveness of laparoscopic Nissen fundoplication (LNF) was assessed in patients with chronic gastroesophageal reflux disease (GERD) using pH study and different quality-of-life indexes. We correlated both types of data and hypothesised that improvement in quality of life following LNF does not necessarily correlate with improvement in pH values.Methods: Seventy patients presenting with typical symptoms of GERD (14 with Barrett's esophagus) underwent LNF between May 1997 and December 2000. All patients were evaluated both prior to and 3 months after surgery using 24-h pH study, endoscopy, and a validated quality-of-life questionnaire.Results: Following LNF. reflux was reduced to normal in all but six patients. Howevers despite persistent reflux, the Gastrointestinal Quality of Life Index (GQLI), of these six patients improved postoperatively from 79.5 +/- 2.2 to 111.7 +/- 8.3. These results correlate with those of patients who had normal postoperative pH studies-namely, 88.5 +/- 19.3 to 112 +/- 16.7. There was no difference in quality-of-life improvement between patients with Barrett's esophagus and those without it.Conclusion: There is only a weak correlation between quality-of-life assessment and pH study. Because the patient's quality of life is likely to improve following LNF, an objective means parameter of assessing the effectiveness of antireflux surgery, such as pH study or endoscopy, is recommended.

Parathyroid Hormone-related Protein (PTHrP), ein funktionelles Analogon zum Parathormon, ist in 63% der primären Mammakarzinome [1] and in 92% der ossären Mammakarzinom-Metastasen nachweisbar [2]. Bisherige Untersuchungen zeigten, daß der Grad der PTHrP-Expression mit der Inzidenz ossärer Filialisierung korrelierte [3]. In einer prospektiven Studie [4] wurde zum Nachweis minimaler Tumorzelldissemination mittels Reverse-Transkription/Polymerase-Kettenreaktion(RT/PCR)-Technik bei n = 71 primären Mammakarzinom-Patientinnen (Pat.) das PTHrP im Knochenmark (KM) und im peripheren Blut (PB) untersucht. Im Nachbeobachtungszeitraum von 27 Monaten (Median) bestätigte sich bei 7/17 Pat. mit initial positivem PTHrP-Nachweis im PB and/oder KM das potentiell erhöhte Rezidivrisiko durch das Auftreten von 4 lokalen and 3 ossären Rezidiven. Aufgrund der Ergebnisse dieser fortgesetzten Studie sollte in zellbiologischen Untersuchungen am Tumorgewebe von Pat. mit einem primären Mammakarzinom, an Tumorzell-Linien, im KM-Mikromilieu and an CD34+ hämatopoetischen Vorläuferzellen aus PB geklart werden, ob PTHrP ein für die Tumorzellproliferation verantwortlicher autokriner/parakriner Wachstumsfaktor ist.

Background: Breast cancer tissues express parathyroid hormone-related protein (PTHrP) and as shown in previous studies the level of PTHrP expression in the primary tumor correlates with the incidence of bone metastasis. Methods/Results: Analysing 49 primary breast cancer tissues by reverse transcription based RT/PCR methods we found an expression of PTHrP in 48/49 patients with a coexpression of the PTH/PTHrP receptor in 42 patient samples. Coexpression of PTHrP and its receptor was also shown in all of five breast cancer cell lines MCF-7, MDA-MB-231, MDA-MB-468, DU 4475 and SK-BR-3. Looking for an autocrine growth modulating loop of PTHrP in breast cancer these cell lines were used as in vitro models for growth stimulation with hPTHrP (1-40). The growth of MCF-7 and MDA-MB-468 as well as the cell line MDA-MB-231, which was unresponsive to exogenous PTHrP, was reduced by a neutralizing monoclonal antibody against PTHrP. In all of the five breast cancer cell lines incubation with hPTHrP(1-40) led to a decrease in PTHrP expression, whereas the expression of the PTH/PTHrP receptor was unchanged. Looking for paracrine sources of PTHrP in normal human bone marrow (bm) and peripheral blood (PB) we investigated hematopoietic and osteoblast cells. In hematopoietic cells only a low-level expression of PTHrP was detected by PCR analysis, by in situ hybridisation and immunocytology in the CD34(+) fraction of peripheral blood stem cell harvests of healthy allogeneic stem cell donors and on the level of early hematopoietic progenitors in stem cell assays (CFU-A). In normal human osteoblast cells and cells of the osteoblast-like osteosarcoma cell line H0S58 expression of PTHrP was found by PCR both on day 1 and on day 32 of cell culture. Conclusion: In conclusion we documented an autocrine growth modulating loop for breast cancer cells by PTHrP, which might be fueled in a paracrine fashion by osteoblasts and hematopoietic progenitor cells (CD34(+)) in the early phase of breast cancer metastasis to the bone.

At the time of surgery, occult metastases (micrometastases) are present in more than 50% of colorectal cancer patients, and the liver is the most frequent site of apparent metastatic disease. Frequently, adjuvant chemotherapy is unable to prevent tumor recurrence. Thus, novel therapeutic strategies are warranted. The aim of this study was to establish a model of human colon cancer metastatic to the liver of nude mice, to assess, in this setting, the therapeutic efficacy of radioimmunotherapy (RAIT) compared to standard chemotherapy and to evaluate, in a Phase I/II trial, the toxicity and therapeutic efficacy of RAIT in colorectal cancer patients with small volume disease metastatic to the liver. Multiple liver metastases of the human colon cancer cell line GW-39 were induced by intrasplenic injection of a 10% tumor cell suspension. Whereas controls were left untreated, therapy was initiated on day 10 or 20 after tumor inoculation with the 131I-labeled, low affinity anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAb), F023C5 (Ka = 10(7) liters/mol), or the high-affinity anti-CEA MAb, MN-14 (Ka = 10(9) liters/mol), or chemotherapy (5-fluorouracil/leucovorin (folinic acid) versus irinotecan) at their respective maximum tolerated doses (MTDs). Twelve colorectal cancer patients with small volume disease metastatic to the liver (all lesions < or = 2.5 cm) were entered into a mCi/m2-based Phase I dose escalation study with 131I-labeled humanized version of MN-14, hMN-14. The patients were given single injections, starting at 50 mCi/m2 and escalating in 10-mCi/m2 increments. The MTD was defined as the dose level at which < or = 1 of 6 patients develop grade 4 myelotoxicity. In the mice, untreated controls died from rapidly progressing hepatic metastases at 6-8 weeks after tumor inoculation. The life span of mice treated with 5-fluorouracil/leucovorin was prolonged for only 1-3 weeks, whereas irinotecan led to a 5-8-week prolongation. In contrast, at their respective MTDs, the 131I-labeled low-affinity anti-CEA MAb, F023C5, led to a 20% permanent cure rate, and the high affinity MAb, MN-14, led to an 80% permanent cure rate, when therapy was initiated at 10 days after tumor inoculation. In the 20-day-old tumor stage, although it prolonged life, 131I-F023C5 was unable to achieve cures, whereas 131I-MN-14 was still successful in 20%. Histologically, no remaining viable tumor cells could be demonstrated in these animals surviving > 6 months. In patients, the MTD was reached at 60 mCi/m2 of hMN-14 (at 70 mCi/m2, two of three grade 4 myelotoxicities). Of 11 assessable patients, 2 had partial remissions (corresponding to an objective response rate of 18%), and 5 (45%) had minor/mixed responses or experienced stabilization of previously rapidly progressing disease. These data suggest that in small volume disease, RAIT may be superior to conventional chemotherapy. Antibodies of higher affinity seem to be clearly superior. The clinical response rates in patients with small volume disease are encouraging, being comparable to the response rates of conventional chemotherapeutic regimens but with fewer side effects. Ongoing studies will show whether treatment at the MTD will further improve therapeutic results.

Since 10/1994 the Interdisziplinäre Kurzzeit-Onkologie (IKO) is an outpatient department for the treatment of patients with cancer used by the departments of hematology/oncology and surgery. Between 09/1995 and 02/1997, 818 patients received 2024 cytotoxic therapies with neoadjuvant (15%), adjuvant (65%) or palliative (20%) intention-mostly within multicenter clinical studies. Ambulatory operations like removal of lymph nodes for diagnosis or the implantation of venous catheter systems prepared the way for specialized modalities of cancer therapy. The high compliance and consent of patients, combined with better understanding of cancer therapy, resulted in an enhanced quality of life and optimized therapy. Standardization in diagnostics and fast realisation of interdisciplinary treatment schedules lead to reduction of costs and to enhancement of quality and security in cancer therapy.

A sensitive and precise radioimmunoassay has been developed. Cholecystokinin (CCK) was labeled by the Bolton-Hunter method. The antibody bound CCK8 and CCK33. The binding sites of the antibody are located by the sulfated tyrosil group in position 27 of the CCK molecule. Human duodenum tissue contains larger forms of CCK33 as well as CCK33 and CCK8.