Frequency and prognostic significance of occult tumor cells in lymph nodes in patients with adenocarcinoma of the papilla of Vater.

BACKGROUND: Occurrence of tumor relapse is frequent in patients with carcinoma of the papilla of Vater despite the absence of residual tumor detectable at primary surgery. Therefore it has to be assumed that current tumor staging procedures fail to identify minimal amounts of tumor cells disseminated to secondary organs, which might be precursors of subsequent metastatic relapse. The aim of the study was to assess the frequency and prognostic impact of minimal tumor cell spread in lymph nodes classified as 'tumor-free' in routine histopathologic evaluation. MATERIALS AND METHODS: A total of 41 'tumor-free' lymph nodes from 23 patients with adenocarcinoma of the papilla of Vater who underwent curative tumor resection (R0) were examined by immunohistochemistry with the monoclonal anti-EpCAM antibody Ber-EP4 for minimal disseminated tumor cells. RESULTS: Twelve (29.3%) of the 41 'tumor-free' lymph nodes obtained from 9 (39.1%) of the 23 patients displayed EpCAM-positive cells. Kaplan-Meier survival analysis revealed that patients with EpCAM-positive cells in lymph showed a clearly reduced relapse-free and overall survival compared with patients without such cells. However, these differences were not statistically significant (p = 0.13 for relapse-free survival, p = 0.11 for overall survival). DISCUSSION: Immunohistochemical assessment may refine the staging of resected lymph nodes in patients with carcinoma of the papilla of Vater. However, the presence of minimal disseminated tumor cells in lymph nodes had no significant impact on the prognosis in these patients.

The detection of oesophageal adenocarcinoma by serum microsatellite analysis.

BACKGROUND AND AIMS: Organ-confined oesophageal cancer in an early stage can be cured in many patients, whereas more extensive lesions have a poor prognosis. We sought to develop a non-invasive test for cancer detection and evaluation of the prognosis of the patients by using a novel molecular approach. MATERIAL AND METHODS: Matched normal-, tumour- and serum-samples were obtained from 32 patients with adenocarcinoma of the oesophagus. DNA was extracted and the samples were subjected to microsatellite analysis using 12 markers. Serum and normal samples from 10 healthy individuals served as controls. RESULTS: Twenty-seven of the 32 patients (84.4%) with malignant tumours were found to have one or more microsatellite DNA alterations in their primary tumour. Twenty-six of the 32 patients (81.3%) had alterations in the serum by microsatellite analysis. Interestingly, all patients without lymphatic metastasis and three early carcinomas (pT1pN0) already displayed LOH alteration in the serum, while all serum DNA of samples from normal control subjects were negative. Survival was not significantly correlated with either LOH in the tumour or LOH in the serum. CONCLUSION: These data suggest that microsatellite DNA analysis in serum specimens might provide a potentially valuable tool for early detection of oesophageal cancer. The evidence of circulating tumour DNA reflects the propensity of these tumours to spread to distant sites. Up to now the follow-up is still too short to draw further conclusions on the prognostic impact of this finding.

Klatskin tumors and Klatskin mimicking lesions of the biliary tree.

AIM: We report on the preoperative capability of imaging modalities and clinical assessment to differentiate between Klatskin tumors and Klatskin mimicking lesions of the biliary tree. Adenocarcinomas of the hepatic ducts (Klatskin tumors) mimic benign fibrosing cholangitis. Extensive resections carry a substantial risk but offer the only chance for cure in patients with a Klatskin tumor. METHODS: Thirty-three consecutive patients who underwent resection for suspicion of a malignant tumor of the hepatic hilum were reviewed. All patients underwent preoperative ultrasonography, computed tomography, ERCP and angiography. The patients were divided into a group of true Klatskin tumors and a group of benign Klatskin mimicking lesions. RESULTS: Twenty-seven of the resected specimens were malignant tumors, and six lesions showed only fibrosing cholangitis. Preoperative clinical presentation and imaging modalities were very similar between Klatskin tumors and fibrosing cholangitis. CONCLUSIONS: Management of obstruction of the liver hilum is dictated by the suspicion of malignancy. Complete removal of the tumor remains the therapeutic aim but clinical presentation and imaging modalities cannot help to differentiate between Klatskin tumors and Klatskin mimicking lesions prior to surgery.

Minimal residual disease in non-small-cell lung cancer.

Early metastatic relapse after complete resection (R0) of apparently localized primary tumors is frequent in patients with non-small-cell lung cancer (NSCLC). This observation indicates an occult tumor cell dissemination already present at the time of primary surgery but undetectable by current tumor staging methods. During the past 10 years ultrasensitive immunohisto-/-cytochemical and molecular assays have been developed that are able to detect single tumor cells and small tumor cell clusters present in lymph nodes classified as tumor-free by conventional histopathologic analysis, bone marrow, or peripheral blood. Here we present an overview of the incidence and prognostic impact of such early disseminated tumor cells in patients with NSCLC.

Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance.

PURPOSE: Data on skip metastases and their significance are lacking for esophageal cancer. This issue is important to determine the extent of lymphadenectomy for esophageal resection. In this study we examined the lymphatic spread in esophageal cancer by routine histopathology and by immunohistochemistry. PATIENTS AND METHODS: A total of 1,584 resected lymph nodes were obtained from 86 patients with resected esophageal carcinoma and evaluated by routine histopathology. Additionally, frozen tissue sections of 540 lymph nodes classified as tumor-free by routine histopathology were screened for micrometastases by immunohistochemistry with the monoclonal antibody Ber-EP4. The lymph nodes were mapped according to the mapping scheme of the American Thoracic Society modified by Casson et al. RESULTS: Forty-four patients (51%) had pN1 disease, and 61 patients (71%) harbored lymphatic micrometastases detected by immunohistochemistry. Skip metastases detected by routine histopathology were present in 34% of pN1 patients. Skipping of micrometastases detected by immunohistochemistry was found in 66%. The presence of micrometastases was associated with a significantly decreased relapse-free and overall survival (56.0 v 10.0 months and > 64 v 15 months, P <.0001 and P =.004, respectively). Cox regression analysis revealed the independent prognostic influence of micrometastases in lymph nodes. Lymph node skipping had no significant independent prognostic influence on survival. CONCLUSION: Histopathologically and immunohistochemically detectable skip metastases are a frequent event in esophageal cancer. Only extensive lymph node sampling, in conjunction with immunohistochemical evaluation, will lead to accurate staging. An improved staging system is essential for more individualized adjuvant therapy.

[Molecular markers in colorectal carcinoma]. / Molekulare Marker beim kolorektalen Karzinom.

Due to introduction of immunohistochemical, cytochemical, molecular and cytogenetic methods in oncologic research, understanding of genetic basis in tumor genesis is improving. Furthermore, different studies gave evidence for prognostic relevance of some (cyto)genetic alterations or residual tumor cells in lymph nodes or bone marrow, respectively. More prospective, large studies are needed, before applying these findings in clinical routine, and the methods have to be standardized.

Expression of 17-1A antigen and complement resistance factors CD55 and CD59 on liver metastasis in colorectal cancer.

Despite radical surgery, the prognosis for colorectal cancer patients with liver metastases has not changed markedly. Furthermore, no standard adjuvant therapeutic regimen has been developed. Adjuvant therapy with monoclonal antibodies (e.g., against 17-1A), which has been shown to be effective in preventing metastatic relapse in patients with Dukes' C colorectal cancer, might be a promising approach for these patients. However, the cytotoxic effects of monoclonal antibodies can be blocked by coexpression of complement resistance factors that inhibit antibody-dependent complement-mediated cytotoxicity. We therefore analyzed immunohistochemically the expression of 17-1A and the membrane-bound complement resistance factors CD55 and CD59 on metastatic tumor cells in the livers of 71 patients with colorectal carcinoma who had undergone resection of their metastases with curative intent. In 67 (94%) of 71 patients, liver metastases with homogeneous expression of 17-1A was seen. Heterogeneous expression of 17-1A was seen in four patients (6%). Heterogeneous expression of CD55 or CD59 was observed in 8 (11%) of 71 patients and 4 (6%) of 71 patients, respectively. None of the patients showed homogeneous expression of either CD55 or CD59. All patients with CD55 or CD59 expression showed homogeneous 17-1A expression, whereas none of the four patients with heterogeneous 17-1A expression was positive for CD55 or CD59. Our data indicate that 17-1A is widely expressed on liver metastases of patients with colorectal carcinoma. Therefore patients with completely resected liver metastases might be suitable candidates for adjuvant therapy with and-17-1A antibody since only a few of these lesions showed coexpression of complement resistance factors.

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer.

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.

[Changes in surgical treatment of cystic teratoma--620 cases]. / Der Wandel in der operativen Behandlung zystischer Teratome--620 Fälle.

Among 3492 patients with ovarian tumors subjected to operation between 1/1957 and 3/1994 at the Department of Obstetrics and Gynaecology at the University of Rostock 620 (17.8%) cases of teratomas were found. Histology findings, age, tumor size, bilaterality and malignity of these 620 cases were analyzed. The histologic differentiation yielded 604 (17.3%) mature teratomas (dermoid cysts), 15 monodermale and 1 immature teratoma. Division of total period in the time before and after 1990-since then we have got the possibility of laparoscopic operation-reveals that presumably by increasing use of ultrasound a decrease in mean age at time of diagnosis from 40.2 +/- 20 to 30.7 +/- 12 as well as in tumor size (9 +/- 4 resp. 4 +/- 2 cm) has been achieved. A secondary malignant transformation of epithelial component has been found in 0.5% (3/604) and bilaterality in 11% of the cases. With regard to general rules of laparoscopic operations the intact dermoid cyst enucleation is recommended in premenopausal and extirpation in postmenopausal women. For opening, reduction of volume, and removal of the dermoid cyst from the abdominal cavity, an endo-bag or endo-catch respectively should be used.

[The role of anxiety as a psychological co-factor in invasive treatment of sterility]. / Zur Rolle der Angst als psychologischer Kofaktor bei invasiver Sterilitätsbehandlung.

To prove the importance of anxiety as a disturbing factor during invasive sterility therapy 87 women of an IVF- and GIFT-series were investigated by a standardized anxiety inventory. We could not find any direct relations between breaking off stimulation and a striking level of anxiety. The role of anxiety as a co-factor in the different kinds of sterility management will be discussed.

[Early diagnosis of dermoid cysts in the treatment of sterility]. / Frühdiagnose von Dermoiden während der Sterilitätsbehandlung.

Two cases of occult dermoid cysts in sterility patients were reported. In one case the follicular puncture during a gamete intra fallopian transfer (GIFT) trial led to diagnosis, in the other case it has been argued by sonography. Early diagnostic and subsequent therapeutic possibilities were discussed.

[Pregnancy following gamete intra-fallopian transfer (GIFT)]. / Schwangerschaft nach GIFT.

In the present paper we will report on a pregnancy following a Gamete Intra Fallopian Transfer (GIFT). This is a 26 years old female, treated in our sterility dispensaire for a secondary sterility since 1982. All basic hormone levels were normal. The andrological examination of her husband showed an oligozoospermia stage 2. A following hormone treatment was unsuccessful. Stimulation, monitoring and laparoscopy are demonstrated.

[Report of experiences in 20 years use of intrauterine fetal transfusion in severe Rh-induced hemolytic disease of newborn]. / Erfahrungsbericht über 20 Jahre der Anwendung der intrauterinen fetalen Transfusion bei schwerem Rh-bedingten Morbus haemolyticus fetalis.

136 intrauterine transfusions in 90 fetuses between the 25th and 34th gestational week with severe hemolytic disease because of Rh-incompatibility have been performed after a prenatal step by step diagnostic in the years 1967 till 1986. The reason of the immunization was mistransfusion or omitted immune prophylaxis in 25 cases. 25 from 67 live born children died. There were 23 still births. 34 from 43 fetuses without hydrops survived, but only 8 from 47 fetuses with hydrops. The survival rate over all was 46.7 per cent.

[Psychological studies of sterile couples within the scope of an in vitro fertilization program]. / Psychologische Untersuchungen steriler Ehepaare im Rahmen eines In-vitro-Fertilisationsprogrammes.

The results of a psychological individual and process diagnostic programme at sterility patients undergoing an in-vitro-fertilization and embryo transfer are demonstrated. The women showed an optimistic emotional disposition and negation of conflict or trouble experience during their stay in the hospital. From the day of laparoscopy till embryo transfer a short labilization sets in, i.e. a slight deterioration of the emotional disposition as an expression of a phase of stress compensation. Questions of motivation, partner constellation and special personality characteristics are discussed.