F. Fend - Academia.edu (original) (raw)
Papers by F. Fend
Chirurgisches Forum 2007, 2007
Introduction: graft dysfunction after liver transplantation due to ischemia-/reperfusion injury r... more Introduction: graft dysfunction after liver transplantation due to ischemia-/reperfusion injury remains a serious clinical problem although there is a marked progress in transplantation medicine. The aim of this experimental study was to compare different types of reperfusion with regard to the ischemia-/ reperfusion injury. Materials and Methods: arterialised orthotopic liver transplantation (OLT) was performed in syngenic male Lewis rats. The animals were devided into 3 experimental groups: I-and II-control groups with antegrade reperfusion, III-retrograde reperfusion group. Laboratory parameters as well as histopathologic changes of the graft were evaluated 1, 24 and 48 hours after the OLT. Results: 24 hours after the OLT the GOT-values showed a significant difference between groups with antegrade/retrograde variant of reperfusion (2613,3 ± 343,9 U/l vs. 1186,4 ± 252,9 U/l; p < 0,001). The GPT-and GOT-values were significanly lower in the group III 48 hours after OLT. The histopathologic evaluation revealed a significantly lower number of necrotic areas in the group III compared to the control-groups (p < 0,002). Conclusion: our results show that the retrograde reperfusion (from the infrahepatic V. cava inferior with opening of the blood stream to the supra-hepatic V. cava inferior and to the Vv. hepaticae retrograde to the liver) has a protective effect on the graft.
Deutsche medizinische Wochenschrift (1946), 2014
amyloid-p-component and kappa light chains could be found. In the bone marrow biopsy plasma cells... more amyloid-p-component and kappa light chains could be found. In the bone marrow biopsy plasma cells were not increased indicating primary immunglobulin light chain (AL) amyloidosis. Conclusion: Prognosis of amyloidosis depends on the type of amyloid and extension of disease. Therefore, an early as possible diagnosis and classification are essential for an adequate therapy.
Human Pathology, 2011
Acquired chromosomal aberrations, including gene copy number alterations, are involved in the dev... more Acquired chromosomal aberrations, including gene copy number alterations, are involved in the development and progression of human malignancies. SOX2, a transcription factor-coding gene located at 3q26.33, is known to be recurrently and specifically amplified in squamous cell carcinomas of the lung, the esophagus, and the oral cavity. In these organs, the SOX2 protein plays an important role in tumorigenesis and tumor survival. The aim of this study was to determine whether SOX2 amplification is also found in squamous cell carcinomas in other organs commonly affected by this tumor entity. In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung. Applying fluorescence in situ hybridization, we assessed squamous cell carcinomas of the cervix uteri (n = 47), the skin (n = 57), and the penis (n = 53) for SOX2 copy number alterations and detected amplifications in 28%, 28%, and 32% of tumors, respectively. Furthermore, we performed immunohistochemical SOX2 staining and found that SOX2 amplification is significantly associated with overexpression of the corresponding protein in squamous cell carcinomas (P b .001). Of the lung cancer entities with neuroendocrine differentiation, only small cell cancers and large cell cancers exhibited SOX2 or TTF1 amplifications at significant frequencies, indicating that at least a subset of these might be dedifferentiated forms of ☆ No conflict of interest. ☆☆ This study was approved by the Institutional Review Board of the University Hospital of Tuebingen (512/2009BO1).
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2010
Zeitschrift für Gastroenterologie, 2013
Transplantation Journal, 2010
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2011
Hintergrund: Die gültigen TNM-Klassifikationen sind die Grundlage für Entscheidungen zur Diagnost... more Hintergrund: Die gültigen TNM-Klassifikationen sind die Grundlage für Entscheidungen zur Diagnostik und Therapie von Krebskrankheiten. Die Histopathologie muss die sachgerechte Einordnung des Tumorbefundes in diese Klassifikationen ermöglichen. Methoden: Zur Bestimmung der Mitoserate des primären Melanoms und zur Aufarbeitung und Beurteilung des Wächterlymphknotens wurde eine systematische Literaturrecherche durchgeführt. Auf der Grundlage der Literaturrecherche wurden Empfehlungen erarbeitet, die von einem Expertengremium aus Dermatohistologen und Pathologen diskutiert und abgestimmt wurden. Ergebnisse: Die folgenden Empfehlungen wurden mit hohem Konsens abgestimmt (93-100 % Übereinstimmung): Die Bestimmung der Mitoserate bei primären Melanomen erfolgt anhand von HE-Schnitten. Die Beurteilung von 1 mm 2 ist ausreichend. Es werden lediglich dermale Mitosen berücksichtigt und in ganzen Zahlen angegeben. Die Mitoserate soll bei Primärtumoren Յ1,00 mm Tumordicke nach der Hot-Spot-Methode bestimmt werden und als ganze Zahl in Relation zu 1 mm 2 Tumorfläche angegeben werden. Bei dickeren Primärtumoren ist die Angabe der Mitoserate wünschenswert. Für die Beurteilung des Wächterlymphknotens sollen in der Regel mindestens 4 Scheiben aus dem Lymphknoten entnommen und untersucht werden. Es sollen bei der Diagnostik der Wächterlymphknoten neben der HE-Färbung auch immunhistochemische Färbungen für jede Gewebescheibe-vorzugsweise mit Antikörpern gegen S100ß, Melan A und HMB-45-durchgeführt werden. Im histopathologischen Befund sollen der Nachweis von Mikrometastasen und ihre größte Ausdehnung in 10tel Millimeter angegeben werden. Schlussfolgerungen: Die vorliegenden Empfehlungen sind geeignet, die Befundung maligner Melanome besser zu standardisieren und so eine bessere
British Journal of Haematology, 1993
authors underestimate the effectiveness of androgens in RA. Because of the lack of information in... more authors underestimate the effectiveness of androgens in RA. Because of the lack of information in the literature about the efficacy of androgen therapy in RA type I FAB, we present here the data of 43 patients with RA treated with oral oxymetholone (Syntex Laboratories, Mexico D.F.) 2 mg/kg body weight. The inclusion criteria were as follows: anaemia and reticulocytopenia, unexplained bicytopenia, dyspoiesis of trilineage cells in the bone marrow (BM). The percentage of BM blasts was less than 5%. In the period 1973-91 we had 150 patients with the diagnosis of RA but only 43 were evaluable long-term. The median age (years) for the whole group was 55 (range 2189) and there were 12 females and 3 1 males. On basis of the predominant cytopenia we divided the 43 patients into three subgroups (I, anaemia, n = 14; 11, bicytopenia, n = 18; 111, pancytopenia, n = 11): median ages were similar in the three subgroups (57, 55 and 42 years respectively). There were four females in each group and 10, 14 and seven males respectively. The response data are shown in Table I. Complete remission (CR) in the whole group was seen in 36 of the 43 patients (83.7%). There was no statistical difference among the subgroups. Median for initial response started at 3 months and was complete in a median of 8 months. The response was characterized by haemoglobin increase and transfusion independence; however, such a response was dependent on oxymetholone treatment for periods of 12, 2 3 and 15 months respectively for the three groups. Median survival is longer than 8 5 months and the risk of transformation to acute myeloid leukaemia and RAEB was 0.8% and 0.4% respectively. Our data suggest that oxymetholone is a useful androgen in the treatment of RA type I FAB however, more studies are necessary for definitive conclusions. ACKNOWLEDGMENT
British Journal of Haematology, 1996
In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD... more In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD44, CD11a, CD11b, CD11c, CD18, CD25 and CD54 was analysed in bone marrow cryostat sections by immunohistochemistry. CD44 expression clearly identified two subgroups of B-CLL patients with different clinical course. In particular, CD44positive patients presented with advanced disease, more often displayed a diffuse pattern of bone marrow infiltration, and had a worse prognosis. 33/61 patients positive for CD44 died within the observation period compared to 7/46 patients negative for CD44 (P 0. 0012). Multivariate analysis emphasized the independent prognostic value of CD44 expression for overall survival (P 0. 022). In contrast, patients positive for CD11c showed a longer survival, with 9/40 patients dying within the observation period compared to 31/67 negative for CD11c (P 0. 0013). Patients lacking CD11c were in advanced Rai and Binet stage. Multivariate analysis confirmed CD11c as a relevant independent prognostic marker (P 0. 033). Moreover, CD11c was able to separate patients with significantly different prognosis in the subgroup of CD44-positive cases. 4/18 patients positive for CD44 and CD11c died before median survival time was reached. Patients positive for CD44 but negative for CD11c had an adverse prognosis: 29/43 patients died, median survival time was 33. 4 months. Our results indicate that CD44 positivity and CD11c negativity are associated with more advanced disease and worse prognosis in B-CLL and suggest CD44-positive/CD11cnegative cases represent a more aggressive form of the disease.
International Journal of Cancer, 2009
Radiotherapy and Oncology, 2016
ESTRO 35 2016 S205 ______________________________________________________________________________... more ESTRO 35 2016 S205 ______________________________________________________________________________________________________ or p16 negative cells, indicating a differential role of p16 protein expression depending on its localization. Strikingly, cells expressing nuclear p16 (p16-NLS)-although showing a similar level of gH2AX induction-were characterized with lower number RAD51 foci formation compared to cells expressing cytoplasmic p16 (p16-NES), suggesting an impaired HRR. Conclusion: Cellular p16 localization is an important factor for stratification of HNSCC patients with nuclear p16 expression showing a superior predictive value for radiotherapy response. OC-0440 Impact of chemokine receptor CXCR4 and its ligand SDF1 expression on loco-regional control in HNSCC
American Journal of Clinical Pathology, 1998
Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated... more Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of
European Urology Supplements, 2009
Introduction & Objectives: The purpose of this study was to determine whether immunization with a... more Introduction & Objectives: The purpose of this study was to determine whether immunization with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-γ (IFN-γ), would be tolerated and able to induce a prolongation of PSA doubling time in patients with progressive androgenindependent prostate cancer (AIPC). Material & Methods: 30 HLA-A0201-matched patients with progressive, hormone refractory prostate cancer, demonstrating three successive elevations in prostate specific antigen (PSA) values, received four intradermal injections on days 1, 15, 29 and 92, and then every 90 days as long as no tumor progression occurred. Three patients received a dose level of 7.5 million cells, 27 patients received 15 million cells. The primary efficacy criterion was the difference in PSA doubling time (PSA-DT) determined in the pre-treatment phase (before start of vaccination) and in the trial treatment phase (during vaccination). Results: The study was completed according to protocol. Immunostimulation could be demonstrated in most of the 30 patients (histological evaluation of injection site biopsies, serial ELISPOT analysis of PBMCs). During vaccination there was a significant prolongation of the PSA-DT compared to the pre-vaccination period that came to 81% (prolongation from 63 days to 114 days (p < 0.0035; ITT)). Twenty two of 30 patients (73%) responded to the vaccine administration as judged by prolongation of PSA-DT. In the majority of patients the administration was followed by a period of PSA stabilisation that was up to 641 days ("PSA plateau"). No dose limiting or autoimmune toxicities were seen. The median overall survival time since first vaccination was 981 days (mean value: 770 days). conclusions: This vaccine strategy showed a prolongation of PSA-DT and was found to be safe and well tolerated. The results of this trial warrant the vaccine's further clinical development.
Ultraschall in der Medizin - European Journal of Ultrasound, 2011
Die Non-Hodgkin-Lymphome stellen eine sehr heterogene Gruppe von Neoplasien dar. Unter den periph... more Die Non-Hodgkin-Lymphome stellen eine sehr heterogene Gruppe von Neoplasien dar. Unter den peripheren B-Zell-Non-Hodgkin-Lymphomen hat das Burkitt-Lymphom mit einem Vorkommen von 30 % aller Lymphome im Kindesalter die größte Relevanz. Das Burkitt-Lymphom ist die aggressivste aller lymphoproliferativen Erkrankungen. Nach WHO-Richtlinien unterscheidet man die endemische, sporadische und HIV-assoziierte Form (H. Gadner et al. Pädiatrische Hämatologie und Onkologie 2006; 63: 732751). Die sporadische Form tritt vor allem in den europäischen Ländern auf. In 80 % der Fälle liegt bei der sporadischen Form eine Translokation des c-Myc-Gens von Chromosom 8 vor (J. A. Ferry et al. The Oncologist 2006; 11:375-383). Klinisch manifestieren sich sporadische Burkitt-Lymphome meist als abdominelle oder tonsilläre Tumoren, die im Kindesalter häufig einen leukämischen Verlauf nehmen, der durch einen Befall des Knochenmarks von > 25 % definiert ist. Knochenmark-und ZNS-Befall kommen bei allen Varianten vor. Aufgrund der hohen Proliferationsrate der Lymphome mit konsekutiv großen Tumormassen ist das Tumorlyse-Syndrom zu Beginn der Chemotherapie eine gefürchtete Komplikation. Therapeutisch sprechen die großzelligen Lymphome jedoch sehr gut auf intensive Chemotherapie an, sodass mit ihrer Einführung und stetigen Optimierung die vormals schlechte Prognose auf eine 5-Jahres-Überlebensrate von über 90 % bei begrenzter Tumorausbreitung (Stadium I nach der Murphy/ St. Jude-Klassifikation) verbessert werden konnte. Auch Patienten mit disseminierter Tumorausbreitung (Stadium III) weisen inzwischen ein 5-Jahres-Überleben von ca. 65 % auf.
World journal of urology, Jan 15, 2015
To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with posit... more To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 mont...
Geburtshilfe und Frauenheilkunde, 2014
Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumou... more Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumours (IPT). They arise most commonly in the abdominopelvic region, lung and retroperitoneum, but virtually any anatomical site may be involved. Predominantly children and adolescents are affected and there is a tendency for local recurrence. In the literature up to the present, 20 patients have been reported with an IPT/IMT of the breast. We would like to present another patient with this unusual tumour entity of the breast and discuss the literature. Patient and Examinations: A 23-year-old woman presented with a painless lump in her left breast. There was no history of breast cancer in her family. Sonography showed a hypoechoic heterogeneous solid mass with irregular margins. A core needle biopsy revealed a tumour of high cellularity and a densely collagenous background. Immunohistochemically, the spindle-shaped cells were immunoreactive to smooth muscle actin and ALK-1 protein. Additional FISH analysis proved ALK rearrangements on chromosome 2p23 leading to the diagnosis of an IMT. Wide surgical excision was performed with no evidence of local recurrence after 12 months. Conclusion: Three of the above mentioned 20 patients with IMT/IPT of the breast developed a recurrent tumour, none presented with distant metastasis. A significant recurrence rate of 15 % leads to a clinically and sonographically close follow-up in these patients.
Proceedings of the National Academy of Sciences, 2006
MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in ... more MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN) types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes ( RET and MEN1 ) and syndromes with an endocrine tumor component ( VHL and NF1 ). We report the fine mapping of the disease locus and the identification of a homozygous frameshift mutation in Cdkn1b , encoding the cyclin-dependent kinase inhibitor p27 Kip1 . As a consequence of the mutation, MENX-affected rats show dramatic reduction in p27 Kip1 protein. We have identified a germ-line nonsense mutation in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with pituitary and parathyroid tumors. Expanded pedigree analysis shows that the mutation is associated with the development of an MEN1-like phenotype in multiple generations. Our findings demonstrate that ge...
Chirurgisches Forum 2007, 2007
Introduction: graft dysfunction after liver transplantation due to ischemia-/reperfusion injury r... more Introduction: graft dysfunction after liver transplantation due to ischemia-/reperfusion injury remains a serious clinical problem although there is a marked progress in transplantation medicine. The aim of this experimental study was to compare different types of reperfusion with regard to the ischemia-/ reperfusion injury. Materials and Methods: arterialised orthotopic liver transplantation (OLT) was performed in syngenic male Lewis rats. The animals were devided into 3 experimental groups: I-and II-control groups with antegrade reperfusion, III-retrograde reperfusion group. Laboratory parameters as well as histopathologic changes of the graft were evaluated 1, 24 and 48 hours after the OLT. Results: 24 hours after the OLT the GOT-values showed a significant difference between groups with antegrade/retrograde variant of reperfusion (2613,3 ± 343,9 U/l vs. 1186,4 ± 252,9 U/l; p < 0,001). The GPT-and GOT-values were significanly lower in the group III 48 hours after OLT. The histopathologic evaluation revealed a significantly lower number of necrotic areas in the group III compared to the control-groups (p < 0,002). Conclusion: our results show that the retrograde reperfusion (from the infrahepatic V. cava inferior with opening of the blood stream to the supra-hepatic V. cava inferior and to the Vv. hepaticae retrograde to the liver) has a protective effect on the graft.
Deutsche medizinische Wochenschrift (1946), 2014
amyloid-p-component and kappa light chains could be found. In the bone marrow biopsy plasma cells... more amyloid-p-component and kappa light chains could be found. In the bone marrow biopsy plasma cells were not increased indicating primary immunglobulin light chain (AL) amyloidosis. Conclusion: Prognosis of amyloidosis depends on the type of amyloid and extension of disease. Therefore, an early as possible diagnosis and classification are essential for an adequate therapy.
Human Pathology, 2011
Acquired chromosomal aberrations, including gene copy number alterations, are involved in the dev... more Acquired chromosomal aberrations, including gene copy number alterations, are involved in the development and progression of human malignancies. SOX2, a transcription factor-coding gene located at 3q26.33, is known to be recurrently and specifically amplified in squamous cell carcinomas of the lung, the esophagus, and the oral cavity. In these organs, the SOX2 protein plays an important role in tumorigenesis and tumor survival. The aim of this study was to determine whether SOX2 amplification is also found in squamous cell carcinomas in other organs commonly affected by this tumor entity. In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung. Applying fluorescence in situ hybridization, we assessed squamous cell carcinomas of the cervix uteri (n = 47), the skin (n = 57), and the penis (n = 53) for SOX2 copy number alterations and detected amplifications in 28%, 28%, and 32% of tumors, respectively. Furthermore, we performed immunohistochemical SOX2 staining and found that SOX2 amplification is significantly associated with overexpression of the corresponding protein in squamous cell carcinomas (P b .001). Of the lung cancer entities with neuroendocrine differentiation, only small cell cancers and large cell cancers exhibited SOX2 or TTF1 amplifications at significant frequencies, indicating that at least a subset of these might be dedifferentiated forms of ☆ No conflict of interest. ☆☆ This study was approved by the Institutional Review Board of the University Hospital of Tuebingen (512/2009BO1).
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2009
Zeitschrift für Gastroenterologie, 2010
Zeitschrift für Gastroenterologie, 2013
Transplantation Journal, 2010
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2011
Hintergrund: Die gültigen TNM-Klassifikationen sind die Grundlage für Entscheidungen zur Diagnost... more Hintergrund: Die gültigen TNM-Klassifikationen sind die Grundlage für Entscheidungen zur Diagnostik und Therapie von Krebskrankheiten. Die Histopathologie muss die sachgerechte Einordnung des Tumorbefundes in diese Klassifikationen ermöglichen. Methoden: Zur Bestimmung der Mitoserate des primären Melanoms und zur Aufarbeitung und Beurteilung des Wächterlymphknotens wurde eine systematische Literaturrecherche durchgeführt. Auf der Grundlage der Literaturrecherche wurden Empfehlungen erarbeitet, die von einem Expertengremium aus Dermatohistologen und Pathologen diskutiert und abgestimmt wurden. Ergebnisse: Die folgenden Empfehlungen wurden mit hohem Konsens abgestimmt (93-100 % Übereinstimmung): Die Bestimmung der Mitoserate bei primären Melanomen erfolgt anhand von HE-Schnitten. Die Beurteilung von 1 mm 2 ist ausreichend. Es werden lediglich dermale Mitosen berücksichtigt und in ganzen Zahlen angegeben. Die Mitoserate soll bei Primärtumoren Յ1,00 mm Tumordicke nach der Hot-Spot-Methode bestimmt werden und als ganze Zahl in Relation zu 1 mm 2 Tumorfläche angegeben werden. Bei dickeren Primärtumoren ist die Angabe der Mitoserate wünschenswert. Für die Beurteilung des Wächterlymphknotens sollen in der Regel mindestens 4 Scheiben aus dem Lymphknoten entnommen und untersucht werden. Es sollen bei der Diagnostik der Wächterlymphknoten neben der HE-Färbung auch immunhistochemische Färbungen für jede Gewebescheibe-vorzugsweise mit Antikörpern gegen S100ß, Melan A und HMB-45-durchgeführt werden. Im histopathologischen Befund sollen der Nachweis von Mikrometastasen und ihre größte Ausdehnung in 10tel Millimeter angegeben werden. Schlussfolgerungen: Die vorliegenden Empfehlungen sind geeignet, die Befundung maligner Melanome besser zu standardisieren und so eine bessere
British Journal of Haematology, 1993
authors underestimate the effectiveness of androgens in RA. Because of the lack of information in... more authors underestimate the effectiveness of androgens in RA. Because of the lack of information in the literature about the efficacy of androgen therapy in RA type I FAB, we present here the data of 43 patients with RA treated with oral oxymetholone (Syntex Laboratories, Mexico D.F.) 2 mg/kg body weight. The inclusion criteria were as follows: anaemia and reticulocytopenia, unexplained bicytopenia, dyspoiesis of trilineage cells in the bone marrow (BM). The percentage of BM blasts was less than 5%. In the period 1973-91 we had 150 patients with the diagnosis of RA but only 43 were evaluable long-term. The median age (years) for the whole group was 55 (range 2189) and there were 12 females and 3 1 males. On basis of the predominant cytopenia we divided the 43 patients into three subgroups (I, anaemia, n = 14; 11, bicytopenia, n = 18; 111, pancytopenia, n = 11): median ages were similar in the three subgroups (57, 55 and 42 years respectively). There were four females in each group and 10, 14 and seven males respectively. The response data are shown in Table I. Complete remission (CR) in the whole group was seen in 36 of the 43 patients (83.7%). There was no statistical difference among the subgroups. Median for initial response started at 3 months and was complete in a median of 8 months. The response was characterized by haemoglobin increase and transfusion independence; however, such a response was dependent on oxymetholone treatment for periods of 12, 2 3 and 15 months respectively for the three groups. Median survival is longer than 8 5 months and the risk of transformation to acute myeloid leukaemia and RAEB was 0.8% and 0.4% respectively. Our data suggest that oxymetholone is a useful androgen in the treatment of RA type I FAB however, more studies are necessary for definitive conclusions. ACKNOWLEDGMENT
British Journal of Haematology, 1996
In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD... more In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD44, CD11a, CD11b, CD11c, CD18, CD25 and CD54 was analysed in bone marrow cryostat sections by immunohistochemistry. CD44 expression clearly identified two subgroups of B-CLL patients with different clinical course. In particular, CD44positive patients presented with advanced disease, more often displayed a diffuse pattern of bone marrow infiltration, and had a worse prognosis. 33/61 patients positive for CD44 died within the observation period compared to 7/46 patients negative for CD44 (P 0. 0012). Multivariate analysis emphasized the independent prognostic value of CD44 expression for overall survival (P 0. 022). In contrast, patients positive for CD11c showed a longer survival, with 9/40 patients dying within the observation period compared to 31/67 negative for CD11c (P 0. 0013). Patients lacking CD11c were in advanced Rai and Binet stage. Multivariate analysis confirmed CD11c as a relevant independent prognostic marker (P 0. 033). Moreover, CD11c was able to separate patients with significantly different prognosis in the subgroup of CD44-positive cases. 4/18 patients positive for CD44 and CD11c died before median survival time was reached. Patients positive for CD44 but negative for CD11c had an adverse prognosis: 29/43 patients died, median survival time was 33. 4 months. Our results indicate that CD44 positivity and CD11c negativity are associated with more advanced disease and worse prognosis in B-CLL and suggest CD44-positive/CD11cnegative cases represent a more aggressive form of the disease.
International Journal of Cancer, 2009
Radiotherapy and Oncology, 2016
ESTRO 35 2016 S205 ______________________________________________________________________________... more ESTRO 35 2016 S205 ______________________________________________________________________________________________________ or p16 negative cells, indicating a differential role of p16 protein expression depending on its localization. Strikingly, cells expressing nuclear p16 (p16-NLS)-although showing a similar level of gH2AX induction-were characterized with lower number RAD51 foci formation compared to cells expressing cytoplasmic p16 (p16-NES), suggesting an impaired HRR. Conclusion: Cellular p16 localization is an important factor for stratification of HNSCC patients with nuclear p16 expression showing a superior predictive value for radiotherapy response. OC-0440 Impact of chemokine receptor CXCR4 and its ligand SDF1 expression on loco-regional control in HNSCC
American Journal of Clinical Pathology, 1998
Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated... more Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of
European Urology Supplements, 2009
Introduction & Objectives: The purpose of this study was to determine whether immunization with a... more Introduction & Objectives: The purpose of this study was to determine whether immunization with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-γ (IFN-γ), would be tolerated and able to induce a prolongation of PSA doubling time in patients with progressive androgenindependent prostate cancer (AIPC). Material & Methods: 30 HLA-A0201-matched patients with progressive, hormone refractory prostate cancer, demonstrating three successive elevations in prostate specific antigen (PSA) values, received four intradermal injections on days 1, 15, 29 and 92, and then every 90 days as long as no tumor progression occurred. Three patients received a dose level of 7.5 million cells, 27 patients received 15 million cells. The primary efficacy criterion was the difference in PSA doubling time (PSA-DT) determined in the pre-treatment phase (before start of vaccination) and in the trial treatment phase (during vaccination). Results: The study was completed according to protocol. Immunostimulation could be demonstrated in most of the 30 patients (histological evaluation of injection site biopsies, serial ELISPOT analysis of PBMCs). During vaccination there was a significant prolongation of the PSA-DT compared to the pre-vaccination period that came to 81% (prolongation from 63 days to 114 days (p < 0.0035; ITT)). Twenty two of 30 patients (73%) responded to the vaccine administration as judged by prolongation of PSA-DT. In the majority of patients the administration was followed by a period of PSA stabilisation that was up to 641 days ("PSA plateau"). No dose limiting or autoimmune toxicities were seen. The median overall survival time since first vaccination was 981 days (mean value: 770 days). conclusions: This vaccine strategy showed a prolongation of PSA-DT and was found to be safe and well tolerated. The results of this trial warrant the vaccine's further clinical development.
Ultraschall in der Medizin - European Journal of Ultrasound, 2011
Die Non-Hodgkin-Lymphome stellen eine sehr heterogene Gruppe von Neoplasien dar. Unter den periph... more Die Non-Hodgkin-Lymphome stellen eine sehr heterogene Gruppe von Neoplasien dar. Unter den peripheren B-Zell-Non-Hodgkin-Lymphomen hat das Burkitt-Lymphom mit einem Vorkommen von 30 % aller Lymphome im Kindesalter die größte Relevanz. Das Burkitt-Lymphom ist die aggressivste aller lymphoproliferativen Erkrankungen. Nach WHO-Richtlinien unterscheidet man die endemische, sporadische und HIV-assoziierte Form (H. Gadner et al. Pädiatrische Hämatologie und Onkologie 2006; 63: 732751). Die sporadische Form tritt vor allem in den europäischen Ländern auf. In 80 % der Fälle liegt bei der sporadischen Form eine Translokation des c-Myc-Gens von Chromosom 8 vor (J. A. Ferry et al. The Oncologist 2006; 11:375-383). Klinisch manifestieren sich sporadische Burkitt-Lymphome meist als abdominelle oder tonsilläre Tumoren, die im Kindesalter häufig einen leukämischen Verlauf nehmen, der durch einen Befall des Knochenmarks von > 25 % definiert ist. Knochenmark-und ZNS-Befall kommen bei allen Varianten vor. Aufgrund der hohen Proliferationsrate der Lymphome mit konsekutiv großen Tumormassen ist das Tumorlyse-Syndrom zu Beginn der Chemotherapie eine gefürchtete Komplikation. Therapeutisch sprechen die großzelligen Lymphome jedoch sehr gut auf intensive Chemotherapie an, sodass mit ihrer Einführung und stetigen Optimierung die vormals schlechte Prognose auf eine 5-Jahres-Überlebensrate von über 90 % bei begrenzter Tumorausbreitung (Stadium I nach der Murphy/ St. Jude-Klassifikation) verbessert werden konnte. Auch Patienten mit disseminierter Tumorausbreitung (Stadium III) weisen inzwischen ein 5-Jahres-Überleben von ca. 65 % auf.
World journal of urology, Jan 15, 2015
To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with posit... more To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 mont...
Geburtshilfe und Frauenheilkunde, 2014
Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumou... more Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumours (IPT). They arise most commonly in the abdominopelvic region, lung and retroperitoneum, but virtually any anatomical site may be involved. Predominantly children and adolescents are affected and there is a tendency for local recurrence. In the literature up to the present, 20 patients have been reported with an IPT/IMT of the breast. We would like to present another patient with this unusual tumour entity of the breast and discuss the literature. Patient and Examinations: A 23-year-old woman presented with a painless lump in her left breast. There was no history of breast cancer in her family. Sonography showed a hypoechoic heterogeneous solid mass with irregular margins. A core needle biopsy revealed a tumour of high cellularity and a densely collagenous background. Immunohistochemically, the spindle-shaped cells were immunoreactive to smooth muscle actin and ALK-1 protein. Additional FISH analysis proved ALK rearrangements on chromosome 2p23 leading to the diagnosis of an IMT. Wide surgical excision was performed with no evidence of local recurrence after 12 months. Conclusion: Three of the above mentioned 20 patients with IMT/IPT of the breast developed a recurrent tumour, none presented with distant metastasis. A significant recurrence rate of 15 % leads to a clinically and sonographically close follow-up in these patients.
Proceedings of the National Academy of Sciences, 2006
MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in ... more MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN) types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes ( RET and MEN1 ) and syndromes with an endocrine tumor component ( VHL and NF1 ). We report the fine mapping of the disease locus and the identification of a homozygous frameshift mutation in Cdkn1b , encoding the cyclin-dependent kinase inhibitor p27 Kip1 . As a consequence of the mutation, MENX-affected rats show dramatic reduction in p27 Kip1 protein. We have identified a germ-line nonsense mutation in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with pituitary and parathyroid tumors. Expanded pedigree analysis shows that the mutation is associated with the development of an MEN1-like phenotype in multiple generations. Our findings demonstrate that ge...