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Biomedical subjects

L Weissbach

Publications and source records attributed to L Weissbach.

At least 73 records · Page 4Linked to original sources

Primary therapy of metastatic prostate carcinoma with depot gonadotropin-releasing hormone analogue goserelin versus estramustine phosphate. The Prostate Cancer Study Group.

OBJECTIVE: To determine if initial chemo-hormone therapy (estramustine phosphate) of metastatic prostate carcinomas can lengthen the period until progression, compared with hormone treatment (goserelin) alone? The time to progression, side effects and prognostic factors were assessed. METHODS: The prospective phase III study (II 86 until V 91) involved 243 patients randomized consecutively in two groups. Progress was assessed according to NPCP criteria. RESULTS: The following prognostic factors were established to be significant: metastatic status, metastatic bone pain, alkaline phosphatase and performance status. No difference was observed between the two methods of treatment in time to progression. However on stratifying according to groups with the same prognostic factors, progression in the high risk group occurred at a later stage during treatment with estramustine than during pure hormone treatment. The quality of life was clearly more heavily restricted by side effects from estramustine. CONCLUSIONS: Thus, when comparing these treatments, there were no statistically significant differences. Patients in the high risk groups with unfavorable prognosis factors benefitted from the chemo-hormone treatment with estramustine phosphate.

Adenocarcinoma↗

Deoxyribonucleic acid ploidy in seminomas with and without syncytiotrophoblastic cells.

Seminomas with human chorionic gonadotropin-producing syncytiotrophoblastic cells have been discussed as a distinctive subgroup with a worse prognosis. In a series of 50 seminomas (30 with immunohistochemically detectable syncytiotrophoblastic cells and 20 without syncytiotrophoblastic cells) deoxyribonucleic acid (DNA) ploidy was determined by flow cytometry in paraffin-embedded histopathological material. Comparatively, in 28 cases the DNA content was assessed by image cytometry on Feulgen-stained slides. DNA aneuploidy was detected in 49 seminomas (98%). No differences in the distribution of DNA index were observed between cases positive and negative for syncytiotrophoblastic cells (average DNA index 1.68 +/- 0.44 for positive cases and 1.71 +/- 0.52 for negative cases). Flow cytometry and image cytometry DNA index values showed a statistically significant correlation (p < 0.01). Intra-tumoral heterogeneity of DNA content was found in 2 seminomas negative for syncytiotrophoblastic cells. Multiploidy and hypertetraploidy were noted more often in negative cases also. DNA ploidy or distinct aneuploid stemlines did not correlate with histopathological tumor stage or clinical course. The results favor the notion that the occurrence of syncytiotrophoblastic cells in seminomas represents only an example of intra-tumoral variability of tumor cell differentiation and does not justify the definition as a separate subgroup with distinct biological behavior.

Adult↗

[Solitary metastasis of prostate cancer in the tibia].

We report about a patient with a solitary tibial metastasis of a prostatic carcinoma. Metastases to the peripheral skeleton are relatively rare with a frequency of only 1-2% and are mainly found in cases of general spread of the disease. Complaints due to peripheral solitary metastases often cause misinterpretations. Bone scintigraphy is the primary method in the diagnosis of skeletal metastases, and is sometimes supported by specific radiographs. MRI yields excellent images of the extension of the tumor. It is therefore of high diagnostic value in the preoperative definition of the metastatic spread in bone and neighbouring soft tissue structures.

Aged↗

[Rare metabolic and cerebral complications after polychemotherapy of a testicular tumor].

In a 21-year-old patient with a tumor of the right testis, CT indicated a pathologically altered lymph node in the interaortocaval region. After high inguinal orchiectomy we performed a modified retroperitoneal lymph node dissection and monitored its success by immediate section for microscopic examination. Pathohistological investigation yielded immature teratoma. The patient was given two courses of adjuvant polychemotherapy containing cisplatin. Two days after the conclusion of the second course he was readmitted with grand mal epilepsy and visual agnosia. Two months later another grand mal epileptic fit occurred. The patient also suffered from marked metabolic disorders, such as hypokalemia, hyperreninism, hyperaldosteronism, kaliuresis, and hypertension. We consider these to be toxic side effects of cisplatin resulting in nephropathy. Evidence of cisplatin-induced encephalopathy was obtained by NMR tomography and EEG which indicated barrier disorders. Symptoms were relieved and continuous normalization of blood pressure, potassium level, and water and electrolyte balance was achieved by the administration of potassium substitution, ACE inhibition, and an aldosterone antagonist. The patient has since remained in a stable condition.

Adult↗

Retroperitoneal lymph node staging of testicular tumours. TNM Study Group.

A prospective multicentre study was carried out to determine the efficiency of various diagnostic methods in the assessment of the retroperitoneal space. The diagnostic findings were confirmed histologically after retroperitoneal lymph node dissection (RLND). The sensitivity was 71% for bipedal lymphography, 41% for computed tomography (CT), 31% for abdominal ultrasound and 37% for alpha-fetoprotein/human chorionic gonadotrophin (AFP/HCG). Specificity was 60, 94, 87 and 93% respectively. When all diagnostic methods were combined, sensitivity was 88% and specificity 48%. The value of all methods depends on the metastatic enlargement of the lymph nodes. The predictive value of a negative diagnosis was 73% for lymphography, 67% for CT, 61% for ultrasound and 65% for AFP/HCG; the predictive value of a positive diagnosis was 58, 85, 69 and 81% respectively. Despite these results, lymphography is indicated only when a surveillance strategy is planned, since it detected 58% of the lymph node metastases that were overlooked by CT and tumour markers. Despite this, 17% of patients with clinical stage I tumours had metastases. False positive rates are detrimental to primary chemotherapy: between 24% (at least 2 methods positive) and 46% (1 or more methods positive) of patients with clinical stage II A/B tumours had a pathological stage I and for these patients primary chemotherapy meant overtreatment.

Biomarkers, Tumor↗

[Is organ saving surgery of testicular tumor justified?].

Eight patients with malignant germ cell tumours of residual testes had organ-conserving surgery. The largest diameters of the tumours were 9-32 mm. In seven patients conservation of the organ was successful without local or systemic progression (n = 5), two patients needed chemotherapy for concurrent or subsequent metastatic spread. In one case the testis had to be removed because of functional loss. Improved surgical techniques and increased knowledge of the importance and treatment of testicular intraepithelial neoplasm (carcinoma in situ) made this approach of enucleating resection possible; it permits the maintenance of endogenous androgen production in a small group of patients. The generally good prognosis of malignant testicular tumours means that in certain circumstances surgical treatment of the primary tumour can be limited.

Adult↗

[Therapy of non-seminomatous testicular tumor stage II A/B (pT+N1/2Mo)].

In these stages standard therapy (RLND + 2 courses PEB) reveals survival rates of more than 95%. The high rates of toxic side effects from two aggressive treatment strategies induce considerations about reducing therapy. We may be able to omit one of the therapeutic methods: (a) RLND alone can cure half of the patients; the others could have chemotherapy if progression is found. (b) Primary chemotherapy shows complete remission in 75% of the cases; only every fourth patient has to undergo surgical resection of a residual tumor. Survival rates for both strategies are no different than those following standard therapy. Further modifications concern surgical techniques (modified unilateral RLND, nerve sparing RLND) in order to preserve an antegrade ejaculation, as well as other chemotherapy regimens by omitting one of the drugs (PE instead of PEB) or replacing one by another with fewer toxic effects (CEB instead of PEB). Current clinical trials should answer the question of which of the therapeutic options impairs quality of life less.

Antineoplastic Combined Chemotherapy Protocols↗

[The "false positive" tumor marker in malignant testicular tumor].

In addition to the histological diagnosis, alpha fetoprotein (AFP) and chorion gonadotropin (HCG) are used in clinical staging, therapy monitoring, and follow-up. Elevated markers without localization of metastases by imaging procedures are generally classified as progressive disease. However, other causes may be responsible for the elevated tumor markers: other malignant or benign diseases such as hepatocellular carcinomas, gastrointestinal tumors, bronchial carcinomas and benign diseases of the liver for AFP, and vesicular mole, hepatocellular, stomach, pancreatic and urothelial carcinomas for HCG. Moreover, technical disturbances in the modern sandwich assays with monoclonal antibodies are possible by heterophilic antibodies. These human anti-animal antibodies are built after immunoscintigraphy, immunostimulation and oral immunization by macromolecules. As a result, if progressive disease of a malignant germ cell tumor is unlikely, several steps have to be taken to determine the true causes for the elevated tumor markers before chemotherapy can be applied.

Adult↗

Carboxy-terminal-extended variant of the human fibrinogen alpha subunit: a novel exon conferring marked homology to beta and gamma subunits.

Similarities between the N-terminal regions of the three subunits of the clotting protein fibrinogen--(alpha beta gamma)2--suggest that they evolved from a common progenitor. However, to date no human alpha chain has been found with the strong C-terminal homology shared by the beta and gamma chains. Here we examine the natural product of a novel fibrinogen alpha chain transcript bearing a separate open reading frame that supplies the missing C-terminal homology to the other chains. Additional splicing leads to the use of this extra sequence as a sixth exon elongating the alpha chain by 35%. Since the extended alpha chain (alpha E) is assembled into fibrinogen molecules and its synthesis is enhanced by interleukin-6, it suggests participation in both the acute phase response and normal physiology.

Amino Acid Sequence↗

A plasminogen-related gene is expressed in cancer cells.

The breakdown of blood clots requires the fibrinolytic action of the serine proteinase plasmin, a two-chain polypeptide derived posttranslationally from its precursor zymogen, plasminogen. While investigating plasminogen gene expression in human extrahepatic tissues, a cDNA sequence was obtained which closely resembled the plasminogen cDNA, yet appeared to represent a distinct gene product. This sequence, which represents the transcript of the recently characterized plasminogen-related gene B, encodes a putative polypeptide of Mr 8800 and is expressed most prominently in malignant cancer cells.

Adult↗

Alternatively spliced annexin XI transcripts encode proteins that differ near the amino-terminus.

Annexins are a family of structurally related calcium-dependent phospholipid binding proteins. We recently described a new member of this family, bovine annexin XI [1]. Two kinds of cDNAs were identified corresponding to annexin XI mRNA variants A and B, which are generated by alternative splicing of identical primary transcripts. Annexin XI isoforms are predicted to differ at the amino-terminus, suggesting that they may have distinct biological roles.

Amino Acid Sequence↗

[The long-term toxicity of polychemotherapy in successfully treated testicular carcinoma].

Of 55 patients with testicular cancer, treated by combination chemotherapy including cisplatin, 21 (mean age 35 [21-51] years) were reexamined for late sequelae of the chemotherapy 1-9 years later. No patient had a recurrence or second malignancy. They all had normal renal function (renal sequence scintigraphy; creatinine clearance). Seven of 20 patients had a polyneuropathy, nine of 18 had high-tone hearing loss. Two patients became fathers after treatment. In nine of 20 patients the serum concentration of follicle-stimulating hormone was raised to above 20 mU/ml, evidence of germ-cell damage. Six of 13 patients had an abnormal ejaculation following retroperitoneal lymphadenectomy or excision of a residual tumour. There was no evidence of any life-limiting toxicity of the chemotherapy.

Adult↗