Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro.

Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype of tumor cells. Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical carcinoma cells using Wst-1-, BrdUrd-, and [³H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage assay and light microscopy techniques. We observed that incubation with griseofulvin for 24-48 h leads to a decrease in the viability and proliferation of NCI-H295R cells in a dose-dependent manner. Significant effects could be observed after incubation with griseofulvin as measured by Wst-1-, BrdUrd-, and [³H]dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent manner up to 4.5-fold after incubation with griseofulvin 40 µM for 24 h as shown by caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere with the microtubule apparatus and inhibit centrosomal clustering, may turn out to be interesting targets for further research.

Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors.

UNLABELLED: Tumor uptake of the amino acid cis-4-[18F]fluoro-L-proline (cis-FPro) was studied with PET in eight patients with urologic tumors. METHODS: Three patients had primary renal cell carcinomas (RCCs), one had a local recurrence of RCC, one had squamous RCC, one had an adrenal hemangioma, one had inguinal metastases of penile squamous carcinoma, and one had suspected metastatic disease from prostate cancer. PET scans of the trunk were acquired at 1 and 3-5 h after intravenous injection of 400 MBq cis-FPro and compared with 18F-FDG PET scans and CT. RESULTS: None of the tumors or metastases showed significant uptake of cis-FPro. FDG uptake was seen in one of the three primary RCCs, in the local recurrence of RCC, in the squamous RCC, and in the metastases of penile cancer. CONCLUSION: Cis-FPro appears not to be a promising PET tracer in oncology.

FDG-PET evaluation of retroperitoneal metastases of testicular cancer before and after chemotherapy.

We describe a patient whose primary tumor was a testicular teratocarcinoma predominantly composed of embryonal carcinoma. Before chemotherapy, the retroperitoneal metastases demonstrated heterogeneous, increased glucose metabolism as measured by 2-[18F]fluoro-2-deoxy-D-glucose and PET (FDG-PET). After chemotherapy, FDG uptake was reduced to normal values despite increased tumor volume. Histology revealed a pure mature teratoma. This observation suggests that further studies are needed to determine whether tumor differentiation of testicular teratocarcinoma metastases can be assessed by measuring glucose metabolism.

Whole-body kinetics and dosimetry of cis-4-[(18)F]fluoro-L-proline.

The whole-body distribution of 4-cis[(18)F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 microGy/mbq). The effective dose according to ICRP 60 was 15.1 microSv/mbq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro.

[Pathogenetic differentiation of the bone superscan using bone marrow scintigraphy]. / Pathogenetische Differenzierung des Skelettsuperscans mittels Knochenmarkszintigraphie.

The case of a 54 year old patient suffering from a prostatic carcinoma is presented. At the time of diagnosis multiple bone metastases were detected by bone scintigraphy. An initial improvement was observed following antiandrogenic therapy. After three years the patient presented with increasing bone pain, which was most prominent in the knee joints. A "superscan" was found in bone scintigraphy with an unusually high uptake in the peripheral skeleton. Bone marrow scinitgraphy showed a nearly complete metastatic displacement of central bone marrow and a peripheral marrow extension as explanation for the bone scan findings.

[Reconstruction of the inferior vena cava for extended resection of malignant tumors]. / Rekonstruktion der Vena cava inferior zur erweiterten Resektion maligner Tumoren.

OBJECTIVES: Malignant tumor invasion in the inferior vena cava (IVC) has for a long time been the limiting factor in the resection of retroperitoneal tumors. The clinical outcome in these patients depends on vascular surgical techniques, the central role of which is played by IVC reconstruction. METHODS: Within the last 7 years, 9,085 vascular reconstructive procedures were performed in our department. Six patients suffered from retroperitoneal invasion of tumor into the IVC. After tumor resection, the involved IVC segments were replaced by polytetrafluorethylene (PTFE) grafts to restore IVC continuity. In three patients, an adjunctive arteriovenous (AV) fistula was constructed. RESULTS: The graft patency after a mean follow-up of 30.2 months (range 1 to 79) was 83.3%. The only graft occlusion occurred in a patient without AV fistula. There were no perioperative deaths and no major complications demanding reoperation. CONCLUSION: In patients with tumor involvement of the IVC, clinical outcome depends on vascular surgical coprocedure. After resection of the IVC, a PTFE graft should be interposed in combination with an AV fistula. Anticoagulation and CT scan are recommended after 3 months before ligation of the AV fistula.

[Results of the West German multicenter study "Urological traumatology"]. / Ergebnisse der westdeutschen Multicenterstudie "Urologische Traumatologie".

The West German Multicenter Study on Urological Traumatology ran from April 1984 to December 1986. During this time, 19 departments of urology evenly scattered over the Federal Republic of Germany including Berlin (West) recorded and evaluated the data pertaining to a total of 385 patients (83% male, 17% female) with urogenital trauma. The distribution of the different mechanisms of injury demonstrates that 41% were due to traffic accidents; 13% each to accidents during sports and work; 8% to sexual activities; and 6% to violence. The trauma was slight in 40% of the cases, moderate in 21%, and severe in 39%. Of a total of 427 urogenital injuries, 27% were combined with intra-abdominal and 24% with pelvic injuries. Renal injuries were recorded in 51%, ruptures accounting for 49% of these and contusions for 48%. Hilar lesions were observed in 7%, with complete destruction of the organ occurred in 6% of these cases. In all, 76% of these traumas were treated conservatively, while 8% each required surgical reconstruction and nephrectomy. Traumatic lesions of the urinary bladder, urethra, penis, and scrotum including the testes and accessory organs were recorded in about 10% each. Macrohematuria was seen with 73% of renal, 83% of urinary bladder, and 73% or urethral injuries. Microhematuria occurred with 24%, 9%, and 13% of all cases, while no hematuria was ascertained in 3%, 5%, and 13% of renal, bladder and urethral traumas, respectively. The injury-related sensitivity of the different imaging methods was calculated at 95% for cystograms, 91% for retrograde urethrograms, and 83% for angiograms.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of computerized tomography in detection of lymph node metastases in bladder cancer]. / Die Bedeutung des Computertomogramms zur Erfassung von Lymphknotenmetastasen beim Harnblasenkarzinom.

The accuracy of computed tomography (CT) in staging of pelvic lymph nodes in bladder cancer was investigated in 50 patients. All patients underwent pelvic lymph node dissection and cystectomy. The results of preoperative CT findings were compared with the histopathological findings in the dissected lymph nodes. Normal lymph nodes free of tumour cells were found in 32 patients. In 6 patients, single lymph node involvement was detected, while in 12 patients two or more lymph nodes were found to be positive for tumour infiltration. CT results were confirmed in 38 patients (76%). Specificity of CT was 100%, but the sensitivity of this method was only 33%. Based on these results, it appears that CT evaluation of pelvic lymph nodes in bladder cancer patients should have only a limited impact on decision making in patient management.

[Late sequelae after urogenital trauma. Results of follow-up studies]. / Spätfolgen nach Urogenitaltrauma. Nachuntersuchungsergebnisse.

In the course of the Multicenter Study on Urological Traumatology ("UMCEST"), 61 patients who had been treated at the Departments of Urology of the Ludwig Maximilian University in Munich and the Heinrich Heine University in Düsseldorf were followed up. These included 39 patients with multiple trauma and 22 patients who had suffered isolated urological injuries. There were 45 patients with renal injuries, 7 with injuries to the bladder, and 11 who had presented with urethral injuries. Late complications were detected in 38% of the 45 patients with renal injuries. Of the 11 patients with urethral injuries, 6 suffered from urethral strictures, 9 from sexual dysfunction and 3 from incontinence. The 7 patients with bladder injuries had no late complications related to the bladder trauma.

[A rare form of metastasis of renal cell cancer. A case report of intra-oral soft tissue metastasis]. / Seltene Metastasierungsform des Nierenzellkarzinoms. Fallbericht über eine intraorale Weichteilmetastase.

Metastatic lesions represent 1%-8% of all malignant tumours of the mouth and jaws, which are regarded as rare sites of metastases from different primary tumours. The vast majority of these lesions (90%) have been observed in the mandibula, and 5%-20% in the maxilla. Metastatic tumours in the oral soft tissue are very rare. The primary tumour that most commonly metastasizes to the mouth and jaws seems to be carcinoma of the lung, followed by breast cancer and renal cell carcinoma. The case of a 47-year-old woman with renal cell carcinoma and an intraoral soft tissue metastatic lesion is presented.

[Open multicenter study of the differential diagnosis of erectile dysfunction with a papaverine-phentolamine combination (BY023)]. / Offene Multizenterstudie zur Differentialdiagnostik der erektilen Dysfunktion mit einer Papaverin-Phentolamin-Kombination (BY023).

We report the results of an open multicenter clinical trial with 115 patients. The results of a pharmacological test using intracavernously applied mixture of papaverine and phentolamine were compared with the results of a multidisciplinary evaluation of erectile dysfunction. Sensitivity and specificity of our test were determined. The injection of our drug solution caused an increase in tumescence and/or rigidity in all patients. The evaluation of the dose dependent erectile response makes it possible to distinguish between the three main pathogenetic principles: non-vascular, arterial and venous etiology of erectile dysfunction. The pharmacological test requires one to four intracavernous injections of 0.5-3.0 ml of the drug solution (7.5-45 mg papaverine hydrochloride, 0.25-1.5 mg phentolamine mesylate).

[The (11C) acetate positron emission tomography in prostatic carcinoma. New prospects in metabolic imaging]. / Die [11C]Acetat-Positronenemissionstomographie beim Prostatakarzinom. Neue Perspektiven in der metabolischen Bildgebung.

The exact staging of prostate cancer is mandatory to allow selection of the appropriate primary therapy. In addition, if the PSA level rises again it is extremely important to find the site(s) of local recurrence or metastatic spread as soon as possible. However, with the morphological and metabolic imaging techniques currently available it is often not possible to answer these questions with adequate sensitivity and specificity, since small metastases < or = 1 cm in diameter are likely to remain undetected by them. In the last few years new radioactive labelled tracers have been introduced for use in positron emission tomography (PET), and it is hoped that the shortcomings in the diagnostic procedures used for prostate carcinoma might be compensated by their use. Besides 11C- or 18F-labelled choline, [11C]Acetate is also attracting attention as a promising PET tracer. In this paper we review the various PET tracers available and evaluate the advantages and the drawbacks of [11C]Acetate in three case studies by comparing [11C]Acetate-PET with histology and with other imaging techniques. The use of [11C]Acetate appears to be feasible and helpful in the diagnosis of prostate carcinoma. However, its final value relative to other imaging techniques needs further investigation, with special reference to initial lymph node involvement, early localisation of recurrence and possible noninvasive differentiation between prostate cancer, prostatis and benign hyperplasia of the prostate.

[Positron emission tomography with [18 F]-2-fluoro-2-deoxy-D-glucose (18FDG-PET) in diagnosis of retroperitoneal lymph node metastases of testicular tumors]. / Die Positronenemissionstomographie mit [18 F]-2-fluoro-2-deoxy-D-glukose (18FDG-PET) bei der Diagnostik retroperitonealer Lymphknotenmetastasen von Hodentumoren.

In 1991, this prospectively designed study was started to assess the potentials of positron emission tomography with 18FDG in the diagnostic workup for the detection of lymph node metastases in testicular cancer, since there were no data available concerning this subject at this time. In 54 patients (27 patients with pure seminoma, 27 patients with non-seminomatous tumors) 18FDG-PET results were compared with the findings obtained with abdominal computed tomography, serum level of tumor markers (AFP, beta-HCG), and the histopathological findings after primary or post-chemotherapy retroperitoneal lymph node dissection. In 21 patients with pure seminoma (clinical stage I according to the Lugano classification) 18FDG-PET results were identical with those of the abdominal computed tomography, so PET does not add relevant informations in this group of patients. In 7 patients presenting with non-seminomatous testicular cancer (stage I), PET was not able to detect the existing micrometastases in 4 patients. In 1/7 case PET examination showed a suspicious focal lesion, this lymph node had 2 micrometastases within inflammatory changes. In 1/7 patient 18FDG-PET definitely revealed metastatic lesions, while the CT scans where judged to be unobtrusive and tumor marker levels were within the normal range. In the 4 patients with pure seminomas stage II B and II C (N = 6), that have undergone retroperitoneal lymph node dissection following chemotherapy, 18FDG-PET correctly predicted absence of tumor in 3 out of these 4, and in 1/4 patient the benign nature of a persistent large tumor after two cycles of polychemotherapy was correctly identified which eventually turned out to be a ganglioneuroma. This lesion falsely was classified as malignant tumor with abdominal computed tomography, and in 2/4 patients post-chemotherapy residual retroperitoneal lesions in the CT scans could not be assessed exactly whether or not malignant tumor was present. In 20 patients presenting with non-seminomatous testicular cancer (stage II and III) 18FDG-PET was able to demonstrate therapeutic effects of chemotherapy by showing decreasing tracer activity in those regions, that had hypermetabolic foci prior to chemotherapy. It became evident in testicular cancer that there is a single entity which is not characterized by increased glucose metabolism, the mature teratoma. In lesions detected by abdominal computed tomography which do not present increased 18FDG uptake, mature teratoma as well as scar/necrosis or rare other tumors with normal glucose metabolism can be supposed, but additional characteristics based on different 18FDG uptake were not observed. In 1/20 case post-chemotherapy PET scan detected a hypermetabolic lesion, which was suspicious for metastatic spread, but in the histopathological examination this lesion was identified as inflammatory tissue reaction. Based on the data reported here in 18FDG-PET cannot be considered a standard diagnostic tool in the staging examinations in testicular cancer. It is of clinical relevance in patients who present residual tumor after chemotherapy. In this situation 18FDG-PET is helpful in deciding whether or not a residual mass post-chemotherapy contains active tumor. 18FDG-PET can not replace retroperitoneal lymph node dissection for staging purposes.

[Vasectomy on request: still a moot point for discussion]. / Gefalligkeitsvasektomie -- nach wie vor ein umstrittenes Thema.

PIP: In the Federal Republic of Germany, 35.000-40.000 individuals undergo sterilization annually for family planning. A great amount of legal uncertainty surround penal, civil, and tort law (damage and liability of doctor) accountability because of conflicting statutes and interpretations of laws. The penal code on sterilization and abortion has been recently rewritten. Some of the indications for vasectomy are medical, medical-criminological, medical-social, and eugenic. Vasectomies are also performed on request of the patient; this is defined in different ways. A 1871 penal law pronounced the making of a person infertile a bodily injury punishable by 10 years in jail, but if the doctor could adduce special circumstances justifying it, the act was exonerated. Voluntary choice was not acceptable, only medical indication was valid. In 1933, the legal justification of voluntary choice of sterilization was confirmed, and even severe bodily injury was justifiable as long as it was accepted by the affected person, except if the act conflicted with accepted standards of habit, custom, and morals. Medical, eugenic and criminological-sexual medical reasons for sterilization were allowed, other reasons were punishable. In 1943, sterilization by radiation and hormone treatment also became punishable, except in the above allowances. In 1946, the penal code was annulled to extirpate Nazi thinking. The law that replaced it was put out of force in 1955, thus restoring the formed edict about moral conflict in voluntary choice. In 1963, a doctor was punished for 140 voluntary sterilizations, but the 1933 law reduced his sentence to 6 months instead of several years. After that, voluntary sterilization was no longer punished by a German court, but, in 1976, the controversial issue of legal justification of sterilization under free will was tackled in a verdict of the Bundesgerichtshof or Federal Court (BGH) under civil law. A 34-year old mother of 3 children was sterilized in the course of the delivery of the third child. She demanded compensation for pain, but the courts rejected her request on grounds of voluntary choice of procedure. Since, in 1970 and 1976, the Convention of German Doctors endorsed only medical-genetical and severe social reasons for sterilization, the BGH decision was also meant to indicate that the free choice of sterilization was not without limits. The doctor had to make sure that his act was legally acceptable by observing the rules of medical law: exact clarification of the type of treatment, disclosure of attendant consequences, side effects, risks and complications, the danger of failure of sterilization, and education about alternative methods. On demand vasectomy should be undertaken with restraint, since there is no recourse against the doctor; thus, unpleasant consequences could be avoided.^ieng

[Human fibrin glue as a new therapeutic concept in cyclophosphamide-induced cystitis and macrohematuria]. / Humaner Fibrinkleber als neues Therapiekonzept bei Cyclophosphamid-induzierter Zystitis und Makrohämaturie.

Successful treatment of hemorrhagic cystitis after systemic chemotherapy with cyclophosphamide yields up great problems up to now, because all therapeutic modalities that have been done were accompanied with severe side-effects. A 16 year old girl presented massive chemical cystitis and severe bleedings of the bladder mucosa after systemic long-term low-dose chemotherapy with cyclophosphamide. In this case bladder lesions could be cured completely by endoscopic application of fibrin adhesive through a cystoscope. Side-effects were not noted.

[Intraoral soft tissue metastases of a renal cell carcinoma]. / Intraorale Weichteilmetastase eines Nierenzellkarzinoms.

Face, mouth and jaws represent seldom localisations of metastatic lesions. 5-20% of these lesions are reported with localisation in the maxilla, whereas 90% are found in the mandibula. Metastatic tumours in the oral soft tissue are very rare. The most common primary tumour seems to be the renal cell carcinoma. Only histological examination can give a differentiation against benign tumours. The diagnostic and therapeutic management of a 46 years old woman with a metastatic intraoral lesion of a renal cell carcinoma is presented.

Bacteremia during extracorporeal shock wave lithotripsy of renal calculi.

An increasing incidence of bacterial endocarditis has been observed since the beginning of the last decade. An explanation for this fact is the expansion of diagnostic and therapeutic procedures in diverse medical disciplines. In a clinical study performed on 49 consecutive patients undergoing extracorporeal shock wave lithotripsy a 14.3% rate of bacteremia was detected during treatment. The bacterial spectrum consisted of gram-positive cocci, gram-negative cocci, Bacteroides capillosus and Proteus mirabilis. In principle, these results do not call for an antibiotic prophylaxis. Nevertheless, according to the recommendations of the American Heart Association and the Deutsche Gesellschaft für Herz- und Kreislaufforschung, patients with a cardiac risk predisposing to bacterial endocarditis must receive perioperative antibiotic prophylaxis.

Neurological risk profile in organic erectile impotence.

Thirty men who presented with erectile impotence to the urological department underwent a thorough urological, angiological, and neurological examination with complementary neurophysiological tests of somatosensory and sympathetic and parasympathetic function. Most had vascular and neurological abnormalities. Clinical findings and electrophysiological tests for autonomic dysfunction had the highest yield of abnormal results. Nerve conduction studies and pudendal nerve somatosensory evoked potentials were far less informative. The lack of correlation between vascular and general neurological abnormalities emphasises that patients must be screened for both vascular and neurological dysfunction to prevent unrewarding vascular operation in impotent men.