Biomedical subjects
Publications and source records attributed to A Hegele.
We present a rare case of cystitis emphysematosa in an 85-year-old female patient in whom the typical risk factors were present: diabetes of long standing, neurogenic bladder and urinary infection with E.coli. Thanks to early diagnosis by cystoscopy and abdominal CT, after antibiotic treatment, appropriate insulin therapy and continuous bladder drainage the course was uneventful. The patient was fit to leave hospital after 14 days.
PURPOSE: On the basis of promising first-line data we have evaluated the safety and efficacy of a combination therapy comprising interleukin-2 (IL-2) and thalidomide in patients with metastatic renal cell carcinoma (RCC) refractory to both immuno- and chemotherapy. PATIENTS AND METHODS: 14 patients with progressive metastatic RCC, in whom prior immunochemotherapy had failed but who desired further active therapy, were enrolled in this study. Oral thalidomide was started at 200 mg/d and escalated after two days to 400 mg/d at week 0. IL-2 at 7 MIU/m (2) was given by subcutaneous injection, starting at week 1, days 1 to 5, weeks 1 to 4, with no IL-2 at weeks 5 and 6. The response was assessed every other therapy cycle. RESULTS: 12 patients were evaluable for response. There was no objective response; 4 patients showed stable disease for 21, 15, 13 and 9 months, respectively. Toxicities were predominantly grade 1 - 3 and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after seven weeks due to increasing confusion. 11 patients required IL-2 dose reduction. Time on therapy ranged from 3 - 44 weeks (median, 19 weeks). Median overall survival was 22 months. Up to date, all patients have discontinued treatment. CONCLUSIONS: We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable and the clinical benefit is uncertain. Therefore thalidomide/IL-2 may not represent a promising therapeutic approach for this subgroup of patients.
OBJECTIVES: Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10-35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment. MATERIALS AND METHODS: This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity. RESULTS: Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy. CONCLUSIONS: Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.
Bacillus Calmette-Guérin is established in the prophylaxis of recurrent intermediate and high-risk superficial bladder cancer and induces an unspecific, Th1-biased local immune response. Small CpG oligonucleotides (CpG ODN) containing a central unmethylated CpG motif are able to mimic the immunostimulatory activity of bacterial DNA. The purpose of the present study was to evaluate the antineoplastic properties of intravesically administered CpG ODN in an orthotopic murine bladder cancer model. MB49 tumor cell suspension was instilled transurethrally in female C57/BL6 mice on day 0. Mice were divided in three groups of 12 animals. Four mice in each group received either stimulative CpG ODN, non-stimulative GpC ODN or PBS intravesically: group I on day 3, group II on day 5, group III on day 7. After sacrifice 7 days after treatment, bladders were removed and histological examinations were performed. Single instillation of CpG ODN revealed antineoplastic effects in every group demonstrated by significantly lower bladder weight compared with non-stimulative GpC ODN- and PBS-treated mice. Histological examination showed extensive infiltration of macrophages and lymphocytes in CpG ODN-treated mice, whereas PBS- and GpC ODN-treated mice showed solid tumor growth with only few leucocytes. Intravesically applied immunostimulative DNA demonstrated antitumoral activity in an orthotopic murine bladder cancer model. A single instillation seems to be sufficient to reduce tumor load.
INTRODUCTION: Infected sinus pilonidalis is common in young patients, causing much discomfort. Up to now, many different therapy options have been described. The aim of this study was to evaluate the longterm results for infected pilonidal sinus disease after primary drainage of the abscess, secondary rhomboid excision, and Limberg flap procedure. METHODS: 38 patients (5 female, 33 male, mean age 27,mean BMI 26.7 kg/m(2)) suffering from infected pilonidal sinus were first treated by incision of the abscess. After control of the inflammation (8-14 days), radical excision of the pilonidal sinus and defect closure by the Limberg flap procedure were performed. RESULTS: Two patients (5.2%) developed seroma and two (5.2%) developed infected hematoma. During follow-up, one patient (2.6%) showed recurrence. In 33 (87%), postoperative course and follow-up were uneventful (mean 23 months, range 1-36). The mean length of hospital stay was 3.2 days (range 1-4). CONCLUSIONS: In infected sinus pilonidalis disease, primary drainage of the abscess by incision, secondary radical rhomboid excision, and the Limberg flap procedure to close the defect can be recommended as a good therapeutic option due to its low complication rate, acceptable long-term results, and simple operative technique.
INTRODUCTION: The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. MATERIAL AND METHODS: The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBoTech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. RESULTS: Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer's recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. CONCLUSIONS: Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.
Tumors of the spermatic cord are rare. Up to 20% are malignant and usually located in the paratesticular region. We report the rare case of an inguinal fibrolipoma of the spermatic cord with discrepancies between clinical and histopathological findings.
cG250 is an IgG1 kappa light-chain chimeric monoclonal antibody that binds to a cell surface antigen found on 95% of clear-cell renal cancer. A multicentre phase II study was performed to evaluate the safety and efficacy of repeated doses of cG250. Thirty-six patients with metastatic RCC were included. All patients were nephrectomized for the primary tumour. Twenty-one patients were pretreated (e.g. with IL-2, IFN-alpha). A weekly dose of 50 mg cG250 was given by i.v. infusion for 12 weeks. Patients with SD or tumour response (PR, CR) after 12 weeks of treatment could receive additional treatment for 8 more weeks. None of the 36 enrolled patients had any cG250 grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. ELISA testing gave no evidence for relevant amounts of HACA. Eleven patients presented with SD and ten were eligible for extension treatment. After the end of the study in the follow-up period, one patient demonstrated a CR in week 38 and another patient with SD showed a significant reduction of the overall tumour load in week 44. Six additional patients with progressive disease at study entry were stable for more than six months after the treatment start. The weekly schedule of i.v. cG250 in patients with metastatic RCC was safe, very well tolerated and non-immunogenic in a 12-week treatment regimen. cG250 showed anti-tumour activity.
Complete dissociation of testis and epididymis is rare. An isolated torsion of the epididymis has not been reported so far. We report two cases: a 6-month-old boy who was admitted with fever and swollen hemiscrotum and an 18-year-old youth with acute onset of pain in the left hemiscrotum. Immediate inguinal surgical exploration of the baby showed a complete infarction of the epididymis due to an isolated epididymal torsion with dissociation of testis and epididymis. Epididymectomy was carried out and the testis was sutured down. In the case of the youth, the surgical exploration also showed an isolated epididymal torsion due to dissociation of testis and epididymis. The epididymis could be rescued by raising the torsion. The isolated torsion of the epididymis should be included in the differential diagnosis of acute scrotum in childhood.
Renal cell carcinoma (RCC) expresses an isoform of the glycolytic enzyme pyruvate kinase (type M2). The dimeric form (TuM2-PK) is over expressed in tumor cells and is detectable in blood with a sensitive enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for RCC. The TuM2-PK concentration in EDTA-plasma was determined quantitatively and immunologically using an ELISA. We measured the TuM2-PK plasma levels of 83 patients before and after surgery. Ninety-seven patients with various non-malignant diseases were also recruited as a control group. The control group displayed mean levels of 11.37 U/ml of TuM2-PK. Values were elevated in patients with RCC prior to surgery (mean 21.88 U/ml). The plasma levels increased after surgery until day 5 (mean 53.97 U/ml). At day 10, marker levels started to decrease without reaching preoperative values (mean 43.5 U/ml). Plasma levels in the renal vein (obtained during surgery) were not different from those in the peripheral blood. Follow-ups after 2-6 months showed a decrease to below preoperative levels (mean 16.3 U/ml). A significant difference was obtained by comparing the patients according to their Robson score. We found a significant difference (P < 0.01, Wilcoxon's two-sample test) in TuM2-PK levels between patients with RCC and the control group. Nevertheless, using the manufacturer's recommended cut-off value (15 U/ml), sensitivity was only 50.6% and specificity was 80.4%. Our results suggest that TuM2-PK is not a suitable tumor marker for RCC.
A case of an unusually large, proximal urethral calculus located very close to the external sphincter and caused by recurrent urethral stricture is presented.
There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine-sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q in the 39 cancer patients and in 10 healthy controls. Serum DNA alterations were identified in 84.5% (33 of 39 patients) and tumor-specific urine DNA alterations indicating the diagnosis were present in 72% (27 of 39 patients) of cases. None of the healthy controls displayed serum DNA alterations. The highest frequency of serum DNA aberrations (56%) was detected for chromosomal region 8p. The most frequent alterations in urine-sediment DNA, 36% and 26%, were detected in chromosomal regions 8p and 9p, respectively. Identification of serum DNA and urine-sediment DNA alterations was not related to stage of disease or grade of tumor (p > 0.05). Thus, MSA offers a highly sensitive and specific method for serum- and urine-bound diagnosis of bladder TCC.
A case of alpha-fetoprotein-producing gastric hepatoid adenocarcinoma mimicking an extragonadal testicular cancer in a 28-year-old man is presented. This rare kind of tumor should be included in differential diagnosis in young patients without evidence of primary testicular malignancies.
OBJECTIVE: The contralateral adrenal gland is a rare metastatic site in renal cell carcinoma (RCC). We describe our experiences with this metastasis in a cohort of 610 radical nephrectomy patients analysed. To our knowledge this study is the first to demonstrate an inferior vena cava tumour thrombus from metachronous contralateral adrenal metastasis. PATIENTS AND METHODS: After radical nephrectomy for RCC, 610 patients treated at our institution from 1985-99 were retrospectively investigated for the incidence of contralateral adrenal metastasis, additional clinical findings, treatment modalities and survival after treatment for contralateral adrenal gland metastasis. RESULTS: The incidence of contralateral adrenal metastasis was 1.1% (7/610 patients), while the incidence of ipsilateral metastasis was 3.4% (21/610). In 3 of 7 cases the contralateral adrenal metastasis occurred simultaneously with primary RCC in the kidney. The contralateral adrenal gland was affected by distant tumour spread metachronously in 4 of 7 cases (3/4 bilateral adrenal involvement, 1/4 unilateral disease). In 1 case a metachronous contralateral adrenal metastasis caused vena cava tumour thrombus by propagation via the suprarenal venous route. After a mean follow-up of 20 months (range 1-54 months), 4 of 6 patients showed no evidence of disease after contralateral adrenalectomy. CONCLUSIONS: The probability of contralateral adrenal metastasis from RCC is 1.1%. Adrenalectomy in these cases offers a good chance of cure. In 71% of cases contralateral adrenal metastasis occurs in conjunction with ipsilateral disease, which provides a strong argument for routine ipsilateral adrenalectomy during radical nephrectomy. Care must be taken in preoperative diagnostics, as metachronous adrenal metastasis is capable of causing vena cava tumour thrombus.
Studies in mice have identified the ob gene product, leptin, as a signaling factor regulating body weight homeostasis and energy balance. Defective production of the encoded protein may be one of the causes for the development of obesity. Using a high affinity antibody, that in immunohistochemical studies specifically stained human adipocytes, a radioimmunoassay was established and leptin immunoreactivity was quantified in plasma of lean and obese human subjects. Chromatographic analysis suggested that the immunoreactive material in plasma is identical to that found in extracts from human fat and represent a protein with a molecular size of approximately 16 kD. Fasting levels were measured in plasma of 75 lean and obese human subjects (body mass index (BMI) 17.7 - 87.3). The mean concentration of leptin in plasma of lean subjects (BMI < or = 28) was 69.3 +/- 36.9 fmol/ml plasma (mean +/- SD, n=27). The highest concentration measured in obese was 533.3 fmol/ml plasma. The levels showed a strong positive correlation with BMI (r=0.77, p<0.001). A subgroup of diabetic patients did not significantly differ in their leptin plasma levels from non-diabetic subjects with similar BMI.