Clinical course of plasmacytoid urothelial carcinoma of the upper urinary tract: a case report

Plasmacytoid urothelial carcinoma of the bladder represents a rare and aggressive variant of urothelial carcinoma, which is usually diagnosed at an advanced pathologic stage. Until now, no reports exist on this rare tumor type in the upper urinary tract. Herein, we present the first report on the clinical course of a metastatic plasmacytoid urothelial carcinoma of the renal pelvis and show its unfavorable outcome despite multimodal therapy.     

Postnatal cortical development in congenital auditory deprivation

The study investigates early postnatal development of local field potentials (LFPs) in the primary auditory cortex of hearing and congenitally deaf cats. In hearing cats, LFPs elicited by electrical intracochlear stimulation demonstrated developmental changes in mid-latency range, including reductions in peak and onset latencies of individual waves and a maturation of their shape and latencies during the first 2 months of life. In long latency range (>80 ms), the P(1)/N(1) response appeared after the fourth week of life and further increased in amplitude and decreased in latency, reaching mature shapes between the fourth and sixth months after birth (p.n.). Cortical activated areas became increasingly smaller during the first 3 months of life, reaching mature values at the fourth month p.n. The layer-specific pattern of synaptic activity matured 4 months p.n. In congenitally deaf cats, the developmental pattern was different. The lowest cortical LFP thresholds were significantly smaller than in hearing controls, demonstrating a "hypersensitivity" to sensory inputs. The development of N(b) waves was delayed and altered and the long latency responses became smaller than in controls at the second and third months. The activated areas remained smaller than in controls until the third month, then they increased rapidly and exceeded the activated areas of age-matched controls. From the fourth month on, the activated areas decreased again and smaller synaptic currents were found in deaf cats than in controls. The presented data demonstrate that functional development of the auditory cortex critically depends on auditory experience.     

Recent strategies for the use of paclitaxel in the treatment of urological malignancies

Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an active broad-spectrum antitumor agent, including its use in urological malignancies, particularly urothelial tract cancer and testicular cancer. The mechanism of action, based on the premature stabilization of the microtubule assembly with disruption of the cytoskeletal framework, is completely different from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer, with an overall response rate of 40–50% being obtained in previously untreated patients. These promising single-agent results have prompted the use of combination regimens including, in particular, cisplatin and paclitaxel. A high degree of activity for the cisplatin-paclitaxel combination as reflected by responses in 50–80% of patients, including a substantial number of complete responses (>30%), has been identified. The role of other agents such as vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two-drug combination currently remains open. The combination of paclitaxel plus ifosfamide or vinorelbine in the absence of a platinum derivative has yielded rather disappointing results. Of particular interest may be the combination of paclitaxel and carboplatin. Both drugs can be given to patients with impaired renal function. Overall response rates of 45–60% have been reported in phase II studies. The so-called platelet-sparing effect of paclitaxel given in combination with carboplatin has resulted in a surprisingly low frequency of myelotoxicity, particularly thrombocytopenia. The combination of paclitaxel with carboplatin is being compared in an ongoing trial against the current standard MVAC regimen (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic disease. Furthermore, the activity of paclitaxel-based combinations is currently being explored in the neoadjuvant setting in phase II studies, and the potential for the combination with the other new promising agent – gemcitabine – will be evalutated in a phase I setting. In prostate cancer, estramustine phosphate is widely used as palliative treatment for patients with hormone-refractory disease. In vitro synergistic activity has been observed between estramustine and paclitaxel in prostate-cancer cell lines, although paclitaxel has not demonstrated single-agent activity in patients with hormone-refractory prostate cancer. In clinical trials the combination of the two agents was associated with increased gastrointestinal toxicity. The addition of etoposide as a third drug has yielded prostate-specific antigen (PSA)-response rates of >50%, but data on quality of life and survival time have not been reported for these combinations. A true clinical role for paclitaxel in prostate cancer has therefore not been established. Paclitaxel has finally demonstrated single-agent activity in relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials, indicating different mechanisms of resistance to cisplatin and paclitaxel. These results have formed the rationale for the introduction of paclitaxel as part of combination chemotherapy regimens in patients with relapsed but chemosensitive testicular cancer. Preliminary results demonstrate that paclitaxel can be safely included into these conventional-dose combination regimens. When it is used prior to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but it appears that paclitaxel-based combinations can achieve a substantial response rate in patients with relapsed disease.     

Twins in spirit part II: DOTATATE and high-affinity DOTATATE—the clinical experience

Purpose

Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1–5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr³-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of ⁶⁸Ga-DOTA-iodo-Tyr³-octreotate [⁶⁸Ga-DOTA,3-iodo-Tyr³,Thr⁸]octreotide (⁶⁸Ga-HA-DOTATATE; HA, high-affinity) compared to the established ⁶⁸Ga-DOTA-Tyr³-octreotate (⁶⁸Ga-DOTATATE) in vivo.

Methods

The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.

Results

⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE showed comparable uptake in the liver (SUV_mean 8.9?±?2.2 vs. 9.3?±?2.5, n.s.), renal cortex (SUV_mean 13.3?±?3.9 vs. 14.5?±?3.7, n.s.) and spleen (SUV_mean 24.0?±?6.7 vs. 22.9?±?7.3, n.s.). A somewhat higher pituitary uptake was found with ⁶⁸Ga-HA-DOTATATE (SUV_mean 6.3?±?1.8 vs. 5.4?±?2.1, p?<?0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. ⁶⁸Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and ⁶⁸Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUV_max of all lesions was not significantly different between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE (17.8?±?11.4 vs. 16.7?±?10.7, n.s.).

Conclusion

Our analysis demonstrated very good concordance between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE PET data. As the availability and use of ⁶⁸Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other ⁶⁸Ga-labelled hsst analogues.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Mammary Involution and Breast Cancer Risk: Transgenic Models and Clinical Studies

Postlactational involution is the process following weaning during which the mammary gland undergoes massive cell death and tissue remodeling as it returns to the pre-pregnant state. Lobular involution is the process by which the breast epithelial tissue is gradually lost with aging of the mammary gland. While postlactational involution and lobular involution are distinct processes, recent studies have indicated that both are related to breast cancer development. Experiments using a variety of rodent models, as well as observations in human populations, suggest that deregulation of postlactational involution may act to facilitate tumor formation. By contrast, new human studies show that completion of lobular involution protects against subsequent breast cancer incidence.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Serial evaluation of left ventricular function by radionuclide ventriculography at rest and during exercise after orthotopic heart transplantation

Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients <6 months, 7–12 months, 13–24 months and >24 months after transplantation. Ejection fraction decreased significantly from <6 months to 13–24 months after transplantation (rest: 69.1%±9.7% to 56.7%±8.3%, P<0.05; exercise: 70.4%±11.3% to 59%±8%, P<0.05). Heart rate increased significantly during exercise after >2 years (90.2±10.5 beats/min to 103.5±15 beats/min, P<0.05) but not within 6 months after transplantation (98.5±12.8 beats/min to 99.07±15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2±0.96 edv/s <6 months after transplantation to 3.3±0.66 edv/s (P<0.05) 13–24 months and 3.3±0.64 edv/s (P<0.05)>24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation.     

Determinants of bone mass in end-stage renal failure patients at the time of kidney transplantation

Abstract: Background:  Patients with chronic renal failure (CRF) are at high risk of renal osteodystrophy. Our study aimed to identify predictors of bone mass and cumulative fracture rate at the time of renal transplantation (RTx). This is important since the patients experience further substantial bone loss the first month post-transplant.
Material and methods:  Altogether 133 renal transplant patients were examined for bone mineral density (BMD) using dual-energy X-ray absorptiometry shortly after RTx.
Results:  The patients' Z -scores were significantly lower at the time of RTx compared to the reference population (p < 0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical activity (p = 0.027) were associated with high BMD. Cumulative fracture rate (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and osteopenia (p < 0.001) at the time of RTx.
Conclusion:  In a representative CRF population, BMD was reduced. Independent predictors of BMD were as for the general population, and uremia associated predictors were time on HD, previous transplantation and serum iPTH level. Fracture rate was high, and physical inactivity had the strongest association with fractures.