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Biomedical subjects

K Junker

Publications and source records attributed to K Junker.

At least 73 records · Page 4Linked to original sources

Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer.

PURPOSE: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable. RESULTS: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%. CONCLUSION: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.

Adult↗

Interphase cytogenetic diagnosis of bladder cancer on cells from urine and bladder washing.

In order to determine the value of fluorescence in situ hybridization (FISH) in the diagnosis and follow-up of bladder cancer interphase cytogenetics was performed on cells from urine and bladder washings. 50 ml of urine or bladder washings were collected. FISH was carried out using centromere probes for chromosomes 7, 8, 9 and 12 according to standard protocols. In each case 100 cell nuclei were analysed. Fifty-four samples from urine and 67 samples from bladder washing were analysed by FISH in comparison with results obtained by conventional cytology. Sensitivity of detection of tumor cells by FISH was 68.5% in urine and 63% in bladder washings regardless of tumor stage and grade. Sensitivity obtained by conventional cytology was 50% in urine and 77.3% in bladder washings. FISH on cells from urine samples is an effective complement to the standard urine cytology. Using centromere probes this approach is characterized by high specificity and sensitivity in tumors with T-category higher than pTa and grade higher than G1.

Carcinoma, Transitional Cell↗

Determination of telomerase activity in multifocal renal cell carcinoma.

In a consecutive series of 245 patients with renal cell carcinoma (RCC) all nephrectomy specimens were examined regarding the presence of additional multifocal lesions. Therefore, 3-mm step sections were performed and investigated by macroscopical and histopathological examination. Twenty-six multifocal tumors were found in 19 specimens by this procedure. In order to characterize the biological activity of these multifocal lesions in more detail, their telomerase activity was analyzed. Fourteen of the 23 investigated multifocal tumors (60.9%) displayed telomerase activity. In three cases the tissue probes were too small for further investigations. Telomerase activity was also detected in 10 out of 15 (66.7%) matched primary renal cell carcinomas. In contrast, all corresponding normal kidney cortex tissues used as control were telomerase negative. From our results we conclude, that small tumor lesions of RCC must be expected to have a malignant potential similar to that of primary carcinomas. Hence, nephron-sparing surgery cannot be routinely carried out even in patients with small tumors.

Carcinoma, Renal Cell↗

Pentastomid infections in Nile crocodiles (Crocodylus niloticus) in the Kruger National Park, South Africa, with a description of the males of Alofia simpsoni.

Two Nile crocodiles were obtained from two different localities in the Kruger National Park, one a healthy specimen, the other in a severely debilitated condition. Both were males over 3 m long and both harboured the three pentastome genera Sebekia, Alofia and Leiperia. The genus Sebekia was represented by three species, Sebekia wedli Giglioli, 1922, Sebekia cesarisi Giglioli, 1922 and Sebekia okavangoensis Riley & Huchzermeyer, 1995. Of the genus Alofia two species, Alofia simpsoni Riley, 1994 and Alofia nilotici Riley & Huchzermeyer, 1995 were found. The male of A. simpsoni, formerly unknown, is described and the description of the females emended. Leiperia cincinnalis Sambon, 1922 was the only Leiperia present. Whereas Sebekia and Alofia were recovered from the bronchioles and lung parenchyma, female Leiperia occurred in the trachea and bronchi, and infective larvae as well as immature males and females, were collected from the lungs, the heart and the aorta. Adult Subtriquetra (Family Subtriquetridae) were not present in the nasopharynx of either crocodile. The intensity of infection was low in the healthy crocodile and had no negative effect on the host. In contrast, the debilitated crocodile was heavily infected and its poor condition is ascribed to its high pentastome burden. Histopathology revealed lesions in the tracheal wall and the lungs accompanied by chronic granulomata with secondary fungal infection as well as severe chronic multifocal granulomatous pneumonia.

Alligators and Crocodiles↗

Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene.

Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia.

3T3 Cells↗

Familial renal oncocytoma: clinicopathological study of 5 families.

PURPOSE: We analyzed familial renal oncocytoma to provide a foundation for studies aimed at defining genes involved in the pathogenesis of renal oncocytoma. MATERIALS AND METHODS: We describe 5 families with multiple members affected with renal oncocytoma. Tumors were analyzed pathologically, and affected and nonaffected members were screened clinically and genetically. RESULTS: We identified 12 affected male and 3 affected female (ratio 4:1) individuals in the 5 families. In affected family members renal oncocytomas were often multiple and bilateral. No metastatic disease was observed. Most renal oncocytomas were detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal oncocytoma families. One identical twin pair was affected with bilateral multiple renal oncocytomas. CONCLUSIONS: Renal oncocytoma may be inherited in some families.

Adenoma, Oxyphilic↗

Experimental studies on the life-cycle of Sebekia wedli (Pentastomida: Sebekidae).

Four young Nile crocodiles (Crocodylus niloticus) were infected with infective pentastome larvae obtained from naturally infected Mozambique bream, Oreochromis mossambicus, and red-breasted bream, Tilapia rendalli swierstrai in the Kruger National Park. At day 95 post infection one of the crocodiles died and three female and four male S. wedli were recovered from its lungs. One pair was found in copula but the uteri of the females were not yet developed. Males and females were of about equal size. After 226 d post infection the three remaining crocodiles were sacrificed. Two of these harboured no pentastomes but eight were taken from the lungs of the third. The sex ratio had shifted in favour of the females, seven females and one male being present. One of the females recovered from the crocodiles was placed in saline and produced 3,400 eggs. These were used to infect eight guppies, Poecilia reticulata. Within 31 d two infective stages of S. wedli had developed in one of the guppies thus completing the life-cycle of the pentastome. S. wedli recovered from experimentally infected final hosts were slightly smaller than those recovered from a wild-caught final host.

Alligators and Crocodiles↗

Pentastomid infections in cichlid fishes in the Kruger National Park and the description of the infective larva of Subtriquetra rileyi n. sp.

During 1995, studies were conducted on the pentastome fauna of the cichlid fishes Tilapia rendalli and Oreochromis mossambicus in the Kruger National Park. The prevalence of infective pentastome larvae was 40.5% in T. rendalli and 9.2% in O. mossambicus. Encapsulated nymphs of Leiperia cincinnalis were taken from the mesentery, while Sebekia wedli was either encapsulated or free-living in the swim bladder. The subtriquetrids moved about freely in the swim bladder. L. cincinnalis was present in 0.5% of T. rendalli and 0.8% of O. mossambicus and additional descriptions and measurements of the nymphs are presented. S. wedli was present in 2.5% of O. mossambicus and a new Subtriquetra species, for which the name Subtriquetra riley n. sp. is proposed, in 7.5%. This ratio in T. rendalli was 40.5% and 2.2%, respectively. Of the infected T. rendalli, 89% harboured one or two sebekiid larvae, while a single fish harboured eight. Fish infected with S. rileyi contained only one larva each. The condition factor of infected T. rendalli was compared statistically to that of uninfected fish and no significant difference found. However, infected fish were significantly shorter and lighter than uninfected ones. S. rileyi differs from the other three known Subtriquetra spp., Subtriquetra subtriquetra, Subtriquetra megacephala and Subtriquetra shipleyi in both hook size and annulus counts. Furthermore, S. subtriquetra occurs in South American crocodilians (Riley 1986), and S. megacephala and S. shipleyi in crocodilians in India (Fain 1961). This is the first record of the genus occurring in Africa and although adult specimens of S. rileyi n. sp. were not obtained, we assume that the new species is specific to Nile crocodiles.

Animals↗

[Neoadjuvant combined therapy in stage IIIA if non-small-cell bronchial cancer].

BACKGROUND AND OBJECTIVE: The overall prognosis of patients with stage IIIA non-small-cell lung cancer is unfavourable (median survival time 12 months). Tolerance to and efficacity of a multimodal neoadjuvant treatment was assessed in a prospective study. PATIENTS AND METHODS: 25 patients (median age 59 [37-69] years), with histologically confirmed mediastinal lymph node metastases, underwent chemotherapy. Immediately after two cycles with carboplatin/Ifosfamid (dimethoate)/etoposide they received hyperfractionated accelerated radiotherapy (45 Gy; 2 x 1.5 Gy daily) with simultaneous administration of carboplatin and vindesine. This was followed by tumour resection. RESULTS: After conclusion of the neoadjuvant treatment 19 of 25 patients (76%) had a remission. Of the 20 operated patients complete resection (R0) was possible in 17 (85%) and 14 of the 20 patients with resection (70%) had histologically demonstrated marked tumour regression. Critical toxicity consisted of pneumonitis and bronchial stump problems. Median survival time of all patients was 24.8 months and for patients with R0 resection 35.9 months. CONCLUSION: Neoadjuvant multimodal treatment of stage IIIA non-small-cell lung cancer can achieve prolongation in survival time. The place of radiotherapy or radiotherapy with chemotherapy in such a treatment concept will need to be defined in a randomized study.

Adult↗

Cytogenetic, histopathologic, and immunologic studies of multifocal renal cell carcinoma.

BACKGROUND: Multifocal tumor areas occurred in 12-22% of patients with renal cell carcinoma. It is unknown whether these tumors have malignant potential and characterize a higher risk for metastases. The performance of nephron-sparing surgery in patients with low grade or low stage tumors is controversial. METHODS: Primary and secondary tumors were analyzed by conventional cytogenetics and fluorescence in situ hybridization. Production of interleukin (IL)-6, IL-10, IL-11, and transforming growth factor (TGF)-beta1 were determined using standard enzyme-linked immunosorbent assay and bioassays. RESULTS: In 15.2% of the renal cell carcinoma cases evaluated, multifocal tumors were detected. Cytogenetics revealed a concordance of primary and secondary tumors in 9 of 14 cases (64%). In 11 of 12 multifocal tumors (94%), the same immunologic activity status was observed in both primary and secondary tumors. CONCLUSIONS: Secondary tumors must be expected to have malignant potential similar to that of the primary tumors. This was underscored by the high concordance of cytogenetic, histopathologic, and immunologic data in this study.

Carcinoma, Renal Cell↗

Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment.

In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ("responders") the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ("non-responders") with a median survival period of 13.7 months (log-rank test, P = 0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.

Adenocarcinoma↗

[Discontinuous lymph node metastases ("skipping") in malignant lung tumors].

In 50 lung cancers (25 small cell lung cancers, 17 squamous cell carcinomas, 8 adenocarcinomas) pulmonary, mediastinal and cervical lymph node-metastases were analyzed. Lymph-node "skipping" was demonstrated in 46% of the investigated tumors. In seven of these cases the lymph nodes were skipped, which showed complete hyalinization as a consequence of preexisting anthracosilicosis. In 5 other tumors additional lymph nodes with preserved structure were skipped by the metastatic process. Fibrosis of lymphatic tissue after tuberculosis or exposure to ionizing radiation were further reasons for lymph-node skipping. The skipping of intact lymph nodes can be explained by anatomically demonstrable intra- and perinodal short circuit connections. Apart from that, preexisting lymph node changes (silicosis, fibrosis) play an important part.

Adenocarcinoma↗

[Regression grading of neoadjuvant non-small-cell lung carcinoma treatment].

In the scope of a multi-center-study 35 resection specimens from patients with locally advanced non-small cell lung cancer after neoadjuvant chemotherapy and radiation were processed histologically and graded according to the following regression grading system: grade I: no or only slight, in general spontaneous tumor regression, grade IIa: incomplete tumor regression with more than 10% and grade IIb less than 10% vital tumor tissue as well as grade III: complete tumor regression. In 15 patients with grade II a to III tumor regression roughly concentric foci of various size with a sequence of central tumor necrosis, narrow foam cell rim, vascular granulation tissue and peripheral scar formation were demonstrated as characteristic feature of response to neoadjuvant therapy. In patients with grade IIb to III tumor regression ("responders") median survival time of 27.9 months was significantly longer than in patients with grade I to II a tumor regression ("non-responders") with a median survival time of 12.7 months.

Adult↗

[EMLA for anesthesia of puncture sites for large lumen indwelling venous catheters for autologous plasma and erythrocyte concentrate donation].

OBJECTIVE: The analgetic effect of EMLA-Creme (Lidocaine-Prilocaine-Cream) was studied in 52 patients undergoing preoperative autologous blood and/or plasma donation. METHOD: 95 venous punctures were performed with a 18 G or 16 G cannula. Puncture pain was estimated by the patients using a visual analog painscore (VAS 0-100). The data were evaluated regarding reaction time, puncture spot and cannula diameter. RESULTS: Within 15 minutes we find a clear reduction of puncture pain. The diameter of the cannula does not correlate with the painscore. Puncture of hand-back veins seems to be more painful than cubital vein puncture. CONCLUSION: The application of EMLA-Creme results in an effective analgesia for venous puncture. 37% of our patients were punctured without any pain and 67% felt a tolerable pain (VAS: 0-10).

Anesthetics, Local↗

Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation.

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.

Adjuvants, Immunologic↗