Cases reported "Disease Progression"

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1/33. p53 and p16INK4A mutations during the progression of glomus tumor.

    Glomus tumors are significantly rare tumors of carotid body. The great majority of these tumors are benign in character. Here we present two brothers with hereditary glomus jugulare tumor who had consanguineous parents. radiotherapy was applied approximately 8 and 10 years ago for treatment in both cases. Eight years later, one of these cases came to our notice due to relapse. The mutation pattern of p53, p57KIP2, p16INK4A and p15NK4B genes which have roles in the cell cycle, was analyzed in tumor samples obtained from the two affected cases in the initial phase and from one of these cases at relapse. The dna sample obtained from the case in initial diagnosis phase revealed no p53, p57KIP2, p16INK4A or p15INK4B mutation. He is still in remission phase. Despite the lack of p53, p57KIP2, p16INK4A and p15INK4B mutation at initial diagnosis the tumor dna of the other case in relapse revealed p53 codon 243 (ATG-->ATC; met-->ile) and p16 codon 97 (GAC-->AAC; asp-->asn) missense point mutations. No loss of heterozygosity in p53 and p16INK4A was observed by microsatellite analysis of tumoral tissues in these cases. P53 and p16INK4A mutations observed in relapse phase were in conserved regions of both genes. No previous reports have been published with these mutations in glomus tumor during progression. The mutation observed in this case may due to radiotherapy. In spite of this possibility, the missense point mutations in conserved region of p53 and p16INK4A genes may indicate the role of p53 and p16INK4A in tumor progression of glomus tumors.
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2/33. Development of IgG lambda multiple myeloma in a patient with cutaneous CD30 anaplastic T-cell lymphoma.

    We report a patient with an epidermotropic cutaneous T-cell lymphoma which transformed into an anaplastic cutaneous CD30 T-cell lymphoma. Repeated relapses required prolonged systemic puva therapy. Two years after diagnosis, the patient had several episodes of infections of the respiratory tract. serum electrophoresis now revealed significantly reduced polyclonal immunglobulin production and an additional band in the gamma fraction corresponding to IgG lambda monoclonal gammopathy. Thereafter, the patient suffered a pathologic fracture of the dorsolateral 5th rib on the right side and an accumulation of monoclonal plasma cells in the bone marrow confirmed the diagnosis of multiple myeloma (IgG lambda). Accordingly, 6 cycles of cytoreductive chemotherapy (alkeran, decortin) were given. After one year of steady state disease the patient lost weight and bone pain increased while only a few papular eruptions were detectable. radiography showed multiple small osteolytic areas. A few months later he died with signs of bone marrow insufficiency.
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3/33. Prolonged remission of recurrent, metastatic placental site trophoblastic tumor after chemotherapy.

    BACKGROUND: Placental site trophoblastic tumor (PSTT) is a form of gestational trophoblastic neoplasm that is frequently resistant to chemotherapy. In most cases disease is confined to the uterus and can be cured by curettage or simple hysterectomy. patients with metastases, however, frequently have progression of disease and die despite aggressive multiagent chemotherapy. CASE: A 31-year-old woman was found on review of uterine curettings to have a PSTT. Imaging studies revealed multiple lung lesions, a liver lesion, and an enlarged irregular uterus. hysterectomy and staging surgery revealed a large tumor in the endometrial cavity and multiple metastases. She was treated with etoposide-methotrexate-dactinomycin and cyclophosphamide-vincristine and had a complete clinical remission. Six months later, however, she had a recurrence. She was then treated with six cycles of etoposide-methotrexate-dactinomycin and etoposide-cisplatin. Three years after completion of the second regimen she is without evidence of disease. CONCLUSION: Treatment with multiagent chemotherapy can produce long-term remission, even in patients with recurrent, metastatic PSTT. Addition of platinum may be helpful in patients who have recurred or progressed after treatment with non-platinum-containing regimens.
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4/33. FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).

    The hallmark of the 8p12 stem cell myeloproliferative disorder (MPD) is the disruption of the FGFR1 gene, which encodes a tyrosine kinase receptor for members of the fibroblast growth factor family. FGFR1 can be fused to at least 3 partner genes at chromosomal regions 6q27, 9q33, or 13q12. We report here the cloning of the t(8;9)(p12;q33) and the detection of a novel fusion betweenFGFR1 and the CEP110 gene, which codes for a novel centrosome-associated protein with a unique cell-cycle distribution. CEP110 is widely expressed at various levels in different tissues and is predicted to encode a 994-amino acid coiled-coil protein with 4 consensus leucine zippers [L-X(6)-L-X(6)-L-X(6)-L]. Both reciprocal fusion transcripts are expressed in the patient's cells. The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of circa 150-kd, which retains most of CEP110 with the leucine zipper motifs and the catalytic domain of FGFR1. Transient expression studies show that the CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm. (blood. 2000;95:1788-1796)
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5/33. cell cycle proteins as molecular markers of malignant change in vulvar lichen sclerosus.

    Lichen sclerosus (LS) has a known association with the development of squamous cell carcinoma of the vulva. The purpose of this study was to investigate molecular markers, which could indicate premalignant changes. Multiple sequential vulvar biopsies were taken over a period of 11 years from a patient with longstanding LS. Immunohistochemical staining was used to demonstrate a range of molecular markers. Increased expression of p53 and Ki67 was found in areas of squamous hyperplasia (SH) and differentiated vulvar intraepithelial neoplasia (dVIN) which correlated with the subsequent development of invasive squamous cell carcinoma (SCC). Molecular changes have been found to accompany histologic changes in the progression of vulvar LS to malignancy. Such markers may prove a useful addition in the clinical management of these conditions.
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6/33. Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure.

    BACKGROUND: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. CASE REPORT: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m(2) (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). CONCLUSION: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure.
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7/33. Decline in long-term circadian rest-activity cycle organization in a patient with dementia.

    Continuous measurement of the circadian rest-activity cycle for 598 days in a demented patient with probable Alzheimer's disease revealed slow progressive changes in temporal organization until death. Circadian and sleep analysis of the actigraphic data provided objective documentation of the gradual insertion of wakefulness into rest and rest into wake periods. Pacing, a nonphotic zeitgeber strengthening, led to improved synchronization of the rest-activity cycle.
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8/33. Concurrent occurrence of chylothorax, chylous ascites, and protein-losing enteropathy in systemic lupus erythematosus.

    We describe 2 patients with systemic lupus erythematosus (SLE) who presented with chylothorax, chylous ascites, and protein-losing enteropathy. Analysis of pleural or peritoneal fluid revealed a high level of triglyceride and elevated 24 h stool alpha1-antitrypsin clearance in keeping with protein-losing enteropathy. One patient failed to respond to high dose corticosteroid therapy but recovered after 3 cycles of monthly cyclophosphamide treatment. The other patient initially responded to high dose corticosteroid therapy, but succumbed to infectious complications. This is the first report of occurrence of chylothorax and chylous ascites associated with SLE.
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9/33. endoreduplication in conjunction with tumor progression in an aneuploid laryngeal squamous cell carcinoma.

    We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied dna flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM dna index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a dna index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation.
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10/33. hepatic artery aneurysm complicating intra-arterial chemotherapy for hepatocellular carcinoma.

    We present a rare case of asymptomatic hepatic artery aneurysm that developed during therapy in a 65-year-old man who received hepatic intra-arterial chemotherapy for an inoperable hepatocellular carcinoma. The aneurysm remained unchanged although the intra-arterial chemotherapy was continued for five more cycles after its appearance.
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