Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis.
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The transcription factor nuclear factor kappaB (NFkappaB) is constitutively active in many types of cancercells and regulates the expression of several antiapoptotic genes. Previous studies demonstrated a role for the inhibition of NFkappaB in cancer therapyusing a transgenic approach in mice. We found that NFkappaB was transiently activated much greater than background constitutive levels during colon cancer cell readhesion, which rendered the readhering colon cancer cells exquisitely susceptible to apoptosis in the presence of soluble NFkappaB inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NFkappaB inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis. (+info)
KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma.
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The clinical and histopathological distinction between benign and malignant pheochromocytomas and paragangliomas is difficult, and reliable diagnostic markers are lacking. Here we have evaluated the prognostic value of human telomerase reverse transcriptase (hTERT) gene expression detected by reverse transcription PCR (RT-PCR); telomerase activity (TA) measured by TRAP (telomeric repeat amplification protocol) assay; immunohistochemical staining for Ki-67/MIB-1; and the mRNA expression of matrix metalloproteinase (MMP)-2 and EMMPRIN (extracellular matrix metalloproteinase inducer) analyzed by in situ hybridization in 32 primary pheochromocytomas or abdominal paragangliomas. hTERT was expressed in 7/11 malignant tumors (defined as presence of metastasis and/or extensive local invasion) as compared with in 2/21 benign tumors. All of the benign tumors showed <1% proliferative activity, as measured by Ki-67/MIB-1 staining. In all three patients with malignant tumors who developed metastases and/or invasive local recurrence during follow-up, the tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. TA was not a significant discriminator between benign and malignant tumors, and the value of EMMPRIN and MMP-2 as predictive markers was limited. In conclusion, the findings imply that the combined use of Ki-67/MIB-1 and hTERT, in addition to histopathology, provides a highly specific tool to identify benign pheochromocytoma and abdominal paraganglioma cases that are not at risk of developing recurrent or metastatic disease. (+info)
Role of surgery for nonmetastatic abdominal rhabdomyosarcomas: a report from the Italian and German Soft Tissue Cooperative Groups Studies.
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BACKGROUND: In the current study, the authors aim to evaluate clinical features and treatment results observed in patients from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS). METHODS: One hundred sixty-one patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the Italian studies between April 1975 and December 1995. The age range of the patients was 0-18 years (median, 4 yrs). The distribution of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal, 34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40-44 Gy); 133 Group III patients underwent neoadjuvant CT +/- surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not recommended for patients age < 3 years. RESULTS: The 10-year overall survival (OS) and progression-free survival (PFS) were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4% vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (> 5 cm, 42.1% vs. < 5 cm, 81% [P = 0.005]), age (< 10 yrs, 51.4% vs. >or= 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (+/-RT) (70.4% vs. 34.4% without it [P = 0.0015]). Most patients who achieved the delayed local control had responded well to neoadjuvant CT. CONCLUSIONS: Tumor size, histology, age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable outcomes. (+info)
Coexistence of cystic intra-abdominal lymphangiomas and diffuse venous haemangiomas in adult life.
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Diffuse haemangioma and intra-abdominal lymphangioma are rare in adults. In this case report, we present a 33-year-old female with coexisting multiple cutaneous and visceral cavernous haemangiomas and two huge intra-abdominal lymphangiomas of 25 and 35 cm in diameter. The organs involved were the liver, pericardium, renal hilus and bladder. She died due to disseminated intravascular coagulation and multiorgan failure, which resembled Kasabach-Merritt syndrome. The coexistence of generalised haemangiomas and intra-abdominal lymphangiomas and the lack of complaints until the age of 33 years makes her an unusual case in the literature. We also emphasise the other clinical conditions that should be considered in the differential diagnosis. (+info)
Fatal abdominal thorotrast granuloma.
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We report a case of fatal abdominal thorotrast granuloma seen in a 65-year-old man who had undergone a femoral angiography of thorotrast with some accidental extravasation 49 years previously. As the thorotrast granuloma gradually increased in size, it caused ureteral obstruction, venous thrombosis, and perforation of the urinary bladder and rectum. Symptomatic abdominal thorotrast granuloma is quite rare and this is the first reported case of the granuloma associated with perforation through the urinary bladder and rectum. (+info)
Neuroblastoma in adolescents.
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BACKGROUND: Less than 5% of neuroblastomas are diagnosed in adolescent patients. Previous studies of patients who were treated with less intensive chemotherapy regimens relative to currently available regimens suggested that adolescents survived longer than younger children, and this finding was related to a lack of myc-N amplification. Those reports prompted the authors to study a cohort of adolescent patients who had been included in more recent trials. METHODS: The authors investigated the presentation, treatment, and outcome in 28 adolescent patients who were enrolled in studies of the French Society of Pediatric Oncology during the period from 1987 to 1999 and who were older than age 10 years at the time they were diagnosed with neuroblastoma. The results were used to compare this subpopulation with a control group of children. RESULTS: None of the six patients with Stage I-II disease either developed recurrent disease or died. At 5 years, disease progression was high (progression-free survival [PFS], 28%) for the 9 adolescents with Stage III disease, but so was survival (overall survival [OS], 86%). The 13 adolescent patients with metastatic neuroblastoma had very poor outcomes (PFS, 18%; OS, 27%). Despite intensive therapy, advanced neuroblastoma appeared to carry a poorer prognosis in adolescent patients compared with children, although patients with Stage III disease had a more indolent course. No difference was found between adolescent patients and children regarding the clinical presentation, treatment schedule, or doses and tolerance of chemotherapy. The incidence of elevated urinary catecholamine metabolite secretion was lower in adolescents compared with children. CONCLUSIONS: Adolescent patients with advanced neuroblastoma had less favorable outcomes compared with children, even if survival in adolescents with Stage III disease seemed longer. (+info)
Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolaemic haemodilution.
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BACKGROUND: The volume expansion effect of a recently introduced hydroxyethyl starch, HES 130/0.4, was compared with the commonly used HES 200/0.5 after rapid infusion of a single large dose (up to 2 litres) administered during acute normovolaemic haemodilution (ANH). METHODS: This prospective, randomized, double-blind study included 40 patients scheduled for major abdominal surgery with no contraindication to ANH. Patients were randomized to undergo ANH with either HES 130/0.4 (n=20) or HES 200/0.5 (n=20). Blood was collected to reach a target haemoglobin level of about 8.0 g dl(-1) and simultaneously replaced by the same volume of colloid (HES 130: 1825 [SD 245] ml; HES 200: 1925 [183] ml). Heart rate, mean arterial pressure, cardiac filling pressure, and cardiac output were measured before induction of anaesthesia (baseline), 10 min after completion of ANH, before surgery, at the end of surgery and on the following morning (postoperative day 1; POD1). ANH blood was systematically retransfused during surgery or before POD1. RESULTS: Exchange of about 40% of blood volume resulted in similar haemodynamic changes in both groups. Filling pressures increased significantly, while cardiac index remained unchanged (HES 130: from 3.3 [0.4] to 3.2 [0.7] litre min(-1) m(-2); HES 200: from 3.0 [0.6] to 3.1 [0.7] litre min(-1) m(-2)). Need for crystalloids and colloids was similar between the groups during surgery and on POD1. Total blood loss (HES 130: median 2165 ml, range 660-2970 ml; HES 200: median 2464 ml, range 640-19 380 ml) and amount of allogeneic red blood cells transfused (HES 130: median 0, range 0-4 units; HES 200: median 0, range 0-18 units) were comparable in the two groups. CONCLUSIONS: This study demonstrates a good immediate and medium-term plasma volume substitution effect of HES 130 compared with HES 200. HES 130 could represent a suitable synthetic colloid for plasma volume substitution during extensive ANH. (+info)
Abdominal malignancies in patients with Wilson's disease.
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BACKGROUND: Wilson's disease is associated with heavy copper overload, primarily in the liver. Copper is a toxic metal, and might be expected to be associated with cancer induction, as iron is in haemochromatosis. However, liver cancer is currently believed to be extremely rare in this disease, and other intra-abdominal malignancies have not been reported. AIM: To assess the frequency of abdominal malignant disease in patients with Wilson's disease on long-term follow-up. DESIGN: Retrospective study in two specialist Wilson's disease clinics: Cambridge/London and Uppsala. METHODS: We reviewed the case records of 363 patients seen at three centres: Addenbrooke's Hospital, Cambridge, 1955-1987; the Middlesex Hospital, London, 1987-2000; and the University Hospital, Uppsala, Sweden, 1966-2002. Patients were grouped by length of follow-up: 10-19 years; 20-29 years; 30-39 years; and 40 years or more. RESULTS: No cancers were seen in patients followed for <10 years. For patients in the 10-19 years group, the frequency was 4.2%; at 20-29 years, it was 5.3%; and at 30-39 years, 15%. No cancers were seen in the 40+ years follow-up group. The cancers consisted of hepatomas, cholangiocarcinomas, and poorly differentiated adenocarcinomas of undetermined primary site. DISCUSSION: Patients with Wilson's disease appear to be vulnerable to the formation of aggressive malignant intra-abdominal tumours during long-term follow-up, irrespective of treatment. Ultrasound scanning of the abdomen seems to be a useful screening procedure. (+info)