1/17. Mutations of the adenomatous polyposis coli and p53 genes in a child with Turcot's syndrome.Turcot's syndrome is a rare heritable complex that is characterized by an association between a primary neuroepithelial tumor of the central nervous system and multiple colonic polyps. The aim of this study was to analyze genetic alterations in a case of Turcot's syndrome in a 10.5-year-old boy in whom a colorectal tumor developed 3.5 years following astrocytoma. An APC germline non-sense mutation at codon 1284 leading to a truncated protein was identified, as was a somatic p53 mutation in the colorectal carcinoma in exon 7, codon 244. The latter was not identified in the primary astrocytoma. However, immunohistochemistry revealed high p53 protein expression in both tumors, suggesting an additional p53 mutation in the primary astrocytic tumor. The diverse p53 mutations observed in this unique syndrome in two different sites and stages of the disease may shed light on the multistep progression of the malignant events.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/17. Colorectal cancer: dilemmas regarding patient selection and toxicity prediction.Irinotecan (Campto, Rhone-Poulenc Rorer) is probably the most studied drug used as second-line treatment for colorectal cancer. Its main disadvantages are toxicity and cost. Delayed diarrhea and neutropenia are the most common toxic side effects, both of which can usually be predicted, by knowing the criteria for patients who are at increased risk for those side effects. These criteria include poor performance status (>2), bulky disease, previous abdominal-pelvic irradiation, hyperleukocytosis and increased bilirubin >1.5 x normal upper range. There are some other less common toxic effects of irinotecan, such as pneumonitis, cardiac arrhythmia, paralytic ileus, liver dysfunction, tumor lysis syndrome. While these side effects are very rare, physicians should be able to recognize them, because the number of patients being treated with irinotecan is increasing. The authors report four cases of probable irinotecan-related toxicity with fatal outcome in all 4 patients. Two of these 4 patients were not in the known risk categories for irinotecan toxicity. One patient died with signs of hepato-renal syndrome, the other with signs of rapid tumor lysis-like syndrome. Two other patients with bulky disease and performance status 2, had increased urea, creatinine and bilirubin serum levels after irinotecan administration, that could not be explained as manifestation of disease progression only. Data on all uncommon irinotecan toxic effects should be gathered and analyzed so that toxic effects, other than diarrhea and neutropenia, are better defined and predicted.- - - - - - - - - - ranking = 69.488871564216keywords = disease progression, progression (Clic here for more details about this article) |
3/17. Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway.The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyperplastic polyposis syndrome associated with two synchronous carcinomas, one of which arises within a pre-existing hyperplastic lesion. comparative genomic hybridization was used to determine genetic changes in both carcinomas and several associated hyperplastic lesions. Microsatellite analysis at five loci was performed on carcinomas and representative hyperplastic polyps, and p53 status was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. microsatellite instability was not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic polyp with mild adenomatous change associated with the carcinoma, or a separate serrated adenoma. allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic progression followed the typical genetic pathway of common colorectal carcinoma and occurred synchronously with mutation of p53.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
4/17. Oxaliplatin-induced fever and release of IL-6.BACKGROUND: Oxaliplatin is a novel cytotoxic agent with documented activity in colorectal cancer. Side effects are generally moderate, and include peripheral neuropathy along with mild bone marrow suppression and gastrointestinal side effects. To our knowledge, induction of febrile episodes by this agents has not been described in the literature. CASE REPORT: We present the case of a 74-year-old male patient admitted to our institution for palliative treatment of metastatic colorectal carcinoma. Due to progression during treatment with 5-fluorouracil and leucovorin, chemotherapy consisting of oxaliplatin 85 mg/m(2) on days 1 15 plus mitomycin C 8 mg/m(2) on day 1 repeated every 28 days was initiated. The first cycle of this combination was tolerated without side effects, but the patient experienced fever up to 39 degrees C starting 2 h after oxaliplatin administration on day 15 of the second cycle, which persisted for 3 days. fever again recurred at the same interval following administration of oxaliplatin on day 1 of the next cycle. blood samples taken at regular intervals disclosed an increase in IL-6 serum levels parallel to the body temperature curve, with the peak corresponding to the highest temperature, while c-reactive protein values remained unchanged. In spite of intensive premedication with steroids, antipyretics and clarithromycin, fever promptly recurred during the third cycle of treatment. CONCLUSION: Our data suggest a clear- cut correlation between fever, the release of IL-6 and oxaliplatin administration. Whether IL-6 release is directly triggered by the application of oxaliplatin or is a bystander phenomenon, however, remains unclear at the moment.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
5/17. Irinotecan and thalidomide in metastatic colorectal cancer.Fifteen patients with metastatic colorectal cancer were treated with irinotecan (CPT-11, Camptosar) at 300 to 350 mg/m2 every 21 days and thalidomide (Thalomid) at 400 mg/d. Of the 15 patients, 11 were in a pilot study and 4 were in an ongoing phase II protocol. There were 12 men and 3 women, with a median age of 56 years (range: 29 to 79 years). patients were treated with a median of three cycles (range: one to eight cycles). The four patients enrolled in the formal protocol were not evaluable for response at the time of this report. Of the 11 patients in the pilot study, 10 were evaluable for response; there were two complete responses, two partial responses, and six progressions. Investigators noted a remarkable absence of grade 3/4 gastrointestinal toxicities, and concluded that further testing of the complete response and toxicity profile of the irinotecan/thalidomide regimen was warranted.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
6/17. 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.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
7/17. A case of colorectal carcinoma in adenoma analyzed by a cDNA array.PATIENT AND methods: A 68-year-old woman presenting with bloody stools and anemia was referred to our hospital. colonoscopy showed a Is-type tumor of 45 mm in diameter in the cecum and three Is-type tumors in the ascending colon. Ileocecal resection with regional lymph node dissection was performed. Microscopically, the large tumor consisted of a well-differentiated adenocarcinoma with a tubulovillous adenoma (TVA) component (carcinoma in adenoma). Some carcinoma (CA) cells had invaded the submucosal layer, but the lymph nodes were negative for malignancy. The other three polyps were diagnosed as TVAs. Because her family history fulfilled the Amsterdam criteria II for hereditary non-polyposis colorectal cancer (HNPCC), genetic analysis was performed. All of the four tumor tissues were classified as microsatellite stable (MSS) according to the National Cancer Institute guideline for analysis of microsatellite instability (MSI). K-ras mutation was detected in both CA and TVA lesions of the carcinoma in adenoma. To clarify relevant alterations of gene expression associated with adenoma-carcinoma progression, the gene expression profiles of these tumor tissues were analyzed by a cDNA array. RESULTS: Although the gene expression profiles were similar, insulin-like growth factor-II (IGF-II) was expressed most differentially in CA and TVA tissues. The results were further substantiated by comparison of the gene expression profiles of CA and TVA lesions of the carcinoma in adenoma. CONCLUSION: The results suggest that overexpression of IGF-II played an important role in the progression of adenoma to carcinoma in this patient.- - - - - - - - - - ranking = 2keywords = progression (Clic here for more details about this article) |
8/17. Oncologic emergencies secondary to advanced colorectal cancer successfully treated with oxaliplatin/5-fluorouracil/leucovorin: report of three cases.Metastatic/advanced colorectal cancer is considered a resistant disease and oncologic emergencies secondary to advanced disease may be regarded with a nihilistic attitude. The objective of this report is to emphasize the efficacy of the oxaliplatin/5-fluorouracil/leucovorin regimen (FOLFOX-4) in three patients presenting oncologic emergencies secondary to advanced colon cancer. The first case was a 40-year-old man with severe respiratory insufficiency due to massive carcinomatous lymphangitis; subsequently a cecal adenocarcinoma was diagnosed. The patient's conditions became life-threatening and he was admitted to the intensive care unit. The second case was a 41-year-old woman presenting with fever, abdominal mass and pain. Ultrasound and CT-scan revealed two hepatic masses (13 x 15 and 15 x 20 cm), diagnosed as liver metastases from colon cancer. The patient's condition deteriorated with intestinal obstruction secondary to the large left liver mass. The third case was a 58-year-old woman presenting with hepatic mass, fever and weight loss. Ultrasound and CT-scan showed a liver lesion occupying the right lobe (12 x 14 cm). Ultrasonically-guided biopsy and colonoscopy showed liver metastases from cecal cancer. A 5-fluorouracil/leucovorin regimen failed to improve her clinical condition and she had disease progression, inferior vena cava neoplastic thrombosis and right hydronephrosis. All three patients rapidly improved after a few cycles of oxaliplatin-containing chemotherapy. These cases demonstrate that even patients with advanced colorectal cancer presenting with oncologic emergencies and life-threatening conditions can be successfully treated with the FOLFOX-4 regimen.- - - - - - - - - - ranking = 69.488871564216keywords = disease progression, progression (Clic here for more details about this article) |
9/17. Capecitabine-induced severe hypertriglyceridemia: report of two cases.OBJECTIVE: To report 2 cases of severe hypertriglyceridemia associated with the use of oral capecitabine. CASE SUMMARIES: The first patient was a 73-year-old woman with metastatic breast carcinoma who received capecitabine 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 324 mg/dL; after 2 cycles of capecitabine, levels increased to 916 mg/dL. Although lipid-lowering treatment was initiated, triglyceride levels peaked at 1782 mg/dL by the end of the seventh cycle. Eight weeks after capecitabine treatment was stopped, triglyceride levels decreased to 118 mg/dL. The second patient was a 59-year-old man with metastatic colorectal carcinoma who was placed on capecitabine treatment at a dosage of 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 244 mg/dL; levels peaked at 1455 mg/dL at the end of the fifth cycle. Capecitabine treatment was discontinued due to disease progression, and triglyceride levels decreased to 154 mg/dL after 11 weeks. DISCUSSION: The most frequently reported adverse effects of capecitabine are gastrointestinal and hematologic effects and palmar-plantar erythrodysesthesia. Drug-induced hyperlipidemia may appear more readily in individuals with hereditary lipoprotein lipase deficiency because decreased lipoprotein lipase activity might make these individuals more susceptible to a rise in triglyceride levels. The Naranjo probability scale indicated a probable relationship between capecitabine and severe hypertriglyceridemia. CONCLUSIONS: Capecitabine should be prescribed with care, especially in patients with preexisting hypertriglyceridemia. The question of whether capecitabine actually causes hypertriglyceridemia needs careful consideration, and the possible mechanism by which it may cause this adverse effect requires further investigation.- - - - - - - - - - ranking = 69.488871564216keywords = disease progression, progression (Clic here for more details about this article) |
10/17. Sequential preoperative ipsilateral portal and arterial embolization in patients with colorectal liver metastases.BACKGROUND: Preoperative portal vein embolization (PVE) induces ipsilateral atrophy of the hepatic parenchyma to be resected, as well as contralateral compensatory hypertrophy of the residual liver. However, there are two potential problems with this technique: inadequate contralateral hypertrophy and tumor progression while waiting for the non-embolized liver to hypertrophy. We devised a strategy to deal with these two problems by performing an ipsilateral hepatic artery embolization 6 weeks after an unsatisfactory PVE in an effort to accelerate the hypertrophy of the remnant liver. MATERIALS AND methods: Two patients with colorectal liver metastases underwent to this sequential preoperative treatment in order to achieve resectability of their metastatic disease. RESULTS: Both patients successfully underwent major hepatic resection. CONCLUSIONS: In our experience sequential ipsilateral portal vein and hepatic artery embolization extended the indications for liver resection for metastatic colorectal cancer.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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