Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of combination therapy with irinotecan and capecitabine has been demonstrated for the first-line treatment of metastatic colorectal cancer (MCRC). The aim of this trial was to evaluate the efficacy and safety of this combination in MCRC as second-line treatment after failure of 24-h infusional 5-fluorouracil (5-FU24h) and folinic acid (FA). Patients pre-treated with 5-FU24h/FA were recruited at two institutions to receive 6 x weekly irinotecan 70 mg/m2 and capecitabine (1000 mg/m2 b.i.d. days 1-14 and 22-35). Courses were repeated on day 50. In elderly patients (>65 years) a 20% dose reduction of both drugs was scheduled. Twenty-eight patients [M/F 20/8; median age 65 years (range 44-79); median ECOG score 1] were enrolled. The most frequent sites of metastases were liver, n=20, lymph nodes and lungs, n=10, respectively. Half of the patients had two or more metastatic sites. A total of 71 treatment courses (median 2, range 1-8) were administered. Main toxicities [worst per patient (%); CTC grade 1/2/3/4] were: anaemias 18/14/-/-; leukocytopenia 11/21/-/-; thrombocytopenia 11/-/-/-; diarrhea 18/36/21/-; nausea/vomiting 43/29/4/-; mucositis 4/11/-/-; alopecia 7/25/-/-; hand-foot syndrome 7/21/-/-; fatigue 14/14/-/-; renal insufficiency (caused by diarrhea and exsiccosis) -/-/-/7. Dose intensity in the first course was [median/mean (%)]: irinotecan 92/83; capecitabine 88/82. Twenty-three patients are evaluable for response analysis (five did not complete the first course): three patients showed partial remissions (13%) and 11 patients had stable disease (48%). Median time to progression was 3.0 months for the total population (range 1.4-17.3) and 6.5 months for responders (partial response plus no change). Seventy-four percent of the patients received a third-line therapy. Overall survival was 15.7 months calculated from the start of study treatment. Second-line therapy with irinotecan and capecitabine yielded a tumor control in 61% of patients with MCRC. Efficacy and toxicity data are comparable to 5-FU/irinotecan combinations, although the likelihood of severe diarrhea appears to be higher with capecitabine/irinotecan.
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PMID:Irinotecan and capecitabine as second-line treatment after failure for first-line infusional 24-h 5-fluorouracil/folinic acid in advanced colorectal cancer: a phase II study. 1561 2

Osteotropic radiopharmaceutical uptake has been reported in a wide variety of benign and malignant soft tissue tumors. We present an unusual case of pancreaticoblastoma with mesenteric and omental metastases detected by bone scan in a 69-year-old man who presented with fever, weight loss, and renal insufficiency. Pancreaticoblastoma is a rare childhood tumor that may occur in adults, although only two cases of adults with metastatic disease have been described.
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PMID:Adult metastatic pancreaticoblastoma detected with Tc-99m MDP bone scan. 1602 62

Hepatic resection is the treatment of choice for primary and secondary hepatic tumors but only 15-25% of patients with hepatic colorectal metastases are eligible for a curative hepatic resection. Cryosurgical ablation (CSA) is employed when curative resection of metastases cannot be obtained. Sixty-four patients (35 males, 29 females, mean age 58.8 years, range 30-79 years) with hepatic colorectal metastases underwent CSA, under laparoscopic control (15 cases) or with open surgery (49 cases), with subsequent close follow-up. Intraoperative bleeding occurred in 32 out of 49 patients in the open group and only in 2 patients in the laparoscopic group. Minor morbidity that resolved with conservative treatment was 54.8% in the open group and 53.3% in the laparoscopic group. Major morbidity occurred in 11 cases (26.2%) in the open group and in 1 case (6.7%) in the laparoscopic group. Mortality occurred in two patients, both in the open group, from renal insufficiency in one case and from liver failure in the other case. Mean hospital stay was 16.7 days in the open group (range 8-72 days) and 10.6 days in the laparoscopic group (range 3-18 days). No patient was lost to follow-up. At a mean follow-up of 87.1 months (range 52.2-125.2 months), selected patients undergoing laparoscopic CSA had an overall survival rate of 66.7% (10 patients), with 30% of patients (3) who are disease-free. Median survival was 94.2 months. Recurrence was observed in seven patients. None of the intrahepatic recurrences was at the cryoablation site. In the open group, median survival was 22.9 months with a survival rate of 30.9% (13 patients) at a mean follow-up of 39.3 months (range 1.9-124.5 months); 9 patients (19.1%) are disease-free. In selected patients, laparoscopic CSA is associated with survival rates which are similar to those after hepatic resection. In patients with a larger tumor burden, CSA offers a curative treatment to patients with otherwise a dismal prognosis and it improves survival as compared to patients receiving chemotherapy alone. However, the procedure is associated with substantial morbidity, particularly bleeding, and therefore careful patient selection is recommended.
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PMID:Cryosurgical ablation of hepatic colorectal metastases. 1805 96

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients. Among them, 50-60% had decreased renal function defined as CrCl below 90 and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of RI or were potentially nephrotoxic drugs. Since patients and drugs used differ depending on the type of tumour, the IRMA Study Group started analyses in different subgroups of patients. In the 1898 IRMA patients with breast cancer, the prevalence of RI was still very high in spite of a normal serum creatinine in almost all cases. Some anticancer drugs, as in particular some bisphosphonates, capecitabine and platinum salts, may be nephrotoxic and/or need dosage adjustment. However other important drugs in breast cancer do not require dose reduction, and do not present with potential nephrotoxicity (anthracyclines, taxanes, trastuzumab). Both issues seem to be slightly but significantly more important in patients with bone metastases as compared to patients with a non-metastatic disease.
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PMID:Prevalence of renal insufficiency in breast cancer patients and related pharmacological issues. 1870 81

A 59-year-old man underwent total gastrectomy and splenectomy for gastric cancer 14 months before admission. The pathological diagnosis was neuroendocrine carcinoma of the stomach. Eight months after the operation, systemic chemotherapy with irinotecan and cisplatin was started because of multiple metastases to lymph nodes. After two courses of chemotherapy, renal function continued to decline. Renal biopsy showed acute tubular necrosis with cast formation, where needle crystallization was found. These clinicopathological findings suggested that tumor lysis syndrome was the cause of acute renal insufficiency. Moreover, diffuse, global bubbling and focal segmental spike formation were revealed by periodic acid-silver methenamine stain in the glomerular basement membrane. Electron microscopy showed an infolding of the cytoplasm of podocytes into the basal basement membrane and spotty electron-lucent areas. These ultrastructural findings, but not epimembranous deposits, corresponded with the bubbling on PAM staining. The present case was a rare case of glomerulopathy associated with podocytic infolding, which was not associated with collagen disease but with tumor lysis syndrome.
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PMID:A case report of glomerulopathy-associated podocytic infolding in a patient with tumor lysis syndrome. 1897 61

Advanced or metastatic renal carcinoma represents a frequent disease in oncologic practice. Few years ago, in immunotherapy era, treatments had quickly reached deadlock. New therapies targeting vascular endothelial growth factors and their receptors (VEGF-R), sorafenib, sunitinib and bevacizumab, and the mammalian target of rapamycin (mTOR), temsirolimus and everolimus, have modified these patients prognosis and their quality of life in a few years. Nevertheless, patients included in randomized trials presented severe inclusion criteria. Then in the daily practice, patients have distinctive characteristics which were not evaluated in large pivotal studies: poor performance status, older patients, renal dysfunction, cerebral metastases or non clear cell renal cancer. In published trials, a few data concerning these situations are reported, and these studies have often included small samples, were retrospective or not randomised. However compared to global population, tolerance have not been very different in geriatric patients, or patients with poor performance status, or with central neurological metastases, or with papillary and chromophobe sub-types. On the contrary progression free or overall survivals increases are more difficult to confirm. Also before starting treatment, ratio between potential benefit and possible toxicities have to be evaluated. In patients with renal insufficiency, VEGF receptor inhibitors seem to be cautiously initiated at reduced doses, and to be increased according to tolerance. Due to these poor proof levels, clinical trials are needed for these specific populations.
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PMID:[Advanced renal carcinomas with special situations. How to treat them?]. 2041 7

Superscans on bone scintigraphy have been described mostly in metastatic and metabolic bone diseases, with different patterns and appearances of radiotracer uptake. This is a report of bone scintigraphy demonstrating superimposed metastatic and metabolic superscan in a patient with prostate cancer, who subsequently developed renal osteodystrophy. Two years after the first bone scintigraphy showing multiple metastases, the patient developed renal insufficiency, hyperphosphoremia, and hypocalcemia. Repeat bone scintigraphy demonstrates significantly different appearance from that of the first study. Caution should be exercised when interpreting a bone scintigraphy in patients with known malignancy and coexisting renal failure or metabolic bone disease. Superimposed appearances of metastatic and metabolic superscan may obscure recognition of osseous metastases.
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PMID:Super-superscan on a bone scintigraphy. 2128 85

Intravenous cis-Diamminedichloroplatinum-II (CDP) was administered to 10 patients with osteosarcoma to treat the primary tumor in 8 and bone metastases in 2. Three patients also had pulmonary metastases. The intent was to deliver 7 courses (150 mg/M2 q 2 weeks) over 3 months (total cumulative dose 1050/mg/M2). However, this was only accomplished in 2 patients; in the remaining 8 the full course was not administered because of temporary renal insufficiency (3), tumor escape (1) and apparent response after 4-6 courses suggesting that no further benefit would accrue (4). Overall, clinical and/or radiologic responses were observed in 9 patients. In 6 of 9 tumors subjected to surgical resection (66%), necrosis in excess of 65% was observed. Optimum results were achieved with a cumulative dose of 600 mg/M2 administered over 6 weeks. These results suggest that intravenous CDP may be as efficacious as intra-arterial CDP which has produced similar responses.
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PMID:Pediatric osteosarcoma - treatment of the primary tumor with intravenous cis-diamminedichloroplatinum-ii (cdp) - comparison of the results with the reported efficacy of intraarterial cdp. 2157 59

Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span. DISEASE NAME AND SYNONYMS: Glucose-6-phosphatase deficiency or G6P deficiency or glycogen storage disease type I or GSDI or type I glycogenosis or Von Gierke disease or Hepatorenal glycogenosis.
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PMID:Glucose-6-phosphatase deficiency. 2159 42

Three patients who had metastatic urothelial carcinoma have been administered gemcitabine monotherapy (GEM). A 78-year-old male who underwent nephroureterectomy for right ureteral cancer presented with liver and retroperitoneal lymph node metastases postoperatively. GEM was administered because of severe renal insufficiency. Although 8 cycles of this therapy were done, we discontinued it because of progressive disease. A 68-year-old male who underwent nephroureterectomy for left ureteral cancer presented with retroperitoneal lymph node metastasis postoperatively. GEM for the purpose of maintenance therapy was administered after first-line chemotherapy. He maintained a stable disease after 9 cycles. A 70-year-old female who underwent transurethral resection of a bladder tumor presented with neck lymph node metastasis postoperatively. She was administered GEM for second-line chemotherapy as an outpatient because she did not want hospital treatment. However, it failed due to progressive disease after 3 cycles. There were few adverse events that forced the patient to be admitted into the hospital, although bone marrow suppression of grade 3 or 4 occurred in 2 patients. GEM for metastatic urothelial carcinoma may be adapted for patients who have severe renal insufficiency and need maintenance therapy.
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PMID:[Experience with gemcitabine monotherapy in three patients with metastatic urothelial carcinoma]. 2219 Dec 80


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