Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An effective locoregional therapy is needed for adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may enhance the effect of radiation therapy (RT). Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent RT (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer. This finding suggested that paclitaxel/RT was a rational treatment approach for other malignancies that frequently harbor p53 mutations, such as upper gastrointestinal malignancies. We completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancer. The maximum tolerated dose of paclitaxel was 50 mg/m2/wk for 6 weeks with abdominal RT. The dose-limiting toxicities were abdominal pain within the radiation field, nausea, and anorexia. Phase II studies are now under way. Twenty-five patients with locally advanced pancreatic cancer have been entered at the phase II dose level of paclitaxel 50 mg/m2/wk with concurrent RT (total dose, 50 Gy). Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions (n = 2), asymptomatic grade 4 neutropenia (n = 3), and nonneutropenic biliary sepsis (n = 1). Of the first 18 assessable patients with pancreatic cancer treated on the phase II study, six obtained a partial response, for a preliminary response rate of 33%. In the phase II study for locally advanced gastric cancer, 20 patients have been enrolled. Of the first 19 patients who have completed treatment, nine (47%) had grade 3/4 toxicities, including nausea, anorexia, esophagitis, and gastritis. Of the first 16 patients with gastric cancer, complete and partial responses have been observed in one and eight patients, respectively, for a preliminary response rate of 56%. We have also completed treatment on 24 patients with potentially resectable adenocarcinomas of the gastroesophageal junction with neoadjuvant paclitaxel 60 mg/m2 and cisplatin 25 mg/m2, weekly for 4 weeks, with concurrent RT (total dose, 40 Gy) followed by surgical resection. Ten patients (41%) had grade 3/4 toxicities, including neutropenia, nausea, and dehydration. Of 24 patients, four complete responses (17%) and 14 partial responses (58%) were observed, for an overall response rate of 75%. Severe esophagitis was uncommon, making this a well-tolerated outpatient regimen for adenocarcinomas of the distal esophagus. These findings demonstrate that paclitaxel-based chemoradiation for locally advanced upper gastrointestinal malignancies is well-tolerated with substantial activity.
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PMID:Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. 1021 May 40

To determine the clinical usefulness of the autopsy in elderly patients, we studied a total of 231 autopsies performed during 1986 and 1995 at Jikeikai hospital. Autopsies were done after 231 of 609 deaths (38%). The autopsy rate in our hospital fell from 63% in 1986 to 17% in 1995. Most primary causes of deaths as established by clinicians before autopsy were pulmonary, neoplastic, and cardiovascular diseases. The probability of a major unexpected finding at autopsy was higher in acute pneumonia, acute myocardial infarction, and cerebrovascular disease. No primary pathological cause of death was established by pathologists at autopsy in 13 cases (The clinical diagnoses in those patients were acute pneumonia in 5 patients, acute myocardial infarction in 2 patients, sepsis in 2 patients, bronchiale asthma, cerebral infarction, uremia, gastrointestinal bleeding each in 1 patient.) The mean age of these 13 patients was higher by 5 years than the age of the group as a whole. This indicate that elderly patients have many complications and that these deaths were caused by many small changes that were not be detected at autopsy. Latent cancer was found in 23 cases (12%): thyroid and colon cancer in 6 patients each, gastric cancer in 4, prostate cancer in 3, ovarian cancer in 2, and other cancers (renal, uterine, lung, urethral, pancreatis and liver) each 1 in patient.
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PMID:[Clinical usefulness of the autopsy in elderly patients]. 1021 66

A total of 42 Japanese centenarians (9 males & 33 females) autopsied in Tokyo Metropolitan Geriatric Hospital during 22 years (1975-1996) were clinico-pathologically examined to determine details of the main cause of death. The main cause of death of the 42 cases were sepsis (16 cases), pneumonia (14 cases), suffocation (4 cases), heart failure (4 cases), cerebrovascular disorder (2 cases) and malnutrition (2 cases). Most pneumonias were caused aspiration of foreign bodies, and the origins of sepsis were pyelonephritis (7 cases), biliary tract infection (3 cases), necrotic lesions of the intestine due to ileus, ischemia and pseudomembranous colitis (3 cases) and indwelling vein catheter (3 cases). Malignant neoplasms were observed in 16 cases (38%), and 5 of them had 2 or 3 lesions. Thus, the total number of lesions of malignant neoplasms were 22, as follows; colonic cancer (36%), urinary bladder cancer (14%), lung adenocarcinoma (9%), gastric cancer (9%), malignant lymphoma (9%) and others. However, none of these malignant neoplasms were directly related with the cause of death. All 42 centenarians died not of simple "senile decay", but due to diseases.
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PMID:[Pathologic evaluation of the main cause of death in Japanese centenarians]. 1036 29

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.
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PMID:Weekly 24-h infusion of high-dose 5-flurouracil and leucovorin in patients with advanced gastric cancer. 1037 69

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.
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PMID:Misoprostol therapeutics revisited. 1119 38

Peritoneovenous shunt placement has been reported as a treatment of refractory ascites by general surgeons, but without a clearly established role. The authors successfully inserted shunts under ultrasonographic and fluoroscopic guidance in 12 patients who had symptomatic refractory ascites (nine men, three women; mean maintenance duration, 88.5 d). Nine patients had advanced liver cirrhosis (five with superimposed hepatoma). Other patients had stomach cancer, colon cancer, and complicated polycystic kidney disease. The mortality rate was 83%. Causes of death included bleeding from preexisting varices, sepsis, hepatic failure, rupture of hepatoma, and disseminated intravascular coagulation. The authors describe the feasibility, technical details, and short-term results of percutaneous peritoneovenous shunt placement.
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PMID:Percutaneous peritoneovenous shunt creation for the treatment of benign and malignant refractory ascites. 1174 23

The aim of this study was to report on 8 patients with all different non-ischemic etiologies for portal-venous gas and to discuss this rare entity and its potentially misleading CT findings in context with a review of the literature. The CT examinations of eight patients who presented with intrahepatic portal-venous gas, unrelated to bowel ischemia or infarction, were reviewed and compared with their medical records with special emphasis on the pathogenesis and clinical impact of portal-venous gas caused by non-ischemic conditions. The etiologies for portal-venous gas included: abdominal trauma ( n=1); large gastric cancer ( n=1); prior gastroscopic biopsy ( n=1); prior hemicolectomy ( n=1); graft-vs-host reaction ( n=1); large paracolic abscess ( n=1); mesenteric recurrence of ovarian cancer superinfected with clostridium septicum ( n=1); and sepsis with Pseudomonas aeruginosa ( n=1). The clinical outcome of all patients was determined by their underlying disease and not negatively influenced by the presence of portal-venous gas. Although the presence of portal-venous gas usually raises the suspicion of bowel ischemia and/or intestinal necrosis, this CT finding may be related to a variety of non-ischemic etiologies and pathogeneses as well. The knowledge about these conditions may help to avoid misinterpretation of CT findings, inappropriate clinical uncertainty and unnecessary surgery in certain cases.
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PMID:Portal-venous gas unrelated to mesenteric ischemia. 1204 50

After surgical therapy the survival outcome of gastric cancer is still poor. Early diagnosis and radical surgery are the two most important means to improve the prognosis. Radical surgery must include all lymph nodes embryologically related to stomach. The aim of this study was to verify whether an aggressive surgical strategy can increase postoperative survival rate. In the period 1990-1994 eighty two patients with gastric cancer were operated on. The M:F ratio was 1.6:1 and the mean age was 65.3 years (range 23-89). Palliative operations (6 gastroenterostomy) were performed in 7.3% of cases. In the other patients, 36 total gastrectomies (43.9%), 8 total gastrectomies extended to spleen, pancreas and colon (9.7%), 32 distal subtotal gastrectomies (39.1%) were performed. Gastric exeresis was always associated with lymph node dissection extended to level I and II (R2). In some cases level III and IV lymphadenectomy (R3) was performed according to Maruyama-Mishima technique. There were no intraoperative deaths. The operative mortality was 13.6% for total gastrectomies and 3.1% for subtotal gastrectomies. Postoperative complications occurred in 15.9% of total gastrectomies (3 anastomotic fistula, 2 wound infection, 1 subphrenic abscess, 1 melena) and in 3.1% of subtotal gastrectomies (1 sepsis). Stage III and IV cancers represented 74.4% of all cases (stage IIIA 19.6%, IIIB 21.9%, IV 32.9%). Metastatic lymph node involvement (N2+) affected 53.1% of T3 and 88.2% of T4 cancers. The mean survival rate of patients subjected to gastroenterostomy was 6 months. The 2-year survival for total gastrectomies was 42%, for subtotal gastrectomies 28.1%. In our experience, wide removal of lymph nodes and total or extended gastrectomies were performed without any increase of mortality and morbidity. In advanced stages, a wider exeresis increased survival and prevented local recurrence.
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PMID:[Radical surgical treatment of gastric cancer. Personal experience]. 1261 Dec 56

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.
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PMID:Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer. 1522 70

5-fluorouracil (5FU) and cisplatin are commonly used in the treatment of gastric cancer. Continuous 5FU appears to be more effective and less toxic than bolus administration, while increasing the dose intensity of cisplatin may be advantageous. We conducted a phase I study to establish the maximum tolerated dose (MTD) of cisplatin, which could be combined with a hybrid bolus/continuous 5-FU regimen (LV5FU2), given every 2 weeks. Thirty-six patients with advanced upper gastrointestinal carcinomas entered the study. Starting cisplatin dose was 40 mg/m2 and it was increased by 10 mg/m2 in cohorts of 3-6 patients. The pharmacokinetics of 5-fluorouracil in 14 patients were compared with those of 6 patients receiving LV5FU2 alone. All patients received prophylactic granulocyte colony-stimulating factor at cisplatin doses > or =50 mg/m2. MTD was reached at 100 mg/m2 of cisplatin and, therefore, the 90 mg/m2 dose is recommended for phase II studies. Bone marrow toxicity was the most frequent dose-limiting toxicity with 1 patient dying of neutropenic sepsis. Grade III/IV neutropenia was observed in 10 patients (27.7%). Nonhematological toxicity was infrequent and mild. Pharmacokinetic analysis showed that the addition of 90 mg/m2 or 100 mg/m2 of cisplatin to LV5FU2 significantly reduced the 5FU area under the curve. Objective response rate in 23 evaluable patients was 39.2%. The combination of LV5FU2 with bimonthly 90 mg/m2 cisplatin is feasible and active and should be further evaluated in patients with advanced gastric cancer.
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PMID:Intensified bimonthly cisplatin with bolus 5-fluorouracil, continuous 5-fluorouracil and high-dose leucovorin (LV5FU2) in Patients with advanced gastrointestinal carcinomas: a phase I dose-finding and pharmacokinetic study. 1559 12


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