Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme involved in the degradation of 5-FU. DPD activity in peripheral blood mononuclear cells of 30 esophageal cancer patients treated with 5-FU and low-dose CDDP with irradiation was determined at the beginning of each cytostatic cycle, the objective being to determine if DPD activity is related to the occurrence of side-effects and responses to therapy. The DPD activity showed interpatient variability (mean: 325.5 pmol/min/mg protein). 5-FU-related side-effects tended to be registered more frequently in patients with low DPD activity. In particular, nausea occurred in 30.8% of patients in the high DPD activity group but, in 70.6% in those with low DPD activity (p < 0.05). The relationship between the histological response to therapy and DPD activity was nil. We propose that determination of DPD activity prior to initiation of 5-FU-based chemotherapy for patients with esophageal cancer could aid in identifying those at risk for toxicity.
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PMID:Role of dihydropyrimidine dehydrogenase activity in patients with esophageal cancer. 1255 94

Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m(2)) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m(2). Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m(2)) with docetaxel fixed at 35 mg/m(2). Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11% of patients. Severe neutropenia was rare (grade 4: 2%, grade 3: 23%). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m(2) and irinotecan 60 mg/m(2) on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.
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PMID:Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. 1264 88

Esophageal squamous papilloma is an uncommon benign squamous epithelial polypoid tumor and is usually identified as a solitary lesion in the lower esophagus. Chronic mucosal irritation and infection with human papilloma virus (HPV) are two proposed etiologies. However, the natural history of esophageal squamous papilloma is unknown, and whether it can develop to esophageal cancer is also controversial. The authors report a case of esophageal papillomatous polyposis in which the presence of high-risk HPV DNA was proven by type-specific polymerase chain reaction (PCR). The patient was an 83-year-old man referred to our hospital with complaints of nausea and dysphagia. Esophago-gastroduodenoscopy (EGD) was carried out, and diffuse polyposis of the entire length of the esophagus and stenosis in the antrum of the stomach were revealed. Histological examination of the tissue confirmed the diagnosis of squamous papilloma of the esophagus and poorly differentiated adenocarcinoma of the stomach. Furthermore, HPV type-specific PCR was carried out in the biopsied specimens, and HPV type-16 and type-33 were detected. One month after total gastrectomy performed for the treatment of gastric cancer, follow-up EGD was carried out, and complete regression of the esophageal polyps was noted. This case is rare and supports the evidence that esophageal squamous papilloma is caused by infection with HPV. Furthermore, this case also reflects a unique aspect of the natural history of esophageal papillomatous polyposis.
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PMID:Regression of esophageal papillomatous polyposis caused by high-risk type human papilloma virus. 1285 74

Advanced thoracic esophageal cancer has a poor prognosis despite advances in surgery, such as three-field lymph node dissection. Multimodal therapy is needed to improve local control, resectability and survival rate. Fifteen patients with advanced squamous cell carcinoma of the thoracic esophagus were treated with neoadjuvant chemoradiotherapy (NAC) combined with concurrent radiation (30 Gy/12 f) and 3 courses of 5-FU and CDDP (CDDP 5 mg/m2/day + 5-FU 250 mg/m2/day: day 1-5: div). In the absence of unresectable disease and surgical risk, 12 patients underwent esophagectomy (Group 1) and 3 patients underwent additional chemoradiotherapy because of high surgical risk (Group 2). Side effects consisted of nausea, vomiting and myelo-suppression in 8 patients, but all patients tolerated and completed a full course of NAC. The effective rate (CR + PR) of NAC was 58.3% in Group 1 and 66.7% in Group 2. No patients showed pathological CR. Two-year survival rate was 28.1% in Group 1 (PR: 33.3%, NC: 20.0%) and 33.5% in Group 2. This protocol had acceptable toxicities but did not show survival benefit. Further trials are necessary to improve survival rate.
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PMID:[Neoadjuvant chemoradiotherapy for advanced squamous cell carcinoma of thoracic esophagus]. 1475 Mar 20

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.
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PMID:Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results. 1568 29

Disease associated with exposure to mycotoxins is known as the "Great Masquerader" of the 21st century because of its complex natural history involving different tissues and resembling different diseases at each stage in its evolution. It can present with a variety of nonspecific clinical signs and symptoms such as rash, conjunctivitis, epistaxis, apnea, cough, wheezing, nausea, and vomiting. Some cases of vomiting illness, bone marrow failure, acute pulmonary hemorrhage, and recurrent apnea and/or "pneumonia" are associated with exposure to mycotoxins. Familiarity with the symptoms of exposure to the major classes of mycotoxins enables the clinician to ask pertinent questions about possible fungal exposures and to remove the infant or child from the source of exposure, which could be contaminated food(s), clothing and furniture, or the indoor air of the home. Failure to prevent recurrent exposure often results in recurrent illness. A variety of other conditions, including hepatocellular and esophageal cancer and neural tube defects, are associated with consumption of foods contaminated with mycotoxins. Awareness of the short- and long-term consequences of exposures to these natural toxins helps pediatricians to serve as better advocates for children and families.
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PMID:What the primary care pediatrician should know about syndromes associated with exposures to mycotoxins. 1693 59

A 64-year-old woman with advanced esophageal cancer underwent chemotherapy with docetaxel/5-FU/CDDP (DFP). Adverse reactions were severe nausea and general fatigue, so the patient decided to discontinue DFP therapy. The treatment was changed to S-1/docetaxel. Adverse reactions were not so severe, so she could receive 1 course of the medication completely. After the treatment, the primary lesion showed a partial response, so we performed surgery. In the resected specimen, no malignant cell could be seen microscopically. Though the advanced esophageal cancer was regarded as a systemic disease, the appropriate combination of chemotherapy and surgery proved effective.
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PMID:[Complete response in a case of advanced esophageal cancer treated with docetaxel/5-FU/CDDPand S-1/docetaxel as neoadjuvant chemotherapy]. 1840 33

A 65-year-old woman, who had been operated by subtotal esophagectomy for esophageal cancer, was diagnosed as multiple liver metastases and celiac lymph node metastases one year after operation. The response evaluation revealed progressive disease after she had been suffering from nausea and anorexia throughout 2 courses of FP therapy. She refused to continue any more systemic chemotherapy, so we proposed an alternative to her, hepatic arterial infusion chemotherapy (HAI) for multiple liver metastases and radiation therapy for celiac LN metastases. Despite the marked reduction of all target lesions and maintenance of tumor marker level below the normal limits after 50 Gy of irradiation and 5 courses of HAI, a novel solitary tumor had appeared in S3 of the liver and an abdominal pain during HAI had occurred at the end of 5th course of HAI. The angiogram revealed occlusion of hepatic artery, suggesting that the emergence of new lesion was attributed to unequal distribution of the drug. Six weeks after a cessation of HAI, a subsequent CT scan showed a rapidly enlarged new lesion in S3, so that a surgical resection for this tumor was performed. The patient is alive without recurrence more than 10 months after the diagnosis of multiple liver metastases (2 months after the last surgery).
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PMID:[A case of multiple liver and celiac lymph node metastases after curative esophagectomy for esophageal cancer successfully treated with hepatic arterial infusion and radiation therapy]. 2003 19

Curative treatment of esophageal cancer with definitive or preoperative high-dose chemoradiotherapy inflicts a major strain on the patients with potentially severe physical, emotional, and social consequences. The aim of this study was to assess various aspects of quality of life and fatigue in long-term survivors following such a treatment. Patients undergoing a potentially curative treatment between 1996 and 2007, and still alive (n= 41) completed quality of life questionnaires of the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30) and esophageal cancer module (QLQ-OES18). Twenty patients were treated by surgery alone, and 21 patients were scheduled for high-dose chemoradiotherapy followed by surgery. Five of those patients did not undergo planned surgery. Preoperative chemoradiotherapy consisted of three courses of chemotherapy, cisplatin 100 mg/m(2) and 5-fluorouracil 5000 mg/m(2) in each course and concomitant radiotherapy of a median dose 66 Gy. Quality of life in esophageal cancer patients receiving high-dose chemoradiotherapy was compared with that for esophageal cancer patients who received only surgery, head and neck cancer patients, laryngectomized patients, and a random sample of the general Norwegian population. Esophageal cancer patients treated by high-dose chemoradiotherapy had significantly worse global quality of life as reflected by almost all functional scales and higher fatigue compared with esophageal cancer patients who received surgery alone, head and neck cancer patients, and the general Norwegian population. There were no significant differences in quality of life between the esophageal cancer patients receiving high-dose chemoradiotherapy and the laryngectomy patients. Further, the esophageal cancer patients receiving high-dose chemoradiotherapy had higher intensity of other symptoms like general pain, insomnia, nausea/vomiting, diarrhea, and constipation compared with the esophageal cancer patients who received surgery alone, head and neck cancer patients, and the general Norwegian population. High-dose chemoradiotherapy with cisplatin and 5-fluorouracil had a considerable negative long-term effect on global quality of life in patients with resectable esophageal cancer. Fatigue was a prominent long-lasting symptom in these patients.
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PMID:Health-related quality of life in long-term survivors after high-dose chemoradiotherapy followed by surgery in esophageal cancer. 2081

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5-fluorouracil (5-FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5-FU. The main treatment-related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1-2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3-4, 53% of the patients experienced grade 1-2 mucositis, and 40% experienced grade 1-2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3-4 dysphagia in weeks 3-4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1-2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1-2 dysphagia and 26% patients experienced grade 3-4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2-year disease-free survival was 53%. The median survival was 3.2 years with the 2-year overall survival of 73%. Preoperative oxaliplatin/5-FU-based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.
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PMID:Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5-fluorouracil for locally advanced esophageal cancer. 2114 94


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