Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS>70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity.
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PMID:A phase II irinotecan-cisplatin combination in advanced pancreatic cancer. 1461 93

Pancreatic cancer is a devastating disease often associated with other comorbid conditions that can complicate treatment and impact quality of life. Obstruction of the bile duct by pancreatic cancer can cause bile stasis and infection, a condition known as acute ascending cholangitis (AAC). Signs and symptoms include fever, pain, and increased serum bilirubin levels. Serious complications (e.g., sepsis, death) may be avoided with careful and timely patient assessment, prompt initiation of antibiotics, and drainage of the biliary system. AAC may present quickly, and patients can deteriorate rapidly. Nurses need to be aware of the clinical manifestations of AAC to ensure timely treatment of this sometimes fatal event.
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PMID:Acute ascending cholangitis. 1510 17

Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m(-2), 30-min infusion). Maintenance gemcitabine (1000 mg m(-2) weekly x 3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.
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PMID:Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. 1522 65

Advanced adenocarcinoma of the pancreas has a very poor prognosis. The aim of this study was to assess the efficacy and tolerability of a combination of the chemotherapeutic agents gemcitabine and raltitrexed. Chemonaive patients with advanced adenocarcinoma of the pancreas were treated with a combination of raltitrexed (3.5 mg m(-2) on day 1 of a 21-day treatment cycle) and gemcitabine (800 mg m(-2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle). Between April 2000 and February 2003, 27 patients were enrolled onto the study. The mean duration of treatment was 11 weeks. Four of 27 patients experienced at least one episode of grade 3 or 4 neutropenia. One patient with grade 4 neutropenia died due to sepsis. Four of 27 patients experienced grade 4 diarrhoea. There was one partial remission (4%) and 12 patients experienced disease stabilisation (44%). The 6-month and 1-year survival rates were 37 and 11%, respectively. Symptomatic benefit occurred in seven (26%) patients. We conclude that a combination of raltitrexed and gemcitabine, using the schedule and doses in this study, cannot be recommended for patients with advanced pancreatic cancer.
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PMID:A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma. 1566 4

Endoscopically placed biliary stents have supplanted surgical decompression as the preferred treatment option for patients with obstructive jaundice from advanced pancreatic cancer. An unusual complication of indewelling biliary stents is duodenal perforation into the retroperitoneum. We describe the case of a patient with end-stage pancreatic cancer who presented with an acute abdomen from erosion of a previously placed bile duct stent through the wall of the second portion of the duodenum. Although our patient presented with advanced symptoms, clinical presentations can vary from mild abdominal discomfort and general malaise to overt septic shock. Definitive diagnosis is best made with computed tomography (CT) imaging, which can detect traces of retroperitoneal air and fluid. Treatment options vary from nonoperative management with antibiotics, bowel rest, and parenteral alimentation in the most stable patients to definitive surgery with complete diversion of gastric contents and biliary flow from the affected area in patients with clinical symptoms or radiologic evidence suggesting extensive contamination. Complications of management can include duodenal fistulization, residual retroperitoneal or intrabdominal abscess, and ongoing sepsis. This report highlights the salient issues in the presentation, diagnosis, and modern management of patients with this rare complication of indwelling biliary stents.
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PMID:Retroperitoneal perforation of the duodenum from biliary stent erosion. 1612 9

Erlotinib has been FDA approved to be used in combination with gemcitabine as the first line treatment in advanced pancreatic cancer patients. Skin rash has been documented as one of the commonest adverse reactions in patients receiving erlotinib and other EGFR inhibitors. Draw back to this reaction leads to: 1) drug discontinuation or dose reduction; 2) impairs quality of life; and 3) Puts patients at risk of superinfection. Monitoring patients closely and initiating immediate skin care is recommended. However, patients forget how the rash started and when. No standard treatments exist secondary to the diversity of symptoms, variability and intermittent occurrence in relation to the cancer therapy. In addition, there is slow improvement with medical treatment. Also, patients need to make extra visits to doctor's office for skin management when in needed in addition to chemotherapy appointments. Late presentation for medical attention leading to complications, such as sepsis. We here experience a novel way of assessing and managing the skin rash using the electronic media. We suggest that electronic communication is of crucial importance to detect early, diagnose and treat anti-EGFR related skin rash in order to continue the benefit of anti-EGFR.
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PMID:Management of skin toxicities of anti-EGFR agents in patients with pancreatic cancer and other GI tumors by using electronic communication: effective and convenient. 2020 31

Non-small-cell lung cancer (NSCLC) and pancreatic cancer represent two major causes of cancer-related morbidity and mortality worldwide. Conventional cytotoxic agents seem to have reached a therapeutic plateau in the last decade but prognosis remains dismal for both tumour types. Recent advances in molecular biology have allowed the development of novel molecular agents that target specific pathways implicated in the process of neoplastic transformation. Epidermal growth factor receptor (EGFR) represents an appealing therapeutic target in both malignancies and a number of EGFR-targeting agents have recently been approved for the first- or second-line treatment of locally advanced, recurrent or metastatic disease. Erlotinib, an orally administered EGFR tyrosine kinase inhibitor has recently received approval by both the US FDA and the European Medicines Agency (EMA) for the treatment of advanced NSCLC after chemotherapy failure and in combination with gemcitabine for the treatment of advanced pancreatic cancer, on the basis of large, randomized, phase III trials that demonstrated survival benefit over standard therapy or best supportive care. Erlotinib toxicity, as reported in these trials, seems to be modest, with the most prevalent adverse events being fatigue, acneiform rash and diarrhoea. However, recent pharmacovigilance reports, as well as sporadic case reports from the literature, raise concern of some serious adverse events, including pulmonary toxicity, sepsis and some rare cases of treatment-related deaths. In the current review, we present an evidence-based summary of the benefits and risks associated with erlotinib treatment in both advanced NSCLC and pancreatic cancer. Evidence for survival benefit in each of the drug's indications is provided, and treatment-related risks and costs are discussed. Finally, synthetic evaluation of the benefit-risk equilibrium is attempted, in order to help clinicians put this drug into perspective.
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PMID:A benefit-risk assessment of erlotinib in non-small-cell lung cancer and pancreatic cancer. 2133 42

Multicentric Castleman's disease (MCD) is a rare polyclonal lymphoproliferative disorder that manifests with lymphadenopathy and inflammatory symptoms. In order to clarify the clinical features and actual management of MCD in Japan, we analyzed 21 patients diagnosed with MCD and treated in Kyoto University Hospital between 2005 and 2012. There were 12 men and 9 women. The median age at disease onset was 46 years, and the median follow-up period was 98 months. Common symptoms included splenomegaly (13/20), renal dysfunction (11/21), interstitial pneumonia (7/21), pleural effusion and/or ascites (7/21), and thrombocytopenia (6/21). The results of the anti-human immunodeficiency virus antibody and human herpes virus-8 DNA tests in the blood were available in 13 and 5 cases, respectively, and no patient was positive for either. Among 12 patients treated with tocilizumab, an anti-interleukin-6 receptor antibody, 11 exhibited an improvement in MCD-related symptoms and 3 achieved complete resolution of all these symptoms. In 8 patients treated with tocilizumab for over 1 year, the mean Hb level increased from 7.4 to 12.2 g/dL while the mean serum C-reactive protein level decreased from 13.2 to 0.4 mg/dL. Three patients died during the observation period due to sepsis, secondary leukemia, or pancreatic cancer. The clinical courses of most cases were indolent; however, in some cases with pleural effusion, ascites, renal dysfunction, and/or thrombocytopenia, the disease manifestation was serious. A nationwide survey is required to further clarify the epidemiology, clinical features, and optimal treatment strategies of MCD in Japan.
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PMID:Clinical features and treatment of multicentric castleman's disease : a retrospective study of 21 Japanese patients at a single institute. 2380 Nov 37

The lack of bile flow from the liver into the intestine can have devastating complications including hepatic failure, sepsis and even death. This pathologic condition known as cholestasis can result from etiologies as diverse as total parenteral nutrition (TPN), hepatitis and pancreatic cancer. The intestinal injury associated with cholestasis has been shown to result in decreased intestinal resistance, increased bacterial translocation and increased endotoxemia. Anecdotal clinical evidence suggests a genetic predisposition to exaggerated injury. Recent animal research on two different strains of inbred mice demonstrating different rates of bacterial translocation with different mortality rates supports this premise. In this study, a microarray analysis of intestinal tissue following common bile duct ligation (CBDL) performed under general anesthesia on these same two strains of inbred mice was done with the goal of identifying the potential molecular mechanistic pathways responsible. Over 500 genes were increased more than 2.0 fold following CBDL. The most promising candidate genes included MUPs, Serpina1a and LCN-2. RT-PCR validated the microarray results for these candidate genes. In an in vitro experiment using differentiated intestinal epithelial cells, inhibition of MUP-1 by siRNA resulted in increased intestinal epithelial cell permeability. Diverse novel mechanisms involving the growth hormone pathway, the acute phase response and the innate immune response are thus potential avenues for limiting cholestatic intestinal injury. Changes in gene expression were at times found to be not only due to the CBDL but also due to the murine strain. Should further studies in cholestatic patients demonstrate inter-individual variability similar to what we have shown in mice, then a "personalized medicine" approach to cholestatic patients may become possible.
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PMID:CANDIDATE GENES FOR LIMITING CHOLESTATIC INTESTINAL INJURY IDENTIFIED BY GENE EXPRESSION PROFILING. 2417 76

The aim of this study was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose (RD) of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) plus oral S-1 in patients with resectable pancreatic cancer. Thirteen patients with radiologically proven resectable pancreatic cancer were included in this study. S-1 was administered orally for 14 consecutive days, and GEM was administered on days 8 and 15 for two pre-operative cycles. The dose of S-1 in this study was planned with fixed doses of GEM (1,000 mg/m²): 20, 30 and 40 mg/day for levels 0, 1 and 2, respectively. Treatment was initiated at level 1 in 3 patients, while adverse events occurred in 2 patients during the second course, leading to a dose reduction to level 0 for the 8 remaining patients. Two of the 10 patients enrolled at level 0 were excluded. Of the remaining 8 patients, GEM administration was terminated due to DLT on day 15, during the first course in 3 patients, while level 0 dosage reached MTD. Surgery was performed for the remaining 11 patients included in the study. Post-operative complications included pancreatic fistulas in 5 patients and Pseudomonas aeruginosa sepsis in 1 patient. Two of the 11 patients exhibited a partial response and 9 patients stable disease. Eight of the 11 tumor specimens showed histopathological evidence of tumor cell injury. In conclusion, NAC with GEM and S-1 was not well-tolerated in this study. However, pre-operative chemotherapy may be effective against pancreatic cancer. Therefore, it is necessary to reconsider NAC regimens for pancreatic cancer.
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PMID:A phase I study of neoadjuvant chemotherapy with gemcitabine plus oral S-1 for resectable pancreatic cancer. 2464 44


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