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Biomedical subjects

A Wein

Publications and source records attributed to A Wein.

At least 19 recordsLinked to original sources
PubMed2006

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Adenocarcinoma↗
PubMed2005

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer.

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

Adenocarcinoma↗
PubMed2005

Neoadjuvant chemotherapy does not increase postoperative complication rate after resection of colorectal liver metastases.

BACKGROUND: This paper discusses, whether neoadjuvant chemotherapy has an impact on the rate of postoperative complications after primary resection of liver metastases from colorectal carcinoma. METHODS: Of 183 patients 64 were studied. The patients were subdivided into two matched groups of 32 patients each-prior neoadjuvant chemotherapy (CT-group) vs. (control-group, primary resection). RESULTS: There were no postoperative complications in 24 patients of the control group (75%) and 26 patients of the CT-group (81%). Following prior chemotherapy, no major complications such as liver failure were observed, even after extended resections. CONCLUSION: Neoadjuvant chemotherapy prior to surgical resection of colorectal liver metastases does not result in an increase of postoperative morbidity and mortality.

Adult↗
PubMed2005

[A case of attenuated familial adenomatous polyposis coli (AFAP)].

We describe an asymptomatic female patient who was diagnosed with multiple tubular and tubulovillous adenomas in the right-sided colon on routine colonoscopy at the age of 59 years. Genetic testing identified a germline truncating mutation at codon 405 (R405X) of the adenomatous polyposis coli (APC) gene. This mutation is located in the alternatively spliced region of exon 9, a region that is associated with an attenuated phenotype of familial adenomatous polyposis (AFAP). To our knowledge this report describes for the first time the R405X germline mutation in association with AFAP. Our patient had no extracolonic manifestations of AFAP. Treatment consisted of a right hemicolectomy with ileotransversal anastomosis plus complete endoscopic polypectomy in the left-sided colon. AFAP is a poorly defined condition with unknown prevalence and penetrance that requires individual therapy and life-long surveillance. Because of marked intrafamilial phenotypic variance, it is crucial to identify these patients and implement proper endoscopic surveillance at an early age in family members carrying this mutation.

Adenomatous Polyposis Coli↗
PubMed2004

Complete remission with long-term survival in a patient with esophageal carcinoma and a tracheoesophageal fistula after treatment with the AIO regimen and bi-weekly cisplatin.

INTRODUCTION: To date, only few reports are available on patients with esophageal carcinoma containing a tracheoesophageal fistula under chemotherapy. CASE REPORT: A 56-year-old patient presented to the hospital with a stenosing squamous cell carcinoma of the esophagus containing a tracheoesophageal fistula 3 cm above the carina. After placement of a Port-a-Cath and adequate hydration he received weekly 500 mg/m (2) i. v. folinic acid (FA) as a 1 - 2-hour infusion and 2000 mg/m (2) 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) (AIO regimen) with prior application of bi-weekly 50 mg/m (2) i. v. cisplatin. A tracheal Y-Dumont metallic stent was inserted prior to initiating systemic treatment. The patient's alimentation was completely parenteral. After three cycles of chemotherapy (six months) the patient revealed complete remission (CR) with closure of the tracheoesophageal fistula. The tracheal Y-Dumont stent could be removed and the patient had oral alimentation restored. 29 months after initiating treatment he is without evidence of disease. CONCLUSION: Patients with esophageal carcinoma containing a tracheoesophageal fistula might benefit from chemotherapy and should not be generally excluded from systemic treatment.

Antineoplastic Agents↗
PubMed2003

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study.

The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 h-continuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m(-2) in 2 mg m(-2)-steps to a maximum of 10 mg m(-2) were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m(-2)) as 24 h infusion and folinic acid 500 mg m(-2) prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10 mg m(-2)), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first- and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI(95%), 0-16) in colorectal and six (50%; CI(95%), 21-79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI(95%), 28-64%) and two gastric cancer patients (17%; CI(95%), 2-48%). The median progression-free survival was 3.1 months (range, 0.9-9.1) in colorectal and 4.6 months (range, 0.7-12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9-15.6) in colorectal and 7.1 months (range, 1.7-20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.

Adenocarcinoma↗
PubMed2003

Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy.

Connective tissue turnover plays a prominent role in tumour growth and metastasis. We followed serum levels of seven connective tissue parameters in 37 patients with colorectal cancer metastatic to the liver prior to and during chemotherapy. Serum samples with episodes of tumour control (n=112) showed an increase of matrix metalloproteinase-2 (MMP-2) (P<or=0.01) and a decrease of tissue inhibitor of MMPs (TIMP-1) levels (P<or=0.01), while serum samples with episodes of tumour progression displayed the reverse pattern (P<or=0.01 and P<or=0.05, resp.). The ratio of circulating MMP-2/TIMP-1 was also significantly higher in episodes of tumour control vs tumour progression and prior to treatment (P<or=0.0001). We conclude that serum MMP-2 appears to reflect tumour resorption, while serum TIMP-1 may mirror tumour expansion.

Adult↗
PubMed2003

[Radio-frequency-ablation (RFA) with wet electrodes in the treatment of primary and secondary liver tumours].

INTRODUCTION: The majority of patients with primary and secondary tumours of the liver cannot be treated curatively by surgery. The treatment of these patients with radio-frequency thermoablation using perfused needle applicators (wet electrodes) was evaluated in a feasibility study. METHOD: Patients with primary and secondary tumours of the liver and contraindications against surgery or LTX were included into the feasibility study. RFA was performed percutaneously under ultrasound guidance. The patients were followed up sonographically and by computed tomography. RESULTS: 20 patients (9 male, 11 female) with 35 lesions were treated with RFA. 12 patients (22 tumour locations) suffered from HCC and 8 patients (13 tumour masses) had liver metastases (colorectal, breast, pancreas, carcinoid). The median age was 65.6 years (36 to 83 years). The median tumour size was 33.5 mm. 59 RFTA applications (1.7 applications per tumour mass) were performed. The mean duration of RFTA per patient was 16.2 minutes. During the procedure isotonic saline was injected at a mean flow rate of 6.63 ml/min. All patients received local anaesthesia. In 33 sessions an additional analgosedation was necessary (average dose 63.8 mg Pethidine and 1.4 mg Midazolam). In 2 cases a reduction of the haemoglobin level, occurred, necessitating a blood transfusion. 3/4 of the treated metastases could be eradicated completely. Within a median follow-up of 145 days no intrahepatic local recurrence but 4 distant metastases occurred. 2/3 of the treated HCC could initially be brought into complete remission (CR). After a median follow-up of 329 days 5 of the 8 initially successfully treated patients with HCC were still in complete remission. In 3 cases an intrahepatic local recurrence developed. CONCLUSION: RFA with wet electrodes is a safe, effective and inexpensive treatment for primary and secondary tumours of the liver, measuring less than 4 cm in diameter.

Adult↗
PubMed2003

Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). PATIENTS AND METHODS: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. RESULTS: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. CONCLUSION: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.

Aged↗
PubMed2002

DNA microarrays: a new diagnostic tool and its implications in colorectal cancer.

Effective treatment of colorectal cancer requires early detection and diagnostic and prognostic accuracy in characterizing patients of various risk groups. The development of DNA microarray makes it possible to analyze thousands of genes in a single tissue sample in one experiment and to characterize the biological behavior of colorectal cancer cells. Different cluster algorithms have been used to analyze large datasets on gene expression data, and initial results show significant differences between colorectal cancer and normal colon tissue. Although more than 6000 genes have been analyzed between colorectal cancer and normal tissue, different expression levels have been found in only 100-500 transcripts depending on the cluster algorithm. Most transcripts belong to genes involved in cell growth regulation, differentiation of cells, ribosomal proteins or metalloproteinase. A future goal in microarray technology will be the development of clustered gene chips which characterize each tumor type specifically and focus on gene expression that specifies cell identity.

Biomarkers, Tumor↗
PubMed2002

[Palliative second-line treatment with oxaliplatin, gemcitabine and weekly high-dose 5-fluorouracil as 24-h infusion in patients with metastatic pancreatic adenocarcinoma].

The most commonly used treatment in the palliative first-line therapy of metastatic pancreatic adenocarcinoma is the Gemcitabine (Gem) monotherapy, while several combination therapies are currently being tested in clinical trials. With regard to pancreatic cancer, a palliative second-line therapy has not been established, yet. The four patients presented in this paper received a palliative second-line therapy with Oxaliplatin (L-OHP), Gem and high-dose 5-Fluorouracil (5-FU) as a 24-h infusion after a first-line therapy with Gem and weekly high-dose 5-FU as a 24-h infusion. During second-line therapy, four patients received 67 chemotherapy applications, which were well tolerated. As severe symptom of toxicity, thrombocytopenia (CTC toxicity grade 4) was observed in one patient. As a result of second-line therapy, stable disease (SD) with a significant decrease of CA 19 - 9 was achieved in three patients and partial remission (PR) in one patient. After palliative first- and second-line treatment the survival time of the patients was 9, 9, 15 and 20 months. Currently, a multicentre phase I study has been started aiming at an optimisation of the three-drug combination dosage.

Adenocarcinoma↗
PubMed2001

High-risk groups of patients with Stage II colon carcinoma.

BACKGROUND: It is unclear whether patients with Stage II colon carcinoma should be offered adjuvant chemotherapy. Therefore, the authors analyzed the risk factors of these patients to identify high-risk subgroups who may benefit from such treatment. METHODS: The data from 305 patients with Stage II colon carcinoma documented in the Erlangen Registry of Colorectal Carcinoma were analyzed to identify risk factors for distant metastasis and disease-related survival. The patients were divided into two subgroups: those in a low-risk group and those in a high-risk group. The data were then compared with those from 306 patients with Stage II colon carcinoma from the German Study Group for Colorectal Carcinoma (SGCRC). RESULTS: Emergency presentation, a primary tumor site in the left colon, pT3 tumors with a depth of invasion of > 15 mm beyond the outer border of the muscularis propria, and pT4 lesions were identified as the major risk factors for Stage II colon carcinoma. On dividing patients into subgroups according to these risk factors, it was found that patients in the high-risk group had a significantly higher risk of distant metastases and a significantly lower disease-related survival rate compared with patients in the low-risk group. On analyzing the SGCRC data, the authors also found a significantly higher rate of distant metastases in the high-risk group, but the disease-related survival rate differed only marginally. CONCLUSIONS: Among patients with Stage II colon carcinoma, it is possible to identify a high-risk group of patients who may be candidates for adjuvant chemotherapy. Stratification by the risk factors emergency presentation, tumor site, depth of tumor invasion, and surgical department should be employed in further clinical studies.

Adult↗
PubMed2001

[Prevention and therapy of diabetic foot syndrome. Preventing complications].

Selective prevention and stage-orientated treatment of the diabetic foot syndrome helps to avoid late complications. A prerequisite is good blood sugar control, early use of ACE inhibitors, CSE inhibitors and--based on the vascular situation, with consideration given to indications--platelet aggregation inhibitors. Regular inspection of the feet must be taken seriously. Every diabetic should be taught the rules of behavior in young years. The primary physician is responsible for coordinating further treatment and early referral to specialized foot clinics. In the event of an infection, specific treatment of the usually polymicrobial infection should be initiated. Long-term antibiotic treatment is not to be recommended. Wherever necessary, the calculated antibiotic therapy must be corrected on the basis of the results of antibiotic sensitivity testing of swabs taken from deep tissue (better: exudate from the floor of the wound. In the case of superinfected ulcers, wound debridement by the specialist surgeon is considered a must. Also, late stages of diabetic foot can be successfully managed in specialized centers by "foot-relieving" measures, revascularization, arthrodesis, etc.

Aged↗
PubMed2001

Treatment of overactive bladder: long-term tolerability and efficacy of tolterodine.

Previously available antimuscarinic therapies for overactive bladder are poorly tolerated due to a high incidence of adverse events, notably dry mouth. Tolterodine is a bladder-selective, antimuscarinic agent for the treatment of frequency, urgency, and urge incontinence that characterize overactive bladder. In a 9-month open-label study, the safety, tolerability, and clinical efficacy of tolterodine 2 mg twice daily was evaluated in 854 patients with overactive bladder symptoms who had completed one of four 12 week randomized, controlled trials of tolterodine. Safety and tolerability were assessed in terms of adverse events and clinical/laboratory variables. Efficacy was assessed using micturition diaries and patient perception of their bladder condition. In all, 70% of patients remained on treatment for 9 months. Dry mouth was the most frequently reported adverse event, occurring in 28% of patients (intensity: 19% mild, 7% moderate, 2% severe). A total of 9% of patients withdrew due to adverse events. Dosage reduction occurred in 13% of patients. Significant improvements (P < 0.0001) in micturitions per 24 h (-22%), urge incontinence episodes per 24 h (-76%) and volume voided per micturition (+22%) were observed after 9 months of treatment, with 65% of patients reporting an improvement in perception of their bladder problems. The incidence of adverse events and improvements in micturition diary variables during open-label treatment were comparable with those observed during a 12 week randomized treatment. It was concluded that tolterodine is well tolerated and maintains its clinical efficacy during 9 months of treatment. The high proportion of patients remaining on treatment indicates that tolterodine is an effective long-term treatment for overactive bladder.

Adult↗
PubMed2001

The basis for drug treatment of the overactive bladder.

The normal bladder functions, storage and elimination of urine, are dependent on neural circuits in the brain and spinal cord that coordinate the activity of the detrusor and that of the smooth and striated muscles of the outflow region. Disturbances at different levels may cause the overactive bladder (OAB) syndrome, characterized by urge, frequency and urge incontinence. Knowledge about the mechanisms controlling both normal and abnormal micturition is mandatory for the detection of targets for pharmacological intervention. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. Traditionally, drugs for treatment o

Central Nervous System↗
PubMed2001

[Liver metastases--primary or multimodal therapy?].

Multimodal therapeutic concepts for the treatment of liver metastasis are currently undergoing evaluation--prompted by the fact that few patients have lasting benefit from resection alone. Thus, for example, in practice, virtually only metastases from colorectal carcinoma or neuroendocrine tumors can be referred to surgical treatment, and, of these, only 20-25% are technically resectable. Furthermore, even after an R0 resection, recurrent disease subsequently develops in 60-75% of the cases. In primarily non-resectable colorectal liver metastases, prior systemic treatment with 5-FU/folinic acid and oxaliplatin can result in partial or complete remission in 50-60% of cases and, depending on patient selection criteria, a secondary R0 resection rendered possible in 14-38%. Theoretical oncological considerations suggest that neoadjuvant treatment should be applied in the case of resectable liver metastases too. The question of whether the prognosis is then improved compared with resection alone is currently being investigated in a prospective multicentre study conducted by the EORTC. The value of adjuvant therapy administered with the aim of lowering the risk of recurrence following "curative" resection of liver metastases is presently not considered to have been adequately demonstrated. With regard to the efficacy of regional chemotherapy, the results of two prospective randomized studies are contradictory. Nor can the multimodal approach decisively improve the outcome of non-radical resection of metastatic lesions. This means that primary or secondary resection with a margin of clearance continues to represent the gold standard for the treatment of colorectal liver metastases. Neoadjuvant or adjuvant chemotherapy--where applicable with the additional use of various methods of thermal ablation (cryotherapy, laser therapy, high-frequency thermotherapy)--should be restricted to clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗