[show abstract][hide abstract] ABSTRACT: Background:This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment.Methods:Patients were randomly assigned to receive either cisplatin 75 mg m(-2) and docetaxel 75 mg m(-2) every 3 weeks or oxaliplatin 85 mg m(-2) and docetaxel 50 mg m(-2) every 2 weeks. The primary end point was response rate, and secondary end points were toxicity, time to progression and overall survival.Results:A total of 88 patients (median age: 65 (39-86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17-43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs 27%), any grade leukopenia (84% vs 61%) and grade 3/4 leukopenia (44% vs 14%) and neutropenia (56% vs 27%).Conclusion:Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel.British Journal of Cancer advance online publication, 17 January 2013; doi:10.1038/bjc.2012.555 www.bjcancer.com.
British Journal of Cancer 01/2013; · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genetic alterations within the epidermal growth factor receptor (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately, the addition of cetuximab to chemotherapy did not increase response or survival in patients with advanced pancreatic cancer in phase II and phase III studies. The aim of this study was to evaluate the relationship between KRAS mutations and response or survival in patients with metastatic pancreatic cancer treated with cetuximab plus chemotherapy.
Within a multicenter phase II trial, 64 patients with metastatic pancreatic cancer were treated with cetuximab in combination with gemcitabine and oxaliplatin until disease progression. Analyses of the EGFR pathway, including KRAS mutations, could be performed in 25 patients. Analyses were carried out following microdissection of the tumor.
Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12 of the KRAS gene. No differences between the groups were noted in median progression-free survival (104 days in KRAS wild-type patients vs. 118 days in patients with KRAS mutations). Overall survival was longer in wild-type patients compared to patients with KRAS mutations (263 vs. 162 days), but the difference did not reach statistical significance. A further analysis of our clinical phase II trial showed that the presence of a rash was significantly correlated with overall survival.
KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit.
[show abstract][hide abstract] ABSTRACT: Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention.
This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages.
The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages.
From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review.
Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1-40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%).
Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.
International Journal of Colorectal Disease 03/2011; 26(3):303-11. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Peroxisome proliferator-activated receptor-gamma and cyclooxygenase-2 are frequently overexpressed on cholangiocarcinoma
(CC) cells and adjacent stroma cells, and might be potential therapeutic targets. A pilot phase II trial was started to analyze
the activity of angiostatically scheduled chemotherapy, capecitabine 2 × 1 g/m2from day 15 to 28 every 3 weeks combined with an antiinflammatory/angiostatic therapy, daily 45 mg oral pioglitazone and 25
mg oral rofecoxib day 1+ in advanced CC. All 21 consecutively included patients (mean age 64 years) suffered from non-resectable
far-advanced CC, 62% were pretreated. The median dose of capecitabine per cycle was 76% of that planned; the median duration
of treatment was 6.8 months (range 2 to 30+). Only three patients suffered from grade 3 toxicity (hand-foot syndrome n = 2,
edema n = 1). Therapy continuation was refused in one patient with HFS grade 3. Objective response was achieved in 29% of
the cases including one cCR, 29% achieved SD >6 months. Median overall survival was 8 months. The median overall survival
in this unselected, partially pretreated patient population compares to that observed in selected patient populations receiving
second generation combination chemotherapies which were shown to be accompanied with considerable hematotoxicity. The present
completely oral therapy approach combines convenience, low toxicity and efficacy, and fits to the general patients characteristics:
elderly patients with tumor-associated comorbidity. Randomized trials will definitely clarify the impact of antiinflammatory
treatment strategies on survival.
KeywordsHepatobiliary carcinoma-Metronomic chemotherapy-Pioglitazone-Coxib
[show abstract][hide abstract] ABSTRACT: Gastrointestinal (GI) tract involvement has been observed in the majority of patients with SSc. This has been attributed to an accumulation of extracellular matrix within the GI walls. We visualized the walls of the oesophagus, stomach and duodenum with its layers and measured the thickness in SSc patients and control patients utilizing endoscopic ultrasound (EUS).
Twenty-five SSc patients and 25 controls were evaluated. In addition to analysis of clinical symptoms, endoscopy and EUS (20-MHz miniprobe) were performed. The thickness of the complete wall was measured, and the mucosa, submucosa and muscularis were evaluated separately.
Clinical symptoms of SSc patients were dysphagia (14/25) and heartburn (19/25). Endoscopic findings were hiatal hernia (16/25), oesophagitis (6/25), amotility (19/25) and a dehiscent pylorus (15/25). In comparison with controls, SSc patients had significantly thicker oesophageal [SSc 1.619 (0.454) mm, control 1.392 (0.333) mm; P = 0.025], antral [SSc 1.876 (0.635) mm, control 1.599 (0.291) mm; P = 0.029] and duodenal [SSc 1.730 (0.522) mm, control 1.525 (0.222) mm; P = 0.039] walls. Predominantly, submucosa and muscularis were significantly thicker in SSc patients. The presence of dysphagia or amotility was significantly associated with the thickening of the GI walls.
The EUS revealed a significant thickening of the walls of the upper GI tract in SSc patients. Predominantly, the submucosa and muscularis are enlarged. These results strengthen the hypothesis that increased matrix deposition is an important aspect in the pathogenesis of GI involvement in SSc.
[show abstract][hide abstract] ABSTRACT: Performance of endoscopic retrograde cholangiography (ERC) depends mainly on the skills of the examiner, but also on anatomical variants. The aim of the study was to investigate patient- and papilla-related factors for the successful selective cannulation of the common bile duct (CBD).
50 patients with a papilla with no prior sphincterotomy needing an ERC were enrolled. From a standardized description given by the endoscopist, criteria to characterize the papilla were analyzed.
Success was achieved in 92%. Cannulation time was 460 +/- 561 seconds on average. 70% of the papillae were mastered in 300 seconds or less. Concordance between endoscopists concerning descriptive variables was between 86% and 100%. The judgment of the endoscopist concerning expected difficulty was not significantly related to success, demonstrating the necessity of predictive parameters. Typical position of the duodenoscope and performance of precut were significantly related to success. The joint presence of a visible orifice and a typical position of the duodenoscope had a positive predictive value (PPV) of 96%.
Endoscopists can rely on the joint presence of a visible orifice of the papilla and a typical position of the duodenoscope in X-ray to predict the success of ERC.
North American journal of medical sciences. 07/2009; 1(2):66-73.
[show abstract][hide abstract] ABSTRACT: Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m(-2) at first infusion followed by weekly 250 mg m(-2) combined with gemcitabine 1000 mg m(-2) as a 100 min infusion on day 1 and oxaliplatin 100 mg m(-2) as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31-78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.
British Journal of Cancer 05/2009; 100(7):1032-6. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of our study was to develop a system to grade the risk of the procedures summarized under the term endoscopic retrograde cholangiopancreatography (ERCP).
In a controlled prospective study, we evaluated the early complications of ERCP in 526 consecutive patients at a single endoscopy center in a defined period. The relation between endoscopic procedures and related complications was analyzed for significance. A grading system based on significant risk factors and clinical implications was developed.
Of the ERCP procedures, 29% were diagnostic and 71% therapeutic. A total of 45 complications occurred in 42 patients: pancreatitis (2%), perforation (1%), cardiorespiratory problems (0.6%), stent-related complications (0.5%), leakages (1.5%), and bleeding (3%). A native papilla was a significant risk factor for the development of complications (P = 0.046). On the basis of these findings, we defined five groups of ERCP-related complications: nonnative papillae with either diagnostic (A) or therapeutic interventions (B); native papillae with diagnostic (C) or therapeutic (D) interventions; and special therapeutic interventions (E). Complication rates differed significantly between individual groups, A versus D (P = 0.013), A versus E (P = 0.010), B versus D (P = 0.005), and B versus E (P = 0.003), as well as between A/B and C/D (P = 0.003).
A grading system based on differentiating between native and nonnative papillae and diagnostic versus therapeutic procedures demonstrated significantly different complication rates. This grading system has the potential to predict the risk of ERCP-related complications.
Journal of Gastroenterology 02/2009; 44(2):160-5. · 3.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: Biliary metal stents are a permanent solution for bile duct stenosis. Complications can arise when the stent migrates, breaks or is overgrown by tumour. The following case demonstrates how a Nd:YAG laser can be used to solve these problems. A 93-year-old man presented with jaundice and fever. Two years earlier a 6-cm metal stent had been implanted into a postinflammatory stenosis of the common bile duct after recurrent cholangitis and repetitive plastic stenting. Duodenoscopy showed that the stent was broken. It had migrated about 3 cm into the duodenum, leading to kinking of the stent and breaking of the wires. The stent was also occluded. It was necessary to purge the common bile duct and to introduce a second stent. However, the only way to reach the papilla was through the broken wires. Placing a second stent this way was impossible. Thus we trimmed the stent with a Nd:YAG laser. The piece that had migrated into the duodenum was retrieved. Now the papilla could be reached. The rest of the metal stent was purged with NaCl 0.9%. A second metal stent was placed. Since an Nd:YAG laser is part of the equipment of most endoscopy units, it can be used to trim a broken or migrated biliary metal stent.
Case Reports in Gastroenterology 01/2009; 3(1):16-20.
[show abstract][hide abstract] ABSTRACT: Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary (CUP), yielding response rates of 30% and median overall survival of 9-11 months in selected patients. Yet these combinations have not been subject to a randomised trial to overcome selection bias, a major problem in CUP. We randomised 92 patients to either paclitaxel/carboplatin (arm A) or the non-platinum non-taxane regimen gemcitabine/vinorelbine (arm B). The primary endpoint was rate of practicability as defined: application of >or=2 cycles of therapy (1) with a maximal delay of 1 week (2) and survival of >or=8 months (3). Practicability was shown in 52.4% (95% CI 36-68%) in arm A and in 42.2% (95% CI 28-58%) in arm B, respectively. The median overall survival, 1-year survival -rate and response rate of patients treated in arm A was 11.0 months, 38, and 23.8%, arm B 7.0 months, 29, and 20%. In conclusion, the paclitaxel/carboplatin regimen showed clinically meaningful activity in this randomised trial (Clinical trial registration number 219, 'Deutsches KrebsStudienRegister', German Cancer Society.)
British Journal of Cancer 01/2009; 100(1):44-9. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 68-year-old lady was admitted to a primary care centre with abdominal pain. She presented with a tender abdomen and a lipase level of 29 456 U/L. Cholecystectomy had been performed in 1971. Because her clinical state worsened the patient was transferred to our intensive care unit. Computed tomography and contrast ultrasound revealed necrotising pancreatitis. Antibiotics were started immediately. 10 days later the patient became febrile and an area of liquid necrosis between the spleen and the left kidney was drained under sonographic guidance by a 12 Fr pigtail. Every ten days the drain was replaced by a larger one. ERCP revealed a communication between the pancreatic duct and the growing necrotic cavity. A 7 Fr/ 7 cm plastic stent was put in. After 30 days an unsuccessful endoscopic necrosectomy was attempted with the cholangioscope through a 28 Fr peel-away sheath. In a further session an effective percutaneous necrosectomy was possible through a laparascopy trocar with a standard gastroscope. The patient became afebrile and signs of infection decreased. The persisting communication between the pancreatic duct and the necrotic cavity was closed with onyx. In the following days the dimensions of the necrotic cavity decreased rapidly. Finally the patient could be discharged home in good health. Antibiotics were stopped and the percutaneous drain was taken out after some weeks of ambulatory care.
Zeitschrift für Gastroenterologie 06/2008; 46(5):425-30. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: A seventy-year-old male presented with severe myasthenia gravis and an episode of obscure bleeding. There was a history of gastric ulcer leading to Billroth II surgery twenty-five years ago. Upper endoscopy revealed no pathology. Colonoscopy showed a few solitary diverticula and traces of old blood in the terminal ileum. Capsule endoscopy pictured red smear in the upper jejunum. Diverticula were seen as well. Suspecting bleeding jejunal diverticulosis double balloon enteroscopy was performed. The complete jejunal ascending loop and about 100 cm of the jejunum through the descending jejunal loop could be inspected. Large diverticula with fecoliths were found in both loops. Bleeding had ceased. The patient was discharged to neurology for optimizing therapy for myasthenia gravis.
Diagnostic and Therapeutic Endoscopy 02/2008; 2008:156496.
[show abstract][hide abstract] ABSTRACT: The presence of peritoneal carcinomatosis arising from colorectal cancer is associated with a poor prognosis. It was the purpose of this study to analyze morbidity, mortality, and survival after major cytoreductive surgery and intraperitoneal chemotherapy.
Thirty-two patients with peritoneal carcinomatosis were operated between April 2004 and June 2006 with the aim of complete macroscopical cytoreduction. All had a primary colorectal carcinoma. Surgery in these patients was followed by hyperthermic intraperitoneal chemotherapy (HIPEC) consisting of mitomycin C and doxorubicin. Data were analyzed retrospectively.
Of all patients, 16 had appendix and 16 non-appendiceal colorectal carcinoma. A macroscopically complete cytoreduction was achieved in 24 patients by parietal and visceral peritonectomy procedures. All resections were combined with HIPEC. Overall morbidity was 34%. Most frequent surgical complications were intestinal obstruction (4/32), enteric fistula (2/32), pancreatitis (2/32), and bile leakage (2/32). One patient presented grade 4 renal toxicity. There was no hospital mortality. The median follow-up was 12 months. The 1-year overall survival rate is 96%. All patients after complete cytoreduction are still alive.
Cytoreductive surgery combined with HIPEC is associated with an acceptable morbidity and low mortality. Complete cytoreduction may improve survival, particularly in well-selected patients having a low tumor volume and no extra-abdominal metastases.
International Journal of Colorectal Disease 12/2007; 22(11):1295-300. · 2.24 Impact Factor