Last line therapy with sorafenib in colorectal cancer: A retrospective analysis.

AIM: To analyze the efficacy of last line sorafenib treatment in colorectal cancer patients. METHODS: All patients receiving chemotherapy for colorectal cancer in the outpatient clinic of the University of Mainz since 2006 were retrospectively analyzed for last line sorafenib exposure. Charts of identified patients were analyzed for clinic-pathological parameters, like data on gender, age, date of initial diagnosis, UICC stage, number and kind of the pre-therapies, therapy start and end of sorafenib, sorafenib mediated treatment cessation, side effects, response rates, time to progression and overall survival. RESULTS: Ten patients with a median of 3.0 prior chemotherapy lines had received a last line sorafenib therapy either alone (10%) or in combination with 5-fluorouracil derivates (90%). All patients suffered from colorectal cancer stage UICC 4 and were routinely seen in 2-wk intervals in the oncology outpatient clinic. Median duration of treatment was 142.0 d. At 8 wk 80% of patients showed stable disease but we did not observe any remissions. Median time to progression was 140.5 d (4.7 mo), while median overall survival reached 176.5 d. One patient ceased treatment due to side effects. Reason for treatment stop was bleeding complication in one case and non-specified sorafenib intolerance in another case. Due to the retrospective approach we did not further quantify side effects. CONCLUSION: This retrospective analysis encourages further investigation of sorafenib in colorectal cancer last line therapy.

Analysis of the expression of SDF-1 splicing variants in human colorectal cancer and normal mucosa tissues.

C-X-C motif chemokine ligand 12 (CXCL12), also termed stromal cell-derived factor-1 (SDF-1) is a small protein 8-14 kDa in length that is expressed as six isoforms, consisting of SDF-1α, SDF-1ß, SDF-1γ, SDF-1δ, SDF-1ε and SDF-1θ. All six isoforms are encoded by the single CXCL12 gene on chromosome 10. This gene regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. The potential role of the novel CXCL12 splice variants as components of the CXCR4 axis in cancer development is not fully understood. The present study aimed to analyze the expression profile of the various SDF-1 isoforms and SDF-1 polymorphisms, and the association with the clinicopathological features and overall survival of patients with colorectal cancer (CRC). SDF-1 polymorphism analysis was performed using restriction fragment length polymorphism (RFLP) analysis in 73 histologically confirmed human CRC tissue samples at various stages of disease. The expression pattern of the SDF-1 isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 histologically confirmed human CRC tissue samples obtained at various stages of disease, as well as in matched adjacent normal mucosa samples. The presence of the CXCL12 gene polymorphism rs1801157 demonstrated an association with local progression of the primary tumor, as indicated by the T stage. The frequency of the GG genotype was slightly increased in patients with stage 3 and 4 tumors (78.0%) compared with the incidence of the GA/AA genotype (69.5%; P=0.067). The expression of SDF-1ß was associated with the presence of metastases (P=0.0656) and the expression of SDF-1γ was significantly associated with tumor size (P=0.0423). The present study is the first to analyze the association between the expression profile of the chemokine CXCL12 splice variants in human CRC tissues and their clinical relevance. The present results reveal that the CXCL12 G801A polymorphism is a low-penetrance risk factor for the development of CRC, and was associated with the T stage. All six isoforms of SDF-1 were expressed in CRC tissues. The expression of SDF-1ß was found to be associated with metastases and SDF-1γ appears to be a possible tumor marker for local tumor progression.

Intermittent manually controlled versus continuous infusion of propofol for deep sedation during interventional endoscopy: a prospective randomized trial.

INTRODUCTION: Beside the traditional, intermittent bolus application of propofol, continuous propofol infusion via infusion pump is an alternative procedure for deep sedation during long-lasting interventional endoscopy. However, up to now, there are no randomized comparisons for gastrointestinal endoscopy. METHODS: One hundred patients (ERCP: n = 60, EUS: n = 40) were randomly assigned to receive intermittent bolus application ("bolus group") or continuous infusion ("perfusor group") of propofol sedation after induction with 3 mg midazolam for deep sedation. Patients in the bolus group received an initial propofol dose according to body weight (bw <70 kg: 40 mg; bw ≥ 70 kg 60 mg). In the perfusor group, bw-adapted, continuous propofol infusion (6 mg/kg) via the Injectomat 2000 MC (Fresenius-Kabi) was administered after an initial bolus of 1 mg/kg. Vital signs, dose of propofol, patient cooperation (VAS 1-10), sedation depth, and the recovery time as well as the quality of recovery were evaluated. RESULTS: Total propofol dose in the bolus group 305 ± 155 mg (100-570 mg) and in the perfusor group 343 ± 123 mg (126-590 mg, p = 0.5) were comparable. Oxygen saturation below 90% was seen in four patients of each group, with no need for assisted ventilation. Arterial blood pressure <90 mmHg was documented in two patients in the bolus group and seven patients in the perfusor group (p = 0.16). Patients' cooperation was rated as good in both groups (bolus group, 9.1 ± 0.9; perfusor group, 8.9 ± 1; p = 0.17). Recovery time was significantly shorter in the bolus group compared with the perfusor group (19 ± 5 versus 23 ± 6 min, p < 0.001) whereas the quality of recovery was nearly identical in both groups. CONCLUSION: Both sedation regimens allow nearly identical good controllability of propofol sedation. However, recovery time was significantly slower and hypotension was tended to occur more often in the perfusor group.

Dual access endoscopic necrosectomy of infected pancreatic necrosis: a case report.

A 73-year-old male developed fever and jaundice 6 months after an episode of acute necrotizing pancreatitis. During endoscopic retrograde cholangiography, a distal bile duct compression was documented and stent insertion led to resolution of jaundice, however, the febrile condition persisted. A pancreatic necrosis measuring 11x7 cm was shown by computed tomography (CT) and the patient was referred for necrosectomy. During the first endoscopic session, spontaneous drainage of pus was observed in the duodenal bulb. Therefore, the pancreatic necrosis was first punctured under endoscopic ultrasound-guidance transduodenally. The pancreatic necrosis was then additionally punctured transgastrically and the necrotic cavity was entered with a standard upper gastrointestinal scope. Despite extensive irrigation and necrosectomy we felt the transgastric approach was not sufficient enough to treat the large necrotic cavity and decided to perform the further treatment by using both accesses. Endoscopic debridement was repeated daily through the transgastric as well as the transduodenal approach over 5 days. The clinical condition of the patient dramatically improved and he became afebrile. Two months after the initial endoscopic necrosectomy, a CT scan showed nearly complete resolution of the pancreatic necrosis and the bile duct stenosis resolved. Six months later, CT scans showed no residual necrosis and an atrophic but otherwise normal pancreas.

Routine colonoscopy with a standard gastroscope. A randomized comparative trial in a western population.

BACKGROUND AND AIMS: Colorectal cancer screening increased the workload of colonoscopic procedures in endoscopic units. Recent developments advocated the use of smaller and more flexible scopes to achieve the goal of a complete examination to the cecum. Therefore, the use of an upper GI scope for colonoscopy can be considered. MATERIALS AND METHODS: Six-hundred and fifty consecutive patients (age, 64 +/- 20 years, 395 women) undergoing routine colonoscopy were examined with either a standard colonoscope or an upper GI scope in randomized order. In case of an incomplete examination, colonoscopy was repeated with the alternative instrument in the same session. All patients underwent bowel preparation with 4 1 of a polyethylene glycol solution, and the examinations were performed under conscious sedation (midazolam and pethidine i.v.) by a single investigator. RESULTS: Because of insufficient colonic preparation or refusal to participate, 28 patients had to be excluded. Both groups (colonoscope group, n = 315, upper GI scope group, n = 307) were well comparable with respect to their demographic data, previous abdominal surgery, the presence of diverticulosis, and the number of former colonoscopic examinations, respectively. Successful cecum intubation was achieved in 96% of the cases in the colonoscope group and in 93% of the patients from the upper GI scope group (p = 0.82). However, the time until the cecum was reached was prolonged to 8.7 +/- 2.4 min when using the upper GI scope compared with 8.2 +/- 2.3 min in the colonoscope group (p = 0.006). In the colonoscope group, a switch to the upper GI scope enables a complete colonoscopy in all but three cases (11/14, 79%) whereas this aim was only achieved vice versa in the upper GI scope group (using a colonoscope) in 7 of 21 patients (33%, p = 0.04). CONCLUSION: Routine colonoscopy can be performed effectively with standard upper GI scopes in a western population if no colonoscope is available.

Endoscopic pancreatic duct stenting for relief of pancreatic cancer pain.

INTRODUCTION: Little is known about the effects of endoscopic pancreatic duct (PD) decompression in patients with 'obstructive type' pain from pancreatic carcinoma. METHODS: Twenty patients with unresectable carcinoma of the pancreas, PD obstruction and postprandial epigastric pain were enrolled. The pain intensity, opioid dose and quality-of-life index were documented pre-treatment and at 4-weekly intervals. PD stenting was attempted in all patients. PD stent change was performed if biliary stents had to be changed or intense pain relapsed. RESULTS: Endoscopic PD drainage was successful in 19/20 patients by placement of a 7 F (n = 9) or 10 F (n = 10) plastic stent. Median follow-up was 16 weeks. Two patients were alive at the end of follow-up. Eleven patients received gemcitabine chemotherapy. The pre-interventional pain score was 6.7 +/- 0.9 points and decreased to 3.1 +/-1.4 points at 4 weeks (P < 0.001). It remained lowered significantly at 8/12 weeks and at the final visit (4.2 +/- 1.5 points, n = 13). The mean pre-stenting fentanyl dose was 85.5 +/- 34.7 microg/h, and it was decreased to 57.9 +/- 39.1 microg/h after 4 weeks (P < 0.01), 60.5 +/- 38.9 microg/h after 8 weeks and 64.1+/-39.8 microg/h (P < 0.01 versus pre-treatment) after 12 weeks but increased to 82.7 +/- 41.3 microg/h (NS) at the final visit. The quality-of-life index improved 4 weeks after stenting (from 4.8+/-1 to 6.2+/-1.5 points, P < 0.01) but was lowered to 5.5 +/- 2.3 points at 12 weeks (NS). The response was independent of stent diameter and chemotherapy. CONCLUSION: PD stenting achieved significant pain relief and short-term improvement of the quality of life in the majority of patients with PD obstruction due to pancreatic carcinoma.