Trond Buanes

Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study

Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3–6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85–90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte–macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P=0.006) and high-dose groups (P=0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.

Intradermal ras peptide vaccination with granulocyte‐macrophage colony‐stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

K‐RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte‐macrophage colony‐stimulating factor. Forty‐eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide‐specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end‐stage disease. Patients followed‐up for longer periods showed evidence of induction of long‐lived immunological memory against the ras mutations. CD4+ T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras‐specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non‐responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.

Laparoscopic resection of the pancreas: a feasibility study of the short-term outcome

Background: Laparoscopic resection is not an established treatment for tumors of the pancreas. We report our preliminary experience with this innovative approach to pancreatic disease. Methods: Thirty two patients with pancreatic disease were included in the study on an intention-to-treat basis. The preoperative indications for surgery were as follows: neuroendocrine tumors (n=13), unspecified tumors (n=11), cysts (n=2), idiopathic thrombocytopenic purpura with ectopic spleen (n=2), annular pancreas (n=1), trauma (n=1), aneurysm of the splenic artery (n=1), and adenocarcinoma (n=1). Results: Enucleations (n=7) and distal pancreatectomy with (n=12) and without splenectomy (n=5) were performed. Three patients underwent laparoscopic exploration only. Four procedures (13%) were converted to an open technique. One resection was converted to a hand-assisted procedure. The mortality rate for patients undergoing laparoscopic resection was 8.3% (two of 24). Complications occurred after resection in nine of 24 procedures (38%). The median hospital stay was 5.5 days (range, 2–22). Postoperatively, opioid medication was given for a median of 2 days (range, 0–13). Conclusion: Resection of the pancreas can be performed safely via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Desflurane versus propofol maintenance for outpatient laparoscopic cholecystectomy

Background: The aims of the study were to evaluate costs and clinical characteristics of desflurane‐based anaesthetic maintenance versus propofol for outpatient cholecystectomy.

Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes

The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3–9 weeks after onset of type 1 diabetes in six adult patients (age 24–35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1+ cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.

Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras

K‐ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation‐specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty‐three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long‐term immunological T‐cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T‐helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5‐year survival was 22% and 29%, respectively. Strikingly, 10‐year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long‐term immune response together with 10‐year survival following surgical resection indicates that K‐ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.

Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study

Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes : experiences from the DiViD study

Cholecystectomy rates, gallstone prevalence, and handling of bile duct injuries in Scandinavia: A comparative audit

AbstractBackground: This study was performed to assess three fields of surgical decision making: (a) selecting patients for cholecystectomy, (b) analyzing the value of intraoperative cholangiography (IOC), and (c) surveying the handling of bile duct (BD) injuries. Methods: Yearly numbers of laparoscopic (LC) and open cholecystectomies (OC) were collected from official health care statistics. Data concerning handling of BD injuries were taken from each countrys LC registry. Results: From 1989 to 1995 the median cholecystectomy rate was 6.82 per 10,000 inhabitants in Denmark, 14.20 in Finland, 6.23 in Norway, and 12.17 in Sweden. Deviations from the median yearly rates in each country were −14.8% to +14.4%. Repair of BD injury was performed in the same local hospital where the injury had occurred in 68–98% of cases. Conclusions: Patient selection differed between countries before the introduction of LC, and these differences have persisted. Few patients with BD injury were treated in referral centers.

Single-centre experience of laparoscopic pancreatic surgery†

Laparoscopic resection is regarded as safe and feasible in selected patients with benign pancreatic tumours. Few data exist on laparoscopic surgery for malignant lesions and larger neoplasms in unselected patients.

Outpatient laparoscopic surgery: feasibility and consequences for education and health care costs

BackgroundThe purpose of this paper is to describe the outcome of ambulatory laparoscopic cholecystectomy (LC), antireflux surgery, adrenalectomy and splenectomy and possible implications for surgical education and health care costs.MethodsProspective, observational study 1994–2003.ResultsThe success rate of ambulatory treatment was 83.5% in 1060 LC patients, 80% in 113 antireflux procedures, 100% in 22 laparoscopic adrenalectomies, and 75% in 12 laparoscopic splenectomies. In a total number of 1207 patients, health care costs were reduced by almost