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Rationale and Objectives: Pancreatic lesions are frequently detected in pancreatic phase only, which may lead to false negative findings in CT-guided biopsies. We evaluated the accuracy and complication rate of CT guided biopsies of pancreatic lesions with i.v.-contrast application following needle placement in comparison to biopsy after contrast enhanced CT., Materials and Methods: In 30 patients planning and needle placement was performed on the basis of a native planning CT and prior diagnostic CT or MRT. After needle placement contrast enhanced CT was performed to confirm needle course and adjusted if necessary (group 1). In 30 additional patients biopsy was planned based on contrast enhanced CT and needle was placed in the lesion. Control scans confirmed correct needle position (group 2). An 18G coaxial system was used for both groups. Statistical analysis was performed with Student's t and Fisher's exact test for comparison of lesion size, location as well as accuracy and complication rates., Results: Mean lesion size was significantly smaller in group 1 (31 mm vs. 39 mm; p = 0.02). Diagnostic accuracy and sensitivity for malignancy in group 1 was 93% and 92% versus 80% and 77% in group 2. Complications related to the procedure, i.e. haematoma (n = 5, group 1/n = 2, group 2) and pain (n = 0, group 1/n = 2, group 2) did not statistically differ., Conclusion: CT-guided biopsy of pancreatic lesions with i.v.-contrast application following needle placement is a reliable method and provides superior accuracy compared to biopsies performed after contrast enhanced planning CT.

The purpose was to assess capabilities of the multidetector-row computed tomography (MDCT) with multiplanar reformations (MPR) for predicting of pancreatic adenocarcinoma resectability. Forty-eight patients deemed to have resectable pancreatic adenocarcinoma after assessment using biphasic MDCT with MPRs underwent surgery for potential tumor resection. Imaging findings were retrospectively evaluated for tumor resectability and correlated with surgical and pathological results. Curative resection was successful in 44 of 48 patients. The positive predictive value for tumor resectability made up 91% with four false-negative results. The reasons for unresectability were venous involvement (1), small liver metastases (2) and peritoneal involvement associated with small metastases to lymph nodes (1). MDCT yielded a negative predictive value of 99% (286 of 288 vessels) for detection of vascular invasion. Our results indicate the tendency towards improved prediction of resectability using MDCT compared to single-detector CT.

Background and Purpose: Inclusion of regional lymph nodes usually is indicated when treating upper gastrointestinal malignancies. Lymphatics follow the large vessels of this region. Vascular variability with consequences for planning treatment volume (PTV) was studied., Materials and Methods: Upper abdominal metric relationship of the vascular origins was analysed in CT scans in 104 patients to estimate its influence on PTV variability. PTV volumes were calculated based on these. Additionally, the PTV size of 3D plans of 34 patients with pancreatic adenocarcinoma (PDAC) was analysed depending on different PTV definitions., Results: Vascular origin varied most for the inferior mesenteric artery (IMA) with substantial PTV size differences. Volumetric variability was analysed for PDAC (IMA versus renal hilum as caudal margin). Additional PTV for IMA was < 100 cc (median) but ranged up to 350 cc in CT (100-199 ml in 14/34 and > 200 ml in 3/34 patients). Data from treatment planning confirmed this observation., Conclusions: Considerable vascular and lymphatic variability obliges to base PTV on the individual vascular anatomy. For most patients the caudal PTV margin for PDAC can safely be set at the IMA. But PTV should be restricted when the additional volume would lead to a significant increase to avoid haematotoxicity from concomitant gemcitabine which is proportional with PTV size. The risk of kidney toxicity is also subject to PTV expansion in the caudal direction.

Interferon-alpha (IFN-alpha) is well established in the treatment of neuroendocrine carcinomas (NEC). Treatment is accompanied by fatigue and flu-like symptoms. In patients with chronic hepatitis C, pegylated IFN (PEGIFN) leads to improved antiviral efficacy and good tolerability. Our aim was to assess the efficacy and tolerability of PEG-IFN on the management of patients with well-differentiated NEC of the gastroenteropancreatic system. In 17 patients, the effect of PEG-IFN-alpha2b was studied. After first-line octreotide treatment, IFN-alpha was added at the time of tumor progression. Six patients were switched from conventional IFN-alpha, and 11 patients were IFN naive. Inhibition of tumor growth, including stabilization of disease, occurred in 13 of 17 patients, and biochemical and symptomatic responses were seen in 7 of 10 patients with functionally active tumors. Tolerability of PEG-IFN-alpha2b was much better than that of IFN-alpha. Fatigue occurred in 59% of all patients but was mild in severity. Eleven of thirteen patients who had a benefit remained on therapy for a median time of 20 months (range 6-30 months). PEG-IFN-alpha2b provides symptomatic and antiproliferative efficacy in patients with NEC. Better tolerability of PEG-IFN-alpha2b improved patients' compliance, justifying its use in patients who do not tolerate conventional IFN-alpha treatment.

Purpose: In chemoradiation for pancreatic carcinoma three-dimensional target volume definitions could maximize tolerability and therapeutic effect at the same time because toxicity correlates with treatment volume. We aimed to define guidelines for elective treatment of nodal areas based on pathologic nodal involvement to optimize treatment volume for this tumor., Methods and Materials: Pathologic patterns of regional nodal spread in 175 patients who underwent primary pancreatoduodenectomy with > or =10 assessed nodes and literature data on para-aortic spread were the base of the definition of the target volume. Significant correlations between spread to lymphatic areas and tumor characteristics were determined using Fisher's exact test. Computed tomography scans and a Pinnacle3 (Philips, Best, The Netherlands) system were used for treatment planning., Results: Among 175 resected tumors without pretreatment, 76% had regional nodal metastasis and 22% had spread to distant nodes. High-risk lymphatic areas were identified and selected for elective treatment. A standardized planning procedure was derived and tested under treatment conditions., Conclusions: Histopathologic data allowed us to develop recommendations for standardized treatment planning for ductal carcinoma of the pancreatic head. These are proposed for quality assurance in multicenter studies and routine use.

Objective: The growth behaviour of well-differentiated neuroendocrine carcinomas of the gastro-entero-pancreatic system varies greatly and parameters predicting their prognosis are lacking. The aim of our study was to investigate whether tumour growth could be correlated with the release of proangiogenic factors into the circulation., Patients and Methods: Circulating vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), basic fibroblast growth factor (bFGF) and angiogenin were measured in 38 patients with advanced neuroendocrine carcinomas and compared to healthy age-matched controls. In 20 patients, angiogenic cytokine levels were measured at consecutive time points and correlated to tumour progression as assessed by abdominal CT scan, MRI and chromogranin A levels., Results: VEGF levels were elevated in patients compared to controls (P < 0.002) and clearly associated with tumour progression (P < 0.005). Angiogenin levels were significantly higher in patients than in controls (P < 0.003), while high IL-8 levels were predictive of shorter survival. Angiogenin and bFGF levels were correlated neither with tumour growth nor with patient survival., Conclusions: VEGF and IL-8 are associated with tumour progression and might qualify as markers of prognosis and therapy control in patients with neuroendocrine carcinomas. Our results support the notion that specific anti-angiogenic therapies should be evaluated in neuroendocrine carcinoma patients.

Purpose: Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT). We used a time-dependent schedule to determine the maximal-tolerated dose and dose-limiting toxicities (DLTs; Grade 4 hematologic or Grade 3 other toxicity)., Methods and Materials: Patients with pancreatic cancer (n = 33), periampullary carcinoma (n = 1), or bile duct cancer (n = 2) were treated with 3-day conformal RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost. Concurrent cisplatin (20 mg/m(2)/d on Days 1-5 and 29-33) and gemcitabine (initially 600 mg/m(2), weekly on Fridays 68 h before RT) were administered. Because of DLT, the doses were reduced to 500 mg/m(2) weekly and then 500, 400, or 300 mg/m(2) on Days 2, 5, 26, 33., Results: DLT occurred at all dose levels of gemcitabine >300 mg/m(2). Fourteen patients were treated at the recommended Phase II dose of gemcitabine (300 mg/m(2)) without DLT. The response to chemoradiation allowed 10 of 30 initially unresectable patients with primary pancreatic carcinoma to undergo radical surgery, including a complete response in 2 cases., Conclusions: At the recommended Phase II dose, chemoradiation with gemcitabine and cisplatin can be administered safely in pancreatic carcinoma. However, at higher dose levels, toxicity is severe and frequent. Patients with a chance for conversion to resection could benefit from this schedule.