Peter Goetzinger

NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer.

BACKGROUND Neoadjuvant chemotherapy can facilitate pancreatic resection in patients with initially unresectable pancreatic cancer (PC). We report the results of a phase II trial of gemcitabine-oxaliplatin neoadjuvant chemotherapy for patients with locally advanced, nonmetastatic PC. METHODS A prospective, phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine (900 mg/m(2)) and oxaliplatin (60 mg/m(2)) given as intravenous infusion once a week at day 1 of each treatment cycle (NeoGemOx protocol). Patients received 6-9 cycles of chemotherapy. Those patients with sufficient tumor regression subsequently underwent pancreatic resection and were followed postoperatively to assess long-term survival. RESULTS A total of 33 patients were eligible and were included in the intent-to-treat and evaluable population. On centralized review of the imaging studies, 18 patients had unresectable disease at inclusion, and 15 patients had borderline resectable PC. Eventually, 13 patients (39%) had a curative resection after neoadjuvant therapy. The R0 resection rate was 69%. Median overall survival of patients who underwent tumor resection was 22 months (95% confidence interval [CI], 14-30) compared with 12 months (95% CI, 9-15) for those without resection (P = .046). The median recurrence-free survival rate after resection was 10 months (95% CI, 4-17). CONCLUSION Neoadjuvant gemcitabine plus oxaliplatin is well tolerated and safe. Substantive tumor regression occurs in some patients with locally advanced PC treated with this neoadjuvant protocol, offering the potential for curative resection and improvement in overall survival. Additional studies involving the NeoGemOx protocol should be considered to further evaluate the safety and efficacy of this combination.

Gadobenate Dimeglumine–enhanced 3.0-T MR Imaging versus Multiphasic 64–Detector Row CT: Prospective Evaluation in Patients Suspected of Having Pancreatic Cancer

PURPOSE To compare the diagnostic performance (detection, local staging) of multiphasic 64-detector row computed tomography (CT) with that of gadobenate dimeglumine-enhanced 3.0-T magnetic resonance (MR) imaging in patients suspected of having pancreatic cancer. MATERIALS AND METHODS The institutional review board approved this prospective study, and all patients provided written informed consent. Multidetector CT and MR imaging were performed in 89 patients (48 women aged 46-89 years [mean, 65.6 years] and 41 men aged 46-86 years [mean, 65.3 years]) suspected of having pancreatic cancer on the basis of findings from clinical examination or previous imaging studies. Two readers independently assessed the images to characterize lesions and determine the presence of focal masses, vascular invasion, distant metastases, and resectability. Findings from surgery, biopsy, endosonography, or follow-up imaging were used as the standard of reference. Logistic regression, the McNemar test, and κ values were used for statistical analysis. RESULTS Focal pancreatic masses were present in 63 patients; 43 patients had adenocarcinoma. For reader 1, the sensitivities and specificities in the detection of pancreatic adenocarcinoma were 98% (42 of 43 patients) and 96% (44 of 46 patients), respectively, for CT and 98% (42 of 43 patients) and 96% (44 of 46 patients) for MR imaging. For reader 2, the sensitivities and specificities were 93% (40 of 43 patients) and 96% (44 of 46 patients), respectively, for CT and 95% (41 of 43 patients) and 96% (44 of 46 patients) for MR imaging. Vessel infiltration was determined in 22 patients who underwent surgery, and reader 1 obtained sensitivities and specificities of 90% (nine of 10 vessels) and 98% (119 of 122 vessels), respectively, for CT and 80% (eight of 10 vessels) and 96% (117 of 122 vessels) for MR imaging; for reader 2, those values were 70% (seven of 10 vessels) and 98% (120 of 122 vessels) for CT and 50% (five of 10 vessels) and 98% (120 of 122 vessels) for MR imaging. Both readers correctly assessed resectability in 87% (13 of 15 patients) of cases with CT and 93% (14 of 15 patients) of cases with MR imaging. Nonresectability was assessed correctly with CT in 75% (six of eight patients) of cases by reader 1 and 63% (five of eight patients) of cases by reader 2; nonresectability was correctly assessed with MR imaging in 75% (six of eight patients) of cases by reader 1 and 50% (four of eight patients) of cases by reader 2. None of the differences between modalities and readers were statistically significant (P > .05). CONCLUSION Both CT and MR imaging are equally suited for detecting and staging pancreatic cancer. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101189/-/DC1.

State-of-the-art magnetic resonance imaging of pancreatic cancer.

Technical advances of magnetic resonance imaging (MRI), including ultrahigh-field magnetic resonance at 3.0 T, parallel imaging techniques, and multichannel receive coils of the abdomen, have promoted MRI of the pancreas. For adenocarcinoma, which is the most common malignant pancreatic tumor, helical CT has been most often used for detection and staging, but it has limitations in the detection of small cancers 2 cm in diameter or less (sensitivity, 63%). Moreover, it is not very accurate in determining nonresectability, because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. At ultrahigh field at 3.0 T, gadolinium-enhanced MRI using volume-interpolated 3-dimensional gradient-recalled echo pulse sequences with near-isotropic voxels are very useful for detection of subtle abnormalities. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps to diagnose small cancers. Contrast-enhanced MRI is a problem-solving tool in case of equivocal CT: it helps to differentiate between cancer and focal pancreatitis. Neuroendocrine carcinoma may present with a spectrum of appearances at MRI, but the primary tumor and liver metastases are hypervascular in approximately 70%. In this article, pancreas imaging protocols for 1.5 and 3.0 T are explained. We present the imaging features of pancreatic cancer and the important questions in staging, which should be addressed by the radiologist.

Nitric Oxide Administration Restores the Hepatic Artery Buffer Response During Porcine Endotoxemia

The hepatic artery buffer response, which is lost during endotoxemia, plays a central role in the autoregulation of liver perfusion. A temporarily decreased synthesis of nitric oxide during early endotoxemia might be responsible for this dysfunction; hence exogenous administration of nitric oxide could reestablish the autoregulation of hepatic blood flow and help prevent hepatic damage later in septic shock. Fifteen pigs were treated with lipopolysaccharide +/− the nitric oxide donor nitroprusside-sodium via the portal vein. Hemodynamics were measured, and serum chemistry and liver biopsies for nitric oxide synthase expression were obtained. Lipopolysaccharide decreased arterial liver perfusion after 5 hours by 38% (p =. 012), which was reversed by addition of nitroprusside (8%). Administration of nitroprusside preserved an increase of 28% in hepatic arterial upon portal vein flow reduction (p <. 001). Nitroprusside maintained mRNA levels of constitutive nitric oxide synthase in liver tissue which were decreased by lipopolysaccharide (p =. 026 vs. p =. 114) and tempered the burst in inducible nitric oxide synthase expression at t = 3 hours. The early administration of the nitric oxide donor sodium nitroprusside during endotoxemia is able to reestablish the autoregulatory response of the hepatic artery following reduction of hepatic blood flow. This beneficial effect might help to prevent subsequent hepatic damage in the course of abdominal sepsis.

Gemcitabine-based neoadjuvant chemotherapy for locally advanced pancreatic cancer does not affect mortality and morbidity after pancreatic resection

SummaryBackgroundNeoadjuvant strategies for locally advanced pancreatic cancer (PC) have been increasingly studied over the last decade. The effect of only systemic chemotherapy on postoperative morbidity and mortality remains unclear. The objective of this study was to determine the risk of postoperative complications in patients undergoing pancreatic resection for locally advanced, nonmetastatic PC following neoadjuvant gemcitabine-based chemotherapy.MethodsBetween 1994 and 2010, thirty-five patients who received gemcitabine-based neoadjuvant chemotherapy followed by pancreatic resection (Neo-gem group) were compared with 140 patients who had only pancreatic resection without neoadjuvant chemotherapy (Prim-surg group).ResultsOverall postoperative morbidity was similar in the Neo-gem and Prim-surg groups (57 vs. 51 %; P = 0.545). Major postoperative complications (Grade III–V) requiring radiological or surgical intervention occurred in 23 % of patients in the Neo-gem group and 26 % of patients in the Prim-surg group (P = 0.665). Within the Neo-gem group univariate and multivariate analysis identified the number of intraoperative blood transfusions as an independent risk factor for postoperative complications Grade I–V (P = 0.02), and vascular resection for major complications Grade III–V (P = 0.04).ConclusionsNeoadjuvant gemcitabine-based chemotherapy is not associated with an increase in postoperative complications following pancreatic resection for locally advanced PC.