Impact of the reconstruction method on delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy: a prospective randomized study.

BACKGROUND: Delayed gastric emptying (DGE) is of considerable concern in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prolonged hospital stay, increased cost, and decreased quality of life add on to interventions needed to treat DGE. This study was conducted to determine if performing duodenojejunostomy via the antecolic rather than the retrocolic route improved incidence of DGE. METHODS: Patients undergoing PPPD between April 2007 and November 2009 were randomized for either antecolic or retrocolic reconstruction of the duodenojejunostomy. DGE was then assessed by clinical criteria on postoperative day (POD) 10. A paracetamol absorption test was also administered with a liquid meal, and serial plasma levels of intestinal peptides were measured. RESULTS: Overall, 64 patients were amenable for analysis: 36 in the antecolic group and 28 in the retrocolic group. The incidences of DGE on POD 10 were 17.6 and 23.1 % (antecolic vs. retrocolic, respectively) (p = 0.628). The two groups did not differ in regard to their median (interquartile range) postoperative hospital length of stay [13.0 (10.0­17.5) vs. 12.5 (11.0­17.0) days; p = 0.446], time to regular diet [5 (5­7) vs. 5 (4­6) days; p = 0.353], or morbidity (52.9 vs. 50.0 %; p = 0.777). The median length of nasogastric tube decompression was similar in the two groups [4 (3­7) vs. 3 (3­5) days; p = 0.600]. Levels of paracetamol and glucagon-like peptide-1 were markedly decreased in patients with DGE. CONCLUSIONS: Antecolic reconstruction after PPPD does not improve the occurrence/the incidence of DGE and is similar to retrocolic reconstruction with regard to secondary outcome parameters.

NeoGemTax: gemcitabine and docetaxel as neoadjuvant treatment for locally advanced nonmetastasized pancreatic cancer.

BACKGROUND: About 30% of patients with pancreatic cancer suffer from locally advanced nonmetastatic carcinoma at the time of diagnosis. We conducted a prospective phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine and docetaxel, to assess the rate of complete radical resection and overall survival. METHODS: Gemcitabine (900 mg/m2) and docetaxel (35 mg/m2) were given on days 1, 8, and 15 of a 28-day cycle. Two cycles were administered for a preoperative treatment duration of 8 weeks. Patients experiencing tumor regression or stable disease and improved performance status subsequently underwent surgical exploration and pancreatic resection, if feasible. All patients were followed postoperatively to assess long-term survival. RESULTS: A total of 25 patients were eligible and included in the intent-to-treat and evaluable population. Thirteen patients had unresectable disease at inclusion and 12 patients had borderline resectable pancreatic cancer. Finally, 8 of 25 (32%) patients underwent resection after neoadjuvant chemotherapy; 7 (87%) of these patients had R0 resection. The median overall survival of patients who underwent resection was 16 months (95% confidence interval [CI], 8-24 months) compared to 12 months (95% CI, 8-16 months) for those without resection (p=0.276). The median recurrence-free survival rate after resection was 12 months (95% CI, 2-21 months). CONCLUSIONS: NeoGemTax was safe and resection was feasible in a number of patients after systemic neoadjuvant treatment. Further randomized clinical trials are needed to identify novel multimodal regimens that would be able to increase the percentage of patients undergoing curative pancreatic cancer surgery despite advanced tumor stage at the time of diagnosis.

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.

Successful bridging treatment and healing of enteric fistulae by vacuum-assisted closure (VAC) therapy and targeted drainage in patients with open abdomen.

PURPOSE: The object of this study was to investigate the bridging treatment of enteric fistulae by vacuum-assisted closure (VAC) therapy in patients with open abdomen. METHODS: We retrospectively analyzed patients who have been treated between 1 January 2007 and 31 December 2008 at the intensive care unit of the Department of General Surgery, Medical University Vienna. Control of the fistula was established by VAC therapy to bridge the patients to the time of the fistula resection. RESULTS: In the period of investigation, we treated nine (six men/three women) patients suffering from enteric fistulae with VAC therapy. The median age of the patients was 48 (range, 37-67) years. The median duration of VAC therapy was 76 (range, 53-128) days. The median length of stay in the intensive care unit was 44 (range, 25-127) days. The median APACHE II score was 23 (range, 18-25). The predicted mortality was 40%; the actual mortality was 11% (one patient). Primary fascial closure was achieved after median 91 (range, 89-92) days in three patients (33%) and secondary fascial closure after median 292 (range, 252-546) days in another three patients (33%). Fistulae were cured with VAC (five patients, 56%) and surgical resection (three patients, 33%). None of the patients developed a refistulation at the time of follow-up. CONCLUSIONS: Control of enteric fistulae by VAC therapy can lead to spontaneous fistula closure and is associated with a low mortality.

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.

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.

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.

Detrimental effects of controlled reperfusion on renal function after porcine autotransplantation are fully compensated by the use of Carolina rinse solution.

Despite extensive efforts in the fields of donor selection and management, standardisation of organ retrieval procedures, storage solutions, and novel immunosuppressive protocols, the rates of delayed graft function (DGF) after renal transplantation have been stagnating between 30% and 50%. As DGF exerts negative influences on acute rejection episodes and long-term organ function, the early phase of transplantation immediately following reperfusion deserves special interest. Several studies on machine-controlled reperfusion showed promising results in various organs, in experimental and clinical settings. Moreover, the flushing of organs with Carolina rinse solution (CR) immediately prior to reperfusion has been proven beneficial and is being clinically applied in human liver transplantation in recognised departments. In our study, we set up an autogenic porcine kidney transplantation model and assessed the normal values (control group) for creatinine clearance (ClCr) and urine output per hour (U/h) after "standard" reperfusion similar to clinical transplantation. Subsequently, kidneys of the experimental group 1 were reperfused at a blood pressure (RR) under the systemic level by means of a roller pump. Group 2 kidneys were rinsed with CR before controlled reperfusion, analogous to group 1. Both groups were compared with each other and with the assessed normal values. Our findings for Group 1 are that pressure-reduced reperfusion negatively affected immediate graft function. ClCr was reduced from 9.9 (control group) to 3.4 ml/min, U/h from 233 to 132 ml ( P<0.05). Group 2 showed that rinsing the kidneys with CR before reperfusion improved functional parameters highly significantly, compared with group 1 (ClCr: 13.5 vs 3.4 ml/min, U/h: 384 vs 132 ml; P<0.05) and even showed a positive trend compared with the control group (ClCr: 13.5 vs 9.9 ml/min, U/h: 384 vs 233 ml; P=0.0546). We can conclude that in a model of porcine renal autotransplantation, pressure-reduced reperfusion via a roller pump is detrimental to early kidney graft function. The flushing of organs with CR prior to controlled reperfusion significantly improves ClCr as well as urine output.

Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response.

OBJECTIVE: To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation. SUMMARY BACKGROUND DATA: Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood. METHODS: Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance. RESULTS: The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours. CONCLUSIONS: In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.

How to pass on expertise: pancreatoduodenectomy at a teaching hospital.

Pancreatoduodenectomy (PD) has become a routine procedure. Recent series report perioperative mortality rates of 5% or less, moderate morbidity, and even improved long-term survival. Nevertheless, being one of the most complex abdominal operations, a certain number of surgical procedures (i.e., personal caseload) seems essential for acceptable results. The objectives of this retrospective study were to evaluate whether PD can be safely performed as a teaching operation, and if the personal caseload of the senior surgeon affects morbidity and mortality. A series of 128 consecutive PDs carried out at a large academic teaching hospital were analyzed. The 49 operations performed by 11 residents of the surgical department as teaching operations under supervision of an experienced (senior) surgeon (ES) were compared with operations performed by an ES (group 2, n = 79). Three patients died from non-procedure-related causes (two in group 1). Eleven patients of group 2 had to be reoperated, in contrast to three in group 1 (NS). The total number of complications and number of pancreatic fistulas were comparable in the two groups. Surgeons performing less than one PD per year had significantly more complications. Under direct supervision of an experienced surgeon PD can be performed safely as a teaching operation. A caseload of at least one resection per year seems necessary for consistently good results.