Laureano Fernández-Cruz

Preoperative Staging and Tumor Resectability Assessment of Pancreatic Cancer: Prospective Study Comparing Endoscopic Ultrasonography, Helical Computed Tomography, Magnetic Resonance Imaging, and Angiography

OBJECTIVES:The objective of this study was to evaluate prospectively the efficacy of different strategies based on endoscopic ultrasonography (EUS), helical computed tomography (CT), magnetic resonance imaging (MRI), and angiography (A) in the staging and tumor resectability assessment of pancreatic cancer.METHODS:All consecutive patients with pancreatic carcinoma judged fit for laparotomy were studied by EUS, CT, MRI, and A. Results of each of the imaging techniques regarding primary tumor, locoregional extension, lymph-node involvement, vascular invasion, distant metastases, tumor TNM stage, and tumor resectability were compared with the surgical findings. Univariate, logistic regression, decision, and cost minimization analyses were performed.RESULTS:Sixty-two patients with pancreatic cancer were included. Helical CT had the highest accuracy in assessing extent of primary tumor (73%), locoregional extension (74%), vascular invasion (83%), distant metastases (88%), tumor TNM stage (46%), and tumor resectability (83%), whereas EUS had the highest accuracy in assessing tumor size (r = 0.85) and lymph node involvement (65%). The decision analysis demonstrated that the best strategy to assess tumor resectability was based on CT or EUS as initial test, followed by the alternative technique in those potentially resectable cases. Cost minimization analysis favored the sequential strategy in which EUS was used as a confirmatory technique in those patients in whom helical CT suggested resectability of the tumor.CONCLUSIONS:Helical CT and EUS are the most useful individual imaging techniques in the staging of pancreatic cancer. In those cases with potentially resectable tumors a sequential approach consisting of helical CT as an initial test and EUS as a confirmatory technique seems to be the most reliable and cost minimization strategy.

K-ras Mutations in DNA Extracted From the Plasma of Patients With Pancreatic Carcinoma: Diagnostic Utility and Prognostic Significance

PURPOSE Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed. PATIENTS AND METHODS Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. RESULTS The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P<.005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). CONCLUSION Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.

Laparoscopic distal pancreatectomy combined with preservation of the spleen for cystic neoplasms of the pancreas.

The precise role of laparoscopy in the resection of cystic neoplasms of the pancreas (CyNP) remains unknown. In addition, the question of spleen-preserving distal pancreatectomy is controversial. This report evaluates the feasibility and outcome of laparoscopic spleen-preserving distal pancreatectomy (LapSPDP) in 19 patients (17 women and 2 men) with CyNP. A prospective comparison was made between 11 consecutive patients (group I) with splenic vessel preservation (SVP) and 8 patients (group II) without SVP (Warshaw technique). This study used color-Doppler ultrasound (CDUS) as a tool to identify patients at high risk for postoperative splenic complications. The mean tumor size was, in both groups, 5 cm. In group I, with an intent-to-treat basis of SVP, only in 54.5 % of patients the spleen was preserved with an intact splenic artery and vein; in the remainder, conversion to the Warshaw technique was required for intraoperative bleeding. Evaluation of intraoperative factors showed that the mean operative time was significantly shorter (165 vs. 222 minutes) and the mean blood loss significantly lower (225 vs. 495 mL) in the group of LapSPDP with the Warshaw technique. No patients required blood transfusion in both groups. The overall conversion rate was 0%. The overall rate of pancreatic fistula was 15% and it was classified as biochemical leak (no clinical symptomatology). Overall splenic complications were observed in 16.6 % of patients but occurred only in three patients undergoing LapSPDP with the Warshaw technique; CDUS showed in 2 patients a focal splenic infarct; the third patient had an initial hospital stay of 5 days, was readmitted 2 days later for a massive splenic necrosis, and splenectomy was performed. The overall hospital stay was 5.7 days. At mean follow up of 22 months (range 6–42), there have been no local recurrences.

Pancreatogastrostomy with gastric partition after pylorus-preserving pancreatoduodenectomy versus conventional pancreatojejunostomy: a prospective randomized study.

Objective:To compare the results of postoperative morbidity rate of a new pancreatogastrostomy technique, pylorus-preserving pancreaticoduodenectomy (PPPD) with gastric partition (PPPD-GP) with the conventional technique of pancreaticojejunostomy (PJ). Summary and Background Data:Pancreatojejunostomy and pancreatogastrostomy (PG) are the commonly preferred methods of anastomosis after pancreatoduodenectomy (PD). All randomized controlled trials failed to show advantage of a particular technique, suggesting that both PJ and PG provide equally results. However, postoperative morbidity remains high. The best technique in pancreatic anastomosis is still debated. Method:Described here is a new technique, PPPD-GP; in this technique the gastroepiploic arcade is preserved. Gastric partition was performed using 2 endo-Gia staplers along the greater curvature of the stomach, 3 cm from the border. This gastric segment, 10 to 12 cm in length is placed in close proximity to the cut edge of the pancreatic stump. An end-to-side, duct-to-mucosa anastomosis (with pancreatic duct stent) is constructed. One hundred eight patients undergoing PPPD for benign and malignant diseases of the pancreatic head and the periampullary region were randomized to receive PG (PPPD-GP) or end-to-side PJ (PPPD-PJ). Results:The two treatment groups showed no differences in preoperative parameters and intraoperative factors. The overall postoperative complications were 23% after PPPD-GP and 44% after PPPD-PJ (P < 0.01). The incidence of pancreatic fistula was 4% after PPPD-GP and 18% after PPPD-PJ (P < 0.01). The mean + SD hospital stay was 12 ± 2 days after PPPD-GP and 16 ± 3 days after PPPD-PJ. Conclusions:This study shows that PPPD-GP can be performed safely and is associated with less complication than PPPD-PJ. The advantage of this technique over other PG techniques is that the anastomosis is outside the area of the stomach where the contents empty into the jejunum, but pancreatic juice drains directly into the stomach.

laparoscopic Unilateral and Bilateral Adrenalectomy for Cushing's Syndrome : transperitoneal and Retroperitoneal Approaches

OBJECTIVE This prospective randomized study compares the safety and efficacy of transperitoneal laparoscopic adrenalectomy (TLPA) and retroperitoneal approach (RLPA) in obese patients with Cushings syndrome. SUMMARY BACKGROUND DATA Recently, a retroperitoneal laparoscopic approach has been described with benefits of avoiding the respiratory and hemodynamic effects of carbon dioxide (CO2) pneumoperitoneum and giving direct access without the need to mobilize abdominal organs. METHODS Twenty-one adrenalectomies were performed in 9 patients (2 men, 7 women; mean age, 46.33 +/- 19.41 years old; range, 16 to 74 years old) with Cushings adenoma and in 6 women (mean age, 41.83 +/- 9.97 years old; range, 34 to 62 years old) with Cushings disease. Randomization gave 10 TLPA and 11 RLPA. Arterial blood gas samples, mean arterial pressure, heart rate, and clinical parameters were evaluated. RESULTS The partial pressure of carbon dioxide (PaCO2) increased in both retroperitoneal and transperitoneal CO2 insufflation compared with basal values (p < 0.01), and the TLPA showed a greater rise in the PaCO2 level compared with the RLPA at 30 minutes (p < 0.05); simultaneously, a significant increase (p < 0.05) of mean arterial pressure was observed in the TLPA compared with RLPA. No significant changes in heart rate were observed in both groups. The operative time with the TLPA and RLPA in patients with adenoma was 88.75 versus 105 minutes, respectively (p = not significant [NS]), and in patients with bilateral hyperplasia was 271.66 versus 305 minutes, respectively (p = NS). No patients required blood transfusions. The number of doses of analgesic with TLPA and RLPA in patients with adenoma was 3.25 versus 3.5, respectively (p = NS), and in patients with bilateral hyperplasia was 7.66 versus 7.33, respectively (p = NS). The hospital stay with TLPA and RLPA in patients with adenoma was 3.0 versus 2.75 days, respectively (p = NS), and in patients with bilateral hyperplasia was 6.0 versus 6.66 days, respectively (p = NS). The days to return to normal activity with TLPA and RLPA in patients with adenoma were 12.5 versus 12.25, respectively (p = NS), and in patients with bilateral hyperplasia were 19.66 versus 19.33, respectively (p = NS). Two patients with bilateral hyperplasia and TLPA had urinary infection. CONCLUSIONS Transperitoneal laparoscopic adrenalectomy and RLPA may become the techniques of choice for surgical removal of the adrenal lesions in Cushings syndrome. The retroperitoneoscopic approach might be a better option in patients with previous abdominal surgery and in patients with pre-existing cardiorespiratory disease.

Experimental and clinical experience with urine amylase monitoring for early diagnosis of rejection in pancreas transplantation

Pancreas allograft rejection in dogs with pancreati-cocystostomy can be predicted in advance of hyperglycemia by monitoring the urinary amylase (UA) concentration (U/L): In initial experiments, UA values declined to <1000 1.3±0.2 days before hyperglycemia in non-immunosuppressed dogs, 3.3±1.0 days in dogs treated with cyclosporine (CsA), and 9.3±0.7 days in dogs treated with CsA, azathioprine (Aza), and prednisone (triple therapy). Autotransplanted control dogs maintained high urine amylase concentrations indefinitely (mean 125,544±36,931). In a subsequent experiment, in 19 dogs with bladder-drained pancreas allografts on CsA only for prophylactic immunosuppression, a five-day course of antirejection treatment with Aza (5.0 mg/ kg) and antilymphocyte globulin ALG (1 mg/kg) was started in group A (n = 10) when a raise in serum glucose was detected, and in group B (n = 9) when a drop of UA below 1000 was observed. The functional allograft survival rate was 9.2±0.5 days in group A (treatment started after hyperglycemia) and 29.0±5.7 days in group B (treatment started after drop in UA) (P = .002). The UA dropped in all dogs before hyperglycemia, at a mean of 2.7 days in group A and 20.8 days in group B. Clinically, 8 patients received a whole cadaver pancreas transplant with urinary drainage of the exocrine secretions. All were followed with UA monitoring. Three recipients lost the grafts for technical reasons. One had a primary nonfunction and UA was below 1000 U/24 hr; two developed abscesses and the grafts were removed while functioning with high UA values. Five grafts are currently functioning; 3 recipients had no rejection episodes and their UA values ranged from 30,000 to 100,000 U/24 hr during their entire postoperative course. The other two had rejection episodes. In both cases UA decreased to baseline levels 1 and 4 days in advance of the hyperglycemia. After antirejection treatment UA rose again to high values and plasma glucose levels declined. Both patients are currently in.

Activation of alveolar macrophages in lung injury associated with experimental acute pancreatitis is mediated by the liver.

OBJECTIVE To evaluate (1) whether alveolar macrophages are activated as a consequence of acute pancreatitis (AP), (2) the implication of inflammatory factors released by these macrophages in the process of neutrophil migration into the lungs observed in lung injury induced by AP, and (3) the role of the liver in the activation of alveolar macrophages. SUMMARY BACKGROUND DATA Acute lung injury is the extrapancreatic complication most frequently associated with death and complications in severe AP. Neutrophil infiltration into the lungs seems to be related to the release of systemic and local mediators. The liver and alveolar macrophages are sources of mediators that have been suggested to participate in the lung damage associated with AP. METHODS Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. The inflammatory process in the lung and the activation of alveolar macrophages were investigated in animals with and without portocaval shunting 3 hours after AP induction. Alveolar macrophages were obtained by bronchoalveolar lavage. The generation of nitric oxide, leukotriene B4, tumor necrosis factor-alpha, and MIP-2 by alveolar macrophages and the chemotactic activity of supernatants of cultured macrophages were evaluated. RESULTS Pancreatitis was associated with increased infiltration of neutrophils into the lungs 3 hours after induction. This effect was prevented by the portocaval shunt. Alveolar macrophages obtained after induction of pancreatitis generated increased levels of nitric oxide, tumor necrosis factor-alpha, and MIP-2, but not leukotriene B4. In addition, supernatants of these macrophages exhibited a chemotactic activity for neutrophils when instilled into the lungs of unmanipulated animals. All these effects were abolished when portocaval shunting was carried out before induction of pancreatitis. CONCLUSION Lung damage induced by experimental AP is associated with alveolar macrophage activation. The liver mediates the alveolar macrophage activation in this experimental model.

Role of P-Selectin and ICAM-1 in Pancreatitis-Induced Lung Inflammation in Rats: Significance of Oxidative Stress

OBJECTIVE To investigate the role of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of lung injury associated with pancreatitis, and the relation between xanthine oxidase-derived oxidants and expression of these adhesion molecules. SUMMARY BACKGROUND DATA In acute pancreatitis, acute respiratory distress syndrome occurs in the early stages of disease. This process is mediated by neutrophil infiltration. METHODS Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. ICAM-1 and P-selectin expression was measured using radiolabeled monoclonal antibodies. Neutrophil infiltration and plasma levels of xanthine oxidase were also evaluated. RESULTS Pancreatitis induces increases in P-selectin expression in lung, whereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of either P-selectin or ICAM-1 prevents the infiltration of neutrophils into the lung. Xanthine and xanthine oxidase activity were increased after induction of pancreatitis. Xanthine oxidase inhibition prevents the upregulation of P-selectin in lung and neutrophil infiltration. CONCLUSIONS During acute pancreatitis, P-selectin is upregulated in the pulmonary endothelium and is a key determinant of leukocyte recruitment. Constitutive ICAM-1 is also involved in the process of cell infiltration into the lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase released by the damaged pancreas.

Comparison of Endoscopic Ultrasonography and Magnetic Resonance Cholangiopancreatography in the Diagnosis of Pancreatobiliary Diseases: A Prospective Study

OBJECTIVES:To compare the diagnostic value of endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) in: (a) patients with a dilated biliary tree unexplained by ultrasonography (US) (group 1), and (b) the diagnosis of choledocholithiasis in patients with nondilated biliary tree (group 2).METHODS:Patients were prospectively evaluated with EUS and MRCP. The gold standard used was surgery or EUS-FNA and ERCP, intraoperative cholangiography, or follow-up when EUS and/or MRCP disclosed or precluded malignancy, respectively. Likelihood ratios (LR) and pretest and post-test probabilities for the diagnosis of malignancy and choledocholithiasis were calculated.RESULTS:A total of 159 patients met one of the inclusion criteria but 24 of them were excluded for different reasons. Thus, 135 patients constitute the study population. The most frequent diagnosis was choledocholithiasis (49% in group 1 and 42% in group 2, P = 0.380) and malignancy was more frequent in group 1 (35% vs 7%, respectively, P < 0.001). When EUS and MRCP diagnosed malignancy, its prevalence in our series (35%) increased up to 98% and 96%, respectively, whereas it decreased to 0% and 2.6% when EUS and MRCP precluded this diagnosis. In patients in group 2, when EUS and MRCP made a positive diagnosis of choledocholithiasis, its prevalence (42%) increased up to 78% and 92%, respectively, whereas it decreased to 6% and 9% when any pathologic finding was ruled out.CONCLUSIONS:EUS and MRCP are extremely useful in diagnosing or excluding malignancy and choledocholithiasis in patients with dilated and nondilated biliary tree. Therefore, they are critical in the approach to the management of these patients.

Outcome after laparoscopic enucleation for non-functional neuroendocrine pancreatic tumours

BACKGROUND Non-functional endocrine pancreatic tumours (NPT) of more than 2 cm have an increased risk of malignancy. The aim of the present study was: (i) to define the guidelines for laparoscopic enucleation (LapEn) in patients with a non-functional NPT ≤3 cm in diameter; (ii) to evaluate pancreas-related complications; and (iii) to present the long-term outcome. METHODS Between April 1998 and September 2010, 30 consecutive patients underwent laparoscopic surgery for a non-functional NPT (median age 56.5 years, range 44-83). Only 13 patients with tumours ≤3 cm in size underwent LapEn. Local lymph node dissection to exclude lymph node involvement was performed in all patients. RESULTS The median tumour size, operative time and blood loss were 2.8 cm (range 2.8-3), 130 min (range 90-280) and 220 ml (range 120-300), respectively. A pancreatic fistula occurred in five patients: International Study Group of Pancreatic Fistula (ISGPF) A in two patients and ISGPF B in three patients. The median follow-up was 48 months (12-144). Three patients with well-differentiated carcinoma are free of disease 2, 3 and 4 years after LapEn and a regional lymphadenectomy. One patient, 5 years after a LapEn, presented with lymph node and liver metastases. CONCLUSIONS The present study confirms the technical feasibility and acceptable morbidity associated with LapEn. Intra-operative lymph node sampling and frozen-section examination should be performed at the time of LapEn; when a malignancy is confirmed, oncologically appropriate lymph node dissection should be performed.