Three-dimensional heterocycles: new uracil-based structures obtained by nucleophilic substitution at the sp2 carbon of bromoisoxazoline.

The regioisomeric cycloadducts of bromonitrile oxide and N-benzoyl-2,3-oxaza-norborn-5-ene were easily prepared and elaborated into a novel class of uracil-based scaffolds. The key-synthetic step is the nucleophilic substitution at the sp2 carbon atom of the bromoisoxazoline three-dimensional heterocycles. The protocol to perform the nucleophilic substitution of uracil anions was optimized and adapted to the steric requirements of the substrates. A library of pyrimidine derivatives was prepared in very good yields and the products were fully characterized. They are proposed as nucleoside analogues and as synthons for ß-turn motifs within PNA structures.

Defining a therapeutic program for recurrent acute pancreatitis patients with unknown etiology.

AIM: To define a therapeutic program for mild-moderate acute pancreatitis (AP), often recurrent, which at the end of the diagnostic process remains of undefined etiology. MATERIAL AND METHODS: In the period 2011-2012, we observed 64 cases of AP: 52 mild-moderate, 12 severe; biliary 39, biliary in alcoholic chronic pancreatitis 5, unexplained recurrent 20. The clinical and instrumental evaluation of the 20 cases of unexplained AP showed 6 patients with biliary sludge, 4 microlithiasis, 4 sphincter of Oddi dysfunction, and 6 cases that remained undefined. RESULTS: Among 20 patients with recurrent, unexplained AP at initial etiological assessment, we performed 10 video laparo cholecystectomies (VLCs), 2 open cholecystectomies and 4 endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomies (ERCP/ES) in patients who had undergone previous cholecystectomy; 4 patients refused surgery. Among these 20 patients, 6 had AP that remained unexplained after second-level imaging investigations. For these patients, 4 VLCs and 2 ERCP/ES were performed. Follow-up after six months was negative for further recurrence. CONCLUSION: The recurrence of unexplained acute pancreatitis could be treated with empirical cholecystectomy and/or ERCP/ES in cases of previous cholecystectomy.

Laparoscopic cholecystectomy: evaluation of liver function tests.

AIM: The changes in liver function tests (LFTs) after laparoscopic cholecystectomy (LC) have been described in the literature. The aims of this study are to value the increases of the LFTs and its clinical appearance after LC. Furthermore we studied the correlation of the changes of LFTs with the operative time and the role of elevated BMI. MATERIAL OF STUDY: In the period October 2012 - May 2013, 81 patients undergone to elective LC were analyzed by examining bilirubin, AST, ALT, ALP, GGT at the admission, 1 and 3 days after surgery. Correlations of the length of intervention and BMI with changes of LFTs are evaluated. During surgery, the intrabdominal pressure has been 12 mmHg in all patients. The Student t test, PCC (Pearson's correlation coefficient) OR (odds ratio) were performed to determine statistical significance. RESULTS: The level of (serum) AST, ALT increased significantly during 24-48 hours after LC (p < 0,0001). The increase of (total and direct) bilirubin has not the statistical significance. On the contrary ALP, GGT was significantly decreased (p < 0,001). Three days after surgery LFTs returned to normal level in the patients with previous normal level of tests. The length of intervention doesn't show correlations with changes of LFTs (PCC 0.2). the BMI >28 led increased risk of changes of LFTs (OR 2.44). CONCLUSIONS: The changes of LFTs are transient and clinically silent in patients with a normal liver function. Nevertheless must be evaluated preoperative BMI and liver dysfunction.

Common bile duct lithiasis: therapeutic approach.

INTRODUCTION: Treatment of cholecysto-choledocholithiasis has been revisited from the standpoint of either endoscopic or laparoscopic mini invasive approach. A standard diagnostic-therapeutic procedure has not been unanimously defined. PATIENTS AND METHODS: Since 1997 to 2011 we have treated 924 patients: 555 gallbladder lithiasis, 276 acute biliary pancreatitis and 93 choledocholithiasis (without pancreatitis). We have compared, by the review of the literature, our results of two stage endoscopic stones removal followed by laparoscopic cholecystectomy versus one stage laparo-endoscopic rendezvous technique/VLC and laparoscopic approach alone. RESULTS: In our experience endoscopic removal of stones have been performed in 82 patients (88.17%); 11 patients (11.82%),not eligible for endoscopic approach, have been submitted to laparotomic therapy. In sum preoperative ERCP/ES with CBD cleaning followed by VLC, not with standing the valid results of laparoscopic approach alone remains the strategy more frequently applied in clinical practice, because the good results. CONCLUSIONS: The results of the treatment of CBD lithiasis of sequential laparo-endoscopic approach (two or one stage) and of laparoscopic approach alone are roughly overlappable. Therefore the first has remained the treatment of reference and comparison in all the clinical evaluation of different procedure.

Severe acute pancreatitis: clinical forms of different gravity.

INTRODUCTION AND AIMS: Severe Acute Pancreatitis (SAP) is characterized by some degree of severity. The aim of this study is to indentify within severe forms the critical, early severe acute pancreatitis (ESAP). METHODS AND PATIENTS: Since 1997 to 2011 we have treated 276 acute biliary pancreatitis. SAP was 21.7% (60); among SAP were defined 13 (21.6%) ESAP as presence of organ dysfunction within 72 hours after onset of symptoms. Clinical features, organ failure, therapeutic choices and results between SAP (47) and ESAP (13) were compared. RESULTS: The comparison has shown the following results: impairment degree of pancreas (Balthazar CT score): SAP 2.3 - ESAP 3.85; abdominal compartment syndrome (ACS): ESAP 7.6% (1/13); MODS: ESAP 46.1% (6/13); simgle organ dysfunction: SAP 51% (24/47) - ESAP 53.8% (7/13) ; hypoxemia: SAP 65.9 % (31/47) - ESAP 76.9% (10/13); pancreatic infections: SAP 6.3% (3/47) - ESAP 23% (3/13); mortality: SAP 4.2% (2/47) - ESAP 15.4% (2/13). DISCUSSION: ESAP is characterized early by major incidence of ACS, MODS, impairment degree of the pancreas. In a later phase the gravity of severe pancreatitis lies on the septic complications of fluid necrotic collections. In ESAP the mortality is higher: 15.4% because of multiorgan dysfunction (in first phase); in SAP is 4.3% because of septic complications (in later phase). CONCLUSIONS: Treatment of SAP and ESAP is now more conservative and less invasive than in the past: intensive care, prevention of intestinal failure and assure papillary patency in the first phase of the disease. In the later phase therapeutic procedure for fluid necrotic collections is US/CT percutaneous catheter drainage.