Franco Stagnitti

Activation of alpha1-adrenergic receptors stimulate the growth of small mouse cholangiocytes Via calcium-dependent activation of nuclear factor of activated T cells 2 and specificity protein 1†‡

Small cholangiocytes proliferate via activation of calcium (Ca2+)‐dependent signaling in response to pathological conditions that trigger the damage of large cyclic adenosine monophosphate–dependent cholangiocytes. Although our previous studies suggest that small cholangiocyte proliferation is regulated by the activation of Ca2+‐dependent signaling, the intracellular mechanisms regulating small cholangiocyte proliferation are undefined. Therefore, we sought to address the role and mechanisms of action by which phenylephrine, an α1‐adrenergic agonist stimulating intracellular D‐myo‐inositol‐1,4,5‐triphosphate (IP3)/Ca2+ levels, regulates small cholangiocyte proliferation. Small and large bile ducts and cholangiocytes expressed all AR receptor subtypes. Small (but not large) cholangiocytes respond to phenylephrine with increased proliferation via the activation of IP3/Ca2+‐dependent signaling. Phenylephrine stimulated the production of intracellular IP3. The Ca2+‐dependent transcription factors, nuclear factor of activated T cells 2 (NFAT2) and NFAT4, were predominantly expressed by small bile ducts and small cholangiocytes. Phenylephrine stimulated the Ca2+‐dependent DNA‐binding activities of NFAT2, NFAT4, and Sp1 (but not Sp3) and the nuclear translocation of NFAT2 and NFAT4 in small cholangiocytes. To determine the relative roles of NFAT2, NFAT4, or Sp1, we knocked down the expression of these transcription factors with small hairpin RNA. We observed an inhibition of phenylephrine‐induced proliferation in small cholangiocytes lacking the expression of NFAT2 or Sp1. Phenylephrine stimulated small cholangiocyte proliferation is regulated by Ca2+‐dependent activation of NFAT2 and Sp1. Conclusion: Selective stimulation of Ca2+‐dependent small cholangiocyte proliferation may be key to promote the repopulation of the biliary epithelium when large bile ducts are damaged during cholestasis or by toxins. (HEPATOLOGY 2010;53:628‐639)

Pancreaticojejunostomy with Applicationof Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil®) in Roux-en-Y Reconstruction after Pancreaticoduodenectomy

To the Editor We read with great interest the article by Wellner and colleagues about the comparison between pancreaticogastrostomy (PG) and Roux-en-Y pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD) with regard to postoperative pancreatic fistula (POPF) and other complications. The authors concluded that PG was superior to PJ in terms of clinically relevant POPF; although this study is retrospective, the use of a large case number and standardized measures in evaluation of the surgical outcome makes the results not negligible. Instead, the results of our previously described technique of Roux-en-Y reconstruction show that PJ may have a lower prevalence of POPF than that reported by Wellner and colleagues and suggest that outcome after Roux-en-Y reconstruction with regard to POPF can be further improved using fibrinogen/thrombincoated collagen patch (TachoSil®, Nycomed, UK Ltd.) in carrying out PJ. Briefly, we reviewed the clinical records of 54 consecutive patients who underwent PD by one surgeon (P.C.) at “La Sapienza” University (Rome, Italy) from January 1995 to December 2008. The underlying diseases were: pancreatic carcinoma in 31 cases; pancreatic serous cystadenoma in six cases; mucinous cystadenoma in one case; pancreatic endocrine tumor in two cases; ampullar carcinoma in seven cases; distal bile duct carcinoma in six cases; and chronic pancreatitis in one case. In all patients, the surgical procedure comprised PD with suprapyloric gastric resection and Roux -en-Y reconstruction with anastomosis of the isolated Roux limb to the stomach and single Roux limb to both the pancreatic stump and hepatic duct. Small catheters were inserted in the main duct, passed through the anastomosed bowel loop and fixed to the abdominal wall (Fig. 1a, b). A drainage tube was placed near to the pancreaticojejunostomy; external biliary drainage was not used. Pancreaticojejunal end-to-end anastomosis was done by simple invagination of the pancreatic stump into the jejunal loop for 2 cm and sutured all around with a singlelayer interrupted pledget-supported Ticron stitches between the seromuscularis of the jejunum and the pancreatic capsule. From January 2005, TachoSil® has been layered on suture line of pancreaticojejunal anastomosis (Fig. 1c, d). All 27 consecutive patients had pancreaticojejunostomy without TachoSil® (group A) whereas 27 consecutive patients had pancreaticojejunostomy with TachoSil®. All patients in our study received octreotide during the first six postoperative days. The postoperative surgical outcome within 60 postoperative days was assessed. POPF, postoperative hemorrhage J Gastrointest Surg (2009) 13:1396–1398 DOI 10.1007/s11605-009-0894-7

A systematic review on the use of topical hemostats in trauma and emergency surgery

BackgroundA wide variety of hemostats are available as adjunctive measures to improve hemostasis during surgical procedures if residual bleeding persists despite correct application of conventional methods for hemorrhage control. Some are considered active agents, since they contain fibrinogen and thrombin and actively participate at the end of the coagulation cascade to form a fibrin clot, whereas others to be effective require an intact coagulation system. The aim of this study is to provide an evidence-based approach to correctly select the available agents to help physiciansxa0to use the most appropriate hemostat according to the clinical setting, surgical problem and patient’s coagulation status.MethodsThe literature from 2000 to 2016 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] protocol. Sixty-six articles were reviewed by a panel of experts to assign grade of recommendation (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development and Evaluation] system, and a national meeting was held.ResultsFibrin adhesives, in liquid form (fibrin glues) or with stiff collagen fleece (fibrin patch) are effective in the presence of spontaneous or drug-induced coagulation disorders. Mechanical hemostats should be preferred in patients who have an intact coagulation system. Sealants are effective, irrespective of patient’s coagulation status, to improve control of residual oozing. Hemostatic dressings represent a valuable option in case of external hemorrhage at junctional sites or when tourniquets are impractical or ineffective.ConclusionsLocal hemostatic agents are dissimilar products with different indications. A knowledge of the properties of each single agent should be in the armamentarium of acute care surgeons in order to select the appropriate product in different clinical conditions.

Risk management in surgery.

Malpractice is the responsible for the greatest number of legal claims. At the present time, legal actions against physicians in Italy are 15,000 per year, and a stunning increase about costs to refund patients injured by therapeutic and diagnostic errors is expected. The method for the medical prevention is Risk Management, that is the setting-up of organizational instruments, methods and actions that enable the measurement or estimation of medical risk; it allows to develop strategies to govern and reduce medical error. In the present work, the reconstruction about the history of risk management in Italy was carried out. After then the latest initiatives undertaken by Italy about the issue of risk management were examined.

Visual acuity changes in retinitis pigmentosa during pregnancy

Most of the information available on the effect of pregnancy on the progression of retinitis pigmentosa, a retinal degenerative disease potentially leading to blindness, is limited to the impressions of the patients [1]. The aim of the present study was to investigate visual function during pregnancy in patients with retinitis pigmentosa to provide recommendations for preconception and pregnancy counseling. Twenty-two pregnant patients with retinitis pigmentosa were enrolled (age range 20–32 years, each patient had 2 functioning eyes). The patients provided written informed consent and the procedures adhered to the tenets of the Declaration of Helsinki. All patients underwent a complete ophthalmologic examination and particular attention was paid to best corrected visual acuity (BCVA), which was assessed at 1 month, 3 months, 5 months, and 7 months of pregnancy, immediately after the delivery, and at 3 months, 5 months, and 8 months post partum. Statistical analysis was performed using the t test. Pb0.05 was considered statistically significant. None of the patients felt they experienced visual changes during pregnancy. Mean BCVA scores were 0.11±0.48 logMAR (logarithm of the minimum angle of resolution) at 1 month; 0.12±0.45 logMAR at 3 months; 0.14±0.45 logMAR at 5 months; 0.15±0.45 logMAR at 7 months; 0.17±0.46 logMAR immediately after delivery; 0.19±0.45 logMAR at 3 months post partum; 0.21±0.44 logMAR at 5 months post partum; and 0.17±0.42 logMAR at 8months post partum (Fig.1). There was no statistically significant correlation between visual acuity behavior and pregnancy. The only statistically significant result was the decrease in BCVA between the beginning of pregnancy and