CENTRAL PANCREATECTOMY FOR BENIGN PANCREATIC PATHOLOGY/TRAUMA: IS IT A REASONABLE PANCREAS‐PRESERVING CONSERVATIVE SURGICAL STRATEGY ALTERNATIVE TO STANDARD MAJOR PANCREATIC RESECTION?

BACKGROUND: The aim of this study was to assess the technical feasibility, safety and outcome of central pancreatectomy (CP) with pancreaticogastrostomy or pancreaticojejunostomy in appropriately selected patients with benign central pancreatic pathology/trauma. Benign lesions/trauma of the pancreatic neck and proximal body pose an interesting surgical challenge. CP is an operation that allows resection of benign tumours located in the pancreatic isthmus that are not suitable for enucleation. METHODS: Between January 2000 and December 2005, eight central pancreatectomies were carried out. There were six women and two men with a mean age of 35.7 years. The cephalic pancreatic stump is oversewn and the distal stump is anastomosed end-to-end with a Roux-en-Y jejunal loop in two and with the stomach in six patients. The indications for CP were: non-functional islet cell tumours in two patients, traumatic pancreatic neck transection in two and one each for insulinoma, solid pseudopapillary tumour, splenic artery pseudoaneurysm and pseudocyst. Pancreatic exocrine function was evaluated by a questionnaire method. Endocrine function was evaluated by blood glucose level. RESULTS: Morbidity rate was 37.5% with no operative mortality. Mean postoperative hospital stay was 10.5 days. Neither of the patients developed pancreatic fistula nor required reoperations or interventional radiological procedures. At a mean follow up of 26.4 months, no patient had evidence of endocrine or exocrine pancreatic insufficiency, all the patients were alive and well without clinical and imaging evidence of disease recurrence. CONCLUSION: When technically feasible, CP is a safe, pancreas-preserving pancreatectomy for non-enucleable benign pancreatic pathology/trauma confined to pancreatic isthmus that allows for cure of the disease without loss of substantial amount of normal pancreatic parenchyma with preservation of exocrine/endocrine function and without interruption of enteric continuity.     

Formalin‐Induced Short‐ and Long‐Term Modulation of Cav Currents Expressed in Xenopus Oocytes: An In Vitro Cellular Model for Formalin‐Induced Pain

Abstract: Xenopus oocytes expressing high voltage‐gated calcium channels (Ca_v) were exposed to formalin (0.5%, v/v, 5 min.) and the oocyte death and Ca_v currents were studied for up to 10 days. Ca_v channels were expressed with α₁β₁b and α₂δ sub‐units and the currents (I_Ba) were studied by voltage clamp. None of the oocytes was dead during the exposure to formalin. Oocyte death was significant between day 1 and day 5 after the exposure to formalin and was uniform among the oocytes expressing various Ca_v channels. Peak I_Ba of all Ca_v and A₁, the inactivating current component was decreased whereas the non‐inactivated R current was not affected by 5 min. exposure to formalin. On day 1 after the exposure to formalin, Ca_v1.2c currents were increased, 2.1 and 2.2 currents were decreased and 2.3 currents were unaltered. On day 5, both peak I_Ba and A₁ currents were increased. Ca_v1.2c, 2.2 and 2.3 currents were increased and Ca_v2.1 was unaltered on day 10 after the exposure to formalin. Protein kinase C (PKC) may be involved in formalin‐induced increase in Ca_v currents due to the (i) requirement for Ca_vβ₁b sub‐units; (ii) decreased phorbol‐12‐myristate,13‐acetate potentiation of Ca_v2.3 currents; (iii) absence of potentiation of Ca_v2.3 currents following down‐regulation of PKC; and (iv) absence of potentiation of Ca_v2.2 or 2.3 currents with Ser→Ala mutation of Ca_vα₁2.2 or 2.3 sub‐units. Increased Ca_v currents and PKC activation may coincide with changes observed in in vivo pain investigations, and oocytes incubated with formalin may serve as an in vitro model for some cellular mechanisms of pain.     

9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol, from Eulophia ochreata, inhibits inflammatory signalling mediated by Toll-like receptors

Background and purpose:

9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol (RSCL-0520) is a phenanthrene isolated from Eulophia ochreata, one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti-inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti-inflammatory properties of RSCL-0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll-like receptors (TLRs).

Experimental approach:

The in vitro anti-inflammatory activities of RSCL-0520 were investigated in LPS-stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor-κB (NF-κB). Tumour necrosis factor (TNF)-α levels in serum following LPS stimulation in mice and carrageenan-induced paw oedema in rats were used as in vivo models.

Key results:

Pretreatment with RSCL-0520 effectively inhibited LPS-induced, TLR4-mediated, NF-κB-activated inflammatory genes in vitro, and reduced both LPS-induced TNF-α release and carrageenan-induced paw oedema in rats. Treatment with RSCL-0520 reduced LPS-stimulated mRNA expression of TNF-α, COX-2, intercellular adhesion molecule-1, interleukin (IL)-8 and IL-1β, all regulated through NF-κB activation. RSCL-0520, however, did not interfere with any cellular processes in the absence of LPS.

Conclusions and implications:

RSCL-0520 blocked signals generated by TLR4 activation, as shown by down-regulation of NF-κB-regulated inflammatory cytokines. The inhibitory effect involved both MyD88-dependent and -independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant-derived TLR antagonists, as potential anti inflammatory agents.