Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology. Historical remarks & present stateThe first known description of pancreatic cancer is attributed to Giovanni Battista Morgagni in his 1761 publication 'de Sedibus Et Causis Morborum Per Anatomen Indagatis Libri Quinque' [1]. However, the lack of a microscopic evaluation makes the true diagnosis of ductal adenocarcinoma uncertain. The next important advancement in our understanding of pancreatic cancer did not come until 1858, when Jacob Mendez Da Costa revisited Morgagni's original work and also described the first microscopic diagnosis of adenocarcinoma, manifesting pancreatic cancer as a true disease entity [2].The history of pancreatic surgery is fairly recent and involves a combination of brave surgical pioneers, the development of surgical anesthesia and modern aseptic techniques. Some landmarks in the history of pancreatic surgery deserve to be mentioned. The first reported attempt at a pancreaticoduodenectomy was performed in 1898 by the Italian surgeon Alessandro Codivilla for a tumor involving the head of the pancreas [3]; however, the patient did not survive the postoperative period. In the same year, William Stewart Halsted from Johns Hopkins Hospital performed the first successful resection for ampullary cancer by excising portions of the duodenum and the pancreas [4]. The first successful pancreaticoduodenectomy is credited to the German surgeon Walther Carl Eduard Kausch, as part of a two-stage procedure [5]. In 1914, Georg Hirschel performed the first successful pancreaticoduodenectomy in one stage [6] and then in 1935, Allen Oldfather Whipple presented the results of a two-stage procedure involving the resection of the head of the pancreas and duodenum for ampullary carcinoma at the annual meeting of the American Surgical Association, which renewed interest in pancreatic surgery [7]. During his career, Whipple performed 37 pancreaticoduodenectomies, with the procedure evolving into a one-stage technique [8,9], and 1964-1968 1969-1973 1974-1978 1979-1983 1984-1988 1989-1993 1994-1998 1999-2003 2004-2008 2009-2013 Period of diagnosis Whipple is generally credited with popularizing the operation that still bears his name. In 1937, Alexander Brunschwig performed the first successful pancreaticoduodenectomy for pancreatic adenocarcinoma [10]. Today, with the concentration of experience in high-volume hospitals, pancreatic surgery has become a safe procedure associated with an operative mortality below 3% [11][12][13]. While major advances have been made ...

Using a rabbit model, the involvement of the L-arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4-8 V, 20-30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of: (1) the slope of the initial, ascending part of the pressure increase; (2) delta P, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of delta P. Intrapenile administration of the L-arginine/nitric oxide synthesis inhibitor NG-nitro-L-arginine had no effect on systemic arterial blood pressure. However, NG-nitro-L-arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and delta P decreased significantly. NG-nitro-D-arginine (2.19), on the other hand, had no inhibitory effect. L-arginine (21.07 mg), given either directly or after NG-nitro-L-arginine had no consistent effect on the functional response to cavernous nerve stimulation. The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively, and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG-nitro-L-arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.

1. NG‐nitro‐L‐arginine (L‐NOARG, 10(‐4) M), an inhibitor of nitric oxide (NO) synthesis, had no contractile effect on isolated preparations of rabbit and human corpus cavernosum at baseline tension, but increased tension in preparations contracted by noradrenaline (rabbit 10(‐5) M, man 3 x 10(‐7)‐3 x 10(‐6) M) or K+ (rabbit 60 mM). 2. Electrical field stimulation (supramaximal voltage, 0.8 ms pulses, 5 s train duration, 0.5‐35 Hz) of rabbit and human corpus cavernosum preparations contracted by noradrenaline (rabbit 10(‐5) M, man 3 x 10(‐6) M) or endothelin‐1 (rabbit 10(‐8) M) produced relaxations that were sensitive to tetrodotoxin (10(‐6) M), and dependent on the frequency and number of pulses delivered. L‐NOARG (10(‐6)‐10(‐4) M), but not NG‐nitro‐D‐arginine (D‐NOARG, 10(‐6)‐10(‐4) M), inhibited electrically induced relaxations in a concentration‐dependent manner, and at 10(‐4) M the relaxations were virtually abolished. L‐Arginine (10(‐3) M), but not D‐arginine (10(‐3) M), partly reversed the inhibitory effect of L‐NOARG (10(‐4) M). In rabbit corpus cavernosum preparations, as with Methylene Blue (3 x 10(‐5) M), an inhibitor of the soluble guanylate cyclase, and haemoglobin (10(‐5) M), sequestering NO in the extracellular space, significantly reduced electrically evoked relaxations. Scopolamine (10(‐6) M) had little or no effect on relaxations induced by electrical field stimulation. 3. Preparations of rabbit and human corpus cavernosum contracted by noradrenaline (rabbit 10(‐5) M, man 3 x 10(‐6) M) were relaxed by carbachol (10(‐9)‐10(‐4) M) in a concentration‐dependent manner. Scopolamine (10(‐6) M) and L‐NOARG (10(‐4) M) abolished, and Methylene Blue (3 x 10(‐5) M) and haemoglobin (10(‐5) M) greatly reduced, the carbachol‐induced relaxation, while D‐NOARG (10(‐4) M) had no significant effect. 4. In rabbit corpus cavernosum preparations contracted by noradrenaline (10(‐5) M), L‐NOARG (10(‐4) M) had no significant effect on relaxations induced by vasoactive intestinal polypeptide (10(‐6) M). 5. SIN‐1 (3‐morpholino‐sydnonimin hydrochloride, 10(‐8)‐3 x 10(‐4) M), which spontaneously liberates NO, relaxed preparations of rabbit and human corpus cavernosum contracted by noradrenaline (rabbit 10(‐5) M, man 3 x 10(‐6) M) or endothelin‐1 (rabbit 10(‐8) M, man 3 x 10(‐9) M) in a concentration‐dependent way.(ABSTRACT TRUNCATED AT 400 WORDS)

80-kVp 16-row MDCT with optimization of injection parameters may be performed with preserved diagnostic quality, using markedly reduced CM doses compared with common routine practice, which should be to the benefit of patients at risk of CIN.