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Objectives: Since the early 1990s, low long-term survival rates following pancreatic surgery for pancreatic ductal adenocarcinoma have challenged us to improve treatment. In this series, we aim to show improved survival from pancreatic ductal adenocarcinoma during the era of centralized pancreatic surgery.Methods: Analysis of all pancreatic resections performed at Helsinki University Hospital and survival of pancreatic ductal adenocarcinoma patients during 2000–2013 were included. Post-operative complications such as fistulas, reoperations, and mortality rates were recorded. Patient and tumor characteristics were compared with survival data.Results: Of the 853 patients undergoing pancreatic surgery, 581 (68%) were pancreaticoduodenectomies, 195 (21%) distal resections, 28 (3%) total pancreatectomies, and 49 (6%) other procedures. Mortality after pancreaticoduodenectomy was 2.1%. The clinically relevant B/C fistula rate was 7% after pancreaticoduodenectomy and 13% after distal resection, and the re-operation rate was 5%. The 5- and 10-year survival rates for pancreatic ductal adenocarcinoma were 22% and 14%; for T1-2, N0 and R0 tumors, the corresponding survival rates were 49% and 31%. Carbohydrate antigen 19-9 >75?kU/L, carcinoembryonic antigen >5?µg/L, N1, lymph-node ratio >20%, R1, and lack of adjuvant therapy were independent risk factors for decreased survival.Conclusion: After centralization of pancreatic surgery in southern Finland, we have managed to enable pancreatic ductal adenocarcinoma patients to survive markedly longer than in the early 1990s. Based on a 1.7-million population in our clinic, mortality rates are equal to those of other high-volume centers and long-term survival rates for pancreatic ductal adenocarcinoma have now risen to some of the highest reported.

Background and Aims: The rainage (PBD) prior to pancreaticoduodenectomy (PD) is controversial. If PBD is required, large bore self-expandable metallic stents (SEMS) are thought to maintain better drainage and have fewer postoperative complications than plastic stents. The confirming evidence is scarce. The aim of the study was to compare outcomes of surgery in patients who underwent PBD with SEMS or plastic stents deployed at endoscopic retrograde cholangiopancreatography (ERCP).Material and Methods: This is a retrospective study of 366 patients having had PD during 2000–2009. Preceding endoscopic PBD was performed in 191 patients and nine had had percutaneous transhepatic drainage (PTD). At the time of operation, 163 patients had a plastic stent and 28 had SEMS. Due to stent exchanges, 176 plastic stents and 29 SEMS were placed in all.Results and Conclusions: The stent failure rate was 7.4% for plastic stents and 3.4% for SEMS (p= 0.697). A bilirubin level under 50 µmol/L was reached by 80% of the patients with plastic stents and by 61% of the patients with SEMS (p= 0.058). A postoperative infection complication and/or a pancreatic fistula was found in 26% while using plastic stents and in 25% using SEMS (p= 1.000). In unstented patients with biliary obstruction, the bile juice was sterile significantly more often than in endoscopically stented patients (100% vs 1%, p< 0.001). When the stented and unstented patients were compared regarding postoperative infection complications, there was no significant difference between the groups (p= 0.365). Plastic stents did not differ from SEMS regarding the stent failure rate, bilirubin level decrease, amount of bacteria in the bile juice, or postoperative complications when used for PBD. The significantly higher price of SEMS suggests their use in selected cases only.

Tissue pH in the immediate subepithelial layer of rat gastric mucosa was measured using H+-selective microelectrodes. Exposure of the mucosa to luminal acid (50–150 mM) caused a significant acidification of the subepithelial tissue. Contrary to expectation, disruption of the mucosal barrier with taurocholate (10 mM), acetylsalicyclic acid (10 mM), or ethanol (20% vol/vol) during acid (100 mM HCl) perfusion promoted no further acidification of the subepithelial tissue but rather caused an alkalinization of the primarily acidified subepithelial tissue. When hemorrhagic shock was induced during acid perfusion, a profound acidification of the subepithelial tissue occurred even though a much lower luminal acidity (10 mM HCl) was used. Also, taurocholate had no alkalinizing influence on subepithelial pH during hemorrhagic shock, but caused a rapidly progressing and irreversible drop of the subepithelial tissue pH. The findings suggest that in normal stomach with intact “mucosal barrier”, H+back-diffusion occurs during exposure to acid. However, disruption of the mucosal barrier seems to lead to alkali (HCO3posts taggered −) efflux from the mucosa, which neutralizes the influxing H+, thus “masking” H+back-diffusion and protecting the mucosa. Yet, when adequate supply of HCO3post staggered −to the mucosa is blocked during exposure to a barrier-breaking agent and acid, increased H+back-diffusion becomes again “unmasked”, leading to extensive acidification and ulceration of the mucosa.

Features of “H+back-diffusion” after disruption of the gastric mucosal barrier were investigated by assessing, with a microelectrode technique, the influence of three barrier-breaking agents, taurocholate (10 mM), ethanol (20% vol/vol), and acetylsalicylic acid (10 mM) on intracellular pH and epithelial membrane potentials and resistances in isolated Necturusantral mucosa exposed to luminal acid (pH 3). Exposure of the mucosa to each of the three agents induced intracellular acidification of surface epithelial cells, but the pattern of pHibehavior was different for each agent: taurocholate induced immediate acidification of pHi, ethanol acidified pHiafter a delay of 4–6 min, whereas acetylsalicyclic acid initially alkalinized pHi, whereafter a rapid acidification of pHioccurred. Assessment of intraepithelial membrane resistances indicated that taurocholate primarily increases cellular conductance, decreasing in particular Ra. In contrast, ethanol mainly increased paracellular conductance, but also decreased cellular resistance, in particular Ra. Acetylsalicylic acid initially increased cell membrane resistances and Ra/Rbwhereafter a rapid decrease of Ra/Rband Rtoccurred. In each instance, the decrease of Ra/Rbpreceded acidification of pHi. The data suggest that all three agents induce intracellular acidification by increasing the conductance of the apical cell membrane to H+, but in ethanol-treated tissues paracellular conductance primarily contributes to H+backdiffusion.

Intracellular pH (pHi) was measured with protonsensitive liquid sensor microelectrodes in isolated Necturusantral mucosa, paying special attention to arranging experimental conditions to simulate conditions frequently associated with in vivo “stress ulceration.” Intracellular pH in mucosas perfused under standard conditions (Ringer's solution containing HCO3staggered−/CO2) was 7.22 + 0.02 (n = 27). Removal of Na+and HCO3staggered−or addition of amiloride or 4-acetamido-4-isothiosyanostillbene-2,2disulfonic acid (blockers of Na+/H+and Cl−/HCO3staggered−exchangers) had no influence on steady-state pHi, suggesting that these ion exchangers do not significantly contribute to the maintenance of pHiin the presence of normal external pH. Acidification of mucosal (luminal) perfusate to pH 3 (mimicking the presence of gastric acid) had no influence on pHi, but mucosal pH 2 (10 mM HCl) acidified pHito 6.93 ± 0.07. Acidification of serosal (nutrient) perfusate to pH 6 (mimicking intramucosal acidosis caused by back-diffusion of luminal H+) acidified pHito 6.72 ± 0.10. Removal of Na+from and addition of amiloride to the serosal perfusate during exposure to serosal pH 6.0 induced further acidification of pHi, suggesting that in this acidotic situation (with very low ambient HCO3staggered−concentration) a Na+/H+exchanger does contribute to the maintenance of steady-state pHi. Increased Pco2(10% vol/vol in the gas) in a slightly acidic milieu (mimicking mucosal ischemia) likewise acidified pHito 6.73 ± 0.05. A combination of mucosal acid (pH 3), high Pco2(10% CO2), and low serosal pH (pH 6) (mimicking conditions that prevail, for example, during hemorrhagic shock) acidified pHiand ultimately resulted in cell death. These derangements of intracellular acid-base balance may have pathogenetic importance also in in vivo stress ulceration.