Long-term results of laparoscopic Nissen fundoplication due to gastroesophageal reflux disease. A ten year follow-up in a low volume center.

BACKGROUND AND AIMS: Laparoscopic 360 degrees nissen fundoplication has been our routine surgical procedure since 1995, in the treatment of gastroesophageal reflux disease (GERD). We have reviewed our results of patients treated with laparoscopic Nissen fundoplication (LNF) during 1995-1998. MATERIAL AND METHODS: 170 patients have undergone LNF in our hospital since 1995. during the period of 1995-1998, 33 patients were treated. all patients were asked to return a structured follow-up questionnaire, using a Visick grading scale, after an average of 69 months (2003) and 117 months (2007). 29 questionnaires (90%) were answered in 2003, and 31 questionnaires (97%) were answered in 2007. one patient died at home before the first questionnaire in 2003, and is therefore not included. We present our results on LNF after an observation time of 117 months (range 99-144 months). RESULTS: patient satisfaction after LNF is rated as very good or good (Visick 1-2) in 93% in 2003 and 97% in 2007. 97% of the patients would recommend the same treatment to other patients with similar symptoms at ten year follow up. One patient has undergone resurgery during follow up. Daily gas bloat and flatulence is reported in 52% in 2003 and 39% in 2007, and is the most common reason for reduced satisfaction. Five patients report of reflux symptoms, one patient daily and four patients sometimes, where the first patient still uses proton pump inhibitor (PPI) daily and three patients use PPI occasionally. CONCLUSIONS: patient satisfaction after LNF treatment for gerd is high at long-term (10 years) follow-up. Bloating and flatulence persistently occurred to a great extent and the need for preoperative information regarding these symptoms is important.

In vivo characterization of ischemic small intestine using bioimpedance measurements.

The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

Doxepin and cimetidine in the treatment of duodenal ulcer: an open clinical and endoscopic study.

In an open clinical endoscopic study, 50 patients with duodenal ulcer showed no significant difference in ulcer healing during a 6-week treatment period with doxepin HCl (50 mg h.s.) versus cimetidine (1000 mg/day in divided doses). Possible tricyclic mechanisms of action in the treatment of peptic ulcer, e.g., histamine H2 blockade, are discussed.

Effects of protease inhibitor pretreatment on hemodynamic performances and survival rate in experimental, acute pancreatitis.

Acute pancreatitis was induced in pigs by manual retrograde injection of Na-Taurocholate into the pancreatic duct. Using chromogenic peptide substrate assays, increased plasma kallikrein activity (KK), paralleled by a reduction in functional plasma kallikrein inhibition values (KKI) were found in the peritoneal exudate in untreated animals. Several of the untreated animals experienced an increased trypsin activity (TRY) in the same exudate. Five out of eight animals died during a 6 hour observation period. Pretreatment with either Cl-INH or aprotinin given intravenously, resulted in a significantly increase in KKI capacity paralleled by unchanged KK and TRY activities in the peritoneal exudate. Furthermore, inhibitor pretreatment significantly improved hemodynamic performances (AP and CO) and the survival rate. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute, severe pancreatitis.

Studies on the kallikrein-kinin system in plasma and peritoneal fluid during experimental pancreatitis.

Using chromogenic peptide substrate assay technique, components of the plasma kallikrein-kinin system and trypsin activity were studied in plasma and peritoneal exudate during acute pancreatitis in pigs. In the plasma no significant changes occurred, but increased kallikrein activity was found in the peritoneal exudate. This finding was paralleled by a reduction in prekallikrein levels and functional kallikrein inhibition values. The trypsin activity in peritoneal exudate, however, increased inconstantly. These results emphasize the significance of peritoneal protease-antiprotease imbalance during acute pancreatitis.

Evaluation of patients with acute pancreatitis by means of chromogenic peptide substrate assays and the proenzyme functional inhibition index.

Using chromogenic peptide substrate assays the severity and clinical course were evaluated in 37 patients with acute pancreatitis. Retrospective clinical evaluation revealed that 20 patients had a severe disease, whereas 17 patients had mild acute pancreatitis. Seven of the patients with severe acute pancreatitis died. The proenzyme functional inhibition index (PFI index) is defined as the sum of deviations from the normal plasma pool values of plasma prekallikrein, functional kallikrein inhibition, plasminogen, antiplasmin, prothrombin and antithrombin III. Increased values are counted as positive, whereas reductions compared with the normal plasma pool values are recognized as negative. During the second day after admission the PFI index revealed significantly more negative values in severe cases than in patients with mild acute pancreatitis, -159 in severe case, -74 in mild cases (median values, P less than 0.05). The PFI index values were maintained strongly negative for the following 3 days in severe cases whereas the index was brought to positive values during the same period in patients with mild acute pancreatitis. The fatal cases revealed strongly negative PFI index values for the whole observation period. The patients with severe acute pancreatitis were earlier identified by means of the PFI index than by individual parameters also used for calculating the index. The results show that by means of the PFI index severity of acute pancreatitis can be recognized during early stages of the disease.

Effects on peritoneal proteolysis and hemodynamics by high doses of methyl-prednisolone in experimental acute pancreatitis.

Acute pancreatitis was induced in 15 anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. Seven animals were pretreated with methyl-prednisolone sodium succinate 30 mg/kg intravenously. Using chromogenic peptide substrate assays, values of trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and arterial pressure (AP) were regularly monitored before and during a six hour observation period. In acute untreated pancreatitis a 40% reduction of PKK levels was found paralleled by an increased KK activity and a reduction of KKI capacity. High TRY levels were found in several animals. The mortality rate was 63%. The pretreated animals all survived. CO and AP were significantly less reduced than in the untreated animals. Components of the plasma kallikrein-kinin system and TRY in the exudate remained mainly unchanged. Methyl-prednisolone given as pretreatment significantly improves hemodynamic parameters and increases the survival rate. Methyl-prednisolone suppresses generation of trypsin activity and activation of the plasma kallikrein-kinin system in the peritoneal exudate which may be of significant importance to the outcome.

Bacterial shock due to transfusion with Yersinia enterocolitica infected blood.

A fatal case (a 55-yr-old man) of bacterial shock and sepsis following a transfusion with erythrocytes infected with Yersinia enterocolitica serotype 03, is reported. The blood donor had slight diarrhea 6 days before the blood donation. A serum sample from the donor showed high titre of both IgG and IgM antibodies against Y. enterocolitica 03, indicating a recent infection. Y. enterocolitica 03 was isolated from blood cultures from the patient. The remaining portion of the transfused erythrocyte concentrate also yielded abundant growth of the same organism on direct plating of the material on blood agar indicating that profuse multiplication of the organism had occurred within the transfusion bag during storage at 4 degrees C.

Sodium taurocholate-induced acute pancreatitis in pigs. Pathomorphological studies of the pancreas in untreated animals and animals pretreated with high doses of corticosteroids or protease inhibitors.

Acute pancreatitis was induced in anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. The pigs were allocated to 4 groups. One group remained untreated while the other groups received either C1-inhibitor, aprotinin or methyl-prednisolone intravenously as pretreatment. Extensive necroses of the pancreatic parenchyma, peripancreatic oedema and accumulation of large amounts of fluid in the abdominal cavity developed within a few hours in all experimental groups. Pretreatment significantly improved hemodynamics and increased the survival rate at 6 hours. It is concluded that the most essential effect of the pretreatments were reduction of proteolytic activities which are secondary to the pancreatic lesions.

Effects on peritoneal proteolysis and hemodynamics of prophylactic and therapeutic infusions of high doses of aprotinin in experimental acute pancreatitis.

Acute pancreatitis was induced in pigs by retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activity (KK), parallel with a reduction of plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) values, in the peritoneal exudate in untreated animals. Intravenous high-dose pretreatment or therapy with aprotinin starting 3 h after the induction of acute pancreatitis resulted in significantly increased KKI capacity and unchanged KK and TRY activities in the peritoneal exudate. In test animals receiving aprotinin intravenously a significantly increased survival rate and improved cardiac output and arterial blood pressure were found during the 6-h observation period. All animals treated with aprotinin survived the observation period, whereas 63% of the untreated animals died. The study emphasizes the pathophysiological importance of the plasma kallikrein-kinin system in acute pancreatitis.

Effects on peritoneal proteolysis and hemodynamics of prophylactic infusion with C1 inhibitor in experimental acute pancreatitis.

Acute pancreatitis was induced in pigs by manual retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activities (KK), parallel with a reduction of prekallikrein (PKK) levels and functional plasma kallikrein inhibition (KKI), in the peritoneal exudate in untreated animals. Pretreatment with C1 inhibitor (C1 INH) concentrate significantly increased the KKI capacity, parallel with unchanged KK and TRY activities in the peritoneal exudate. Furthermore, C1 INH pretreatment significantly improved the hemodynamic performance and the survival rate during a 6-h observation period. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute pancreatitis. C1 INH concentrates given intravenously prevent activation of this system locally in the peritoneal exudate during experimental acute pancreatitis.

Haemodynamic effects of intravenous injection of peritoneal exudate in experimental acute pancreatitis.

The haemodynamic effects of intravenous injection into the test animals themselves of peritoneal exudate obtained during experimental acute pancreatitis in pigs were studied. The exudate had a distinct but moderate vasodilating effect when injected into the test animal. This decrease in afterload and a slight compensatory increase in heart rate led to a small increase in cardiac output. The profound hypotensive effect of intravenous injection of peritoneal pancreatic exudate observed by others when injecting the exudate into healthy animals could not be reproduced. In an organism severely affected by pancreatitis, the added pharmacological insult of peritoneal exudate intravenously seems to be of little haemodynamic consequence. Some of the effects previously reported may be caused by trypsin added to the fluid injected intraductally to produce the ailment.

Peritoneal lavage efficiently eliminates protease-alpha-2-macroglobulin complexes and components of the contact system from the peritoneal cavity in patients with severe acute pancreatitis.

Trypsin (Try), plasma kallikrein (KK) and plasmin activities together with coagulation factor XII (F XII, Hageman factor), high-molecular-weight kininogen (HMWK), plasma prekallikrein (PKK), alpha 2-macroglobulin (alpha 2-M), C1 inhibitor (C1Inh), and functional plasma kallikrein inhibition (KKI) values were studied in peritoneal fluid and lavage taps of 9 patients with severe acute pancreatitis treated with peritoneal lavage. Both immunochemical methods and functional techniques based on chromogenic peptide substrate assays were used. In the exudate obtained before peritoneal lavage was performed, F XII was 52%, HMWK was 30%, PKK was 40%, alpha 2-M was 29% and C1Inh was 57% of standard plasma pool values, determined by immunochemical technique. Functional plasma KKI values were zero, whereas Try activities determined by chromogenic peptide substrate technique were markedly elevated in the exudate. Using a prepacked HR 10/30 Superose Tm 12 column (Pharmacia, Uppsala, Sweden) and chromogenic peptide substrate assays, Try and KK activities were detected in the alpha 2-M containing fractions of the peritoneal exudate demonstrating KK-alpha 2-M and Try-alpha 2-M complex formation. The peritoneal lavage procedure efficiently eliminated components of the contact system and protease activities. In the first lavage tap, Try activities were markedly reduced compared to values found in the exudate and concentrations of F XII, HMWK, PKK, alpha 2-M and C1Inh were all zero. In consecutive lavage taps Try values were also zero. The study shows that the lavage procedures efficiently clears the peritoneal cavity for protease-alpha 2-M complexes generated during acute pancreatitis. Also, components of the contact system found in peritoneal exudate, and which might serve as substrates for the protease-alpha 2-M complexes, are rapidly eliminated by the procedure.

Studies on pathological plasma proteolysis in patients with acute pancreatitis. A preliminary report.

Changes in the plasma proteolytic enzyme systems were studied in 14 patients with acute pancreatitis. Ten patients survived whereas four died. In both survivors and fatal cases a high frequency of reduced values of plasma prekallikrein (PKK) functional antithrombin III (AT III) and platelets were found during the first week after admission. These changes were seen together with increased serum FDP values and the presence of soluble fibrin. In the fatal cases PKK, AT III, platelets and functional kallikrein inhibition values observed during the first week after admission, were found significantly more reduced than in the survivors. These observations underline that activation of proteases in plasma is an important pathophysiological mechanism in this state, and that evaluation of this process in patients with acute pancreatitis might give information of prognostic value.

[Abdominal metastases from signet cell carcinoma of the appendix vermiformis]. / Metastaser i bukhulen fra signetcellekarsinom i appendix vermiformis.

Signet cell carcinomas are often aggressive tumours. A patient with this tumour, originally located in the appendix, was diagnosed with peritoneal metastases. When she later got abdominal symptoms, computer axial tomography indicated large infiltrating tumour masses in the pelvis. However, when a laparotomy was performed, the only macroscopic tumour masses was localised to the ovaries (Krukenberg tumour). The surgical intervention gave the patient an improved quality of life, and most likely prolonged survival. We stress the importance of thinking of this possibility.

Studies on components of the plasma kallikrein-kinin system in peritoneal fluid and plasma before and during experimental acute pancreatitis in pigs. A preliminary report.

Acute pancreatitis was induced in pigs by retrograde injection of Na-Taurocholate into the pancreatic duct. Using a chromogenic peptide substrate assay, increased plasma kallikrein activity was found in the peritoneal exudate. This finding was paralleled by reduced prekallikrein and functional kallikrein inhibition values. In plasma, however, no changes in the kallikrein-kinin system were found during the 6 hours observation time. These findings emphasize the significance of peritoneal protease-antiprotease imbalance during acute pancreatitis.

Modulation of the proteolytic cascade systems by high dose corticosteroids.

The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.

Studies on the plasma kallikrein-kinin system in peritoneal exudate and plasma during experimental acute pancreatitis in pigs.

Acute pancreatitis was induced in pigs by retrograde injection of Na-taurocholate into the pancreatic duct. By means of chromogenic peptide substrate assays, increased plasma kallikrein activity, parallel with a reduction of plasma prekallikrein and functional kallikrein inhibition values, was found in peritoneal exudate. In plasma, however, no changes in the kallikrein-kinin system were found during the 6-h observation time. The study demonstrates the presence of components of the plasma kallikrein-kinin system in peritoneal fluid and suggests that the peritoneal cavity to a great extent is a functionally separate compartment from plasma. Activation of the plasma kallikrein-kinin system in peritoneal exudate during acute experimental pancreatitis appears to be of importance for the initial symptoms and the development of shock seen during this condition.

Plasma kallikrein generation in endotoxemia is abolished by ultra high doses of methyl-prednisolone: in vivo studies in a pig model.

Thirty-one healthy young pigs were studied to evaluate the effects of methylprednisolone sodium succinate (MP) on cellular, proteolytic, and hemodynamic parameters in normal and endotoxin-exposed animals. Fourteen animals served as controls, whereas 17 test animals received a continuous infusion of endotoxin, 0.01 mg/kg/3hr. Seven of the test animals and seven of the control group received a total of 200 mg/kg body weight over 5 hr of MP, 100 mg/kg as pretreatment before the endotoxin infusion was started. The administration of MP to control animals did not cause changes in the plasma kallikrein-kinin system, as determined with chromogenic peptide substrate assays. Only temporary effects, which normalized during the observation period, were seen in hemodynamic parameters. The pretreatment with MP significantly counteracted the increases in plasma kallikrein activity (KK) and the decreases in functional kallikrein inhibition capacity (KKI) seen after endotoxin infusion in untreated animals. Marked reductions in the number of circulating leukocytes and platelets were observed in untreated endotoxemia, together with increases in hematocrit. Furthermore, increases in pulmonary vascular resistance (PVR) and decreases in cardiac output (CO), left ventricular stroke work (LVSW), and mixed venous oxygen saturation (SvO2) ensued. The changes in circulating cells, PVR, and SvO2 were significantly counteracted by MP treatment, whereas changes in hematocrit, CO, and LVSW were only moderately improved.