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    Magnus Bergenfeldt

    Surgery remains the only hope for cure in pancreatic cancer. The most common procedures are reviewed. Postoperative morbidity and mortality below 30% and 5%, respectively, are the standard. The benefit of extended lymph node dissection... more
    Surgery remains the only hope for cure in pancreatic cancer. The most common procedures are reviewed. Postoperative morbidity and mortality below 30% and 5%, respectively, are the standard. The benefit of extended lymph node dissection and portal-mesenteric vein resection is dubious. Selected patients with locally advanced cancer may be down-staged with chemo-radiotherapy and eventually resected. Endoscopic stent placement is the preferred method to relieve biliary and/or gastrointestinal obstruction. The outcome is better for patients treated at high-volume centres than at smaller hospitals.
    A 70 year-old female presented with a 40 x 40 cm unresectable liposarcoma which showed progression during chemotherapy. After renewed evaluation, a radical resection was done. The second case concerns a 64 year-old male with a 19 x 15 cm... more
    A 70 year-old female presented with a 40 x 40 cm unresectable liposarcoma which showed progression during chemotherapy. After renewed evaluation, a radical resection was done. The second case concerns a 64 year-old male with a 19 x 15 cm liposarcoma in the upper abdomen. A radical tumour resection together with the pancreatic tail, the spleen and the transverse mesocolon/colon was carried out. Both patients recovered without complications, and remain disease-free at two years. Retroperitoneal sarcomas are notoriously "silent", and may grow to considerable size before diagnosis. The evaluation is difficult, and radical resection frequently demands multiorgan surgery. Management at a national "Sarcoma Unit" is essential for the prognosis.
    Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin,... more
    Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin, irinitecan, bevacizumab and cetuximab may result in a median survival > 20 months. Selected patients may be down-staged and resected with good long-time survival. Bilateral, multiple and large metastases can also be treated by complex combinations of portal vein embolization/ligature, staged resections and local (radiofrequency) ablation.
    This paper reports a retrospective study of 51 consecutive pancreatico-duodenectomies from a Swedish university hospital concerning postoperative morbidity, number of reoperations and mortality. Resection of the distal common bile duct,... more
    This paper reports a retrospective study of 51 consecutive pancreatico-duodenectomies from a Swedish university hospital concerning postoperative morbidity, number of reoperations and mortality. Resection of the distal common bile duct, duodenum, and head of the pancreas with hemigastrectomy and cholecystectomy was done in 48 patients and modified pancreaticoduodenectomy with preservation of the pylorus was done in three patients. Three patients (6%) died within 30 days. Nine patients required reoperation, three more than once. The most common major complications were anastomotic breakdown (n = 7), severe hemorrhage (n = 3) and abscess formation (n = 3). We conclude that a low postoperative morbidity and mortality can be achieved outside large, specialist centres, but the operation should be done by experienced surgeons. The results may justify carrying out the operation when the chances of cure are small, but it has yet to be evaluated as a palliative procedure.
    The contents of three lysosomal enzymes (beta-hexosaminidase, beta-glucuronidase and alpha-fucosidase) were studied in plasma and different tissues of pregnant and steroid treated rats. All these enzymes were found to be increased in... more
    The contents of three lysosomal enzymes (beta-hexosaminidase, beta-glucuronidase and alpha-fucosidase) were studied in plasma and different tissues of pregnant and steroid treated rats. All these enzymes were found to be increased in plasma from pregnant rats in analogy with the findings in pregnant women. In liver tissue only beta-hexosaminidase and alpha-fucosidase were significantly increased. In rats with diethylstilbestrol (DES) and a combination of DES and progesterone, there was an increase of alpha-fucosidase in plasma and liver. No significant changes were observed for the other two enzymes. Thus, steroid treatment did not fully reproduce the enzyme changes seen in pregnancy, which may indicate that these are not solely due to a hormone effect.
    After an intravenous injection of 35Sulphur-labelled secretory leukocyte protease inhibitor (SLPI) in four dogs, there was a rapid initial clearance (half-life 10 min) of radioactivity and immunoreactive SLPI from plasma. Later, the... more
    After an intravenous injection of 35Sulphur-labelled secretory leukocyte protease inhibitor (SLPI) in four dogs, there was a rapid initial clearance (half-life 10 min) of radioactivity and immunoreactive SLPI from plasma. Later, the immunoreactive SLPI cleared more rapidly (T1/2 = 60 min) than the radioactivity, indicating the gradual appearance of radioactive degradation products. Intact recombinant human SLPI as well as radioactive fragments appeared in the urine. The urinary excretion of radioactivity during the first 3 h was less than 10% of the injected dose. After killing at 3 h, the kidneys contained more radioactivity per gram tissue than the other parenchymatous organs. Following an intravenous injection of 125Iodine-labelled native SLPI in three human volunteers, a rapid initial clearance of both protein-bound and total plasma radioactivity (half-life 10 min) was seen. Later, the protein-bound radioactivity cleared slower (half-life 120 min) than the total radioactivity, indicating a progressive degradation of SLPI with release of radioactive fragments to plasma. After 54 h 80-96% of the radioactivity had been excreted in the urine, mainly as free 125Iodine. No intact SLPI was found in the urine. A renal metabolism of SLPI is assumed, which is supported also by the finding of elevated serum levels of SLPI in uraemic patients. The possible therapeutic use of SLPI is briefly discussed.
    Leukocyte activation is a property of systemic infection. Animal experiments indicate interleukin-1 (IL-1) as a possible modulator, while contradictory results have been reported from in-vitro stimulation of isolated leukocytes. The... more
    Leukocyte activation is a property of systemic infection. Animal experiments indicate interleukin-1 (IL-1) as a possible modulator, while contradictory results have been reported from in-vitro stimulation of isolated leukocytes. The purpose of the present study was to investigate the activation of isolated polymorphonuclear (PMN) leukocytes in vitro by preparations of recombinant human IL-1 beta and IL-1 receptor antagonist, which in earlier studies could elicit and abrogate, respectively, a sepsis-like syndrome in rabbits. They have also been shown to influence acute phase protein synthesis in mice and rats, and release of leukocyte cathepsin G in vivo. It was found that recombinant human IL-1 beta elicited a dose-dependent luminol-enhanced chemiluminescence response in isolated human PMN leukocytes in the dose range 8.8 x 10(-11)-8.8 x 10(-8) M. The effect could be blocked by prior treatment with the IL-1 receptor antagonist, indicating a direct effect on the specific IL-1 receptor. Preincubation by IL-1 beta enhanced the effect of a secondary challenge with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe by 30-40%. The priming effect of rhIL-1 beta could also be blocked by the specific receptor antagonist. In this study, incubation of PMN leukocytes with rhIL-1 beta failed to induce degranulation of both azurophil (neutrophil proteinase 4/proteinase 3) and specific (lactoferrin) granules. rhIL-1 beta has been shown to induce degranulation in vivo, which is thus indicated as an indirect effect. We conclude that IL-1 beta is a direct and specific, but probably weak stimulator of the PMN leukocyte.(ABSTRACT TRUNCATED AT 250 WORDS)
    Background/aims: Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections,... more
    Background/aims: Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections, factors influencing LOS within a fast-track program have been studied only to a limited extent, which was the aim of the present study. Methodology: The present study comprises the first 64 patients included in a fast-track program for liver resections introduced in March 2012. Patient outcomes were compared to a historical cohort of patients (n=62) operated in 2009. Factors prolonging LOS was analyzed by uni- and multivariate analysis. Results: Median LOS was 6 days (range 3-42 days) within the fast-track program as compared with 8 days (range 5-47 days) in the historical cohort (P=0.004). On multivariate analysis, factors increasing LOS in the fast-track group were found to be the presence of complication (P=0.018), extent of resection (major as compared to minor) (P=0.001) and inability to drink > 1250 ml on the day after surgery (P=0.002). Conclusion: Patients who can only drink limited amounts of fluid the day after liver resection represent a subset of patients that should be given special attention within a fast-track program.
    Whole-blood chemiluminescence and levels of leukocyte proteases and plasma protease inhibitors were studied in 43 patients with acute, generalized peritonitis. An almost three-fold increase in whole-blood chemiluminescence was found in... more
    Whole-blood chemiluminescence and levels of leukocyte proteases and plasma protease inhibitors were studied in 43 patients with acute, generalized peritonitis. An almost three-fold increase in whole-blood chemiluminescence was found in acute peritonitis, which may indicate activation or "priming" of the leukocytes by blood-borne factors. High levels of leukocyte elastase and neutrophil proteinase 4(3) were found in plasma and peritoneal exudate. Patients with sepsis had higher plasma levels of both proteases than other patients. Large variations in the plasma levels among patients decreased their sensitivity as markers of infectious complications during the postoperative period. The plasma levels of the protease inhibitors followed three different patterns of reaction. The acute phase proteins alpha 1-proteinase inhibitor and C1-inactivator, increased during the first week of disease, to normalise later in its course. alpha 2-macroglobulin, antithrombin III and alpha 2-antiplasmin were all decreased from onset and normalised later in the course, while secretory leukocyte protease inhibitor showed a slow decrease throughout the course of disease. In peritonitis exudate, the levels of the main protease inhibitors, alpha 1-Proteinase Inhibitor and alpha 2-Macroglobulin, were decreased, probably due to complexation and subsequent elimination, as a part of the defense against liberated leukocyte proteases. The immunoreactive and especially functional levels of the protease inhibitors alpha 2-Antiplasmin, Antithrombin III and C1-Inactivator were also decreased in the exudate, indicating an increased turn-over of these proteins through activation of the cascade systems and/or break-down by leukocyte proteases. In contrast to the other inhibitors, secretory leukocyte protease inhibitor showed higher levels in exudate than in plasma, and unexpectedly high exudate/plasma-quotients were seen in cases with colonic perforations. Degradation of complement factor 3 (C3) and decreased "opsonic capacity" were found in exudate. The "opsonic capacity" could be correlated to the levels of leukocyte proteases in the exudate, which indicates that degradation of complement factor 3 may have been at least partly due to the action of leukocyte proteases. Further depletion of complement factors in exudates of long-standing peritonitis or abscesses may create a vicious circle of deficient opsonisation and clearance of bacteria, as earlier reported for chronic pleural exudates.
    Plasma clearance of purified human serum beta-hexosaminidase isoenzymes was studied in the rat. The serum beta-hexosaminidase isoenzymes (A, B and P) showed a slow clearance from circulation compared to their tissue counterparts. After... more
    Plasma clearance of purified human serum beta-hexosaminidase isoenzymes was studied in the rat. The serum beta-hexosaminidase isoenzymes (A, B and P) showed a slow clearance from circulation compared to their tissue counterparts. After desialylation, the clearance rate of all serum isoenzymes was markedly enhanced. The uptake of native as well as desialylated serum beta-hexosaminidase isoenzymes was studied in rat liver nonparenchymal cells and hepatocytes. No detectable uptake of any native serum isoenzyme was noticed in either cell type. However, when these isoenzymes were desialylated by neuraminidase treatment, isoenzymes A and B were taken up by the nonparenchymal cells. No uptake was observed for the P form. None of the desialylated serum forms was taken up by hepatocytes.
    Cleavage of C3, fibronectin, antithrombin III and alpha 2-antiplasmin in human plasma following the addition of increasing amounts of human leucocyte elastase was studied using an in vitro model. The cleavage was correlated with the... more
    Cleavage of C3, fibronectin, antithrombin III and alpha 2-antiplasmin in human plasma following the addition of increasing amounts of human leucocyte elastase was studied using an in vitro model. The cleavage was correlated with the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-protease inhibitor and also with varying amounts of secretory leucocyte protease inhibitor. When alpha 1-protease inhibitor approached saturation, there was a prompt cleavage of all the four plasma proteins studied. The secretory leucocyte protease inhibitor was needed in a concentration of 6 mumol/l in the present model to block this consumption completely. This concentration also gave some protection of alpha 1-protease inhibitor and alpha 2-macroglobulin.
    Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade... more
    Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis. alpha 1-proteinase inhibitor (alpha 1-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but alpha 1-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in the medium. Addition of increasing amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation mixtures resulted in binding of leukocyte elastase to this inhibitor and extinction of free proteolytic activity against both natural and synthetic substrates. The progressive binding of leukocyte elastase to SLPI instead of alpha 1-PI was paralleled by an increasing binding of NP4(3) to alpha 1-PI. SLPI is a potent inhibitor of leukocyte elastase and cathepsin G, and although it lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding and inhibition of NP4(3) to alpha 1-PI, by taking care of at least part of the leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for therapeutic use, this effect may prove useful under in vivo conditions and enhance the protective effect of administered recombinant human SLPI.
    e14593 Background: Whether therapy of Ur-LLM from CRC by HAI is superior to SYS is unknown. Methods: First line phase II study of pts. with Ur-LLM from CRC. Included were 88 pts. HAI oxaliplatin (100 mg/m2) was given to 66 pts. every 2nd... more
    e14593 Background: Whether therapy of Ur-LLM from CRC by HAI is superior to SYS is unknown. Methods: First line phase II study of pts. with Ur-LLM from CRC. Included were 88 pts. HAI oxaliplatin (100 mg/m2) was given to 66 pts. every 2nd week (wk) for a median of 11 series (1-12) and capecitabine 3500 mg/m2 day 1-7 every 2nd wk for a median of 12 (2-14) series. Vessel variation made HAI unsuitable for 22 pts. They had systemic oxaliplatin (130 mg/m2) for a median of 8 (1-10) series with capecitabine 2000 mg/m2 day 1-14 every 3rd wk for a median of 8 series (1-45) with bevacizumab 7½ mg/kg day 1 in 14 pts. Primary endpoints were response, secondary median overall and therapy free survival (mOS) and toxicity. KRAS mutation status was determined in all pts. with the DxS kit. Survival was evaluated by the Kaplan Meier method and differences with the log rank test. 95% confidence interval are given in brackets. Results: Pts. treated with HAI and SYS were comparable. HAI yielded higher response rates than SYS (table 1). Pts. with KRAS-WT tumors treated with HAI had a mOS of 61 (43-80) mths, with KRAS-MT tumors 28 (21-35) mths (p< 0.0001). SYS in KRAS-WT and MT types yielded equal mOS 36 (27-45) mths and 27 (12-44) mths. Pts. with KRAS-WT tumors treated with HAI lived longer than when treated with SYS (p=0.05). Pts. with HAI with KRAS-WT tumors lived without any kind of therapy for a median of 27 (16-37) mths with 42% living more than 40 mths. with KRAS-MT tumors 8 (3-13) mths (p<0.0001) with 12% living more than 40 mths. Therapy free mOS with SYS in patients with KRAS-WT and KRAS-MT tumors was19 (0-39) mths.for pts. and 12 (4-20) mths respectively with 17% and 22% living more than 2 years.The findings were independent of cetuximab-based therapy in later lines. The toxicity was comparable. Conclusions: Effect of HAI oxaliplatin combined with capecitabine on response and survival is restricted to pts. with KRAS-WT tumors. [Table: see text]
    A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated... more
    A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated canine leukocyte elastase to other elastases indicated moderate homology with porcine pancreatic elastase and pronounced identity with human leukocyte elastase. Normal canine plasma contains about 66 micrograms/l leukocyte elastase measured as elastase alpha 1-proteinases inhibitor complexes. This represents about 70% of the total amount of leukocyte elastase released in plasma. The remaining 30% is bound by alpha 1 alpha 2-macroglobulin. Blood coagulation leads to a rapid release of elastase from the leukocytes. Slow intravenous infusion of a lethal dose of endotoxin into dogs is followed by a marked drop in leukocyte count and a simultaneous rapid increase in plasma leukocyte elastase concentration reaching a plateau level of 2-3 mg/l plasma. Bile-induced pancreatitis in dogs is accompanied by successive increases in leukocyte elastase levels in plasma as well as in peritoneal exudates, reaching a level of about 15 mg/l in the exudates during the late stages of disease.
    Resection of colorectal liver metastases will increase due to increased life expectancy and widened indications. Complex combinations of chemotherapy, surgery, and local ablation are used in advanced disease. Advances in laparoscopic and... more
    Resection of colorectal liver metastases will increase due to increased life expectancy and widened indications. Complex combinations of chemotherapy, surgery, and local ablation are used in advanced disease. Advances in laparoscopic and telerobotic liver resection are expected. Hepatocellular carcinoma is rare, results are poor, and better treatment is needed. The complex management of liver neoplasms requires a centralized effort. Further advances in xenotransplantation, artificial liver, and stem cell technology may influence liver transplantation as well as cancer surgery.
    A 70 year-old female presented with a 40 x 40 cm unresectable liposarcoma which showed progression during chemotherapy. After renewed evaluation, a radical resection was done. The second case concerns a 64 year-old male with a 19 x 15 cm... more
    A 70 year-old female presented with a 40 x 40 cm unresectable liposarcoma which showed progression during chemotherapy. After renewed evaluation, a radical resection was done. The second case concerns a 64 year-old male with a 19 x 15 cm liposarcoma in the upper abdomen. A radical tumour resection together with the pancreatic tail, the spleen and the transverse mesocolon/colon was carried out. Both patients recovered without complications, and remain disease-free at two years. Retroperitoneal sarcomas are notoriously "silent", and may grow to considerable size before diagnosis. The evaluation is difficult, and radical resection frequently demands multiorgan surgery. Management at a national "Sarcoma Unit" is essential for the prognosis.
    Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections, factors influencing... more
    Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections, factors influencing LOS within a fast-track program have been studied only to a limited extent, which was the aim of the present study. The present study comprises the first 64 patients included in a fast-track program for liver resections introduced in March 2012. Patient outcomes were compared to a historical cohort of patients (n=62) operated in 2009. Factors prolonging LOS was analyzed by uni- and multivariate analysis. Median LOS was 6 days (range 3-42 days) within the fast-track program as compared with 8 days (range 5-47 days) in the historical cohort (P=0.004). On multivariate analysis, factors increasing LOS in the fast-track group were found to be the presence of complication (P=0.018), extent of resection (major as compared to minor) (P=0.001) and inability ...
    A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated... more
    A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated canine leukocyte elastase to other elastases indicated moderate homology with porcine pancreatic elastase and pronounced identity with human leukocyte elastase. Normal canine plasma contains about 66 micrograms/l leukocyte elastase measured as elastase alpha 1-proteinases inhibitor complexes. This represents about 70% of the total amount of leukocyte elastase released in plasma. The remaining 30% is bound by alpha 1 alpha 2-macroglobulin. Blood coagulation leads to a rapid release of elastase from the leukocytes. Slow intravenous infusion of a lethal dose of endotoxin into dogs is followed by a marked drop in leukocyte count and a simultaneous rapid increase in plasma leukocyte elastase concentration reaching a plateau level of 2-3 mg/l plasma. Bile-induced pancreatitis in dogs is accompanied by successive increases in leukocyte elastase levels in plasma as well as in peritoneal exudates, reaching a level of about 15 mg/l in the exudates during the late stages of disease.
    Background. Surgical technique in pancreatic cancer has seen significant developments, but much of the knowledge refers to pancreatic head carcinoma. Reports on the management of tumours of the body and tail have been less frequent.... more
    Background. Surgical technique in pancreatic cancer has seen significant developments, but much of the knowledge refers to pancreatic head carcinoma. Reports on the management of tumours of the body and tail have been less frequent. Current knowledge teaches that adenocarcinomas of the body and tail of the pancreas have a worse prognosis. The aim of this study is to report the short- and long-term outcome in 20 patients with left-sided pancreatic malignancy, where ‘resection for cure’ was done. Patients and methods. Retrospective study of demographic data, symptomatology, diagnostic methods, operative management, pathology report, postoperative morbidity and mortality. Results. Postoperative complications were seen in 40% of patients. One patient died on day 5 from sepsis with multiple organ failure. Other complications were intra-abdominal bleeding, bleeding from the gastroentero-anastomosis, postoperative jaundice, pleural exudate, wound dehiscence and intra-abdominal abscess. The...
    This paper reports a retrospective study of 51 consecutive pancreatico-duodenectomies from a Swedish university hospital concerning postoperative morbidity, number of reoperations and mortality. Resection of the distal common bile duct,... more
    This paper reports a retrospective study of 51 consecutive pancreatico-duodenectomies from a Swedish university hospital concerning postoperative morbidity, number of reoperations and mortality. Resection of the distal common bile duct, duodenum, and head of the pancreas with hemigastrectomy and cholecystectomy was done in 48 patients and modified pancreaticoduodenectomy with preservation of the pylorus was done in three patients. Three patients (6%) died within 30 days. Nine patients required reoperation, three more than once. The most common major complications were anastomotic breakdown (n = 7), severe hemorrhage (n = 3) and abscess formation (n = 3). We conclude that a low postoperative morbidity and mortality can be achieved outside large, specialist centres, but the operation should be done by experienced surgeons. The results may justify carrying out the operation when the chances of cure are small, but it has yet to be evaluated as a palliative procedure.
    Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin,... more
    Isolated colorectal liver metastases should be referred for multispecialist management at a liver centre. Long-time survival is possible after resection and adjuvant therapy. If unresectable, newer chemotherapy with oxaliplatin, irinitecan, bevacizumab and cetuximab may result in a median survival > 20 months. Selected patients may be down-staged and resected with good long-time survival. Bilateral, multiple and large metastases can also be treated by complex combinations of portal vein embolization/ligature, staged resections and local (radiofrequency) ablation.
    A 61-year-old woman presented with a 16 cm retroperitoneal sarcoma, which demanded a multispecialist effort. There was adherence to the left ureter, the iliac vessels, the mesosigmoideum and the small intestine. After angiographic... more
    A 61-year-old woman presented with a 16 cm retroperitoneal sarcoma, which demanded a multispecialist effort. There was adherence to the left ureter, the iliac vessels, the mesosigmoideum and the small intestine. After angiographic embolization, the tumor, sigmoid colon and left ureter were excised. Histology, immunohistology and electron microscopy gave the diagnosis pleomorphic sarcoma. The microscopic radicality was doubtful, but we abstained from adjuvant radiotherapy due to the large field and risk of toxicity. The patient remains disease-free after 24 months.
    Levels of leukocyte elastase and neutrophil protease 4 (NP4(3)) in plasma and peritoneal exudate were studied in 25 patients with severe, acute pancreatitis. Pancreatitis was diagnosed from the clinical picture and an increased serum... more
    Levels of leukocyte elastase and neutrophil protease 4 (NP4(3)) in plasma and peritoneal exudate were studied in 25 patients with severe, acute pancreatitis. Pancreatitis was diagnosed from the clinical picture and an increased serum amylase level. The diagnosis was verified by computerized tomography, ultrasound, and findings at operation or autopsy. Peritoneal exudate on admission contained high concentrations of leukocyte elastase (6100 +/- 2000 micrograms/l) and NP4(3) (2310 +/- 900 micrograms/l). High initial levels were found also in plasma, which contained 659 +/- 110 micrograms/l of leukocyte elastase and 254 +/- 33 micrograms/l of NP4(3). The levels in plasma were still increased 3 weeks after the acute attack, also in the absence of complications, indicating that the resolution of acute pancreatitis is a protracted process. Plasma levels of both leukocyte proteases were persistently increased in patients with pancreatic abscess, in contrast to the gradual decrease seen in patients with a pseudocyst or uncomplicated recovery. The levels were increased already before the abscess was diagnosed clinically, which indicates that determinations of leukocyte elastase and NP4(3) may be helpful in detecting this complication. A pathophysiologic role for leukocyte proteases in the development of severe, acute pancreatitis should be considered.
    Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade... more
    Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis. alpha 1-proteinase inhibitor (alpha 1-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but alpha 1-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in the medium. Addition of increasing amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation mixtures resulted in binding of leukocyte elastase to this inhibitor and extinction of free proteolytic activity against both natural and synthetic substrates. The progressive binding of leukocyte elastase to SLPI instead of alpha 1-PI was paralleled by an increasing binding of NP4(3) to alpha 1-PI. SLPI is a potent inhibitor of leukocyte elastase and cathepsin G, and although it lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding and inhibition of NP4(3) to alpha 1-PI, by taking care of at least part of the leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for therapeutic use, this effect may prove useful under in vivo conditions and enhance the protective effect of administered recombinant human SLPI.
    Cleavage of C3, fibronectin, antithrombin III and alpha 2-antiplasmin in human plasma following the addition of increasing amounts of human leucocyte elastase was studied using an in vitro model. The cleavage was correlated with the... more
    Cleavage of C3, fibronectin, antithrombin III and alpha 2-antiplasmin in human plasma following the addition of increasing amounts of human leucocyte elastase was studied using an in vitro model. The cleavage was correlated with the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-protease inhibitor and also with varying amounts of secretory leucocyte protease inhibitor. When alpha 1-protease inhibitor approached saturation, there was a prompt cleavage of all the four plasma proteins studied. The secretory leucocyte protease inhibitor was needed in a concentration of 6 mumol/l in the present model to block this consumption completely. This concentration also gave some protection of alpha 1-protease inhibitor and alpha 2-macroglobulin.
    After an intravenous injection of 35Sulphur-labelled secretory leukocyte protease inhibitor (SLPI) in four dogs, there was a rapid initial clearance (half-life 10 min) of radioactivity and immunoreactive SLPI from plasma. Later, the... more
    After an intravenous injection of 35Sulphur-labelled secretory leukocyte protease inhibitor (SLPI) in four dogs, there was a rapid initial clearance (half-life 10 min) of radioactivity and immunoreactive SLPI from plasma. Later, the immunoreactive SLPI cleared more rapidly (T1/2 = 60 min) than the radioactivity, indicating the gradual appearance of radioactive degradation products. Intact recombinant human SLPI as well as radioactive fragments appeared in the urine. The urinary excretion of radioactivity during the first 3 h was less than 10% of the injected dose. After killing at 3 h, the kidneys contained more radioactivity per gram tissue than the other parenchymatous organs. Following an intravenous injection of 125Iodine-labelled native SLPI in three human volunteers, a rapid initial clearance of both protein-bound and total plasma radioactivity (half-life 10 min) was seen. Later, the protein-bound radioactivity cleared slower (half-life 120 min) than the total radioactivity, indicating a progressive degradation of SLPI with release of radioactive fragments to plasma. After 54 h 80-96% of the radioactivity had been excreted in the urine, mainly as free 125Iodine. No intact SLPI was found in the urine. A renal metabolism of SLPI is assumed, which is supported also by the finding of elevated serum levels of SLPI in uraemic patients. The possible therapeutic use of SLPI is briefly discussed.
    The contents of three lysosomal enzymes (beta-hexosaminidase, beta-glucuronidase and alpha-fucosidase) were studied in plasma and different tissues of pregnant and steroid treated rats. All these enzymes were found to be increased in... more
    The contents of three lysosomal enzymes (beta-hexosaminidase, beta-glucuronidase and alpha-fucosidase) were studied in plasma and different tissues of pregnant and steroid treated rats. All these enzymes were found to be increased in plasma from pregnant rats in analogy with the findings in pregnant women. In liver tissue only beta-hexosaminidase and alpha-fucosidase were significantly increased. In rats with diethylstilbestrol (DES) and a combination of DES and progesterone, there was an increase of alpha-fucosidase in plasma and liver. No significant changes were observed for the other two enzymes. Thus, steroid treatment did not fully reproduce the enzyme changes seen in pregnancy, which may indicate that these are not solely due to a hormone effect.
    Resection of colorectal liver metastases will increase due to increased life expectancy and widened indications. Complex combinations of chemotherapy, surgery, and local ablation are used in advanced disease. Advances in laparoscopic and... more
    Resection of colorectal liver metastases will increase due to increased life expectancy and widened indications. Complex combinations of chemotherapy, surgery, and local ablation are used in advanced disease. Advances in laparoscopic and telerobotic liver resection are expected. Hepatocellular carcinoma is rare, results are poor, and better treatment is needed. The complex management of liver neoplasms requires a centralized effort. Further advances in xenotransplantation, artificial liver, and stem cell technology may influence liver transplantation as well as cancer surgery.
    Background and objective: Pancreatic and periampullary cancers are sometimes found to have a too advanced disease during surgery to allow resection. The aim was to describe characteristics, treatment, outcome, and time trends for patients... more
    Background and objective: Pancreatic and periampullary cancers are sometimes found to have a too advanced disease during surgery to allow resection. The aim was to describe characteristics, treatment, outcome, and time trends for patients that were planned for pancreatic surgery but found unresectable during surgery. Methods: Data from the Swedish National Pancreatic and Periampullary Cancer Registry were used. All patients registered between January 2010 and August 2018 were included. The patient cohort was divided in two halves based on year of diagnosis. Results: In total, 12,377 patients were included in the registry and finally 4568 patients were scheduled for surgery. During surgical exploration, 3879 (84.9%) patients underwent pancreatic resection, 658 (14.4%) patients were found unresectable, and 31 (0.7%) had no pancreatic resection due to other reasons (e.g. benign lesion, comorbidity). More patients underwent surgical exploration and resection during the second time perio...

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