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J Axelson

Publications and source records attributed to J Axelson.

At least 19 recordsLinked to original sources
PubMed2006

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Aged↗
PubMed2004

Vitamins A and D but not E and K decreased the cell number in human pancreatic cancer cell lines.

BACKGROUND: The four fat-soluble vitamins A, D, E and K have been tested in experimental and human studies to assess their influence on the growth of cancer cells of different origins. Receptors for vitamin A and D have been detected on pancreatic cancer cells, and analogues of these reduced the cell number in vitro. The aim of the present study was to evaluate the effect of fat-soluble vitamins on the growth of pancreatic cancer cells. METHODS: The seven cell lines used were established from patients operated on for pancreatic adenocarcinoma. The effect of incubation with the vitamin A analogues all-trans-retinoic acid (atRA;tretinoin) and 9-cis-retinoic acid (9-cis-RA), the synthetic vitamin D analogue EB 1089, vitamin E succinate and K on the cell number was examined by the XTT method. RESULTS: The vitamin A and D analogues decreased the pancreatic cancer cell number when high concentrations of 10 - 10 M were administered. A combination of retinoids and the vitamin D analogue EB 1089 did not enhance the effect. Vitamin E succinate inhibited cell growth to a small extent (maximal 26%) in 3 out of 7 cell lines, whereas vitamin K increased the pancreatic cancer cell number in 3 out of 7 cell lines. CONCLUSION: High concentrations of vitamin A and D analogues decreased the cell number in pancreatic cancer cell lines. Vitamin E succinate and K did not have this effect. In the treatment of pancreatic cancer, further exploration of vitamin D analogues could be fruitful.

Adenocarcinoma↗
PubMed2001

Differential expression of gastrin, cholecystokinin-A and cholecystokinin-B receptor mRNA in human pancreatic cancer cell lines.

BACKGROUND: It has been assumed that gastrin stimulates the growth of pancreatic cancer in an autocrine way through co-expression of gastrin and the cholecystokinin-B receptor (CCK-BR). However, pancreatic cancer cell lines established directly from patients have revealed a great heterogeneity in cell proliferation when exposed to CCK, gastrin and their receptor antagonists. The aim of this study was therefore to examine co-expression of CCK-A and CCK-B receptor (CCK-AR and CCK-BR), and gastrin mRNA as well as the secretion of CCK and gastrin peptides in these cell lines. METHODS: Fourteen cell lines were established from primary pancreatic cancers or their metastases. Total RNA was isolated from the cell lines and reverse-transcribed into single-stranded cDNA. A PCR technique based on Taq polymerase-antibody interaction and CCK-AR, CCK-BR and gastrin-specific primers, followed by Southern blot analysis, were the methods used. The incubation mediums were analysed for the presence of secreted CCK/proCCK and gastrin/progastrin peptides by specific radioimmunoassays (RIA). RESULTS: By means of nested Reverse-Transcribed Polymerase Chain Reaction (nested RT-PCR), combined with Southem blot analysis of the PCR amplified products, CCK-AR and gastrin mRNA co-expression was detected in cell lines LPC-6p and LPC-10m, whereas CCK-BR and gastrin mRNA could be detected in cell lines LPC-8p and LPC-12m. A low level of secreted CCK peptides was detected in cell line LPC-6p, which also expressed CCK-AR mRNA. In no other cases were CCK or gastrin peptides detected in the cell culture mediums. CONCLUSION: The lack of CCK-BR and gastrin mRNA co-expression, and not detectable levels of secreted CCK and gastrin in culture media, does not lend support to the hypothesis that concomitant gene-expression of CCK receptors and gastrin or CCK are essential to maintaining pancreatic cancer cell proliferation.

Adenocarcinoma↗
PubMed2001

The method of administration of cholecystokinin determines the effects evoked in the pancreas.

Earlier studies have shown different effects on cell proliferation and weight characteristics by sulfated cholecystokinin-8 (CCK-8S) in the rat pancreas when the peptide has been administered continuously rather than intermittently. The aim of this study was as follows: (i) to compare the effect of continuous infusion and of intermittent injections of CCK-8S on cell proliferation, weight gain, and induction of apoptosis and (ii) to examine the effect of injections of CCK-8S on CCK-A receptor gene expression in the rat pancreas. Male Sprague-Dawley rats had subcutaneous continuous infusion of CCK-8S in a dose of 5 microg/kg/h or 1% bovine serum albumin (BSA) (vehicle) by implanted osmotic minipumps. The rats were killed after 4 days. Other rats were either injected subcutaneously only once or injected twice daily for 3 days with either 6 microg of CCK dissolved in 0.5 mL BSA or 0.5 mL BSA alone. The rats were killed 1, 3, 6, and 12 hours after the last injection. One hour before death they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally to localize and quantitate the cell proliferation. Plasma was collected for analysis of CCK. The pancreas was dissected and immunohistochemistry was performed for analysis of the expression of the apoptosis promoting protein bax and the apoptosis inhibiting protein bcl-2, and for BrdU and CCK-A receptor localization. In situ hybridization (ISH) was used for examination and semiquantification of CCK-A receptor mRNA expression. Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight without any effect on BrdU labeling. Immunohistochemistry revealed decreased tissue expression of bax but unaffected expression of bcl-2. Intermittent injections of CCK-8S led to hyper-CCK-emia with increased incorporation of BrdU, indicating increased cell proliferation but no increase in pancreatic weight. Immunohistochemistry showed increased expression of bax, whereas bcl-2 remained unchanged. Immunofluorescence and ISH for the CCK-A receptor and its gene expression, respectively, showed a lowest intensity at 3 hours after CCK-8S injections. The results indicate that decreased apoptosis could explain the increased pancreatic weight during continuous infusion of CCK-8S. An increased apoptosis could explain the lack of pancreatic weight gain upon intermittent injections of CCK-8S despite the stimulation of cell proliferation. Injections of CCK-8S only transiently decreased the tissue levels of its receptor.

Animals↗
PubMed2001

Altered expression of TGFB receptors and mitogenic effects of TGFB in pancreatic carcinomas.

Alteration of the transforming growth factor beta (TGFB) signalling pathway is important in pancreatic carcinogenesis, as shown by the frequent inactivation of the downstream target SMAD4. We recently analysed a series of pancreatic carcinoma cell lines with respect to alterations of five SMAD genes involved in TGFB signalling, and showed that SMAD4 was structurally rearranged in 42% of these. This pathway may, however, also be affected by alterations of genes whose products regulate the activation of TGFB as well as of TGFB receptor genes. We therefore studied the expression of UPA, UPAR, IGF2R, ALK5 (TGFBR1), TGFBR2, TGFBR3, ENG, ALK1, TGFB1, TGFB2, and TGFB3 in a series of 14 pancreatic carcinoma cell lines. We also analysed ALK5 and TGFBR2 for mutations, cell surface localisation of TGFBR2 and ENG, and TGFB1 response. No mutations of ALK5 or TGFBR2 were found. However, 4 cell lines were methylated within the ALK5 promoter region. ALK5 expression was strongly reduced in 9 cases, whereas TGFBR2 expression was increased in 12 of the cell lines. The TGFB signalling associated receptors ENG and ALK1 were co-expressed in 4 of the cell lines. There was no evidence for disruption of the UPAR-IGF2R TGFB activating pathway. The response to TGFB1 was analysed in 12 cell lines, and 6 of these (50%) showed increased proliferation. The cell lines stimulated by TGFB showed frequent mutations of SMAD4, KRAS2, and TP53, as well as frequent absence of CDKN2B expression. These results suggest that the ALK5-SMAD4 part of the TGFB signalling pathway is a major target for inactivation in pancreatic carcinomas, that the expression of TGFBR2, TGFBR3, and receptors involved in TGFB activation are maintained, and that alterations of components of the TGFB signalling pathway may be accompanied by a positive effect of TGFB on cell growth.

Activin Receptors, Type I↗
PubMed2000

Preoperative ropivacaine infiltration in breast surgery.

PURPOSE: The aim of the study was to investigate whether preoperative infiltration with ropivacaine in conjunction with breast surgery improves postoperative pain management and attenuates postoperative nausea and vomiting. METHOD: Prospective, randomised, double-blind study, including 60 healthy women (ASA 1-2) allocated to one of two groups. Thirty patients were given 0.3 ml/kg saline in the operating field before surgery. Another 30 patients received a similar volume of ropivacaine 3.75 mg/ml. A visual analogue scale (0-100 mm) was used for evaluation of postoperative pain, nausea and vomiting. If the score was more than 30 mm at rest, the patients were given ketobemidone i.v. as treatment for postoperative pain, and dixyrazine i.v. against nausea and vomiting. The intra-and postoperative analgesic requirements and postoperative nausea and vomiting were registered. RESULTS: The intraoperative fentanyl consumption was similar in the saline group 81 +/- 22 microg vs 76 +/- 28 microg; (ns) in the ropivacaine group. The postoperative 24-h ketobemidone consumption was also similar to those treated with ropivacaine (4.2 +/- 2.6 mg vs 4.2 +/- 4.3 mg; ns). Postoperative nausea and vomiting (PONV) occurred with similar frequencies in both groups. The 24-h dixyrazine consumption was the same in the two groups (2.1 +/- 2.7 mg in the saline group compared to 2.4 +/- 2.8 mg in the ropivacaine group; ns). After 6 h recovery, 41% of all patients had experienced nausea and 20% vomiting. CONCLUSION: We found no differences in postoperative pain management between 3.75 mg/ml ropivacaine and saline wound infiltration before breast surgery. The data show similar postoperative needs of analgesics and antiemetics with a similar frequency of PONV.

Amides↗
PubMed2000

Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas.

BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation.

Animals↗
PubMed2000

Operations for extrahepatic bile duct cancers: are the results really improving?

OBJECTIVE: To find out if our results for the treatment of extrahepatic bile duct cancer have improved we reviewed our latest patients as a comparison to a previously reported series from this department. DESIGN: Retrospective study. SETTING: Tertiary referral centre, Sweden. SUBJECTS: 102 patients who presented with extrahepatic bile duct cancer 1979-1995. MAIN OUTCOME MEASURES: Morbidity, mortality, and short and long term survival. RESULTS: 16 patients had various types of resection, which were radical in 14 according to the surgeon and in 10 according to the pathologist. One patient (6%) died in hospital, and 1 (44%) developed complications. 13 patients had other operations that did not involve resection, 23 had laparotomy alone, 61 had biliary drainage either by percutaneous transhepatic cholangiography (PTC) or endoscopy, and 10 had no active treatment. One patient of the 16 (6%) who had resections has survived for more than five years and another one is still alive after 40 months. CONCLUSION: Long term survival has not improved for patients with extrahepatic bile duct cancer in our hospital during the last decades.

Adult↗
PubMed2000

Effects of intraluminal trypsin and bile on the exocrine and endocrine pancreas after pancreaticobiliary diversion and biliodigestive shunt.

Pancreaticobiliary diversion (PBD) and biliodigestive shunt (BDS) cause long-standing hypercholecystokininemia followed by pancreatic hyperplasia. These changes have been suggested to be due to the lack of intraluminal trypsin and bile, respectively, in the upper small intestine. The aim of these experiments was to study the effect of restoration of intraluminal trypsin and bile on plasma levels of cholecystokinin (CCK) and the changes found in exocrine and endocrine pancreas after PBD and BDS. Male Sprague-Dawley rats were used. PBD was done in 16 rats, eight of which had trypsin dissolved in 50 mM sodium bicarbonate (SB), and eight had SB only by gastric intubation twice daily. BDS was done in another 16 rats, eight of which had bile dissolved in SB, and eight had SB in a similar manner. Sham-operated rats had SB and served as controls. After 4 weeks, the rats were killed, and the concentrations of circulating CCK, gastrin, glucose, glucagon, and insulin were determined. The pancreas was removed, weighed, and analyzed for contents of water, protein, and DNA. In another study, PBD-operated rats got trypsin in varying dosages or trypsin and taurocholate in combination for 2 weeks before death. The concentrations of plasma CCK and glucagon were elevated after both PBD and BDS. PBD decreased the concentration of gastrin in plasma. PBD caused an increase of pancreatic weight and the contents of protein and DNA. Trypsin substitution to PBD-operated rats did not affect plasma CCK or glucagon levels, but the PBD-induced increases in weight and DNA content were counteracted by trypsin. Higher dosages of trypsin did not further influence the effects seen after PBD. Pancreatic weight and DNA content were increased after BDS. Bile administration completely abolished the increase in plasma CCK and glucagon, as well as the gain in pancreatic weight, and reduced the increase in pancreatic DNA. Substitution with bile to BDS-operated rats abolished the increase in the plasma levels of CCK and glucagon, as well as the trophic effects on the pancreas. Trypsin substitution to PBD-operated rats partly reversed the trophic effects on the pancreas but not the hormonal changes in plasma. Thus the trophic effects on the pancreas exerted by BDS seem to be dependent on the lack of bile in the upper small intestine, whereas the effects of PBD only partly are a consequence of the absence of intraluminal trypsin.

Animals↗
PubMed2000

Acute taurodeoxycholate-induced pancreatitis in the rat is associated with hyperCCKemia.

BACKGROUND: Cholecystokinin (CCK) has been suggested to be involved in the development and course of acute pancreatitis. In the present study we measured plasma CCK concentrations in acute experimental pancreatitis (AEP) in the rat, and evaluated the role of circulating CCK levels on the initial pancreatic damage in pancreatitis. METHODS: Endogenous hyperCCKemia was induced by surgical biliodigestive shunt (BDS) and exogenous hyperCCKemia by infusion of CCK-8S. The CCK-A receptor antagonist devazepide was used to antagonize the effect of CCK. Pancreatitis was induced by pancreatic duct infusion of sodium taurodeoxycholate 4 wk after the BDS operation or 1 wk after the start of the infusions. Nonpancreatitic sham- and BDS-operated rats, respectively, were used as control animals as were groups of otherwise untreated rats with pancreatitis. The animals were sacrificed 6 h after induction of pancreatitis. Concentrations of CCK were determined in plasma as were protein and amylase levels in the pancreas and peritoneal exudates. The extent of pancreatic necroses was assessed microscopically. RESULTS: Pancreatitis caused an 11-20-fold increase of circulating CCK as measured after 6 h. In pancreatitic rats with induced hyperCCKemia, there was a further marked increase of plasma CCK. Pancreatic weight and edema, protein and amylase contents, and extent of necroses were the same regardless of the level of plasma CCK. Devazepide had no influence on the studied pancreatic parameters. CONCLUSION: We conclude that acute taurodeoxycholate-induced pancreatitis in the rat is associated with elevated plasma CCK concentrations. There seems, however, not to be any correlation between the degree of hyperCCKemia and the extent of initial pancreatic damage.

Acute Disease↗
PubMed2000

Transforming growth factor alpha (TGF-alpha) increases cell number in a human pancreatic cancer cell line but not in normal mouse pancreas.

BACKGROUND: The pancreas harbors growth factors such as the epidermal growth factor (EGF) family. The physiological and pathophysiological roles of growth factors in normal pancreas remain unsettled. Human pancreatic cancer overexpresses the EGF receptor, and the ligands EGF and transforming growth factor alpha (TGF-alpha). The aim of the present experiments was to study the effect of TGF-alpha in a pancreatic cancer cell line and in normal mouse pancreas. METHOD: The LN-36 cell line, established from a pancreatic duct cell adenocarcinoma, was incubated with TGF-alpha or EGF. The effect of an EGF receptor-specific, tyrosine kinase inhibitor (tyrphostin B56) with or without growth factors was also studied. The cell number was measured with the XTT-colorimetric method. TGF-alpha, the tyrphostins A25, B48, and B56, were in separate experiments infused during 1 wk to normal female mice by subcutaneous (sc) minipumps. RESULTS: The LN-36 cell line responded to TGF-alpha and EGF with increased cell number; +61% with 10(-10) M TGF-alpha and +34% with 10(-9) M EGF. Tyrphostin B56 at a concentration of 10(-5) M reduced the cell number by 76%, but when incubated together with growth factors the reduction was only 44% with TGF-alpha, and 39% with EGF. Infusion of TGF-alpha increased mouse pancreatic wet weight and protein content but was without effect on DNA synthesis, measured as incorporation of tritiated thymidine. Infusion of three different tyrphostins did not influence mice pancreas. CONCLUSION: The results support the role of TGF-alpha to maintain growth of pancreatic cancer cells by the EGF receptor. Infusion of TGF-alpha induced hypertrophy in normal mouse pancreas.

Animals↗
PubMed1999

Pancreatic biopsy: why? When? How?

For final diagnosis of pancreatic cancer histologic or cytologic confirmation is needed. Tissue or cell material can be achieved by percutaneous puncture as part of the preoperative workup. During operation core-needle, incisional, and wedge biopsies or fine-needle aspiration cytology (FNAC) can be chosen. Sensitivity and diagnostic accuracy are high for both histologic and cytologic examinations, and false-positive results are exceptional, giving a specificity of 100% in most published series. The complication rate is low, also for knife biopsies in recent reports, provided biopsy of seemingly normal tissue is avoided. Percutaneous puncture is currently restricted to patients found to have advanced disease and who are not candidates for laparotomy. Microscopic confirmation is required in all patients in whom chemotherapy, radiotherapy, or both are planned. However, for attempted radical surgery per se, biopsy is not mandatory if the clinical suspicion of cancer is high and the surgical team has documented low postoperative mortality and morbidity rates.

Biopsy, Needle↗
PubMed1999

The effect of bombesin, cholecystokinin, gastrin, and their antagonists on proliferation of pancreatic cancer cell lines.

BACKGROUND: The role of cholecystokinin (CCK) and gastrin in the development and growth of pancreatic cancer cells is controversial. The aim of this study was to evaluate the role of CCK-8S, gastrin-17, bombesin, and their antagonists on cell lines from patients with pancreatic cancer. METHODS: Cell lines were established from pancreatic cancers operated on at our department. The cells were grown in 10% fetal calf serum (FCS). The effects of CCK-8S, gastrin-17, bombesin, and their antagonists in different concentrations and for different time intervals were studied. The cell number was evaluated with the XTT method. RESULTS: The cell line LN 36 responded with increased cell number to stimulation by gastrin-17 and decreased cell number to inhibition by the CCK-B receptor antagonist L-365,260. In contrast, LPC 1 responded with increased cell number to CCK-8S and decreased cell number to the CCK-A receptor antagonist devazepide. LPC 2, 6, and 7 were stimulated by CCK-8S, gastrin-17, and their antagonists. LPC 3 showed decreased cell number after inhibition by the antagonists, and LPC 5 and 10 showed increased cell number after stimulation by CCK-8S and gastrin-17. LPC 4 was stimulated by CCK-8S, and LPC 8 was stimulated by all substances except gastrin-17. Intermittent administration of the substances to LN 36 led to a greater effect on the cell number than administration every day, which was not the case with LPC 1 and LPC 3. Bombesin led to an increased growth in LPC 5 but not in LPC 3. CONCLUSION: CCK-8S and gastrin-17 led to an increased cell number in some cell lines. A blockade of the CCK-A and CCK-B receptors by their antagonists led to an increased, an unaffected, or a decreased cell number of the cell lines. The effect of bombesin on different cell lines also varied. This shows a great heterogenicity among pancreatic cancer cells from different patients.

Benzodiazepinones↗
PubMed1999

Pancreatic growth after pancreatico-biliary diversion does not increase the capacity to secrete amylase.

BACKGROUND/AIM: Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats. MATERIAL AND METHODS: Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo. RESULTS: PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7-12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period. CONCLUSION: PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.

Amylases↗
PubMed1999

Pancreaticogastrostomy after subtotal pancreatectomy for cancer.

BACKGROUND: Failure of the pancreaticodigestive anastomosis after pancreatoduodenectomy is still a major clinical problem. Pancreaticogastrostomy has recently been suggested to be associated with a low risk of leakage. The aim of this report was to add to previously reported experience. METHODS: Data on the postoperative course were prospectively registered in 19 patients operated on with subtotal pancreatectomy because of periampullary cancer. They all had a duct-to-mucosa pancreaticogastrostomy. RESULTS: There were no recognizable leakages from the pancreaticogastrostomy. However, the overall postoperative complication rate was 47% (9/19), the most common complications being delayed gastric emptying (26%, 5/19), wound infection (21%, 4/19), and wound rupture (11%, 2/19). Excluding delayed gastric emptying, the rate of intra-abdominal complications was 16% (3/19). There was 1 in-hospital death. CONCLUSION: The results support the opinion that pancreaticogastrostomy can be done with a low risk of leakage.

Aged↗
PubMed1999

CCK stimulates growth of both the pancreas and the liver.

BACKGROUND: The pancreas is the main target of the trophic effect of cholecystokinin (CCK), with a transient increase in cell proliferation and persistent effect on DNA content and weight gain when given continuously. Whether CCK exerts similar effects on the liver and biliary tract is not known. Most studies on this subject have hitherto been done in the rat. The aim of the present experiments was therefore to study the possible concomitant trophic effects of CCK on these three organs in a gallbladder-bearing animal, the hamster. METHODS: CCK-8S or the CCK-A receptor antagonist devazepide were infused subcutaneously by osmotic minipumps for 4 weeks in 11 and 7 hamsters, respectively. Fifteen animals served as untreated controls. One hour before sacrifice tritiated thymidine was injected intraperitoneally. Plasma was collected for determination of CCK and the pancreas, liver, common bile duct and gallbladder were excised. The pancreas and liver were weighed and processed for the contents of protein, DNA and water. Tissue specimens were taken for autoradiography. RESULTS: The concentration of CCK in plasma increased fourfold during the infusion of CCK-8S. The pancreas and, to a lesser extent, the liver increased in weight, DNA and protein contents after infusion of CCK-8S, whereas the pancreas, but not the liver, decreased in weight and protein content after infusion of devazepide. Pancreatic amylase content was increased after CCK-8S treatment, but unaffected by devazepide. Labelling index of pancreatic acinar cells, hepatocytes and gallbladder epithelium was no different from that of controls after four weeks of infusion of CCK-8S or devazepide. A correlation was found between the concentration of plasma CCK on one hand and the weights and DNA contents in pancreas and liver on the other. CONCLUSION: The results suggest that CCK stimulates growth of both the pancreas and the liver in the hamster.

Animals↗
PubMed1998

The effect of intermittent injections of CCK-8S and the CCK-A receptor antagonist devazepide on cell proliferation in exocrine rat pancreas.

CONCLUSION: Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration. BACKGROUND: Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether intermittent administration of CCK-8S or devazepide prevents receptor desensitization and thereby affects exocrine pancreatic cell proliferation persistently. METHODS: Male Sprague-Dawley rats were injected subcutaneously twice daily with CCK-8S (6 micrograms), devazepide (240 micrograms) or bovine serum albumin (BSA). The rats were sacrificed after 18 and 36 h and 3 and 7 d. One hour before sacrifice, the rats were injected intraperitoneally with 1 mCi/kg of tritiated thymidine. The pancreatic weight and the contents of water, protein, and DNA were determined. The LI (number of labeled cells/100 cells) of exocrine pancreatic cells was determined microscopically after autoradiography. RESULTS: The concentration of plasma CCK was slightly increased by devazepide, but the increase was more pronounced by CCK-8S. The pancreatic wet weight was transiently increased 18 h after the start of CCK-8S injections (+14%), whereas devazepide caused a reduction after 7 d (-22%). The protein content was uninfluenced and the DNA content was decreased at 36 h with either treatment. CCK-8S increased the LI in acinar and centroacinar cells throughout the study period, but the ductal cell LI was increased only after 18 and 36 h. Injection of devazepide was followed by decreased LI of acinar cells throughout the study period. Also, the centroacinar and ductal cell LI decreased initially but returned to control values after 7 d.

Animals↗