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Hannu Paimela

Publications and source records attributed to Hannu Paimela.

8 recordsLinked to original sources
PubMed2005

Surgery for colorectal cancer in a low-volume unit: assessment of key issues in the achievement of acceptable clinical results.

BACKGROUND: The maintenance of modern therapeutic principles requires a proper case load to achieve acceptable surgical results. This may obligate administrative reorganization to overcome these problems and to provide an adequate level of cancer surgery. AIM: To assess the surgical results of patients coming for surgery for colorectal cancer in a low-volume non-academic unit during the past 15 yr. METHODS: 458 consecutive patients referred for surgery between 1988 and 2001 in Kanta-Häme Central Hospital in Finland were analyzed regarding their disease, mode of surgery, and the immediate and long-term result. The data were collected from patient journals and from the National Centre of Statistics and analyzed in two successive periods. RESULTS: The number of patients with a localized disease (Dukes A + Dukes B) decreased during the followup from 49% to 45%. A curative procedure was achieved in 68% in the first half and in 73% in the second half of the observation period. The immediate mortality was 5% and 2% in the two periods, respectively. The corrected 5-year survival according to the Dukes Classification was 92% (A), 69% (B), 41% (C ), and 6% (D). In curative surgery for rectal cancer, the incidences of local recurrence decreased from 21% to 9% (NS) and the use of permanent colostomy from 59 to 42% (NS). CONCLUSIONS: Acceptable immediate and long-term results in curative surgery for colorectal cancer can be achieved in a low-volume surgical unit. Nevertheless, owing to the low volume, the improvement of the results obligates team-based institutional specialization and careful consideration about the extensiveness of the primary procedure in case of cancer obstruction.

Adult↗
PubMed2005

Deteriorating stage profile of gastrointestinal cancer in Finland.

BACKGROUND: The prognosis of patients with gastrointestinal (GI) cancer is mainly due to the stage of the tumor at the diagnosis. Regardless of several innovations in diagnostic and therapeutic gastroenterology, there is no longitudinal data of the trends of stage profile of patients with gastrointestinal cancer in Finland. AIM: To study the incidence by stage of GI cancer in Finland in the past 15 yr in the entire country as well as in two subpopulations with different population profile: in a population with a small number of residents over 65 yr of age (Jorvi district) and in a population with a large number of residents over 65 yr of age (Kanta-Häme district). METHODS: The hospital discharge records of patients with upper or lower GI cancer between 1986 and 2000 were evaluated in Finland as well as in Jorvi and Kanta-Häme hospital districts. The data were obtained from the National Research and Development Centre for Welfare and Health, from the Centre of Statistics and from the Finnish Cancer Registry. RESULTS: The relative incidence of a localized esophagogastric cancer against more severe stages decreased from 37.9% to 29.3% in the entire country, from 40.8% to 19.1% in Kanta-Häme, and from 44.2% to 33.3% in Jorvi area. Respectively, the relative incidence of localized colorectal cancer decreased from 53.6% to 48.0% in the entire country, from 49.7% to 42.5% in Kanta-Häme, and from 54.5% to 48.4% in Jorvi area. CONCLUSIONS: During the past 15 yr the incidence by stage of both upper and lower GI cancer is deteriorating in the entire country as well as in areas with low and high percentage of residents over 65 yr of age indicating the increase of the more severe cases. The deterioration has become more pronounced in the 1990s, which requires a careful scrutiny of the function of primary diagnostic services.

Aged↗
PubMed2005

Long-term results after surgery for gastric cancer with or without jejunal reservoir: results of surgery for gastric cancer in Kanta-Häme central hospital in two consecutive periods without or with jejunal pouch reconstruction in 1985-1998.

BACKGROUND: Gastric cancer still has a disease-specific 5-yr survival less than 30% and an overall survival of about 15%. The quality of life of patients who undergo gastrectomy is poor owing both to the severity of the disease itself and to the mutilation of the upper gastrointestinal channel after the reconstruction. Therefore, the combination of a jejunal pouch with gastrectomy has been claimed to improve the life quality and nutritional status of these patients. AIM: To assess the clinical results after surgery for gastric cancer in two consecutive periods with or without jejunal-pouch reconstruction. METHODS: 271 consecutive patients referred for surgery for gastric cancer in 1985-1991 (116 patients) and in 1992-1998 (155 patients) in Kanta-Häme central hospital were retrospectively analyzed regarding their disease, mode of surgery, and the immediate and long-term results. In the former observation period gastrectomy was performed with Roux-en-Y esophagojejunostomy without a reservoir, and in the latter period this procedure was combined with a jejunal reservoir. The data were collected from patient journals and from the death certificate obtained from the National Centre of Statistics in Finland. RESULTS: During the study period the incidence of cancer in the cardia increased among the surgical patients from 13.1 to 26.7% (p <0.05). Despite this proximal migration, the cancer-specific 5-yr survival remained practically unchanged during the two study periods, 29.4% and 32.2% (NS). During the period of jejunal-pouch reconstruction there were non-significant increases of the incidences of local recurrence (from 18.9% to 26.5%), of immediate postoperative anastomotic fistulae (from 0.9% to 4.5%) as well as of the immediate mortality (from 2.6% to 3.7%) (NS for each). CONCLUSIONS: Despite proximal migration of gastric cancer and the application of a jejunal reservoir, the long-term as well as the immediate results after curative surgery (i.e., D2-gastrectomy) for gastric cancer have remained relatively unchanged. The jejunal-pouch reconstruction with the present technique after gastrectomy can therefore be safely applied.

Adult↗
PubMed2005

Calcium signaling is involved in ethanol-induced volume decrease and gap junction closure in cultured rat gastric mucosal cells.

Ethanol is a well-established "barrier breaker" in gastric mucosa, but its detailed effects at the cellular level remain unclear. We have previously shown that the intracellular free calcium concentration is increased, gap junctions are closed, and cell volume is decreased after exposure to 5% (v/v) ethanol in primarily cultured rabbit gastric epithelial cells. Rat gastric mucosal (RGM) cells were grown to confluence on a coverslip or on a filter membrane. Gap junctional diffusion was measured in 5-carboxyfluorescein-loaded cells by bleaching a small area with a laser and measuring the recovery with confocal microscope. Intracellular calcium was measured spectrofluorometrically in fura-2-loaded cells. For cell volume measurements the cell monolayer was loaded with calcein and imaged along the Z-axis with a confocal microscope. The changes in fluorescence intensity were intercepted as a measure of cell volume change. TMB-8 was used to inhibit intracellular calcium release and lanthanum to block plasma membrane calcium selective ion channels, while BABTA served as an intracellular calcium chelating agent. Results showed that ethanol (7.5%, v/v) exposure increased intracellular calcium from 69 +/- 7 to 142 +/- 11 nM (N = 5; P < 0.05), decreased cell volume by -23 +/- 5% (N = 8; P < 0.05), and induced gap junction closure (fluorescence recovery from 37 +/- 9 to 15 +/- 3%; N = 6; P < 0.05). A serosal potassium channel blocker, quinine, almost completely prevented the ethanol-induced cell volume decrease (from -23 +/- 5 to -3 +/- 3%), suggesting that opening of basolateral potassium channels underlies cell shrinkage. BABTA inhibited completely (from 35 +/- 3 to 39 +/- 4 nM; N = 6; P < 0.05), and TMB-8 + lanthanum partially (from 60 +/- 6 to 92 +/- 12 nM; N = 6; P < 0.05), the ethanol-induced intracellular calcium increase. BABTA also abolished the ethanol-induced volume decrease (from -23 +/- 5 to 1 +/- 4%; N = 6; P < 0.05), while TMB-8 + lanthanum had a lesser effect on it (from -23 +/- 5 to -11 +/- 3%; N = 9; P < 0.05). They also abolished the closure of gap junctions induced by ethanol (fluorescence recovery, 38 +/- 5% for BABTA and 30 +/- 4% for TMB-8 + lanthanum). We conclude that luminal ethanol opens basolateral calcium-dependent potassium selective channels with resultant shrinkage of the cells and blocks the intercellular gap junctions. These actions are mediated by intracellular calcium signaling.

Animals↗
PubMed2004

Structural signaling regulates inflammation-induced enhanced restitution and increased Mib-1 and Bax-indexes after superficial injury in isolated guinea pig gastric mucosa.

Several growth factors and cytokines are involved in regulation of the immediate repair of gastrointestinal mucosa, a process also called restitution. Few data exist on the effect of inflammation on this process using an explant model, where the folded basal lamina is included. The aim of the present study was to investigate the effect of simulated inflammation on restitution and on concomitant proliferation and apoptosis in isolated guinea pig gastric mucosa. Paired gastric mucosae were mounted in Ussing chambers (37 degrees C) and a superficial injury was induced (1.25 M NaCl/5 min) followed by a 4-hr restitution (pH 7.3-7.5). During perfusion, simulated inflammation was induced (with 0.5 or 5.0 ng/ml IL-1beta or with activated polymorphonuclear [PMN] cells). The PI (proliferative index) and AI (apoptotic index) are expressed as the number of Mib-1- or Bax-immunopositive cells per 300 foveolar cells, respectively. The mean recovery of electrophysiological resistance of tissues (R) after injury and exposure to serosal IL-1beta during restitution was 95.2 +/- 5.3% (mean +/- SD), whereas the value for control tissues was 89.6 +/- 6.9% (P = 0.016; N = 9). The mean recovery of R in tissues exposured to activated serosal PMN cells during restitution was 97.6 +/- 2.7%, whereas the value for unexposed control tissues was 93.8 +/- 2.9 (P = 0.004; N = 9). The enhancing effect of PMN cells was partially eliminated by serosal anti-ICAM, whereas serosal cytochalasin D abolished the process completely. The PI of tissues exposed to serosal PMN cells was 34.6 +/- 17.3, whereas the value for unexposed controls was 24.7 +/- 15.5 (P = 0.04; N = 5). The corresponding AI values were 17.0 +/- 2.8 and 12.0 +/- 5.7, respectively (NS; N = 4). Simulated inflammation either with serosal IL-1beta or with activated PMN cells enhances restitution and proliferation, whereas their effect on AI is only suggestive. Exogenous serosal anti-ICAM modulates restitution, whereas cytochalasin D abolishes it completely, suggesting that the structural signaling system including focal adhesions and cytoskeleton plays a significant role in the regulation of restitution.

Animals↗
PubMed2003

Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism.

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.

Animals↗
PubMedDate not supplied

Regulation of restitution after superficial injury in isolated guinea pig gastric mucosa.

The immediate response of the gastrointestinal epithelium to superficial (i.e. microscopic) injury is primarily directed towards restoring the disturbed epithelial continuity. Both structural (i.e. cytoskeleton) and humoral (i.e. growth factors and cytokines) involvement in the process has recently been documented. Yet it is unclear whether humoral signaling regulating mucosal recovery after superficial injury is associated with tyrosine phosphorylation, and whether there are other signs of downstream activation of the signaling pathway. To evaluate the effects of exogenous genistein and phorbol-myristate acetate in the assessment of the role of tyrosine receptor-mediated signaling in the immediate repair of gastric mucosa after superficial injury. Guinea pig gastric mucosa was mounted in a Ussing chamber, injured with 1.25 M NaCl, and perfused for 4 h. Simultaneously, potential difference and tissue resistance were recorded. In some sets of experiments the tissue was exposed bilaterally either to genistein in order to inhibit tyrosine receptor-mediated signaling or to 4-phorbol-myristate 13-acetate (PMA) in order to enhance PKC signaling during the 4 h recovery. Phosphotyrosine (PTYR) and protein kinase C (PKC) immunoreactivity were assessed by immunoblotting and by immunohistochemistry. Proliferative activity was determined morphometrically after staining of the tissue for Ki-67 nuclear antigen and expressed as proliferative index (PI). The inhibition of tyrosine kinases with exogenous genistein resulted in a significant decrease of the PTYR and the stimulation of PKC with PMA increased the PTYR. Nevertheless, no change in the PTYR was observed by immunoblotting after superficial injury alone. Several PKC isoenzymes were found in the guinea pig gastric mucosa, including PKC-alpha, -epsilon, -zeta and -iota. They were unaffected either by the injury or the PMA treatment. The mean PI of tissues subjected to NaCl-injury was higher than that of uninjured control tissues (p<0.05) (n=7). Exposure of tissue to genistein during recovery decreased the PI, while stimulation with PMA increased it (p<0.05 for both) (n=6). Both electrophysiologic and morphologic restitution were sensitive to genistein, but not to PMA. Superficial injury alone does not influence tyrosine phosphorylation to a degree which could be assessed by immunoblotting. Nevertheless, exogenous modulation of tyrosine receptor-mediated signaling results in downstream signaling effects. The injury-associated induction of proliferation is sensitive to modulation of tyrosine phosphorylation and PKC, suggesting that superficial epithelial injury results in endogenous activation of the epithelium, presumably after paracrine stimulation of the neighboring cells.

Animals↗