Sauna-bathing with sutures. A prospective and randomised study.

BACKGROUND AND AIMS: Bathing in sauna is a Finnish habit with numerous beliefs and traditions. One belief has been that one is not allowed to go to sauna postoperatively with sutures. This belief is in practically every patient information sheet in Finland on postoperative wound care. There is no scientific proof of the harmfulness of sauna-bathing with sutures and no articles on the matter, either. The aim of this study was to evaluate whether sauna-bathing has a negative impact on wound healing. MATERIALS AND METHODS: Prospective, randomised study with 79 patients scheduled for an elective hernioplasty in a day care surgical department. The other group was advised to go to sauna from 3rd postoperative day on, and for the other group, sauna was prohibited until sutures were removed. RESULTS: There was no differences in wound healing between two groups. CONCLUSION: There is no reason to prohibit sauna-bathing with sutures in this patient group.

Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients.

Undesired bone loss around implants is considered to occur mainly because of a stress-shielding phenomenon. Bone surrounding the total knee arthroplasty (TKA) adjusts its mineral density and structure to meet new mechanical demands. Immobilization, in combination with local operative trauma to the bone and soft tissues, has an additional impact on bone loss. The clinical survival of TKA is associated with the quality and quantity of the surrounding bone environment. Poor bone quality and quantity may predispose to aseptic implant loosening and periprosthetic fractures. We investigated the efficacy of oral bisphosphonate (alendronate, Fosamax) with calcium (Calcichew) for the inhibition of early bone mineral density (BMD) loss after TKA in a prospective, randomized, one-year follow-up study. Periprosthetic BMD changes were measured with fan-beam dual-energy X-ray absorptiometry (DXA) in 19 patients with knee osteoarthrosis. Patients (n = 8) treated with 10 mg alendronate and 500 mg calcium daily maintained distal femoral BMD values close to the baseline values (P > 0.04), while patients receiving only 500 mg of calcium daily (n = 11) showed significant bone loss during the one-year follow-up (P < 0.015). The treatment groups differed significantly in metaphyseal anterior, posterior, diaphyseal, and metaphyseal total regions of interest (ROIs) (repeated measures ANOVA analyses, P = 0.019, P = 0.010, P = 0.022, and P = 0.024, respectively). Our results indicate that oral alendronate reduces early postoperative periprosthetic bone loss significantly. This therapeutic strategy may improve the results and longevity of primary total knee arthroplasties.

Bone histomorphometry in celiac disease.

BACKGROUND AND AIMS: Bone metabolism in celiac patients is not well understood and there are no previous histomorphometric studies on bone of patients with celiac disease. The aim of the study was to investigate bone metabolism in celiac patients using bone histomorphometry, measurement of bone mineral density (BMD) and biochemical parameters. MATERIAL AND METHODS: The patient groups included 19 men and 23 women with previously diagnosed celiac disease in remission (group I), 7 women not in remission (group II) and 19 women and 9 men with newly diagnosed celiac disease (group III). Static and dynamic parameters of bone structure, formation and resorption were measured using undecalcified sections. The following parameters were obtained: bone volume (BV/TV; %), osteoid volume (OV/BV; %), osteoid surface (OS/BS; %), resoprtion surface (ES/BS; %), osteoid thickness(Oth; microm), mineral apposition rate (MAR; microm/day), and mineralization lag time (MinLag; day). BMD was measured at the spine (L2-4) and left femoral neck, trochanter and Ward's triangle. Serum calcium (S-Ca; mmol/L), alkaline phosphatase (AP; U/L), intact parathyroid hormone (S-PTH; ng/L), 25-hydroxyvitamin D (S-25(OH)D; nmol/L), cross-linked carboxyterminal telopeptide of human type I collagen (S-ICTP; microg/L) and C-terminal extension peptide of type I procollagen (S-PICP; microg/L) were analysed. RESULTS: In the histomorphometric analysis there were no significant differences in static or dynamic parameters between the groups. Very low bone mass (< 10%) was found in one patient in every group. OV/BV was increased (> 3.5%) in all groups (31% in group I, 13% in group II and 29% in group III). OS/BS was increased (> 36.5%) in groups I and III (17% and 29% respectively). In group II OS/BS was normal in all patients. Mineralization defect was found in four patients in group I and in two patients in group III with otherwise normal histomorphometric results. ES/BS was increased in three patients in group I and III and in one patient in group II. One female patient in group III had increased osteoid parameters, resorption surface, S-PTH and low concentration of vitamin D reflecting hyperparathyroid changes in bone. S-PTH was increased (66-87 ng/L) in four patients in group III and one of these patients had hyperparathyroid histological changes in bone. CONCLUSIONS: Static and dynamic histomorphometry of iliac crest bone biopsy are useful tools to evaluate bone metabolism in celiac disease especially if hyperparathyroidism or mineralization defect are suspected. Hyperparathyroidism may be a problem in the patients before introducing gluten-free diet. Mineralization defect and osteomalacic changes are common later on irrespective of whether the patients are in remission or not.

Expression of transcription factor AP-2 in colorectal adenomas and adenocarcinomas; comparison of immunohistochemistry and in situ hybridisation.

AIMS: To investigate whether the three different AP-2 isoforms are expressed differently in colorectal adenomas and carcinomas. METHODS: The study comprised 43 randomly selected patients diagnosed and treated at Kuopio University Hospital in 1996 for colorectal adenocarcinoma (n = 30) and colorectal adenoma (n = 13). The expression of AP-2alpha, AP-2beta, and AP-2gamma was analysed by immunohistochemistry (IHC) and the mRNA status of AP-2alpha was determined by in situ hybridisation (ISH) and confirmed by reverse transcription polymerase chain reaction (RT-PCR). AP-2 expression patterns were correlated with clinicopathological variables. RESULTS: In adenomas and carcinomas, AP-2beta cytoplasmic positivity was higher than that of AP-2alpha or AP-2gamma. AP-2alpha expression was reduced in advanced Dukes's stage carcinomas. In high grade carcinomas, both AP-2alpha and AP-2gamma expression was reduced. ISH demonstrated increased AP-2alpha values in high grade carcinomas. Seven of 30 carcinoma specimens displayed a moderate or strong mRNA signal, despite being negative for AP-2alpha protein. RT-PCR from AP-2alpha mRNA and protein positive tumours confirmed that the positive signal in ISH originated from the exon 2 of TFAP2A. CONCLUSIONS: AP-2alpha was reduced in advanced Dukes's stage adenocarcinomas. Together with reduced AP-2gamma expression in high grade carcinomas, this might contribute to tumour progression. The discrepancy between mRNA and protein expression suggests that post-transcriptional regulatory mechanisms might modify the availability of functional AP-2alpha protein in colorectal carcinoma.

Monitoring of periprosthetic BMD after uncemented total hip arthroplasty with dual-energy X-ray absorptiometry--a 3-year follow-up study.

Insertion of a metallic implant into the femur changes bone loading conditions and results in remodeling of femoral bone. To quantify changes in bone mass after uncemented total hip arthroplasty (THA), we monitored femoral bone with dual-energy X-ray absorptiometry (DXA). The periprosthetic bone mineral density (BMD) was measured with Lunar DPX densitometry in seven Gruen zones and the total periprosthetic area at scheduled time intervals in 22 patients during a 3-year follow-up. BMD decreased significantly almost in all Gruen zones during the first 3 months, ranging from 3.4% to 14.4% (p < 0.05 top < 0.001). At the end of the first year, the most remarkable decrease in BMD was found in the calcar (zone 7; -22.9%). During the second postoperative year, a slight restoration of periprosthetic bone mass was recorded. During the third year, no significant changes in BMD were found. The preoperative BMD was the only factor that was significantly related to the periprosthetic bone loss. Clearly, the early periprosthetic bone loss noticed during the 3 months after THA is caused by mainly limited weight bearing to the operated hip and stress shielding. We suggest that the restoration of bone mass is a sign of successful osteointegration between bone and metallic implant. DXA is a suitable tool to follow the bone response to prosthetization and will increase our knowledge on the behavior of bone after THA.

Reduced CD44 standard expression is associated with tumour recurrence and unfavourable outcome in differentiated thyroid carcinoma.

CD44 was detected with an antibody recognizing all forms of CD44 (CD44 standard) and others specific for its v3 and v6 variant isoforms; their prognostic value was evaluated in 213 patients with differentiated thyroid carcinoma (DTC). The staining patterns of CD44 standard (s) and CD44v6 in tumour tissue were quite similar, 176 cases (83%) being highly positive for CD44s and 153 cases (72%) for CD44v6. Only 18 (9%) tumours showed high expression of CD44v3. Papillary carcinomas were significantly more often high expressors of CD44s and CD44v6 than follicular carcinomas (p<0.001 for both). Age older than 60 years, distant metastases, and advanced pTNM stage were related to loss of expression of CD44s (p<0.001, p=0.021, and p=0.003, respectively). Tumour recurrence and cancer-related mortality were related to the reduced level of CD44s (p=0.049 and p=0.042). CD44v3 did not associate with any of the clinicopathological factors. In univariate analysis, CD44s was the only significant prognostic factor for disease-free survival (p=0.0488). In multivariate analysis, CD44s and thyroglobulin level were significant prognostic factors for disease-free survival (p=0.040 and p<0.001, respectively). The reduced level of CD44s in DTC patients seems to be an independent prognostic factor for unfavourable disease outcome.

Reduced level of CD44 and hyaluronan associated with unfavorable prognosis in clinical stage I cutaneous melanoma.

The cell surface glycoprotein CD44 and its ligand, hyaluronan (HA), enhance growth and metastatic capacity of melanoma cells in vitro, but their clinical significance in primary cutaneous melanoma is still unclear. Therefore, we studied whether the levels of CD44 and HA associate with disease progression and survival of cutaneous melanoma. A series of 292 clinical stage I cutaneous melanomas was analyzed by immunohistochemistry using an anti-CD44H antibody (clone 2C5). HA was demonstrated histochemically using a biotinylated HA-specific affinity probe (bHABC). The reduced staining levels of CD44 and HA were associated with each other and indicators of progressive disease. Reduced CD44 and HA level, high tumor thickness, high pT category, high Clark's level, bleeding, and male gender predicted short univariate recurrence free survival (RFS) and overall survival (OS). In Cox's multivariate analysis (N: = 251), the decreased level of CD44, high tumor thickness, and bleeding predicted independently short RFS. High tumor thickness and bleeding were associated with short OS. We conclude that the reduced cell surface CD44 and HA levels associate with poor prognosis in clinical stage I cutaneous melanoma. The notion that the decreased level of CD44 independently predicts short RFS suggests that reduced cell surface CD44 enhances the spreading potential in localized cutaneous melanoma and that quantification of CD44 offers a prognostic tool for its clinical evaluation.

Laparoscopic or open cholecystectomy: a prospective randomised trial to compare postoperative pain, pulmonary function, and stress response.

OBJECTIVE: Open cholecystectomy (OC) has been superseded by laparoscopic cholecystectomy (LC) for the treatment of cholelithiasis, although this fashion has not been validated by prospective studies. Our aim was to compare the two techniques. DESIGN: Prospective, randomised, open study. SETTING: University hospital, Finland. PATIENTS: 49 patients who required cholecystectomy for cholelithiasis confirmed by ultrasound. INTERVENTIONS: 49 patients were randomly allocated to LC (n = 27) or OC (n = 22): 25 and 22, respectively, eventually had the operation. LC was done using a four-trocar technique, and OC through a transverse right subcostal incision, as short as possible. MAIN OUTCOME MEASURES: Length of hospital stay and the duration of the sick leave were the primary outcome measures. Secondary outcome measures were: postoperative pain evaluated by visual analogue scale (VAS) and the need for opioids; pulmonary function measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak flow velocity (PEFV), and arterial oxygen tension (PaO2), and endocrine stress measured by plasma catecholamines, cortisol and glucose concentrations. RESULTS: The median (range) hospital stay was significantly shorter after LC than OC, being 2.0 (1-15) compared with 4.5 (2-19) days p < 0.01. The duration of sick leave was also significantly shorter after LC than OC, being 14 (7-17) compared with 29 (4-34), p < 0.01. Patients had significantly less postoperative pain after LC than OC as reflected by the need for opioids. Pulmonary function and arterial oxygen tension deteriorated significantly less after LC than OC. The stress response was equal. There were three documented complications, one pneumonia after LC and two wound infections after OC. CONCLUSIONS: LC gives significantly better results in terms of less postoperative pain, better pulmonary function, better arterial oxygenation, and shorter hospital stay and duration of sick leave.

Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2alpha in cutaneous melanoma.

The loss of transcription factor AP-2alpha expression has been shown to associate with tumourigenicity of melanoma cell lines and poor prognosis in primary cutaneous melanoma. Altogether these findings suggest that the gene encoding AP-2alpha (TFAP2A) acts as a tumour suppressor in melanoma. To learn more of AP-2alpha's down-regulation mechanisms, we compared the immunohistochemical AP-2alpha protein expression patterns with the corresponding mRNA expression detected by in situ hybridization in 52 primary melanomas. Of the 25 samples with AP-2alpha protein negative areas, 16 (64%) expressed mRNA throughout the consecutive section. Nine specimens (36%) contained equally mRNA- and protein-negative areas, suggesting that the loss of AP-2alpha protein associated with lack of the mRNA transcript. The highly AP-2alpha protein-positive tumours (n = 27) were concordantly mRNA positive in 25 (92.6%) cases. Thirteen primary tumours were further analysed using microsatellite markers D6S470 and D6S263 for loss of heterozygosity (LOH) of a locus harbouring TFAP2A. LOHs or chromosome 6 monosomy were found in four out of five (80%) informative AP-2alpha mRNA- and protein-negative tumour areas, but also within five out of 13 (38%) informative AP-2alpha mRNA-positive tumour areas. This chromosome region is thus suggestive of harbouring a putative tumour suppressor gene of cutaneous melanoma, but this referring specifically to TFAP2A could not be completely verified in this analysis. We conclude that a failure in post-transcriptional processing of AP-2alpha is a possible inactivation mechanism of AP-2alpha in cutaneous melanoma.

Gastric tonometry in assessing splanchnic tissue perfusion in acute pancreatitis.

BACKGROUND: Hypovolemia is typical early in acute pancreatitis. Despite fluid resuscitation splanchnic hypoperfusion may be present and may have a role in the course of pancreatitis. To test this hypothesis, we assessed gastric mucosal pH (pHi) and P(CO)2 during the first 48 h of hospitalization for acute pancreatitis. METHODS: Thirty-three patients were studied. A gastric tonometer was inserted on admission, and gastric mucosal pH and P(CO)2 were measured on admission and then every 12 h during next 48 h. RESULTS: On the basis of the Atlanta classification there were 22 cases of mild and 8 of severe pancreatitis. Three patients were excluded because of consent withdrawal. The groups were similar with regard to age, sex ratio, and etiology of pancreatitis. Independently of disease severity the gastric pHi decreased, and the gastric mucosal-arterial P(CO)2 difference and pH difference both increased over time as compared with base line. No difference was seen in these values between mild and severe pancreatitis. CONCLUSIONS: Moderate gastric mucosal hypoperfusion was found early in acute pancreatitis. However, gastric pHi measurement with tonometry has no obvious value as a screening tool to assess the severity of pancreatitis.

Expression of inducible nitric oxide synthase in colorectal cancer and its association with prognosis.

BACKGROUND: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. METHODS: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. RESULTS: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. CONCLUSIONS: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.

Gut permeability in patients with acute pancreatitis.

BACKGROUND: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. Increased gut permeability may be the initial phenomenon in this process. To test the hypothesis that gut permeability is increased in acute pancreatitis a clinical study was made where gut absorption and permeability were assessed with multi-sugar probes in patients with acute pancreatitis within 2 days after admission to hospital and again after recovery of disease. METHODS AND RESULTS: Twenty-three patients with acute pancreatitis and 20 healthy controls were studied. According to Atlanta classification, 15 patients had mild and 8 patients severe pancreatitis. Gut absorption, assessed as the 5-h urine excretion of L-rhamnose, D-xylose and 3-O-methylglucose, was decreased in patients with acute pancreatitis and more pronounced in patients with severe pancreatitis (L-rhamnose and D-xylose: P < 0.001; 3-O-methylglucose: P < 0.05). Gut permeability, assessed as the ratio of lactulose/L-rhamnose, was increased in severe pancreatitis (0.16 +/- 0.13, 0.07 +/- 0.03, 0.04 +/- 0.04; severe pancreatitis, mild pancreatitis, controls, respectively; P < 0.001 between three groups, P < 0.05 between pancreatitis groups). CONCLUSIONS: Gut absorption capacity is decreased and gut permeability is increased in patients with acute pancreatitis. Patients with severe pancreatitis may be more exposed to impaired gut barrier function.

p22/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis.

p21/WAF1 expression was studied in a series of 162 colorectal carcinoma patients and its relation to p53- and activator protein (AP)-2 expressions and to stage as well as survival was assessed. p21 expression was moderate or intense in 33% of the tumours, and 53% of the tumours had moderate or strong p53 staining intensity. Eighty-nine percent of the tumours showed a weak cytoplasmic AP-2 signal. As expected, p21 and p53 stainings were inversely related to each other (P < 0.001). There was a significant positive association between p21 and AP-2 expression levels (P= 0.01). p21 intensity and percentage were higher in Dukes' A and B stages (P< 0.001). The cancer-related survival and recurrence-free survival (RFS) rates were significantly lower among patients with a low signal for p21 (P< 0.001) and low p21 percentage in tumour epithelium (P < 0.001). High p53 staining intensity in tumour epithelium predicted poor survival (P = 0.01) and RFS (P = 0.003). In the multivariate analysis, p21 percentage distribution independently predicted cancer-related survival in all cases, and p21 expression intensity in T1-4/N0-3/M0 and T1-3/N0/M0 cases. p21 percentage distribution was an independent predictor of RFS in all and T1-3/N0/M0 cases. AP-2 staining did not reach any prognostic significance. These results suggest that the immunohistochemical detection of cyclin-dependent kinase inhibitor p21 could be used to predict more precisely the outcome of colorectal cancer patients.

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma.

AIMS: To investigate alpha catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. METHODS: Immunohistochemistry was used to compare the expression of alpha catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of alpha catenin and its distribution in cancer cells is correlated with survival was tested with the long-rank test, hazard ratios, and their confidence intervals. RESULTS: Uniform membranous alpha catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative alpha catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak alpha catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of alpha catenin (p < 0.001). In multivariate analysis, the intensity of alpha catenin expression in tumour epithelium predicted cancer related survival independently; alpha catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. CONCLUSIONS: A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of alpha catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that alpha catenin has prognostic significance in colorectal cancer.

Splanchnic tissue perfusion in acute experimental pancreatitis.

BACKGROUND: Gut hypoperfusion may have a role in the pathogenesis of multiple organ failure, which is a the main cause of death in severe acute pancreatitis. We hypothesized that gut hypoperfusion is present early in acute pancreatitis and that supporting the systemic hemodynamics by fluid resuscitation would prevent this. METHODS: In a pig model of randomized, controlled experimental hemorrhagic pancreatitis induced by Na-taurocholate the animals were divided into four groups (n = 6 for each): 1) pancreatitis, 2) control, 3) pancreatitis and fluid resuscitation to keep the pulmonary capillary wedge pressure at 5 to 6 mmHg, and 4) control and fluid resuscitation as in group 3. Splanchnic perfusion was assessed by means of local PCO2 gap with intestinal tonometer, oxygen delivery and consumption, lactate production, and blood flow. The follow-up time was 6 h. RESULTS: The Pco2 gap increased in pancreatitis (1.72+/-0.17, 1.94+/-0.29, 1.75+/-0.22, 2.32+/-0.33; 9.40+/-2.16, 3.72+/-1.78, 0.84+/-0.39, 1.11+/-0.21 kPa, respectively; P < 0.05). Oxygen delivery in portal-drained organs decreased in pancreatitis (2.5+/-0.3, 2.6+/-0.2, 2.8+/-0.4, 2.3+/-0.2; 1.7+/-0.3, 2.3+/-0.3, 2.4+/-0.5, 2.3+/-0.3 ml/min x kg, respectively; P < 0.05). Regional oxygen consumption did not change. Arterial plasma lactate increased (1.20+/-0.19, 1.33+/-0.16, 1.14+/-0.15, 1.43+/-0.33; 3.81+/-1.31, 1.48+/-0.48, 1.12+/-0.18, 1.18+/-0.35 mmol/l, respectively; P < 0.05). The portal venous blood flow decreased 50% in pancreatitis, but with fluid resuscitation it increased 50%. CONCLUSIONS: Splanchnic hypoperfusion is present early in acute hemorrhagic pancreatitis. The signs of hypoperfusion can be prevented with fluid resuscitation.

Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate.

Hyaluronan (HA), an extracellular high-molecular-mass polysaccharide, is supposed to be involved in the growth and progression of malignant tumours. We studied the cellular expression of HA in 215 operated stage I-IV gastric cancer patients using a specific biotinylated probe. Most (93%) of the tumours showed HA staining in their parenchyma, whereas the stroma inside and around the tumour was stained in every case. When HA expression was compared with the clinical and histological features of the tumours, a strong staining intensity in the tumour parenchyma was found to be associated with deep tumour invasion (pT3 or 4) and with mixed type of Laurén. A high proportion of HA-positive cells of all neoplastic cells was significantly associated with deep tumour invasion, nodal metastasis, positive lymphatic invasion, poor differentiation grade, as well as with inferior prognosis in univariate survival analysis. However, in multivariate analysis, only pT, pN, and vascular and lymphatic invasion emerged as independent predictors of survival in gastric cancer. The results indicate that ectopic HA expression is a frequent feature of gastric adenocarcinoma, and is associated with tumour progression and poor survival rate.

p21(WAF1/CIP1) expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival.

The expression of p21, p53 and proliferating cell nuclear antigen (PCNA) was analysed by immunohistochemistry in a consecutive series of 369 clinical stage I cutaneous malignant melanoma patients. Correlation of the detected expression levels with each other, with clinicopathological data and with melanoma survival were statistically evaluated. p21 expression was significantly associated with p53 and PCNA expression levels. In addition, high levels of p53 and PCNA were significantly interrelated. Tumour thickness, recurrent disease, high TNM category and older (> or = 55 years) age at diagnosis were inversely associated with p21 expression. Gender, bleeding, tumour thickness, Clark's level of invasion, TNM category and p53 index were all important predictors of both recurrence-free and overall survival of melanoma. In Cox's multivariate analysis including 164 patients with a complete set of data, only high tumour thickness and bleeding predicted poor recurrence-free survival (P = 0.0042 and 0.0087 respectively) or overall survival (P = 0.0147 and 0.0033 respectively). Even though elevated p21 expression may be associated with more favourable prognosis in clinical stage I cutaneous melanoma, our results suggest that cell cycle regulatory effects of p21 can be overcome by some other and stronger, partly yet unknown, mechanisms.

Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma.

PURPOSE: The transcription factor, activator protein (AP)-2, a 52-kd DNA-binding protein, is suggested to inhibit tumor growth through the activation of p21. To test this hypothesis, we analyzed AP-2 and p21 protein expressions in stage I cutaneous malignant melanomas to clarify their significance with regard to tumor progression and survival. PATIENTS AND METHODS: A consecutive series of 369 clinical stage I cutaneous malignant melanoma patients were investigated using immunohistochemistry. The detected expression levels were correlated with each other, with clinicopathologic data, and with melanoma survival. RESULTS: The loss of AP-2 expression was significantly associated with low p21 expression (P=.007), high tumor thickness (P=.001), high Clark's level (P=.046), high tumor-node-metastasis (TNM) category (P=.006), recurrent disease (P=.001), and male sex (P=.03). Tumor thickness, Clark's level, TNM category, bleeding, AP-2 index, and sex were all important predictors of both recurrence-free survival (RFS) and overall survival (OS) of melanoma in this order. In Cox's multivariate analysis, high tumor thickness (P=.0001), low AP-2 index (P=.0153), and bleeding (P=.0143) predicted poor RFS. Poor OS was predicted by high tumor thickness (P=.0008) and bleeding (P=.0092). CONCLUSION: The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma.

Mitotic rate and S-phase fraction as prognostic factors in stage I cutaneous malignant melanoma.

Clinical data from 369 patients with clinical stage I cutaneous malignant melanoma treated in Kuopio University Hospital district between 1974 and 1989 with a mean follow-up of 6.4 years were analysed. Clinical parameters, histology, DNA index, S-phase fraction (SPF) and mitotic indices [mitotic activity index (MAI) and volume-corrected mitotic index (M/V index)] were correlated with the outcome of the disease to establish their value as predictors of stage I cutaneous malignant melanoma. In univariate survival analyses, bleeding, gender, tumour thickness, level of invasion according to Clark, TNM category, MAI, M/V index and SPF were the most significant predictors of recurrence-free (RFS) and overall survival. In Cox's multivariate analysis, tumour thickness (P = 0.0021), bleeding (P = 0.0106) and M/V index (P = 0.0058) predicted poor RFS in the 259 patients available for the analysis. Poor overall survival was predicted by MAI (P = 0.0002), bleeding (P = 0.004), SPF (P = 0.009) and male gender (P = 0.034). The present results indicate that mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and S-phase fraction (SPF) are important prognostic factors in addition to the well-established Breslow thickness in stage I cutaneous malignant melanoma.

Lipid peroxidation products and antioxidant capacity in portal venous and systemic arterial plasma during gradual intestinal ischemia and reperfusion in pigs.

Intestinal ischemia may evoke an inflammatory response and eventually multiple organ failure. We investigated whether intestinal ischemic injury induces systemic lipid peroxidation and changes in the plasma antioxidant capacity in a pig model. Together with cardiovascular parameters, arterial and portal venous blood of 7 pigs were measured for thiobarbituric acid-reactive material diene conjugates, fluorescent chromolipids and plasma antioxidant capacity during graded occlusion of superior mesenteric artery and reperfusion. Plasma levels of lipid peroxidation products did not change significantly during graded ischemia and reperfusion. Portal venous plasma antioxidant capacity increased slightly during reperfusion (from 96.16 +/- to 3.91 to 142.49 +/- 12.01 mumol/l, p < 0.05). Although elevated levels of free radical reaction products have been found in ischemia-reperfusion, we found no evidence of systemic lipid peroxidation in our intestinal ischemia model.