Blood Transfusions in Major Pancreatic Surgery: A 10-Year Cohort Study Including 1404 Patients Undergoing Pancreatic Resections in Finland.

BACKGROUND: Despite guidelines on blood transfusion (TF) thresholds, there seems to be great variation in transfusion policies between hospitals and surgeons. In order to improve and unify blood transfusion policies, the Finnish Red Cross Blood Service carried out a project concerning the optimal use of blood products (Verivalmisteiden optimaalinen käyttö) between 2002 and 2011. In this study, we determined the blood transfusion trends in major pancreatic surgery in Finland. METHODS: Initially, 1337 patients who underwent major pancreatic resections between 2002 and 2011 were classified into the TF+ or TF- groups. Centers were divided into high-, medium-, and low-volume centers. The blood transfusion trends and the trigger points for blood transfusions in these patients were determined. RESULTS: There were no differences between high-, medium- and low-volume centers in blood usage, trigger points or the use of reserved blood units after pancreatoduodenectomy or total pancreatectomy. However, the trigger points were lowered significantly during the study period at high-volume centers (p = 0.003), and a better use of reserved blood units was found in high- (p < 0.001) and medium-volume (p = 0.043) centers. In addition, a better use of reserved blood units was found in high-volume centers after distal pancreatectomy (p = 0.020). CONCLUSION: Although only minor changes in blood transfusion trends after pancreatoduodenectomy or total pancreatectomy were found generally, the lowering of the transfusion trigger point and the best use of reserved blood units during the study period occurred in high-volume centers.

Strong claudin 5 expression is a poor prognostic sign in pancreatic adenocarcinoma.

We investigated the expression of claudin 5 in 88 ductal adenocarcinomas of the pancreas. The results were correlated with patient prognosis, with claudin 5 expression in blood vessels, with the expression level of bcl2 and bax and with apoptosis. Claudin 5 expression was detected in 24 (38%) cases. It was not associated with tumour size or spread, but strong claudin 5 expression correlated with a worse survival (p = 0.005). Claudin 5 also associated with a higher extent of apoptosis and greater expression of bax protein. In the tumour vasculature, some vessels displayed a loss of claudin 5 expression. The presence of this loss was associated with tumour grade and the presence of nodal metastases (p = 0.02, p = 0.022, respectively). These results indicate that claudin 5 is upregulated in a proportion of pancreatic ductal adenocarcinomas. The association of strong claudin 5 expression with a worse survival is in line with some earlier reports indicating that this protein is involved with increased locomotion and more aggressive spread of carcinomas. The association of claudin 5 with apoptosis and bax might be due to stronger cellular kinetics found in such tumours. The loss of claudin 5 expression in the tumour vasculature points to a leaky vessel type; this might also ease the access of tumours to vessels and be reflected in its association with the presence of nodal metastases.

Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma.

The aim of this study was to investigate the expression of Nrf2, sulfiredoxin and DJ1 in pancreatic cancer. The expression of Nrf2, sulfiredoxin and DJ1 was studied immunohistochemically in a large set of pancreatic adenocarcinomas consisting of 103 cases. Eighty six percent of the cases showed cytoplasmic Nrf2 and 24% nuclear Nrf2 positivity. Sulfiredoxin positivity was observed in 54% and DJ1 positivity in all cases. Nuclear Nrf2 positivity had an association with sulfiredoxin (p=0.019) and was associated with a poor survival (p=0.010). Stage IV tumors tended to have a more nuclear Nrf2 expression (p=0.080). DJ1 expression was more often found in well-differentiated tumors (p=0.012), and DJ1 expression was associated with better survival (p=0.020). According to the results, nuclear Nrf2 expression predicts a worse survival in pancreatic adenocarcinoma, which is in keeping with its protection of cells against oxidative or xenobiotic stress. In accordance with Nrf2's regulation of the synthesis of sulfiredoxin, there was an association between them (p=0.019). DJ1 had no association with Nrf2, and its expression predicted a better survival of patients.

Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma: association with features of differentiation.

AIM: This study was undertaken to evaluate the expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma. METHODS AND RESULTS: Material tested included 111 operated samples and 47 additional biopsy samples consisting of 26 cases of pancreatitis, 3 cases of pancreatic intraepithelial neoplasia and 18 ductal adenocarcinomas. Samples were stained with antibodies to claudins 7 and 18 and analysed for membranous and cytoplasmic expression. Membrane bound claudin 7 and 18 expression was detected in 62 of 105 (59%) and 78 of 111 (70%) cases, respectively. Membrane bound claudin 7 and 18 were associated with large or intermediate neoplastic ducts (p=0.01, p=0.002, respectively). Well differentiated pancreatic adenocarcinomas displayed more cases with membrane bound claudin 7 or 18 immunopositivity (p=0.003, p=0.03, respectively). All pancreatic intraepithelial neoplasias studied expressed membrane bound claudin 18. Membrane bound claudin 7 or 18 positivity was not associated with survival (p=0.17, p=0.98). In the biopsy cases membrane bound claudin 18 had 100% specificity and 51% sensitivity for a tumour marker. CONCLUSION: Claudin 7 and 18 expression is related to gland size of neoplastic cells and is especially found in tumours with intermediate and large ducts and well differentiated tumours. Membrane bound claudin 18, when present, is a useful marker for diagnosis of pancreatic cancer. Claudins 7 and 18 were not associated with patient survival or spread of tumours.

Feasibility of minilaparotomy versus laparoscopic cholecystectomy for day surgery: a prospective randomised study.

BACKGROUND AND AIMS: minilaparotomy (MC) and laparoscopic cholecystectomy (LC) are commonly applied surgical techniques in the management of symptomatic gallstone disease. Both techniques are used in day surgery patients, but to our knowledge MC and LC have not been compared in randomised trials as day surgery procedures. MATERIAL AND METHODS: in this randomised parallel group clinical trial we compared the suc-cess rate of day surgery of MC with that of LC in 60 consecutive patients with non-complicated symptomatic gallstones presented for elective surgery at the Kuusankoski District Hospital (n = 38) and the Kuopio University Hospital (n = 22). Twenty nine patients underwent MC and 31 LC. The patients' outcome was recorded up to four weeks after the operation. RESULTS: the success rate as a day surgery for MC was 66% (19/29) and that for LC 55% (17/31) with no difference between the two groups. Chronic cholecystitis, postoperative nausea and vomiting were significant variables associated with failure in day surgery. There was no difference between the two groups in operation time, perioperative bleeding, conversion to conventional open cholecystectomy (one with MC and three with LC), length of hospital stay or sick leave. Three patients developed superficial infection (two with MC and one with LC). One patient with conversion in the LC-group developed a common bile duct stricture and was readmitted at the 10th postoperative day. DISCUSSION: both MC and LC are feasible surgical techniques for day surgery. However, appropriate prevention and prompt management of established postoperative nausea and vomit-ing and careful patient selection are important aspects for success of short-stay approach. If there is a sign of chronic cholecystitis preoperatively, it might be considered as a contraindication for day surgery.

Minilaparotomy cholecystectomy as a day surgery procedure: a prospective clinical pilot study.

BACKGROUND AND AIMS: In some studies minilaparotomy cholecystectomy (MC) has been shown to be as good as laparoscopic cholecystectomy (LC) in the surgical treatment of cholecystolithiasis. To our knowledge, the MC operation is rarely considered as a day surgery procedure. PATIENTS AND METHODS: Thirty elective symptomatic non-complicated patients were included in the study during the end of the year 2004 to June 2005. The mean age of patients was 52 years (range 27-68), the mean body mass index 29 kg/m2 (range 19-41). Gallstones were confirmed with ultrasound and the preoperative liver laboratory tests were normal in all patients. A five (+/-2) centimetre-long incision was used avoiding to split the rectus abdominis muscle. All patients were re-evaluated four weeks postoperatively with the follow-up letter. RESULTS: The average operating time was 51 minutes (range 30-105 minutes). Day surgery was possible in 25 cases (83%). Five patients (17%) stayed over night at the hospital. There were four (13%) conversions to conventional cholecystectomy. The average postoperative sick leave was 16 days (range 14-30). Two patients returned to hospital. One patient had wound pain, but no complication was found, and the patient was not admitted. One patient had a wound infection and spent 6 days in the hospital. Twenty-nine (97%) patients were satisfied with the operation and were ready to recommend it for other patients. CONCLUSIONS: The results of this study support the suitability of MC as a day surgery procedure, but a prospective randomised trial is needed to evaluate the relative advantages of MC and LC.

Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized study with special reference to obesity.

BACKGROUND: Minilaparotomy cholecystectomy (MC) has recently challenged the role of the laparoscopic approach (LC) for cholecystectomies. However, the situation is far from clear when operating times and recovery are evaluated. METHODS: Altogether 157 patients with uncomplicated symptomatic gallstones were randomized into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of age, body mass index, American Society of Anesthesiology (ASA) physical fitness classification, and operating surgeon. RESULTS: The mean operating time was 55 +/- 19.5 min in the MC group and 79 +/- 27.0 min in the LC group (p < 0.0001). The postoperative hospital stay and length of sick leave did not differ between the two groups. There were no significant differences in postoperative pain, analgesic consumption, or postoperative pulmonary function between the groups. The body mass index did not influence operating time or patient recovery in either group. No major complications occurred in either groups. CONCLUSION: The MC procedure seems to be a faster technique than the LC approach for noncomplicated gallstone disease, with no difference in recovery times. The MC procedure also seems to be suitable for the obese patient.

The effect of fibrin sealant combined with fibrinolysis inhibitor on reducing the amount of lymphatic leakage after axillary evacuation in breast cancer. A prospective randomized clinical trial.

BACKGROUND AND AIMS: One third of women undergoing mastectomy with axillary evacuation for primary breast cancer suffer from postoperative seromas leading to unnecessary costs and complications such as infections and new operations. Different methods to prevent seroma formation have been tried without permanent success. The aim of this prospective randomised study was to examine the effect of fibrin sealant with fibrinolysis inhibitor firstly on the reduction of the amount of lymphatic leakage after axillary evacuation and secondly on the reduction of days with drains and postoperative seroma punctures. METHODS: 40 patients with primary breast cancer were prospectively randomised to the treatment group (n = 19) getting fibrin glue combined with fibrinolysis inhibitor (aprotinin) sprayed into the axillary fossa and to the control group (n = 21). RESULTS: There were no differences in the incidence of postoperative seromas between the groups. However, the seromas were easier to treat if fibrin clue was used. Total quantity (mean+/-SD) of lymphorrhea and total number of aspirations (mean+/-SD) were almost twice as high in the patients of the control group compared to those having fibrin sealant. In the treatment group seromas resolved after one or occasionally after two aspirations in 71 % of patients, while in the control group 90 % of patients needed three or more aspirations. CONCLUSION: Potentially, fibrin sealant combined with fibrinolysis inhibitor might be used for the treatment of post- axillary evacuation lymphorrhea and seroma.

Expression of HER2 and its association with AP-2 in breast cancer.

The aim of the study was to investigate the relationship between the expression of human epidermal growth factor receptor 2 (HER2) and activator protein 2 (AP-2), as well as the prognostic significance of HER2 in breast cancer. HER2 and AP-2 expressions were immunohistochemically (IHC) analysed in a large prospective, consecutive series of 425 breast cancer patients diagnosed and treated between 1990 and 1995 at the Kuopio University Hospital, Kuopio, Finland. In a subset of patients (n = 71), the gene amplification status was examined by using a chromogenic in situ hybridisation (CISH) analysis. Expression of HER2 was studied in relation to AP-2, clinicopathological parameters and patients' survival. Pathological membranous overexpression of the HER2 receptor was seen in 13% of the carcinomas, which was related both to gene amplification (78% of the cases) and high nuclear expression of AP-2 (67%, P = 0.007). HER2-positivity was most often seen in carcinomas having both high nuclear and high cytoplasmic AP-2 expression (P < 0.001). In the univariate survival analyses HER2-positivity predicted a shorter recurrence-free survival (RFS) (P < 0.0001) and a shorter breast cancer-related survival (BCRS) (P = 0.0063) in the whole patient group, as well as in the subgroup of node-negative patients. In the node-positive patients, HER2-positivity predicted only a shorter RFS. Combined expression of HER2 and nuclear AP-2 resulted in the separation of four groups with different prognoses, the best prognosis being for patients in the HER2-/AP-2+ group and the worse prognosis for those in the HER2+/AP-2- group. In the multivariate survival analyses, HER2-positivity independently predicted a shorter RFS in the whole patient group (P = 0.0067), as well as in the subgroup of node-positive patients (P = 0.0209). In conclusion, pathological membranous overexpression of the HER2 receptor in breast cancer is related both to gene amplification and a high AP-2 expression. Combining HER2 and AP-2 expressions may provide valuable information on the prognosis of breast cancer patients.

Preoperative serum levels of follicle stimulating hormone (FSH) and prognosis in invasive breast cancer.

AIMS: We investigated the association between preoperative serum levels of follicle stimulating hormone (FSH) and the prognosis in women with invasive breast cancer. METHODS: Serum levels of FSH were measured in 182 premenopausal and 581 peri- or postmenopausal women with invasive breast cancer. They were followed for a mean time of 84 months. The study endpoint was death from breast cancer (182 events). Analyses were stratified on menopausal status. RESULTS: None of the estimates showed a statistically significant result. In both pre- and postmenopausal women there was a nominally higher probability of survival with a higher FSH level. Point estimates in multivariate analysis incorporating age, tumour diameter, axillary lymph status, estrogen and progesterone receptor content and year of treatment indicated a stronger association with FSH levels in premenopausal than postmenopausal women (relative hazard 0.63 or 0.85, respectively in the highest compared with the lowest quartile). CONCLUSION: We did not find any statistically significant association between preoperative serum level of FSH and prognosis. Today, FSH is not a clinical target for intervention or a clinically useful prognostic factor and the results of clinical studies up to date can only be used for motivation of further experimental laboratory research.

p21WAF1 expression in invasive breast cancer and its association with p53, AP-2, cell proliferation, and prognosis.

AIMS: To evaluate the expression and prognostic relevance of p21(WAF1) in breast cancer and to investigate its association with p53, activator protein 2 (AP-2), and cell proliferation (as assessed by Ki-67 expression). METHODS: p21(WAF1) expression was analysed immunohistochemically in a large prospective, consecutive series of 420 patients with breast cancer diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. Inter-relations between p21(WAF1) expression and p53, AP-2, and Ki-67 were evaluated. The expression of p21(WAF1) was also compared with clinicopathological parameters and the patients' survival. RESULTS: In general, nuclear p21(WAF1) expression was low in carcinomas (median, 2.5%; range, 0-70%). Expression was lowest in lobular carcinomas (chi(2) = 7.4; p = 0.025). p21(WAF1) positive tumours were more often p53 positive (chi(2) = 4.2; p = 0.041) but expression of p21(WAF1) did not correlate with AP-2 expression or Ki-67 in the whole patient group. In addition, the combined expression of p21 and p53 was not associated with AP-2 expression. High nuclear p21(WAF1) positivity (n = 160; 38%) was associated with poor differentiation (chi(2) = 8.1; p = 0.017). In the univariate analyses, p21(WAF1) expression had no prognostic value for predicting breast cancer related survival (BCRS) or recurrence free survival (RFS) in the whole patient group or in the subgroups investigated. However, in postmenopausal patients with lymph node metastases, and oestrogen receptor (ER) and/or progesterone receptor (PR) positive tumours, high p21(WAF1) expression predicted response to adjuvant hormonal treatment with antioestrogens. In the univariate analysis, the significant factors for predicting BCRS were Ki-67 expression, stage, lymph node status, histological grade, ER and PR status, and those for RFS were Ki-67 expression, stage, and lymph node status. In the multivariate analysis, the independent predictors of shorter BCRS were high cell proliferation activity measured by Ki-67 expression (p < 0.001), advanced stage (p < 0.001), and poor differentiation (p = 0.048). Shorter RFS was independently predicted by high cell proliferative activity (p < 0.001) and advanced stage (p < 0.001). CONCLUSIONS: The regulation of p21(WAF1) seems to occur independently of p53 or AP-2 and analysing p21(WAF1) expression provided no prognostic information for patients with breast cancer.

Polymorphic catechol-O-methyltransferase gene and breast cancer risk.

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genotype in individual susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for breast cancer. When studied separately by menopausal status, the COMT-L allele-containing genotypes were inversely associated with premenopausal breast cancer, especially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22-0.87). Among postmenopausal women a similar decreased risk was seen for local carcinoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31-0.98). The lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index (30 months) use of estrogen (OR, 4.02; 95% CI, 1.13-14.3), or with the COMT-L allele-containing genotypes and early age (

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.

Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer.

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.

Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk.

Superoxide dismutases play a key role in the detoxification of superoxide radicals and thus protect cells from damage induced by free radicals. Within mitochondria manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species. Polymorphism in the mitochondrial targeting sequence of MnSOD has recently been associated with risk of breast cancer. We examined this in a study population consisting of 483 breast cancer cases and 482 controls, all of Finnish Caucasian origin. Odds ratios (OR) and 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression. MnSOD genotypes containing the variant A allele were found to be associated with a 1.5-fold (95% CI 1.1-2.0) increased risk of breast cancer compared with those with the homozygous wild-type genotype (MnSOD VV). This finding supports the proposal that MnSOD genotypes may modify individual breast cancer risk.

Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer.

AIMS: To study the controversial role of transmembrane glycoprotein CD44 as a moderator of tumour spread and as a prognostic factor in gastric cancer. METHODS AND RESULTS: The expression of all CD44 forms and that with exon v3 was assessed in 198 stage I-IV gastric adenocarcinomas using immunohistochemistry. CD44 expression was found in 72% and CD44v3 in 55% of the cases. The intensity of CD44 expression was associated with the level of invasion and with hyaluronan expression, while the frequency of CD44 positive cells was not significantly related to any of the clinical or histological features of the tumours. CD44v3 expression failed to show any association with the clinical or histological variables examined. Neither total CD44 nor CD44v3 expression affected survival. The most important prognostic factors in this cohort were the level of invasion, lymph node status, tumour size and vascular or perineural invasion. CONCLUSIONS: Changes in CD44 or CD44v3 expression level do not predict tumour spread or patient survival in gastric cancer.

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.

GPs' ability to diagnose dyspepsia based only on physical examination and patient history.

OBJECTIVES: To evaluate the diagnostic value of the general practitioner's (GP's) unaided working diagnoses in dyspepsia. To compare the proportions of final diagnoses and the characteristics of patients who would have been referred to gastroscopy or to empirical drug treatment. DESIGN: Clinical study. PATIENTS: 400 consecutive dyspeptic patients consulting their GPs. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive and negative predictive values (PV+ and PV-) were calculated for the GP's working diagnoses in cases of dyspepsia. The outcome of his/her decisions on how to manage dyspeptic patients was also evaluated. RESULTS: Gastroesophageal reflux disease would have been diagnosed accurately, with a sensitivity of 0.59, specificity 0.83, PV+ 0.43 and PV- 0.90. GPs diagnosed functional disorders with a sensitivity of 0.43, specificity 0.69, PV+ 0.56 and PV- 0.54; peptic ulcer with a sensitivity of 0.37, specificity 0.83, PV+ 0.28 and PV- 0.88; and malignancy with a sensitivity of 0.13, specificity 0.97, PV+ 0.08 and PV- 0.98. Patients who would have been referred to gastroscopy had more often lost weight (p = 0.01), suffered from abdominal pain (p=0.03) and from symptoms partly suggesting irritable bowel syndrome (p< or =0.03). CONCLUSIONS: The clinical diagnosis of the causes of dyspepsia is unreliable. In selecting patients for gastroscopy, more attention should be paid to risk factors such as age, use of non-steroidal anti-inflammatory drugs and history of previous peptic ulcer.

Effect of EEG electrode density on dipole localization accuracy using two realistically shaped skull resistivity models.

The effect of number of EEG electrodes on the dipole localization was studied by comparing the results obtained using the 10-20 and 10-10 electrode systems. Two anatomically detailed models with resistivity values of 177.6 omega m and 67.0 omega m for the skull were applied. Simulated potential values generated by current dipoles were applied to different combinations of the volume conductors and electrode systems. High and low resistivity models differed slightly in favour of the lower skull resistivity model when dipole localization was based on noiseless data. The localization errors were approximately three times larger using low resistivity model for generating the potentials, but applying high resistivity model for the inverse solution. The difference between the two electrode systems was minor in favour of the 10-10 electrode system when simulated, noiseless potentials were used. In the presence of noise the dipole localization algorithm operated more accurately using the denser electrode system. In conclusion, increasing the number of recording electrodes seems to improve the localization accuracy in the presence of noise. The absolute skull resistivity value also affects the accuracy, but using an incorrect value in modelling calculations seems to be the most serious source of error.