Petri Juvonen

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 Nrf2s 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.

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

BackgroundMinilaparotomy 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.MethodsAltogether 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.ResultsThe 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.ConclusionThe 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.

Randomized Multicenter Trial Comparing Glue Fixation, Self-gripping Mesh, and Suture Fixation of Mesh in Lichtenstein Hernia Repair (FinnMesh Study).

OBJECTIVE Three different mesh fixation techniques were compared to find out how to perform a safe and cost-effective open inguinal hernioplasty in day-case setting with the best outcomes with regard to chronic pain. SUMMARY BACKGROUND DATA Mesh fixation method may influence on the incidence of chronic pain after Lichtenstein hernioplasty. METHODS Lichtenstein hernioplasty was performed under local anesthesia in 625 patients as day-case surgery in 8 Finnish hospitals. The patients were randomized to receive either a cyanoacrylate glue (Histoacryl, n = 216), self-gripping mesh (Parietex ProGrip, n = 202), or conventional nonabsorbable sutures (Prolene 2-0, n = 207) for mesh fixation. The incidence of wound complications, pain, recurrences, and patients discomfort was recorded on days 1, 7, 30, and 1 year after surgery. The primary endpoint was the sensation of pain measured by pain scores and the need of analgesics after 1 year of surgery. RESULTS The type and size of inguinal hernias were similar in the 3 study groups. The duration of operation was 34 ± 13, 32 ± 9, and 38 ± 9 minutes in the glue, self-gripping, and suture groups, respectively (P < 0.001). There were no significant differences postoperatively in pain response or need for analgesics between the study groups. Two superficial infections (0.3%), 31 wound seromas (5.0%), and 4 recurrent hernias (0.6%) were recorded during a 1-year follow-up. Some 25 patients (4.2%) needed occasionally analgesics for chronic groin pain. A feeling of a foreign object and quality of life were similar in all study groups. CONCLUSIONS This randomized trial failed to prove that mesh fixation without sutures causes less inguinodynia than suture fixation in Lichtenstein hernioplasty. Mesh fixation without sutures is feasible without compromising postoperative outcome.

Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

BackgroundStructural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus.MethodsA total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years) were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31); 70-79 years old (n = 38) and over 80 years old (n = 37). 53 young subjects (20-28 years old) were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1.ResultsFecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P < 0.001) and were significantly lower among subjects over 70 years old compared to controls (controls vs. 70-79 years old and controls vs. over 80 years old, both P < 0.001). Among the over 60 years old subjects, the fecal elastase-1 concentrations were below the cut off level of 200 μg/g in 23 of 106 (21.7%) individuals [mean 112 (86-138) μg/g] indicating pancreatic exocrine insufficiency. Of those, 9 subjects had fecal elastase-1 level below 100 μg/g as a marker of severe pancreatic insufficiency.ConclusionIn our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.

Impact of obesity and associated diseases on outcome after laparoscopic cholecystectomy.

Obesity is a risk factor for operative treatment. This study examined the impact of obesity and associated comorbidities on complications after laparoscopic cholecystectomy (LC). Altogether, 1581 consecutive patients with symptomatic gallstones underwent LC between the years 1995 and 2008. Preoperative data and operative outcome of the 437 obese patients [302 with body mass index (BMI) 30 to 35 kg/m2 and 135 with BMI≥35.1 kg/m2] and 1144 nonobese controls (BMI⩽29.9 kg/m2) undergoing LC were compared. The impact of obesity, diabetes, cholecystitis, coronary heart disease, pulmonary disease, hypertension, and renal insufficiency on the postoperative outcome was analyzed by using multiple logistic regression analysis. The percentage of obese patients undergoing LC did not change during the study period. Over half of obese patients (63%) had 1 or multiple comorbidities, but only 15% of the patients had an acute surgery because of cholecystitis. Conversion to open surgery was required in 11.7% of the obese patients compared with 6.1% in the nonobese controls (P=0.0003). Acute cholecystitis increased the conversions in class II and III obese patients (50%) compared with elective surgery (8.7%, P<0.001). Mortality rate was 0 in obese patients and the rate of complications, except surgical site infections, comparable with nonobese patients. In multivariate analysis, obesity or any of the comorbidities did not associate with an elevated risk for postoperative complications. In symptomatic gallstone disease, obesity and related comorbidities increased the conversion rate, but not the operative risks of LC.

Seasonal variations of acute appendicitis and nonspecific abdominal pain in Finland

AIM To investigate whether seasonal changes had an effect on the incidence of acute appendicitis (AA) or nonspecific abdominal pain (NSAP). METHODS We carried out a national register study of all patients with a hospital discharge diagnosis of AA and acute NSAP in Finland. Data were analyzed for the whole country and correlated to seasonal and weather parameters (temperature, humidity). Moreover, additional sub-analyses were performed for five geographically different area of Finland. RESULTS The observation period spanned 21 years, with 186558 appendectomies, of which 137528 (74%) cases were reported as AA. The incidence of AA declined for 32% over the study period. The average incidence of the NSAP was 34/10000 per year. The mean annual temperature, but not relative humidity, showed clear geographical variations. The incidence of AA decreased significantly during the cold months of the year. No correlation was detected between temperature and incidence of NSAP. Humidity had a statistically significant impact on NSAP. CONCLUSION The incidence of acute appendicitis is declining in Finland. We detected a clear seasonality in the incidence of AA and NSAP.

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.

Minilaparotomy cholecystectomy with ultrasonic dissection versus conventional laparoscopic cholecystectomy: a randomized multicenter study

Abstract Objective. Cholecystectomy by minilaparotomy (MC) or by laparoscopy (LC) has been shown to have equal results of both early and late recovery. Although, the ultrasonic dissection (UsD) technique has seen used in LC, the technique is rarely used in MC. Material and methods. Initially, 88 patients with uncomplicated symptomatic gallstones were randomized into MC with UsD (n = 44) or conventional LC (n = 44) over a 2-year period (2010–2012). The two groups were similar in terms of age and American Society of Anesthesiologists (ASA) physical status score. Results. Both groups were similar in terms of the operative time and the time in the operation theatre, the success of day-surgery and satisfaction with the procedure. The MC group had significantly less postoperative pain than the LC group, p = 0.002, and the MC group used less analgesics doses during the first 24 h: 2.8 (1.2) doses vs. 3.8 (1.4) doses, p = 0.003. The convalescence needed was 3 days shorter in the MC group, 7 (3) days, than that in the LC-group, 10 (8) days, p = 0.024. In the MC group 4 patients and in the LC group 11 (p = 0.046) required more than 14 days of sick leave. In the MC group there was one and in the LC group two conversions to open surgery. Conclusion. The patients in the MC group had less early postoperative pain and had a shorter convalescence than the patients in the LC group.

A prospective, randomized multicenter study comparing conventional laparoscopic cholecystectomy versus minilaparotomy cholecystectomy with ultrasonic dissection as day surgery procedure--1-year outcome.

Abstract Objective. The long-term outcome between laparoscopic cholecystectomy (LC) and minilaparotomy cholecystectomy (MC) with ultrasonic dissection (UsD) technique has not been compared in randomized trials. Therefore, we investigated the outcome after conventional LC and MC with UsD in 78 patients (ClinicalTrials.gov Identifier: NCT0172340). Material and methods. Initially 88 patients with non-complicated symptomatic gallstone disease were randomized into MC (n = 44) or LC (n = 44) over a period of 2 years (2010–2012) and 78 of them (89%) were reached for a follow-up interview at 12 months after the surgery. Results. Baseline parameters were similar in the two groups, and 1/44 MCs and 2/44 LCs were converted to open laparotomy. The prevalence of chronic post-surgical pain (CPSP) one year after the procedure was quite similar in the two groups: 3/36 (8%) in the MC group and 2/42 (5%) in the LC group (p = 0.502). Residual abdominal symptoms were common, but the proportion was similar in both groups (28% in MC and 33% in LC group, p = 0.665). Both groups were very satisfied with the cosmetic outcome (numeric rating scale, p = 0.470). The Quality of life (QoL) improved 34/36 (94%) in the MC group and 33/42 (79%) in the LC group (p = 0.046) and all patients in both groups were satisfied with the operation overall. Conclusion. Day-case MC and LC patients have a quite similar one-year outcome with no significant difference regarding residual abdominal symptoms, cosmetic satisfaction, QoL or CPSP.

A randomized multicenter study of minilaparotomy cholecystectomy versus laparoscopic cholecystectomy with ultrasonic dissection in both groups

Abstract Objective: Ultrasonic dissection (UsD) has been used in laparoscopic cholecystectomy (LC), though it is not the golden standard technique. Applying UsD to cholecystectomy by minilaparotomy (MC) is less common and there are no prospective randomized trials comparing these two techniques. Therefore, we conducted the present study to investigate the use of the UsD in the MC versus the LC procedure. Material and methods: Initially 104 patients with non-complicated symptomatic gallstone disease were randomized into MC (n = 53) or LC (n = 51) groups, both groups using UsD, over a period of 2 years (2013–2015). The study groups were similar in terms of age and American Society of Anesthesiologists (ASA) physical status score. Results: The demographic variables and the surgical data were similar in the study groups. Similar low postoperative pain scores were reported in the two study groups during the first four hours after surgery. The incidence of nausea/vomiting was similar between the two study groups, 47% in the MC group versus 42% in the LC group. However, the patients in the MC group were treated more frequently with antiemetics, the incidence being 39% in the MC group versus 21% in the LC group (p = 0.02). The pain at rest at 24h after the surgery was similar in the two study groups, but the LC patients reported less pain at the normal activity, the mean of numerical rating scale (NRS) of 0–10 score being 3.9 in the MC group versus 2.9 in the LC group (p = 0.05), and the pain at the quick movement/coughing, the mean NRS being 4.9 in the MC group versus 3.2 in the LC group (p = 0.005). The length of sick leave was 17.4 days in the MC group and 14.4 days in the LC group (p = 0.05). Conclusion: Our results suggest that both MC and LC are feasible and safe options for mini-invasive cholecystectomy. A new finding with clinical relevance in the present work is a relatively similar short-term outcome in the MC and LC althought the LC patients reported significantly lower pain score 24 hours postoperatively and a shorter convalescence.