Venous resection for pancreatic cancer, a safe and feasible option? A systematic review and meta-analysis.

BACKGROUND: In pancreatic ductal adenocarcinoma patients with suspected venous infiltration, a R0 resection is most of the time not possible without venous resection (VR). To investigate this special kind of patients, this meta-analysis was conducted to compare mortality, morbidity and long-term survival of pancreatic resections with (VR+) and without venous resection (VR-). METHODS: A systematic search was performed in Embase, Pubmed and Web of Science. Studies which compared over twenty patients with VR + to VR-for PDAC with ≥1 year follow up were included. Articles including arterial resections were excluded. Statistical analysis was performed with the random effect Mantel-Haenszel test and inversed variance method. Individual patient data was compared with the log-rank test. RESULTS: Following a review of 6403 papers by title and abstract and 166 by full text, a meta-analysis was conducted of 32 studies describing 2216 VR+ and 5380 VR-. There was significantly more post-pancreatectomy hemorrhage (6.5% vs. 5.6%), R1 resections (36.7% vs. 28.6%), N1 resections (70.3% vs. 66.8%) and tumors were significantly larger (34.6 mm vs. 32.8 mm) in patients with VR+. Of all VR + patients, 64.6% had true pathological venous infiltration. The 90-day mortality, individual patient data for overall survival and pooled multivariate hazard ratio for overall survival were similar. CONCLUSION: VR is a safe and feasible option in patients with pancreatic cancer and suspicion of venous involvement, since VR during pancreatic surgery has comparable overall survival and complication rates.

In the Era of the Leeds Protocol: A Systematic Review and A Meta-Analysis on the Effect of Resection Margins on Survival Among Pancreatic Ductal Adenocarcinoma Patients.

BACKGROUND AND AIMS: A positive resection margin is considered to be a factor associated with poor prognosis after pancreatic ductal adenocarcinoma resection. However, analysis of the resection margin is dependent on the pathological slicing technique. The aim of this systematic review and meta-analysis was to study the impact of resection margin on the survival of pancreatic ductal adenocarcinoma patients whose specimens were analyzed using the axial slicing technique. MATERIAL AND METHODS: A systematic search in the PubMed, Cochrane, and Embase datasets covering the time period from November 2006 to January 2019 was performed. Only studies with axial slicing technique (Leeds Pathology Protocol or Royal College of Pathology Protocol) were included in the final database. Meta-analysis between the marginal distance and survival was performed with the Inverse Variance Method in RevMan. RESULTS: The systematic search resulted in nine studies meeting the inclusion criteria. The median survival for a resection margin 0 mm ranged from 12.3 to 23.4 months, for resection margin <0.5 mm 16 months, for resection margin <1 mm ranged from 11 to 27.5 months, for resection margin <1.5 mm ranged from 16.9 to 21.2 months, and for resection margin >2 mm ranged from 53.9 to 63.1 months. Five studies were eligible for meta-analysis. The pooled multivariable hazard ratio favored resection margin ⩾1 mm (hazard ratio: 1.32 and 95% confidence interval: 1.03-1.68, p = 0.03). CONCLUSION: Resection margins ⩾1 mm seem to lead to better survival in pancreatic ductal adenocarcinoma patients than resection margin <1 mm. However, there is not enough data to evaluate the effect of oncologic therapy or to analyze the impact of other resection margin distances on survival.

Centralization of Pancreatic Surgery Improves Results: Review.

BACKGROUND AND AIMS: The effect of operation volume on the outcomes of pancreatic surgery has been a subject of research since the 1990s. In several countries around the world, this has led to the centralization of pancreatic surgery. However, controversy persists as to the benefits of centralization and what the optimal operation volume for pancreatic surgery actually is. This review summarizes the data on the effect of centralization on mortality, complications, hospital facilities used, and costs regarding pancreatic surgery. MATERIALS AND METHODS: A systematic librarian-assisted search was performed in PubMed covering the years from August 1999 to August 2019. All studies comparing results of open pancreatic resections from high- and low-volume centers were included. In total 44, published articles were analyzed. RESULTS: Studies used a variety of different criteria for high-volume and low-volume centers, which hampers the evaluating of the effect of operation volume. However, mortality in high-volume centers is consistently reported to be lower than in low-volume centers. In addition, failure to rescue critically ill patients is more common in low-volume centers. Cost-effectiveness has also been evaluated in the literature. Length of hospital stay in particular has been reported to be shorter in high-volume centers than in low-volume centers. CONCLUSION: The effect of centralization on the outcomes of pancreatic surgery has been under active research and the beneficial effect of it is associated especially with better short-term prognosis after surgery.

Pancreatic resections are not only safest but also most cost-effective when performed in a high-volume centre: A Finnish register study.

BACKGROUND: It is not known whether the treatment costs of pancreatic surgery can be reduced by centralisation. The aim of this study was to analyse the impact of hospital volume on the short-term prognosis and costs in a nationwide study. METHODS: The National registry was searched for patients undergoing pancreatoduodenectomy (PD) in Finland between 2012 and 2014. Patient data was recorded up to ninety days postoperatively and Charlson comorbidity index (CCI) calculated. Complications were classified according to Clavien-Dindo. A CCI was calculated for each patient. The hospitals were categorized by yearly resection rate: high (≥20, HVC), medium (6-19, MVC) and low (≤5, LVC). Costs were calculated according to the 2012 billing list. RESULTS: The study population comprised 466 patients. Demographics were similar in the HVC, MVC and LVC groups. Mortality was lower in the HVCs than in MVCs and LVCs at 30 days (0.8% vs. 8.8-12.9%; p < 0.01) and at 90 days (1.9% vs. 10.5-16.1%; p < 0.01). Hospital volume and CCI were significant factors for mortality in multivariate analysis. Median costs among all patients were lower in the HVC group than in the MVC/LVC groups (p = 0.019), among Clavien-Dindo class III (0.020), among patients over 75 years (p < 0.001) and among patients who survived over five days (p = 0.015). CONCLUSIONS: Thirty- and 90-day mortality is 10 times lower when the patient is operated on in an HVC. The study shows that the median overall costs of surgical treatment are 82-88% of the median costs in lower volume centres.

Management of postoperative complications may favour the centralization of distal pancreatectomies. Nationwide data on pancreatic distal resections in Finland 2012-2014.

BACKGROUND: Centralization of pancreatic surgery has proceeded in the last few years in many countries. However, information on the effect of hospital volume specifically on distal pancreatic resections (DP) is lacking. AIM: To investigate the effect of hospital volume on postoperative complications in DP patients in Finland. METHODS: All DP performed in Finland during the period 2012-2014 were analyzed, information having been retrieved from the appropriate national registers. Hospital volumes, postoperative pancreatic fistulae (POPF) and overall complications were graded. High volume centre (HVC) was defined as performing > 10 DPs, median volume centre (MVC) 4-9 DPs and low volume centre (LVC) fewer than 4 DP annually. RESULTS: A total of 194 DPs were performed at 18 different hospitals. Of these 42% (81) were performed in HVCs (2 hospitals), 43% (84) in MVCs (6 hospitals) and the remaining 15% (29) in LVCs (10 hospitals). Patient demographics did not differ between the hospital volume groups. The overall rate of clinically relevant POPF, Clavien-Dindo grade 3-5 complications, and 90-day mortality showed no significant differences between the different hospital volumes. Grade C POPF was found more often in LVCs, being 1.2% in HVCs, 0% in MCVs and 6.9% in LVCs, p = 0.030. More reoperations were performed in LVCs (10.3%) than in HVCs (1.2%) or MVCs (1.2%); p = 0.025. CONCLUSIONS: Even though the rate of postoperative complications after DP is not affected by hospital volume, reoperations were performed ten times more often in the low-volume centres. Optimal management of postoperative complications may favour centralization not only of PD, but also of DP.

Effect of centralization on long-term survival after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Centralization of pancreatic surgery has resulted in improved short-term outcomes in a number of healthcare systems. The aim of this study was to see whether hospital volume influenced long-term prognosis, use of adjuvant therapy or histopathological evaluation of patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical resection of PDAC in Finland between 2002 and 2008 were identified from national registers. Demographic, histopathological, operative and oncological data were recorded, and the histopathological slides of patients who survived for more than 4 years were reviewed. Operative volume was defined according to the annual rate of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who had undergone resectional surgery for PDAC at 22 centres were included. Patient demographics and resection types did not differ between centres. Thirty- and 90-day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus 5·5 per cent (P = 0·001) and 2·5 versus 11·0 per cent (P = 0·003) respectively. Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage IIB: 65·7 versus 40·6 per cent respectively; P < 0·001), but with no greater use of adjuvant therapy. Significantly more patients survived for 2 years (43·3 versus 29·7 per cent; P = 0·034) and 3 years (25·4 versus 14·1 per cent; P = 0·045) after surgery in HVCs than in LVCs. More information was missing in the histopathological reports from LVCs and MVCs than in those from HVCs (P ≤ 0·002). CONCLUSION: Both short- and long-term survival was significantly better for patients operated on in HVCs. Histopathological analysis appears to be more comprehensive in HVCs.

Effect of progressive high-impact exercise on femoral neck structural strength in postmenopausal women with mild knee osteoarthritis: a 12-month RCT.

It is uncertain whether subjects with mild knee osteoarthritis, and who may be at risk of osteoporosis, can exercise safely with the aim of improving hip bone strength. This RCT showed that participating in a high-impact exercise program improved femoral neck strength without any detrimental effects on knee cartilage composition. INTRODUCTION: No previous studies have examined whether high-impact exercise can improve bone strength and articular cartilage quality in subjects with mild knee osteoarthritis. In this 12-month RCT, we assessed the effects of progressive high-impact exercise on femoral neck structural strength and biochemical composition of knee cartilage in postmenopausal women. METHODS: Eighty postmenopausal women with mild knee radiographic osteoarthritis were randomly assigned into the exercise (n = 40) or control (n = 40) group. Femoral neck structural strength was assessed with dual-energy X-ray absorptiometry. The knee cartilage region exposed to exercise loading was measured by the quantitative MRI techniques of T2 mapping and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Also, an accelerometer-based body movement monitor was used to evaluate the total physical activity loading on the changes of femoral neck strength in all participants. Training effects on the outcome variables were estimated by the bootstrap analysis of covariance. RESULTS: A significant between-group difference in femoral neck bending strength in favor of the trainees was observed after the 12-month intervention (4.4%, p < 0.01). The change in femoral neck bending strength remained significant after adjusting for baseline value, age, height, and body mass (4.0%, p = 0.020). In all participants, the change in bending strength was associated with the total physical activity loading (r = 0.29, p = 0.012). The exercise participation had no effect on knee cartilage composition. CONCLUSION: The high-impact training increased femoral neck strength without having any harmful effect on knee cartilage in women with mild knee osteoarthritis. These findings imply that progressive high-impact exercise is a feasible method in seeking to prevent hip fractures in postmenopausal women whose articular cartilage may also be frail.

Light physical activity determined by a motion sensor decreases insulin resistance, improves lipid homeostasis and reduces visceral fat in high-risk subjects: PreDiabEx study RCT.

OBJECTIVE: To examine physical activity (PA) thresholds affecting glucose, insulin and lipid concentrations and body fat composition in high-risk patients for type 2 diabetes (T2D). INTERVENTION: A total of 113 subjects of both genders having abnormal glucose levels in the oral glucose tolerance test were contacted. A total of 78 subjects with age 58.8±10.4 years and body mass index 31.7±5.3 kg m(-2) were randomly assigned to intervention and control groups. INTERVENTION consisted of a supervised walking (60 min three times weekly) for 3 months. All the subjects received standard care for PA and weight reduction and wore an accelerometer during the whole wakeful time. RESULTS: Over 80% of the daily steps clustered at an acceleration level of 0.3-0.7 g (2-3 km h(-1) of walking) and were 5870 in the intervention and 4434 in the control group (P<0.029). Between 0 and 3 months no significant changes were observed in fasting and 2-h glucose, body weight or maximal oxygen uptake. In contrast, changes in fasting and 2-h insulin (-3.4 mU l(-1), P=0.035 and -26.6, P=0.003, respectively), homeostasis model assessment-estimated insulin resistance (-1.0, P=0.036), total cholesterol (-0.55 mmol l(-1), P=0.041), low-density lipoprotein (LDL) cholesterol (-0.36 mmol l(-1), P=0.008) and visceral fat area (-5.5 cm(2), P=0.030) were significantly greater in the intervention than in control subjects. The overall effects of PA were analyzed by quartiles of daily steps of all subjects. There were significant reductions in total and LDL cholesterol and visceral fat area between the highest (daily steps over 6520) and the lowest quartile (1780-2810 daily steps). The changes associated with PA remained significant after adjustments of baseline, sex, age and body weight change. CONCLUSION: Habitual and structured PAs with the acceleration levels of 0.3-0.7 g and daily steps over 6520, equivalent to walking at 2-3 km h(-1) for 90 min daily, standing for the relative PA intensity of 30-35% of the maximal oxygen uptake, are clinically beneficial for overweight/obese and physically inactive individuals with a high risk for T2D.

Leaving the pulp chamber open for drainage has no effect on the complications of root canal therapy.

In this retrospective study the effects of different kinds of emergency treatments on flare-ups and other complications were examined. A total of 197 teeth received emergency treatment after diagnosis at the beginning of the root canal therapy; in 103 the pulp chamber was left open for drainage of pus, 35 were treated with dexamethasone sodium phosphate, and 59 with various other medicaments, followed by routine root canal treatment. In all, 404 teeth received root canal treatment without emergency treatment. If symptoms occurred during treatment, flare-up was said to be present. If a periapical radiolucency was found, long-term calcium hydroxide treatment was used: no sign of periapical healing radiographically after 6 months was described as a complication. The percentage of teeth with no complications varied from 72.2% (dexamethasone) to 78.9% (other modification) and the results showed no differences between the groups in the teeth with no complications, flare-ups or other complications. The number of bacteria detected with Gram's staining was higher in the teeth which were left open. In conclusion, leaving the pulp chamber open for drainage had no effect on the incidence of flare-ups or other complications.

Evaluation of Gram's method of staining for the prognosis of root canal treatment in nonvital dental pulps.

An evaluation of Gram's method of staining of 601 nonvital dental pulps was performed. It gave positive results in 60.1% of the cases, the most frequent finding was gram-positive cocci. Preoperative x-ray status correlated significantly with the staining results but the size of the radiolucency did not. Previously treated teeth gave less positive staining results than other teeth. There was an obvious correlation between presence of bacteria and various complications (p < 0.001), but no differences were noted between the combinations of bacteria. The teeth that were the most resistant to complications seemed to be the lower canines. The staining results did not correlate with sex, systemic diseases, or preoperative symptoms. We believe that Gram's method of staining is a useful, rapid aid in root canal therapy, especially in complicated cases.

Experimental pancreatitis in the rat. Ductal factors in sodium taurocholate-induced acute pancreatitis.

Spreading of injected material and ductal resistance were studied in the rat pancreas after intraductal injection of Indian ink, human serum or sodium taurocholate. Indian ink filled the main pancreatic duct and small ductules revealing the lobular structure in macroscopic preparation. Escape into the interstitium was observed both in the macroscopic preparations and in histologic sections. Human IgG was demonstrated immunohistochemically in single acinar cells and around acinar cells after intraductal injection of human serum. The changes were most pronounced at 15 min and at 6 h after the injection but were almost resolved at 24 h. The intraductal pressure was registered during sodium taurocholate infusion. The pancreatic duct ruptured at the pressure of 82 mm Hg in average. It was concluded that in the ductal model of experimental acute pancreatitis the infusion causes ruptures in pancreatic ducts and the infusate escapes into the interstitium where it remains for several hours.

Experimental pancreatitis in the rat. Changes in pulmonary phospholipids during sodium taurocholate-induced acute pancreatitis.

Acute haemorrhagic pancreatitis was induced in rats by injecting aqueous solution of sodium taurocholate into the common biliopancreatic duct. Lecithin and lysolecithin were separated from pulmonary homogenate by thin layer chromatography and quantified by phosphorus determination. The ratio of lysolecithin to lecithin increased after the sodium taurocholate injection as well as after i.v. administration of porcine pancreatic phospholipase A2. It was concluded that phospholipase A2, released from pancreatic acinar cells into blood, may convert pulmonary lecithin into lysolecithin during acute pancreatitis. Destruction of pulmonary surfactant may contribute to the development of the adult respiratory distress syndrome as seen in patients suffering from severe acute pancreatitis.