SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer.

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2-/- mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer.

Adjuvant chemotherapy in elderly patients with pancreatic cancer.

BACKGROUND: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. METHODS: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. RESULTS: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ≥70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002). CONCLUSION: Patients aged ≥70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.

The prognostic and predictive value of serum CA19.9 in pancreatic cancer.

BACKGROUND: Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used. METHODS: We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC. RESULTS: By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P=0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels>90 U/ml did not benefit from adjuvant chemotherapy (P=0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P=0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P=0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. CONCLUSIONS: Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.

When to operate nonreducible ovary?

During the period from 1992, to 1996, ninety three girls with incarcerated inguinal hernias, mean age 6 weeks, underwent operation at the Clinic for Paediatric Surgery in Novi Sad. All infant girls had incarcerated ovaries or ovaries and fallopian tubes inside hernia sacs. The nonreducible ovaries were present at the time of operation in 35 (37%) girls and in 5 the ovary and tube were twisted. The ovary and tube, were twisted and ischemic at the time of operation, requiring oophorectomy in 2 out of 5 girls. The results of this review and recent experiences reveal that nonreducible ovary is not at risk of compression of its blood supply, but at significant risk of torsion. That is why asymptomatic nonreducible ovary should be treated as every incarcerated hernia--with urgent reduction, manual or operative.

[Rhombencephalitis as a manifestation of neuroborreliosis]. / Rombencefalitis kao manifestacija neuroborelioze.

Rhombencephalitis is a rare neurological manifestation of stage II of Lyme disease. We presented two cases with no recollection of tick bite nor erythema migrans and with cranial nerve nuclei, pyramidal tract and cerebellar tracts involvement of sudden onset, inflammatory syndrome in cerebrospinal liquor, positive oligoclonal bands and elevated IgG index. A spontaneous remission occurred in both cases, but antibiotic was given intravenously for prevention of relapses and disease progression.

[Quantitative evaluation of permeability of root canalicular system]. / Kvantitativno odredivanje propustljivosti kanalikulnog sistema korena zuba.

The purpose of this study was to evaluate the rate of permeability of the canalicular system of the root (apical and central portion) using albumin labelled with 131J-radioisotope. Freshly extracted central maxillar incisors were divided in three groups: I 10 specimens were used to quantity the rate of the tracer penetration through the apical foramen and apical ramification; II 10 specimens were used for the measurement of central root portion permeability for the same tracer; III. This group was the control group; it consisted of 5 samples which were tested to the sealing ability of the used sticky-wax. The results showed: 1). Through an apical foramen and ramification 56% of radiolabelled albumin penetrated into an external saline eluent; 2). When albumin was used as an eluent another amount of 6.5% of 131J-albumin was released; 3) About 38% of total albumin tracer was irreversibly bound to the components of root dentine and cement; 4). Through the central portion of the root canalicular system 50% of radiolabelled albumin penetrated from the root canal; 5). Penetration of large molecules (m.w. 67000), like bacterial endotoxins and protein metabolic products, is absolutely possible and penetration occurs primarily through a system of apical ramification and pulpo-periodontal communication as well as through a canalicular pattern of root dentine and cement.

[Experimental study of accuracy of electro-odontometric device in establishment of apical constriction of a root canal]. / Laboratorijsko ispitivanje tacnosti elektroodontometrijskog odredivanja likocije apeksnog suzenja Korenskog kanala.

The aim of the present study was to investigate the accuracy of an electro-odontometric device "Odontometer" (Goof, Denmark) in the determination of the exact location of the apical constriction in root canals of extracted teeth in experimental conditions. Ninetynine root canals of 91 teeth were used. Following the access to the root canal the teeth were sealed at the level of the cemento-enamel junction in the apertures of a plastic plate. Each plate contained ten tooth samples. The plate was immersed into a gelatine medium. The roots were completely immersed but the crowns were isolated from the medium by the plastic plate and sticky wax seal, remaining at the top surface of the plate. The platinum plate was immersed in the gelatine medium and connected to the passive electrode of the device. The active electrode was a K-reamer n. 15 which was advanced along the canal until "Odontometer" indicated "apical constriction". At this point the reamer was sealed in the canal, and the toot was released from the apparatus. The apical third of the root was then ground parallel to the long axis until the distal segment of the K-reamer and the root canal appeared. The distance between the tip of the reamer and the apical constriction was measured with a microscope precision of 0.125 mm. The absolutely exact location of the apical constriction was determined in 22% of cases. In no case the endocanal electrode passed over the anatomic foramen. With the tolerance of the clinically acceptable odontometric error of 0.5 mm, "Odontometer" was accurate in 83% of cases thus its use in current dental practice is justified.

[Effect of remaining dentine thickness beneath deep cavities on the rate of reparative dentine formation--experimental study]. / Zabisnost produkcije reparacionog dentina od dubine kaviteta. Eksperimentalna studija.

The aim of this study was to investigate the effect of remaining dentine thickness beneath deep cavities on the rate of reparative dentine formation throughout 119 days and to establish the limit value of the remaining dentine thickness that enables greatest amount of tertiary dentine in dogs' teeth. Deep buccal cavities were prepared in all canines and molars of three dogs, lined with four different lining materials for indirect pulp capping and filled with silver amalgam. Tetracycline labelling technique was used to demark the layers of reparative dentine produced during the experimental period of 17 weeks. After sacrificing and isolation the teeth from the jaws slices (1 mm thick) were cut off through the middle of the cavity, perpendicular to the cavity floor and mesio-distal tooth axis. Sections were ground to 100 microns thick; the measuring of the remaining and reparative dentine thickness was carried out with Fluoval, Carl-Zeiss, Jena, DDR fluorescent microscope. The results showed: 1. Cavity depth had a strong effect on the quantity of newly formed tertiary dentine; 2. The greatest rate of reparative dentine (348 microns) was produced beneath the cavities with remaining dentine thickness ranging 501-700 microns; 3. The least quantities of tertiary dentine (219 and 227 microns) were produced beneath the deepest cavities, with remaining dentine thickness less than 500 microns, as well as beneath shallower cavities with remaining dentine thickness of over 900 microns.

[Effects of Anhidrin on dog's dental pulp in vivo]. / Dejstvo Anhidrin-a na pulpu zuba pasa u in vivo uslovima.

The purpose of the article was to investigate in vivo effects of Anhidrin, a cavity cleansing agent, on dog's dental pulp. Following class V cavity preparation, with a depth referred to caries media, dentine walls were cleaned with Anhidrin. Cavity floor was lined with denatured dentine powder and permanently filled with silver amalgam. Animals were sacrificed after experimental period of 14, 45 and 90 days, respectively. Decalcified tooth sections were prepared by standard histologic technique stained with HE. The results achieved using light microscopy showed the most intensive changes in pulp tissue beneath cavity preparations treated with Anhidrin 14 days postoperatively, characterized with hyperaemia and bleeding in odontoblast and subodontoblast layer, reduction in odontoblast number and disturbed cell arrangement. In the second experimental period after 45 days, the changes were less expressed. Ninety days after the operation pulp tissue appeared in normal histologic structure of sound dental pulp, with significant layers of tertiary dentine beneath the area of cavity preparation and application of Anhidrin.

[Electroodontometric determination of location of apical constriction in root canal]. / Mogucnost elektroodontometrijskog odredivanja lokacije apeksnog suzenja radiksnog kanala.

Electronic odontometer (Goof, Denmark) was used in clinical investigation of 169 root canals of 138 teeth, treated for different endodontic reasons. A removable plastic collar was fixed to endocanal electrode (K-reamer) on which the exact length was signalized as apical constriction, followed by radiographic control. The obtained values were statistically elaborated. The exact location of apical constriction was accurately determined in 119 cases (70.41%). Electroodontometer errors were found in 50 root-canals, and deviation ranged from -4 mm to -1 mm with mean of -0.3254 +/- 0.85. The predominant error was failure of the apical constriction (39 cases); in a few samples (11) a canal instrument passed through this location. When pulpo-periodontal condition was considered the greatest number of errors was found in teeth with vital pulp tissue and a significantly smaller number in teeth with gangrenous pulp with or without periapical lesions. The age of sample had no influence on the accuracy of determination of the location of apical constriction.

[The value of intraoperative cholangiography]. / Vrijednost intraoperativne holangigrafije.

The 99 intraoperative cholangiography results from the last two years are analyzed. The indications are mentioned, as the intraoperative cholangiography was not used performing every one cholecystectomy. The authors think that the intraoperative cholangiography is necessary before the exploration of the common bile duct. The results are compared with the preoperative i.v./inf. cholangiography findings performed in 95 cases; the rule is, that we do not operate the bile tract without preoperative cholangiography. The diagnostic intraoperative cholangiography findings value that proves the common bile duct obstruction is 0,90, and 0,70 for the preoperative cholangiography. That two diagnostic values relation is 0,95:0,85 for the intraoperative cholangiography. The choledochotomy findings in this group (66%) were controlled by instrumental exploration and even by choledochoscopy. There were no complications in this group performing intraoperative cholangiography.