Multiple recurrent dermatofibrosarcoma protuberans of the hand

We present a rare case of a dermatofibrosarcoma protuberans arising on the dorsum of the hand in a 51-year-old woman, who had experienced four recurrences of the tumour following local excisions. We performed a radical surgical excision of the lesion and covered the defect with a distal ulnar artery skin island flap. Adjuvant radiation therapy followed the surgical treatment. Forty months postoperatively, the patient has a functional hand without signs of recurrence and no evidence of disease. Wide surgical excision with margins of 2.5-3 cm is the optimal treatment for dermatofibrosarcoma protuberans. For selected patients, like those presenting large tumours involving the hand, adequate removal is not easily obtainable, or may result in major functional deficits. An alternative strategy may be the combination of less extensive surgery and radiotherapy, in order to prevent mutilation, decrease the local recurrence rates, and minimize the risk of metastases.     

A phantom-based evaluation of an exposure equalization technique in mammography

An anatomical filter based exposure equalization technique in mammography is evaluated quantitatively using a phantom. The evaluation is carried out by a comparative observer performance study, comparing the equalization technique with a conventional one based on visualization of low contrast, 6 mm circular details and high contrast, 0.5 mm and 0.25 mm small size details. These details are situated at the phantom edge, simulating the breast periphery. Visualization of these details is studied with respect to the parameters of tube voltage, optical density, detail location and phantom thickness. Phantom images are interpreted independently by three observers using a four-point grading scale. Use of the Wilcoxon signed ranks test for paired data shows statistically highly significant improvement (p < 0.0001) in the visualization of details for the equalization technique for all values of the parameters studied. The improvement is independent of tube voltage but dependent on optical density, detail location and phantom thickness. Optimal performance is obtained for detail location closer to the outer border of the simulated breast periphery and/or further away from the film, as well as for a greater phantom thickness simulating both thick and dense breast.     

Dialysate magnesium level and blood pressure

BACKGROUND: We investigated the way dialysate magnesium (dMg) concentrations could affect blood pressure (BP) during hemodialysis (HD). METHODS: Eight HD patients underwent four midweek HD treatments consecutively, using, during each four-hour HD session, one of the following four dialysate formulations, in randomized order, which differed only with regard to dMg and dialysate calcium (dCa) concentrations (in mmol/L): 0.75 dMg, 1.75 dCa (group I); 0.25 dMg, 1.75 dCa (group II); 0.75 dMg, 1.25 dCa (group III); 0.25 dMg, 1.25 dCa (group IV). Before HD and at four 60-minute intervals during the HD sessions, BP and noninvasive measurements of cardiac index (CI) were obtained. Additionally, 14 HD patients were treated for four weeks with 0.5 mmol/L dMg, followed by four weeks with 0.25 mmol/L dMg, and another four weeks with 0.75 mmol/L dMg, in random order. In all treatments dCa was 1.25 mmol/L. BP and symptoms were recorded during each HD session. RESULTS: Mean arterial pressure (MAP) decreased to a significantly (P < 0.05) greater extent in group IV compared to the other groups. This substantial drop in MAP by 15.2% in group IV, paralleled by a 12.1% and 17% drop in CI and stroke index, respectively, was not seen in group II, despite comparable reductions in intradialytic serum Mg (sMg) of about 35% in both groups. In groups I and III, the increase in sMg by 2% did not compromise BP via vasodilatation. In the second study, treatment with 0.75 mmol/L dMg was superior to the other two treatments regarding intradialytic morbidity (P < 0.001) and BP stability (P < 0.05). CONCLUSION: We (1) identified a dialysis solution containing 0.25 mmol/L Mg and 1.25 mmol/L Ca as a major cause of intradialytic hypotension (IDH) due to an impairment of myocardial contractility, and (2) showed that increasing dMg level to 0.75 mmol/L could prevent IDH frequently seen with the use of 1.25 mmol/L dCa. Thus, manipulating dMg levels independently or in concert with dCa levels might have important implications with regard to dialysis tolerance.     

Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer

Introduction

The aim of the present study was to identify the relationships between the uptake of radiotracers – namely pentavalent dimercaptosuccinic acid [(V)DMSA] and sestamibi (MIBI) – and the following parameters in primary breast cancer: steroid receptor concentrations (i.e. estrogen receptor [ER] and progesterone receptor [PR]), Ki-67 expression, tumor size, tumor grade, age, and levels of expression of p53 and c-erbB-2. In addition, by multivariate regression analysis, we further isolated those factors with independent associations with (V)DMSA and/or MIBI uptake in primary breast cancer.

Methods

Thirty-four patients with histologically confirmed breast carcinoma underwent preoperative scintimammography with technetium-99m (^99mTc)-(V)DMSA and/or ^99mTc-MIBI in consecutive sessions 10 and 60 min after administration of 925–1110 MBq of each radiotracer. The tumor-to-background ratio was calculated and correlated with the presence of ER, PR, Ki-67, tumor size, tumor grade, p53, and c-erbB-2. ER, PR, p53, and c-erbB-2 were determined immunohistochemically. The analysis included tumor-to-background ratio of (V)DMSA and MIBI uptake as dependent and all of the other parameters as independent variables.

Results

Correlation was positive between Ki-67 and (V)DMSA (r = 0.37 at 10 min, P = 0.038; r = 0.42 at 60 min, P = 0.018) and inverse between PR and (V)DMSA uptake (r = -0.46 at 10 min, P = 0.010; r = -0.51 at 60 min, P = 0.003). Multivariate regression analysis demonstrated a positive correlation between Ki-67 and (V)DMSA at 60 min (P = 0.045). Ki-67 was not significantly correlated with MIBI uptake, whereas tumor size was positively correlated with MIBI uptake at 60 min both in univariate (r = 0.45, P = 0.027) and multivariate analysis (P = 0.024). Negative correlations were observed between (V)DMSA uptake and ER, as well as between ER/PR and MIBI uptake, but these were not significant.

Conclusion

Ki-67 appears to represent the major independent factor affecting (V)DMSA uptake in breast cancer. Tumor size was the only independent parameter influencing MIBI uptake in breast cancer. (V)DMSA appears to have an advantage over MIBI in that it can be used to visualize tumors with intense proliferative activity, and thus it can identify those tumors that are more aggressive.     

Ureteropelvic junction obstruction: an innovative approach combining metallic stenting and virtual endoscopy

PURPOSE: We report our experience with auto-expandable metallic stents for treating ureteropelvic junction obstruction. MATERIALS AND METHODS: We treated 4 patients with a mean age of 45 years who had ureteropelvic junction obstruction with placement of a self-expandable intraureteral metallic stent (Wallstent, Schneider, Zurich, Switzerland). All patients presented with recurrent ureteropelvic junction obstruction after open pyeloplasty. Excretory urography and 3-dimensional reconstruction computerized tomography were performed 1 and 6 months after stent insertion. Virtual endoscopy images were obtained at followup due to the need to define ureteral patency. RESULTS: Mean followup was 16 months (range 9 to 24). Wallstent placement was successful and immediate patency was achieved in all cases. During followup 3 patients required no further intervention and the stented ureteropelvic junction remained patent. In the remaining patient stricture recurred 2 months after initial stent insertion due to the ingrowth of scar tissue through the prosthesis. Additional intervention was deemed necessary after placing a longer 6 cm., completely coaxial overlapping metal stent. Virtual endoscopy and excretory urography findings concurred. Virtual endoscopy allows visualization of the stented ureteropelvic junction lumen cephalad and caudal to the prosthesis. It also enables easy navigation within the stent at different angles of view. CONCLUSIONS: The concept of applying metallic stents for ureteropelvic junction obstruction and adjacent adynamic ureteral segments combined with virtual endoscopy is strengthened by the results of this study.     

Arterioureteral fistula--a rare complication of ureterolithotomy: treatment with embolization

Fistula formation between a ureteral branch of a renal artery and the ipsilateral ureter is rare. We describe a case that followed ureterolithotomy of an impacted stone. Selective angiography with embolization of the bleeding branch was curative.     

Cooperativity Between Selectins and β2-Integrins Define Neutrophil Capture and Stable Adhesion in Shear Flow

A cooperative, sequential process of molecular recognition governs leukocyte capture, rolling, and arrest on inflamed endothelium. Flowing neutrophils are captured via heterotypic adhesive interactions mediated by endothelial E-selectin, whereas homotypic interactions between neutrophils are mediated by L-selectin. To elucidate how each selectin facilitates the transition to CD18-mediated stable adhesion, E-selectin and L-selectin were expressed at defined site density in a murine pre-B-cell line. Direct observation of two-body collisions revealed that 30% of neutrophil interactions with E-selectin transfectants formed doublets at low shear rate G = 14 s(-1) whereas a threshold shear rate 14 s(-1) < or = G < or = 10 s(-1) was necessary for L-selectin adhesion. Adhesion via L-selectin resisted rupture at high shear stress, while E-selectin tethered doublets remained intact longer once formed. Moreover, higher expression of L-selectin (1100 sites/microm2) than that of E-selectin (220 sites/microm2) was required for comparable heterotypic adhesion efficiency. With a threefold rise in active CD18 upregulated on chemotactically stimulated neutrophils, homotypic adhesion efficiency increased 10-fold compared to less than 5-fold for heterotypic adhesion to selectin transfectants. Co-expression of E-selectin and ICAM-1 boosted adhesion efficiency threefold more than either receptor alone over the range of active CD18 expression. These data are the first to quantify adhesion efficiency mediated by selectin tethering and conformational activation of beta2-integrin in neutrophils in shear flow.     

Dexamethasone incorporating liposomes: an in vitro study of their applicability as a slow releasing delivery system of dexamethasone from covered metallic stents

Aim: To investigate the possibility of covering PET-covered commercially available metallic stents, with liposomal dexamethasone that will act as a slow releasing drug-depot at the site of interest. Methods: Large multilamellar (MLV), sonicated (SUV) and dried reconstituted (DRV) liposomes entrapping dexamethasone were prepared by thin film hydration, sonication and the DRV method, respectively, and applied on stents using a simple evaporation technique. Drug encapsulation and retention in liposomes were measured by HPLC. The presence of liposomes on the stent surface was confirmed by scanning electron microscopy, while the release of dexamethasone and lipid from the liposome-covered stent was evaluated under different conditions (flow rate, presence of plasma proteins), in an in vitro assembly that was developed to simulate in vivo conditions. Results: The release of dexamethasone from liposome-covered stents ranged from 25% to 50% after 48 h of incubation in buffer, depending on the type of liposome. The release was highest from stents covered with DRV liposomes. When increasing the flow rate from 2 to 6 ml/min a slight increase in release of drug was observed, while a higher release was measured when stents were incubated in plasma proteins. Liposome size does not affect liposome placement on stents. Conclusion: The basic characteristics that should be considered when preparing liposomes to cover stents should be their drug loading capacity and their stability under the conditions prevailing at the site of interest. By preparing the appropriate formulation, it is possible that liposomal drugs may be used to cover stents and serve as drug releasing depots at the site of interest. Further in vitro and in vivo studies are needed in order to exploit the possible applications of this methodology.     

Leukemic recombinations involving heterochromatin in myeloproliferative disorders with t(1;9)

The unbalanced t(1;9) is a rare, recurrent rearrangement in polycythemia vera (PV) resulting in trisomy of both 1q and 9p arms, whereas a balanced t(1;9)(q12;q12), to our knowledge, has never been reported before. We studied two patients with PV and one with idiopathic myelofibrosis bearing an unbalanced t(1;9) and one patient with essential thrombocythemia with a balanced t(1;9). In all cases fluorescence in situ hybridization showed that the breakpoints were located within the satellite II family of heterochromatin of chromosome 1 and the satellite III of chromosome 9. Heterochromatin breakage and reunion produce the unbalanced t(1;9) and may contribute to a gene dosage effect due to gains of 1q and 9p. Case 4 with the balanced t(1;9), however, suggests that translocation of heterochromatin close to critical genes could interfere with their function. The molecular event underlying juxtaposition of satellite II of chromosome 1 and the satellite III of chromosome 9 remains to be elucidated.     

Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage

Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre-replicative complex, is essential for loading the minichromosome maintenance complex (MCM) helicases onto the origins of DNA replication. While several studies have shown that dysregulation of CDT1 expression causes re-replication and DNA damage in cell lines, and CDT1 is highly expressed in several human cancers, whether CDT1 deregulation is sufficient to enhance tumorigenesis in vivo is currently unclear. To delineate its role in vivo, we overexpressed Cdt1 in the mouse colon and induced carcinogenesis using azoxymethane/dextran sodium sulfate (AOM/DSS). Here, we show that mice overexpressing Cdt1 develop a significantly higher number of tumors with increased tumor size, and more severe dysplastic changes (high-grade dysplasia), compared with control mice under the same treatment. These tumors exhibited an increased growth rate, while cells overexpressing Cdt1 loaded greater amounts of Mcm2 onto chromatin, demonstrating origin overlicensing. Adenomas overexpressing Cdt1 showed activation of the DNA damage response (DDR), apoptosis, formation of micronuclei, and chromosome segregation errors, indicating that aberrant expression of Cdt1 results in increased genomic and chromosomal instability in vivo, favoring cancer development. In line with these results, high-level expression of CDT1 in human colorectal cancer tissue specimens and colorectal cancer cell lines correlated significantly with increased origin licensing, activation of the DDR, and microsatellite instability (MSI). © 2022 The Pathological Society of Great Britain and Ireland.