Characteristic Radiological Features of Retrospectively Diagnosed Pancreatic Cancers.

OBJECTIVES: The aim of this study was to assess the characteristic radiological features of early-stage pancreatic cancer (PC). METHODS: Between 2009 and 2016, 510 PC patients were selected from our hospital cancer registry database based on International Classification of Diseases for Oncology-3 (C25). Among them, 64 patients (42 males and 22 females; median age, 74 [range, 59-91]) had received repeated abdominal radiological examinations before their diagnosis of PC and were retrospectively investigated for specific radiological findings. The subjects underwent the following imaging examinations: computed tomography, magnetic resonance imaging, and fluoroglucose-positron emission tomography. RESULTS: Characteristic radiological features before diagnosis of PC were classified into the following 9 features: pancreatic duct ectasia (n = 16), focal low-density area (n = 15), change of cyst size (n = 8), localized tissue atrophy (n = 7), distal atrophy (n = 4), mass in pancreatic lipomatosis tissue (n = 2), mass concomitant with the already known cyst (n = 2), protrusion (n = 1), and parenchymal disproportion (n = 1). Fifty-three cases (84%) had more than one characteristic radiological feature before diagnosis of PC, and their median observation period until diagnosis was 24 (range, 1-120) months. CONCLUSIONS: The 9 characteristic radiological features provide an opportunity to diagnose PC at an early stage.

Analysis of All 34 Exons of the SPINK5 Gene in Japanese Atopic Dermatitis Patients.

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p.K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p.K420E; these variants had already been registered in the SNP database. Among them, p.R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p.S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p.R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients.

Development of Tissue-Engineered Ligaments: Elastin Promotes Regeneration of the Rabbit Medial Collateral Ligament.

When ligaments are injured, reconstructive surgery is sometimes required to restore function. Methods of reconstructive surgery include transplantation of an artificial ligament and autotransplantation of a tendon. However, these methods have limitations related to the strength of the bone-ligament insertion and biocompatibility of the transplanted tissue after surgery. Therefore, it is necessary to develop new reconstruction methods and pursue the development of artificial ligaments. Elastin is a major component of elastic fibers and ligaments. However, the role of elastin in ligament regeneration has not been described. Here, we developed a rabbit model of a medial collateral ligament (MCL) rupture and treated animal knees with exogenous elastin [100 µg/(0.5 mL·week)] for 6 or 12 weeks. Elastin treatment increased gene expression and protein content of collagen and elastin (gene expression, 6-fold and 42-fold, respectively; protein content, 1.6-fold and 1.9-fold, respectively), and also increased the elastic modulus of MCL increased with elastin treatment (2-fold) compared with the controls. Our data suggest that elastin is involved in the regeneration of damaged ligaments.

Ewing Sarcoma of the Bone With EWS/FLI1 Translocation After Successful Treatment of Primary Osteosarcoma.

Although prognosis in patients with localized osteosarcoma has been dramatically improved by the introduction of multiple chemotherapy agents known as combination chemotherapy, there is growing concern about the development of secondary malignant neoplasms. We report the case of a 13-year-old girl in whom the diagnosis of Ewing sarcoma of bone localized on the shaft of left femur was made 2 years after successful treatment without radiotherapy for osteosarcoma of right proximal femur. EWS-FLI1 fusion gene was detected by reverse transcriptase-polymerase chain reaction. To our knowledge, this is the first case with Ewing sarcoma of the bone as a secondary malignant neoplasm developed in osteosarcoma survivor. We collected 15 cases, included this case, with secondary Ewing sarcoma family of tumor by utilizing the PubMed search and might consider the causes of this secondary cancer.

Validation of a protocol based on Raman and infrared spectroscopies to nondestructively estimate the oxidative degradation of UHMWPE used in total joint arthroplasty.

UNLABELLED: As a matter of fact, the in vivo oxidative degradation of highly cross-linked polyethylene (HXLPE) still remains one of the limiting factors that affect the long term survivorship of joint replacements. Recent studies clearly pointed out that also the new generation of highly cross-linked and remelted polyethylene components in total hip and knee replacement underwent unexpected oxidation after 5-10years of implantation. The standard methodology to investigate the oxidation of polyethylene (PE) relies on the use of infrared spectroscopy, which, if from one hand is a reliable technique for the detection of oxidized species containing carbonyl group, on the other hand it is not capable of discriminating the fraction of carboxyl acids that is responsible for chain scission and subsequent deterioration of the mechanical properties of the polymer. In the present study we validate a new protocol based on Raman spectroscopy, which is suitable on assessing the structural degradation of polyethylene induced by oxidation. Following in vitro accelerated aging experiments, the oxidation index (OI) of different commercially available HXLPEs, as calculated by infrared spectroscopy according to ASTM standard, has been univocally correlated to the most severe variation of crystalline phase (αc), as calculated by Raman spectroscopy. In each material, locations with equal values of OI showed different degree of recrystallization induced by chain scission, confirming that infrared spectroscopy might overestimate the effective mechanical degradation of the polymer. In addition, as compared to the standards based on infrared spectroscopy, this new method of assessing oxidation enables to investigate the degradation occurring on the original surface of HXLPE components, due to the nondestructive nature of Raman spectroscopy and its high spatial resolution. STATEMENT OF SIGNIFICANCE: In the present study we validate a new protocol based on Raman spectroscopy, which is suitable on assessing the structural degradation of polyethylene induced by oxidation. In fact, the standard methodology to investigate the oxidation in polyethylene relies on the use of infrared spectroscopy, which is capable of detecting the presence of oxidized species containing carbonyl group, the main products of oxidation in polyolefins. If from one hand this technique enables quantitative analysis of oxidation, on the other hand it is not capable of discriminating the fraction of species with carbonyl groups responsible for the chain scission. In fact, esters, ketones and carboxyl acids are products of oxidation with carbonyl groups commonly formed on polyethylene at the end of the oxidative cascade initiated by the presence of free radicals, but only the latter are responsible for the chain scission and the subsequent deterioration of the mechanical properties. The oxidation index as obtained according to the ASTM standards is not univocally correlated to a certain degree of mechanical deterioration, but, in simple words, two retrievals with the same amount of carbonyl groups might have had different degradation of the mechanical properties. Recrystallization is a direct consequence of the reduction of molecular weight that occurs after chain scission. Raman spectroscopy (RS) is a viable non-destructive method to assess the fraction of crystalline phase in polyethylene and, due to its high spatial resolution, is perfectly suitable to analyze the microstructural modification at the mesoscopic scale, where the effects of oxidation manifest themselves. The aim of the present paper is twofold: i) to compare the microstructural modifications caused by in vitro oxidation on 5 different types of polyethylene currently available on the market of joint replacements; ii) to establish a protocol based on the comparative analysis of IR and RS results to obtain a phenomenological correlation capable to judge the mechanical deterioration of the material induced by the oxidative degradation.

In-vivo degradation of middle-term highly cross-linked and remelted polyethylene cups: Modification induced by creep, wear and oxidation.

In this study Raman (RS) and Fourier Transform Infrared (FT-IR) spectroscopic techniques were exploited to study 11 retrieved liners made of remelted highly cross-linked polyethylene (HXLPE), with the intent to elucidate their in-vivo mechanical and chemical degradation. The retrievals had different follow-ups, ranging from a few months to 7 years of implantation time and belong to the first generation of highly cross-linked and remelted polyethylene clinically introduced in 1999, but still currently implanted. Raman assessments enabled to discriminate contributes of wear and creep on the total reduction of thickness in different locations of the cup. According to our results, although the most of the viscoelastic deformation occurred during the first year (bedding-in period), it progressed during the steady wear state up to 7 years with much lower but not negligible rate. Overall, the wear rate of this remelted HXLPE liner was low. Preliminary analysis on microtomed sections of the liners after in-vivo and in-vitro accelerated aging (ASTM F2003-02) enabled to obtain a phenomenological correlation between the oxidation index (OI) and the amount of orthorhombic phase fraction (αc), which can be easily non-destructively measured by RS. Profiles of αc obtained from different locations of the cups were used to judge the oxidative degradation of the 11 retrievals, considering also the ex-vivo time elapsed from the revision surgery to the spectroscopic experiments. Low but measurable level of oxidation was detected in all the short-term retrievals, while in the middle-term samples peaks of OI were observed in the subsurface (up to OI=4.5), presumably induced by the combined effect of mechanical stress, lipid absorption and prolonged ex-vivo shelf-aging in air.

Evidence for the intrinsic nature of band-gap states electrochemically observed on atomically flat TiO2(110) surfaces.

Using an ultra-high vacuum (UHV) electrochemistry approach with pulsed laser deposition (PLD), we investigated the band-gap state for TiO2(110). In the PLD chamber, a TiO2(110) surface was cleaned by annealing in O2 enough for it to exhibit a sharp (1 × 1) reflection high energy electron diffraction (RHEED) pattern. The cleaned TiO2(110)-(1 × 1) sample then underwent electrochemical measurements without exposure to air, showing the band-gap state at -0.14 V vs. Ag by Mott-Schottky plot analysis. The band-gap state gradually disappeared under UV illumination at +0.6 V vs. Ag due to photoetching, and reappeared on reduction in a vacuum and/or deposition of a fresh TiO2 film. These results indicated that the electrochemically observed band-gap state for TiO2(110) was a defect state due to oxygen deficiency, most probably identical to that observed under UHV, which does not necessarily exist on the surface. A quantitative analysis of the defect density suggests that the origin of this defect state is not the surface bridging hydroxyls or oxygen vacancies, but rather the interstitial Ti(3+) ions in the subsurface region.

Novel p53 splicing site mutation in Li-Fraumeni-like syndrome with osteosarcoma.

We describe a 15-year-old girl with a novel germline p53 splice site mutation who developed an osteosarcoma. She received several cycles of chemotherapy with complete resection of the primary tumor without amputation, and has maintained remission for 18 months. Li-Fraumeni-like syndrome was suspected based on familial history. Sequence analysis revealed the presence of a novel germline p53 gene mutation resulting in a G to A transition at position +1 at the donor splice site of intron 6, creating a 6 amino acid insertion. This case provides interesting insight into the phenotype-genotype correlation in LFL syndrome with a TP53 splicing mutation.

Merkel cell-poor trichoblastoma with basal cell carcinoma-like foci.

We reexamined 11 cases of trichoblastoma, and two cases of trichoblastoma with basal cell carcinoma (BCC)-like foci were found. In these two trichoblastomas with BCC-like foci, the BCC-like foci were often localized in peripheral or deep areas of lesions extending out of the fibrocytic stroma. Immunohistochemistry was performed in five conventional trichoblastomas and in two trichoblastomas with BCC-like foci, using antibodies against CK20 and CK15. No CK20-positive Merkel cells and no expression of CK15 were seen in any neoplastic aggregations of the two trichoblastomas with BCC-like foci. In contrast, increased numbers of Merkel cells and positive staining for CK15 were observed in all five trichoblastomas without BCC-like foci. The five trichoblastomas without BCC-like foci included two trichoblastomas with a popped out or shelled out appearance, which characteristically had a thick fibrous capsule surrounding the fibrotic stroma, demonstrating numerous Merkel cells in the aggregations. Some trichoblastomas may undergo mutations, resulting in the development of foci of BCC and in the loss of the expression of CK15 as well as the disappearance of Merkel cells.

Development of self-expandable covered stents.

We newly developed self-expandable covered stents by combining two of our original technologies. Of these, the first is the dip-coating covering method that was developed previously for balloon-expandable stents; the other is the newly developed self-expandable Nitinol stents, namely, Sendai stents. The three types of covered stents with the expansion diameter of 4.5, 5.0, or 6.0 mm thus obtained had a laser-processed microporous elastomeric cover film (pore diameter: 100 microm, interpore distance: 250 microm). Although the film was extremely thin (approximately 15 microm), the film could be expanded without causing any damage, the strut was completely embedded within the film, and the luminal surface of the film was smooth and flat. Mechanical properties such as ideal flexibility to follow the shapes of arteries were almost retained even after covering. As appropriate drugs, the blood-contacting inner and tissue-contacting outer surfaces of the film were differentially coated with argatroban for antithrombogenicity or FK506 for anti-inflammation, respectively. The preliminary in vivo study indicated that the covered stents mounted in the delivery catheter were navigated and placed to appropriate position in the arteries, and permissible neointimal thickening after 1-month implantation was observed similarly in noncovered stents.

Atrophic dermatofibrosarcoma protuberans with diffuse eosinophilic infiltrate.

Atrophic dermatofibrosarcoma protuberans (atrophic DFSP) is a variant of dermatofibrosarcoma protuberans (DFSP), and is clinically characterized by depressed lesions. We report a patient with a typical atrophic DFSP lesion with marked eosinophilic infiltration. The patient was a 55-year-old woman with a dark-red, depressed lesion in the epigastric region. Histopathological examination of the lesion showed proliferation of fibroblast-like cells in a storiform pattern in the dermis and subcutaneous tissue. Immunohistochemical staining of tumor cells was positive for CD34. The lesion was histopathologically typical of DFSP, but no elevated lesion was clinically observed. Thus, a diagnosis of atrophic DFSP was made. Moreover, this tumor tissue exhibited marked eosinophilic infiltration. To our knowledge, they are no reports of eosinophilic infiltration in DFSP tissue. Therefore, this seems to be an extremely rare case of DFSP.

Epithelioid cell histiocytoma with underlying artery damage.

Although epithelioid cell histiocytoma is considered a variant of fibrous histiocytoma (dermatofibroma), the histogenesis of this condition remains controversial. A recent investigation suggested the possibility that epithelioid cell histiocytoma is an angioformative fibrous histiocytoma. We report a case of epithelioid cell histiocytoma underlying a damaged artery. This epithelioid cell histiocytoma with a central area of hemorrhage was associated with a medium-sized artery in the reticular dermis running vertically up to the lesion. Both the artery in the reticular dermis and its centrally branched artery in the subcutaneous tissue showed mural injury and intraluminal epithelioid endothelial proliferation. Immunohistochemically, the labeling rate for each of the antibodies studied in the epithlioid cells was as follows: 40% for Factor XIIIa, 5% for CD34, 20% for factor VIII-related antigen, and 10% for alpha-smooth muscle cell actin. This case may support the view that epithelioid cell histiocytoma is a vascular and angioformative fibrous histiocytoma.

Giant polypoid basal cell carcinoma with features of fibroepithelioma of Pinkus and extensive cornification.

We report on a case of a 61-year-old woman with a giant polypoid BCC, measuring 7.1 x 5.0 x 2.2 cm, on the genital region (the pubic area). The histopathological features of this BCC interestingly showed fibroepithelioma of Pinkus with cornification, and merging with nodular BCC with extensive cornification (so-called keratotic BCC). The giant BCC with features of fibroepithelioma of Pinkus is exceedingly rare.