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Incorporation of surrounding tissues after implantation of synthetic vascular prostheses potentially varies in accordance with implanted prostheses. To evaluate post-implant tissue incorporation, we examined surgical, histological and ultrastructural findings after implantation in animal models. Three types of commercially available prostheses were tested (Gelweave™; Group G, J Graft SHIELD NEO®; Group J and Triplex®; Group T). Prostheses were implanted into Sprague–Dawley rats subcutaneously or sutured on abdominal aorta of Japanese white rabbits. The tissues were surgically examined for adhesion and were subjected to histological evaluations for cellular and tissue infiltration and ultrastructural observations by scanning electron microscopy (SEM). Group G exhibited less tendency in adhesion formation in early phase (rat: G vs J, P

IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ inflammatory disorder caused by tissue infiltration of lymphocytes with IgG4-secreting plasma cells. Herein, we discuss a case of a patient with IgG4-RD who had involvement of multiple organs: the kidneys, lymph nodes, bone marrow (biopsy performed), lungs, liver, and small intestine (imaging abnormalities). Although several case reports and series of IgG4-RD involving different organ involvement are in the literature, our patient has extensive simultaneous multi-organ involvement. We utilized the four domains (serologic, pathologic, radiologic, and pathologic) as discussed in the new 2019 ACR/EULAR classification criteria to provide a useful framework in considering an alternative tool for IgG4-RD in multi-organ involvement, where biopsy is more invasive and not always accessible. We highlight the findings of each organ involved that increase the likelihood that the patient has IgG4-RD. In our patient, the IgG4-RD classification criteria was fulfilled with total points adding up to 48. Our case meets the classification criteria for IgG4-RD, since at least one organ is involved to meet entry criteria (biopsy proven), no exclusion criteria are present, and the total points are ≥ 20. When such extensive involvement of IgG4-RD occurs, early diagnosis and treatment are recommended to avoid irreversible organ damage and better outcomes.

Local anaesthetics agents (LAA) are used ubiquitously in the medical field and in a wide variety of ways: tissue infiltration, perineural, intra-articular and intravenous. The purpose of this review is to explore the pharmacology of LAAs and to examine the clinical applications for LAAs.

IgG4-related disease (IgG4-RD) is a clinical entity characterized by elevated serum IgG4 and tumor-like inflammation, with tissue infiltration by IgG4 and plasma cells. IgG4-RD is rare, but clinically significant, and its urologic manifestations have been reported in the literature. The present review covers a broad spectrum, describing the pathologies related to the area of urology. In 2003, Terumi Kamisawa was the first to recognize IgG4-RD, characterized by multiorgan lesions in patients with autoimmune pancreatitis and classified as an inflammatory and fibrotic entity with a dense lymphoplasmacytic infiltrate, positive for IgG4.(1–3) It presents in middle-aged patients, between 59-68 years of age, with no clear distribution by sex, (4–6) and has different clinical presentations. The main urologic manifestations are inflammatory pseudotumors and lower urinary tract symptoms. The present article offers a clear, general overview of the disease, encompassing its pathophysiology, diagnosis, and treatment, from the perspective of urology.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome which shares similar pathologic, serologic, and clinical features in the affected organs. Subacute development of a mass or diffuse enlargement of the organ is a common presenting feature. It is more commonly seen in middle-aged or older men. Lymphadenopathy is common in them. Tissue infiltration with lymphoplasmacytic collection, predominantly of IgG4-positive plasma cells, accompanied by “storiform” pattern of fibrosis, obliterative phlebitis, and increased tissue eosinophils are the hallmark histologic findings. Rapid response to systemic steroids is characteristic. If present, the typical cutaneous findings such as papulonodules or plaques in the head-and-neck region may serve as an initial clue to the underlying systemic involvement in IgG4-RD. Hence, dermatologists need to be aware of this entity for early recognition of underlying organ involvement and thus the prompt management.

Background Limited research exists examining the influence of age on the passive mechanical properties of the muscle-tendon unit. The purpose of the present study was to 1) investigate the age-related differences in maximum range of motion (MRoM), stretch tolerance (maximal tolerable torque), and the dissipation coefficient (DC), and 2) examine the influence of plantarflexor muscle size and quality on the age-related differences in the DC. Methods Twenty-one young and 14 older men completed a MRoM assessment to determine peak torque (PTpass), energy stored (area under the loading curve), energy restituted (area under the unloading curve), and the DC (normalized hysteresis) from the angle-torque curve. Ultrasonography was used to determine muscle cross-sectional area (CSA) and subcutaneous fat corrected echo intensity (EI) of the gastrocnemii. Findings The PTpass, MRoM, and energy restituted were greater (P ≤ 0.046) in the young men, whereas the DC and EI were greater (P ≤ 0.024) in the older men. When accounting for CSA, differences between groups for the DC remained (P = 0.028), while there were no longer differences between groups when accounting for EI (P = 0.120). PTpass was also strongly related to MRoM (r = 0.755, P Interpretation Older men exhibited lower dorsiflexion MRoM and a greater DC, which may be explained by an altered stretch tolerance and qualitative changes (i.e., non-contractile tissue infiltration) in aged skeletal muscle leading to greater energy dissipated, respectively.

Macrophages are a major component of the immunoresponse. Diversity and plasticity are two of the hallmarks of macrophages, which allow them to act as proinflammatory, anti-inflammatory, and homeostatic agents. Research has found that cancer and many inflammatory or autoimmune disorders are correlated with activation and tissue infiltration of macrophages. Recent developments in macrophage nanomedicine-based disease treatment are proving to be timely owing to the increasing inadequacy of traditional treatment. Here, we review the role of macrophages in nanomedicine-based disease treatment. First, we present a brief background on macrophages and nanomedicine. Then, we delve into applications of macrophages as a target for disease treatment and delivery systems and summarize the applications of macrophage-derived extracellular vesicles. Finally, we provide an outlook on the clinical utility of macrophages in nanomedicine-based disease treatment.

Dermal regenerative templates (DRTs) provide an option for management of complex lower extremity wounds. DRTs may be used to achieve definitive wound closure by serving as a scaffold for local tissue infiltration. Healing with a DRT interface leads to histologic and structural properties similar to native skin. DRTs can be applied over deep wounds with exposed critical structures that may have required a local or free flap. DRTs are a valuable option for lower extremity limb reconstruction.

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disease of the mononuclear phagocyte system, characterised by tissue infiltration of CD1a+ CD207+ histiocytes. The clinical presentation is variable, ranging from unifocal asymptomatic bone involvement to life-threatening multisystem disease, requiring aggressive therapeutic approaches. Intraocular involvement is uncommon and associated to poor visual and general prognosis. Herein, we report a case of LCH in a newborn with ocular and multisystem risk organ involvement, unresponsive to several lines of chemotherapy. Off-label administration of vemurafenib led to dramatic improvement at systemic level; however, chronic sequelae of ocular involvement resulted in poor visual prognosis.

Paraneoplastic syndromes are observed in less than 1% of patients with cancer and include a variety of disorders that do not depend on direct tumor mechanisms, such as tissue infiltration, compress...

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disease of the mononuclear phagocyte system, characterised by tissue infiltration of CD1a + CD207+ histiocytes. The clinical presentation is variable, ranging from unifocal asymptomatic bone involvement to life-threatening multisystem disease, requiring aggressive therapeutic approaches. Intraocular involvement is uncommon and associated to poor visual and general prognosis. We report a case of LCH in a newborn with severe ocular and multisystem risk-organ involvement, unresponsive to several lines of chemotherapy. Off-label administration of vemurafenib led to dramatic improvement at systemic level; however, chronic sequelae of ocular involvement resulted in poor visual prognosis. Intraocular LCH involvement may be asymptomatic and clinical signs delayed, leading to severe complications, especially in newborns and young children. Screening for ocular involvement is essential for early treatment initiation, which can possibly improve the visual outcome. Vemurafenib is effective on systemic involvement, and its role in ocular LCH needs to be evaluated.

In order to develop small-diameter vascular grafts, it is necessary to evaluate endothelialization, especially, in the center part at early stage. For implantation of vascular grafts of 1 cm in length to abdominal aortae of rat, endothelial cells can be formed easily by stretching anastomosis. We evaluated the endothelialization in the center part of vascular grafts by implanting vascular grafts using transgenic (TG) silk fibroin (SF) of 3 cm in length. Vascular grafts were prepared 1.5 mm in diameter and 1 and 3 cm in length using wild type (WT) SF and TG SF by braiding structure, respectively. The grafts were removed after 2 weeks or 3 months and evaluated pathologically. Endothelialization was not confirmed totally after 3 months of implantation. However, endothelialization in the center part of grafts was significantly higher in TG SF than in WT SF. No significant difference was found regarding tissue infiltration and internal diameter. The TG SF revealed migration of the endothelial cells into the center part of the vessels at the early stage. Also, tissue infiltration and remodeling is expected using SF. The 3 cm length vascular grafts can be evaluated as a new experimental system.

Los síndromes eosinofílicos pulmonares (SEP) comprenden un grupo heterogéneo de enfermedades que tienen en común la infiltración eosinofílica en el lavado broncoalveolar y la infiltración tisular en el análisis histopatológico. Se expone un caso correspondiente a una paciente de sexo femenino de 42 años quien consultó por un cuadro clínico agudo de tos, disnea y eosinofilia periférica, con estudios de imágenes torácicas compatibles con con- solidación alveolar en ambos segmentos basales posteriores, la língula y el segmento lateral del lóbulo medio derecho. Se descartó parasitosis, infección por micobacterias, infección por hongos, virus respiratorios, patología oncológica y reumatológica. La biopsia de pulmón mostró un engrosamiento de los tabiques interalveolares con proliferación celular de linfo- citos e histiocitos con hiperplasia alveolar, neumocitos atípicos y ocupación difusa de la luz con abundantes eosinófilos. El curso clínico y los hallazgos histopatológicos confirman el diagnóstico de neumonía eosinofílica aguda (NEA).

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413-420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77-84, 2019. © 2019 Wiley Periodicals, Inc.

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptom...

Background:Elevated serum IgG4 (sIgG4) and IgG4+ plasma cell tissue infiltration are outstanding features of IgG4-related disease (IgG4-RD). However, elevated IgG4 is not specific for IgG4-RD. Our previous study reported elevated sIgG4 in 46% of rheumatoid arthritis (RA) patients (Mediators Inflamm 2014). Whether synovium from RA patients show similar characteristics of IgG4-RD and how about the clinical characteristics of RA patients with IgG4-related synovitis have not been reported yet.Objectives:To explore the serum and synovial IgG4 level and their correlation with disease indicators in RA.Methods:Active RA patients who underwent needle synovial biopsy with qualified synovium tissue were recruited. Demographic and clinical data were collected simultaneously. Synovium tissue were stained with H&E for Krenn synovitis score and immunohistochemistry for positive cell densities of CD20, CD38, IgG and IgG4. Serum IgG4 level was detected by immunonephelometry.Results:Among 96 RA patients recruited, 74 (77.1%) were female, the median age was 55.0 (46.0~61.0) years, disease duration was 42.0 (12.0~120.0) months and SDAI was 31.2 (22.1~42.8).The median sIgG4 was 1.38 (0.86~2.42) g/L and 49(51.0%) patients had elevated sIgG4. Compared with those with normal sIgG4, RA patients with elevated sIgG4 had significantly higher levels of PrGA [7 (5~8) vs. 6 (4~7)], ESR [90 (64~116) mm/h vs. 61 (38~75) mm/h], CRP [46.20 (17.20~74.20) mg/L vs. 18.90 (9.46~49.20) mg/L], DAS28-ESR [6.3 (5.6~7.4) vs. 5.7 (4.7~6.4)], SDAI [34.2 (25.3~48.8) vs. 27.8 (18.9~35.9)] and HAQ-DI [1.70 (0.61~2.28) vs. 0.88 (0.40~1.75), all P2 vs. 1020(354~1777) /mm2], IgG4+ plasma cells [106 (39~249) /mm2 vs. 68 (3~123) /mm2], and higher ratio of IgG4+/IgG+ plasma cells [26.3 (15.5~38.0) % vs. 15.2 (0.9~24.7) %, all PThe median IgG4+ plasma cells count was 83 (10~192) /mm2 and median ratio of IgG4+/IgG+ plasma cells was 19.1 (8.4~31.5)%. Both of them correlated positively with ESR, CRP and sIgG4 (r=0.216~0.394, all P10/HPF, who had significant higher ESR [86 (50~109) mm/h vs. 65 (40~84) mm/h] and CRP [43.35 (16.93~77.85) mg/L vs. 26.15 (9.54~52.53) mg/L, both P40%, and 11 (11.5%) patients with both IgG4+ plasma cells >10/HPF and IgG4+/IgG+ plasma cells ratio >40% (IgG4-related synovitis). RA patients with IgG4-related synovitis had significant higher ESR than the others [106 (53~125) mm/h vs. 69 (41~91) mm/h, PThere were 10 (10.4%) patients showing elevated sIgG4 and IgG4-related synovitis. Four patients completed 1-year follow-up and all of them achieved remission at 6th month (SDAI≤3.3, Figure 1). Only one patient had radiographic progression at 12th month.Figure 1.Dynamic disease activity of 4 RA patients with elevated sIgG4 and IgG4-related synovitis during 1-year follow-up.Conclusion:IgG4-related synovitis can be found in RA patients. Their clinical significance in disease characteristics and outcomes are worth further study.Acknowledgements:This work was supported by National Natural Science Foundation of China (no. 81971527, 81801606 and 81801605), Guangdong Natural Science Foundation (no. 2018A030313541 and 2018A030313690), Guangdong Medical Scientific Research Foundation (no. A2018062), Guangdong Basic and Applied Basic Research Foundation (no. 2019A1515011928 and 2020A1515110061), and Science and Technology Program of Guangzhou (no. 201904010088).Disclosure of Interests:None declared

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing–remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids.In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD.With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.

A long-acting buprenorphine subdermal implant, Probuphine, was approved by the Food and Drug Administration (FDA) in May 2016, for the maintenance treatment of patients with opioid-use disorder. Long-acting implants offer the potential benefits of improved medication adherence, consistent daily dosing, and reduced risk of medication diversion. Sets of 4 implants are typically inserted for a period of 6 months and then removed. Similar technology has been successfully utilized in implantable formulations of birth control medications; however, there is currently little clinical experience involving buprenorphine implants that have remained in the body for extended periods of time. This is a case report involving an early clinical study subject who had been lost to follow-up at the time of the original study because of incarceration. Despite the protracted duration of time since initial implantation, all 4 implants remained easily palpable, and displayed little physical deterioration or tissue infiltration. All implants were able to be removed using the standard explant technique of midline incision and limited tissue dissection. While extending length of treatment beyond the indicated 6-month period is not being espoused, this case demonstrates that although situations may arise where implants may remain in an individual for longer than the intended dosing period, implants may be removed safely despite remaining implanted for longer than intended.

Objective: To explore the imaging features of local recurrences (LRs) based on magnetic resonance imaging (MRI) after oncological orthopaedic surgery with prosthesis reconstruction. Methods: A total of 78 cases totalling 157 scans were retrospectively reviewed. Patients with nodule/mass-like signals were retrospectively classified into LR, infectious pseudotumour, and asymptomatic pseudotumour according to clinicopathological data. LRs were histologically confirmed, and the patients without recurrences were followed up for at least 2 years. Mass size distribution and radiological characteristics were analysed for differential diagnosis of the LR versus pseudotumour. Results: Thirty-three of 78 cases were positive with nodule/mass-like signal findings on the post-operative MRI images. By analysing the size distribution, we found that masses >2.1 cm (14) were almost attributable (98% specificity) to LRs and mostly (84.6%) timely treated. Contrarily, masses ≤2.1 cm (19) are challenging for differential diagnosis of LRs versus pseudotumour and were undertreated in five of the nine LR cases. MRI characteristics of masses ≤2.1 cm were found to be highly heterogeneous, with solid appearance, adjacent infiltration, and less peritumour oedema being significant indicators for LRs (P＜0.05). Receiver operating characteristic curve showed area under curve of 0.93 for this predictive model. Conclusions: For the post-operative MRI surveillance of oncological orthopaedic surgery with prosthesis reconstruction, a mass larger than 2.1 cm was highly specific for recurrence. When a mass was smaller than 2.1 cm, more solid property, more adjacent tissue infiltration, and less muscular oedema indicated recurrence rather than a benign mass. The translational potential of this article: There has been very little data associated with the post-operative magnetic resonance imaging features indicating recurrence in patients with malignant bone sarcoma after prosthesis replacement. This study could help develop diagnostic features of magnetic resonance imaging for differentiating recurrence from benign changes in these patients after prosthesis replacement. Keywords: Magnetic resonance imaging, Post-operative, Prosthesis, Recurrence

Xanthoma cystitis of urinary bladder is a rare entity and may present as an intravesical mass. A 38-year-old female presented with abdominal pain and imaging was done which was suggestive of a malignant mass with surrounding tissue infiltration. Partial cystectomy was performed, and histological examination of the mass showed xanthomatous cystitis.

Highlights • The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8–105). • Histological examination of the submandibular gland showed an adenoid cystic carcinoma with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma., Introduction Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory condition associated with elevated serum IgG4 levels and tissue infiltration by IgG4-expressing plasma cells. We present a case of adenoid cystic carcinoma (ACC) of the submandibular gland with possible involvement of IgG4-RD. Presentation of case The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8–105). An initial open biopsy for histological diagnosis showed chronic sialadenitis. The region was monitored on an outpatient basis, and finally the right submandibular was totally resected because malignant tumor could not be excluded. Histological examination of the submandibular gland showed an ACC with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma. Discussion We have described a case that indicated a possible involvement of ACC with IgG4-RD. This allows us to speculate that longstanding IgG4-RD may progress to malignancy or infiltration of IgG4-positive plasma cells through the signals of tumor stimuli. Further investigations are required to determine the potential pathogenic mechanism underlying this unique tumor. Conclusion This case underscores that caution is needed in the diagnosis of masses with high serum IgG4 levels, as the differential diagnosis includes malignancy.

IgG4-related disease, a newly described immune-mediated disorder with tissue infiltration of IgG4-positive plasma cells, has been reported in nearly every organ. In the kidney, it manifests as IgG4-related tubulointerstitial nephritis (TIN) but may also present as membranous nephropathy. We report a patient with IgG4 renal disease who had membranous nephropathy as well as TIN.

Bone-patellar tendon-bone (BPTB) autografts are the gold standard for anterior cruciate ligament (ACL) reconstruction because the bony ends allow for superior healing and anchoring through bone-to-bone regeneration. However, the disadvantages of BPTB grafts include donor site morbidity and patellar rupture. In order to incorporate bone-to-bone healing without the risks associated with harvesting autogenous tissue, a biodegradable and synthetic tri-component graft was fabricated, consisting of porous poly(1,8-octanediol-co-citric acid)-hydroxyapatite nanocomposites (POC-HA) and poly(l-lactide) (PLL) braids. All regions of the tri-component graft were porous and the tensile properties were in the range of the native ACL. When these novel grafts were used to reconstruct the ACL of rabbits, all animals after 6 weeks were weight-bearing and showed good functionality. Histological assessment confirmed tissue infiltration throughout the entire scaffold and tissue ingrowth and interlocking within the bone tunnels, which is favourable for graft fixation. In conclusion, this pilot study suggests that a tri-component, biodegradable graft is a promising strategy to regenerate tissue types necessary for ACL tissue engineering, and provides a basis for developing an off-the-shelf graft for ACL repair. Copyright © 2014 John Wiley & Sons, Ltd.

Case report We report the case of a 48 year-old male with bilateral involvement of the salivary and lacrimal glands, which was diagnosed as Mikulicz's disease by incisional biopsy of the affected lacrimal glands, which was completely resolved after corticosteroid treatment. Discussion Sclerosing sialadenitis and/or dacryoadenitis are chronic inflammatory diseases that are currently classified into IgG4-related diseases. Specifically, Mikulicz's disease is defined by a persistent and symmetrical swelling of the lacrimal and salivary glands together with elevated serum concentration of IgG4 and tissue infiltration by IgG4 (+) plasma cells.

IgG4-related disease (IgG4-RD) is a recently recognized disease covering different fibroinflammatory disorders with common histopathological findings. Virtually all organs can be involved, but the most frequently affected are the pancreas, biliary tree, salivary and lacrimal glands, retroperitoneum and aorta, kidneys, and lymph nodes. Several organ manifestations can develop simultaneously or metachronously in the same patient. Clinical and radiological presentation is usually pseudotumoral with mass-forming lesions, requiring rigorous clinicopathological examination and exclusion of alternative diagnoses, especially cancer. Histopathological abnormalities include polyclonal lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. Immunohistology shows tissue infiltration by numerous IgG4-positive plasma cells. Steroids are usually dramatically effective in this condition, but relapses are frequent and second-line treatments are often necessary. An overview on main clinical and therapeutic aspects of the disease is proposed in this chapter.

Waldenstrom macroglobulinemia (WM) is an un- common clinico-pathological syndromic manifesta- tion of lymphoplasmacytic lymphoma. In the more common sub-types of non-Hodgkin lymphoma (NHL) there are internationally accepted robust and reproducible response criteria (1). As with other forms of NHL, WM can lead to tissue infiltration resulting in the clinical, laboratory, and radiological manifestations of lymphadenopathy, hepato-spleno- megaly, and peripheral blood cytopenias. In common with the standard response criteria for NHL, evalua- tion of reduction or complete resolution of these manifestations can be determined using routine clinical evaluation, laboratory, imaging, and bone marrow histologic evaluation criteria. However, WM potentially has two unique addi- tional manifestations which complicate response assessment. First, by definition, all cases of WM are associated with a monoclonal immunoglobulin M (IgM) paraprotein. Extrapolating from observations and conventions derived from studies in multiple myeloma (MM), in WM, while there is modest utility in comparing monoclonal IgM levels across patients as a measure of relative tumor burden, serial measurements of the monoclonal IgM paraprotein level in an individual patient are accepted as a quantitative measure of disease burden. While in MM disease progression can occur in the absence of a paraprotein rise, characterized by an increase of the free light chains in the serum only ('light chain escape'), particularly after a long course of disease with several lines of treatment (2), to our knowledge this has not been reported for WM. In the relatively rare case of WM-transformation to a high-grade lymphoma, this can occur either with or without increasing levels of the pre-existing paraprotein (3). Thus, appropriately quantitative measurement of the serum monoclonal IgM is included in response criteria for WM (4).

7558Background: In DLBCL, hepatic and/or renal dysfunction may occur due to tissue infiltration with lymphoma, bulky lymphadenopathy leading to obstruction or tumor lysis leading to renal dysfuncti...

The purpose of this study is to help in the choice of an appropriate reconstructive technique by reference to the dimensions of the defect, the required functional and esthetic outcomes, and retention of adequate surgical safety margins to prevent primary tumor recurrence. Material and methods A total of 158 patients were treated. We indicate how the most appropriate reconstructive method may be chosen, with reference to the size and position of the cancer and depth of tissue infiltration. Result Of all patients, 89 (56.3%) had T1 (lesions up to 2 cm long, less than 1/3). The remaining patients had T2 lesions >2 cm, from 1/3 to 2/3 of lip involvement (50 patients), T3 lesions >4 cm, more than 2/3 of lip involvement (18), and a T4 lesion > 5.5 cm with commissure involvement (1). Conclusion We share the widespread view that a surgeon who performs a reconstruction using the minimal tissue components required to close the lesion will achieve the best results. Reconstruction does not influence prognosis and overall should be oriented to the defect. Careful, clean, and safe resection of lip carcinoma, with creation of healthy margins, can be followed by functional and esthetic lip reconstruction.

Acute or chronic inflammation is thought to play a major role in the etiology and/or pathogenesis of autoimmune disease. Often viral infections are the initial cause for a local inflammatory reaction resulting in tissue infiltration by activated leukocytes. The activation and trafficking of these leukocytes to the site of inflammation is conducted by chemoattractant cytokines, termed chemokines. Depending on the genetic background and the history of previous infections, such infiltrating leukocytes can potentially include autoaggressive lymphocytes with specificity to tissue antigens. The number of specific precursor lymphocytes, strength of activation and degree of counteracting immunoregulatory measures determine whether such an autoimmune incident ultimately results in autoimmune disease. Thus, by blocking the initial inflammatory insult one could in theory prevent the excessive attraction of autoaggressive lymphocytes to the inflammation site and the subsequent formation of a pattern that leads to autoimmune disease. This review focuses on blocking of chemokines in animal models of type 1 diabetes and discusses the possible applications of such treatments in human autoimmune disease.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized idiopathic systemic disorder associated with elevated serum IgG4 level and tissue infiltration by IgG4-positive plasma cells. Multiple neurological manifestations, including peripheral neuropathy, have been described in IgG4-RD. Our objective is to discuss a case report and review of the literature, which would expand the spectrum of IgG4-RD.We describe the clinical features and biopsy findings in a patient with IgG4-RD who presented with features suggestive of neuromyopathy in the setting of recurrent pleural effusion and weight loss.Electrodiagnostic findings were suggestive of an irritable myopathy and polyradiculoneuropathy with primary demyelination and secondary axonal degeneration. Pleural biopsy and laboratory studies confirmed the diagnosis. Improvement was sustained with steroid therapy.We describe the first case, to our knowledge, of IgG4-related neuromyopathy associated with recurrent pleural effusion. Our case expands the clinical spectrum of IgG4-RD. Neurologists should be aware of this treatable disorder and in the appropriate clinical context consider it in the differential diagnosis of neuromyopathy.

In this study, we assessed the feasibility and clinical advantages of single photon emission computed tomography with CT (SPECT/CT) for sentinel lymph node (SLN) detection in vulvar cancer.This is a unicentric prospective trial. Vulvar cancer patients underwent preoperative SLN marking (10MBq Technetium (TC)-99m-nanocolloid) and subsequent planar lymphoscintigraphy (LSG) and SPECT/CT for SLN visualization. Directly before surgery, a patent blue dye was injected. We assessed detection rates of SPECT/CT and those of planar LSG and intraoperative detection. We analyzed the sensitivity, negative predictive value and false negative rate.At Hannover Medical School, 40 vulvar cancer patients underwent SLN dissection after preoperative LSG and SPECT/CT. The mean diameter of all tumors in final histology was 2.23 (0.1-10.5) cm with a mean tissue infiltration of 3.93 (0.25-11) mm. In preoperative imaging, SPECT/CT identified significantly more SLNs (mean 8.7 (1-35) LNs per patient) compared to LSG (mean 5.9 (0-22) LNs, p0.01). In addition, SPECT/CT led to a high spatial resolution and anatomical localization of SLNs. Thus, SPECT/CT identified aberrant lymphatic drainage in 7/40 (17.5%) patients. There were no significant differences, but significant correlation was found between SPECT/CT and intraoperative SLN identification. Regarding inguino-femoral LNs, for all patients who underwent complete groin dissection, sensitivity was 100%, NPV was 100% and false negative rate was 0%.SPECT/CT leads to higher SLN identification compared to LSG in vulvar cancer. Due to its higher spatial resolution and three-dimensional anatomical localisation of SLNs, SPECT/CT provides the surgeon with important additional information, facilitates intraoperative SLN detection and predicts aberrant lymphatic drainage.

Introduction: Calcium hydroxyapatite (CaHa; also spelled “hydroxylapatite”) is the main mineral component of bone, calcified cartilage, and teeth. It has been used since the 1970s in many specialties, including orthopedics, urology, otolaryngology, maxillofacial surgery, and radiology, as a bioactive implant that promotes chemical attachment of the soft tissue to its surface. In 2001, Radiance FN (now Radiesse) was introduced as a CaHa-based product and approved by the US Food and Drug Administration (FDA) as a radiographic tissue marker, for soft tissue vocal fold augmentation, and for implants in maxillofacial defects. Currently, it is also used outside the United States and off-label in the United States for facial soft tissue augmentation. Microspheres of CaHa are suspended in a mixture of water, glycerin, and carboxymethylcellulose gel that provides a scaffold for tissue infiltration. Once injected, the gel is degraded and the CaHa infiltrates the surrounding cells. CaHa is nonirritating, and the carrier gel components are classified as safe by the FDA. Although a great variety of fillers are currently on the market, CaHa (Radiesse) has demonstrated the longest duration in tissue without any reports of antigenicity, migration, or granuloma formation. In this study, we report our experience with CaHa (Radiesse) for aesthetic soft tissue augmentation. Materials and Methods: A total of 139 patients were treated over an 18-month period at 2 private offices in Argentina and the United States. Exclusion criteria included previous use of permanent tissue fillers in the treatment area. Patients with previous use of hyaluronic acid fillers in the treatment area (up to 1 year prior to the study) were allowed to participate in the study. Radiesse was injected from 1-mL prefilled syringes with 27½-gauge needles in different areas such as nasolabial folds, lips, marionettes lines, cheeks, and cellulite dimples. Patient satisfaction and adverse effects were assessed by both physicians and patients during the procedure and during follow-up visits up to 1 year later. Results: Minimal pain, erythema, edema, and bruising were noted during and immediately after the procedure. All of the patients treated were satisfied with their results after one visit. There were no long-term adverse effects during the study period or on follow-up visits. Evaluation of 75% of the patients 1 year after treatment revealed persistence of filling effects. Discussion: CaHa used for aesthetic soft tissue augmentation yields immediate clinical results with high patient satisfaction.

The aim of this study was to assess the influence of inflammatory reactions in herniated lumbar disc specimens on pain resolution after lumbar disc surgery. Disc specimens of 200 patients who underwent surgery for lumbar disc herniation were studied immunohistologically. Preoperatively each patient received a verbal rating scale (VRS) for classification of the pain level and general clinical data were recorded prospectively. Varying amounts of macrophages could be demonstrated. Eighty-nine percent of patients could be followed up for a mean period of 7 months. A statistically significant correlation between the histologically observed macrophage infiltration and postoperative pain grading according to the VRS was found. Patients with evidence of inflammatory reactions rated their postoperative complaints lower than patients with no evidence of inflammatory reactions on the VRS (P=0.04). In our study, a statistically significant correlation between inflammatory changes in the herniated lumbar disc specimen and outcome after lumbar disc surgery could be demonstrated.

Erdheim-Chester disease (ECD) is a rare non–Langerhans cell histiocytosis characterized by the accumulation of foamy CD68+CD1a− histiocytes. Tissue infiltration preferentially affects long bones and retroperitoneal and peri-aortic spaces, but almost any organ or system can be affected.1 Cardiac and neurologic involvements are associated with significantly higher levels of mortality and morbidity.2

Osteopetrosis is a rare disorder characterised by a defect in osteoclastic bone resorption. This report describes osteopetrosis in a neonatal donkey that suffered a displaced tibial fracture. Radiographic examination identified generalised reduction in medullary cavity size, thickened mid-diaphyseal cortices and conical metaphyseal bone extending toward the mid-diaphysis of long bones. Postmortem examination identified additional fractures and brittle bones. Histologically, osteoclasts were absent in multiple bone sections. Diaphyseal cortices consisted of concentric bone lamellae with marrow tissue infiltration. Large wedges of secondary spongiosa extended from the metaphyseal growth plate. Clinical and histopathological features were similar to an osteoclast-deficient, autosomal recessive form of osteopetrosis in humans.

We report the case of a 58-year-old man presenting with successive development of two uncommon tumors of soft tissue in the gastric location. The initial histological examination diagnosed a gastrointestinal stromal tumor (GIST) which was treated by surgical resection. Two years later a new tissue infiltration appeared at this surgical site. Our hypothesis suggested a GIST recurrence, but histological examination and genetic analysis diagnosed a desmoid tumor. Association of these two rare tumors localised at the same site has never been described.

Approximately 10% of newborn infants with Down Syndrome develop a form of megakaryoblastic leukemia which usually disappears spontaneously during the first months of life. The evidence that this "Transient Leukemia" is truly leukemia includes the following: it is clonal proliferation, it can be fatal and tissue infiltration of leukemic cells occurs. Also in approximately 25% of cases that recover, Acute Megakaryoblastic Leukemia will develop in the first four years of life, which, if not treated, is fatal. Evidence regarding the megakaryoblastic nature of the leukemic cells is presented as well as a description of the lethal forms of the disease. The study of Transient Leukemia is of considerable importance because it can provide insight into both the nature of leukemia and its relation to trisomy 21.

Although IgG4-related disease (IgG4-RD) is a novel and important disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells, its clinical diagnostic criteria have not been fully established. Many patients with IgG4-RD have lesions in multiple organs, either synchronously or metachronously, and the pathological features of each organ differ. We established comprehensive diagnostic criteria for IgG4-RD for the practical use of specialists and nonspecialists.

7069Background: Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are disorders marked by tissue infiltration with macrophages or dendritic cells. > 80% of ECD and LCH patients ...

Although eosinophils play an important role in host defense mechanisms, they also are involved in many inflammatory conditions. Many pulmonary inflammatory disorders are characterized by tissue infiltration with eosinophils, with or without peripheral blood eosinophilia. Treatment often includes imm

Multicentric reticulohistiocytosis (MRH) is a rare and possibly devastating systemic disorder characterized by tissue infiltration by histiocytes and multinucleated giant cells. The disease commonly involves the skin, joints, and mucous membranes, with the rare involvement of other organ systems. We describe a patient with MRH presenting with papules and nodules on both hands and a rapidly progressive arthritis who may have had pulmonary involvement of the disease.

Objective: A new concept of IgG4-related sialadenitis characterized by high serum IgG4 levels and tissue infiltration of IgG4-expressing plasmacytes has recently been proposed. To determine appropriate serum levels of IgG4 for monitoring disease activity, a total of 36 serum samples and 8 tissue samples from patients with IgG4-related sialadenitis were studied.Method: The patient group consisted of 6 men and 4 women with an average age of 60 years (range, 47 to 74 years). Serum levels of IgG4 and the density of IgG4-positive plasmacytes in affected tissues were studied.Results: All patients had elevated serum IgG4 levels (>135 mg/dL), and IgG4-positive plasmacytes (IgG4+ plasma cells/IgG+ plasma cells >50%) were observed in the involved salivary glands. Six patients with IgG4-related sclerosing sialadenitis with high IgG4/IgG ratios and prominent infiltration of IgG4-positive plasmacytes in the involved salivary glands had systemic complications, including pancreatitis, retroperitoneal fibrosis, and/or in...

Background Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and immunity. This process can be negatively regulated by vertebrate chitinases. Chitinolytic activity is significantly increased in nasal polyps (NPs) compared with that in normal turbinate mucosa. Dexamethasone (DEX) or methotrexate (MTX) is an effective treatment for chronic inflammatory diseases. The aim of this study was to investigate the effects of DEX or MTX on chitinolytic activity in organ-cultured NPs. Methods NP tissues were cultured using an air-liquid interface culture model. Cultures were maintained for 24 hours in the absence or presence of DEX (10 or 100 micromolar) or MTX (10 or 100 micromolar). Acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) activities in tissue samples were measured at a range of pH values by using the fluorogenic substrate 4-methylumbelliferyl-beta-(D)-N,N',N″-triacetyl-chitotriose. Results AMCase and ChT chitinolytic activities were significantly lower in NPs treated with 100 micromolar DEX or 100 micromolar MTX than that in fresh or untreated NPs. AMCase chitinolytic activity tended to be lower in DEX-treated polyps than in MTX-treated polyps, although the difference was not statistically significant. Conclusion DEX or MTX reduced chitinolytic activity in NPs. We suggest that DEX or MTX may inhibit the growth of NPs via local regulation of NP chitinolytic activity.

Idiopathic hypereosinophilic syndrome (IHES) is a rare clinical disorder associated with blood and tissue infiltration by eosinophils. Cardiac involvement in patients with IHES can have varied presentations, and is often associated with significant morbidity and mortality. On the other hand, cardiac tamponade is a very rare presentation of IHES, and few anecdotal cases exist in literature. We report on IHES in a patient who presented with cardiac tamponade.

Wrist arthroscopy can be carried out without infusing water as simple traction will suffice to keep the working space clear. The lack of tissue infiltration by fluid keeps soft tissues in pristine condition in the event that open surgery is needed after the arthroscopic exploration. The fact that the dry technique makes watertightness irrelevant opens a new set of possibilities by combining arthroscopy with moderate-sized incisions. Despite the fact that any modification of a technique with which one is familiar can be regarded with major reticence, the advantages of the dry technique well merit giving it a try. As a matter of fact, although in simpler arthroscopic procedures there are probably no differences, the complex ones are much more easily performed under dry conditions. Sooner or later, even the most reluctant wet arthroscopists will have to swap to the dry technique to get the most out of what arthroscopy might offer. On the other hand, any accomplished wrist arthroscopist will have minimal problems to swap from wet to dry and vice versa. Purposefully, to stress the benefits of the dry technique, the procedures dealt with in this chapter rank among the most difficult one can perform arthroscopically, namely distal radius fractures; arthroscopic guided osteotomy; arthroscopic intercarpal arthrodesis; and perilunate fracture dislocations.

The preoperative diagnostic capability of CT and angiography for demonstrating extension of pancreatic cancer behind the pancreas was evaluated. Subjects were 19 patients out of 69 patients operated on for a pancreatic cancer at the department in a recent 11-year period (1980-1990), whose tissue infiltration behind the pancreas was examined in detail and preoperative extension of the cancer was pathologically diagnosed. As to V factor, the total accuracy was 84.2% by CT, that was superior to that (63.2%) by angiography. As to Rp factor, the total accuracy was 52.6% by CT and 68.4% by angiography. Among Rp (-) cases diagnosed by CT and angiography, histologic infiltration-positive ‹rp (+)› cases represented over 80%. Preoperative diagnostic ability of single use of CT or angiography was extremely low. However, when positive findings by either CT or angiography were noted, the correct diagnosing rate was about 80%. It is concluded that positive results accepted aggressively by CT and angiography was correlated with pathological findings. Preoperative CT or angiography was not effective for predicting PLX factor.

Dear Editor,Idiopathic hypereosinophilic syndrome (HES) is a myelo-proliferative neoplasm characterized by persistent eosino-philia due to abnormal proliferation of eosinophilprecursors [1]. Tissue infiltration by eosinophils and therelease of their granuli content cause organ damage. Thereis no specific treatment for HES; however, similar to mostcases of eosinophilias harboring rearrangement ofPDGFRA, some patients respond to the tyrosine kinaseinhibitor Imatinib [2].A 61-year-old female patient was referred to ourinstitution for persistent eosinophilia (3.1×10

Desmoids are rare benign neoplasms of the connective tissue that arise from the deep muscle fascia, aponeuroses, tendons and scar tissue [14, 19, 29]. The Anglo-American literature describes them as “aggressive fibromatosis” [14, 32]. The disease has been known since the 19th century: The terms desmoid and desmoidfibrom were coined by the famous German physiologist and comparative anatomist Johannes Muller (1801-1858) from Berlin in 1838 [56]. The name is derived from ancient Greek and indicates a band-like appearance. In 1832, the surgeon John McFarlane from Glasgow was the first to mention the entity in the English-speaking literature. First neoplasms in the abdominal walls of women who recently had given birth were described [34]. Later, similar tumors were found in other anatomic regions. The term fibromatosis was introduced for the first time by Arthur Purdy Stout from New York [76]. He stated that desmoids are masses of proliferated, scar-like tissue, which in spite of the fact of tissue infiltration rarely recur (which is not true today!) and do not become true malignant neoplasms.

We present a patient with a recurrent glioblastoma and abnormalities of the corpus callosum seen on diffusion tensor MRI that were not seen on conventional imaging. These abnormalities preceded the development of the tumour. We describe the technique of diffusion tissue signatures to assess tissue infiltration by tumours compared with values from normal volunteers.