Ovarian borderline tumors in pre-menarche girls.

By reason of a new case of an ovarian mucinous borderline tumor (BOT) in a pre-menarche girl, a research of current literature was implemented. Low-grade malignant epithelial tumors are extremely rare in young children and, as far as we know, only a few case reports exist. The patients presented with vomiting, pain, and a swollen lower abdomen. Pre-operative diagnosis primarily consists of imaging techniques. At Stage Ia, the tumor is confined to the ovary without penetration of the capsule, no malignant ascites or peritoneal implants. Treatment consists of removal of the tumor combined with concurrent salpingo oophorectomy, appendectomy, omentectomy, and peritoneal lavage. Although the treatment recommendations are not uniform, basically, preservation of fertility is the main objective. The prognosis is very good, but recurrence is possible even after 10 years.

Clinical trial for safety evaluation of hyaluronidase as diffusion enhancing adjuvant for infiltration analgesia of skin with lidocaine.

BACKGROUND: Infiltration anesthesia of the skin is an analgesic procedure often practiced before minor surgical interventions or punctures. The addition of hyaluronidase is a possible option to improve the effectiveness of the local anesthetic with respect to expansion of effect. OBJECTIVE: To validate the safety of intracutaneous application of hyaluronidase as a lidocaine adjuvant. MATERIALS AND METHODS: The influence of adjuvant hyaluronidase on wound healing was investigated using the suction blister method in a prospective, single-center, placebo-controlled, double-blind, intraindividual comparison study with 20 participants. The target parameters were defined as the time of normalization of transepidermal water loss, hemovascular perfusion, and complete macroscopic epithelization of the wound. RESULTS: No evidence was found that adjuvant application of hyaluronidase retards wound healing. CONCLUSION: The addition of hyaluronidase to lidocaine in intracutaneous infiltration analgesia does not lead to retardation of wound healing, and no additional relevant risks were observed.

[Clinical trial: regeneration of skin perception after deep-degree burns in childhood]. / Klinische Studie: Regenerationspotential der Hautsensibilität nach thermischen Hautschädigungen im Kindesalter.

BACKGROUND: Cutaneous aesthesia is frequently impaired following thermal injury. The perception of pressure and touch is compromised. METHODS: We analysed 352 patient files retrospectively and tested the perception in deep burn-damaged skin of children. The skin regions examined were classified into groups according to treatment: group 1: necrosectomy + split-thickness skin graft; group 2: epifascial necrosectomy + split-thickness skin graft; group 3: epifascial necrosectomy + Integra®â€…+ split- thickness skin graft. We used clinically adequate test procedures. RESULTS: 31 children (3 to 16 years old) were included with a total of 228 areas of skin examined, 22 boys and 9 girls, mean total body surface area affected 17.6 %, mean age at time of accident 4.9 years. Perceived sensation in group 3: touching with sharp point = 34 out of 47 areas (6 patients), touching with blunt point = 47 out of 57 areas (6 patients), touching with soft tip = 37 out of 56 areas (7 patients), repositioning hair shafts = 9 out of 12 areas (4 patients), pressure of Frey hair = 40 out of 43 areas (7 patients). In group 1, differentiation of touch stimuli was possible in 7 out of 13 children (70 out of 94 skin areas). The simultaneous threshold was 1.8 cm (SD 1.4), compared with 1.2 cm (SD 1.1) in the control group. The successive threshold was 1.6 cm (SD 0.9) and 1.8 cm (SD 1.5) in the control group. In group 2, differentiation of touch stimuli was possible in 3 out of 6 children (27 out of 52 skin areas). The simultaneous threshold was 3.4 cm (SD 1.3) and 3.4 cm (SD 1.1) in the control group. The successive threshold was 2.4 (SD 1.0) and 1.7 (0.7) in the control group. One patient was examined in group 3. Differentiation of touch stimuli was possible in 4 out of 15 skin areas. The simultaneous threshold was 3.9 cm (SD 0.8) and 2.9 cm (SD 1.1) in the control group. The successive threshold was 2.7 (SD 1.4) and 2.1 (1.0) in the control group. In 93 % to 100 % of tested areas, vibration aesthesia was detectable. Vibration aesthesia did not differ between tune fork and biothesiometer. Four children with 11 different skin areas (group 3) were tested with sensory-evoked potentials. There was no significant difference between case group and control group. CONCLUSION: The sensory perception (receptors and nerve cells) of touch and pressure in deep burns suffered during childhood has an unexpected and high potential for regeneration.

Patella Dislocation in Children and Adolescents.

Introduction Patellar dislocation is one of the commonest knee injuries in adolescents. Although treatment usually leads to good results, the influence of anatomical and functional factors on therapeutic strategy has been underestimated, especially in cases of recurrence. Patients and Methods The course of treatment has been analysed in 88 patients with 136 patellar dislocations. The importance of anatomical conditions was studied using X-ray and MRI findings. The treatment results were critically evaluated in comparison with current recommendations. Results From 2000 to 2015, 109 patellar dislocations occurred in 88 patients; a further 27 previous dislocations were reported by the patients (mean age 14 years, 47 boys and 41 girls). About one-third of patients (35.2 %) suffered one or more recurrences. Almost half (48.6 %) of the dislocations occurred during physical exercise, particularly ball sports. Osteochondral flake fracture was found in 9 % of the patients, and a lesion of the medial patellofemoral ligament in 96 %. There was an anatomical predisposition to patellar dislocation in almost all cases. The sulcus angle, patellar and trochlear dysplasia, and patellar height were highly significantly different between the patient group and controls. The TT-TG distance was subsequently calculated, but had no impact on therapy. Seventy-seven patients were treated conservatively and 32 patients surgically. The conservative procedure included partial immobilisation for six weeks. Surgical reconstruction or tightening was performed in 27 cases; in five, in combination with other surgical procedures. Plasty of the medial patellofemoral ligament with a tendon graft was performed in five patients, and osteochondral or meniscal lesions were repaired in 10 patients. Recurrences occurred in 41.7 % of conservatively treated knees and in 29.6 % of surgically treated knees (without reconstruction with a tendon graft). No recurrence was seen after reconstruction of the medial patellofemoral ligament with a tendon graft. Fifty-four patients underwent a follow-up examination. Fourteen of these (25.9 %) had suffered a recurrence. The outcome 16 months after the end of treatment was mostly good, as were the results of self-assessment (Larson-Lauridsen Score). Conclusion An anatomical predisposition is detectable in almost all cases of patellar dislocation, but frequently occurs with an accident event, e.g. in ball sports. Primary patellar dislocations without serious concomitant injuries may be treated conservatively. In the event of recurrence, the indication for surgery is given, even in young patients and in any patient with an osteochondral flake fracture. Tightening reconstruction of the MPFL used to be frequently performed, but is associated with a high rate of recurrence.

The expression of CD97EGF and its ligand CD55 on marginal epithelium is related to higher stage and depth of tumor invasion of gastric carcinomas.

CD97EGF is a member of the EGF-TM7 family of class II seven-transmembrane (7TM), and its cellular ligand CD55 (also known as decay accelerating factor; DAF) protects host cells from complement attack. To determine whether the expression levels of these two molecules are correlated with the clinicopathological features of gastric carcinomas, a total of 35 gastric carcinomas and their corresponding margins and normal specimens were investigated by RT-PCR, Western blot analysis and immunohistochemistry. Transcript levels of CD97EGFand CD55 were higher in tumors than those in the margin and normal epithelial mucous tissues (P<0.05). However, the expression levels of CD97EGF and CD55 mRNA had no correlation with the clinicopathological features of gastric carcinoma patients. All three groups of specimens were immunoreactive for CD97EGF and the CD55 protein. Strong and specific immunoreactivities of CD97EGF were located in the mucosal epithelia of the marginal basal membrane. Expression of CD97(EGF) in the margins showed a marked difference between the depth of tumor invasion T1 and T2, 3 and 4, and stages I and II/III/IV of gastric carcinomas (P<0.05). The expression of CD55 protein was highly correlated with CD97EGF (R=0.6483, P<0.001). Western blot analysis confirmed the expression and distribution patterns of CD97EGF and CD55. Our findings suggest that CD97EGF may play a role in the development and invasion of gastric carcinomas by binding its cellular ligand CD55. Detection of the CD97EGF expression in the tumor margin could be referred to as the molecular edge of gastric carcinomas.

Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT): a representative literature review occasioned by a rare IMT of the transverse colon in a 9-year-old child.

AIMS AND BACKGROUND: Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) represent different entities. However, it is only in recent years that this has been taken into increasing consideration. Some authors still use both terms synonymously or interchangeably. Inflammatory myofibroblastic tumor is a real neoplasm because of the proliferation of myofibroblastic cells. Inflammatory pseudotumor is a more inflammatory reactive or regenerative entity and shows an overlapping with immunoglobulin G4-related disease. METHODS AND STUDY DESIGN: To analyze the current situation, 443 publications from the last 5 years (2009 to February 2014) were included. Reports involved 938 patients and 956 organ sites. The age distribution is twin peaked with one maximum in childhood and the other between 50 and 60 years of age. This distribution is questionable due to the more frequent occurrence of IPT in the liver and of IMT in the lung. Inflammatory pseudotumors mainly occur in older patients; IMTs in children and young adults. RESULTS AND CONCLUSIONS: The liver and biliary tract were the most commonly affected of all body regions, at 32%. This was followed by the lung, including the respiratory tract, at 27%, and by the gastrointestinal tract, at 10%. Lesions of the large bowel, as in the present case of a 9-year-old boy, are very rare. There were organ-related as well as nonspecific clinical symptoms, such as fever, weight loss, and fatigue. Laboratory test results revealed anemia and elevated inflammation-dependent parameters. The patterns in medical imaging are variable and nonspecific. Morphology often suggests a malignant process. For this reason, therapy in most cases is surgical, but this is required more often in IMTs. Many IPTs could be treated conservatively.

CD82, and CD63 in thyroid cancer.

CD82 (KAI1) and CD63 (ME491) are highly glycosylated proteins which belong to the transmembrane 4 superfamily (TM4SF). CD82 has been implicated as a possible prostate cancer metastasis suppressor gene, whereas CD63 is involved in the progression of human melanoma cancer. Down-regulation of both CD82 and CD63 expression has been associated with the metastatic potential of several solid tumors. Currently, information is lacking on the role of CD82 and CD63 during thyroid carcinogenesis. The aim of this study was to determine whether the expression of CD82 and CD63 is a useful prognostic indicator in patients with thyroid carcinoma. The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases). All of the benign goiter tissues showed CD82 expression. By contrast, a significant decrease in CD82 mRNA and protein levels was detected in carcinoma tissues as compared to benign goiter tissues (p<0.001). A similar down-regulation was observed in metastasized tumor tissues when compared with non-metastasized tumors (all p<0.05). CD82 expression was correlated with pTNM status of differentiated and undifferentiated thyroid tumor and the pathologic stage of differentiated thyroid tumor. In contrast to CD82, CD63 mRNA and protein expression was unchanged in all thyroid carcinomas. Benign goiter tissues showed weak expression of CD63. There were no significant correlation between CD63 mRNA/protein expression and any clinical/pathological parameters. Our results support the hypothesis that down-regulation of CD82 expression may reflect an increased in vivo metastatic potential of thyroid cancer cells. CD82 may serve as a prognostic marker of metastasis in thyroid cancer. Constitutive expression of CD63 may indicate that this factor does not play a direct role in thyroid carcinogenesis.

Severity of cardiac impairment in the early stage of community-acquired sepsis determines worse prognosis.

INTRODUCTION: In sepsis, the reduced systemic vascular resistance (SVR) can lead to a compensatory increase in cardiac output (CO). This may mimic a normal cardiac function although there is already a sepsis-induced myocardial depression. On a cohort of patients with septic multi-organ dysfunction syndrome, we have recently developed a method to correlate the actual CO to the afterload (estimated by SVR) and introduced the parameter "afterload-related cardiac performance" (ACP), which indicates if the rise of CO is adequate for the particular SVR. In this present study it was to be investigated, if ACP can reveal septic cardiomyopathy in patients with community-acquired sepsis in the early state soon after admission to the emergency department (ED), and if there is a prognostic relevance of septic cardiomyopathy defined by ACP. Results were compared to cardiac index (CI) and cardiac power index (CPI). METHODS: Adults presenting at the ED with sepsis were included. ACP, CI and CPI were calculated at the time of admission, after 24, and 72 h. They were correlated to severity of disease and the prognostic values were analyzed. RESULTS: A total of 141 patients were included. Only ACP was significantly influenced by severity of sepsis, whereas CI and CPI were not. ACP was the only hemodynamic parameter predicting mortality: nonsurvivors had lower ACP values at the time of admission to the ED (66.9 vs. 88.9 %, p < 0.05) and ACP predicted non-survival with an AUC value of 0.72, p = 0.003. Cardiac impairment defined by an ACP value of 80 % or below determined worse prognosis. CONCLUSIONS: Septic cardiomyopathy occurs already at the early stage of disease and is of prognostic relevance. It might be recognized best, if cardiac function is correlated to afterload.

Proteomic approach reveals novel targets for retinoic acid-mediated therapy of thyroid carcinoma.

Our previous studies demonstrated that retinoic acid (RA)-induced reduction of both, the key glycolytic enzyme ENO1 and proliferation-promoting c-Myc, resulted in decreased vitality and invasiveness of the follicular thyroid carcinoma cell lines FTC-133 and FTC-238. By employing two-dimensional electrophoresis and mass spectrometry, we identified proteins affected by RA treatment. In addition to previously reported decrease in ENO1 expression, we found that RA led to significantly reduced levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase isoenzymes M1/M2 (PKM1/M2), peptidyl-prolyl cis-trans isomerase A (PPIA), transketolase (TKT), annexin A2 (ANXA2), glutathione S-transferase P (GSTP1) and peroxiredoxin 2 (PRDX2) as compared to untreated control. The same proteins investigated on thyroid tissues were found to be significantly up-regulated in follicular, papillary and undifferentiated thyroid carcinomas when compared with goiter and adenoma tissues. These findings identify new target proteins for RA-mediated anti-tumor and re-differentiation therapies and provide novel insights into treatments for thyroid carcinoma.

The role of AUF1 in thyroid carcinoma progression.

AUF1/heterogeneous nuclear ribonucleoprotein D is an adenylate-uridylate-rich elements (AREs) -binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines, and cell cycle-regulatory genes. Several studies demonstrated AUF1 involvement in the processes of apoptosis, tumorigenesis, and development by its interactions with ARE-bearing mRNAs. We report here that AUF1 may be involved in thyroid carcinoma progression. Investigations on thyroid tissues revealed that cytoplasmic expression of AUF1 in malignant tissues was increased when compared with benign thyroid tissues. In thyroid carcinoma cell lines, AUF1 was mostly detectable in the nucleus; however, in dividing cells, its increased production was also observed in the cytoplasm. We found AUF1 in complexes with ARE-bearing mRNAs, previously described to be crucial for proliferation and cell cycle of thyroid carcinoma. Total or exon-selective knockdown of AUF1 led to growth inhibition accompanied by induction of cell cycle inhibitors and decreased levels of cell cycle promoters. Our data demonstrate the existence of a complex network between AUF1 and mRNAs encoding proteins related to cell proliferation. AUF1 may control the balance between stabilizing and destabilizing effects, both of which are exerted on cell cycle machinery in thyroid carcinoma. Although we cannot exclude participation of other factors, thyroid carcinoma may recruit cytoplasmic AUF1 to disturb the stability of mRNAs encoding cyclin-dependent kinase inhibitors, leading to uncontrolled growth and progression of tumor cells. Thus, AUF1 may be considered as a new, additional marker for thyroid carcinoma.

Retinoic acid-mediated down-regulation of ENO1/MBP-1 gene products caused decreased invasiveness of the follicular thyroid carcinoma cell lines.

Retinoic acid (RA) acts as an anti-proliferative and redifferentiation agent in the therapy of thyroid carcinoma. Our previous studies demonstrated that pretreatment of follicular thyroid carcinoma cell lines FTC-133 and FTC-238 resulted in decreased in vitro proliferation rates and reduced tumor cell growth of xenotransplants. In addition to the previous results, we found that RA led to decreased vitality and invasiveness of FTC-133 and FTC-238 cells as they reacted with reduction of intracellular ATP levels and number of migrated cells respectively. However, the molecular mechanisms by which RA mediates these effects are not well understood. Two-dimensional (2D) screening of the proteins related to ATP metabolism and western blot analysis revealed alpha-enolase (ENO1) to be down-regulated in FTC-133 and FTC-238 cells after RA treatment. 2D gel detection and mass spectrometric analysis revealed that ENO1 existed as three separate protein spots of distinct pIs (ENO1-A1-A3). Comparative 2D difference gel electrophoresis analysis of fluorescently labeled protein samples of RA-treated and untreated FTC-133 demonstrated a selective down-regulation of ENO1-A1 which we identified as a phosphoprotein. RA caused the dephosphorylation of ENO1-A1. Both, RA-mediated and specific knock-down of ENO1/MBP-1 resulted in the reduction of MYC oncoprotein, and simultaneously decreased proliferation rates of FTC-133 and FTC-238 cell lines. In summary, the RA-mediated down-regulation of the ENO1 gene products and MYC oncoprotein provides a novel molecular mechanism facilitating the anti-proliferative effect of RA in human thyroid carcinoma cells and suggests new pathways for supportive RA therapies.

Multiple malignant and benign lesions in the liver in a child with adrenocortical carcinoma.

We report 4-year-old girl who was diagnosed with adrenocortical carcinoma when she was 2 years old. At the time of diagnosis there were no metastases, but 6 months later multiple liver metastases appeared. Following intensive chemotherapy the metastases resolved completely. Multifocal lesions were detected in the liver by US 16 months later. Their morphology on US and MRI differed from the previous metastases. Histopathological examination confirmed focal nodular hyperplasia. We discuss the origin and the uncommon appearance of multifocal nodular hyperplasia in hormone-active tumours such as adrenocortical carcinoma in children.

Intramural bladder-wall abscess: a late complication arising after a urethrocystoscopy?

Intramural bladder-wall abscesses are serious but rather rare. In the few reported cases, their aetiology has not been explicitly explained. In our case, we found a traumatic outcome induced by a urethrocystoscopy that had taken place 4 years prior to the diagnosis of abscess. To date, there has not been much published on these bladder-wall abscesses or urinary tract infections from urethrocystoscopies and Burkholderia cepacia bacteria. As a result, their pathogenesis and aetiology have not been fully explained. In this paper we report on the clinical as well as the subjective well-being of a female child who was diagnosed with a massive full-blown intramural bladder-wall abscess that developed 4 years after she had undergone a urethrocystoscopy.