Addressing the Challenges in the Diagnosis and Management of Pediatric Wilson's Disease-Case Report and Literature Review.

Wilson's disease (WD) is an autosomal recessive disorder, in which the metabolism of copper is affected by metal accumulation in several organs that causes gradual organ degeneration. Since Wilson's initial description of WD over a century ago, there have been significant improvements in understanding and managing the condition. Nevertheless, the ongoing gap between the onset of symptoms and diagnosis highlights the difficulties in identifying this copper overload disorder early. Despite being a treatable condition, detecting WD early remains a challenge for healthcare professionals at all levels of care, likely due to its rarity. The key challenge is, therefore, to educate physicians on how to identify atypical or infrequent symptoms of WD, prompting them to consider the diagnosis more carefully. The purpose of our review is to draw attention to the difficulties associated with diagnosing pediatric WD, starting from our personal experience of a complex case and then examining relevant literature. In summary, the diagnosis of WD in children is intricate and requires a heightened level of suspicion to identify this infrequent condition. A thorough evaluation by a multidisciplinary team of physicians, along with genetic testing, histopathologic examination, and specialized imaging studies, may be necessary to confirm the diagnosis and guide treatment.

The Management of Pediatric Acute Appendicitis-Survey among Pediatric Surgeons in Romania.

Background and Objectives: To assess the current practice pattern in the management of pediatric acute appendicitis in Romania. Materials and Methods: A questionnaire was emailed to all the members of the Romanian Society of Pediatric Surgery between June-July 2022. Results: 118 answers were received, 79.7% responses being from permanent staff members. In the diagnosis of appendicitis, complete blood count, C-reactive protein and abdominal ultrasound are the most commonly used diagnostic tools, while appendicitis scores are not widely used (25% of surgeons). In the case of simple appendicitis, 49.2% of surgeons prefer the conservative approach-oral/intravenous antibiotics. Those who choose the operative approach begin preoperative antibiotics in 56.7% of patients. In case of a stable patient, only 16.7% of surgeons will operate during the night. Laparoscopic approach is chosen by 51.7% of surgeons. In the case of a complicated appendicitis, 92.4% of surgeons will perform the appendectomy, prescribing preoperative antibiotics in 94% of the cases and continuing the therapy postoperatively in 98.2%. Laparoscopic approach is used by 28.8% of surgeons in case of complicated appendicitis. In presence of appendicular mass, 80% prefer a conservative approach with a delayed appendectomy within 6 months. Appendicular abscesses are managed operatively in 82.2% of the cases. The appendix is sent for histological analysis by 95.8% of surgeons. If the peritoneal cavity is contaminated, 95% of the respondents will take a sample for microbiological analysis, 71% will always place a drainage and 44% will always irrigate (71.9%-saline). Conclusions: Clearly, there seems to be a lack of consensus regarding several aspects of the management of acute appendicitis in children. In addition, minimally invasive surgery is not as widely used as reported, despite literature support.

Laparoscopic Repair of a Left Retrocaval Ureter in a 16-Year-Old Girl.

Left retrocaval ureter is an extremely rare congenital malformation which is associated with situs inversus, duplicated or translated inferior vena cava (IVC). We report a female adolescent who presented with a history of intermittent, colicky lumbar pain. Diagnostic workup revealed left retrocaval ureter and left ureterohydronephrosis. The girl underwent laparoscopy. The renal pelvis and ureter posterior to the vena cava were dissected, transected at the caudal point of the dilated ureteral segment, and uncrossed and repositioned lateral to the vena cava. Ureteroureterostomy was performed over a double-J ureteral stent after spatulation of the distal ureter. The postoperative course was uneventful and the ureteral stent removed after 5 weeks. During follow-up, the patient is symptom-free. Our case demonstrates that our laparoscopic approach is feasible in this rare anatomic anomaly.

Development of present and future of telepathology in Hungary.

Pathologists in Hungary evaluate several hundred thousand histological specimens yearly, and a second opinion is requested in 5-10 percent of cases. Application of multimedia systems (i.e. telepathology) is convenient and efficient to establish a correct diagnosis in such cases. The first telepathology connection in Hungary has been established between the 1st Department of Pathology and Experimental Cancer Research, Semmelweis University and the Department of Pathology, Central Hospital of the Ministry of the Interior. Further development occurred in the course of various projects, supported by the EU (Inter-path, Re-transplant, Be Pro): new stations were established in three university institutes and six county hospitals. Electronic fixation of the images and their transmission by telephone line (ISDN) is easily available and an important feature of the multimedia system applied in telepathology. The system used by us is suited to evaluate frozen or paraffin-embedded histologic sections, as well as immunohistochemical and cytologic specimens, if necessary supplemented with transmission of macroscopic pictures. Our experience with bilateral consultations has proven the importance of telepathology. The telepathology system established in Hungary is now ready to join the telepathology network of the EU.

Changes of cell adhesion and extracellular matrix (ECM) components in cervical intraepithelial neoplasia.

Cell-cell and cell-extracellular matrix interaction is crucial in tumor progression. Tight junction (TJ) proteins as occludin and claudins (CLDNs) play important role in this process together with several extracellular matrix components, as syndecan. Our previous work suggested significant changes in the expression of claudins even in the early stages of cervical carcinogenesis. The aim of our present work was to study the expression of occludin and syndecan-1, as compared to CLDNs, in early phases of cervical carcinogenesis. Paraffin sections of 50 samples were studied by immunohistochemistry, including cervical intraepithelial neoplasias (CINI-II-III), in situ carcinomas (CIS) and normal cervical samples. Occludin and CLDN-2 were found colocalized in the basal layer, while syndecan-1 and CLDN-1, -4 and -7 were coexpressed in the parabasal and intermedier layers in normal epithelia. Intensity of occludin staining decreased in CIN/CIS lesions, although it was more extended towards the upper epithelial layers with inverse relation with grades, as seen in the case of CLDN-2 expression. CLDN-1, -2, -4 and -7 were detected in the entire epithelium in CIN, showing decrease in CIS. The progression of CIN was associated with reduced syndecan-1 expression, in contrast to CLDN-1, -4 and -7 which increased toward CIS. The obtained data suggest that significant changes occur in the composition of cell adhesion complexes even in early stages of cervical carcinogenesis. The pattern of expression is characteristic for the alteration, the changes in the different components, however, are not parallel with each other.

Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma.

Claudins (CLDNs), of which 24 types have been identified, are integral transmembrane proteins of the tight junctions that are critical for maintaining cell adhesion and polarity. They also act as selective barriers. Cells and tissues are characterized by individual CLDN patterns; the composition and levels of expression change during differentiation and tumor formation. Alterations in the expression of individual CLDNs have been detected in several carcinomas and shown to be related to progression and invasion; however, their role in carcinogenesis is controversial. Using a panel of polyclonal (CLDNs 1, 3, and 7) and monoclonal (CLDNs 2 and 4) antibodies, CLDN pattern and expression were studied by immunohistochemistry in 105 cervical tissue specimens, including normal epithelia (n = 20), cervical intraepithelial neoplasias (CINs; CIN 1/2, n = 27; CIN 3, n = 10), carcinoma in situ (CIS, n = 15), and 33 squamous keratinizing and nonkeratinizing invasive carcinomas. No CLDN 3 was observed in normal or intraepithelial neoplastic cells, but significantly increased expression of CLDNs 1, 2, 4, and 7 was detected in the CIN/CIS lesions and invasive carcinomas compared with the normal tissues (P < .001) and reduced reactivity of CLDNs 1 and 2 was observed in invasive cervical cancers compared with CIN 3/CIS (P = .0001) and of CLDNs 2, 4, and 7 compared with CIN 1/2. These results indicate increased expression of CLDNs in the early phase of carcinogenesis in intraepithelial lesions, which decreases during progression to invasive disease. Expression of CLDN 1 was strongest in premalignant stages; thus, it may serve as a good diagnostic marker for the detection of CIN.

Chlamydia pneumoniae in coronary bypass grafts of redo patients. The concept of the 'adventitial baseline infection'.

The pathogenic role of Chlamydia pneumoniae in late coronary bypass graft failure has not yet been extensively investigated. We examined failed and new arterial/venous bypass grafts using immunohistochemistry, polymerase chain reaction (PCR), and serology. Thirty-four long-term failed grafts and 28 new grafts were examined in 21 patients undergoing redo coronary artery bypass grafting (CABG). Immunohistochemically, 28 (82%) failed grafts were positive in the intimal-medial compartment, and 33 grafts (97%) were positive for C. pneumoniae in the adventitia. Thirteen (46%) and 27 (96%) new grafts showed infection in the intima-media and in the adventitia, respectively (p < 0.05). Immunohistochemically, the overall presence of C. pneumoniae in all vessels examined was 66% in the intima-media and 97% in the adventitia (p < 0.05). C. pneumoniae was detected by PCR in 19 (31%) of all the vessels examined. C. pneumoniae seems to be frequently present in grafts of patients considered for redo CABG in Hungary. The adventitia of both failed, and new grafts particularly often contained C. pneumoniae. The results suggest that there exists an adventitial baseline infection from which infection of the inner wall layers develops, depending on local microenvironmental conditions. This is the first study to evaluate chlamydial infection in arterial/venous coronary grafts by immunohistochemistry, PCR, and serology.

[Summary of our clinical experience with the determination of serum prostate-specific antigen level in the first five years]. / A prosztataspecifikus antigén-szint meghatározásának elsô öt éve során szerzett tapasztalataink összefoglalása.

The authors determined serum PSA levels in combination with digital rectal examination (DRE) and evaluated their role in the differential diagnosis of prostate diseases with special reference to cancer. The possible causes of differences between the observed cut-off level of PSA and the standard level PSA were analyzed. In the last few years the PSA determination found its clinical role in the diagnosis of prostate cancer.

Early atherosclerosis and Chlamydia pneumoniae infection in the coronary arteries.

In non-atheromatous segments of coronary arteries a sequence of preatherosclerotic changes was identified which consisted of medial thickening followed by intimal thickening. More recently, Chlamydia pneumoniae seropositivity was associated with enhanced intima-media thickness of arteries. In the present study the intimal and medial thickness of coronary artery of young adults were measured, and were correlated with the presence of Chlamydia pneumoniae antigens. Proximal and distal segments of the left anterior descending coronaries (LAD) obtained at autopsy from young adults (15-34 years) were studied. The thickness and cellular density of the intima and of the media without clear-cut atherosclerotic changes were measured by image analysis. The hypertrophy index was calculated as the ratio of cell density and the thickness of the respective layer. Atherosclerotic lesions occurring elsewhere in the same coronary were noted and graded by severity. The presence of Chlamydia pneumoniae verified by immunohistochemistry was correlated with the severity of lesions and with the hypertrophy index. In the proximal segments, atherosclerosis of LAD was associated with the widening of both the intima and the media of lesion free-sites. In the distal coronary segments the proportion of the intimal thickening had a significant association with atherosclerosis. Compared to non-infected arteries, Chlamydia pneumoniae infection was associated with higher hypertrophy index in the intima as well as in the media. The rate of Chlamydia pneumoniae positivity increased with the severity of lesions. As a conclusion: in the LAD coronary, the intimal thickening is the main preatherosclerotic change. Chlamydia pneumoniae may favour arterial wall hypertrophy and plays a role in lesion progression.

[Role of osteopontin in the formation of microcalcifications in breast cancer]. / Az osteopontin szerepe a microcalcificatiók kialakulásában emlócarcinomákban.

INTRODUCTION: Osteopontin, a non-collagen, Ca-binding phosphoprotein, plays roles in both physiological and pathological mineralisation processes. Its expression may be severely altered in malignant tumours. AIM: To investigate the presence of this protein in breast tumours showing mammographic microcalcifications. MATERIAL: In this study the authors investigated immunohistochemically the osteopontin expression in 26 breast tumours. The elemental composition of the microcalcifications of the same tumours was also examined with energy dispersive spectrometer linked to a scanning electron microscope. RESULTS: Osteopontin expression was found within the tumours in the tumour cells, in vascular smooth muscle cells, in the myoepithelial cells of the normal ducts, and in macrophages. Extracellular osteopontin positivity was seen around calcified foci. There was no correlation between osteopontin positivity and the examined prognostic factors: grade, type and size of the tumour, axillary lymph nodes status, or age. Two types of microcalcifications were seen: 1. Ca-phosphate only, 2. Those composed of various other elements. CONCLUSION: The presence of osteopontin in the vicinity of calcified foci and in the vessel walls seems to support the hypothesis that osteopontin takes part in calcification process.

Extracellular matrix components in breast carcinomas.

A malignant process interferes with the normal 'programme' of extracellular matrix biosynthesis and can modify extensively the structure and composition of the matrix. This effect appears to be attributable to several processes such as direct production of some selected matrix macromolecules by malignant cells or indirectly by the production of factors by malignant cells interfering with the regulation of normal matrix production. Other possibilities may also exist, such as the direct action of an environmental carcinogen on otherwise normal mesenchymal cells. The result is a more or less profound modification of tissue structure and composition with possible feedback effects on the malignant process. Some examples will be discussed such as elastin production by some tumours as well as the biosynthesis of some other selected matrix macromolecules as tenascin and osteopontin by breast tumours. Although the detailed mechanisms of these specific matrix productions is not yet completely elucidated, the rapidly increasing knowledge on the regulation of specific matrix production process and deranged matrix production might represent a new area of crosstalk between cancer research and matrix biology.

Chlamydia pneumoniae in different coronary artery segments in the young.

UNLABELLED: Chlamydia pneumoniae has emerged as the most likely pathogen to have a causative role in the development and/or for progression of atherosclerosis. Evidence for this is based on epidemiological and pathological studies. In an effort to better understand the significance of finding C. pneumoniae in atheromata, we examined coronary artery segments of young adults (15-34 years) with and without atherosclerosis. Left anterior descending coronary arteries (LAD) of 74 young adults who died suddenly were examined histologically and for the presence of C. pneumoniae by immunohistochemistry. C. pneumoniae was identified in advanced lesions (Stary types III to VI) in 17 of 32 cases (53%), and in early lesions (Stary type I-II) in 8 of 37 cases (21%), mainly at the proximal segments of the LAD. C. pneumoniae was not found in the intimal and medial layer of normal-appearing coronary arteries. C. pneumoniae was detected in the adventitia in 51 (67%) coronary arteries: in 27 of normal arteries and early lesions (64%), and in 24 of atherosclerotic lesions (75%). C. pneumoniae was found most often in macrophages, less offen in smooth muscle cells. We also observed a correlation between C. pneumoniae positivity and cigarette smoking. IN CONCLUSION: C. pneumoniae may relate to the severity of atherosclerosis in young people, and it may thus initiate atherosclerotic injury or facilitate its progression with other risk factors.