Utility of expression of 4-hydroxynonenal tested by immunohistochemistry for cervical cancer.

Introduction: Cervical cancer (CC) is a leading cause of mortality in women around the world, with the highest incidence rate still being in developing countries. The most common aetiological factor is infection with high-risk human papilloma virus viral strains. Oxidative stress through generation of reactive oxygen species leads to lipid peroxidation and DNA damage. Studies show that reactive lipid electrophiles such as 4-hydroxynonenal (4-HNE) produced in the process play an important role in cancer signalling pathways and are a good biomarker for oxidative stress. We aim to investigate the prognostic role of 4-HNE as a biomarker for oxidative stress in patients in early and advanced stages of CC measured by immunohistochemistry. Material and methods: This is a retrospective study of 69 patients treated at our Department of Oncogynaecology. Paraffin embedded tumour tissues were immunohistochemically tested for the levels of expression of 4-HNE. The results for H-score, Allred score, and combined score were investigated for association with tumour size, lymph node status, andInternational Federation of Gynaecology and Obstetrics stage. Results: 4-hydroxynonenal showed higher expression in more advanced stages of CC and in cases with involved lymph nodes. Tumour size was not associated with the levels of 4-HNE. Conclusions: To best of our knowledge, this is the first study to use immunohistochemistry to examine the expression of 4-HNE as a prognostic factor in CC. The 3 score systems showed similar results. The pattern of 4-HNE histological appearance is dependent on the histological origin of cancer and is not universal.

The Clinical Significance of Pollen and Fungi Concentrations for Allergic Rhinitis: A Three-Year Study.

INTRODUCTION: The relationship between disease severity and exposure to allergens in allergic rhinitis (AR) patients is not fully clarified presently. We aimed to detect the correlation between airborne pollen and fungi concentrations in a Mediterranean region with symptom scores. METHODS: A total of 98 patients suffering from AR rated their symptoms at the time of exacerbation using the Total 5 Symptoms Score (T5SS) and the Visual Analogue Scale (VAS). Patients' quality of life (QoL) was estimated by using either disease-specific (Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and mini-RQLQ) or generic (Short-Form 36 (SF-36) and Beck Depression Inventory (BDI)) questionnaires. All patients' responses were correlated with aerobiological data. Skin prick tests (SPTs) were used to detect sensitivities to the most common registered pollen and fungi species. RESULTS: A significant positive correlation between total pollen and fungi counts and disease-specific questionnaires was found only for the RQLQ. Accordingly, a significant positive correlation was found between total pollen and fungi counts and T5SS (r = 0.655, p = 0.021), with breathing (r = 0.620, p = 0.032) and sneezing (r = 0.660, p = 0.020) being strongly affected. Moreover, a tendency toward a higher VAS score was found as total pollen and fungi counts increased (r = 0.523, p = 0.081). CONCLUSION: We found a significant correlation between patients' symptoms and pollen and fungal air concentrations. Our results emphasize the clinical significance of pollen and fungi maps in everyday clinical practice.

Lynch-like syndrome with germline WRN mutation in Bulgarian patient with synchronous endometrial and ovarian cancer.

BACKGROUND: Synchronous endometrial and ovarian cancer (SEOC) accounts for 50-70% of all synchronous gynecology cancers in women. Approximately 14% of SEOC cases are caused by Lynch syndrome (LS). The widespread introduction of "universal screening" at LS (all cases with CRC and all EC cases diagnosed before age 60 should be tested for MMR deficiency) has led to an increasing number of suspected LS cases- MMR-deficient tumors without germline mutation in the MMR genes. These cases are attributed to the so-called Lynch-like syndrome (LLS). CASE PRESENTATION: We present a case of LLS with a detected germline, likely pathogenic variant in the WRN gene. The proband was a woman diagnosed with SEOC at the age of 51 years. Histology of both tumors (endometrium and ovary) was endometroid and showed loss of MLH1 and PMS protein expression. Genetic testing by next generation sequencing (NGS) detected a germline mutation (in the heterozygous state) in the WRN gene - c.4109del, p.(Asn1370ThrfsTer23) in the proband. CONCLUSIONS: The presented case contributes to the etiology of LLS and confirms the need for specific genetic testing, together with genetic counseling, in hereditary cancer syndromes. The use of combined information from clinicians, pathologists, genetic counselors, and data from NGS testing for cancer predisposition, clinical surveillance, and follow-up management in women with gynecology cancers, especially SEOC, could be improved.

The effects of ROMO1 on cervical cancer progression.

INTRODUCTION: More than 95% of the cases of Cervical cancer (CC) are now linked to infection with Human papilloma virus (HPV) but the infection alone is not sufficient for starting the oncogenesis. Reactive Oxygen Species (ROS) can promote CC cancerogenesis. ROMO1 is a protein that regulates the production of intracellular ROS and influences cancer cell invasion and proliferation. We aimed to investigate the impact of ROS in CC progression, measured by the expression of ROMO1. METHODS AND MATERIALS: This is a retrospective study of 75 patients treated at the Department of Oncogynecology, Medical University of Pleven, Bulgaria. Paraffin embedded tumor tissues were immunohistochemically tested for the levels of expression of ROMO1. The results for both Allred score and H-score were investigated for association with tumor size, lymph node status and FIGO stage. RESULTS: Levels of ROMO1 were significantly higher in FIGO1 stage compared to FIGO2 and FIGO3 according to both scores (for H-score FIGO1 vs FIGO2 p = 0.00012; FIGO 1 vs FIGO3 p = 0.0008; for Allred score FIGO1 vs FIGO2, p = 0.0029; FIGO1 vs FIGO3 (p = 0.012). Statistically significant difference was found according to the H-score between patients with and without metastatic lymph nodes (p = 0.033). CONCLUSION: To the best of our knowledge this is the first study testing immunohistochemically the expression of ROMO1 for CC progression. The levels of ROMO1 were significantly higher in early stage tumors compared to advanced. Bearing in mind that only 75 patients were tested, further studies are required to evaluate the value of ROS in CC.

[Our preferred Approaches to the distal Radius]. / Unsere bevorzugten Zugänge zum distalen Radius.

This article describes our preferred approaches to the distal radius treating acute fractures and malunion by plating.

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer.

Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME-tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)-in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes' involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes' statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient's stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.

[Fractures and Non-Unions of the Scaphoid: Our preferred surgical Approaches]. / Skaphoidfrakturen und -pseudarthrosen: Unsere Wahl des Zugangs.

This article describes our algorithm for approaching and fixing scaphoid fractures and non-unions.

[Effect of a single proximal interphalangeal Joint Fusion of the Index, Middle or Ring Finger on the Grip and Finger Force and Load Distribution in the Hand]. / Auswirkungen der Arthrodese eines einzelnen Mittelgelenkes von Zeige-, Mittel- oder Ringfinger auf Hand- und Fingerkraft sowie auf die Druckverteilung der Hand.

BACKGROUND: Due to the functional coupling of adjacent finger joints and the quadriga effect, arthrodesis of the proximal interphalangeal joint (PIPJ) can be assumed to lead to a different grip pattern resulting in altered force distribution of the hand. PATIENTS AND METHOD: Ten patients with isolated arthrodesis of the PIPJ due to posttraumatic osteoarthritis (4×PIPJ II, 4×PIPJ III, 2×PIPJ IV) were assessed 59 (17-121) months postoperatively on average. The angle of arthrodesis was assessed by radiographs. Grip force and load distribution of both hands were measured by manugraphy using 3 differently sized cylinders. Grip force was separately assessed and compared for the whole hand as well as for each of the fingers and each phalanx. RESULTS: Average total grip force of the affected hand compared to the uninjured opposite side was 74% (38-136%) for the small cylinder, 104% (68-180%) for the mid-sized cylinder and 110% (69%-240%) for the large cylinder. Arthrodesis of the PIPJ of the index finger led to a reduction of the grip force (91%) for the small cylinder, but increased grip force for the mid-sized (120%) and large cylinder (139%). Grip force was reduced for all cylinder sizes by arthrodesis of the PIPJ of the middle finger (56%, 88% and 91%). Arthrodesis of the PIPJ of the ring finger resulted in a grip force of 76%, 105% and 91%, respectively, for the different cylinder sizes.The finger force of the affected finger was reduced after arthrodesis of the PIPJ, with the exception of the index finger, which was stronger than the unaffected opposite finger when using the large cylinder. The force of the healthy fingers on the affected side was greater when compared with the same finger on the opposite side, which led to increased grip force for the mid-sized and the large cylinder of the affected hand. A reduction in load distribution was measured mostly for the middle phalanx but also for the distal phalanx of the operated-on finger. CONCLUSION: Arthrodesis of the PIPJ almost always led to force reduction in the middle and distal phalanx of the affected finger. However, the total grip force of the hand was compensated by a higher force of the adjacent healthy fingers. In many cases, total grip force was even higher on the affected side. However, arthrodesis of the PIPJ resulted in a noticeable force reduction when smaller objects were gripped.

[Incisions in surgical Treatment of Dupuytren's Disease]. / Zugänge bei Operationen einer Dupuytren'schen Kontraktur.

Therapeutic options to treat Dupuytren`s disease vary considerably. Nevertheless, limited fasciectomy remains the method of choice in advanced disease. Correct incisions are of crucial importance in this kind of surgery.With the inclusion of relevant literature, we present principles of correct incisions and our personal approach in different stages of the disease. History and a subtle clinical examination are essential to plan the surgery. Important details are quality of skin and extent and characteristics of pathological tissue. Generally accepted basic incisions are longitudinal incisions with subsequent Z-plasties and Zig-Zag-Incisions with several modifications. Extensive deficit of skin necessitates local flaps. In the palm we prefer an ulnar-based flap design and in special cases a Z-plasty. Depending on the extent of the disease, various combinations of these basic techniques are necessary. Incisions must respect general principles in hand surgery, allow exposition of the pathological tissue, utilise mobile parts of skin for usage as flaps and respect vascularisation of resulting flaps.In complex cases, individualised incisions or general hand surgical principles and correction of the resulting skin deficit are crucial elements necessary for successful surgery. By sticking to these principles, experienced hand surgeons can implement different solutions.

[Amputations of fingers and the hand]. / Amputationen an den Fingern und der Hand.

Revision amputation, ray amputation and narrowing of the hand can be indicated for pathological alterations of fingers and thumbs due to traumatic, inflammatory or vascular causes but also for functional deficits regarding mobility, sensibility, perfusion, and/or pain. Surgical amputation is considered if reconstructive options are no longer possible, not desired and are no longer meaningful with respect to effort and risks. Patients need to be informed about the expected deficits in function and esthetic appearance due to the amputation in advance. On the other hand, surgical amputations represent a good treatment option, for which the duration of treatment and scope are well estimated. Therefore, they are good options for patients with comorbidities, with concerns about extensive reconstructive surgery and with limited compliance. It is essential to respect anatomical and functional aspects to guarantee favorable surgical results and avoid complications, which might compromise the function of the hand beyond that which is unavoidable. The most frequent complications after creating a stump or ray resection are persistent pain, unstable skin and soft tissue conditions, mobility disorders, disturbing stumps without function, uncontrolled growth of nail remnants and recurrent inflammation.

Prognostic Utility of CD47 in Cancer of the Uterine Cervix and the Sensitivity of Immunohistochemical Scores.

INTRODUCTION: Cancer of the uterine cervix (CUC) is still one of the most frequent oncological diagnoses in women. The specific interactions between the tumor cells of CUC and the cells and tissues in the tumor microenvironment can affect cancer cells' invasive and metastatic potential and can modulate tumor's progression and death. CD47 is a trans-membranous immunoglobulin, expressed in many cells. It protects the cells from being destroyed by the circulating macrophages. AIM: We aimed to evaluate the prognostic role of CD47 expressed in the tumor tissues of patients with CUC for tumor progression and to find the most sensitive immunohistochemical score for defining the cut-off significantly associated with tumor biology and progression. MATERIALS AND METHODS: Paraffin-embedded tumor tissues from 86 patients with CUC were included in the study. Clinico-morphological data for patients, such as age and stage at diagnosis according to FIGO and TNM classification, were obtained from the hospital electronic medical records. Immunohistochemical staining was performed with rabbit recombinant monoclonal CD47 antibody (Clone SP279). The final result was interpreted based on three reporting models in immunohistochemistry: H-score, Allred score and combined score. RESULTS: The expression of CD47 was higher in tumors limited in the cervix compared with those invading other structures, and it did not depend on the nodal status. The results of immunohistochemical staining were similar regardless of which immunohistochemical method was used. The most significant correlation with TNM stage was observed with the H-score (p = 0.00018). The association with the Allred and combined score was less significant, with p values of 0.0013 and 0.0002, respectively. CONCLUSION: The expression of CD47 in the cancer cells is prognostic for tumor invasion in the surrounding structures, independent of lymph node engagement. The H-score is the most sensitive immunohistochemical score to describe tumor stage. To the best of our knowledge, this is the first study evaluating the significance of CD47 expression in CUC.