Challenges in the Routine Praxis Diagnosis of Hydatidiform Mole: a Tertiary Health Center Experience.

INTRODUCTION: Hydatidiform moles (HM), presenting as complete (CHM) and partial (PHM) form, are rare pregnancy disorder. Diagnosis is based on clinical presentation, ultrasound imaging findings and pathological examination of products of conception. Protein p57, encoded by CKDN1C gene, is paternally imprinted and maternally expressed gene and provides quick insight in genetic basis of HM and allows distinction of CHM from all other conceptions. compare the preevacuational and pathohistological diagnosis with outcome of p57 immunostaining. MATERIAL AND METHODS: All cases of HM diagnosed between January 2011 and December 2015 were included in this research. Maternal age, gestational age and input diagnosis data were recored. p57 immunostaining was performed in order to evaluate the diagnosis based on tissue slides examination. RESULTS: There were 198 cases of histologically confirmed HM, 185 PHM, 12 CHM and one case of undefined HM. Mean maternal age in the CHM group was 24,7 and in the PHM group 26,9 years, with no significant differences among these two groups (p=0,27). For CHM mean gestational age was estimated at eight and for PHM 9,2 gestational weeks. Pregnant woman older than 40 years present significant earlier compared with younger woman (p<0,01), and those younger than 20 years tend to present at the beginning of the second trimester more often than older women (p<0,05). In the CHM group, 9 (75%) input diagnoses were mola in obs, and 3 (25%) of them were signed as abortion, unlike the PHM where 126 (67%) were qualified as abortion, 35 (19%) as blighted ovum, and 26 (14%) were suggestive for molar pregnancy. p57 immunostaining results confirmed all pathohistological diagnosis of CHM whereas 8% of PHM demonstrated divergent p57 expression. CONCLUSION: PHM, compared with CHM, represent a greater diagnostic challenge for both gynecologist and pathologist even when presenting in more advanced pregnancies.

Prognostic Parameters of Acute Myeloid Leukaemia at Presentation.

INTRODUCTION: The treatment response and outcome in acute myeloid leukaemia (AML) is heterogeneous. AIM: To analyze the prognostic parameters of AML at presentation. METHODS: The total sample of 44 AML patients was analyzed on the basis of age <55 and ≥55 years, sex, WBC count <50x10/9/l and ≥50x10/9/l, the Hb concentration <100 g/l and ≥100 g/l, PLT count <100x10/9/l and ≥100x10/9/l, Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type and types of treatment (standard and reduced induction chemotherapy, high-dose chemotherapy/stem cell transplantation - autologous and HLA matched, related, allogeneic, together and separately). RESULTS: The age <55 years, Karnofsky score >60% and standard induction chemotherapy statistically correlated with the higher complete remission (CR) rates, longer relapse free survival (RFS), lower relapse rate (RR), and longer overall survival (OS) (p<0.01). The difference in terms of CR and RR between the sexes were not statistically significant (p<0.05), however women had statistically lower OS comparing to men (9.71±4.54 months vs. 38.03±9.17 months) (p<0.01). WBC count ≥ 50x10/9/l and the Hb concentration <100 g/l statistically correlated with shorter OS (p<0.05), while the WBC count ≥50x10/9/l statistically correlated with shorter RFS (p<0.05). The PLT count <100x10/9/l and ≥100x10/9/l was not found as prognostically significant for CR, RR, RFS, and OS (p<0.05). In comparison to the standard induction chemotherapy, both types of high dose chemotherapy/stem cell transplantation (HDT/SCT) (10/22), together and separately, resulted in longer RFS, lower RR, and longer OS (p<0.05). The frequency of cytogenetic risk was intermediate 81.6%, unfavorable 13.2%, and favorable 5.3%, respectively. CD56 + expression statistically correlated with the lower PLT count, higher RR, shorter RFS, and shorter OS (p<0.05). Statistical analysis of the cytogenetic risk and morphological types of AML were not possible due to the small number of patients in stratified groups. CONCLUSIONS: Female sex, the WBC count >50x10/9/l, the concentration of Hb <100 g/l, and CD56 + expression, at presentation of AML, should be considered as parameters of adverse risk, especially in latter decisions considering post-remission treatment with HDT/SCT.

Estimate of cervical cancer incidence and mortality rate in Bosnia and Herzegovina.

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

Histopathological spectrum of lumbar disc changes in obesity: analysis of intervertebral discs in lumbar hernia patients in Zenica-Doboj Canton, Bosnia and Herzegovina.

Aim To investigate the correlation of body mass index (BMI) with severity of intervertebral disc degeneration. Methods The study enrolled patients who had undergone surgical intervention for a herniated disc at the Department of Neurosurgery of the Cantonal Hospital Zenica. Patients underwent thorough preoperative evaluation, including medical history, neurological and physical assessments, and radiological analysis. The surgical intervention consisted of a posterior lumbar discectomy, and the excised disc material was preserved and subjected to histopathological analysis based on Histopathologic Degeneration Score (HDS). Patients were divided in two groups according to Body Mass Index (BMI): study group with BMI≥25 and control group with BMI<25. Results Among 69 patients with herniated IVD, 26 (37.7%) were with BMI≥25 (study group), and 43 (62.3%) were with BMI<25 (controls). The study group displayed substantial increase in height, 1.80±0.06 m compared to controls, 1.74±0.06 m (p=0.001). Weight and BMI were significantly higher in the study group of patients (weight: 91.60±10.22 vs. 67.37±9.20 kg, BMI: 28±2 vs. 22±2; p<0.001). Differences were confirmed in HDS values in the study group comparing to the control group (p<0.001). The study group exhibited significant differences in chondrocyte proliferation, tears and clefts, granular changes, and mucous degeneration (p<0.05), and positive correlations were found between BMI and these alterations found in the herniated discs (p<0.05). Therefore, HDS showed positive correlations with BMI (R=0.599; p<0.001) and weight (R=0.696; p<0.001). Conclusion The study's findings confirmed that BMI has a significant impact on intervertebral disc degeneration, emphasizing the importance of weight management in preventing disc degeneration.

Laser capture microdissection shows HPV11 as both a causal and a coincidental infection in cervical cancer specimens with multiple HPV types.

AIMS: To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16(INK) (4a) expression. METHODS AND RESULTS: Three squamous cell ICC specimens showing coinfection with HPV11 and carcinogenic HPV16 or HPV31 were selected from the Institut Català d'Oncologia international survey of anogenital carcinomas, and coinfection was confirmed by SPF10 -DEIA-LiPA25 analysis. In two cases LCM-PCR identified HPV11 in low-grade and high-grade squamous intraepithelial lesions (SILs) adjacent to the ICC, and HPV16 or HPV31 in the ICC. In one case, HPV11 was the only genotype found in the ICC. P16(INK) (4a) expression was diffuse in ICC associated with carcinogenic HPV, but focal in ICC with HPV11. CONCLUSIONS: Our results confirm that a single cervical, cancerous or precancerous lesion is associated with a single HPV type. Detecting low-risk HPV as a coinfection in whole tissue from ICC does not prove a causal association. HPV11 may be found only in an adjacent SIL with carcinogenic HPV in the ICC. It is also found alone in carcinoma. LCM-PCR and differential P16(INK) (4a) expression can clarify the causal role of each type when multiple HPVs are present in whole tissue from carcinomas.

Guidelines for breast cancer management in Bosnia and Herzegovina.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina, accurate data on the status of breast cancer are lacking due to the absence of a central registry. Multiple international guidelines imply that institutions that monitor breast cancer patients should have optimal therapeutic options for treatment. In addition, there have been several international consensus guidelines written on the management of breast cancer. Application of consensus guidelines has previously been demonstrated to have a positive influence on breast cancer care. The importance of specialty breast centers has previously been reported. As part of the 2021 Bosnian-Herzegovinian American Academy of Arts and Sciences (BHAAAS) conference in Mostar, a round table of multidisciplinary specialists from Bosnia and Herzegovina and the diaspora was held. All were either members of BHAAAS or regularly participate in collaborative projects. The focus of the consortium was to write the first multidisciplinary guidelines for the general management of breast cancer in Bosnia and Herzegovina. Guidelines were developed for each area of breast cancer treatment and management. These guidelines will serve as a resource for practitioners managing breast cancer in the Bosnia and Herzegovina region. This might also be of benefit to the ministry of health and any future investors interested in developing breast cancer care policies in this region of the world.

Tissue reaction to absorbable endoloop, nonabsorbable titanium staples, and polymer Hem-o-lok clip after laparoscopic appendectomy.

BACKGROUND AND OBJECTIVES: The standard technique for securing the base of the appendix during laparoscopic appendectomy is by absorbable endoloop ligature, although clinical reports favor the use of the stapler. Nonabsorbable Hem-o-lok clips have been shown to be an alternative technique to this. However, it is currently not clear whether nonabsorbable clips have any effects on the intestine or promote infection in the surgical area. MATERIALS AND METHODS: Sixty Wistar albino rats were randomized into 3 treatment groups: group I (n=20) the base of the appendix was secured by endoloop 2-0 ligature; group II (n=20) dissection of the appendix was performed by a 45-mm thick stapler; and group III (n=20) the base of the appendix was secured by a Hem-o-lok plastic clip. The animals were sacrificed on the 14th and 28th days after surgery. The secured stump was used for histopathological examination. RESULTS: There were no significant differences in histopathological changes observed on the 14th postoperative day between the groups. On the 28th postoperative day, it was proved that mild and moderate inflammation is more frequent in the endoloop and Hem-o-lok groups than in the stapler group. Reaction to a foreign body is more frequent in the endoloop than in stapler and Hem-o-lok groups. CONCLUSION: The mildest postoperative inflammatory changes were seen in the stapler group, followed by the Hem-o-lok group. However, because of the price of the plastic clip and the simplicity of its application, its use is still favored during laparoscopic appendectomy.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Methylene Blue as Inexpensive and Reliable Sole Sentinel Lymph Node Mapping Agent for Patients with Invasive Ductal Carcinoma.

BACKGROUND: Invasive ductal cancer (IDC) represents about 75% of all breast malignancies. There are many breast cancer prognostic factors, but the ones that have the most impact on the survival rates in advanced breast cancer are tumor size and regional lymph node involvement. Axillary lymph node dissection (ALND) has particularly important and undoubtful role in current surgical options for breast cancer treatment. With the introduction of sentinel lymph node biopsy (SLNB) for breast cancer patients it was possible to identify those to whom regional spread of the disease did not occur at the time of surgery, and thus spare them an unnecessary ALND procedure. OBJECTIVE: To determine the rate of sentinel lymph node (SLN) detection using only methylene blue dye as a mapping agent, as well as to correlate the number of positive SLNs with the number of positive non-sentinel lymph nodes (non-SLNs). METHODS: The study represents a prospective study that included 50 female patients with histologically confirmed invasive ductal carcinoma (IDC) who underwent SLNB using only methylene blue dye as the mapping agent, while the detection and harvest of SNL was done by visual control only. All patients also underwent an obligatory complete ALND, which was as that time the institutional oncological protocol for surgical treatment of histologically confirmed IDC. The final data such as tumor size, SLN and non-SLN status were obtained by further analysis of pathohistological reports from tumor biopsy and other surgical specimens. RESULTS: The accuracy rate of SLN detection was 98%. The number of detected SLN was in the range of 1 to 6, with an average of 2 for each patient. The number of positive SLN was in significant correlation with the number of tumor-affected non-SNL (p<0,001). Further analysis showed that for each increase in the number of positive SLN by 1, the risk of positive non-SLN increased 6-fold, OR=6,22 (p<0,001). CONCLUSION: Use of methylene blue dye as a sole mapping agent when performing SLNB in patients with IDC is a reliable and effective method that can be safely implemented in medical institutions that lack availability of nuclear medicine services or significant monetary funds.

An epidemiological study of neuroendocrine tumours at tertiary hospitals in Bosnia and Herzegovina.

Aim Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours with varying clinical expression and behaviour. Because of indolent behaviour of NENs, reviewing and evaluation of epidemiological characteristics is a challenge. The aim of this study was to assess prevalence of NENs at tertiary hospitals considering age, gender, location, and grade. Methods Electronic files were used for a retrospective assessment of the patients with NENs of the gastroenteropancreatic tract and bronchopulmonary system in tertiary hospitals in Bosnia and Herzegovina over the past 15 years (2005-2020). Results Among 438 patients, 291(66.4%) were males and 147 (33.6%) females; the median age was 62 years. The lungs were the most frequent site, 304 (69.4%), followed by the pancreas, 22 (5.0%), colon, 14 (3.2%), stomach, 13 (2.9%), appendix, 13 (2.9%), rectum,11 (2.5%), small intestine, eight (1.8%) and gallbladder, one (0.2%). Metastases were most frequently found in the liver, 35 (8%) and lymph nodes, 15 (3.42%). Conclusion The results were largely consistent with those in literature, including age, gender, location, and the degree of differentiation. Most metastases originated from high-grade tumours and greater impairment of the liver.

Prevalence of high-risk human papillomavirus infection and cervical cytology abnormalities among women up to age 40 in the Tuzla Canton, Bosnia and Herzegovina.

INTRODUCTION: Cervical cancer is the second leading cause of female cancer in Bosnia and Herzegovina, and it is the most common female cancer in women 15 to 44 years old. Cervical cancer is etiologically associated with high-risk human papillomaviruses (HRHPV). Data on the prevalence of HRHPV in Bosnia and Herzegovina are scant. This study investigates the prevalence of HRHPV infection among women of reproductive age compared with cervical cytology in the Tuzla Canton. METHODS: We analyzed the results of HRHPV testing and Papanicolaou (Pap) test results in women up to 40 years old diagnosed at the Tuzla University Clinical Center (UCC) from January 2019 to March 2020. RESULTS: Among 880 women tested for HRHPV, 27.2% (n = 239) were ≤ 40 years. In this age group HRHPV was detected in 33.5% (n = 80) of women, and 23.8% (n = 19) were women < 30 years. Out of 239 women tested for HRHPV, 60.2% had an abnormal Pap smear result. Therefore, 40.7% (n = 59) of HRHPV-positive women had an abnormal Pap test result. Women with a normal Pap test result had an HRHPV-positive test in 22.3% (n = 21) of cases. CONCLUSION: The results obtained contribute to the knowledge about HPV prevalence and the incidence of squamous cell abnormalities in the most populous canton in Bosnia and Herzegovina, possibly reflecting the situation nationally. The high prevalence of HRHPV in women of reproductive age calls for urgent implementation of an organized cervical cancer screening program and HPV vaccination.

Clinical Characteristics and Outcome of Malignant Eyelid Tumors: A Five-Year Retrospective Study.

INTRODUCTION: To the best of our knowledge, this is the first study about malignant eyelid tumors in the region of Tuzla, Bosnia and Herzegovina, and it shows similar results comparing with other countries (the annual incidence of eyelid tumors in Tuzla region is about 3.73/100 000 population). Malignant eyelid tumors are relatively uncommon, but potentially fatal disease. However, if detected early and treated adequately, the prognosis is generally excellent. AIM: The aim of this study was the clinical and microscopical analysis of malignant eyelid tumors in treated patients, the presentation of surgical treatment and reconstructive methods of eyelid tumors. METHODS: This retrospective study included 60 patients surgically treated at the University Clinical Center Tuzla from January 2012 to December 2016, who were initially diagnosed with malignant eyelid tumors in accordance to the final results obtained by histological examination of excised lesions. RESULTS: In the group of malignant tumors, the most common tumors were BCC (85%), which were predominantly found on the lower eyelids (92.16%) and showed female predominance (51.06%). SCC was the second most common eyelid malignancy (15%) and showed a predilection for the lower eyelid involvement and male predominance (55.56%). Tumors up to 2 cm in diameter (clinical stage T1) were found in 78.33% of cases, 95.74% of which with radical excision, while 4.26% with non-radical excision. CONCLUSION: Treatment by complete excision with histological confirmation of tumor clearance is recommended. Perineural spread is an adverse prognostic sign, which may require postoperative radiotherapy. Orbital invasion is a rare complication but, if recognized early, it can be treated effectively with exenteration. Because presentation varies and histological examination is required for accurate diagnosis, any suspicious lesion occurring on the eyelids should be excised or biopsied. All patients with malignant tumors should be advised of the risk of recurrent or new tumors and encouraged to attend lifelong follow up.

Direct immunofluorescence and immunohistochemistry in diagnostics of glomerulonephritis.

The needle biopsies from 60 transplanted and native kidneys have been processed and a prospective analysis of pattern, intensity and distribution of immunoglobulin deposits (IgA, IgG and IgM) and complement components (C3c and C1q) identified in these lesions has been carried out by immunohistochemistry with three step immunoperoxidase, in the period from 2000 to 2004. Those deposits were previously detected and analyzed by immunofluorescence. The samples consisted of 30 renal biopsies, previously diagnosed with glomerulonephritis and positive immunofluorescence and 30 renal biopsies without morphologic changes and deposits on immunofluorescence. 78,7% of the analyzed samples showed the identical results of the deposits of immunoglobulin and components of the complement with both, immunohistochemistry and immunofluorescence method. Sensitivity of the immunohistochemistry method with three step immunoperoxidase for all analyzed immunoglobulin and complement components is high (0,93), while specificity for the same method is 0,79. Standardized method of the three step immunoperoxidase on the paraffin embedded, formalin fixed needle renal biopsies could successfully replace the immunofluorescence method in diagnostic of GN, with the emphasis on a follow up and control of each single step in the procedure of the method.

Giving Birth After Fertility Sparing Treatment of Embrional Carcinoma Figo III C: Case Report and Literature Review.

INTRODUCTION: Malignant ovarian germ cell tumors (MOGCTs) account for 2-5% of all ovarian cancers and among them pure embryonal cell cancer is rare condition (1, 2, 3, 4). AIM: To show successful pregnancy after unilateral salpingooopherectomy and chemotherapy in a girl with embryonal carcinoma of ovary (ECO). CASE REPORT: Patient had FIGO stage III c disease. After the surgical removal of the tumour, the patient underwent six cycles of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP). Eight years after chemotherapy she conceived spontaneously. The patient went through regular antenatal checkups in a consultation with a gynecological oncologist. In addition to all regular examinations and controls, monthly monitoring of carbohydrate antigen (CA) 125, human epididymis protein 4 (HE 4), Roma Index is also recommended. Congenital malformation excluded at 20 weeks of gestation by level III ultrasonography. At 39th gestational week, laparotomy as well as a C-section was done and the patient was managed successfully in giving birth to a healthy female baby. Three months after delivery, the woman was recurrence free and the infant did not show any problems. At the last follow-up visit (May 5, 2018), all the tumor markers were negative, and the control MRI and ultrasound examinations did not reveal tumor recurrence or pathological lymph nodes. CONCLUSION: Normal gonadal function and fertility are possible after fertility preservation surgery for ovarian germ cell malignancies, even with adjuvant chemotherapy.

Monitoring of chemotherapy successfulness of platina/taxol chemotherapy protocol by using determination of serum urokinase plasminogen activator (uPA) and soluble urokinase plasminogen activator receptor (suPAR) in patients with ovarian carcinoma FIGO II and III stage.

In about 70% of cases, ovarian carcinoma has been diagnosed at an advanced stage. Invasion and metastasis of solid tumors request protease activity resulting in basal membrane destruction and surrounding matrix. In that process, urokinase plasminogen activator (uPA) and its receptor, urokinase plasminogen activator receptor (suPAR) play a key role, that via plasmin activation lead to basal membrane and matrix degradation in surrounding of the tumor, enable to its invasion and metastasis. Determination of serum concentration of those tumor markers can be useful in preoperative as well as in postoperative period. Their serum concentrations in ovarian cancer patients may help in good monitoring of remission or progression during chemotherapy treatment. In late 1950s and ear1y 1960s, when it was found out that malignant ovarian tumors were chemosensitive, their chemotherapy treatment has begun. In the beginning it was used only mono-therapy, and by discovering new cytostatics it was replaced by poly-chemotherapy. Now days, in the therapy of advanced stages of ovarian carcinoma combination of cisplatine or carboplatine with paclitaxel is considering as standard treatment. Aim of this study was to determine serum uPA, suPAR and CEA in FIGO II and III patients with different histological type (serous, mucinous, clear cell tumor) before and after PT chemotherapy protocol during following three cycles. In this prospective study we have analyzed 17 patients with ovarian carcinoma, those have been after surgery treated by chemotherapy. Serum levels of uPA and suPAR have been determined by ELISA-test (Imubind uPA, Imubind uPAR, American Diagnostica), and CEA by OPUS Imunoassay method. Results of this study have shown that uPA, suPAR and CEA met criteria for prognostic markers for monitoring of successfulness of platina/taxol chemotherapy protocol for serous, mucinous and clear cell tumor FIGO II and III stage of ovarian carcinoma. In case of PT chemotherapy protocol suPAR was better prognostic marker for monitoring of chemotherapy successfulness (Pearson coefficient 0,9 do 1,0; p<0,00l) than uPA (Pearson coefficient between 0,86 and 0,92; p<0,02) and CEA (Pearson coefficient 0,5 do 0,89; p<0,04).

Association of Hodgkin's lymphoma with Epstein Barr virus infection.

The role of Epstein Barr virus (EBV) in the onset of Hodgkin's lymphoma has been a subject of ongoing research. However, confirmation of EBV oncogenic involvement was not possible due to the small number of neoplastic cells characteristic for this type of tumor. Presence of EBV infection in neoplastic and non-neoplastic cells was analyzed in 81 cases of Hodgkin's lymphoma. In neoplastic cells, using an immunohistochemical method, latent membrane protein 1 (LMP1) was found in 33,3% of cases, while in situ hybridization results demonstrated the presence of EBER RNA in 48,1% of the cases. EBER RNA was found in non-neoplastic lymphocytes in 38,3% of cases. EBV is most frequently associated with Hodgkin's lymphoma in the first and seventh decade of life, specifically the nodular sclerosis subtype. No apparent difference was observed in the association of Hodgkin's lymphoma with EBV between genders, or in relation to clinical stage of the disease and average age of the patient. However, association with childhood age is significantly greater in comparison to adults. EBV associated disease shows a significantly greater prevalence in T lymphocytes. Slightly more abundant are cytotoxic T lymphocytes, which are also more frequently in contact with Reed-Sternberg cells, although there is no difference in number and positioning of histiocytes. Variations between the data on the association of EBV with Hodgkin's lymphoma among studies from different parts of the world suggest that factors of age, gender, ethnic background and social status might present biological modifiers of EBV influence on the pathogenesis of this neoplasm. The differences in non-neoplastic infiltrate EBV+ and EBV- lymphoma indicate the effect of the virus on the immune interaction of tumor and host in this disease.

Efficacy in treatment of cervical HRHPV infection by combination of beta interferon, and herbal therapy in woman with different cervical lesions.

Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). The HPV infections are treated through destroying the clinical lesions: laser, cryotherapy, podophyllin... The hope is that by causing local tissue inflammation that the body will be stimulated to mount an antibody response and thereby prevent recurrence. In contrast to other prevention approaches, vaccines can reduce susceptibility in uninfected partners by stimulating the immune system. Aloe vera has also been reported to retard tumour growth and stimulate the immune response to viruses. A list of possible actions of propolis includes: antibacterial, antifungal, antiviral, antioxidant, anticarcinogenic, antithrombotic and immunomodulatory. Research on the possible role of some B vitamins in preventing cancer began in the last few decades, but however this complex have an influence on immune status. The aim of our study is to try to treat the HPV infection as confirmed cause of neoplastic transformation with some herbal therapy and interferon and to try define the guidelines in the management of the HPV positive patients. Goal of this paper is to search for evidence of efficacy of any treatment for HPV infection of the cervix mostly in woman with no concomitant CIN. Fifty five woman affected by HPV genital infection were enrolled in the study from September 2005 to April 2006. Patients were classified according to the results of the HPV testing prior and after the therapy. Patients were randomized into two groups: the first group was HPV positive woman treated with other than recommended therapy (n=20), (control group); the second group was pharmacologically treated with intravaginal administration of an interferon and aloe vera-propolis in recommended scheme (n=35) with treatment of the possible fungal or bacterial genital infection prior to the specific therapy. The almost same therapy was recommended to the male partner. Patients from the second group used B complex during the therapy. Patients were retested for the HPV presence after three or six month from therapy depend of the presence bacterial or fungal genital coinfection. Three months after applied therapy HPV infection was still present in more than 90% of the patients in the first group. In the second group treated according to the recommended therapy scheme HPV infection disappeared in 71.42% of the patients after three months and in 100% of patients after six months. Samples of the cervical smear for the HPV analysis were being taken during routine gynecological examinations, by using sticks with cotton, taken from the Digene Specimen Collection Kit, from the whole surface of a portion, and by mild rotating moves from the outer cervical entrance. Our results suggest that the combination of interferon and herbal therapy with B complex is effective, atraumatic and simple non-surgical treatment of HPV infection. Since prospective efficacy trials will take several years to complete, considering alternative approaches is also worthwhile.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Ovarian cancer in the Federation of Bosnia and Herzegovina during the 1996 - 2010 period.

AIM: To investigate the ovarian cancer incidence for the period 1996-2010 in the Federation Bosnia and Herzegovina (FBandH) emphasizing that there is no official cancer database for that period. METHODS: This retrospective study analyzed ovarian cancer incidence in the period 1996-2000 and an estimation of incidence for the period 2000-2010 based on this data, as well as on 2007 -2010 incidence according to the Federal Public Health Institute. RESULTS: The incidence of ovarian cancer in the period 1996-2000 was 3.68-6.38/100.000. The estimate of incidence for the period 2000-2010 resulted with the rate of 14.6 at the end of the analyzed period. According to the Federal Public Health Institute, incidence for the period 2007-2010 was 11.4-12.4/100.000. CONCLUSION: According to different sources incidence of ovarian cancer in the Federation BH varies from 11.4-12.4/100.000, which is lower than the incidence for Southern Europe and neighboring countries. Incidence published by the International Agency for Research on Cancer (2008) for BH (both entities) was 10.1/100.000. An increasing trend of incidence is evident too. However, in FBiH a cancer database does not exist, while the system of cancer registration does not function or operate without proper coordination. A further main task for health authorities is to establish a functional system of cancer registration and a database, which would enable a follow-up and work on prevention and early detection of ovarian cancer.

Human papillomavirus genotype distribution in invasive cervical cancer in Bosnia and Herzegovina.

PURPOSE: Countries of the former Yugoslavia bear some of the highest cervical cancer burden in Europe. In Bosnia and Herzegovina (B&H), data on human papillomavirus (HPV) genotype distribution among cervical cancer cases is scarce. This baseline information is critical in order to evaluate the impact of prophylactic HPV vaccines. This study aims to provide specific information for B&H. METHODS: The final analysis comprised 283 cases of invasive cervical cancer identified at the Polyclinic for Laboratory Diagnostic, University Clinical Center Tuzla in B&H between 1984 and 2004. HPV was detected through amplification of HPV DNA using SPF-10 broad spectrum primers followed by deoxyribonucleic acid enzyme inmunoassay and genotyping by reverse line probe assay (LiPA(25), version 1). RESULTS: Most cases (92.2%) were histologically classified as squamous cell carcinoma (SCC). A total of 268 cases (94.7%) were positive for HPV. Infections were mainly present as single (95.5%) and HPV16 and 18 accounted for 77.8% of the positive cases. The next most common HPV types were HPV45 (4.4%), HPV33 (3.1%), HPV51 (2.3%) and HPV31 (2.2%). The mean age of cases infected with the seven most common types worldwide (HPV16/18/45/31/33/52/58) was 51.1 (SD=11.6), six years younger than the one for cases infected with other types (56.3, SD=12.9). CONCLUSIONS: Available HPV vaccines could potentially prevent 77.8% of Bosnian cervical cancer cases (i.e. those associated with HPV16/18). If the reported magnitude of the cross-protection of licensed vaccines for non-vaccine HPV types is long lasting, an additional 6 to 10% of cases could be prevented.