The Influence of Platelet-Rich Fibrin on the Healing of Bone Defects after Harvesting Bone-Patellar Tendon-Bone Grafts.

Background and Objectives: A bone-patellar tendon-bone (BTB) autograft in anterior cruciate ligament reconstruction (ACLR) is still considered the gold standard among many orthopedic surgeons, despite anterior knee pain and kneeling pain being associated with bone defects at the harvest site. Bioregenerative products could be used to treat these defects, perhaps improving both the postoperative discomfort and the overall reconstruction. Materials and methods: During a year-long period, 40 patients were enrolled in a pilot study and divided into a study group, in which bone defects were filled with Vivostat® PRF (platelet-rich fibrin), and a standard group, in which bone defects were not filled. The main outcome was a decrease in the height and width of the bone defects, as determined by magnetic resonance imaging on the control exams during the one-year follow-up. The secondary outcomes included an evaluation of kneeling pain, measured with a visual analog scale (VAS), and an evaluation of the subjective knee scores. Results: The application of Vivostat® PRF resulted in a more statistically significant reduction in the width of the defect compared with that of the standard group, especially at 8 and 12 months post operation (p < 0.05). Eight months following the surgery, the study group's anterior knee pain intensity during kneeling was statistically considerably lower than that of the standard group (p < 0.05), and the statistical difference was even more obvious (p < 0.01) at the last follow-up. Each control examination saw a significant decrease in pain intensity in both the groups, with the values at each exam being lower than those from the prior exam (p < 0.01). A comparison of subjective functional test results 12 months post operation with the preoperative ones did not prove a statistically significant difference between the groups. Conclusions: The use of Vivostat® PRF reduces kneeling pain and accelerates the narrowing of bone defects after ACLR with a BTB graft, but without confirmation of its influence on the subjective knee score.

Prognostic Factors for Post-Recurrence Survival in Stage II and III Colorectal Carcinoma Patients.

Background and objectives: This study aimed to evaluate prognostic factors for post-recurrence survival in local and locally advanced colorectal cancer patients. Materials and Methods: A total of 273 patients with stage III and high-risk stage II colorectal cancer were prospectively enrolled. All patients underwent operative treatment of the primary tumor and adjuvant fluorouracil-based chemotherapy. Results: Over the three-year period (2008-2010), a cohort of 273 patients with stage III and high-risk stage II colorectal cancer had been screened. During follow up, 105 (38.5%) patients had disease recurrence. Survival rates 1-, 3- and 5-year after recurrence were 53.9, 18.2 and 6.5%, respectively, and the median post-recurrence survival time was 13 months. Survival analysis showed that age at diagnosis (p < 0.01), gender (p < 0.05), elevated postoperative Ca19-9 (p < 0.01), tumor histology (adenocarcinoma vs. mucinous vs. signet ring tumors, p < 0.01) and tumor stage (II vs. III, p < 0.05) had a significant influence on post-recurrence survival. Recurrence interval and metastatic site were not related to survival following recurrence. Multivariate analysis showed that older age (HR 2.43), mucinous tumors (HR 1.51) and tumors expressing Ca19-9 at baseline (HR 3.51) were independently associated with survival following recurrence. Conclusions: Baseline patient and tumor characteristics largely predicted patient outcomes after disease recurrence. Recurrence intervals in local and locally advanced colorectal cancer were not found to be prognostic factors for post-recurrence survival. Older age, male gender, stage III and mucinous histology were poor prognostic factors after the disease had recurred. Stage II patients had remarkable post-recurrence survival compared to stage III patients.

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy.

BACKGROUND: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated. PATIENTS AND METHODS: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy. Determination of uPA and PAI-1 concentrations in the breast cancer tissue extracts was performed using FEMTELLE® uPA/PAI-1 ELISA. An insertion (5G)/deletion (4G) polymorphism at position - 675 of the PAI-1 gene was detected by PCR-RFLP analysis. RESULTS: Our research showed that patients with uPA tumor tissue levels higher than 3 ng/mg of protein had significantly reduced disease-free survival (DFS) and overall survival (OS) when compared to patients with uPA tumor tissue levels lower or equal to 3 ng/mg of protein. Patients with PAI-1 tumor tissue levels higher than 14 ng/mg of protein had significantly decreased OS in comparison with patients with PAI-1 tumor tissue levels lower or equal to 14 ng/mg of protein. ROC analysis confirmed the uPA and PAI-1 discriminative potential for the presence/absence of relevant events in these patients and resulted in higher cut-off values (5.65 ng/mg of protein for uPA and 27.10 ng/mg of protein for PAI-1) than standard reference cut-off values for both biomarkers. The prognostic importance of uPA and PAI-1 ROC cut-off values was confirmed by the impact of uPA higher than 5.65 ng/mg of protein and PAI-1 higher than 27.10 ng/mg of protein on poorer DFS, OS and event-free survival (EFS). We observed that patients with dominant allele in PAI-1 genotype (heterozygote and dominant homozygote, - 675 4G/5G and - 675 5G/5G) had significantly increased DFS, OS and EFS when compared with patients with recessive homozygote genotype (- 675 4G/4G). CONCLUSION: Our study indicates that uPA and PAI-1 tumor tissue levels and 4G/5G variants of PAI-1 gene might be of prognostic significance in early node-negative luminal HER2-negative breast cancer patients treated with adjuvant endocrine therapy.

Progress of the Journal of the Balkan Union of Oncology in the second decade of its existence.

PURPOSE: To investigate the progress of the Journal of the Balkan Union of Oncology (JBUON) in the second decade of its existence. METHODS: We investigated 10 volumes of JBUON, consisting of 42 issues, with regard to the number and category of articles, the contribution of authors from Balkan and non-Balkan countries, and the (co)authorship in published articles. RESULTS: In period 2006-2015, 1407 articles of different categories were published in JBUON. Most were original articles. In 2009, JBUON became listed in Science Citation Index (SCI) database and gained impact factor (IF). After that, the values of some investigated parameters (e.g. submission rate, total number of papers and the number of original articles) correlated with constant rise of the IF value. CONCLUSION: During the second decade of JBUON the journal has been gradually progressing in regard to the submission rate, the percentage of original papers, contribution of more countries other than Balkan countries, and the number of authors per article. This progress is the consequence of indexing in the SCI list in 2009, and to steadily rise of the IF value.

The influence of breast cancer subtypes on the response to anthracycline neoadjuvant chemotherapy in locally advanced breast cancer patients.

PURPOSE: The objective of neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC) is downstaging to achieve resectability. According to the protocol for the treatment of LABC more than 10 years ago, the routine NACT for LABC in Serbia consisted of 4 cycles of FAC (fluorouracil, doxorubicin, cyclophosphamide). The aim of this analysis was to assess the influence of biologic subtypes of BC on the response to NACT and on the disease outcome in these patients. METHODS: We analyzed 190 patients with median age of 52 years (range 26-74), diagnosed with LABC between Jun/2002 and Dec/2005 and treated with 4 cycles of FAC. Patients with clinical response to NACT (162/192;85.26%) were subjected to radical mastectomy after which the majority of them received 3 cycles of adjuvant FAC, adjuvant tamoxifen if HR-positive disease, and postoperative radiotherapy. We retrospectively determined by immunohistochemistry estrogen receptor (ER)/ progesterone receptor (PgR)/HER2 status from BC biopsies in all patients who were divided in 4 subgroups. Pathological complete remission (pCR) was defined as ypT0N0. The main end points were disease-free survival (DFS) and overall survival (OS). Statistics included Fisher's exact test, KaplanMeier product-limit method and Log-rank test. RESULTS: After a median follow up of 76 months (range 3-128) 104/190 patients (54.74%) experienced disease relapse, while 78/190 (41.05%) died. Of 157 patients with known receptor status the numbers of 4 subtypes were as follows: 31/190 (16.32%) triple negative (TN) BC, 22/190 (11.58%) HR-/HER2+, 97/190 (51%) HR+/HER2- and 17/190 (8.95%) HR+/HER2+. Ten out of 190 patients (6.17%) achieved pCR and had significantly longer DFS (Log-rank test, p=0.042), and a trend to prolonged OS (Log-rank test, p=0.092). There was a significant difference (Fisher exact test, p=7.7 × 10-6) between pCR rates among 4 BC subtypes: 3/31 (9.68%) in TNBC, 6/22 (27.27%) in HR-/HER2+, 0/97 in HR+/HER2- and 1/17 (5.88%) in HR+/HER2+ patients. This difference was achieved on the account of the difference between TNBC and HR-/HER2+ BC subtypes (Fisher's exact test, p=6.85×10-6, Bonferroni correction: 0.05/6=0.0083). There were no differences in DFS and OS between the 4 BC subtypes. CONCLUSION: Although there was a significantly higher number of patients achieving pCR among HR-/HER2+ subtype compared to other BC subtypes, this did not translate into improvement in long-term disease outcome of these patients.

The impact of different infusion solutions on postoperative recovery following colorectal surgery.

PURPOSE: The purpose of this study was to compare two groups in postoperative recovery, whether there were any complications and whether the length of their hospital stay differed. One group received intraoperatively a combination of crystalloids and a small colloid dose, while the other group received only the crystalloids intraoperatively. METHODS: This randomized prospective study included 80 patients with colorectal cancer prepared for major elective colorectal surgery. The patients were randomly assigned to either the control group (CG) which received only crystalloid solutions intraoperatively or to the research group (RG) which received a combination of colloid and crystalloid solutions. Regional and general endotracheal anesthesia techniques were combined in all patients. Goal-directed fluid therapy was administered to patients in both groups. After extubation, patients were transferred in the Intensive Care Unit (ICU). We measured the administered fluids, fluid balance, the volume of received red packed cells (RPC) and fresh frozen plasma (FFP). Recorded were the first bowel movement, the first flatus, the tolerance on oral food, complications by Clavian-Dindo classification, days of patient's recovery delay in the ICU, Surgery Department (SD) and the total length of hospital stay (LOS). RESULTS: Statistically significant differences were present in all parameters of postoperative recovery. RG patients showed better results relative to the CG patients. RG patients were faster in restoring bowel movement and peristalsis, get the first postoperative stool and re-acquire oral food tolerance. According to the Clavian-Dindo classification of complications, no significant difference between these two groups was noted. CONCLUSIONS: Goal-directed colloid-crystalloid therapy significantly improved postoperative recovery.

The influence of PTEN protein expression on disease outcome in premenopausal hormone receptor-positive early breast cancer patients treated with adjuvant ovarian ablation: a long-term follow-up.

PURPOSE: All breast cancer (BC) patients with detectable hormone receptors (HR) expression should be offered endocrine therapy (ET). In premenopausal patients, tamoxifen and/or ovarian suppression (OvS)/ablation (OA) may improve disease outcome. Alteration of phosphatase and tensin homolog (PTEN) signaling pathways could be one of the possible mechanisms of resistance to antiestrogen therapy. The purpose of this study was to investigate the association of PTEN protein expression with prognostic factors such as tumor histology and grade, estrogen receptor (ER) and progesterone receptor (PgR) status, human epidermal growth factor receptor 2 (HER2) and disease outcome in premenopausal patients with HR-positive early BCs treated with adjuvant OA. METHODS: We analyzed a group of premenopausal early stages I/II HR-positive BC patients who had undergone radical mastectomy followed only with adjuvant OA by irradiation. ER and PgR contents were determined by classical biochemical dextran-coated charcoal (DCC) method, HER2 status by chromogen in situ hybridization (CISH) analysis and PTEN status by immunohistochemistry (IHC). RESULTS: Sixty-six premenopausal patients included into this analysis were followed for a median of 17 years (range 17-29). Compared to PTEN-positive BCs, PTEN-negative BCs were significantly more frequently associated with lobular tumor histology (p<0.05), higher ER content (p<0.05), and had significantly decreased disease-free survival (DFS) and overall survival (OS) (p<0.01 for both) compared to patients with PTEN-positive BCs. CONCLUSIONS: It seems that PTEN status determined by protein expression may discriminate between subgroups with poor and good prognosis in premenopausal HR-positive BC patients receiving adjuvant OA.

Treatment outcome in patients with breast conserving surgery after neoadjuvant therapy for breast carcinoma - a single institution experience.

PURPOSE: The aim of this study was to analyze outcomes of breast conserving surgery (BCS) after neoadjuvant treatment (NAT) in comparison to radical mastectomy (RM) after NAT in terms of disease-free survival (DFS), overall survival (OS) and patients' satisfaction with the esthetic outcomes of surgery. METHODS: This prospective study was conducted at the National Cancer Research Center of Serbia, Belgrade, from January 1st 2011 to December 31st 2015, on breast carcinoma patients receiving NAT. Treatment outcome was assessed by MDAPI (MD Anderson Prognostic Index). Female patients (n=52) with satisfactory clinical response to NAT and MDAPI scores 0 or 1 were included into the treatment group (NAT-BCS group). The control group (NAT-RM group) consisted of patients (n=52) with poorer clinical response and MDAPI scores 2 to 4. On check-ups, local or distant relapses were noted and both groups were asked to value their satisfaction with the esthetic outcomes of surgery using the Likert scale. RESULTS: OS was 100% in both groups. DFS was 96.1% in NAT-BCS group and 100% in NAT-RM group. Local recurrences were observed in two patients from the age group ≥60 years, with initial disease stage IIIA and "clear" resection margins on frozen section study. Patients in the NAT-BCS group were more satisfied with the esthetic outcome of surgery than the control group. CONCLUSIONS: BCS after NAT provides good esthetic outcome and is oncologically safe if adequate clinical response is achieved after NAT and if established criteria for patient selection are followed.

Curative intent for unresectable advanced squamous cell esophageal cancer: Overall survival after chemoradiation.

PURPOSE: To analyse the overall survival (OS) of patients with locally advanced, unresectable esophageal cancer treated with chemoradiation (CRT) with or without surgery. METHODS: CRT was administered to 63 patients with locally advanced (T3-4, N0-1), initially unresectable squamous cell esophageal cancer. After the assessment of tumor response to treatment, medically fit patients converted to operable stage were subjected to surgery. Regular follow-up was performed every 3 months during first 2 years, and then every 6 months. RESULTS: All 63 patients completed the whole radiotherapy course. Forty patients (63%) received complete 4 cycles of chemotherapy. In the remaining 23 patients (37%) chemotherapy was interrupted due to toxicity. Clinical response to CRT was: complete response (CR) in 4 patients (6%), partial response (PR in 27 (43%), stable disease (SD) in 22 (35%) patients, and 10 patients (16%) had disease progression (PD). After reevaluation, 23 patients (15 PR and 8 SD after CRT) underwent surgery (37%), all with R0 resection. OS in the whole group was 53% at one year, and 36% at two years. OS was significantly better in the operated group of patients than in the non-operated group. No statistically significant difference in OS was observed comparing operated to CR patients with no surgery (70 vs 50%). In the non-operated group of patients there was no difference in OS between CR, PR, and SD patients. CONCLUSIONS: With appropriate selection, patients with advanced squamous cell esophageal cancer should be considered for potentially effective treatment.

Tumor response and patient outcome after preoperative radiotherapy in locally advanced non-inflammatory breast cancer patients.

PURPOSE: The purpose of this analysis was to assess the tumor response and long-term outcome in patients treated with preoperative radiotherapy (PRT) without systemic therapy. METHODS: Between 1997 and 2000, 134 patients with non-inflammatory locally advanced breast cancer (LABC) were treated with PRT. The tumor dose was 45 Gy in 15 fractions to the breast and to regional lymph nodes over 6 weeks. Radical mastectomy was performed 6 weeks after PRT to all patients and adjuvant systemic therapy was administered as per protocol. The measures of disease outcome were overall survival (OS) and disease-free survival (DFS) which estimated using the Kaplan-Meier method. RESULTS: Median follow-up was 74 months (range 4-216). Objective clinical tumor response after PRT was observed in 77.6% of the patients. Clinical complete tumor response (cCR) was achieved in 21.6% of the patients. Pathological CR in the breast was achieved in 15% of the patients. The 5- and 10-year OS were 55.1 and 37.8%, respectively. The 5- and 10-year DFS were 39.2 and 27%, respectively. Patients who achieved cCR had significantly longer OS in comparison with patients achieving clinical partial response (cPR) and clinical stable disease (cSD). Similarly, DFS of patients in the cCR group was longer compared with patients with cPR and cSD, yet without statistical significance. CONCLUSIONS: Our results showed that local control in LABC patients achieved by primary PRT, followed by radical mastectomy was comparable with the results reported in the literature. Complete pathologic response to PRT identified a subgroup of patients with a trend toward better DFS and OS.

Vaginal packing volume impact on dose parameters during radiography and computed tomography based postoperative brachytherapy of cervical carcinoma.

PURPOSE: To investigate the influence of the vaginal packing volume on the registered dose parameters evaluated by radiography (2D) and computed tomography (CT) (3D) based brachytherapy planning in cervical cancer patients treated with postoperative radiotherapy. METHODS: The postoperative radiotherapy was performed in 40 cervical cancer patients with increased risk for disease relapse. Both, radiography and CT based brachytherapy planning were done in all patients. Vaginal packing volume was evaluated by clinical target volume (CTV)uk, assessed on CT scans and analyzed according to the registered dose parameters: doses delivered to the organs at risk (OAR) and the defined CTV, using both planning methods. RESULTS: CTVuk volume had statistically significant influence on CTV coverage with the prescribed brachytherapy doses D90 (p<0.01) and D100 (p<0.01), revealing a CTVuk cut-off value of 25.6 cm3. Dividing the patients into two groups according to the cutoff value, we found a statistical significance in the registered doses to the rectal wall and no significance in the bladder wall doses between the groups. Also, a statistically significant, negative correlation was found between CTVuk and following doses: Rmax (rho= -0.34, p<0.05), D0.1cc (rho= -0.76, p<0.01), D1cc (rho= -0.74, p<0.01) and D2cc (rho= -0.72, p<0.01), D90 (rho= -0.80, p<0.01), D100 (rho= -0.7, p<0.01). CONCLUSION: If the brachytherapy vaginal packing is of a large volume (more than 25.6 cm3), an asymmetric deformation of the proximal part of the vaginal cavity might appear, leading to inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a vaginal packing volume larger than 25.6 cm3 made no further reduction in the bladder dose, but it made a statistically significant further reduction in the rectal doses.

Prognostic importance of steroid receptor status for disease free and overall survival after surgical resection of isolated liver metastasis in breast cancer patients.

PURPOSE: Breast cancer (BC) is the most common malignancy among women, while isolated operable liver metastases (LMs) from BC are very rare and occur in only 1-5% of the patients. Besides, positive steroid receptor (SR) status for oestrogen and/or progesterone is known as a factor which improves disease free survival (DFS) and overall survival (OS). The primary aim of this study was to examine the impact of SR status on DFS and OS after liver metastasectomy in female patients with primary BC. METHODS: We analyzed 32 medical records of female patients diagnosed and treated for primary BC with LMS as the first and only site of disease progression, at the Institute of Oncology and Radiology of Serbia (IORS), during 2006- 2009. All of them underwent primary BC surgery as well as LMs resection. RESULTS: Patients with metachronous BC and LMs and positive SR status in both BC and LM (BC+/LM+) had a median time from BC to LM occurrence (TTLM) of 36 months, compared to BC+/LM- and BC-/LM- subgroups, whose medians for TTLM were 30.5 and 14.5 months, respectively (p<0.01). For all patients, positive SR status showed high correlation with longer DFS and OS after LM resection (medians according survival analysis for DFS/OS in subgroups BC-/LM-, BC+/LM- and BC+-LM+ were 10/19, 25/45, 50/not reached months respectively; p<0.01 for DFS/ OS). Cox regression analysis confirmed that the subgroup of patients with BC-/LM- had 10.8 and 18.8 higher risk of events for DFS (disease relapse or death) and event for OS (death only), respectively, compared to BC+/LM+ subgroup of patients. CONCLUSION: Positive SR status in BC and LM has a high impact not only on time from BC to LM occurrence, but also on longer DFS and OS after LM resection.

Lymph node metastases in clinically N0 patients with papillary thyroid microcarcinomas - a single institution experience.

PURPOSE: To register the frequency of central and lateral lymph node metastases (LNMs) from papillary thyroid microcarcinomas (PTMCs), and to assess whether sentinel lymph node (SLN) biopsy of the lateral compartment is an accurate technique to select patients with true positive but clinically negative lymph nodes for one-time selective lateral neck dissection (sLND). The correlation between tumor characteristics (size, multifocality, bilaterality, capsular invasion) and LNMs was analyzed. METHODS: During a 10-year-period (2004-2013), 111 clinically N0 patients with PTMCs had total thyroidectomy, central neck dissection and SLN biopsy of the lateral neck compartment in our institution. SLN mapping was performed by subcapsular injection of 0.2 to 0.5ml of 1% methylene blue dye. If SLNs were positive on frozen section, one-time sLND was done. RESULTS: Forty per cent of PTMCs were multicentric. LNMs were detected in 25% of the patients and isolated central LNMs were found in 18% of the patients. Lateral LMNs were present in 7% of the patients, of which 4% were isolated, skip LNMs. All these patients had therapeutic sLND. Specificity and sensitivity of SLN biopsy were 100% and 57%, positive and negative predictive values were 100% and 97%, respectively. Method's accuracy was 97%. CONCLUSIONS: SLN biopsy of the lateral neck compartment is more precise than physical examination and ultrasonography for detection of lateral LNMs in clinically N0 patients with PTMCs. Intraoperative assessment of lateral lymph nodes (SLNs) provides one-time therapeutic dissection for patients with occult LNMs at initial operation, reducing the need for additional operations. This method provides appropriate disease staging and optimizes treatment.

p21 does, but p53 does not predict pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) is the standard treatment option in locally advanced rectal cancer. The tumor response is assessed through tumor and nodal downstaging and the tumor regression grade. Currently, there is no method to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53 expressions could be a reliable predictors of pathological response to CRT. METHODS: Fifty patients with locally advanced rectal cancer were treated with preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53 immumohistochemical staining was performed on pretreatment biopsies and the results were compared with tumor regression according to grading systems by Dworak (TRG grades) and by Wheeler (RCRG grades). RESULTS: Testing RCRG grades in relation to p21 expression showed statistically significant difference (p=0.021). RCRG 3 (poor response) was more frequent in the group of patients with low p21. According to Dworak, grade 4 (complete regression) was more frequent in the group of patients with positive p21 expression (p=0.032). Significant difference in p21 expression in grade 4 group compared with all other grade groups was also found (p=0.007). Patients with immune expression of p21 had significantly higher percentage of complete regression in comparison to the patients with low expression of p21. We haven't found any correlation between p53 expression and histopathological (HP) as well as regression grades. CONCLUSION: According to both grading systems, our results suggest that p53 expression does not, but p21 expression does predict pathological response to preoperative CRT.

Importance of being indexed in important databases--effect on the quantity of published articles in JBUON.

PURPOSE: To investigate the dynamics of indexing the Journal of the Balkan Union of Oncology (JBUON) in important biomedical databases, the effects on the quantity and type of published articles, and also the countries of the (co)authors of these papers. METHODS: The process of the JBUON indexing started with EMBASE/Excerpta Medica, followed in 2006 (PUBMED/MEDLINE) and continued every second year in other important biomedical databases, until 2012 when JBUON became Open Access Journal (for even more information please visit www.jbuon.com). Including the next two years for monitoring the effect of the last indexing, we analyzed 9 volumes consisting of 36 issues that were published from January 2006 to December 2014, with regard to the number and category of articles, the contribution of authors from Balkan and non-Balkan countries, and the (co)authorship in the published articles. RESULTS: In the period 2006-2014, 1165 articles of different categories were published in J BUON. The indexing progress of JBUON immediately increased the submission rate, and enlarged the number of publications, original papers in particular, in every volume of JBUON. Authors from Balkan countries contributed in 80.7% of all articles. The average number of coauthors per original article grew slowly and was higher at the end of the investigated period than at the start (6.6 and 5.8, respectively). CONCLUSION: The progressing covering of JBUON in important biomedical databases and its visibility on international level attracted the attention of a large readership, and submission rate and the number of published articles grew significantly, particularly the number of original papers. This is the most important consequence of the editorial policy which will hopefully lead to even more progress of JBUON in the near future.

Acceptable adverse outcomes after delayed breast reconstruction using abdominal advancement flap - a 15-year experience.

PURPOSE: To evaluate the adverse outcomes after delayed breast reconstruction (DBR) by abdominal advancement flap (AAF) and permanent prosthesis in patients treated with mastectomy due to unilateral breast carcinoma, as well as to determine which factors are predictive for their occurrence. METHODS: The study included 155 patients operated at the Institute for Oncology and Radiology of Serbia from 1996 to 2010. All patients had total mastectomy and axillary lymph node dissection, followed by specific oncological treatment. Patients were selected for DBR after complete diagnostic evaluation. Adverse events were evaluated in regard to patient, disease and prostheses-related factors. RESULTS: During follow-up, DBR adverse events were observed in 23.237percnt; of the patients - the majority (91.67%) had only one. The most frequent was capsule contracture (47.22%), followed by asymmetry (22.22%), infection (16.67%) and prosthesis rupture (16.67%). There were isolated cases of prosthesis prolapse and local disease recurrence. Infections were treated conservatively in all but one patient. Other events were managed by additional operation. Statistical analysis showed that complications occurred significantly more often in patients ?51 years (vs 18-40, vs 41-50), disease stage IIb (vs Ia), T2 (vs T1) tumors and adjuvant radiotherapy (vs without). Prostheses-related factors were not significant for DBR complications, neither body mass index (BMI), nor smoking habits. CONCLUSIONS: DBR using AAF and permanent prosthesis is a safe technique with acceptable complication rate. It provides one-time surgery with satisfactory aesthetic results and good postoperative recovery. Most frequent complication is capsule contracture. Patients' age and irradiation of the chest wall after mastectomy are predictive factors for complications.

Factors related to local recurrence of non small cell lung cancer and its operability.

PURPOSE: To analyze the correlation of primary tumor (PT) pathological characteristics (size, stage, type and grade) and the extent of initial surgical treatment of non small cell lung cancer (NSCLC) with the incidence and time to local recurrence (LR) and disease-free survival (DFS), as well as to determine in what way these parameters and LR localizations affect the possibility for surgical retreatment. METHODS: The research was conducted on 114 patients with NSCLC and LR that had initial surgery in two reference institutes in Serbia from January 2002 to December 2010. PT size and disease stage were defined according to the revised 2004 WHO classification. PTs were grouped by size into 3 categories. Due to great diversity, surgical procedures were sorted into 6 operation types. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analyses showed significant difference in DFS and LR reoperability that were related to PT size, disease stage and the extent of initial surgery. LR localization on the chest wall was favorable for secondary surgery due to LR. CONCLUSIONS: Squamous cell lung carcinoma relapses locally more frequently than other lung tumor types, and the commonest LR site is the chest wall. This localization provides high possibility for surgical retreatment. Adequate staging, proper indications for surgical treatment and quality surgery provide longer DFS in patients with NSCLC. All these suggest that the surgeon may be considered as the most significant factor of prognosis.

Correlation of tumor size as independent factor and disease stage with local recurrence of non-small cell lung carcinoma and its operability.

PURPOSE: To analyze the correlation of non-small cell lung carcinoma (NSCLC) primary tumor size, independently, and the initial disease stage with the incidence of local recurrence (LR) and disease-free survival (DFS), as well as the LR operability. METHODS: The research was conducted on 114 patients operated due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia and the Institute for Oncology and Radiology of Serbia from January 2002 to December 2010, who developed LR during the 5-year follow-up. Diagnostic methods and surgical approaches were standard, defined by protocols. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analysis showed significant difference in DFS and LR incidence in first 2 postoperative years related to primary tumor size and stage. Patients with T1 tumors (vs T2 vs T3), as well as in earlier disease stage, had significantly longer DFS. LR in the first and second year after primary tumor operation occurred more frequently with larger primary tumors. Significant correlation was registered between LR operability and primary tumor size, as well as LR operability and primary tumor stage. CONCLUSIONS: This research highlights size of the primary tumor as independent prognostic factor for patients with NSCLC. The likelihood of LR increases with larger primary tumor and higher primary tumor stages, while DFS decreases. Because larger tumors are more frequently understaged, with occult mediastinal metastases, their LR is not possible to be surgically treated.

Surgical management of well-differentiated thyroid carcinoma in children and adolescents: 33 years of experience of a single institution in Serbia.

Well-differentiated thyroid carcinoma in children and adolescents is rare but demonstrates aggressive behavior. Gross lymph node metastases and distant metastases are common upon first clinical presentation. During a 33-year period (1981-2014) at the Institute of Oncology and Radiology of Serbia, 62 children and adolescents underwent surgery due to well-differentiated thyroid carcinoma. Mean age was 16.7 (range 7-21) years. At the time of diagnosis 6% of patients had lung metastases. Total thyroidectomy or completion thyroidectomy was performed for all patients followed by central neck dissection and frozen section examination of jugular-carotid compartments. Median follow-up was 10.9 (range 0.69-33.05) years and median tumor size was 20 (range 2-60) mm. Papillary carcinoma was found in 96%, and follicular and Hürthle cell carcinoma in 2% of patients. Multifocal tumors were found in 50% and capsular invasion in 60% of patients. Lymphonodal metastases in either central or lateral neck compartments were found in 73% of patients. Multifocality and capsular invasion were significantly more frequent in patients less than 16 years of age (both p < 0.01). Median disease-free interval had not been reached and overall survival rate was 100%. Well-differentiated thyroid carcinoma in children and adolescents is characterized by a high rate of loco-regional aggressiveness, multifocality, capsular invasion, lymph node metastases and distant metastases at the time of diagnosis. Adequate surgical approaches should be performed for both primary and recurrent disease in young patients with well-differentiated thyroid carcinoma in order to achieve loco-regional disease control and longer disease-free survival.

Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: a single institution experience.

PURPOSE: The aim of this research was to examine overall (OS) and disease-free survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC), treated with cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), as well as to analyse factors of prognostic significance. METHODS: We included 61 patients with pathological/and computerized tomography (CT) confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012. Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the CRC-PC extent. We performed CRS following the Sugarbaker's principles in all patients with PCI ≤20 and only in 3/61 (4.92%) patients with PCI >20. HIPEC (oxaliplatin 410 mg/m(2) in 2000mL isotonic solution and 41?C) was performed using RanD Performer® HT perfusion system during 30-60 min. Cox proportional hazard regression was used to determine significant factors for OS and DFS. RESULTS: The follow-up ranged from 1 to 83 months (median 22). Median OS was 51 months (95% confidence interval/ CI 22+). Median DFS for patients without residual disease (57/61, 93.44%) was 23 months (95% CI 16+). One-, 2- and 6-year OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By the end of the study, 55.74% of the patients were still alive. Cox multivariate analysis indicated PCI score as a parameter of highly prognostic significance for patients treated with CRS+HIPEC (p<0.001). Patients with PCI (13 (vs PCI ≥13) had significantly longer OS and DFS (p<0.001), also confirmed for PCI subcategories (PCI <7 vs 7≤ PCI <13 vs PCI ≥13). All patients with PCI <7 are still alive. CONCLUSION: Our study indicates that CRS+HIPEC significantly improves the survival of CRC-PC patients. This treatment modality should be considered as the most suitable in well-selected patients with this disease.