Risk-factors for locally advanced rectal cancer relapse after neoadjuvant chemoradiotherapy: A single center experience.

The overall prognosis of locally advanced rectal cancer (LARC) remains unsatisfactory due to a high incidence of disease relapse. The present understanding of the factors that determine the likelihood of recurrence is limited or ineffective. We aimed to identify the main risk factors influencing tumor relapse in LARC patients after neoadjuvant chemoradiotherapy (nCRT) and surgical treatment in a single center in Republika Srpska. Patients with stage II or stage III who received nCRT before surgery for primary rectal cancer at the Oncology Clinic, University Clinical Center of Republika Srpska from January 2017 and December 2022 were included in the study. We collected patient demographics, clinical stage and characteristics, neoadjuvant therapy, and surgical methods, along with the pathological response after treatment completion, and analyzed them to identify the risk factors for tumor relapse. Out of 109 patients diagnosed with LARC, 34 (31,2%) had tumor relapse. The median time to relapse was 54 months. Participants with clinical T4 stage had a significantly shorter relapse time compared to the patients with clinical T2/3 stage. Subjects with positive lymph nodes removed, perivascular and perineural invasion, intraoperative perforation and patients without ypN stage improvement had significantly shorter time to relapse. Subjects with T4 stage had more than 4 times higher risk of relapse than patients with clinical T2/3 stage. Higher clinical T stage was an essential risk factor for tumor relapse in LARC patients after nCRT and surgical treatment. Comprehensive understanding and identification of the risk factors for tumor relapse in LARC patients are crucial for improving their long-term outcomes.

Clinicopathological Characteristics, Treatment Patterns, and Outcomes in Patients with Laryngeal Cancer.

BACKGROUND: Various factors can affect the survival of patients with laryngeal cancer (LC). In this retrospective study, we assessed clinicopathological features, their prognostic value, and treatment modalities for patients with confirmed squamous cell LC. METHODS: We collected patient data on demographics, clinicopathological characteristics, treatment patterns, and outcomes. The primary endpoints were overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). We assessed survival using the Kaplan-Meier method and Cox regression model analyses of potential prognostic parameters. RESULTS: After a median follow-up of 76 months, 28 (33.3%) patients had a recurrence. The median OS was 78 months, with an event recorded in 50% of patients. The DSS median was not reached (NR) with a survival rate of 72.6%, the DFS survival rate was 66.7% with median NR, and the LRC survival rate was 72.6% with median NR. After conducting a multivariate analysis of significant variables, we found that only recurrence and lymphatic invasion had an independent effect on OS and recurrence in DSS, while subsite impacted DFS and LRC. CONCLUSIONS: Survival trends were consistent with other studies, except for OS. Recurrence, lymphatic invasion, and subsite location were significant factors that impacted patient survival.

Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients.

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

High Ki67 as negative predictor for response to concurrent radiotherapy plus Capecitabine in chemo-resistant advanced breast cancer.

PURPOSE: The purpose of this study was to evaluate Ki67 as a biomarker for response to concurrent chemo-radiotherapy in previously treated patients with standard chemotherapy protocols in the neoadjuvant setting (NACT). METHODS: Evaluated were 33 patients treated concurrently with radiotherapy and capecitabine. All patients had residual disease after anthracycline-docetaxel based NACT, verified with imaging techniques and clinical exams. Response rate (RR) was evaluated 3 months after completion of the concurrent treatment, and was correlated to tumor immune-histochemical characteristics. Binary logical regression was used for model testing and correlation of Ki67 and RR. An Omnibus test showed the model to be statistically significant and that a set of depending variables can be used as predictors for treatment response with p=0.021. Model -2 log likelihood with Nagelkerke R Square were used to define significance of other tumor characteristics besides Ki67. RESULTS: Only Ki67 showed statistically significant correlation with RR, as high Ki67 predicts that there will be no response to concurrent capecitabine - radiotherapy treatment in chemo-resistant advanced breast cancer. Other characteristics such as histological grade, estrogen or progesterone receptors, HER2 overexpression or lymphovascular or perineural invasion showed no significance. CONCLUSION: High value of Ki67 is a negative predictor for response in concurrent capecitabine-radiotherapy treatment in chemo-resistant advanced breast cancer.

Adjuvant Treatment of the Salivary Duct Carcinoma with Her2 Overexpression.

Malignant salivary gland tumors form 11% of all head and neck tumors. Salivary duct carcinoma (SDC) of the parotid gland is an uncommon and highly aggressive tumor accounting for 2% of all salivary gland malignancies. The fourth edition of the WHO Classification of Head and Neck Tumors reported global annual incidence of 0.4-2.6/100,000 people. Standard treatment for SDC is wide surgical resection along with lymph node dissection followed by adjuvant radiation therapy. The role of adjuvant chemotherapy is not known. Here, we present a case of an SDC of the parotid gland in a 55-year-old female. She presented with a painless swelling behind her right ear. Surgery was performed, and total right parotidectomy was done along with selective neck dissection (levels II, III, VA). The pathology report concluded that it was a G3 (poorly differentiated) SDC (micropapillary variant) with lymphovascular and perineural invasion. The clinical stage of the disease was T4aN2bM0. Adjuvant therapy consisted of concurrent radiation (TD 66 Gy) and chemotherapy with weekly paclitaxel (45 mg/m2), carboplatin (AUC 1.5), and trastuzumab (2 mg/kg; THC) for 6 weeks followed by 4 cycles of THC every 3 weeks. Adjuvant trastuzumab was continued for a total of 1 year. She is still without the evidence of the disease 7 years later. The consensus regarding the use of adjuvant chemotherapy does not exist. Based on all the data that have been presented before, the conclusion is that we need new treatment modalities to improve the outome of this aggressive disease.

Use of the Depression, Anxiety and Stress Scale (DASS-21) Questionnaire to Assess Levels of Depression, Anxiety, and Stress in Healthcare and Administrative Staff in 5 Oncology Institutions in Bosnia and Herzegovina During the 2020 COVID-19 Pandemic.

BACKGROUND Providing oncology services during a pandemic can contribute to mental health challenges among healthcare workers. The present study aimed to evaluate the levels of depression, anxiety, and stress in healthcare and administrative staff in 5 oncology institutions in Bosnia and Herzegovina (BiH) in 2020 during the coronavirus disease 2019 (COVID-19) pandemic using the Depression, Anxiety and Stress Scale (DASS-21) questionnaire. MATERIAL AND METHODS A cross-sectional observational study enrolled 175 healthcare and administrative workers from 5 oncology institutions in BiH during December 2020. Data were collected using a questionnaire that captured general information about the participants and a DASS-21 questionnaire. RESULTS Statistical analysis revealed a statistically significant difference in the levels of depression, anxiety, and stress (P=0.003, P=0.011, and P=0.022, respectively) among participants with comorbidities connected with increased risk of severe illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with participants without comorbidities. There was also a statistically significant difference in the levels of stress among participants from different cities (P=0.031). Supplement intake and educational level were significantly related (P=0.012). High levels of stress and anxiety were accompanied by high levels of depression among participants (P<0.01). CONCLUSIONS The findings from the present study showed that the COVID-19 pandemic has had an effect on depression, anxiety, and stress levels in oncology staff in BiH. Monitoring these levels and providing interventions and support to oncology staff are increasingly important for their wellbeing and retention at a time of global crisis in healthcare.

2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

Lymph Node Metastases Papillary Thyroid Carcinoma and their Importance in Recurrence of Disease.

BACKGROUND: The purpose of this study is to establish whether the lymph node metastases of the papillary thyroid carcinoma are a significant factor in recurrence of the disease by analyzing the time until recurrence of the disease and frequency of recurrence of the disease. METHODS: From 1 January 1995 until 30 June 2017, 102 patients were treated at the Public Health Institute Hospital "Sveti Vracevi" in Bijeljina for PTC. In all patients, surgery of the thyroid gland and/or lymph nodes of the neck was performed. Total thyroidectomy (TT) was performed in 20 patients and near-total thyroidectomy leaving <1 g thyroid tissue adjacent to the recurrent laryngeal nerve in 7 patients. TT and lymph nodes dissection were performed in 71 patients. Palliative surgery and biopsy due to locally advanced disease were performed in 3 patients. RESULTS: In our study, 102 patients with PTC were analyzed. 82 patients experienced pure PTC (80.4%), the other 20 patients (19.6%) experienced other variants of PTC. 24 patients (23.5%) experienced multi centric or bilateral tumors. 71 patients (69.6%) experienced histologically verified metastases in the lymph nodes of the neck. 7 patients (6.8%) experienced distant metastases. 20 patients underwent total thyroidectomy (TT), and 7 near-total thyroidectomy. Total thyroidectomy + dissection of central and lower jugular lymph nodes with frozen section histopathology verification was performed in 71 patients (69.6%). Out of these 71 patients, in 50 patients (70.4%) metastases were verified in the lower jugular lymph nodes. A modified lymph node dissection (MRND) was also performed in these patients. CONCLUSION: Lymph node metastases of the papillary thyroid carcinoma are a plausible prognostic factor. They are important for recurrence of the disease, but not for survival.

IMMUNOHISTOCHEMICAL EXPRESSION OF P16INK4a IN INFLAMMATORY, PRENEOPLASTIC AND NEOPLASTIC CERVICAL LESIONS.

INTRODUCTION: High-risk human papilloma viruses play a main role in the development of cervical dysplasias and carcinomas. p16INK4a can be considered as a surrogate marker of active high-risk human papillomaviruses infection in dysplastic and neoplastic cells of the cervix. This study was aimed at determining the presence and level of pl6INK4a expression in inflammatory, preneoplastic and neoplastic lesions of the cervix. MATERIAL AND METHODS: The study was performed on 109 samples of cervical biopsy. Cervical cancer was diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia) in stratified squamous cervix epithelium and a nonspecific inflammatory process was found in 39 patients. In all samples, immunohistochemical analysis using antibodies to pl6INK4a was performed. RESULTS: The expression of pl6INK4a was verified in all cases of cervical cancer (100%), in 67.65% of dysplastic cervical lesions and in 38.5% of inflammatory lesions. A statistically highly significant difference was found in the presence and level of expression among neoplasic, dysplastic and inflammatory lesions of the cervix (χ2 = 76.02, p <0.001). The expression was more frequent and had a higher level in neoplastic and high grade dysplastic lesions compared to expression in inflammatory lesions and low grade dysplasias. CONCLUSION: The analysis of the presence of pl6INK4a can differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of the cervix. The use of pl6INK4a in interpreting borderline lesions of the cervix can enable a rational theraDeutic treatment of patients.