Evaluation of PD-L1 Expression in Colorectal Carcinomas by Comparing Scoring Methods and Their Significance in Relation to Clinicopathologic Parameters.

BACKGROUND: This study aims to evaluate PD-L1 expression in colorectal carcinomas (CRCs) by using the tumor proportion score (TPS) and the combined positive score (CPS), and to investigate whether there is a correlation with clinicopathologic features. METHODS: A cross-sectional study was conducted that included samples from patients with colorectal adenocarcinoma treated with colon resection and rectal resection after neoadjuvant radio- and chemotherapy at the Department of Abdominal Surgery at Pozega Hospital in the period from 2017 to 2022. The study included 102 tumor tissue samples from patients after resection and the pathohistological diagnosis of adenocarcinoma. RESULTS: In our study, the PD-L1 positivity rate after the TPS was 42 (41%) samples, and after the CPS, 97 (95%) of them (p < 0.001). The positive expression of PD-L1 in tumor cells using the TPS method showed a statistically significant association with adenocarcinoma (TPS ≥ 10-50% and ≥50%). There were significantly more that were moderately differentiated, with TPS ≥ 50%, and those poorly differentiated had values ≥ 10-50%. There were significantly more patients with a status of more than one positive lymph node with TPS values ≥ 10-50%. Patients without metastases in the lymph nodes are significantly more likely to have CPS values > 50%, compared with other lymph node statuses. CONCLUSIONS: These results suggest that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive biomarker than the number of PD-L1-expressing tumor cells alone in CRC.

Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. The levobupivacaine PCA group had the best-preserved HGS after 1 year (P = 0.022). The most significant predictor of the 5-year outcome was HGS (P = 0.03). Survival at 10 years was 85%, 92%, and 77% in the diclofenac, levobupivacaine bolus, and levobupivacaine PCA groups (ns. P = 0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival (P = 0.03). A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study-trial number NCT05829707.

FACTORS AFFECTING OUTCOME IN THE TREATMENT OF GLIOBLASTOMA.

Treatment of glioblastoma is challenging due to its aggressive and highly invasive nature, and no significant advances in survival have been achieved recently. The aim of our retrospective study was identification of predictive factors and consequent survival outcome in patients who underwent surgical and oncologic treatment of glioblastoma. The study was conducted at the Department of Neurosurgery, Osijek University Hospital Centre. The authors designed a retrospective cohort study in 63 patients who underwent surgical and oncologic treatment between January 1, 2012 and December 31, 2017. Data were collected by reviewing medical records of the patients with histologically proven glioblastoma. Statistical analysis of study results revealed a significant impact of postoperative radiotherapy (p=0.002) and chemotherapy (p=0.016) on progression-free survival and overall survival (p=0.001 and p=0.009, respectively). Postoperative Karnofsky performance scale (p=0.027) was found to be significant in progression-free survival, and so was the interval between surgery and commencement of oncologic therapy (p=0.049). In conclusion, overall survival and prognosis in the treatment of glioblastoma remain poor, although prompt approach in postoperative adjuvant treatments improved progression-free survival.

IMPACT OF NEUROTROPIC VIRUSES ON SURVIVAL OF PATIENTS WITH SURGICALLY TREATED GLIOBLASTOMA.

Introduction: Glioblastoma represents the most aggressive tumor of the brain with an estimated survival rate of twelve to fifteen months after the primary diagnosis. The role of neurotropic viruses in pathogenesis of the tumor has remained unclear to date. During the last two decades, many studies were conducted with the aim of confirming viral influence in the development of glioblastoma. Methods: We conducted a retrospective study in a time period of five years using formalin-fixed paraffin-embedded tissues of glioblastoma. Immunohistochemistry was performed for three viruses: CMV, EBV and HSV-1, using an automated staining system. Results: Mean age of patients in our group was 66.7±8.5 years. A slight male dominance was noted. Negative immunohistochemistry results were obtained for CMV and EBV, which were excluded from further investigation. Based on IRS score, we confirmed six HSV-1 samples which were rated as IRS score 2. Five more samples of HSV-1 were rated as IRS score 1 and were excluded from the study. Conclusion: According to our retrospective study and its results, we found no impact of neurotropic viruses in the survival rate of glioblastoma. Further studies should be conducted including a wider range of viral detection methods.

Impact of the coronavirus disease pandemic on cancer care in Croatia: a multicentre cross-sectional study.

PURPOSE: The coronavirus disease (COVID-19) pandemic has greatly affected the oncology community worldwide. Lockdowns, an epidemiological measure, have made it difficult for oncologists to provide care. In this study, we analysed the impact of the COVID-19 pandemic on Croatian cancer care. METHODS: This was a multicentre cross-sectional observational study of 422 patients who received systemic oncology therapy during the pandemic. The patients completed a survey to capture their views on the impact of the COVID-19 pandemic on their cancer care. Univariate descriptive and bivariate analyses were performed to analyse the relationship between the patients' perspective on the impact of the COVID-19 pandemic on cancer care and the quality of Croatian cancer care and their clinical and sociodemographic data. RESULTS: Discontinuation or change in cancer treatment during the COVID-19 pandemic was observed in 10.2% of cases. Most did not change their place of treatment owing to the lockdown (97.6%). 14.7% of the patients felt that the quality of cancer care received had changed during the pandemic. CONCLUSIONS: In the first few months of the pandemic, Croatia had a favourable epidemiological situation. However, 25% of patients with cancer reported that the pandemic affected cancer treatment and the quality of cancer care.

Smoking Cessation after a Cancer Diagnosis: A Cross-Sectional Analysis in the Setting of a Developing Country.

Since smoking accounts for around 30% of all cancer deaths, public health campaigns often focus on smoking cessation as a means of primary prevention. However, smoking after cancer diagnosis is also associated with a higher symptom burden and lower survival rate. As data regarding smoking cessation vary dramatically between different populations, we aimed to analyze smoking prevalence in cancer patients, smoking cessation after cancer diagnosis, and the factors associated with smoking cessation in the setting of a developing country. We performed a cross-sectional survey on 695 patients in two clinical hospital centers. After cancer diagnosis, 15.6% of cancer patients stopped smoking. Male gender, younger age, and smoking-related cancer were the main factors associated with greater smoking cessation (p < 0.05). A total of 96% of breast cancer patients continued to smoke after cancer diagnosis and, compared to lung and colorectal cancer patients, exhibited a lower reduction in the number of cigarettes smoked (p = 0.023). An alarming rate of smoking prevalence was recorded in younger patients (45.6% at the time of cancer diagnosis) suggesting a future rise in smoking-related cancers and complications. These results should guide anti-smoking public health campaigns in transitional countries with a critical focus on younger and breast cancer patients.

Calcium-axonemal microtubuli interactions underlie mechanism(s) of primary cilia morphological changes.

We have used cell culture of astrocytes aligned within microchannels to investigate calcium effects on primary cilia morphology. In the absence of calcium and in the presence of flow of media (10 µL.s-1) the majority (90%) of primary cilia showed reversible bending with an average curvature of 2.1 ± 0.9 × 10-4 nm-1. When 1.0 mM calcium was present, 90% of cilia underwent bending. Forty percent of these cilia demonstrated strong irreversible bending, resulting in a final average curvature of 3.9 ± 1 × 10-4 nm-1, while 50% of cilia underwent bending similar to that observed during calcium-free flow. The average length of cilia was shifted toward shorter values (3.67 ± 0.34 µm) when exposed to excess calcium (1.0 mM), compared to media devoid of calcium (3.96 ± 0.26 µm). The number of primary cilia that became curved after calcium application was reduced when the cell culture was pre-incubated with 15 µM of the microtubule stabilizer, taxol, for 60 min prior to calcium application. Calcium caused single microtubules to curve at a concentration ≈1.0 mM in vitro, but at higher concentration (≈1.5 mM) multiple microtubule curving occurred. Additionally, calcium causes microtubule-associated protein-2 conformational changes and its dislocation from the microtubule wall at the location of microtubule curvature. A very small amount of calcium, that is 1.45 × 1011 times lower than the maximal capacity of TRPPs calcium channels, may cause gross morphological changes (curving) of primary cilia, while global cytosol calcium levels are expected to remain unchanged. These findings reflect the non-linear manner in which primary cilia may respond to calcium signaling, which in turn may influence the course of development of ciliopathies and cancer.

PROGNOSTIC IMPACT OF LOW ESTROGEN AND PROGESTERONE POSITIVITY IN LUMINAL B (HER2 NEGATIVE) BREAST CANCER.

- Luminal B (HER2 negative) subtype is the most diversiform type of breast cancers, with a high Ki-67 proliferation index (>20%) or/and low progesterone (PR; <20%) with various intensity and distribution of hormone receptors. Considerable difference has also been noticed in disease outcome, wherefore there is the need for a more detailed classification of this tumor subtype. The clinical and pathologic parameters of 147 luminal B (HER2 negative) breast cancers were examined. The expression of hormone receptors in correlation with other prognostic factors and disease outcome was analyzed by Kaplan-Meier curves and multivariate Cox regression analysis. The Kaplan-Mayer analysis showed that low positivity of estrogen (ER) and PR receptors in tumors was associated with a significantly worse disease outcome (overall survival (ER), p=0.020; disease free survival (ER), p=0.019; overall survival (PR), p=0.026; disease free survival (PR), p=0.038)), unlike Ki-67, which did not show a statistically significant connection (overall survival, p=0.343; disease free survival, p=0.322). The intensity of receptor staining and Ki-67 relative to other histopathologic prognostic factors showed a statistically significant correlation solely with histologic grade of tumor. By using the Cox regression model, PR proved to be an independent prognostic factor for overall survival (p=0.004) and disease free survival (p=0.029). The luminal B (HER2 negative) breast cancer with low expression of hormone receptors, independent of the Ki-67 proliferation index, and in correlation with a higher histologic grade, could be a unique subtype of cancer.

Computer-aided evaluation of radiologist's reproducibility and subjectivity in mammographic density assessment.

Mammographic density is an independent risk of breast cancer. This study has evaluated the radiologists' reproducibility and subjectivity in breast density estimation and in order to decrease the radiologists' subjective errors the computer software was developed. The very good reproducibility existed in the strong correlation with the first and the second mammogram assessment after three month period for each radiologist (correlation coefficient 0.73-1, p < 0.001). The strong correlation was present in the case of all 5 radiologists when compared among themselves and compared with software aided MDEST-Mammographic Density Estimation (correlation coefficient 0.651-0.777, p < 0.001). Detected differences in glandular tissue percentage determination occurred in the case of two experienced radiologists, out of 5 (one radiologist with more than 5 year experience and one with more than 10 year experience, p < 0.01), but in the case of breast type determination (American College of Radiology-ACR I-IV), the detected difference occurred in one radiologist with the least experience (less than 5 years, p < 0.001). It can be concluded that the estimation of glandular tissue percentage in breast density is rather subjective method, especially if it is expressed with absolute percentage, but the determination of type of breast (ARCI-IV) depends on the radiologist's experience. This study showed that software aided determination of glandular tissue percentage and breast type can be of a great benefit in the case of less experienced radiologists.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with colorectal cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od kolorektalnog raka.

Colorectal cancer is the third most common malignant tumour in males and the fourth most common malignancy in women in the Republic of Croatia. It is usually manifested as stool forming disorders, feeling that bowel does not empty completely, finding blood in the stool, weight loss and fatigue. In-time diagnosis, confirmed by pathohistological findings, is cornerstone of successful treatment. The decision about treatment is made based on clinical assessment of disease stage and other risk factors, after completion of the diagnostic process. Depending on that, treatment options include surgery, the application of systemic therapy (chemotherapy, immunotherapy) and radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with colorectal cancer in the Republic of Croatia.

"Signet-ring" cell invasive lobular carcinoma of the breast - accidental finding associated with intraductal papilloma: a case report.

BACKGROUND: A 57-year old woman had only unilateral milky dischardge of the right breast. Clinical and mammography findings were normal. CASE PRESENTATION: Cytological diagnosis of intraductal papilloma was established which was galactographically confitmed and patient underwent to surgery. Ductulolobular segmentectomy was made. Histopathologically beside intraductal papilloma numerous single dispread malignant "signet ring" cells in the fibrous retromammilary stroma were found. Imunohistochemically findings were: cytokeratin 8 positive, ER H-score 80, PR H-score 50, HER-2/neu negative. Diagnosis of "signet ring" cell lobular invasive carcinoma was made, followed by mastectomy, axillary limphadectomy and contra lateral breast biopsy. CONCLUSION: Residual tumor were found only in the breast tissue, while axillary lymph nodes and contra lateral breast biopsy were negative. Patient underwent to oncology therapy.

[Side effects of radiotherapy in oral cavity: diagnosis, prevention and treatment guidelines]. / Nuspojave radioterapije u usnoj supljini: dijagnostika, prevencija i terapijske smjernice.

To avoid, or at least to reduce complications in patients who require head and neck radiotherapy, adequate oral cavity treatment is necessary before the therapy. Recent management guidelines speak of possibilities of preventing osteoradionecrosis with hyperbaric oxygen, using long-wave ultrasound in stimulating osteoblasts growth, and surgical transfer of submandibular salivary glands to submental area with 99% effectiveness in preventing xerostomia, besides traditional therapy. Preventive measures are naturally the best choice, since late complications treatment is not needed as often, and should draw special attention of physicians and patients. Since wide a spectrum of preventive and curative measures is required, the need exists for standard teams to look after the patients during and after radiotherapy, and which should include, besides radiotherapist, oral or maxillofacial surgeon in cooperation with oral medicine specialist.

Total skin electron treatment of extensive cutaneous lesions in Kaposi sarcoma.

We report on a 62-year-old HIV-negative male patient with Kaposi sarcoma. After 8 years of treatment of smaller localized skin lesions with surgery and local radiotherapy, the patient developed extensive lesions of the whole skin. The extent of the lesions required the administration of the total skin electron therapy (TSET). Until then, TSET had been used at our Department only for the treatment of mycosis fungoides. The dose delivered was 30 Gy higher than in a conventional radiotherapy treatment, where doses are usually between 8 and 24 Gy. Six months after the TSET therapy, the lesions completely regressed, except for two large facial lesions, which were surgically removed. Major side effects were mild erythema and hyperpigmentation of the skin. Erythema disappeared a month after the therapy.