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.

A rare presentation of leiomyosarcoma metastasis to the cervical spine: A case report and a brief review.

Background: Leiomyosarcoma (LMS) is a rare malignancy that originates from smooth muscle. The most common sites of metastases include the lungs, liver, kidney, and skin. Notably, metastases of LMS to the central nervous system/or spine are extremely rare. When a cervical spinal LMS lesion was encountered, the patient successfully underwent gross total tumor resection with negative margins. Case Description: A 63-year-old female had undergone an anterior cervical C5-C7 diskectomy and fusion 18 years ago and resection of a retroperitoneal LMS 3 years ago. She newly presented with right-sided numbness and pain of 2 months duration that correlated with a focal right-sided C5-level hemiparesis (i.e., 4/5 motor strength). When the cervical magnetic resonance demonstrated a right-sided C5 intralaminar mass with extension into the C5-C6 foramen, she underwent posterior tumor resection; pathologically, this proved to be an LMS metastasis. Respectively, 1- and six months postoperatively, follow-up magnetic resonance imaging scans showed no tumor recurrence; she tolerated adjuvant oncological treatment accompanied by physical therapy. However, in one postoperative year, the lesion recurred, and she is presently under consideration for additional surgical management. Conclusion: Gross total surgical resection is the first line of treatment for patients with metastatic LMS. Here, a patient with a C5 laminar/C5-C6 foraminal bony LMS metastasis underwent posterior tumor resection accompanied by adjuvant oncological treatment but exhibited disease recurrence within one postoperative year.

Placental Findings in Infants Gestational Age < 34 Weeks and Impact on Short-Term Outcomes.

AIM: To analyse placental changes in infants' gestational age < 34 weeks and its correlation to short-term respiratory outcomes or death until hospital discharge. MATERIAL AND METHODS: Information regarding all in-house born preterm infants born before 34 weeks gestation and born from January 2009 until December 2014 were collected and included among others, placental pathology and relevant data on demographics and outcomes of infants. RESULTS: Placental abnormalities was found in 157/253 (65.05%) cases. Acute placental inflammation was found to be the most common in both groups of premature neonates, followed by maternal vascular underperfusion. Maternal vascular underperfusion was significantly more common in GA ≤ 27 weeks compared to infants GA 28-33 weeks (35.2% vs. 13.7%; p = 0.018). Similarly, chronic placental inflammation was more common in infants GA ≤ 27 weeks compared to infants GA 28-33 weeks (14.3% vs. 3.3%; p = 0.014). Infants with placental pathology had a lower median birth weight (1460g vs. 1754g; p = 0.001, and were of shorter median GA at birth (31 vs. 32; p = 0.001). Infants with any placental disease had higher rates of death until hospital discharge (10.2% vs. 3.1%; p = 0.039) and higher rates of any stage of bronchopulmonary dysplasia (41.4% vs. 26.0%; p = 0.013). There were no significant differences in mechanical ventilation rates, duration of mechanical ventilation and duration of supplemental oxygen therapy. CONCLUSION: Identifiable placental abnormalities were found in most infants born < 34 weeks gestation. Placental pathology is associated with increased rates of bronchopulmonary dysplasia and death until hospital discharge.

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.

Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer.

CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR. Our study showed a significant association between CDX2 expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed that CDX2 expression loss can be used as a predictive factor for dMMR, which should be confirmed by further studies.

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.

Right Heart Morphology and Its Association With Excessive and Deficient Cardiac Visceral Adipose Tissue.

Visceral adipose tissue is an independent risk factor for the development of atherosclerotic coronary disease, arterial hypertension, diabetes and metabolic syndrome. Right heart morphology often involves the presence of adipose tissue, which can be quantified by non-invasive imaging methods. The last decade brought a wealth of new insights into the function and morphology of adipose tissue, with great emphasis on its role in the pathogenesis of heart disease. Cardiac adipose tissue is involved in thermogenesis, mechanical protection of the heart and energy storage. However, it can also be an endocrine organ that synthesises numerous pro-inflammatory and anti-inflammatory cytokines, the effect of which is accomplished by paracrine and vasocrine mechanisms. Visceral adipose tissue has several compartments that differ in their embryological origin and vascularisation. Deficiency of cardiac adipose tissue, often due to chronic pathological conditions such as oncological diseases or chronic infectious diseases, predicts increased mortality and morbidity. To date, knowledge about the influence of visceral adipose tissue on cardiac morphology is limited, especially the effect on the morphology of the right heart in a state of excess or deficient visceral adipose tissue.

Impact of Meteorological Factors on Suicide Attempts and Completed Suicides in Croatia, Osijek-Baranja County.

BACKGROUND: Significant changes in the values of temperature, pressure, humidity and cloud cover can participate in the human behaviour including the mood disorders (especially depression and bipolar disorders) which can trigger suicidal ideas or their realization. The aim of this study is to estimate the connection between the aforesaid weather changes and a committed suicide along with the suicide attempts. SUBJECTS AND METHODS: We conducted a retrospective study in Osijek-Baranja County in the period from 2000 to 2011. Meteorological, demographic and epidemiological analysis was performed on 569 suicides and 478 suicide attempts (total of 1047 events). We analyzed the values of the above-mentioned meteorological parameters at the exact time when the event had happened, as well as three days before the event and one day after the event, comparing it with the monthly mean values. RESULTS: The results showed that the changes of temperature and pressure were significantly related with the suicides i.e. suicide attempts in general, while by separating genders, a connection with all examined meteorological factors was found by woman whereas men expressed significance only in the matter of temperature changes. CONCLUSIONS: Despite the fact that suicidality is caused by numerous factors, this study confirms that a sudden change of weather in the days preceding the suicide can be a trigger to suicidal behaviour. The study also suggests that in the matter of suicidal behaviour, female population is more susceptible to sudden weather changes.

Presence of Intramyocardial Fat Tissue in the Right Atrium and Right Ventricle - Postmortem Human Analysis.

Histologic and radiologic studies describe intramyocardial fat tissue as a normal finding or as part of cardiac pathology. The role of fat cells within the myocardium is not fully understood. The aim of this study was to assess fat tissue distribution in the myocardium of right atrium (RA) and right ventricle (RV) and age differences in subjects free from cardiac disease. The study included 10 males without cardiac disease divided into two groups according to age (below/above 50 years). Three cross sections were performed (RV free wall and apex and RA free wall) with histomorphological analysis on digital photographs. The shares of total myocardial fat (TMF), peri-vascular fat (PVF) and non-perivascular (nPVF) fat were calculated. Samples from the older group had larger amounts of fat in the epicardium and myocardium, without statistically significant differ-ence (TMF p=0.847, PVF p=0.4 and nPVF p=0.4). The largest quantities of fat tissue were found in the RV apex samples (14.9%), followed by RV free wall (7.5%) and RA (4.5%), where total apical RV fat share was significantly larger than in RA sample (p=0.044). Intramyocardial fat cells were present within the non-diseased RA and RV in all samples, mostly in the apex. Further investigations on age difference, effect of visceral obesity and sex differences are needed.

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.

High Tumor Stroma Proportion is a Worse Prognostic Factor in Colorectal Cancer

High stroma proportion appears to be a very important prognostic factor in esophageal and breast cancer. Previous researches have shown that it might have a similar effect on colorectal cancer. The aim of this study was to determine whether tumor stroma proportion influenced patient survival. This retrospective study included 236 patients with colorectal cancer having undergone surgery in 2006 and 2007 at Osijek University Hospital Center. Location with the highest stroma proportion at the site of deepest tumor invasion was determined. Patients were divided into the groups with high stroma proportion (>50%) and low stroma proportion (≤50%). Stroma proportion showed a statistically significant correlation with tumor stage. Kaplan-Meier survival curves yielded a statistically significant difference in patient overall survival (Cox ph model p=0.016) and progression-free survival (Cox ph model, p=0.0188) according to stroma proportion. Study results showed a statistically significantly shorter overall survival and progression-free survival in patients with high stroma proportion.

Prognostic role of Nectin-4 expression in luminal B (HER2 negative) breast cancer.

Nectins are Ca2+-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions and regulate several cellular activities including the entry of some viruses. Nectin-4 has recently been shown as a metastasis-associated protein in several cancers. In the following study, we have evaluated the expression of Nectin-4 inthe luminal B HER2 negative subtype breast cancer. The study group consisted of 147 patients presenting with primary unilateral breast carcinoma with no evidence of distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry and the results were correlated with the clinical data using Kaplan-Meier curves, univariate and multivariate stepwise proportional-hazard analysis (Cox model). Nectin-4 overexpression was significantly correlated with the tumour size (p<0.05; Fisher's Exact Test), also Nectin-4 expression was negatively associated with overall survival, disease free survival and distant relapse free survival with the same significance (p<0,001; Kaplan-Meier, Cox model). We did not find statistically significant correlation between Nectin-4 and age, ER, PR, age, lymph node metastasis, tumour differentiation, histologicalsubtype and Ki-67proliferation index. We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer.

Giant primary pleomorphic adenoma of the lung presenting as a post-traumatic pulmonary hematoma: a case report.

BACKGROUND: Pleomorphic adenomas, also known as benign mixed tumors, are the most common tumors of glandular origin in the head and neck and although they are generally benign they can undergo malignant transformation. Primary pleomorphic adenomas of the lung are extremely rare tumors with less than 40 cases reported in the literature by now. This is the first case in the literature describing overlapping with a traumatic event and also one of the rare cases describing primary adenoma of the lung reaching this impressive size. CASE PRESENTATION: We report a rare case of a giant primary pleomorphic adenoma of the lung presenting as a post-traumatic pulmonary hematoma. A 38-year-old Caucasian male patient came to the Urgent Trauma Center after being hit in the chest by a bull and, after a number of tests, was diagnosed with primary pleomorphic adenoma of the lung. Operative treatment was performed and the surgical excision was successfully done. CONCLUSIONS: Our conclusion is that the surgical excision is the main treatment for pleomorphic adenoma of the lungs and we recommend lifelong follow-up and regular check-ups. Furthermore, we consider our case an interesting one due to its concurrence with the chest trauma and the dilemma about the optimal approach considering the entity could have been a large interlobular hematoma.

Kikuchi-Fujimoto disease: the first reported case in Croatia.

Kikuchi-Fujimoto disease (KFD) is an extremely rare disease known to have a worldwide distribution with higher prevalence among Japanese and other Asiatic individuals. KFD presents as benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild to high fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting and sore throat. Final diagnosis can only be determined on the basis of typical morphological changes in the lymph node, therefore lymph node biopsy is crucial for proving the diagnosis. Here we present a 16-year-old, native Croatian, Caucasian girl with KFD, as a first case of KFD reported in Croatia. We suggest that this disease should be considered as a possible cause of fever of the unknown origin followed by lymphadenopathy.

Angiosarcoma of the hypopharynx: case report.

Angiosarcomas are malignant neoplasias of rapid growth that emerge from endothelial cells. They are rarely found in the area of the head and neck and account less than 0.1% of all head and neck malignancies. In some cases it has been linked to trauma, radiation and angiectasia but the etiology mainly remains unknown. Here we report a case of angiosarcoma of pyriform sinus manifested by dysphagia and dysphonia. The patient underwent endoscopic hypopharyngeal excision followed by radiation therapy with a good result. Our patient remains tumor free after two years. The purpose of this article is to add another case of primary angiosarcoma of a rare site, the hypopharynx.