Abstract
Immunohistochemical level of IMP3-protein in patients with rectal cancer in clinical stage II (141), were correlated with sociodemographic, pathohistological and clinical indicators and ...duration of overall-survival and progression-free-survival. Vascular invasion was associated with IMP3-positive immunostaining (p < 0.001). Vascular invasion ratio in the group of poorly-differentiated-tumors was 21 times higher than in the group of well-differentiated-tumors. IMP3-positive patients lived 2.2 times shorter than negative (p < 0.001). Patients with well-differentiated-tumors lived 1.7 times longer than the subjects with poorly-differentiated-tumors (p < 0.001). Patients without vascular invasion lived 2.7 times longer than the subjects with vascular invasion (p < 0.001). The risk of mortality was 2.3 times higher for IMP3 positive patients (p = 0.027) and 10.4 higher for the patients with vascular invasion (p < 0.001). IMP3-negative participants had 2.3 times longer free interval without disease (p < 0.001). The free interval without disease was 3.6 times longer in the group without vascular invasion (p < 0.001). The risk of disease relapse in the IMP3 positive group was 5.3 times higher (p < 0.001) and with vascular invasion was 8 times longer (p < 0.001). The risk of disease relapse was 6.8 times higher in the group with vascular invasion (p < 0.001). Patients with rectal cancer and high IMP3-protein level will have a shorter overall survival relative to patients without or with low levels of IMP3. The analysis of IMP3 expression by immunohistochemistry pointed IMP3 as an independent prognostic factor of clinical stage II rectal cancer.
Triple negative breast cancer (TNBC) consists of a group of tumors with poor prognosis, owing to aggressive tumor biology and lack of targeted therapy. The aim of this study was to assess the ...immunostaining for androgen receptors (ARs) in the group of TNBC, in addition to basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors and to demonstrate its prognostic relevance in this group of tumors. The study included 83 patients. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER2, CK5/6, CK14, EGFR, Ki-67 and AR. Of the 83 TNBC samples, 32.5% showed positive immunostaining for AR, 66.3% had BL immunophenotype, and 48.2% had BL morphology. Positive AR immunostaining was inversely correlated with higher clinical stage, higher mitotic score, higher histological grade and higher proliferation index measured by Ki-67. Significantly more AR negative tumors were observed among the tumors with BL immunophenotype and BL morphology. There was no significant association between positive AR immunostaining and disease free survival or overall survival. More than one third of TNBC were AR-positive, and this represents a potential opportunity for novel targeted treatment in the group of breast tumors for which therapeutic options are currently limited.
"Basal-like" (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the ...morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy.
Background New hemostatic technologies are often employed in open and laparoscopic surgery to reduce duration of surgery and complications. Monopolar diathermy, Harmonic scalpel and LigaSure are ...routinely used in open and laparoscopic surgery for tissue cutting and hemostasis. We compared lateral thermal damage following in vivo application of 3 commonly used instruments. Methods We used monopolar diathermy, Harmonic scalpel and LigaSure to coagulate and divide the peritoneum of patients who underwent median laparotomy. After anesthesia, median supraumbilical laparotomy was performed, and the peritoneum of each patient was coagulated using different devices. Using light microscopy and morphometric imaging analysis, the width of tissue lateral thermal damage was measured from the point of the peritoneal incision. Results We included 100 patients in our study. After a peritoneal incision, the mean lateral thermal damage of monopolar diathermy, Harmonic scalpel (output power 3), Harmonic scalpel (output power 5) and LigaSure were 215.79 μm, 90.42 μm, 127.48 μm and 144.18 μm, respectively. Conclusion The degree of lateral thermal spread varied by instrument type, power setting and application time. LigaSure and Harmonic scalpel were the safest and most efficient methods of tissue coagulation. Monopolar diathermy resulted in the greatest degree of thermal damage in tissues.
Due to recent changes in breast cancer treatment strategy, significantly more patients are treated with neoadjuvant systemic therapy (NST). Radiological methods do not precisely determine axillary ...lymph node status, with up to 30% of patients being misdiagnosed. Hence, supplementary methods for lymph node status assessment are needed. This study aimed to apply and evaluate machine learning models on clinicopathological data, with a focus on patients meeting NST criteria, for lymph node metastasis prediction.
From the total breast cancer patient data (
= 8381), 719 patients were identified as eligible for NST. Machine learning models were applied for the NST-criteria group and the total study population. Model explainability was obtained by calculating Shapley values.
In the NST-criteria group, random forest achieved the highest performance (AUC: 0.793 0.713, 0.865), while in the total study population, XGBoost performed the best (AUC: 0.762 0.726, 0.795). Shapley values identified tumor size, Ki-67, and patient age as the most important predictors.
Tree-based models achieve a good performance in assessing lymph node status. Such models can lead to more accurate disease stage prediction and consecutively better treatment selection, especially for NST patients where radiological and clinical findings are often the only way of lymph node assessment.
Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of ...markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.
Background
Our objective was to assess the effects of COVID‐19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers ...in the Republic of Croatia.
Subjects, Materials, and Methods
We performed a retrospective, population‐ and registry‐based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases.
Results
The average monthly percent change after the initial lockdown measures were introduced was −11.0% (95% confidence interval − 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017–2019.
Conclusion
It seems that national health care system measures for controlling the spread of COVID‐19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID‐19 control measures were relaxed, and it has not reoccurred during the second COVID‐19 wave. Although the COVID‐19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020.
Implications for Practice
It is possible to compensate for the adverse effects of COVID‐19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non‐negligible extent.
This article assesses the effects of COVID‐19 on the number of newly diagnosed breast cancer patients in the Republic of Croatia.
Non-small cell lung cancer (NSCLC) has become the best example of precision oncology's impact on outcomes in everyday clinical practice, significantly changing the expectations of all stakeholders, ...including medical professionals, society, and most importantly, patients. Consequently, the implementation of the precision oncology concept in medical systems, in order to achieve optimal and proven curative effects in NSCLC, is imperative. In this study, we investigated the development, challenges, and results associated with the implementation of precision oncology in NSCLC on a national level in Croatia. We conducted a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients with metastatic lung cancer, on whose tumors specimen comprehensive genomic profiling (CGP) testing was performed during 2020 and 2021. A total of 48 patients were included in the study. CGP revealed clinically relevant genomic alterations (CRGA) in 37 patients (79%), with a median of 2 (IQR 1-3) CRGA per patient. From the panel of recommended tests,
,
, and
were the most common alterations, detected in 16 (34%), 5 (11%), and 3 (6%) patients, respectively. CGP revealed additional targetable mutations in 29 (60%) patients who would not have been tested (and consequently, whose mutations would not have been detected) according to the existing everyday standard of practice in Croatia. The tumor mutational burden was reported as high (≥10 Muts/Mb) in 19 patients (40%). CGP analysis reported some kind of targeted therapy for 34 patients (72%). CGP revealed other potentially targetable mutations, and it also determined TMB to be high in a significant number of patients. In conclusion, when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.
Purpose: The purpose of this retrospective study is to identify potential predictors of academic success or failure in Doctor of Philosophy (PhD) programmes in the field of biomedicine. Based on ...these, the policies and structure of academic programmes granting PhD degrees in biomedicine might be improved. Literature review (State of the art): At the present moment, most European and all of the EU doctoral education systems in biomedicine are regulated by the Salzburg principles of the Bologna process. Almost all the programmes formally comply with regulations, but the degree to which rules are applied varies greatly. The European Research Council (ERC) and various stakeholders’ associations, such as the Organisation for PhD Education in Biomedicine and Health Sciences in the European System (ORPHEUS), have recognised this and in their policies, they recommend regular evaluation of PhD programme structures. One such evaluation that was conducted at our institution motivated us to search for quantifiable factors that can help the process of PhD programme structural reform. Since the literature is scarce on this matter, we decided to conduct analysis of our own data and thus study the relationships between recommended EU policies and real-world data. Methods: Biology of Neoplasms is a PhD programme founded under Bologna process rules. It enrols students with Doctor of Medicine (MD), Doctor of Dental Medicine (DMD) or similar degrees in the biomedical field. A large portion of enrolled PhD students work full time in medical practices. A retrospective analysis was conducted on students who enrolled between 2006 and 2017. In order to quantify academic success, outcome measures of graduation (completion) rate, time to graduation, average impact factor of published papers comprising a PhD thesis and the ratio of the latter two were formed. Age, sex, employment institution, mentor experience and tuition subsidy were considered as potential predictors. Results: A total of 124 students were enrolled in the study—38% male. Out of the total, 21 (16.94%) students discontinued the study programme and 22 students graduated (17.7%). The average impact factor (IF) of published papers was 2.66 ± 1.51. Mentor experience (Odds ratio (OR) = 6.7) and student employment in academia (OR = 11.7) were significant predictors of successful graduation. Stricter criteria for graduation had no effect on graduation in newly enrolled students. Likewise, sex, tuition subsidy and age did not affect graduation rates. Surprisingly, time to graduation was not affected by any of the considered predictors. On the other hand, students that were mentored by experienced mentors and employed in academia outperformed their peers in terms of impact factors of publications related to their thesis. Conclusion: Characteristics such as gender, age at enrolment and even tuition paid by the institution do not have a significant impact on completion rate. Experienced mentors and employment in academic institutions seem to be the factors that predict a successful completion of a PhD programme. Furthermore, our results give a quantifiable support to the ORPHEUS and ERC recommendations and policies. These conclusions can be easily applied to any PhD programme formed under the tenets of the Bologna process.
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