Profound Nanoscale Structural and Biomechanical Changes in DNA Helix upon Treatment with Anthracycline Drugs.

In our study, we describe the outcomes of the intercalation of different anthracycline antibiotics in double-stranded DNA at the nanoscale and single molecule level. Atomic force microscopy analysis revealed that intercalation results in significant elongation and thinning of dsDNA molecules. Additionally, using optical tweezers, we have shown that intercalation decreases the stiffness of DNA molecules, that results in greater susceptibility of dsDNA to break. Using DNA molecules with different GC/AT ratios, we checked whether anthracycline antibiotics show preference for GC-rich or AT-rich DNA fragments. We found that elongation, decrease in height and decrease in stiffness of dsDNA molecules was highest in GC-rich dsDNA, suggesting the preference of anthracycline antibiotics for GC pairs and GC-rich regions of DNA. This is important because such regions of genomes are enriched in DNA regulatory elements. By using three different anthracycline antibiotics, namely doxorubicin (DOX), epirubicin (EPI) and daunorubicin (DAU), we could compare their detrimental effects on DNA. Despite their analogical structure, anthracyclines differ in their effects on DNA molecules and GC-rich region preference. DOX had the strongest overall effect on the DNA topology, causing the largest elongation and decrease in height. On the other hand, EPI has the lowest preference for GC-rich dsDNA. Moreover, we demonstrated that the nanoscale perturbations in dsDNA topology are reflected by changes in the microscale properties of the cell, as even short exposition to doxorubicin resulted in an increase in nuclei stiffness, which can be due to aberration of the chromatin organization, upon intercalation of doxorubicin molecules.

Oncologists and Breaking Bad News-From the Informed Patients' Point of View. The Evaluation of the SPIKES Protocol Implementation.

The way that bad news is disclosed to a cancer patient has a crucial impact on physician-patient cooperation and trust. Consensus-based guidelines provide widely accepted tools for disclosing unfavorable information. In oncology, the most popular one is called the SPIKES protocol. A 17-question survey was administered to a group of 226 patients with cancer (mean age 59.6 years) in order to determine a level of SPIKES implementation during first cancer disclosure. In our assessment, the patients felt that the highest compliance with the SPIKES protocol was with Setting up (70.6%), Knowledge (72.8%), and Emotions (75.3%). The lowest was with the Perception (27.7%), Invitation (30.4%), and Strategy & Summary (56.9%) parts. There could be improvement with each aspect of the protocol, but especially in Perception, Invitation, and Strategy & Summary. The latter is really important and must be done better. Older patients felt the doctors' language was more comprehensible (r = 0.17; p = 0.011). Patients' satisfaction of their knowledge about the disease and follow-up, regarded as an endpoint, was insufficient. Privacy was important in improving results (p < 0.01). In practice, the SPIKES protocol is implemented in a satisfactory standard, but it can be improved in each area, especially in Perception, Invitation, and Summary. It is suggested that more training should be done in undergraduate and graduate medical education and the effectiveness of the disclosure continue to be evaluated and improved.

Reflections: Improving Medical Students' Presentation Skills.

Both good communication and presentation skills on the part of an academic teacher are crucial when trying to generate students' interest in the subject of a lecture. More generally, our task is to share knowledge in the most effective way possible. It is also worth teaching students presentation skills, as today's students are tomorrow's teachers. An engaging presentation is a powerful tool. There are some rules for presenting which I consider worthy of being discussed and taught at a medical university.

A Fulbright Specialist in Poland.

One of the greatest rewards in cancer education is working with colleagues from around the world. This manuscript reports on the development and conduct of a cancer research training program in Wroclaw, Poland, supported by the Fulbright Commission. The precipitating need for this program was the desire and lack of opportunity for medical trainees to develop skills necessary to conduct cancer education research. A 2-week program was developed consisting of didactic, Socratic, and individual/group consultations. Support from the Fulbright Commission was essential to the success of this program. Information will be presented in this paper on the completion of the funding application as well as lessons learned in the development and implementation of this program.

Stress In An Oncologist's Life: Present But Not Insurmountable : (Students Should Not Be Discouraged Choosing Oncology as Their Future Specialisation).

Burnout is a serious problem facing the majority of oncologists. Many medical students may regard oncology as depressive part of medicine. This false picture may discourage them from choosing oncology as their future specialization. To learn problems experienced by oncologists and to answer the students' question: is it dangerous to choose oncology? We conducted an anonymous survey among 69 oncologists. Young doctors (up to 5 years of service) accounted for 31 %, specialists 69 %, with a median length of practice of 14 years. The most frequently reported symptoms included irritability (84 %) and tension (74 %). Forty-five percent reported headaches, 25 % sleep disorders, 51 % negative impact on their personal lives. Excessive bureaucratization, overwork, and haste, with the disparity between undertaken effort and compensation were the most common sources of stress. Stress reduction methods were as follows: their relationship with family and/or friends (69 %), reading books/watching movies (66 %), emotional distance from their problems (63 %), and contact with nature (62 %). Ninety-six percent of physicians were satisfied with their choice of pursuing work with cancer patients. However, as many as 49 % of oncologists experienced moments of doubt regarding their sense of vocation. Students and young doctors considering pursuing an oncological speciality should not be discouraged by the likely degree of sacrifice or burden, but rather aim to develop effective ways to reduce stress, along with remembering one's own health needs. This could be valuable part of both pregradual and postgradual medical education, worth to become part of medical curricula.

Reflections: Surgical Education-the Times they are a-Changin': Lessons Learned from the 3rd MAYMET-ESO Joint Meeting.

Technical skills are not sufficient for successful surgical care. Non-technical skills such as team work, decision-making in cancer treatment, communication with the patient, ethical challenges, situation awareness, and communication in the operating room are mandatory for favorable outcomes. Although formally taught in other high-demand disciplines, such skills were traditionally rarely discussed in surgical oncology. The 3rd MAYMET-ESO Joint Meeting "Professionalism for Breast Surgeons" held in Istanbul, Turkey, 5 October 2013 was dedicated to the development of non-technical skills in the everyday activity of breast surgeons. We briefly discuss information from this very interesting and inspiring educational event and how it relates to more recent changes in surgical oncology education.

Petrophysical examination of CO2-brine-rock interactions-results of the first stage of long-term experiments in the potential Zaosie Anticline reservoir (central Poland) for CO2 storage.

The objective of the study was determination of experiment-induced alterations and changes in the properties of reservoir rocks and sealing rocks sampled from potential reservoir for CO2. In the experiment, rocks submerged in brine in specially constructed reactors were subjected to CO2 pressure of 6 MPa for 20 months at room temperature. Samples of Lower Jurassic reservoir rocks and sealing rocks (sandstones, claystones, and mudstones) from the Zaosie Anticline (central Poland) were analysed for their petrophysical properties (specific surface area, porosity, pore size and distribution) before and after the experiment. Comparison of the ionic composition the brines before and after the experiment demonstrated an increase in total dissolved solids as well as the concentration of sulphates and calcium ions. This indicates partial dissolution of the rock matrix and the cements. As a result of the reaction, the properties of reservoir rocks did not changed significantly and should not affect the process of CO2 storage. In the case of the sealing rocks, however, the porosity, the framework density, as well as the average capillary and threshold diameter increased. Also, the pore distribution in the pore space changed in favour of larger pores. The reasons for these changes could not be explained by petrographic characteristics and should be thoroughly investigated.

Robotic versus Laparoscopic Liver Resections for Colorectal Metastases: A Systematic Review and Meta-Analysis.

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small.

Preoperative treatment does not improve the therapeutic results of abdominosacral amputation of the rectum.

BACKGROUND: This study reviewed the impact of preoperative chemoradiotherapy/short-term radiotherapy on abdominosacral amputations of the rectum (ASAR) for the treatment of low-rectum cancers in terms of postoperative morbidity, local recurrence rates, and survival. METHODS: A total of 198 patients with stage II and III tumors located within 6 cm of the anorectal junction underwent ASAR between 1998 and 2008 and were selected for further analysis. Patients were compared according to the following groups: those who had surgery only (Group A) and those who had preoperative chemoradiotherapy/short-term radiotherapy (Group B). RESULTS: There were 44 and 154 patients in Groups A and B, respectively, including 135 males. The median age of the subjects was 63 years (range = 35-88). The median follow-up period was 81 months (range = 23-138). Neither the local recurrence rates (6.8% in Group A vs. 4.6% in Group B, p = 0.544) nor the 5-year relative survival rates (72.4% in Group A vs. 69.3% in Group B, p = 0.127) differed significantly between the groups. CONCLUSION: Preoperative therapy in low-rectum cancer does not improve the therapeutic results of ASAR.

Safety and Efficacy of Indocyanine Green in Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis of 11,047 Patients.

Despite the technological advances and improved surgical skills, the incidence of anastomotic leakage following colorectal cancer surgery still ranges from 4% to 19%. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of indocyanine green (ICG) use in colorectal cancer surgery. An online search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (from inception to 10 November 2021) was performed, in addition to manual screening. Thirty-two studies involving 11,047 patients were considered eligible for the meta-analysis. The anastomotic leak rate in the ICG and non-ICG groups varied and amounted to 3.7% vs. 7.6%, respectively (RR = 0.46; 95% CI: 0.39-0.56; p < 0.001). The rate in randomized controlled trials (RCTs) was 8.1% in the ICG group compared with 12.1% in the non-ICG group (RR = 0.67; 95% CI: 0.46-0.98; p = 0.04). In non-RCTs, it equaled 3.1% vs. 7.3%, respectively (RR = 0.43; 95% CI: 0.35-0.52; p < 0.001). Although the publications encompassed in our meta-analysis present different patients, with different factors influencing the results, a pooled analysis revealed a lower incidence of anastomotic leak in cases with ICG use. There are several other convincing advantages: safety, simplicity, and short time of the method adjustment. The presented meta-analysis indicates ICG perfusion assessment as a tool worth considering to decrease the rate of complications following colorectal surgery-valuable in the context of other, well-known risk factors.

Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients.

Robotic-assisted surgery is expected to have advantages over standard laparoscopic approach in patients undergoing curative surgery for rectal cancer. PubMed, Cochrane Library, Web of Science, Scopus and Google Scholar were searched from database inception to 10 November 2021, for both RCTs and observational studies comparing robotic-assisted versus standard laparoscopic surgery for rectal cancer resection. Where possible, data were pooled using random effects meta-analysis. Forty-Two were considered eligible for the meta-analysis. Survival to hospital discharge or 30-day overall survival rate was 99.6% for RG and 98.8% for LG (OR = 2.10; 95% CI: 1.00 to 4.43; p = 0.05). Time to first flatus in the RG group was 2.5 ± 1.4 days and was statistically significantly shorter than in LG group (2.9 ± 2.0 days; MD = -0.34; 95%CI: -0.65 to 0.03; p = 0.03). In the case of time to a liquid diet, solid diet and bowel movement, the analysis showed no statistically significant differences (p > 0.05). Length of hospital stay in the RG vs. LG group varied and amounted to 8.0 ± 5.3 vs. 9.5 ± 10.0 days (MD = -2.01; 95%CI: -2.90 to -1.11; p < 0.001). Overall, 30-days complications in the RG and LG groups were 27.2% and 19.0% (OR = 1.11; 95%CI: 0.80 to 1.55; p = 0.53), respectively. In summary, robotic-assisted techniques provide several advantages over laparoscopic techniques in reducing operative time, significantly lowering conversion of the procedure to open surgery, shortening the duration of hospital stay, lowering the risk of urinary retention, improving survival to hospital discharge or 30-day overall survival rate.

Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment.

OBJECTIVE: The aim of the study was to identify factors associated with worse physical and emotional functioning of breast cancer survivors with upper extremity lymphedema. METHODS: 1250 sets of questionnaires consisting of WHO-DAS II, EORTC QLQ-C30, EORTC QLQ-BR23 and GHQ-30 were mailed to women who underwent a breast cancer surgery at the Lower Silesian Oncology Center in Poland between January 1998 and December 2005. RESULTS AND CONCLUSIONS: The response rate was 33.47%. 117 women were included into a lymphedema group and 211 into a group without this complication. Women with lymphedema were more disabled (overall disability (DAS) score 39.78 versus 34.67; p<0.001), reported symptoms from the upper extremity (shoulder or arm pain and difficulties in arm movement) and from the operated breast (pain and swelling) 2-3 times more often, experienced poorer quality of life (global quality of life (QOL) score 0.50 versus 0.57; p=0.005) and higher psychological distress (GHQ score 10.61 versus 8.01; p=0.007) in comparison to breast cancer survivors without lymphedema. The factors associated with higher DAS score, higher GHQ score and lower QOL score in women with lymphedema were as following: pain in the upper limb (mainly shoulder and arm), pain in operated breast, difficulties with arm movement, localization of lymphedema within the hand or in operated breast, a history of dermatolymphangitis and of receiving chemotherapy. Severity of lymphedema, younger age, BMI and localization of lymphedema within the dominant limb were not considerably related to worse outcomes in these women.

Evaluation of MDA-MB-468 Cell Culture Media Analysis in Predicting Triple-Negative Breast Cancer Patient Sera Metabolic Profiles.

Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive 1H NMR metabolic characterization of the MDA-MB-468 cell line, a commonly used model of TNBC, followed by an analysis of serum samples obtained from TNBC patients and healthy controls. MDA-MB-468 cells were cultured, and changes in the metabolic composition of the medium were monitored for 72 h. Based on time courses, metabolites were categorized as being consumed, being produced, or showing a mixed behavior. When comparing TNBC and control samples (HC), and by using multivariate and univariate analyses, we identified nine metabolites with differing profiles). The serum of TNBC patients was characterized by higher levels of glucose, glutamine, citrate, and acetoacetate and by lower levels of lactate, alanine, tyrosine, glutamate, and acetone. A comparative analysis between MDA-MB-468 cell culture media and TNBC patients' serum identified a potential systemic response to the carcinogenesis-associated processes, highlighting that MDA-MB-468 cells footprint does not reflect metabolic changes observed in studied TNBC serum fingerprint.

Correlation of metallothionein expression with clinical progression of cancer in the oral cavity.

UNLABELLED: This study aimed at finding out whether the expression of metallothionein (MT), laminin, Ki-67 antigen and minichromosome maintenance-2 (Mcm-2) protein changes with growing invasiveness of the tumour. The expression of these markers in primary tumours with no metastases to lymph nodes (PT N-) was compared with the expression in primary tumours with metastases in draining lymph nodes (PT N+). The difference in marker expression was also evaluated between metastatic lymph nodes (LN+) and the corresponding primary tumours (PT N+). PATIENTS AND METHODS: The studies were performed on tumour samples from 39 patients with squamous cell carcinoma of the oral cavity floor or of the oral part of the tongue. All the patients had been subjected to radical surgery, accompanied by the removal of lymph nodes. In 20 patients post-operative histopathology disclosed the presence of metastases in the draining lymph nodes (pN+), while in 19 patients the presence of such metastases was excluded (pN0). RESULTS: The PT N+ group was found to contain a significantly higher percentage of cells with cytoplasmic expression of MT, than the PT N- group. In turn, a significant increase in the intensity of reaction of cytoplasmic MT and an increased percentage of cancer cells demonstrating MT expression in the cell nuclei was demonstrated in the LN+ compared to the PT N+ group. The expression of the remaining parameters did not significantly differ between PT N-, PT N+ and LN+. CONCLUSION: A gradual increase in MT expression (both cytoplasmic and nuclear) takes place with progression of the tumour and the increased nuclear expression of MT in LN+ cells may suggest a role of MT in metastasis development in the studied tumours.

[GEOLOGICAL OVERVIEW OF THE VILNIUS REGION BY J. E. GILIBERT (1741-1814), THE FIRST PROFESSOR OF NATURAL HISTORY AT THE UNIVERSITY OF VILNIUS]. / GEOLOGICZNY OGLAD WILENSZCZYZNY J.E. GILIBERTA (1741-1814), PIERWSZEGO PROFESORA HISTORII NATURALNEJ UNIWERSYTETU WILENSKIEGO.

In 1775-1783, Jean-Emmanuel Gilibert (1741-1814) stayed in Respublica Poloniae to oranize a veterinary school, the Royal Botanic Garden and the Royal School of Physicians in Grodno, and since 1781 he worked in Vilnius as Professor of Natural History at the Principal School of the Grand Duchy of Lithuania. Little is known about his work conducted in Lithuania in the field of geology and earth sciences. The author has decided, on the basis of Gilibert's publications and analysis of the literature (works of J. Garbowska and P. Daszkiewicz and others), to present his teaching and research activities in this field. In Grodno, Gilibert looked after and multiplied the collections of the natural history cabinet at the Royal School of Physicians, renowned for its rich mineralogical and fossil collections watched and admired by, among others, King Stanislaw August, J. Bernoulli (1744-1807) and M. Patrin (1742-1815) who mentions the amber rosary with a different species of insects preserved in each bead. Gilibert's tours around Lithuania were the opportunity to enlarge the geological collections and to adapt them to the needs of the school. He also appreciated the importance of ordinary specimens representing the geology of the area. These specimens not only enriched the natural history cabinet, but also defined the way of working and collecting. Ha was the first to found and gather fossil animals from near Grodno. The signs of mineralogical and geological interests of Gilibert can be found in the works of other authors of that epoch (L. Viteta (1736-1809) and J. Bernoulli). In Vilnius, Gilibert conducted a one year-long full lecture on natural history (zoology, botany and mineralogy). In his lectures on mineralogy, he presented not only the systematics, but also emphasized the usefulness of minerals in medicine, for the production of ornamental items and in different sectors of the economy. He adapted the process of teaching to the needs of practical life, based on observations and experiments, and was using the local wildlife specimens in his lectures. Thanks to the French naturalist, the teaching of natural science remained at a good European level since the time the Department was founded at the University of Vilnius. A treatise on physical geography of the Grand Duchy of Lithuania is Gilibert's best-known published work in Poland. Based on own observations, he determined, e.g., the causes of drying of ponds and marshes, as well as of the formation of peat, limonitic iron and ocher, the origin of rivers in Lithuania and the presence of amber, and described a number of fossils. He provided the characteristics of geological deposits (now included in the Quaternary), described their origin and age, and drew attention to the issues of dynamic geology (e.g. erosional activity of rainwater, river erosion, formation of sand dunes). From the period of his eight-year stay in Lithuania, Gilibert also submitted observations on the climate of Lithuania, documented by temperature measurements. He indicated that the climate of this part of Europe was milder than the French believed, with clearly noticeable two seasons: winter and summer. He pointed out that the autumn rains give rise to muddy areas persisting to the end of November, and the most severe frost, usually several days long, occurs in late December and January, when the winds blow from the northeast. June and July are typically the hottest months, but the northern winds sometimes cause July ground frosts. He compared Lithuania's climate to that of the Alpine foreland. Gilibert was the first scholar who studied the natural environment of Lithuania based on scientific principles. Interesting are his observations on the amber resin, for example, unequivocal statement that amber is a resin, at the time when the idea was still much discussed. Worth noting are the geological elements in the physiographic description of Lithuania, published by Gilibert (1806) in Histoires des Plantes d'Europe. It should also be pointed to the methodological aspect of Gilibert's works: the facts precede interpretations, the results are attempted to be universalized by transposition into areas other than those investigated by Gilibert, and the observations are linked with scientific theories, which were new at those times, in the field of geology, chemistry and physics. Gilibert's descriptions were often the first ones available to the naturalists in western and southern Europe. They were all the more valuable that contained a lot of data on the geology, meteorology, physical geography etc., useful in various fields.

Cryosurgery in the treatment of women with breast cancer-a review.

Cryoablation could be an alternative to surgical excision of breast cancer. The cytotoxic potential of cryosurgery has been shown in both animal models and studies conducted on humans. There are several advantages to be gained from ablation performed at very low temperatures and these include the method's simplicity, lack of pain, low morbidity, cost-effectiveness, and potential for positive cryo-immunologic effects. This manuscript reviews data concerning the use of cryoablation in the treatment of breast cancer.