Incidence of different types of cancer in the follow-up period after primary diagnosis and treatment of melanoma. Single-centre 4-year follow-up on a population of 709 patients.

Introduction: Follow-up plays a key role in melanoma management, especially in the first years after diagnosis. During this period it is crucial to assess possible recurrence, progression of the disease or treatment complications. An important aspect is also the possibility of formation of new primary foci or other skin cancers. Aim: To assess the coincidence of skin lesions and cancers among the melanoma patients. Material and methods: Patients treated in the Comprehensive Cancer Centre between 2019 and 2022 were retrospectively analysed for occurrence of skin lesions diagnosed during the follow-up, and confirmed by biopsy. The lesions considered included skin cancers, dysplastic nevus and actinic keratosis. Results: In 100 (14%) out of 709 enrolled patients, 184 lesions were diagnosed. In 7 patients it was melanoma, in 49 BCC, and in 16 SCC. Dysplastic nevus and actinic keratosis were excised in 28 and 14 patients, respectively. More than one site of the skin lesion was observed in 39 patients, and more than one type of the lesion in 13 patients. Patients with lesions were on average 8.6 years older (p < 0.001), had less advanced tumours (p = 0.010), and primary melanoma was more often located on the head and neck (p = 0.056). Conclusions: Among melanoma patients, particular attention must be paid to, apart from early detection of melanoma recurrence and progression, the occurrence of new primary foci or independent skin cancers.

An analysis of clinical effectiveness of electrochemotherapy in the treatment of advanced metastatic malignant melanoma performed in the eastern part of Central Europe: a single-centre experience.

Introduction: Patients with cutaneous malignant melanoma (MM), in case of non-resectability of the lesions, have only a limited pool of the available treatment options. In recent years especially electrochemotherapy (ECT) has become an increasingly important therapy in locoregionally advanced MM. Aim: In this study an analysis of the ECT treatment of locoregionally advanced malignant melanoma was presented. Material and methods: Six ECT cycles in 5 patients were performed in the Wroclaw Comprehensive Cancer Centre. Treatment response, long-term observation, technical data downloaded from electroporator and photographs taken before and after the ECT were assessed in the analysis. Results: In total, 200 nodules in 5 patients were treated with ECT in palliative intent. After 5 out of 6 ECT cycles, the particular clinical response has been observed. Four patients with primary unresectable lesions underwent 11 surgeries of the cutaneous metastases. In long-term follow-up in 2 patients, of whom one died 19 months after the ECT, the disease progressed and in another two, no recurrence was observed. Conclusions: ECT is an encouraging therapy for patients in whom the recurrent cutaneous melanoma cannot be treated with other methods, however, access to this method in eastern part of Central Europe is limited. The presented study seems to confirm the usefulness of this palliative approach in a specific group of patients suffering from cutaneous MM.

The report and analysis concerning the usefulness of basic telemedicine tools in the skin cancer diagnostic screening process during COVID-19 pandemics.

Introduction: A rapid spread of the emerging COVID-19 pandemic limited the availability of professional medical advice. As a result, a significant increase in the number of undiagnosed and chronically ill patients without medical care was noticed. In reaction to the urgent need, the telemedical consultation, instead of the classical form, may be introduced as a vulnerable tool in preclinical evaluation of patients with potentially malignant skin lesions. Aim: In this study the results of the implementation of telemedical consultation programme with the intention to early detect the skin cancers in patients who, due to the COVID-19 pandemic, could not undergo the standard consultation was presented. Material and methods: The programme of remote dermatological consultation, which was introduced on 1 June 2020, covered all patients who had no possibility or will to visit the standard healthcare units. In case of suspicion of life-threatening skin lesions patients were invited for additional diagnostics or surgery. Obtained data, including demography, age, surgery description and pathomorphological examination were descriptively analysed. Results: In total, 80 consecutive patients were enrolled during the screening programme. In total, 31 lesions in 25 patients were excised. In this group there were 10 serious diagnoses including 5 cases of basal cell carcinoma, melanoma in situ and dysplastic nevi. Moreover, another 10 patients were referred to other specialists or specific recommendations were advised. Conclusions: An alternative track using teledermatology for patients with skin diseases was successfully introduced under the specific conditions of epidemiologic danger. Despite its disadvantages teledermatology enabled the diagnosis and treatment in a significant number of serious cases.

Consensus guidelines for pressurized intraperitoneal aerosol chemotherapy: Technical aspects and treatment protocols.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to treat patients with peritoneal cancer. A recent survey demonstrated considerable diversification of current practice of PIPAC raising issues of concern also regarding safety and efficacy. The study aim was to reach consensus on best practice of PIPAC treatment. METHODS: Current practice was critically discussed during an expert meeting and the available evidence was scrutinized to elaborate a 33-item closed-ended questionnaire. All active PIPAC centers were then invited to participate in an online two-round Delphi process with 3 reminders at least. Consensus was defined a priori as >70% agreement for a minimal response rate of 70%. RESULTS: Forty-nine out of 57 invited PIPAC centers participated in Delphi 1 and 2 (86%). Overall, there was agreement for 21/33 items. Consensus was reached for important aspects like advanced OR ventilation system (91.8%), remote monitoring (95.9%), use of the PRGS (85.7%) and use of a safety checklist (98%). The drug regimens oxaliplatin (87.8%) and cisplatin/doxorubicin (81.6%) were both confirmed by the expert panel. Important controversies included number and location of Biopsies during repeated PIPAC and the combination of PIPAC with additional surgical procedures. CONCLUSION: This consensus statement aims to allow for safe and efficacious PIPAC treatment and to facilitate multi-center analyses of the results. Additional preclinical and clinical studies are needed to resolve the remaining controversies.

Porphyrin Based 2D-MOF Structures as Dual-Kinetic Sorafenib Nanocarriers for Hepatoma Treatment.

The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.

Additive manufacturing technologies enabling rapid and interventional production of protective face shields and masks during the COVID-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets and contact routes, hence the demand for personal protective equipment (PPE) has increased during the outbreak of coronavirus disease 2019 (COVID-19). Among the most noticeable shortages was the lack of face shields. The urgent demand for PPE induced interdisciplinary cooperation to overcome the shortages, and additive manufacturing proved to be ideal for the crisis situation. OBJECTIVES: To investigate the possibilities of implementing additive manufacturing technologies in the interventional fabrication of protective face shields for medical staff. MATERIAL AND METHODS: An Ender 3 Pro 3D printer was used to print headbands and Cura 4.4 was chosen as the slicing software. Open source face shield designs were downloaded as standard tessellation language (STL) files and compared. Only models with scientific support were taken under consideration. RESULTS: The mean time for producing the headbands tested ranged from 59 min to almost 3 h, depending on the design. After setting up our low budget printer and choosing the Prusa RC 3 protective face shield as the main product, we were able to fabricate about 30 face shields per week at a cost of about €1 each. During 4 weeks, 126 face shields were produced and delivered to various hospital wards, which substantially eased the shortages. CONCLUSIONS: Additive manufacturing enables immediate responses to needs in emergency situations, and allows for mass production of personal protective equipment in a short time due the rapid exchange of data among printer users. Despite the unregulated legal situation and insufficient scientific evidence, such protective equipment has been approved by clinicians and is currently used by medical personnel around the world.

Overall clinical and trichoscopic analysis performed in patients who underwent pressurized intraperitoneal aerosol chemotherapy (PIPAC) treatment for peritoneal carcinomatosis - initial trial preliminary report.

INTRODUCTION: Cutaneous adverse events are among the remaining problematic issues of current oncology. The term peritoneal carcinomatosis (PC) refers to the advanced cancer stage. The innovative treatment of PC includes the use of pressurized intraperitoneal aerosol chemotherapy (PIPAC). AIM: To present a preliminary report from an initial trial aimed at an overall clinical and trichoscopic analysis performed in patients who underwent PIPAC treatment due to PC. MATERIAL AND METHODS: For all steps of this study we obtained the consent of the local bioethics commission #KB 196/2018. Three different hair assessment methods were used in our study: 1) general clinical and patient self-feeling assessment; 2) hair pull test; 3) and trichoscopic analysis. RESULTS: No hair or scalp disorders were noted in the observation period. In the self-feeling test assessment the vast majority recognized their hair as being of comparable quality or even better in quality compared to previous forms of chemotherapy they had undergone. In all patients we observed a reduction of hair loss in the pull test in the hospitalization period. In trichoscopic analysis we found all determinants and signs of hair disorders in the assessed group. CONCLUSIONS: The PIPAC is safe and is not a burdensome or aggressive form of therapy, especially according to the very important factors influencing the potential quality of hair and hair loss. The authors, however, realize that to obtain comprehensive results and evaluate this novel and promising method we need to perform more research without any limitations like those in our study.

The different expression of key markers on urothelial holoclonal, meroclonal, and paraclonal cells in in vitro culture.

Urothelial cell populations which differ in morphology and proliferation capacities can be isolated from the urinary bladder. The goal of this study was to analyze a clonal, proliferative, and self-renewing potential of porcine urothelial cells and to compare expression of selected adhesion and tight junction molecules, urothelial and stem cell markers for the urothelial clone types. Urothelial cells were isolated from 10 porcine urinary bladders. Three different clone types: holoclone-, meroclone-and paraclone-like colonies were identified based on their morphology. To characterize and compare the urothelial clones the immunofluorescent stains were performed. Expression of pancytokeratin (PanCK), Ki-67 and p63 was higher for holoclone- like cells compared to meroclone-and paraclone-like cells (P < 0.05). Meroclone-like cells expressed higher levels of p63 compared to paraclone- like cells (P < 0.05). The level of Ki-67 and PanCK for meroclone- and paraclone- like cells was comparable (P > 0.05). ß1 and ß4 integrins were not expressed. Expression of zonula occludens-1 (ZO-1) in cell-cell junctions for paraclone-, meroclone-and holoclone-like cells was 17.6 ± 0.6, 14.7 ± 0.5, and 16.1 ± 0.4, respectively. The results of actin filaments (F-actin) expression were 253,634 ± 6,920 for meroclone-like cells, 198,512 ± 7,977 for paraclone-like cells and 133,544 ± 3,169 for holoclone-like cells. Three urothelial cell types with differing features can be isolated from the bladder. Holoclone-like cells are the richest in stem cells and should be used in further studies for construction of neo-bladder or neo-conduit using tissue engineering methods.

A new drug combination significantly reduces kidney tumor progression in kidney mouse model.

Tuberous sclerosis complex (TSC) disease is associated with tumors in many organs, particularly angiomyolipoma (AML) in the kidneys. Loss or inactivation of TSC1/2 results in high levels of HIF-α activity and VEGF expression. mTOR inhibitor (rapamycin) and the AMPK activator 5-aminoimidazole-4-carboxamide (AICA)-riboside (AICAR) are currently used separately to treat cancer patients. Here, we investigated the effect of a novel combination of rapamycin and AICAR on tumor progression. Our data show that treatment of AML human cells with drug combinations resulted in 5-7-fold increase in cell apoptosis compared to each drug alone. In addition, drug combinations resulted in 4-5-fold decrease in cell proliferation compared to each drug alone. We found that drug combinations abolished Akt and HIF activity in AML cells. The drug combinations resulted in decrease in cell invasion and cell immigration by 70% and 84%, respectively in AML cells. The combined drugs also significantly decreased the VEGF expression compare to each drug alone in AML cells. Drug combinations effectively abolished binding of HIF-2α to the putative Akt site in the nuclear extracts isolated from AML cells. Treatment TSC mice with drug combinations resulted in 75% decrease in tumor number and 88% decrease in tumor volume compared to control TSC mice. This is first evidence that drug combinations are effective in reducing size and number of kidney tumors without any toxic effect on kidney. These data will provide evidence for initiating a new clinical trial for treatment of TSC patients.

The scientific report from the first pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures performed in the eastern part of Central Europe.

Objective To perform a single-centre, detailed analysis of the preparations for the introduction of the first pressurized intraperitoneal aerosol chemotherapy (PIPAC) programme in the eastern part of Central Europe. Methods The study analysed the 14-month preparation period prior to the performance of the first PIPAC procedure with respect to: (i) general preparations; (ii) patient referral and qualification; (iii) the first PIPAC procedure; (iv) the 2 weeks following PIPAC programme establishment; and (v) general problematic issues that arose. Results The length of time needed to prepare our institution for the first PIPAC procedure was extremely long compared with other European Union PIPAC centres: 14 months versus a standard 3-6 months of preparation. The longest amount of time (12 months) was required to prepare the required paperwork. Conclusions A new PIPAC programme was successfully established in the eastern part of Central Europe. The length of time to implement this method was significantly longer because of lengthy bureaucratic processes. These current findings should help new centres, especially in this part of Europe, to establish a PIPAC programme more quickly.

Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: Case report and review of the literature.

We report the first application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-year-old woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m2 and doxorubicin at 1.5 mg/m2 for 30 min at 37 °C. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis (RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: An international survey study.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings. METHODS: An online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017. RESULTS: Nine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6-8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m2 and 1.5mg/m2, respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC. CONCLUSION: These data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials.

Does the presence of sentinel lymph node macrometastases in breast cancer patients require axillary lymph node dissection?-Single-center analysis.

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long-term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow-up time for patients after ALND was 36.2 months (6-74 months); 18.8 months (6-38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6-74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long-term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.

Stem cells and differentiated cells differ in their sensitivity to urine in vitro.

Urinary tract regeneration using tissue engineering is one of the most challenging issues in the field of reconstructive urology. Cells seeded on scaffold are exposed to urine immediately after the implantation. The outcome of urinary bladder regeneration is depended on the ability of these cells to survive, proliferate, and regenerate. The aim of this study was to compare a sensitivity of three different cell lines to urine in vitro. Three different cell lines were isolated from porcine bladder (urothelial cells, UCs and smooth muscle cells, SMCs) and adipose tissue (adipose-derived stem cells, ADSCs). Cell viability (MTT assay), proliferation (real-time cell analysis using xCELLigence system) and apoptosis/necrosis (flow cytometry) were analyzed after exposition to urine. ADSCs were the most sensitive to urine compared to two other tested cell lines. Among the bladder cell lines the UCs were more resistant to urine than SMCs. Twenty four hour incubation of UCs, SMCs, and ADSCs with urine lead to ∼40%, ∼70%, and ∼90% reduction of their viability, respectively. The mechanism of urine mediated cytotoxicity differed depending on the tested cell type. Urothelial and SMCs seems to be more suitable for urinary bladder regeneration compared to mesenchymal stem cells, however, these cells have limited application especially in the case of urinary bladder cancer.

Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis.

The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis.

Changes of Langerhans cells during skin ageing.

INTRODUCTION: During the process of skin ageing, changes occur in all skin layers and all cells, including the Langerhans cells. AIM: To assess whether any quantitative difference in the number of CD1a+ LC cells/mm2 and HLA-DR+ LC cells/mm2 as well as in their morphological features can be observed during the course of different types of skin ageing. MATERIAL AND METHODS: The study was conducted in a group of 60 women, which was divided into three independent groups: group I with symptoms of menopausal skin ageing, group II with symptoms of photoageing, group III with symptoms of chronological ageing. Skin biopsy samples were taken from the pre-auricular region from all of the participants. The number of CD1a+ LC cells/mm2 and HLA-DR+ LC cells/mm2 as well as their morphological features were evaluated. RESULTS: The frequency of CD1a+ LC and HLA-DR+ LC in all the studied groups was diverse. In groups I and III, the LC with large cell bodies and long, multi-branched processes were the majority. In group II, the LC had small cell bodies and their processes were mainly short and unbranched. CONCLUSIONS: The obtained results indicate the presence of quantitative and morphological changes of the CD1a+ LC and HLA-DR+ LC during the course of different types of skin ageing.

Are agricultural and natural sources of bio-products important for modern regenerative medicine? A review.

[b] Abstract Introduction and objectives[/b]. As tissue engineering and regenerative medicine have continued to evolve within the field of biomedicine, the fundamental importance of bio-products has become increasingly apparent. This true not only in cases where they are derived directly from the natural environment, but also when animals and plants are specially bred and cultivated for their production. [b]Objective.[/b] The study aims to present and assess the global influence and importance of selected bio-products in current regenerative medicine via a broad review of the existing literature. In particular, attention is paid to the matrices, substances and grafts created from plants and animals which could potentially be used in experimental and clinical regeneration, or in reconstructive procedures. [b]Summary.[/b] Evolving trends in agriculture are likely to play a key role in the future development of a number of systemic and local medical procedures within tissue engineering and regenerative medicine. This is in addition to the use of bio-products derived from the natural environment which are found to deliver positive results in the treatment of prospective patients.

Vascularization Potential of Electrospun Poly(L-Lactide-co-Caprolactone) Scaffold: The Impact for Tissue Engineering.

BACKGROUND Electrospun nanofibers have widespread putative applications in the field of regenerative medicine and tissue engineering. When compared to naturally occurring collagen matrices, electrospun nanofiber scaffolds have two distinct advantages: they do not induce a foreign body reaction and they are not at risk for biological contamination. However, the exact substrate, structure, and production methods have yet to be defined. MATERIAL AND METHODS In the current study, tubular-shaped poly(L-lactide-co-caprolactone) (PLCL) constructs produced using electrospinning technology were evaluated for their potential application in the field of tissue regeneration in two separate anatomic locations: the skin and the abdomen. The constructs were designed to have an internal diameter of 3 mm and thickness of 200 µm. Using a rodent model, 20 PLCL tubular constructs were surgically implanted in the abdominal cavity and subcutaneously. The constructs were then evaluated histologically using electron microscopy at 6 weeks post-implantation. RESULTS Histological evaluation and analysis using scanning electron microscopy showed that pure scaffolds by themselves were able to induce angiogenesis after implantation in the rat model. Vascularization was observed in both tested groups; however, better results were obtained after intraperitoneal implantation. Formation of more and larger vessels that migrated inside the scaffold was observed after implantation into the peritoneum. In this group no evidence of inflammation and better integration of scaffold with host tissue were noticed. Subcutaneous implantation resulted in more fibrotic reaction, and differences in cell morphology were also observed between the two tested groups. CONCLUSIONS This study provides a standardized evaluation of a PLCL conduit structure in two different anatomic locations, demonstrating the excellent ability of the structure to achieve vascularization. Functional, histological, and mechanical data clearly indicate prospective clinical utilization of PLCL in critical size defect regeneration.