Tebentafusp (IMCgp100) in the treatment of uveal melanoma — from preclinical evidence to clinical practice

Tebentafusp (IMCgp100) is a novel bispecific immunotherapy that contains a specifically engineered soluble T-cellreceptor (TCR) capable of recognising the gp100 epitope on the surface of tumour cells presented by human leukocyteantigen-A*02:01 (HLA- A*02:01 (HLA-A2) is a specific allele within the HLA-A2 group). The HLA-A2 is then fused tothe single-chain variable fragment of anti-CD3, which binds to T-cells and destroys them. Tebentafusp has been shownto cause a significant increase in pro-inflammatory cytokine levels that are detrimental to the tumour. The preliminaryresults of tebentafusp in solid tumours are encouraging, particularly in advanced/metastatic uveal melanoma (UM).In a randomised phase III study (IMCgp100-202; n = 378), patients with untreated HLA*02:01 positive metastatic UM(mUM), tebentafusp significantly improved overall survival (OS) with a hazard ratio (HR) of 0.51 compared to the investigator’schoice, mainly pembrolizumab (82%). The one-year OS rate for tebentafusp was 73% compared to 59%for pembrolizumab. For comparison, the single-arm GEM1402 study (n = 52) reported a one-year OS rate of 52% forthe combination of nivolumab and Ipilimumab in metastatic UM. The most common adverse reactions related totebentafusp include cytokine release syndrome (CRS) and dermatological reactions such as rash. It is the first drugwith OS benefit in advanced/metastatic UM patients. However, further research is needed to optimise its use, improvepatient selection, develop combination therapies and identify predictive and prognostic biomarkers

Organizing pneumonia - analysis of 18 own cases

Organizing pneumonia (OP) is a rarely diagnosed disease, however the incidence ratio was estimated as 6-7 /100 000. Disease can occur in cryptogenic form or as a secondary reaction to various noxious agents, drugs, and ionising radiation, as a concomitant disease to infections, lympho- and myeloproliferative disorders, and connective tissue diseases. Symptoms of OP are non-specific therefore lung biopsy and histological examination are necessary for diagnosis. Eighteen cases of OP, 15 women and 3 men, aged 40 to 76 years, are presented with analysis of clinicopathological characteristic and therapeutic problems. In all cases diagnosis was confirmedby open lung biopsy. In one case radiotherapy and in one transtuzumab treatment was the cause of OP. In further 3 women atybodies against Chlamydia pneumoniae and in one -against Mycoplasma pneumoniae were found in serum. Probably Hashimoto disease was the cause of one case. In 12 patients the OP was idiopathic. Majority of patients were treated by prednisone (0.5mg/kg). In one patient regression without any treatment was noticed and in other one - after cessation of transtuzumab. Five women were treated by clarithromycine. In 3 of them regression was observed but in other 2 corticotherapy was necessary. The observation period ranged from 1 month to 9 years, mean 34 months

Colorectal neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

Nowotwory/guzy neuroendokrynne (NEN/NET) jelita grubego są rozpoznawane coraz częściej, szczególnie guzy odbytnicy. To zjawisko jest najprawdopodobniej związane z powszechnym wykonywaniem kolonoskopii przesiewowych. Coraz więcej przemawia za tym, że NEN odbytnicy i okrężnicy to dwie odrębne choroby. Nowotwory neuroendokrynne odbytnicy są najczęściej zmianami niewielkich roz­miarów, cechują się niskim lub umiarkowanym stopniem złośliwości histologicznej, dobrym rokowaniem i większość z nich kwalifikuje się do leczenia endoskopowego. Natomiast NEN okrężnicy to często nowotwory agresywne, niskozróżnicowane, o złej lub niepewnej prognozie, wymagające operacji. Zasady postępowania z tymi chorymi stale się zmieniają. Opierając się na najnowszym piśmiennictwie oraz ustaleniach wypracowanych na spotkaniu roboczym Polskiej Sieci Guzów Neuroendokrynnych (grudzień 2016 r.) w pracy uzupełniono i uaktualniono dane i wytyczne postępowania dotyczące NEN jelita grubego, opublikowane w Endokrynologii Polskiej 2013; 64: 494–504.Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer­tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358–368.

Institutions of supervision and regulation of the banking market in Poland

Praca przedstawia instytucje nadzoru oraz regulacji rynku bankowego w Polsce, to znaczy Komisję Nadzoru Finansowego, Bankowy Fundusz Gwarancyjny oraz Narodowy Bank Polski. W każdym z rozdziałów opisuje każdą z nich, przedstawiając jej strukturę, organizację, cele oraz wpływ na rynek bankowy w Polsce.The aim of the thesis is to look at institutions of supervision and regulation of the banking market in Poland, which means Polish Financial Supervision Authority, Bank Fund Guarantee Fund and National Polish Bank. In each chapter there is a part about the structure, organization, goals and impact on the polish banking market

The Role of circHIPK3 in Tumorigenesis and Its Potential as a Biomarker in Lung Cancer

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC

Outcomes of Liver Transplantation with Incidental Intrahepatic Cholangiocarcinoma—Own Experience and a Systematic Review

Background: Cholangiocarcinoma, the second most common primary liver cancer, is still a contraindication for performing liver transplantation in most patients. Despite various trials being performed in large clinical centers, the results are still not satisfactory. The aim of this study was to present cases from our own cohort and perform a systematic review of the results of liver transplantation in patients with incidental intrahepatic cholangiocarcinoma. Materials and methods: We retrospectively reviewed the records of all patients who underwent liver transplantation and identified two patients with incidental intrahepatic cholangiocarcinoma via histopathological examination of the explanted liver. The results of radiological and biochemical screening performed during liver transplantation, standardized histopathological examination and follow-up data are presented. Additionally, a systematic review of PubMed and Cochrane Reviews based on the PRISMA protocol was performed, yielding 413 similar cases. Results: We present two cases of incidental intrahepatic cholangiocarcinoma found after liver transplantation. The patients were managed according to a standard protocol with no consecutive modification of immunosuppression or chemotherapy. There was no recurrence or mortality. In this systematic review, the mean reported number of lesions ranged between 1 and 2 per patient. A total of 42 recurrences were reported. The percentage of recurrences ranged between 28.6% and 80%. Conclusions: Despite not being a frequent finding, follow-up and further treatment of patients with incidental iCCA should be reported and analyzed. Extra carefulness in screening is advised in patients who are already diagnosed with oncological disease of the liver. In long-term follow-up, recurrence of the disease is rather probable

Outcomes of Bridging Therapy in Liver Transplantation for Hepatocellular Carcinoma

Background: Liver transplantation (LT) is a method for treating hepatocellular carcinoma (HCC) with satisfactory outcomes. One of the novel methods for predicting LT outcomes is the Metroticket 2.0 model. The disease in patients initially within the Milan criteria (MC) may progress while on a transplantation waitlist; thus, various transplantation bridging therapy (BT) methods are proposed for patients to stay within the MC and optimize the LT outcome. Methods: We performed a retrospective analysis of patients who underwent LT for HCC at an oncological and transplantation center in northern Poland. Patients who underwent (n = 10) or did not undergo (n = 11) BT were included. The primary endpoints of the study were mortality among the patients, HCC recurrence, and Metroticket 2.0 scores based on LT qualification results and explant pathology outcomes. The median follow-up length was 44.03 months. Results: Patients who underwent BT had significantly lower Metroticket 2.0 scores and greater AFP concentrations at baseline. At LT, there was no significant difference in Metroticket 2.0 scores or AFP concentrations between the groups. Explant Metroticket 2.0 scores were significantly lower in patients who received BT. A complete pathologic response was achieved in 30.0% of patients who underwent BT. The recurrence-free survival rates were 100% and 90.91% in patients who underwent and did not undergo BT, respectively. Overall survival was 80.0% and 81.81% in patients who underwent and did not undergo BT, respectively. Conclusions: BT should be considered only as a means of remaining within the LT criteria. Routine BT does not appear to be justified for LT patients