Skuteczna alkoholowa ablacja guza insulinowego trzustki, obserwacja 4-letnia. Opis przypadku i przegląd literatury

Introduction: EUS-guided ethanol ablation of insulinoma is a new method of treatment of this neuroendocrine tumour. Ablation is recommended in patients who are poor surgical candidates or refuse surgery. We present a case of an 81-year-old female with symptomatic insulinoma, treated successfully with EUS-guided alcoholic ablation, along with a literature review including 28 other previously described cases. The effectiveness, safety of the therapy, and technical procedure-related issues are summarised. To the best of our knowledge, this is the first described case of successful insulinoma EUS-guided ablation in Poland. Material and methods: We searched the PubMed/Medline database to identify cases of EUS-guided alcoholic ablation. Our analysis included 14 articles (case reports or case series), with a total of 27 patients and 31 tumours described, published before February 2017. Results: The described tumours were relatively small (mean 13 mm), and the most common location was pancreatic head. The mean ethanol volume injected to the tumour was 1.8 ml and the concentration of infused alcohol varied from 95% to 98%.Side effects were observed in six cases; apart from one, they were mild and self-limiting. There was only one severe adverse event, treated conservatively with success. The median follow-up was 14.4 months (2–55 months). In all described cases ablation led to improvement of the symptoms and normalisation of glycaemia. Conclusions: The EUS-guided alcoholic ablation of insulinoma is a safe and effective method of treatment in patients who are poor surgical candidates and/or refuse surgery. The adverse effects are rare and mild and were observed when the volume of injected ethanol was equal to or above 3.0 ml. However, the data is limited, the follow-up is relatively short, and prospective studies are needed to confirm the long-term effects of treatment. The study shows also that there are important procedural differences (concentration and volume of alcohol, needle gauge, number of sessions) between the endoscopists, which should be specified.Wstęp: Przedstawiono 81-letnią chorą z objawowym guzem insulinowym głowy trzustki. Pacjentka, z uwagi na liczne choroby współistniejące, została zdyskwalifikowana z leczenia chirurgicznego. Leczona diazoksydem, ciągłymi wlewami z glukozy, analogami somatostatyny bez istotnej poprawy(obserwowano działania niepożądane). Następnie pod kontrolą EUS wykonano alkoholową ablację zmiany. Nie obserwowano powikłań. Odstawiono diazoksyd, obserwując normalizację glikemii. Pacjentka w 4-letniej obserwacji pozostaje bez objawów klinicznych hipoglikemii. Według naszej wiedzy jest to pierwszy opisany przypadek skutecznej alkoholowej ablacji guza insulinowego w Polsce. W pracy przeprowadzono przegląd literatury i podsumowanie wcześniej przeprowadzonych i opisanych zabiegów alkoholowej ablacji guzów insulinowych, ze szczególnym naciskiem na skuteczność i bezpieczeństwo, czas obserwacji po leczeniu i szczegóły techniczne przeprowadzenia procedury. Materiał i metody: Przeszukano bazę Pub Med/Medline, aby zidentyfikować opisane przypadki alkoholowej ablacji guza insulinowego trzustki. Do analizy włączono 14 artykułów opublikowanych przed końcem lutego 2017, w których opisano łącznie 27 przypadków i 31 guzów insulinowych. Wyniki: Opisane guzy były stosunkowo małymi zmianami (średnio 13 mm), ich najczęstsza lokalizacją była głowa trzustki. Średnia objętość podawanego alkoholu to 1,8 ml, a stężenie wynosiło 95–98%. Efekty uboczne obserwowano w 6 przypadkach, poza jednym były one łagodne i ustępowały samoistnie. Zaobserwowano tylko jedno poważne powikłanie leczone zachowawczo z sukcesem. Średni czas obserwacji pacjenta wyniósł 14,4 miesiąca (od 2 do 55 miesięcy). U wszystkich opisanych chorych ablacja doprowadziła do ustąpienia objawów i normalizacji glikemii. Wnioski: Alkoholowa ablacja guza insulinowego trzustki pod kontrolą EUS jest bezpieczną i skuteczną metoda leczenia tego guza u pacjentów z przeciwwskazaniami do zabiegu lub takich, którzy nie godzą się na zabieg. Większość powikłań ma charakter łagodny i były one obserwowane, gdy objętość podawanego do guza etanolu przekraczała 3,0 ml. Krótki czas obserwacji pacjentów i niewielka liczba opisanych przypadków, sprawiają że konieczne jest zaplanowanie badań prospektywnych, które mogłyby potwierdzić długoterminowe efekty leczenia. Analiza pokazuje również, że występują istotne różnice pomiędzy endoskopistami w zakresie sposobu przeprowadzenia samej procedury (stężenie i objętość alkoholu, rozmiar igły, liczba sesji). Powinno dążyć się do sprecyzowania sposobu jej wykonania.

Dietary Intervention Effectiveness, Clinical Outcomes and Nutrient and Salicylate Intakes in Older Adults Living in Long-Term Care Homes: The Results from the Senior’s Plate Project

Optimal nutrition is an important part of the therapeutic process offered to patients in long-term care, as it can significantly influence their nutritional and health status. The aim of this study was to assess the impacts of a dietary intervention on the nutritional status, clinical outcomes and selected nutrient and salicylate intakes among older adults living in a long-term care nursing home. To achieve the research goal, a prospective, non-randomized, baseline-controlled intervention study was conducted. The study was conducted within the framework of the “Senior’s Plate Project”, a project established in 2018 by the Polish Society of Dietetics. Methods: A 3 month dietary intervention, which included one serving of supplementary food, served as a second breakfast (Nestle Sinlac). Energy, nutrients and salicylates intakes were estimated on the basis of the menus. Food and beverage intakes among residents were verified by health care personnel. Anthropometric measurements and clinical examinations were conducted according to standard procedures at baseline and after intervention. Results: Of the 38 residents qualified for the study, 29 completed the program. Residents’ body mass index (BMI) values ranged from 13.3 kg/m2 to 34 kg/m2. A BMI < 22 kg/m2, indicating underweight, was found in 19 subjects. The dietary intervention resulted in increased body weight (57.8 ± 12.3 vs. 59.4 ± 12.6 kg), BMI (22.4 ± 4.0 vs. 23.0 ± 4.1 kg/m2) and body fat (19.2 ± 8.7 vs. 20.6 ± 8.9 kg). Significant changes in the levels of biochemical parameters, including serum calcium (8.7 vs. 9.5 mg/dL), potassium (4.1 ± 0.6 vs. 4.5 ± 0.5 mmol/L) and zinc (74.1 ± 10.9 vs. 109.0 ± 20.4 µg/dL), were observed. Energy, protein, fat and carbohydrate intakes were significantly higher in the third month of the intervention as compared to the baseline. The estimated medial daily intake of salicylates was low and ranged from 0.34 mg to 0.39 mg. Conclusions: The dietary intervention resulted in beneficial and significant changes in the nutritional status, biochemical parameters and nutrition of residents of the long-term care home. These results suggest that practical and individualized approaches are required to improve the nutritional status and clinical outcomes of nursing homes residents

Genetics, Genomics and Emerging Molecular Therapies of Pancreatic Cancer

The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for 5 years from the diagnosis, 8% live for 2 years, and almost half live for only about 3 months. A family predisposition to pancreatic cancer occurs in about 10% of cases. Several oncogenes in which somatic changes lead to the development of tumours, including genes BRCA1/2 and PALB2, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, are involved in pancreatic cancer. Between 4% and 10% of individuals with pancreatic cancer will have a mutation in one of these genes. Six percent of patients with pancreatic cancer have NTRK pathogenic fusion. The pathogenesis of pancreatic cancer can in many cases be characterised by homologous recombination deficiency (HRD)—cell inability to effectively repair DNA. It is estimated that from 24% to as many as 44% of pancreatic cancers show HRD. The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others

Genetics, Genomics and Emerging Molecular Therapies of Pancreatic Cancer

The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for 5 years from the diagnosis, 8% live for 2 years, and almost half live for only about 3 months. A family predisposition to pancreatic cancer occurs in about 10% of cases. Several oncogenes in which somatic changes lead to the development of tumours, including genes BRCA1/2 and PALB2, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, are involved in pancreatic cancer. Between 4% and 10% of individuals with pancreatic cancer will have a mutation in one of these genes. Six percent of patients with pancreatic cancer have NTRK pathogenic fusion. The pathogenesis of pancreatic cancer can in many cases be characterised by homologous recombination deficiency (HRD)—cell inability to effectively repair DNA. It is estimated that from 24% to as many as 44% of pancreatic cancers show HRD. The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field