[Focal congenital hyperinsulinism]. / Focalis congenitalis hyperinsulinismus.

In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.

Can the transection plane be optimized in pancreatic resections?

Purpose: According to current protocol, the separation of pancreatic head and body is performed at the level of superior mesenteric vein (SMV). Previous data indicate that the resection plane should be modified in portal annular pancreas. We presumed that the optimal line of pancreatic resections could also be different in other cases. Our aim is to simulate pancreatic resections in different planes and find the optimal resection line with the minimum number of cut vessels. Main methods: 25 abdominal vascular corrosion casts were prepared, the aorta and the portal vein were cannulated. CT scans were taken on the casts, and specific planes were reconstructed simulating different resection lines. The total amount of cross sections of vessels were calculated in the different planes. Results: In our series, the optimal plane is the SMV in 11/25, 2 cm left in 10/25, 1 cm left in 4/25, 1 cm right in 1/25 and 2 cm right in none of our cases. The group of left sided extension contain more than half of the cases. With left sided resections, the cut surface of the vessels may be lowered to even 29% compared to the SMV plane. Conclusion: Our study revealed that pancreatic resections should be extended to the left side of the SMV in more than half of our cases. Therefore, the resection plane should be determined by preoperative imaging methods. Using DICOM viewer with multiplanar reconstruction, the resection planes can be simulated in clinical practice, which would reduce the risk of postoperative bleeding.

Quantitative Software Analysis of Endoscopic Ultrasound Images of Pancreatic Cystic Lesions.

Endoscopic ultrasonography (EUS) is the most accurate imaging modality for the evaluation of different types of pancreatic cystic lesions. Our aim was to analyze EUS images of pancreatic cystic lesions using an image processing software. We specified the echogenicity of the lesions by measuring the gray value of pixels inside the selected areas. The images were divided into groups (serous cystic neoplasm /SCN/, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms /Non-SCN/ and Pseudocyst) according to the pathology results of the lesions. Overall, 170 images were processed by the software: 81 in Non-SCN, 30 in SCN and 59 in Pseudocyst group. The mean gray value of the entire lesion in the Non-SCN group was significantly higher than in the SCN group (27.8 vs. 18.8; p < 0.0005). The area ratio in the SCN, Non-SCN and Pseudocyst groups was 57%, 39% and 61%, respectively; significantly lower in the Non-SCN group than in the SCN or Pseudocyst groups (p < 0.0005 and p < 0.0005, respectively). The lesion density was also significantly higher in the Non-SCN group compared to the SCN or Pseudocyst groups (4186.6/mm2 vs. 2833.8/mm2 vs. 2981.6/mm2; p < 0.0005 and p < 0.0005, respectively). The EUS image analysis process may have the potential to be a diagnostic tool for the evaluation and differentiation of pancreatic cystic lesions.

Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation.

Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases. A higher number of natural killer cells and more mature B cells along with PD-1+ expressing cells were observed in the main tumor area as compared to metastases. A higher number of metastatic lymph nodes were associated with significantly lower B cell counts. With more advanced lymph node metastatic status, higher leukocyte-particularly T cell numbers-were observed. Eleven differentially expressed immune-related genes were found between primary tumors and liver metastases. Also, alterations of the innate immune response and the tumor necrosis factor superfamily pathways had been identified.

Relationship between the coronavirus epidemic and the use of complementary and alternative medicine prior to elective surgical procedures / A koronavírus-járvány hatása a komplementer terápiás gyógymódok igénybevételére elektív sebészeti mutétek elott.

Összefoglaló. Bevezetés: A 2019 végén Vuhanból kiinduló, SARS-CoV-2 okozta koronavírus-járvány jelentos hatást gyakorolt életünkre. Specifikus terápia hiányában az emberek egy része alternatív gyógymódokhoz fordult. Célkituzés: Vizsgálatunk célja annak feltárása volt, milyen hatást gyakorolt a koronavírus-járvány a betegek komplementer gyógymódokhoz való viszonyulására elektív sebészeti mutétek elott. Módszer: Egy magyarországi klinika és egy városi kórház elektív sebészeti mutétre váró betegei körében végeztünk anonim kérdoíves felmérést 2020. augusztus 3. és december 18. között. 279 kérdoívet dolgoztunk fel, a válaszadási arány 69,7% volt. Eredmények: A koronavírus-járvány hatására a válaszadók 91,4%-ának nem változott meg a véleménye a nem konvencionális kezelésekrol, 8,2%-a bizakodóbban tekintett ezekre. A komplementer terápia betegségmegelozo hatása iránt a kitöltok 16,8%-a volt bizakodó, 25,4%-a elutasító, 57,7%-a nem formált véleményt. A válaszadók 24,7%-a vett igénybe élete során alternatív módszereket, a koronavírus-fertozés megelozésére csak a nyilatkozók 10%-a alkalmazna ilyen gyógymódokat. Kizárólag a pandémia hatására senki nem kezdett el komplementer gyógymódokat használni. A kérdoívet kitöltok 55,6%-a használt gyógynövénykészítményt élete során. A járvány ideje alatt a válaszadók 27,5%-a vett igénybe gyógynövénykészítményeket; a gyógymód alkalmazása és a vizsgált szociodemográfiai tényezok között nem találtunk összefüggést. A gyógynövények alkalmazása alacsonyabb mértéku volt a daganatos és a thromboemboliás betegek között. Következtetés: Vizsgálatunk alapján a komplementer gyógymódok használata feltehetoen a járvány miatt elrendelt korlátozásokból adódóan csökkent, a gyógynövények alkalmazása azonban nem változott lényegesen. A válaszadók tizede használt komplementer gyógymódot a koronavírus-fertozés megelozésére. Orv Hetil. 2021; 162(42): 1678-1686. INTRODUCTION: The coronavirus epidemic caused by SARS-CoV-2 from Wuhan at the end of 2019 had considerable impact on our lives. In the absence of specific therapy, some people have resorted to alternative therapies. OBJECTIVE: The aim of our study was to explore the effect of the coronavirus epidemic on the patients' attitudes toward complementary and alternative medicine. METHOD: We have performed anonymous questionnaire survey among patients of a Hungarian university hospital and a city hospital waiting for elective surgery between August 3, 2020 and December 18, 2020. We received 279 questionnaires, the response rate was 69.7%. RESULTS: As a result of the coronavirus epidemic, 91.4% of the respondents did not change their opinion about complementary and alternative treatments, 8.2% were more optimistic about them. 16.8% of respondents were optimistic, 25.4% rejected, and 57.7% did not form an opinion about the disease-preventing effect of complementary therapy. A quarter of respondents (24.7%) had used complementary therapies in their lifetime, with only 10% of respondents using such therapies to prevent coronavirus infection. As a result of the pandemic, no one started using complementary therapies. 55.6% of the respondents used a herbal preparation during their lifetime. In the course of the epidemic, a high proportion of respondents (27.5%) used herbal preparations; no correlation was found between the use of the treatment and the socio-demographic factors examined. The use of herbs was lower among cancer and thromboembolic patients. CONCLUSION: Based on our study, the use of complementary therapies presumably decreased due to the restrictions imposed in the epidemic, however, the use of herbs did not change significantly. One-tenth of the respondents used naturopathic cure to prevent coronavirus infection. Orv Hetil. 2021; 162(42): 1678-1686.

Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology.

Extracellular vesicles (EV) are considered as a promising diagnostic tool for pancreatic ductal adenocarcinoma (PDAC), a disease with a poor 5-year survival that has not improved in the past years. PDAC patient-derived 3D organoids maintain the intratumoral cellular heterogeneity, characteristic for the tumor in vivo.Thus, they represent an ideal in vitro model system to study human cancers. Here we show that the miRNA cargo of EVs from PDAC organoids largely differs among patients. However, we detected a common set of EV miRNAs that were present in matched organoids and blood plasma samples of individual patients. Importantly, the levels of EV miR-21 and miR-195 were higher in PDAC blood EV preparations than in healthy controls, albeit we found no difference compared to chronic pancreatitis (CP) samples. In addition, here we report that the accumulation of collagen I, a characteristic change in the extracellular matrix (ECM) in both CP and PDAC, largely increases EV release from pancreatic ductal organoids. This provides a possible explanation why both CP and PDAC patient-derived plasma samples have an elevated amount of CD63 + EVs. Collectively, we show that PDAC patient-derived organoids represent a highly relevant model to analyze the cargo of tumor cell-derived EVs. Furthermore, we provide evidence that not only driver mutations, but also changes in the ECM may critically modify EV release from pancreatic ductal cells.

Correlation between Expression Profiles of Key Signaling Genes in Colorectal Cancer Samples from Type 2 Diabetic and Non-Diabetic Patients.

Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight into diabetes-specific modulation of colon cancer signaling, we analyzed gene expression patterns of more than five hundred genes encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts were found to be differentially expressed in tumors of T2DM patients as compared to healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics) functional profiling tool revealed that the underlying genes can be classified into five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/ß-catenin; Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase B), and platelet activation), implying that targeted downregulation of these signaling cascades might help combat CRC in diabetic patients. Transcript levels of some of the differentially expressed genes were also measured from surgically removed diabetic and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays using the adjacent normal tissue mRNA levels as an internal control. The most significantly altered genes in diabetic tumor samples were largely different from those in non-diabetic ones, implying that T2DM profoundly alters the expression of signaling genes and presumably the biological characteristics of CRC.

Non-active implantable device treating acid reflux with a new dynamic treatment approach: 1-year results : RefluxStop™ device; a new method in acid reflux surgery obtaining CE mark.

BACKGROUND: RefluxStop™ is an implantable, non-active, single use device used in the laparoscopic treatment of GERD. RefluxStop™ aims to block the movement of the LES up into the thorax and keep the angle of His in its original, anatomically correct position. This new device restores normal anatomy, leaving the food passageway unaffected. METHODS: In a prospective, single arm, multicentric clinical investigation analyzing safety and effectiveness of the RefluxStop™ device to treat GERD, 50 subjects with chronic GERD were operated using a standardized surgical technique between December 2016 and September 2017. They were followed up for 1 year (CE-mark investigation 6-months). Primary safety outcome was prevalence of serious adverse events related to the device, and primary effectiveness outcome reduction of GERD symptoms based on GERD-HRQL score. Secondary outcomes were prevalence of adverse events other than serious adverse events, reduction of total acid exposure time in 24-h pH monitoring, and reduction in average daily PPI usage and subject satisfaction. RESULTS: There were no serious adverse events related to the device. Average GERD-HRQL total score at 1 year improved 86% from baseline (p < 0.001). 24-h pH monitoring compared to baseline showed a mean reduction percentage of overall time with pH < 4 from 16.35 to 0.80% at the 6-month visit (p < 0.001), with 98% of subjects showing normal 24-h pH. At 1 year: No new cases of dysphagia were recorded, present in 2 subjects, which existed already at baseline. Regular daily PPI usage occurred in all 50 subjects at baseline. At 1-year follow-up, only 1 subject took regular daily PPIs due to a too low placement of the device thereby prohibiting its function. None or minimal occasional episodes of regurgitation occurred in 97.8% of evaluable subjects. Gas bloating disappeared in 30 subjects and improved in 7 subjects. CONCLUSION: The new principle of RefluxStop™ is safe and effective to treat GERD according to investigation results. At 1-year follow-up, both the GERD-HRQL score and 24-h pH monitoring results indicate success for the new treatment principle. In addition, with the dynamic treatment for acid reflux, which avoids compressing the food passageway, prevalence of dysphagia and gas bloating are significantly reduced. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02759094 . Registered 3 May, 2016.

Treatment of bile duct injuries during cholecystectomy / Cholecystectomia során bekövetkezo epeútsérülések ellátása

Biliary injury is a rare but a very serious complication of laparoscopic cholecystectomy (LC). Our aim was to analyse the incidence of the biliary injuries and its therapeutic outcome on patients who underwent LC or converted LC. Our research was conducted at the 1st Department of Surgery, Semmelweis University, Budapest between 2006 and 2016, retrospectively. We analysed the LCs and converted LCs performed at our Department and as well as cases where the primary operations were conducted at other institutions but they were unable to provide the adequate therapy for the injury, thus the patients were transferred to our institution. At the 1st Department of Surgery complications occurred in 0,66% (30/4885) of all LCs. 327 converted LCs were done, complications occurred in 26 (7.95%) times. 22 patients were transferred to the 1st Department of Surgery from other institutions. Bilio-vascular injuries occurred in 61% (41/78). ERCP was performed in 25 cases with a 92% success rate. Reoperation was needed in 41% (28/41). Biliary reconstruction during the reoperation was performed via hepaticojejunostomy in 82% of all reoperations. The therapeutic solutions of LC's complications are complex. Therefore, the treatment is recommended only in institutions with appropriate experience.

[The use of herbal remedies prior to elective surgical procedures at an urban hospital and a university clinic in Hungary. Descriptive study]. / Gyógynövények használata elektív mutéti beavatkozás elott. Kérdoíves felmérés egy egyetemi klinika és egy városi kórház betegei körében.

Introduction: Herbal medicine use has become widespread in recent years. This is the first study in Hungary evaluating the use of nutraceutical agents in patients undergoing elective surgery. Aim: The aim of this study was to assess the types, frequency of use and predisposing factors of the most commonly used herbs among patients of an urban hospital and a university clinic. Method: We conducted an anonymous survey questionnaire at the Jávorszky Ödön Hospital and at the 1st Department of Surgery of Semmelweis University. A total of 1000 questionnaires were distributed. Results: In total, 612 questionnaires were returned. 34.3% of patients used herbal remedies, 19.6% of them two weeks prior to surgery. The most commonly used herbs were garlic, chamomile and lemongrass, while in the two-week period before surgery were garlic, ginger and rosehips. 58.5% of the patients had some type of co-morbidity; in this group, the use of herbal remedies was significantly more frequent. 64.4% of patients were expected to undergo general surgical intervention; in this group, the use of herbs was more popular. Analyzing the sociodemographic factors, women, people with a higher level of education, the ones that live in the capital and are over 60 years of age are more likely to use these compounds. Conclusion: One third of patients waiting for surgery used herbal remedies, one fifth of them two weeks prior to surgery. Only one fifth of the patients reported the use of these compounds to their doctors. Orv Hetil. 2020; 161(1): 17-25.

[Survival impact of diabetes and paraneoplastic thrombocytosis in women with breast cancer]. / A cukorbetegség és a daganatos thrombocytosis túlélésre gyakorolt hatásának vizsgálata emlotumoros nokben.

Introduction: Thrombocytosis and type 2 diabetes have negative effect on the survival of tumor patients. Previously, their joint effect has not been studied in breast cancer. Aim: The aim of our retrospective study was to investigate the occurrence and effects of thrombocytosis and/or type 2 diabetes in breast cancer patients who attended the 2nd Department of Internal Medicine or the 1st Department of Surgery, Semmelweis University, between 2014 and 2017. Laboratory and anamnestic data were compared at the time of tumor diagnosis between diabetic and non-diabetic groups. Survival analysis was performed to study the effects of thrombocytosis and/or type 2 diabetes. Method: 274 study participants were followed until 31 December 2018, or until their last appearance at the University, or until their death. Results: 5% of the patients had elevated platelet counts (over 400 G/L), and 52 were diabetics. Diabetics were significantly older (non-diabetics: 56.8 ± 13.8 years, diabetics: 67.8 ± 11.0 years, p<0.0001). Triple negative subtype (p = 0.0366), and T1 stage (50%) were present more often in non-diabetics. Stage T2 was more common in diabetic patients (51.9%). Type 2 diabetes was associated with a shorter survival time (p = 0.0032). Thrombocytosis did not affect patient survival. Conclusion: At the diagnosis of breast cancer, existing type 2 diabetes is associated with a more severe clinicopathological stage and shorter survival. We recommend that during routine diabetes controls, women should be made aware of the importance of mammography screening. Moreover, diabetes should be considered as a risk factor; after 30 years of age, diabetics should be screened at least every two years. Orv Hetil. 2019; 160(51): 2012-2020.

A novel percutaneous transhepatic treatment of a benign bile duct stricture - a pilot study.

AIM: To assess the effectiveness and outcome of repeated percutaneous transhepatic balloon dilatation combined with targeted intramucosal corticosteroid injection in patients with benign biliary stricture. METHODS: This single-center pilot study, conducted between February 2014 and June 2016, involved five patients with benign biliary stricture (4 men and 1 woman, mean age 58.2 years). The study included only patients in whom previous surgical or/and non-surgical treatments failed or could not be performed due to patients' medical history and local status. RESULTS: We successfully developed an alternative treatment for patients with benign biliary stricture and performed it without side effects. There were no major complications, and the only one minor complication was cholangitis. In the median follow-up period of 30.24 months (range 14.5 to 44.6 months), no re-occlusion was detected. The disease-free survival, calculated after excluding the first patient (who died of heart attack), was 34.175 months. CONCLUSION: Percutaneous transhepatic corticosteroid injection combined with balloon dilatation could provide an alternative method for the treatment of benign biliary strictures that is effective in the long term and results in positive outcomes.

[Decreasing morbidity after Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) with technical modification and patient selection]. / Speciális májmutét (Associating Liver Partition and Portal vein ligation for Staged hepatectomy, ALPPS) morbiditásának csökkentése átértékelt betegkiválasztási elvek és mutéttechnikai módosítás révén.

Introduction: Resecability of liver tumors is exclusively depending on the future liver remnant (FLR). The remnant can be hypertrophised using portal vein occlusion techniques. The latest hypertrophising method is Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS), which provides the most significant induced hypertrophy in the shortest time. Morbidity and mortality of this procedure were initially unacceptably high. Aim: Reducing complications by better patient selection and modified surgical technique. Method: The First Department of Surgery, Semmelweis University, Budapest, prefers the 'no touch' technique, instead of 'complete mobilization'. For optimizing patient selection, an international registry (including our patients' data) was established. In addition to the surgical, we collected demographic, disease, liver function, histology, morbidity (Clavien-Dindo) and mortality parameters. Volume and function measurements were performed by using CT-volumetry and 99mtechnecium-mebrofenin SPECT/CT. Data were analyzed by multivariate analysis (significance: p<0.05). Results: We performed 20 ALPPS procedures from 2012 to 2018. The relative volume increment and resectability in our department and among the 320 registry patients were 96% vs. 86% and 95% vs. 98%. Using 'no touch' technique, the Clavien-Dindo III-IV morbidity and mortality rates were significantly lower (22%-0%) than with 'complete mobilization' (63%-36%) (p<0.05). Based on the multivariate analysis of the registry patients, age over 60 years, liver macrosteatosis, non-colorectal liver tumor, >300 minutes operation time, >2 units of red blood cell transfusion, or insufficient FLR function before stage 2 were identified as independent factors influencing mortality (p<0.05). Conclusion: Mortality and morbidity of ALPPS can be reduced by proper patient selection and 'no touch' surgical technique. Orv Hetil. 2019; 160(32): 1260-1269.

Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors.

Extracellular vesicles (EVs) are membrane-surrounded structures that transmit biologically important molecules from the releasing to target cells, thus providing a novel intercellular communication mechanism. Since EVs carry their cargo in a protected form and their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. By 3D culturing, we provide evidence that colorectal cancer (CRC) patient-derived organoids, representing a state-of-the-art established and essential approach for studying human CRC, is a suitable model for EV analysis. When testing the effects of major factors promoting CRC progression on EV release in the organoid model, we observed that Apc mutation, leading to uncontrolled Wnt activation and thus to tumorigenesis in the vast majority in CRC patients, critically induces EV release by activating the Wnt pathway. Furthermore, the extracellular matrix component collagen, known to accumulate in tumorigenesis, enhances EV secretion as well. Importantly, we show that fibroblast-derived EVs induce colony formation of CRC organoid cells under hypoxia. In contrast, there was no major effect of tumor cell-derived EVs on the activation of fibroblasts. Collectively, our results with CRC and Apc-mutant adenoma organoids identify Apc mutation and collagen deposition as critical factors for increasing EV release from tumors. Furthermore, we provide evidence that stromal fibroblast-derived EVs contribute to tumorigenesis under unfavorable conditions in CRC.