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Bevezetés: A végbéldaganatok kezelési protokolljában az elmúlt évtizedekben jelentős változások történtek, melyek nagymértékben csökkentették a helyi kiújulások és a távoli áttétek számát, ezzel növelve a teljes túlélést. Az egyik jelentős előrelépést a kombinált neoadjuváns kezelés bevezetése jelentette. Módszer: A Debreceni Egyetem Sebészeti Klinikáján 2010. január 1. és 2017. december 31. között lokális neoadjuváns kemoradioterápiában részesített, majd műtéten átesett 362, rectumtumoros beteg adatainak retrospektív feldolgozását végeztük statisztikai elemzéssel. A lokális neoadjuváns kezelésre adott válasz mértékét és késői túlélési eredményeinket összehasonlítottuk az időközben megjelent nagy nemzetközi tanulmányokban közölt teljes neoadjuváns kezeléssel elért eredményekkel. Eredmények: Betegeink között 8,6%-ban tapasztaltunk teljes patológiai regressziót. A műtét időpontjára, valamint az azt követő 3 hónapon belül betegeink 10,7%-ában tapasztaltuk távoli áttét kialakulását. Vizsgálataink során a neoadjuváns kezelésre adott válasz mértéke a felismerési stádiumtól független prognosztikai faktornak bizonyult. A jobb választ adó csoportok szignifikánsan jobb túlélési eredményeket produkáltak. Következtetés: A legújabb nemzetközi tanulmányokban teljes neoadjuváns kezelés hatására a teljes patológiai választ adó betegek száma megduplázódott, a távoli áttét pedig 7%-kal kevesebb volt a lokális neoadjuváns csoporthoz képest. Betegeink 85%-a a felismerés pillanatában T3–4N+ stádiumú volt. Tekintettel a műtét pillanatában vagy 3 hónapon belül felismert távoli áttétek 10,7%-os arányára megállapítható, hogy betegeink mintegy felében eredményesebb lett volna a teljes neoadjuváns kezelés alkalmazása. Ennek megfelelően a jövőben intézetünkben is a teljes neoadjuváns protokoll szerint kívánunk eljárni. Orv Hetil. 2022; 163(30): 1196–1205.

Enhancements of hetero-fluorescence resonance energy transfer (FRET) and homo-FRET have been observed upon excitation with circularly polarized light as compared to excitation with the linearly pol...

Highly conserved 2D receptor clusters (membrane rafts) of immunological signaling molecules with MHCI and MHCII antigens as their cores have been observed in the past on the surface of T- and B-cell lines of lymphoid origin, as well as on cells from patients with colon tumor and Crohn’s disease. Conservativity is related to the ever presence of MHCI molecules. Although they are suspected to play a role in maintaining these clusters and facilitating transmembrane signaling, their exact role has been left largely enigmatic. Here we are suggesting stochastic resonance (SR), or “noise-assisted signal detection”, as a general organizing principle for transmembrane signaling events evoked by processes like immune recognition and cytokine binding taking place in these clusters. In the conceptual framework of SR, in immune recognition as a prototype of transmembrane signaling, the sea of self-peptide-MHC complexes around a nonself-peptide presenting MHC is conceived as a source of quickly fluctuating unspecific signal (“athermal noise”) serving the extra energy for amplifying the weak sub-threshold specific signal of the nonself-peptide presenting MHC. This same noise is also utilized for a readjustment of the threshold – and also the sensitivity and specificity – of detection by a closed loop feedback control of the TcR-CD8 (CD4) proximity on the detecting T-cell. The weak sub threshold specific signal of nonself-peptide presenting MHC is amplified by the superposing unspecific signals of the neighboring self peptide-MHC complexes towards the T-cell receptor as the detector. Because in a successful detection event both self- and nonself-peptides are detected simultaneously, the principle of coincidence (or lock-in) detection is also realized. The ever presence of MHC islands gets a natural explanation as a source of extra power – in a form of “athermal noise” – needed for coincidence detection and frequency encoding the evoked downstream signals. The effect is quite general, because the actual type of molecules surrounding a chief signaling molecule – like nonself-peptide holding MHC, interleukin-2 and -15 cytokine receptors (IL-2R/15R) – as the fluctuating interaction energy sources is immaterial. The model applies also for other types of signaling, such as those evoked by cytokine binding. The phenomenon of SR can also be interpreted as sampling of a low frequency, specific signal with a high frequency unspecific signal, the “noise”. Recipes for identifying other forms of SR in membrane clusters with biophysical tools are recommended.

Introduction: There have been significant changes in the treatment protocol for rectal tumors in recent decades, greatly reducing the rate of local recurrence and distant metastasis, thereby increasing overall survival. Method: We performed a retrospective processing and statistical analysis of the data of 362 patients with rectal cancer who underwent local neoadjuvant chemoradiotherapy and then underwent surgical treatment between 1 January 2010 and 31 December 2017 at the Institute of Surgery of the University of Debrecen. We compared the response rate and overall survival results of our patients with local neoadjuvant treatment to the outcomes of total neoadjuvant treatment reported by the recent large international studies. Results: We experienced complete pathological regression in 8.6% of our patients. After neoadjuvant therapy, 10.7% of our patients experienced distant metastasis at the time of the operation or within 3 months period thereafter. In our study, the rate of response to the neoadjuvant treatment was a prognostic factor independent of the stage at di-agnosis and recognition. The groups with better response produced significantly better survival results. Conclusion: The total neoadjuvant treatment doubled the number of patients with complete pathological response, and the incidence of distant metastasis was by 7% lower in both recent international studies compared to the local neoadjuvant group. 85% of our patients were T3-4N+ stage at the time of recognition. Given the 10.7% rate of dis- tant metastases detected at the time of surgery or within 3 months in our patient population, we can state that ap- proximately half of our patients would have benefited from the administration of total neoadjuvant therapy which produced better outcomes. Based on this conclusion, we decided to introduce the total neoadjuvant therapy protocol in our department for treatment of patients with advanced rectal tumors.Bevezetés: A végbéldaganatok kezelési protokolljában az elmúlt évtizedekben jelentős változások történtek, melyek nagymértékben csökkentették a helyi kiújulások és a távoli áttétek számát, ezzel növelve a teljes túlélést. Az egyik jelentős előrelépést a kombinált neoadjuváns kezelés bevezetése jelentette. Módszer: A Debreceni Egyetem Sebészeti Klinikáján 2010. január 1. és 2017. december 31. között lokális neoadjuváns kemoradioterápiában részesített, majd műtéten átesett 362, rectumtumoros beteg adatainak retrospektív feldolgozását végeztük statisztikai elemzéssel. A lokális neoadjuváns kezelésre adott válasz mértékét és késői túlélési eredményeinket összehasonlítottuk az időközben megjelent nagy nemzetközi tanulmányokban közölt teljes neoadjuváns kezeléssel elért eredményekkel. Eredmények: Betegeink között 8,6%-ban tapasztaltunk teljes patológiai regressziót. A műtét időpontjára, valamint az azt követő 3 hónapon belül betegeink 10,7%-ában tapasztaltuk távoli áttét kialakulását. Vizsgálataink során a neoadjuváns kezelésre adott válasz mértéke a felismerési stádiumtól független prognosztikai faktornak bizonyult. A jobb választ adó csoportok szignifikánsan jobb túlélési eredményeket produkáltak. Következtetés: A legújabb nemzetközi tanulmányokban teljes neoadjuváns kezelés hatására a teljes patológiai választ adó betegek száma megduplázódott, a távoli áttét pedig 7%-kal kevesebb volt a lokális neoadjuváns csoporthoz képest. Betegeink 85%-a a felismerés pillanatában T3–4N+ stádiumú volt. Tekintettel a műtét pillanatában vagy 3 hónapon belül felismert távoli áttétek 10,7%-os arányára megállapítható, hogy betegeink mintegy felében eredményesebb lett volna a teljes neoadjuváns kezelés alkalmazása. Ennek megfelelően a jövőben intézetünkben is a teljes neoadjuváns protokoll szerint kívánunk eljárni. Orv Hetil. 2022; 163(30): 1196–1205.

Absztrakt: Bevezetés: Akut pancreatitis miatti necrectomiát ideálisan a betegség kezdetétől számított 4–6. héten javasolt elvégezni, amikor az ún. demarkált necrosis (walled-off pancreatic necrosis –WOPN) már kialakult. A szerzők ismertetik a kiterjedt WOPN miatt végzett sebészi transgastricus necrectomiák során nyert tapasztalataikat. Betegek és módszer: Kiterjedt WOPN miatt 2012. január 1-től 2017. december 31-ig terjedő időszakban 17 (12 férfi, 5 nő, átlag életkor 64,00 ± 15,14 év) betegnél végeztek sebészi transgastricus necrectomiát. Valamennyi betegnél a műtétet megelőzően konzervatív és szemikonzervatív kezelés történt átlagosan 61,00 ± 33,47 napig. A WOPN mérete átlagosan 14,00 ± 5,23 cm volt és valamennyi esetben a retrocolicus, retroduodenalis terekbe is beterjedt. A necrosis minden esetben bakteriálisan kontaminált volt. Eredmények: A műtétekkel kapcsolatos szövődmény nem volt. Az ápolási napok száma a műtétet követően 10,00 ± 3,08 nap volt. A mortalitás 5,9% volt. Késői műtét vagy egyéb beavatkozás pseudocystaképződés, vagy pancreas fistula miatt nem volt. Két betegnél a WOPN és a gyomor közötti anastomosis-endoszkópos tágítása és öblítése történt lázas állapot miatt. Frissen kialakult diabetest nem, a meglévő súlyosbodását 6,3%-ban észleltük. Következtetés: A kiterjedt, fertőzött demarkált necrosis kezelésében a sebészi transgastricus necrectomia jó eredménnyel alkalmazható. A műtét előnye, hogy a necrectomia után nem alakulhat ki külső pancreas sipoly és pseudocysta.

Those who ever used a stream-in-air flow cytometer and when running their most interesting samples they just got an air bubble...

Anatomically independent tumor foci represent biologically distinct neoplasias, potentially featured by different progressivity and treatment responsiveness. To demonstrate the biological complexity, a metastatic colon adenocarcinoma patient originally presenting with four independent primary tumors of the right colon half and altogether eight distant metastases was followed by molecular testing. Next-generation sequencing results highlighted the mutational profile of the individual primaries and the dynamics of the different gene variants observed during follow-up. The four primary colon tumors presented with four different KRAS genotypes, one of them with a wild-type and three with pathogenic variants, without overlap. These were the following: c.35G > A; p.Gly12Asp with 40.6% variant allele frequency (VAF); c.34G > T; p.Gly12Cys with 16.2% VAF and c.35G > T; p.Gly12Val with 15.1% VAF. In metastatic tumors, with one exception where no mutation was detected, only the KRAS c.34G > T; p.Gly12Cys mutation could be detected. TP53 gene variants were variable in the primary tumors, with a single dominant variant evolving in the follow-up metastases (c.820G > T; p.Val274Phe). Genetic profiling of individually developing synchronous malignancies uncovers the clonal relations of metastatic tumors. NGS gene panels provide a solution to follow the dynamics of key oncogene variants during the course of the disease and greatly contribute to therapy optimization.

About the common features behind the mechanism of molecular rotors, photoswitching of engineered fluorescent proteins (GFPs), and Forster resonance energy transfer (FRET). Besides explining the common mechanism, we also offer a new method for increasing sensitivity of viscosity determination even in living cells, by the combination of polarization energy transfer (polFRET) method and a molecular rotor dye either as an energy donor or acceptor.

Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening still does not belong to standard of care in Hungary. In this study, we performed a comprehensive screening in order to identify patients with mismatch repair (MMR) mutation between the years of 2011 and 2014. Identified mutations were compared with those already published in the international databases.Patients who underwent treatment for colorectal cancer at the Surgical Institute of the University of Debrecen were screened using the modified Amsterdam and Bethesda Criteria. Immunohistochemistry and microsatellite analyses were performed in order to identify possible mutation carrier cases. Suspicious cases underwent DNA sequencing to detect mutations in the mismatch repair genes (hMLH1, hMSH2).All together 760 colorectal cancer patients were screened. A total of 28 patients were identified as possible MMR mutation carrier and underwent further genetic evaluation. Pathogenic sequence variants of the MMR gene were found in 5 patients. Hypermethylation of the promoter region of the hMLH1 gene was identified in 2 patients. Two out of the 5 pathogenic sequence variants of the MMR gene were first identified by our group while other 2 mutations were previously published as possible founder mutations.Identification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome.

Primary pancreatic hydatid disease is extremely rare. Diagnosis of the disease is difficult because hydatid cysts can be confused with a pseudocyst or neoplastic cystic diseases. Authors report a case of a surgically treated hydatid disease of the uncinate process of pancreas. In a 34-year-old patient with minor symptoms, a cystic disease of the pancreas was accidentally identified. CT scan revealed a multivesicular cystic mass with a maximum of 13-cm diameter and with a calcificated wall. During laparotomy, the uncinate process of pancreas was resecated and the cystic lesion was enucleated. Patient was recovered without complications and recurrence of the disease. There must be a suspicion of hydatid disease when cysts are identified in good conditioned, asymptomatic patients, or in case of wall calcification or multivesicular cysts revealed by radiological images. Surgical procedures are recommended in uncertain diagnoses too, because differentiation preoperatively between cystic pancreatic lesions is often impossible.

A quick and robust approach for the simultaneous detection of donor and acceptor anisotropies and FRET efficiency is presented based on changing the angle of polarization of the exciting light in a single-laser dual channel ratiometric detection scheme of FRET in a flow cytometer. The convenience of the method lies in that for the extra assessment of anisotropies it does not necessitates alteration of the detection side of the optics conventionally used in measuring FRET in the steady state. The detection of anisotropies is pushed to the side of excitation where anisotropies are enabled by just a few sequential measurements at different polarization angles of the exciting light. The power of the method is illustrated by comparing results on the homo-associations and inter-subunit FRET on the MHCI receptor on the surface of Kit-225K6 T cells obtained with the angle-resolved approach to those obtained by the dual-T format approach as a validation. In flow conditions, but not in imaging microscopy, a minor drawback of this method is that due to the sequential nature of anisotropy detection, the mutual cell-by-cell correlations of anisotropies with each other and with FRET are lost. The merit of the approach is that besides the degree of molecular associations probed by the FRET efficiency, information can also be gained on the rotational dynamics and extent of homo-FRET prevailing in the the donor and acceptor dye systems during the hetero-FRET process, and as a consequence, orientation factor for FRET can also be estimated. FRET efficiencies at the different polarization angles are shifted depending on the donor and acceptor anisotropy, enabling quantitation of anisotropy changes by FRET efficiency. Attention is called for polarization biases when using even depolarized excitation and detecting not concerning with fluorescence polarization. When established in polarization contrast microscopy, the approach might be applied for also controlling FRET. A new formula for the determination of the sensitivity calibration factor for FRET α (or Get) has also been deduced based on the donor and acceptor anisotropies.

Abstract: Introduction: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. Aim: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. Materials and method: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. Results: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182–1187.

Abstract: Introduction: The eventrated, giant abdominal wall hernias represent a considerable challenge in our practice. Presently, preoperative evaluation of the musculo-aponeurotic elements of the abdominal wall by CT imaging is not part of routine planning of surgery. Aim: Evaluation of the abdominal wall hernia progression in time. Moreover, follow up the changes of the abdominal wall structures following series of intraabdominal surgeries. Method: Abdominal CT imaging were performed on the 1st, 3rd, 6th, 12th, 18th, and 24th postoperative months after the primary series of surgeries in the cases of 12 patients, whose reconstructive surgeries were not possible. A prospective data collection was applied. Changing of the bilateral rectus muscle morphology, the evolution in time of the midline gap, and the progressive dynamism of the midline wall defects were determined. Results: A characteristic and progressive midline defect enlargement could be settled. Data analysis yielded that the combined width of the bilateral rectus muscles is sufficient to cover the midline abdominal wall defect, although there is an “optimal” timeframe for performing the intervention. Conclusion: CT evaluation of abdominal wall prior to reconstructive surgeries of loss of abdominal wall domain has a strong significance on determining and designing the adequate surgical procedure. Orv. Hetil., 2017, 158(7), 257–263.

Highlights • This is the first applied autologous dermal graft for eventrated hernia in an emergency case. • Terminal ileum and ascending colon were perforated into the hernia sac causing dirty operating field. • It was impossible to close the 223 cm2 gap with sutures, biological mesh was not available. • Specially prepared grafts were applied to reconstruct the gap in a double- layer tension free fashion. • No hernia recurrency was observed 8 months after the surgery., Introduction Double-layer dermal grafts are used for the management of complicated abdominal wall hernias in obese, high risk patients. The method has not yet been used in case of emergency in septic/dirty environment. Case report A 76-year old female patient (BMI 36.7 kg/m2) was admitted with mechanical bowel obstruction and sepsis caused by a third time recurred, incarcerated and eventrated abdominal wall hernia. During the emergency surgery perforation of the terminal ileum and the ascending colon was detected, along with a feculent peritonitis and extended abdominal wall necrosis. Extended right hemicolectomy and necrectomy of the abdominal wall were performed. The surgery resulted in an abdominal wall defect measuring 223 cm2, for the management of which direct closure was not possible. Using a specific method, an autologous dermal graft was prepared from the redundant skin. The first dermal graft was placed under the abdominal wall with 5 cm overlap, and the second layer was placed onto the first layer with 3 cm overlap in a perforated fashion. The operating time was 250 min. No significant intra-abdominal pressure elevation was measured. No reoperation was performed. On the fifth postoperative day, the patient was mobilised. She was discharged in satisfactory general condition on the 18th postoperative day. There is no recurrent hernia 8 months after the surgery. Discussion Abdominal wall reconstruction was possible in a necrotic, purulent environment by using a de-epithelised autologous double layer dermal graft, without synthetic or biological graft implantation. The advantage of the procedure was cost-effectivity, and the disadvantage was that only in an obese patient is the sufficient quantity of dermal graft available. Conclusion A homogeneous internal and perforated outer dermal graft was suitable for bridging the abdominal gap in the case of an obese, high risk patient. Autologous dermal grafts can be a safe and feasible alternative to biological meshes in emergency abdominal wall surgeries. Evaluation of a case series can be the next cornerstone of the method described above.

In severe acute pancreatitis the timing of necrosectomy is ideally should be postponed 4-6 weeks after the onset of the disease when the walled-of pancreatic necrosis (WOPN) has developed. The authors present their experience with open transgastric necrosectomy for extended WOPN.The authors performed 17 (12 male, 5 female with a mean age of 61.6 ± 15.1 years) open transgastric necrosectomies for extended WOPN in a period of 1, January 2012 and 31, December 2017. Before the operations conservative and semiconservative therapy was used for an average of 74.6 ± 83.1 days. The mean size of the WOPNs was 13.8 ± 5.2 cm with localisation of the retrocolic and retroduodenal regions. All necroses were septic.Complications related to the operation were not observed. The mean time of hospitalization after the surgery was 11.6 ± 12.8 days. The mortality rate was 5.9%. Late operation or other interventions for pseudocyst or pancreas fistula formation was not performed. Two patients needed endoscopic dilatation with lavage in the early postoperative period because of fever. New diabetes mellitus was not observed but worsening of previously existed diabetes developed in 6.3% of the cases.The open transgastric necrosectomy is safe and effective for extended WOPN. The advantage of this type of necrosectomy is the prevention of pancreatic pseudocyst and fistula formation.Absztrakt: Bevezetés: Akut pancreatitis miatti necrectomiát ideálisan a betegség kezdetétől számított 4–6. héten javasolt elvégezni, amikor az ún. demarkált necrosis (walled-off pancreatic necrosis –WOPN) már kialakult. A szerzők ismertetik a kiterjedt WOPN miatt végzett sebészi transgastricus necrectomiák során nyert tapasztalataikat. Betegek és módszer: Kiterjedt WOPN miatt 2012. január 1-től 2017. december 31-ig terjedő időszakban 17 (12 férfi, 5 nő, átlag életkor 64,00 ± 15,14 év) betegnél végeztek sebészi transgastricus necrectomiát. Valamennyi betegnél a műtétet megelőzően konzervatív és szemikonzervatív kezelés történt átlagosan 61,00 ± 33,47 napig. A WOPN mérete átlagosan 14,00 ± 5,23 cm volt és valamennyi esetben a retrocolicus, retroduodenalis terekbe is beterjedt. A necrosis minden esetben bakteriálisan kontaminált volt. Eredmények: A műtétekkel kapcsolatos szövődmény nem volt. Az ápolási napok száma a műtétet követően 10,00 ± 3,08 nap volt. A mortalitás 5,9% volt. Késői műtét vagy egyéb beavatkozás pseudocystaképződés, vagy pancreas fistula miatt nem volt. Két betegnél a WOPN és a gyomor közötti anastomosis-endoszkópos tágítása és öblítése történt lázas állapot miatt. Frissen kialakult diabetest nem, a meglévő súlyosbodását 6,3%-ban észleltük. Következtetés: A kiterjedt, fertőzött demarkált necrosis kezelésében a sebészi transgastricus necrectomia jó eredménnyel alkalmazható. A műtét előnye, hogy a necrectomia után nem alakulhat ki külső pancreas sipoly és pseudocysta.

A new method of flow cytometric dual-laser FRET calibration is presented based on an information theoretical description of the FRET signals. This method belongs to the so called two-channel or ratiometric FRET methods, whose crucial and common element is the determination of a calibration factor called α (alpha- or G-factor), to place the detected FRET signal on the absolute scale of efficiency. Generally α is determined by extra cell samples labeled with only donor and only acceptor, where the donor-acceptor ratio is known. Alternatively, when the donor-acceptor ratio is not known, standard donor-acceptor FRET pairs of known FRET efficiency can also be used for determining α. In our approach, there is no need for extra information presented by the known acceptor-to-donor ratio or the standard FRET efficiency. Our approach proceeds solely on the signals of the interested FRET-pair applying only a single FRET sample, not necessitating extra ones. The missing information of extra cell samples is replaced by an information theoretic balance equation written for the actual FRET sample. Our method has been proven to be robust, inasmuch as both donor and acceptor appear in adequate levels in the FRET sample used for finding α.

Introduction: Indication and timing of allograft nephrectomy is still uncertain in some cases. Aim: The aim of the authors was to summarize their experience with graftectomies. Method: Data from patients who underwent kidney transplantation between January 1, 2004 and December 31, 2015 were retrospectively analyzed. Frequency, indications, timing, complications as well as early and late allograft nephrectomies were reviewed. Results: From 480 renal transplants, 55 graftectomies were performed (11%). Frequent indications included chronic allograft nephropathy (47%), arterial blood supply complications (13%), ureter complications (9%). 22 cases (40%) of allograft nephrectomies were urgent while 33 cases (60%) were elective. 24% of graftectomies were performed within 30 days after transplantation and 76% thereafter. Conclusions: The main indications for early graftectomies were arterial complications (31%) and chronic allograft nephropathy (62%) in cases of late graftectomies. The majority of the graftectomies were elective. Leading indication was chronic allograft nephropathy. Early and late graftectomies have different characteristics. Orv. Hetil., 2016, 157(24), 964–970.

Dual laser flow cytometric energy transfer (FCET)--elaborated by Trón et al. in 1984--is an efficient and rapid way of measuring FRET on large cell populations. FRET efficiency and the donor and acceptor concentrations are determined from one donor and two acceptor signals. In this communication this method is extended towards the domain of receptor dynamics by the detection of polarized components of the three intensities. By enabling a complete description of the proximity and dynamics of FRET-systems, the new measuring scheme allows a more refined description of both the structure and dynamics of cell surface receptor clusters at the nano-scale and beyond. Associated donor fraction, limiting anisotropy and rotational correlation time of the donor, acceptor anisotropy and cell-by-cell estimation of the orientation factor for FRET (κ2) are available in the steady state on a single FRET sample in a very rapid and statistically efficient way offered by flow cytometry. For a more sensitive detection of conformational changes the "polarized FRET indices"--quantities composed from FRET efficiency and anisotropies--are proposed. The method is illustrated by measurements on a FRET system with changing FRET-fraction and on a two donor-one acceptor-system, when the existence of receptor trimers are proven by the detection of "hetero-FRET induced homo-FRET relief", i.e. the diminishing of homo-FRET between the two donors in the presence of a donor quencher. The method also offers higher sensitivity for assessing conformational changes at the nano-scale, due to its capability for the simultaneous detection of changes of proximity and relative orientations of the FRET donor and acceptor. Although the method has been introduced in the context of FRET, it is more general: It can be used for monitoring triple-anisotropy correlations also in those cases when FRET actually does not occur, e.g. for interactions occuring beyond the Förster-distance R0. Interpretation of κ2 has been extended.

Sensitivity of FRET in hetero- and homo-FRET systems on the photoselected orientation distribution of donors has been proven by using polarized and depolarized light for excitation. FRET as well as donor and acceptor anisotropies have been simultaneously measured in a dual emission-polarization scheme realized in a conventional flow cytometer by using single laser excitation and applying fluorophore-conjugated mAbs against the MHCI and MHCII cell surface receptors. Depolarization of the originally polarized light have been achieved by using crystal depolarizers based on Cornu's principle, a quarter-wave plate for circular polarization, and a parallel beam splitter acting as a diagonal-polarizer for dual-polarization excitation. Simultaneous analysis of intensity-based FRET efficiency and acceptor depolarization equivocally report that depolarization of light may increase FRET in an amount depending on the acceptor-to-donor concentration ratio. Acceptor depolarization turned to be more sensitive to FRET than donor hyper-polarization and even than intensity-based FRET efficiency. It can be used as a sensitive tool for monitoring changes in the dynamics of the donor-acceptor pairs. The basic observations of FRET enhancement and increased acceptor depolarization obtained for hetero-FRET are paralleled by analog observations of homo-FRET enhancements under depolarized excitation. In terms of the orientation factor for FRET, the FRET enhancements on depolarization in the condition of the macroscopically isotropic orientation distributions such as those of the cell surface bound fluorophores report on the presence of local orientation mismatches of the donor and acceptor preventing the optimal FRET in the polarized case, which may be eliminated by the excitation depolarization. A theory of fluorescence anisotropy for depolarized excitation is also presented.

The effects of donor homo-Forster resonance energy transfer (homo-FRET) taking place in hetero-FRET systems is described in the context of hetero-FRET detection via donor and acceptor fluorescence anisotropies in cell surface receptor clusters. Donor homo-FRET can influence both the efficiency of detection as well as the magnitude of the detectable hetero-FRET. A 4-fold polarized FRET detection scheme-tetrapolarization FRET (4polFRET)-is proposed not only for discriminating the effects of homo-FRET from those of hetero-FRET, but also for correlating homo-associations of the donors and acceptors at different donor-acceptor distances, even beyond the critical Forster distance for hetero-FRET ( R0). The method is based on suppressing homo-FRET at the donor side with red-edge excitation. After the anisotropy effects of physical rotation and homo-FRET were separated by site-selective spectroscopy, the magnitude of the effect of homo-FRET on hetero-FRET has been estimated. It has been found significant, offering a new sensitive technique for detecting conformational dynamics via the homo-FRET mediated component of hetero-FRET, the "homo-FRET enhanced hetero-FRET" or "homo-FRET gate". The method is realizable in flow, as well as in image cytometry equipped with polarization detecting facility.

LB

Inhomogeneous broadening and red-edge effects have been detected on a highly mobile system of fluorescently conjugated mAbs targeted to cell surface receptors. By exploiting site-selective spectroscopy and the characteristic loss of homo-FRET on increasing excitation and decreasing emission wavelengths, contributions of physical rotation and homo-FRET to the depolarization of fluorescence anisotropy have been separated. Absolute homo-FRET efficiency has been determined by ratioing two anisotropies: a homo-FRET-sensitive one, which is excited at the absorption main band and detected at the long wavelength region of emission, and a homo-FRET-insensitive one, which is excited at the long wavelength region of absorption and detected at the short wavelength region of emission. Because the anisotropies are simultaneously detected in a unified detection scheme of a dual T-format arrangement, the method is applicable for the real-time tracking of dynamical changes of physical rotations and proximities. The utility of the method is demonstrated in the context of the MHCII molecule and the heavy and light chains of the MHCI molecule, a system of three receptors with well-characterized close mutual proximities. Although the method is presented for a flow cytometer, it can also be realized in a fluorescence microscope capable for dual-laser excitation and dual-anisotropy detection.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering.We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years.To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out.A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182-1187.

The eventrated, giant abdominal wall hernias represent a considerable challenge in our practice. Presently, preoperative evaluation of the musculo-aponeurotic elements of the abdominal wall by CT imaging is not part of routine planning of surgery.Evaluation of the abdominal wall hernia progression in time. Moreover, follow up the changes of the abdominal wall structures following series of intraabdominal surgeries.Abdominal CT imaging were performed on the 1st, 3rd, 6th, 12th, 18th, and 24th postoperative months after the primary series of surgeries in the cases of 12 patients, whose reconstructive surgeries were not possible. A prospective data collection was applied. Changing of the bilateral rectus muscle morphology, the evolution in time of the midline gap, and the progressive dynamism of the midline wall defects were determined.A characteristic and progressive midline defect enlargement could be settled. Data analysis yielded that the combined width of the bilateral rectus muscles is sufficient to cover the midline abdominal wall defect, although there is an "optimal" timeframe for performing the intervention.CT evaluation of abdominal wall prior to reconstructive surgeries of loss of abdominal wall domain has a strong significance on determining and designing the adequate surgical procedure. Orv. Hetil., 2017, 158(7), 257-263.

Keywords: fluorescence lifetime; flow cytometry; time-correlated single photon counting (TCSPC); burst integrated fluorescence lifetime (BIFL); time-tagged time-resolved (TTTR); fluorescence resonance energy transfer (FRET)

Complicated incisional hernias (at least one time recurrent and/or multilocular and/or infected synthetic mesh) still represent a significant problem.Presentation of operating techniques desribed so far, as well as publication of a novel procedure and results invented by the authors.Between 01/2011 and 09/2015, 41 patients with recurrent and/or infected incisional hernias with or without entero- and subcutaneous fistulas were operated using the method of the s.c. double-layer autologous tension free dermal flap technique. An accurate follow-up method and a continuous registration of the results was conducted in case of every patient. The body mass index (BMI) and presence of diabetes mellitus (DM) were distinguished factors out of the patients' clinical data. Surgical complications, bulking or laxity, recurrence and the patients' satisfactory index - among other things - were recorded considering the procedure. Patients' clinical data and results: Average age was 59.2 years (13 male / 28 female) in the cohort. 1, 2, 3 times recurrent incisional hernias had 12, 23, 6 patients, respectively. Average BMI was 32,1 kg/m2. 12 patients were treated with type II diabetes. 13 patients had entero- or subcutaneous fistulas and/or infected synthetic meshes at the time of operations. Average follow-up time was 32 months (2-58 months). Seroma formation was registered in 13 cases (31.7%). Fistula formation was registered in one case (2.4%). Bulking formation or laxity was observed in 3 patients (7.3%) and recurrence was noticed in 3 patients (7.3%), 13, 17 and 19 months later in the postoperative period. All the entero- and subcutaneous fistulas developed prior to the last procedure were completely healed. There was no lethal outcome.The method developed by the authors is recommended and suitable for the solution to complicated and/or infected incisional abdominal wall hernias especially in cases of obese (BMI ≥ 25 kg/m(2)) and diabetic, high risk patients. After acquiring the precise operative technique, the method is safe, feasible and it comes along with lower complication and recurrence rate, compared to other applied and well established ones. Further clinical trials need to be conducted in the future in order to be evaluated definetely this procedure.

Indication and timing of allograft nephrectomy is still uncertain in some cases.The aim of the authors was to summarize their experience with graftectomies.Data from patients who underwent kidney transplantation between January 1, 2004 and December 31, 2015 were retrospectively analyzed. Frequency, indications, timing, complications as well as early and late allograft nephrectomies were reviewed.From 480 renal transplants, 55 graftectomies were performed (11%). Frequent indications included chronic allograft nephropathy (47%), arterial blood supply complications (13%), ureter complications (9%). 22 cases (40%) of allograft nephrectomies were urgent while 33 cases (60%) were elective. 24% of graftectomies were performed within 30 days after transplantation and 76% thereafter.The main indications for early graftectomies were arterial complications (31%) and chronic allograft nephropathy (62%) in cases of late graftectomies. The majority of the graftectomies were elective. Leading indication was chronic allograft nephropathy. Early and late graftectomies have different characteristics.

The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant.The authors retrospectively compared the trends.Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015).The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m(2) increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively.Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards.

Introduction: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. Aim: The authors retrospectively compared the trends. Method: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). Results: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m2 increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. Conclusions: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards. Orv. Hetil., 2016, 157(24), 925–937.

Stage-adapted surgery guarantees the best outcome for patients with gastric cancer. Successful identification of lymph node involvement may help to reduce the number of extended lymphadenectomies. Preoperative diagnostic tools have low sensitivity and specificity for determining lymph node involvement. Evaluation of sentinel lymph nodes (SLNs) intraoperatively has good results, while the accuracy of the Maruyama computer program (MCP) is controversial.We investigated 40 patients by the Maruyama computer model and labeled lymph nodes with blue dye for SLN mapping. To compare the probability calculations by MCP and the results of SLN mapping, we had to define a cutoff level; we did this using receiver-operating characteristics analysis. Sentinel lymph nodes were examined in frozen sections intraoperatively and by standard hematoxylin and eosin staining postoperatively.A total of 795 lymph nodes were removed and examined. The Maruyama computer model had a sensitivity of 91.3 %, specificity of 64 %, and accuracy of 80 % by the best cutoff point. The false-negative rate was 8.7 %. The sensitivity of SLN mapping was 95.7 %, the false-negative rate was 4.3 %, and the specificity was 100 %. The accuracy of SLN mapping was 97.4 %. Only the sensitivity of MCP and SLN biopsy was proven equivalent.Our results suggest that intraoperative SLN examination is superior to preoperative estimation with the MCP. Correct definition of lymph node involvement helps in planning the best stage-adapted surgery in gastric cancer.

Absztrakt Bevezetés: A sebészeti sebgyógyulási zavar (Surgical Site Infection, SSI) a harmadik leggyakoribb nosocomialis fertőzés, az összes infekciót tekintve megközelíti a 14–16%-ot. A jelentős költségvonzattal is járó magas infekciós ráta javítása, valamint a triclosannal bevont varrófonalakról szóló pozitív nemzetközi tanulmányok arra ösztönöztek, hogy randomizált vizsgálat keretében győződjünk meg a triclosan hatásosságáról – a magas infekciós rátájú – colorectalis műtétek kapcsán. Módszer: Hét sebészeti osztály bevonásával indítottuk prospektív, randomizált, multicentrikus vizs-gálatunkat, mely során triclosannal bevont (PDS plus®), valamint azonos anyagból készült, nem bevont varróanyag (PDS II®) hasfali varratként való összehasonlítását végeztük a sebfertőzés gyakoriságát illetően elektív colorectalis műtéteket követően. A vizsgálat alapvető célja a posztoperatív sebinfekció jelenlétének, az azt kiváltó kórokozók törzseinek, valamint az SSI okozta többletköltségeknek a meghatározása volt. Eredmények: 485 beteget randomizáltunk, ebből 47 (12,5%) esetben fordult elő SSI, 23 (12,23%) beteg a triclosanos csoportból (n = 188), 24 (12,18%) beteg pedig a nem bevont csoportból (n = 197) került ki (p = 0,982). 13 (27,66%) betegnél alakult ki késői sebgyógyulási zavar, ebből 4 (8,51%) esetben a triclosanos fonalat és 9 (19,15%) esetben a nem bevont fonalat (p = 0,041) alkalmaztuk. Nem találtunk különbséget a colon- és a rectumműtéteket követő SSI aránya között. Következtetések: A triclosan Gram-pozitív baktériumok elleni, korábbi tanulmányokban bizonyított hatását – a kis esetszám miatt – nem tudtuk bizonyítani. Szintén nem tudtunk igazolni a triclosan hatékonyságát a Gram-negatív colonflóra esetében sem. A retrospektív vizs-gálatunkhoz viszonyítva sebinfekciós eredményeink 50%-os javulást mutattak, függetlenül attól, hogy a PDS loop be volt-e vonva triclosannal, vagy sem. Az SSI előfordulásának szempontjából az operatív faktorok lényegesebbnek bizonyultak, mint a beteg rizikófaktorai/kísérőbetegségei. Tanulmányunk igazolta, hogy az SSI megnyújtja a hospitalizációt, és jelentősen növeli a kezelési költségeket.

Absztrakt Bevezetés: Gyomorrák miatt operált betegek közel 40 százaléka feleslegesen esik át kiterjesztett nyirokcsomó-dissectión R0 resectio során. Sikeres sentinelnyirokcsomó-biopszia segíthet elkerülni ezt, így csökkenthető a műtéti morbiditás és mortalitás. A gyomortumorok őrszemnyirokcsomójának jelölésére számos metódus ismert. Anyag és módszerek: 40 betegnél történt gyomorresectio vagy teljes gyomoreltávolítás sentinel-nyirokcsomó kék festékkel történő jelölésével és módosított D2-es lymphadenectomiával. 16 betegnél (A csoport) a festék injektálását endoscopos végezte submucosusan, míg 24 beteg (B csoport) őrszemnyirokcsomó-jelölése a sebész által történt subserosusan. Az intraoperatív jelölést és a lymphadenectomiát egyazon sebész felügyelte. Eredmények: A 40 beteg vonatkozásában összesen 795 nyirokcsomó került eltávolításra és szövettani vizsgálatra. Az A csoportban betegenként átlagosan 4,1, a B csoportban 4,8 nyirokcsomó jelölődött meg a kék festékkel. A találati arány 100%-nak (A csoport), illetve 96%-nak (B csoport) bizonyult. Az álnegatív arány az endoscopos jelölés során 0%-nak, míg a subserosus jelölés után 7,7%-nak igazolódott. A submucosus jelölés specificitása és szenzitivitása egyaránt 100%, a subserosus vizsgálat specificitása 100%, szenzitivitása 92,3% lett. A kétfajta jelölési metódus 90% konfidencia-intervallumnál ekvivalensnek bizonyult a találati arány, a szenzitivitás és a specificitás tekintetében. Következtetések: Eredményeink alapján a kizárólagosan kék festékkel történő őrszemnyirokcsomó-jelölés biztonságos eljárásnak bizonyult, magas specificitása és szenzitivitása miatt alkalmazhatónak tűnik T1-es és T2-es tumorok műtétei során.

Clusters of MHCI, ICAM-1, CD44, CD59, IL-2R, and IL-15R molecules have been studied on the surface of CD4(+) T-cells from peripheral blood and lymph nodes of patients in Crohn's disease and healthy individuals as controls by using a dual-laser flow cytometric fluorescence resonance energy transfer (FRET) technique and fluorescently stained Fabs. When cells from patients in Crohn's disease are compared to those of controls, the surface expression level for the MHCI reduced by ∼45%, for CD44 enhanced by ∼100%, and for IL-2Rα, IL-15Rα, and common γ(c) enhanced by ∼50%, ∼70%, and ∼130%, respectively. Efficiencies of FRET monitoring homoassociation for the MHCI and CD44 reduced, that for IL-2Rα enhanced. While efficiencies of FRET monitoring the association of γ(c) and ICAM-1 with the MHCI reduced, those monitoring association of IL-2/15Rα, CD44, and CD59 with MHCI enhanced. Efficiencies of FRET measured between the MHCI and IL-2Rα, IL-15Rα differently enhanced to the advantage of IL-15Rα, the one measured between γ(c) and IL-2Rα reduced, suggesting modulations in the strength of interaction of MHCI with IL-2R, IL-15R, and γ(c). The increases in density of surface bound cTx and in the associations of the receptors with the G(M1)-ganglioside lipid molecules suggest stronger lipid raft interactions of the receptors. The observed alterations of MHC-rafts in Crohn's disease--summarized in models of receptor patterns of diseased and control cells--may have functional consequences regarding signaling by the raft components.

Az enyhe akut pancreatitis kezelése alapvetően konzervatív, míg súlyos esetekben a sebészi kezelésnek jelentős szerepe van. Módszer: A szerzők az utóbbi 10 évben megjelent, a műtét kérdéseit taglaló közlemények alapján elemzik a sebészi kezelés indikációit, időzítését és a műtét technikai kérdéseit. Eredmények/következtetések: A steril pancreasnecrosis csak ritkán, a szeptikus necrosis azonban műtéti indikációt képez, ha a konzervatív kezelés eredménytelen. A terápiarezisztens sokszervi elégtelenség, a súlyos hasi kompartmentszindróma és egyéb sebészi szövődmény, mint a vérzés, perforáció is műtéti beavatkozást tesz szükségessé. Pancreatitist okozó epekövesség talaján kialakult cholestasis esetén sürgős endoszkópos sphincterotomia és később cholecystectomia javasolt. Pancreasnecrosis esetén a műtét ideális időpontja a betegség kezdetétől számított 21. nap utánra tehető, mivel a „korai” műtétek szövődmény- és halálozási aránya magas. Fontos a gondos necrectomia, amelynek a retrocolicus és retroduodenalis terekre is ki kell terjednie. A nyitott has kezelésének több a szövődménye, ezért csak válogatott esetekben javasolják. A műtétet posztoperatív bursa omentalis lavage-zsal érdemes kiegészíteni. Orv. Hetil., 2010, 41, 1697–1701.

Absztrakt A perioperatív antithromboticus megelőzés, illetve a tartósan antithromboticus kezelésben részesülő betegek műtéti ellátása (ún. áthidaló kezelés) mind a vénás thromboemboliák (VTE) megelőzése, mind a műtéti vérzéses szövődmények számának és súlyosságának csökkentése szempontjából kiemelt jelentőségű feladat. A nagyszámú irodalom és a nyomukban született ajánlások – érthető módon – elsősorban a hagyományos, általában többnapos hospitalizációt igénylő, nyílt műtétek különféle formáival foglalkoznak, sokkal kevesebb figyelem jutott ez ideig az egynapos sebészet során fellépő VTE kockázataira, illetve megelőzésére. A szerzők áttekintik az egynapos sebészeti eljárásokhoz kapcsolódó VTE epidemiológiáját, ismertetik az új nemzetközi, illetve a 4. Magyar Antithrombotikus Irányelv ajánlásait. Ezek lényege: amennyiben a műtétre kerülő betegnél egyidejűleg szerzett vagy veleszületett thrombosisra hajlamosító tényezők igazolhatók, az általános, nem gyógyszeres thrombosismegelőzési módszereken túlmenően egynapos sebészeti eljárások során is indokolt a gyógyszeres (kis molekulatömegű heparin) profilaxis.

Spontaneous rupture of the oesophagus is an extremely serious condition with high morbidity and mortality. Primary surgical repair may be followed by numerous complications. A 29-year-old man had undergone primary surgical repair due to spontaneous rupture of the lower third of the oesophagus. After the operation he developed suture insufficiency, which could not have been stented, and transgastric drainage was performed therefore. After a slow healing of the fistula, we could avoid another operation and his oesophagus was preserved. Fortunately, a stricture did not develop either. Transgastric drainage of the oesophagus could be a good therapeutic choice in selective and complicated cases.

The mental and emotional state of the individuals have a strong effect on the course of their illnesses as well as the speed of recovery. Adequate quantity and quality of information and social support are a prerequisite for mental, and often for physical well-being. In our investigation at the DE OEC, we gathered data on the psychological and physical states of 100 breast cancer patients in order to reveal the role of a helping atmosphere in the recovery phase of their illness. The results suggested that patients attending the HIVAS support group could cope with their disease and its side effects better, and experienced a higher level of well-being.