Randomized experimental study of two novel techniques for transanal repair of dehiscent low rectal anastomosis.

BACKGROUND: Anastomotic leak after low anterior rectal resection is a dreadful complication. Early diagnosis, prompt management of sepsis followed by closure of anastomotic defect may increase chances of anastomotic salvage. In this randomized experimental study, we evaluated two different methods of trans-anal anastomotic repair. METHODS: A model of anastomotic leak was created in 42 male pigs. Laparoscopic low anterior resection was performed with anastomosis created using a circular stapler with half of the staples removed. Two days later, animals were randomized into a TAMIS (trans-anal minimally invasive surgery) repair, endoscopic suture (ENDO) or control group with no treatment (CONTROL). Signs of intraabdominal infection (IAI), macroscopic anastomotic healing and burst tests were evaluated to assess closure quality after animals were sacrificed on the ninth postoperative day. RESULTS: Closure was technically feasible in all 28 animals. Two animals had to be euthanized due to progressive sepsis at four and five days after endoscopic closure. Healed anastomosis with no visible defect was observed in 10/14 and 11/14 animals in TAMIS and ENDO groups, respectively, versus 2/14 in CONTROL (p < 0.05). Overall IAI rate was significantly lower in TAMIS (4/14; p = 0.006) and ENDO (5/14; p = 0.018) compared to CONTROL (12/14). Burst tests confirmed sealed closure in healed anastomosis with a median failure pressure of 190 (110-300) mmHg in TAMIS and 200 (100-300) mmHg in ENDO group (p = 0.644). CONCLUSION: In this randomized experimental study, we found that both evaluated techniques are effective in early repair of dehiscent colorectal anastomosis with a high healing rate.

Acute appendicitis during the spring COVID-19 pandemic in 2020 - a comparative retrospective study.

INTRODUCTION: Acute appendicitis (AA) is the most common abdominal emergency. This article aims to document the impact of the ongoing COVID-19 pandemic on timely diagnosis of AA, duration of symptoms before examination in a medical institution, levels of laboratory inflammatory markers, and the length of hospital stay. Collected data were compared with current world literature. METHOD: Two datasets were created, comprising patients with the histological diagnosis of AA determined from March 1 to June 30, 2019 (before of the onset of the COVID-19 pandemic) and in the same period of the spring pandemic of COVID-19 in 2020. The following information was obtained from patient medical records: Demographic data, information on symptom duration before AA diagnosis, information on laboratory inflammatory marker levels, the used surgical method, antibiotic treatment, histopathological findings, and the length of hospital stay. These data were processed using descriptive statistics methods and the two created datasets were compared with the use of statistical methods (an unpaired t-test and Welchs t-test). RESULTS: Thirty seven patients (26 men and 11 women) with the median age of 41 years were operated on for acute appendicitis at the Department of Surgery, Military University Hospital in Prague from March 1 to June 30, 2019. Thirty four patients (19 men and 15 women) with the median age of 42 years were operated on in the same period of 2020. No significant differences were found between these two compared datasets in terms of symptom duration, laboratory inflammatory marker levels or the length of hospital stay. The distributions of histopathological findings and used antibiotic treatments were also similar. CONCLUSION: In our study, we were unable to demonstrate any statistically significant differences between the datasets of patients operated on before and after the onset of the COVID-19 pandemic.

Minimally invasive pancreatic resection in the light of evidence state of the art.

The trend of minimally invasive surgery expands even into the most technically demanding areas, including HPB surgery. Faster recovery and elimination of surgical site infections achieved with a minimally invasive approach provides, in addition to a better quality of life, the possibility of starting adjuvant treatment earlier. However, evidence of non-inferiority of short-term and oncological results compared to open surgery is required. In minimally invasive distal pancreatectomy, there is sufficient evidence to suggest that it as the method of choice for benign tumors and low-grade malignancies. For pancreatic cancer, the long-term results so far appear to be equivalent, although this still needs to be confirmed by ongoing randomized controlled trials (RCT). Enucleation of accessible lesions is also a suitable procedure for the minimally invasive approach. In contrast, in pancreaticoduodenectomy, available evidence does not demonstrate a clear benefit of the minimally invasive approach. Safety concerns still remain, and not even formal training has been successful in eliminating the consequences of the long learning curve for perioperative outcomes. Robotic approach appears to be more promising than laparoscopy for pancreaticoduodenectomy. Key words: pancreaticoduodenectomy distal pancreatectomy minimally invasive - laparoscopic robotic.

Robotic-assisted surgery for rectal cancer results of a non-randomized study.

INTRODUCTION: The Czech Republic belongs to countries in which colorectal cancer significantly contributes to the overall oncological burden. Radical removal of tumor-affected tissues plays a key role in the multimodal therapy of rectal cancer. In the first decade of the third millennium the mini-invasive approach in rectal cancer surgery gradually expanded to include robotic-assisted surgeries. The aim of this paper is to present the results of a non-randomized study with prospectively collected data from robotically assisted rectal cancer surgeries. METHODS: 204 patients with rectal cancer (.

Regenerative abilities of a nanofiber wound dressing based on polylactide.

INTRODUCTION: The development of an ideal dressing for wound healing remains an unresolved issue. Thanks to the development of electrospinning technology, polymers in the form of nanofibers have come to the forefront of research interest. A modern and very promising dressing material is a “nonwoven” based on nanofibers of the synthetic polymer polylactide (PLA). The aim of this work was to assess the regenerative abilities of PLA in a standardized wound in a porcine model and compare our results to the literature data. METHODS: We applied PLA-based nanofiber dressings to the standardized wounds created in the porcine model. On the third, tenth, seventeenth and twenty-fourth days after the formation of the defect, we changed the wound dressing while taking a tissue sample for histopathological examination. We continuously monitored serum levels of acute phase proteins. RESULTS: PLA stimulated an inflammatory response. From the third day, the thickness of the fibrin layer with granulocytes increased. It reached its maximum values on the tenth day (mean 340 μm); at the same time the level of serum amyloid A, as a marker of inflammation, culminated. The individual phases of healing intertwined. The highest thickness values of the granulation tissue with cellular connective tissue (diameter 8463 μm) were reached on the seventeenth day. On the twenty-fourth day, the defects were healed macroscopically with a mean reepithelialization layer of 9913 μm. CONCLUSION: PLA-based nanofiber dressing potentiates the inflammatory, proliferative and reepithelialization phases of healing. Its structure perfectly mimics the extracellular matrix and serves as a 3D network for the growth and interaction of cellular elements. In addition to biocompatibility, PLA has a unique ability of two-phase biodegradation. It is a promising material for industrial production of dressing materials. Most of the available studies were performed in vitro. In vivo comparative studies approximating the use of PLA to daily practice are still missing.

Oncosurgery in the Czech Republic.

The article describes the development of oncosurgery in the Czech Republic since the beginning of the century, as well as other perspectives regarding this specialty. The development of surgical treatment of solid malignant tumours in the Czech Republic was evaluated according to the National Cancer Register database and compared to the neighbouring countries, and the educational system of surgeons in oncosurgery was assessed. Although surgery plays a key role in cancer therapy, starting from the beginning of this millennium it has been pushed aside as a service specialty for other disciplines in oncology. In 2002, these changes were supported by the activities of the newly founded Division of Oncosurgery under the Czech Society for Oncology, which became part of the Czech Surgical Society in 2016. An official educational programme of surgeons in oncology was successfully implemented and since 2011, a specialization examination in oncosurgery has been introduced, organized by the subdepartment of oncosurgery of the Institute of Postgraduate Medical Education (IPVZ), Prague. To date, this examination has been completed by 112 physicians and approximately the same number is currently registered in the educational programme. Currently, 34 centres are accredited for education in oncosurgery. The establishment of Complex Oncology Centres based on an initiative of the Czech Society for Oncology of 2006 only addressed pharmaceutical and radiation oncology. Despite progress in oncosurgery, more clearly defined conditions for this specialty are needed. Conclusion: The education of surgeons in oncosurgery should be continued. It is necessary to expand the number of centres with accreditation for oncosurgery and develop a concept for oncosurgery in the Czech Republic which would be associated with rational concentration of this treatment in connection with organization and provision of continuous urgent and acute surgical care in the Czech Republic, including control mechanisms to ensure its quality. This proposal should be discussed by the Czech Surgical Society in order to further enhance the quality of oncosurgery in the Czech Republic.

Circulating tumor DNA as a biomarker in metastatic colorectal carcinoma case report.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignant disease worldwide. The stage of the disease at the time of diagnosis and the capture of an early recurrence have a direct impact on long-term survival. Existing control screening methods often do not reflect real-time metastatic disease. In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool. CASE REPORT: In 2012, we performed sigmoid resection in a 57 years old patient for advanced CRC. The follow-up assessments included: blood samples for CA 19-9 and CEA, endoscopy and imaging methods. We also sampled peripheral blood to determine the level of ctDNA. Its value corresponded to the development of the disease throughout the period. Twice it outperformed imaging methods. CEA showed some degree of unreliability, especially after prolonged illness. CA 19-9 was in the normal range at all times. CONCLUSION: Circulating tumor DNA is an effective tool in the diagnosis of recurrent metastatic CRC. In patients with detectable ctDNA, its level correlates with the tumoral mass in real time. It has a predictive value in monitoring the treatment response. Its implementation in the follow-up of patients with CRC may have an impact on the choice of treatment strategy and consequently on patient survival.

Acute abdomen in drug abusers.

Introduction: Acute abdomen is one of the most important issues in abdominal surgery. Our study aims to describe the differences in clinical presentation of patients, in the course of their hospitalization, and in morbidity and mortality of patients with drug abuse; another aim is to describe our own experience with drug abusers with acute abdomen. Method: Patients with the history of drug abuse and with non-traumatic acute abdomen were included retrospectively to our set. We chose patients hospitalized between 2013 and 2018. We analyzed the demographical data of the patients, types of abused drugs, concordance between the first and final diagnosis, findings of paraclinical examinations, the need of surgical treatment, and the type of surgery. Morbidity, mortality and the length of hospital stay were tracked. All the data was evaluated using descriptive statistics. Results: 8 patients (4.7 per mille of all the patients hospitalized for acute abdomen) fulfilled the criteria of our study. All the patients were men with median age 32 years. Pervitin (methamphetamine) was the most frequently abused drug (in 50%), followed by heroin, benzodiazepines, tetrahydrocannabinol, subutex, hypnotics and tramadol. Peptic ulcer perforation was the most frequent diagnosis in our set (in 50% of all patients). The other diagnoses included: two cases of upper gastrointestinal tract bleeding, one case of Crohn's disease relapse with peritonitis and one case of colitis of the ascending colon. Surgical treatment was necessary in 75% patients. 30-day mortality was zero; an early complication (wound dehiscence) developed in one operated patient. Mean length of hospital stay was 9.7 days in our set, with the median of 7 days. Conclusion: Drug abusers represent only a marginal part of all patients with acute abdomen. This group is characterized by a significantly lower age, by a considerable predominance of men and by the preference of perforated peptic ulcer.

Portal vein ligation with alcohol injection - our first experiences.

INTRODUCTION: Surgical resection of colorectal liver metastases is a gold standard treatment. The indication criteria still continue expanding. The future liver remnant volume (FLRV) remains the only limiting factor of the resection. Many methods have been discussed to increase the FLRV. Injection of absolute alcohol into the portal vein seems to be one of the most effective. PATIENTS AND METHODS: In 2018 we perioperatively injected 25 ml of absolute alcohol into the ligated right portal branch in 3 patients with colorectal liver metastases at our department. All patients were indicated for second-stage right hemihepatectomy. RESULTS: The mean FLRV increase was 206.6 cm3 46 weeks after absolute alcohol injection. A transient elevation of transaminases was observed with spontaneous regression within 10 days from alcohol injection. There was no complication clearly associated with alcohol application. No liver failure was observed. No patient died. All three patients underwent second-stage right hemihepatectomy. CONCLUSION: Portal vein ligation with alcohol injection can be an uncomplicated and highly effective method to achieve FLRV hypertrophy.

Assessment of anastomosis perfusion by fluorescent angiography in robotic low rectal resection: the results of a non-randomized study.

INTRODUCTION: Colorectal cancer is a major contributor to the overall cancer burden in the Czech population. Anastomotic healing defects are a feared complication which may have a fatal impact on the patient. Fundamental conditions for proper anastomotic healing include sufficient blood supply. Fluorescent angiography using indocyanine green in the spectrum of near-infrared light facilitates the monitoring of tissue perfusion during a surgery. The aim of this article is to present the results of a non-randomized study in which we assessed prospectively obtained data from a perioperative assessment of anastomosis perfusion by fluorescent angiography using indocyanine green during robotic resection of the rectum with a malignant tumor. METHOD: Thirty patients with rectal cancer who underwent a robotic resection with primary anastomosis were consecutively included in the study between 1 April 2017 and 21 June 2018. The study included patients due to undergo a minimally invasive procedure with guaranteed health insurance coverage. During the operation, we monitored and assessed the quality of perfusion of the resection line of the sigmoid colon and subsequent anastomosis by means of fluorescent angiography using indocyanine green in the spectrum of near-infrared light. The data were obtained prospectively and subsequently analyzed. RESULTS: Between 1 April 2017 and 21 June 2018, we consecutively included 30 rectal cancer patients in the project: 16 men and 14 women. Monitoring of perfusion of the resection line and anastomosis was successful in all cases and perfusion quality was satisfactory across the sample. Perfusion insufficiency requiring a change in the resection line level or anastomosis adjustments was not detected with any patient. In two cases (12.5 %) of TME, we gave up the planned protective ileostomy owing to good perfusion of the anastomosis. One patient (3.3%) suffered from defective anastomotic healing without clinical symptoms (type A). We found no technical complications related to fluorescent angiography or undesirable effects due to the application of indocyanine green. CONCLUSION: Fluorescent angiography using indocyanine green in the spectrum of near-infrared light is a fast and safe option to monitor the level of blood supply to an anastomosis during surgery, which is a fundamental condition for proper healing. Even though we did not record insufficient perfusion in our sample and hence we did not need to change the resection line level or adjust the anastomosis, we may state that fluorescent angiography performed by an experienced colorectal surgeon may potentially reduce the frequency of complications linked to defective anastomotic healing.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach.

INTRODUCTION: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. METHODS: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. RESULTS: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. CONCLUSION: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Multidisciplinary team in colorectal cancer treatment - analysis of our patients in 2017.

INTRODUCTION: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs actions. This report aims to assess the benefits of MDTs using our own data set for 2017. METHODS: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDTs involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDTs conclusions. RESULTS: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTDs conclusions in less than 5% of patients. CONCLUSION: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDTs members on the CRC patients treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDTs outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.

[Laparoscopic versus open left pancreatectomy: surgical stress response comparison in the porcine model]. / Srovnání operacní záteze u laparoskopické a otevrené levostranné pankreatektomie v experimentu na velkém laboratorním zvíreti.

INTRODUCTION: Although several techniques of laparoscopic left pancreatectomy have already been developed through experiments on animals and human patients, there is still insufficient information about their pathophysiological mechanisms, especially the impact on surgical stress. METHOD: In a group of 10 pigs, open left pancreatectomy was performed, and the other group of 10 pigs underwent laparoscopic left pancreatectomy. Postoperative stress was compared by determining serum levels of leukocytes, interleukin 1, 6 and CRP from peripheral venous blood collection. The blood was collected prior to incision, 1 and 2 hours after incision, 24 hours after the beginning of the procedure, and on the 7th postoperative day. RESULTS: No statistically significant difference was found between open and laparoscopic left pancreatectomy in the measured values of leukocytes, IL-1 and 6 and CRP.Key words: laparoscopy - left pancreatectomy surgical stress response interleukin 1 interleukin 6.

Postoperative monitoring of colorectal anastomosis - experimental study.

INTRODUCTION: Inadequate blood supply is one of the major risk factors for colorectal anastomotic leak. Early postoperative detection of local ischemic changes can predict complicated healing and lead to better outcome. Microdialysis (MD) offers real-time evaluation of adequate bowel perfusion through monitoring of tissue metabolism. The aim of this study was to assess the feasibility of MD for early detection of ischemic changes in colorectal anastomosis. METHOD: Five pigs with end-to-end colorectal anastomosis were included. MD catheter was placed intramurally 5mm from anastomotic edge. Occlusive ischemia was induced after 3 measurements and followed by another 3 hours of monitoring. Tissue levels of different metabolites were measured every 60 minutes before and after ischemia induction. Mann-Whitney test was used to compare pre and post ischemic changes. RESULTS: The monitoring of colorectal anastomosis using MD was technically feasible and associated with no complications. Significant changes caused by local ischemia were observed in decreased levels of glucose or pyruvate and increased levels of lactate and glycerol. All metabolic changes were detectable already in first samples 60 minutes after ischemia induction. CONCLUSION: Postoperative ischemic changes in colorectal anastomosis can be detected by means of microdialysis.Key words: colorectal anastomosis anastomotic leak microdialysis.

[Colorectal cancer the importance of primary tumor location]. / Kolorektální karcinom význam lokalizace primárního nádoru.

Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

[Pneumoperitoneum after colonoscopy - "to cut or not to cut"]. / Pneumoperitoneum po kolonoskopii - "to cut or not to cut".

Colon perforation is a very serious complication of colonoscopy. The correct diagnosis and management of therapy improve the prognosis of patients. The treatment can be conservative, endoscopic and surgical. In this case report we present microperforation as a complication of polypectomy in the caecum during colonoscopy, followed by laparoscopic surgery.Key words: colonoscopy - complication -perforation polypectomy.

[Can robotic rectal cancer surgery improve quality of total mesorectal excision?] / Muze robotická asistence pri chirurgické lécbe karcinomu rekta zlepsit kvalitu totální mezorektální excize?

INTRODUCTION: The introduction of total mesorectal excision (TME) in the 1980s was pivotal in the surgical treatment for rectal carcinoma (RC). Routinely applied TME led to a significant reduction in the incidence of local recurrences. The purpose of our paper is to present the results of our non-randomized study comparing prospectively acquired data from radical resection / rectal extirpation using classic open access, laparoscopy and da Vinci robotic system. METHOD: The study group included 116 patients with RC who underwent radical surgical treatment between 1/2014-12/2016, after which the collected resection specimens were assessed in pathology laboratories of the referring hospital using the Quirkes protocol. Analysis of data collected prospectively over a period of 3 years was done. The surgical procedures were open, laparoscopic and robotic. Robotic surgery could only be performed in patients whose health insurers guaranteed to cover the robotic resection expenses. Those patients whose health insurers did not cover the costs of the robotic assisted procedure were treated using the laparoscopic technique. RESULTS: Over a period of 3 years (2014-2016), the teams at the Department of Surgery of the 2nd Faculty of Medicine, Charles University and Central Military Hospital, Prague treated 116 patients (75 men and 41 women) for RC; resected specimens of the patients were processed according to the Quirkes protocol. Mean age was 63 years (33-80). pCRO positivity was confirmed in 5 patients (4.3%) and complete or nearly complete TME was achieved in 94 patients (81%). More than a half of the procedures were performed using the minimally invasive surgery. No patient died. CONCLUSION: Despite the high rate of technically difficult cases (male sex, tumours in the distal third of the rectum), the robotic assisted treatment showed best results in our study group in terms of quality of the mesorectal excision. Our results thus provide evidence of an unequivocal benefit of robotic assistance compared to manual laparoscopy and open procedures in terms of TME as a quality indicator of surgery in patients with CR. Given the limited time span, there are no long-term results to be assessed in our patients.Key words: rectal carcinoma - TME - evaluation of surgical treatment - robotic rectal surgery.

Pharmacokinetics of the New Hepatitis C Virus NS3 Protease Inhibitor Narlaprevir following Single-Dose Use with or without Ritonavir in Patients with Liver Cirrhosis.

In this study we sought to evaluate narlaprevir (NVR) pharmacokinetics (PK) after a single dose with or without ritonavir (RTV) in cirrhotic versus healthy subjects. NVR at 200 mg was administered to 8 healthy and 8 cirrhotic subjects, and NVR at 100 mg with RTV at 100 mg was administered to 8 healthy and 8 cirrhotic subjects. PK analysis was performed. The geometric mean maximum concentration of a drug in serum (Cmax) and the area under the concentration-time curve from 0 to infinity (AUC0-∞) were 563.1 ng/ml and 4,701.8 ng · h/ml in cirrhotic patients versus 364.8 ng/ml and 1,917.1 ng · h/ml in healthy volunteers, respectively. The geometric mean ratios of the PK parameters of cirrhotic subjects to healthy volunteers were 1.54-fold (90% confidence interval [CI] = 1.05 to 2.27) for Cmax and 2.45-fold (90% CI = 1.56 to 3.85) for AUC0-∞ The geometric mean Cmax and AUC0-∞ in cirrhotic and healthy subjects were similar: 1,225.7 ng/ml for Cmax and 15,213.1 ng · h/ml for AUC0-∞ in cirrhotic subjects and 1,178.9 ng/ml for Cmax and 14,257.2 ng · h/ml for AUC0-∞ in healthy volunteers. The corresponding geometric mean ratios were 1.04 (90% CI = 0.67 to 1.62) for Cmax and 1.07 (90% CI = 0.72 to 1.58) for AUC0-∞ Higher exposures in cirrhotic subjects were safe and well tolerated. We found that NVR exposures after a 200-mg single dose were higher in cirrhotic subjects than in healthy subjects and that a 100-mg single dose of NVR boosted with RTV at 100 mg resulted in no significant PK differences between cirrhotic and healthy subjects.

A comparison of two endoscopic closures: over-the-scope clip (OTSC) versus KING closure (endoloop + clips) in a randomized long-term experimental study.

BACKGROUND: Both over-the-scope clip (OTSC) and KING (endoloop + clips) closures provide reliable and safe full-thickness endoscopic closure. Nevertheless, OTSC clip demonstrated significantly inferior histological healing in the short-term follow-up. AIM: To compare OTSC versus KING closure of a perforation with regard to long-term effectiveness and macroscopic and histological quality of healing. METHODS: We performed a randomized experimental study with 16 mini-pigs (mean weight 43.2 ± 11.2 kg). A standardized perforation was performed on the anterior sigmoid wall. KING closure (n = 8) was attained by approximation of an endoloop fixed to the margins of a perforation with endoclips. OTSC closure (n = 8) was performed by deploying OTSC (OVESCO) over the defect. Pigs underwent a control sigmoidoscopy 8 months after the closure to assess the macroscopic quality of healing. Then, autopsy was performed and the rectosigmoid was sent for histopathological assessment. RESULTS: All closures were completed successfully without air leaks. The duration of closure was similar in both techniques (OTSC 17.8 ± 7.6 min vs. KING 19.6 ± 8.8 min). At autopsy, all KING closures (100 %) were healed with a flat scar without signs of leakage. Microscopically, no inflammatory changes were observed after KING closure. In the OTSC group, microscopic ulcers were present in two pigs (25 %), cryptal abscesses in three pigs (38 %) and significant neutrophil accumulation in all eight pigs (P < 0.01). Giant cell granulomas, dysplasia or abundant scarification was not observed in either group. CONCLUSIONS: Both OTSC and KING closures offer a long-term reliable seal of a gastrointestinal perforation without stenosis or fistulas. KING closure provides long-term histologically superior healing.

[Total pancreatectomy for pancreatic malignancy - from history to the present day]. / Totální pankreatektomie u maligního onemocnení slinivky brisní od historie k dnesku.

Currently, total pancreatectomy (TP) is indicated in approximately one in ten surgical patients with pancreatic cancer. Key role in the decision falls in the competence of the multidisciplinary team, alternatively of the surgeon in the intraoperative period in some cases. Exceptionally, TP is approached in the so-called salvage surgery. Perioperative mortality of TP as an elective procedure does not exceed that of partial resections; however, mortality of up to 50% is associated with salvage surgery in acute postoperative pancreatitis. Postoperatively, patients are afflicted with the so-called brittle diabetes comparable with type 1 diabetes. The aim of our overview is to inform about the current position of TP in the treatment of malignant pancreatic diseases.Key words: pancreatic cancer - total pancreatectomy - multidisciplinary team.