A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Surgery of iatrogenic bile duct injuries.

Iatrogenic bile duct injury still represents a serious complication mostly connected with minimally invasive cholecystectomy. This complication has an important impact both on short- and long-term morbidity and is associated with non-negligible mortality. The objective of our study was to provide a comprehensive summary of information based on the most recent guidelines with recommendations for how to prevent a bile duct injury, how to reach an early diagnosis and finally, how to proceed should they occur in order to minimize further damage. We also present ATOM, a new classification of bile duct injuries that provides clear information not only about the extent of anatomical damage, but also about the time and mechanism of its occurrence.

Intrahepatic cholangiocarcinoma: risk factors affecting survival of operated patients.

INTRODUCTION: The aim of this study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma (IHCHCA) in terms of overall survival and disease-free survival, and to analyse and find potential prognostic factors affecting overall survival and disease-free survival. METHODS: Retrospective evaluation was performed of consecutively enrolled patients operated for IHCHCA from January 2005 to January 2022 (17 years) had undergone surgery. During the monitored period, 38 surgical procedures were performed, of which liver resection was done in 25 cases (65.8%). RESULTS: The 5-year survival in the radically resected group was 44%, and the 5-year disease-free survival was 32%. Based on univariate and multivariate analysis, radicality of surgery (p=0.01116) and lymph node involvement (p=0.00576) were assessed as negative prognostic factors for overall survival. Radicality of surgery (p=0.018) and administration of adjuvant chemotherapy (p=0.044) were significant negative prognostic factors affecting disease-free survival. However, they lost their significance in the multivariate analysis. CONCLUSION: Radical surgical resection of the liver remains an essential treatment option for intrahepatic cholangiocarcinoma aimed at achieving a radical procedure with microscopically negative margins. KEY WORDS: cholangiocarcinoma, resection, recurrence, survival.

Introducing in vivo pancreatic cancer models for the study of new therapeutic regimens

Introduction: Pancreatic cancer is a severe oncological disease with an ever-increasing incidence and a high rate of morbidity and mortality. Therapeutic options are limited and the five-year overall survival rate is 7­20%, depending on the possibility of surgical resection and the earliness of detection. Most patients with this diagnosis die due to the resistance of tumour cells and their microenvironment to the used treatment regimes. Methods: In our study, we focused on the implementation of two in vivo models, which are the cell-line derived xenograft (CDX) and the patient-derived xenograft (PDX). These two models differ significantly from each other methodologically, technically, financially, but also in their achieved results. Results: In a pilot study, we managed to successfully implement the CDX model with a very aggressive and resistant PaCa-44 line of pancreatic cancer in a total of 30 NU/NU strain mice. Furthermore, we created three PDX models with various subtypes of pancreatic cancer from patients operated at the University Hospital Kralovske Vinohrady, Department of General Surgery. These tumours were re-transplanted into subsequent generations of 23 individuals of NOD/SCID strain and 47 NU/NU strain mice. The established CDX and PDX models are then used to compare conventional and experimental chemotherapy regimens. Conclusion: The next steps will be to evaluate the effects of treatment regimens by using imaging and molecular genetic methods and to optimise the entire process for further use in precise personalised medicine for patients with pancreatic cancer. The upcoming goal is to create a library of PDX models of the most common pancreatic ductal adenocarcinoma and other rare subtypes of pancreatic cancer.

KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes.

The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel and experimental taxane SB-T-1216 with the KRAS signalling pathway expression in in vivo and in vitro PDAC models in order to decipher potential predictive biomarkers or targets for future individualised therapy. Mouse PDAC PaCa-44 xenograft model was used for evaluation of changes in transcript and protein levels of the KRAS signalling pathway caused by administration of experimental taxane SB-T-1216 in vivo. Subsequently, KRAS wild-type (BxPc-3) and mutated (MiaPaCa-2 and PaCa-44) cell line models were treated with paclitaxel to verify dysregulation of the KRAS signalling pathway gene expression profile in vitro and investigate the role of KRAS mutation status. By comparing the gene expression profiles, this study observed for the first time that in vitro cell models differ in the basal transcriptional profile of the KRAS signalling pathway, but there were no differences between KRAS mutated and wild-type cells in sensitivity to taxanes. Generally, the taxane administration caused a downregulation of the KRAS signalling pathway both in vitro and in vivo, but this effect was not dependent on the KRAS mutation status. In conclusion, putative biomarkers for prediction of taxane activity or targets for stimulation of taxane anticancer effects were not discovered by the KRAS signalling pathway profiling in various PDAC models.

Laparoscopic versus open liver resections for colorectal cancer liver metastases: short term results.

INTRODUCTION: Analysis and comparison of short-term results of laparoscopic liver resections (LLR) and open liver resections (OLR) for colorectal cancer liver metastases (CRCLM). METHODS: Retrospective analysis of patients operated for CRCLM in the time period from May 2007 to May 2019 (12 years) at the department of surgery, University Hospital Hradec Králové and University Hospital Královské Vinohrady. RESULTS: 206 liver resections were performed; 167 (81.1%) OLR and 39 (18.9%) LLR procedures. Conversion to open surgery was necessary in 6 cases (15.4%). LLR was associated with a longer operation time (194±107 min) vs (129±58 min) for OLR. The ICU stay, 3.5±4.3 days for OLR and 4.1±8.1 days for LLR, and the hospital stay, 11.9±8.3 days (OLR) vs 12.1±11.3 days (LLR), were comparable. Perioperative blood loss was lower in the LLR group, 189±166 ml vs 360±410 ml. Total transfusion rate was similar, 10.8% (OLR) vs 12.8% (LLR). Oncologic radicality was also comparable in both groups; negative resection margin was achieved in 78% (OLR) and 80% (LLR). Postoperative morbidity and mortality was comparable in both groups; morbidity was 33% (OLR) vs 31% (LLR), while mortality was 1.8% (OLR) vs 2.6% (LLR). CONCLUSION: LLR for CRCLM provided comparable short-term results compared to OLR in our group of patients even in the learning curve period. However, it should be noted that the study group is a highly selected group of patients.

Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216.

The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive tumor.

Bile Duct Anastomosis Supplied With Biodegradable Stent in Liver Transplantation: The Initial Experience.

BACKGROUND: The most common biliary complications after orthotopic liver transplantation are bile leaks, anastomotic and intrahepatic strictures, stones, and ampullary dysfunction. These complications can occur in up to 10% to 30% of liver transplant recipients. Leaks occur early in the posttransplant period; the stricture formation typically graduates over time. METHODS: Ten patients underwent transplantation in our preliminary study: 5 were randomized to the group with stent placement and 5 to the control group. We investigated the role of an absorbable biliary stent with the goal of proving patency of duct-to-duct biliary anastomosis. The stents are made of machine-knitted polydioxanone monofilaments. RESULTS: Our initial results show that duct-to-duct biliary reconstruction using an absorbable internal stent had good patency in all 5 patients. There were no signs of biliary leakage accompanying the anastomoses in any of the cases, and there was no stone formation observed after liver transplantation. The biliary stent was completely absorbed, with no adverse effects. CONCLUSIONS: Based on our initial experience and data, we concluded that biodegradable stents can be successfully and safely used in clinical practice. Further large prospective randomized studies are needed to estimate the efficacy of the bioabsorbable stents.

Liver transplantation for adenomatosis: European experience.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

A comparison of portal vein embolization with poly(2-hydroxyethylmethacrylate) and a histoacryl/lipiodol mixture in patients scheduled for extended right hepatectomy.

To determine whether PHEMA [poly(2-hydroxyethylmethacrylate)] is suitable for portal vein embolization in patients scheduled to right hepatectomy and whether it is as effective as the currently used agent (a histoacryl/lipiodol mixture). Two groups of nine patients each scheduled for extended right hepatectomy for primary or secondary hepatic tumor, had right portal vein embolization in an effort to induce future liver remnant (FLR) hypertrophy. One group had embolization with PHEMA, the other one with the histoacryl/lipiodol mixture. In all patients, embolization was performed using the right retrograde transhepatic access. Embolization was technically successful in all 18 patients, with no complication related to the embolization agent. Eight patients of either group developed FLR hypertrophy allowing extended right hepatectomy. Likewise, one patient in each group had recanalization of a portal vein branch. Histology showed that both embolization agents reach the periphery of portal vein branches, with PHEMA penetrating somewhat deeper into the periphery. PHEMA has been shown to be an agent suitable for embolization in the portal venous system comparable with existing embolization agent (histoacryl/lipiodol mixture).

Pancreatic islet autotransplantation after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma.

OBJECTIVE: Pancreatic islet autotransplantation (IAT) has a potential to prevent brittle diabetes in patients after total pancreatectomy. Because of the fear of tumor spread, IAT has rarely been used in case of malignancy. We report our experience with patients who underwent hemipancreatoduodenectomy for carcinoma and later completion pancreatectomy for pancreatic fistula with islet autotransplantation at our institution. METHODS: From August 2007 to December 2012, 5 patients underwent IAT after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma. Islets were isolated from the pancreatic tail with the use of digestion with collagenase. Nonpurified islet suspension was infused into the portal vein during surgery. RESULTS: The median number of islets transplanted was 175,000 islet equivalents (range, 70,000-365,000). One patient died after surgery for reasons unrelated to IAT. Another 3 patients had stable diabetes with partial graft function (fasting C-peptide levels 0.23, 0.41, and 0.61 nmol/L and HbA1c 4.8%, 4.6%, and 6.9% at 24, 24 and 9 months after IAT, respectively). The 1st patient, with pancreatic head carcinoma, was alive 28 months after IAT with lymph node and liver recurrence since 18 months after IAT. The 2nd patient, with gall bladder and distal bile duct carcinoma, died 47 months after IAT with tumor recurrence. The 3rd patient, with ampullary carcinoma, died 12 months after IAT with local recurrence and solitary liver metastasis. The last patient had been off insulin 9 months after IAT without tumor recurrence (fasting C-peptide, 0.89 nmol/L; HbA1c, 4.2%). CONCLUSIONS: Autotransplantation of pancreatic islets isolated from the residual pancreatic tissue in patients who previously underwent hemipancreatoduodenectomy for cancer may provide stable glucose control and thus improve quality of life. In this small series we did not observe early development of multiple liver metastases caused by islet suspension contamination with malignant cells. Oncologic outcome of the patients was not worse than what would be expected without IAT.

Incidental hepatocellular carcinoma: risk factors and long-term outcome after liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) currently represents the treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively known HCC (pkHCC) is diagnosed via imaging methods before OLT or before HCC is found postoperatively in the liver explant, denoted as incidental HCC (iHCC). The aim of this study was a comprehensive analysis of the post-transplantation survival of patients with iHCC and the identification of risk factors of iHCC occurrence in cirrhotic liver. METHODS: We retrospectively reviewed 33 adult cirrhotic patients with incidentally found HCC, comparing them with 606 tumor-free adult cirrhotic patients with end-stage liver disease (group Ci) who underwent OLT in our center from January 1995 to August 2012. Within the same period, a total of 84 patients underwent transplantation for pkHCC. We compared post-transplantation survivals of iHCC, Ci, and pkHCC patients. In the group of cirrhotic patients (Ci + iHCC), we searched for risk factors of iHCC occurrence. RESULTS: There was no difference in sex, Model for End-Stage Liver Disease score, and time spent on the waiting list in either group. In the multivariate analysis we identified age >57 years (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.75-8.14; P < .001), hepatitis C virus or alcoholic liver disease (OR, 3.89; 95% CI, 1.42-10.7; P < .001), and alpha-fetoprotein level >6.4 µg/L (OR, 6.65; 95% CI, 2.82-15.7; P = .002) to be independent predictors of iHCC occurrence. Both the 1-, 3-, and 5-year overall survival (OS) and the 1-, 3- and 5-year recurrence-free survival (RFS) differed in iHCC patients compared with the Ci group (iHCC: OS 79%, 72%, and 68%, respectively; RFS 79%, 72%, and 63%, respectively; vs Ci: OS = RFS: 93%, 94%, and 87%, respectively; P < .001). CONCLUSIONS: The survival of iHCC patients is worse than in tumor-free cirrhotic patients, but similar to pkHCC patients. The independent risk factors for iHCC occurrence in cirrhotic liver are age, hepatitis C virus, or alcoholic liver disease etiology of liver cirrhosis and alpha-fetoprotein level.

Urgent liver transplantation for chemotherapy-induced HBV reactivation: a suitable option in patients recently treated for malignant lymphoma.

BACKGROUND: Hepatitis B (HBV) reactivation induced by chemotherapy is a problem currently encountered in the management of malignancies. HBV reactivation occurs particularly in patients who were not checked for HBV status, and therefore have not undergone antiviral prophylaxis. HBV reactivation may ultimately lead to fulminant liver failure (FLF). Liver transplantation (OLT), the only remaining effective treatment option, is generally denied for subjects with a recent history of malignancy. CASE REPORTS: We described retrospectively three cases of FLF caused by HBV reactivation in two men and one woman undergoing rituximab-containing chemotherapy for malignant lymphomas: follicular, diffuse large B-cell and lymphoplasmacytic types. The two men reactivated after eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and the one woman after 13 cycles of rituximab monotherapy; their hematologic disease was in remission. All three patients were hepatitis B surface antigen (HBsAg)-positive with high HBV DNA levels. Neither man had been screened for HBV before chemotherapy; the woman had been treated with lamivudine (LAM) experiencing an HBV flare-up due to emergence of LAM resistance. All patients fulfilled King's College criteria for urgent OLT upon admission to the transplant center and underwent an urgent OLT. Their hemato-oncologic prognosis was considered to be favorable. All three patients are alive (54, 46, and 37 months post-transplantation), tumor-free and HBsAg negative on a standard HBV prophylaxis regimen: hepatitis B immunoglobulin and LAM + adefovir or tenofovir. CONCLUSIONS: Before chemotherapy appropriate prophylaxis for HBV reactivation should always be administered to at-risk patients. However, if reactivation with FLF occurs, OLT should not be generally denied. The prognosis of the hematologic malignancy should be assessed; OLT should be considered for patients in remission with a favorable long-term prognosis, for our data suggest acceptable survival.

[Surgical techniques to counter the lack of donors]. / Chirurgické techniky v dobe nedostatku dárcu

It has been 30 years since the first successful transplant in the Czech Republic. The number of interventions and their demand has been continuously growing. As a result of a continuous lack of donors, many new techniques have been developed, aimed at increasing the number of liver grafts suitable for transplant, and thus reducing the number of deaths among patients on the waiting list. In the field of paediatric liver transplants, especially in the groups of the lowest body weight, this need is the most urgent. The paper addresses the respective techniques and their availability in the Czech Republic. The most frequently used techniques include liver reduction and liver SPLIT. Furthermore, several successful domino transplants and transplants from a living donor have taken place. So far, no other techniques used elsewhere in the world (nonheart beating transplant, dual transplants, and auxiliary transplants) have been performed.

[Liver transplantation in patients with portal vein thrombosis]. / Transplantace jater u pacientu s trombózou portální zíly.

AIM: The aim of the study was to perform a retrospective assessment in a group of patients with portal vein thromboses who underwent consecutive liver transplantation. MATERIAL AND METHODS: PVT was preoperatively diagnosed with ultrasound and CT portography. The follow up period was 1 to 6 years. Postoperative immunosuppressive medication was administered in combination with cyclosporin A, prednison and imuran upon initiation of the transplantation programme (8 patients). During the follow up period, the treatment protocol was replaced with FK 506, Cell Cept and prednisone. Liver biopsy was indicated when rejection was suspected. RESULTS: During 1996-2009, the team of authors performed a total of 740 liver transplantations in 303 female and 437 male subjects. The procedures included 703 primary procedures, 33 retransplantations and four second retransplantations. Out of the total, 57 recipients (7.7%) had portal vein obliteration. These subjects included 42 male and 15 females, their mean age was 52 (9-67) years. 62 liver transplantations were performed in these 57 patients. The following complications were recorded in the patient group: graft dysfunction in 10.5%, revisions for bleeding in 28%, hepatic artery thrombosis in 10.5%, portal vein rethrombosis in 1.8%, biliary complications in 17.5%, acute rejections in 19.3%. Perioperative mortality rate was 15.8%.The mean blood derivates requirement was 17.1 (0-425) erythrocyte transfusion units, 27.1 (0-132) frozen plasma transfusion units and 2.6 (0-20) thrombocyte transfusion units. CONCLUSION: The results of out retrospective study indicate that portal thrombosis is not a contraindication for liver transplantation. Current surgical techniques make liver transplantations in patients with complete splanchnic venous thrombosis possible.

[Early biliary complications following liver transplantation]. / Casné biliární komplikace po transplantaci jater.

INTRODUCTION: Biliary complications (BC) after liver transplantation (LTx) are serious problems with an incidence rate of 6-35%. There are two types of BC, early and late. Early BC is observed for 30 days post LTx or during the entire period of the patient's first hospital stay after LTx. The main causes of early BC are ischemia of the biliary tree (the bile duct of the transplanted liver is supplied only from the right hepatic artery descendingly; the supply from the gastroduodenal artery is lacking) as well as implementation of the biliary anastomosis surgical technique. Treatment of BC is administered by a surgeon, a gastroenterologist and a radiologist. AIM: To evaluate early biliary complications after LTx PATIENTS AND METHODS: We reviewed patients with early BC after LTx from 4/2004 - 12/2009. We defined early BC as a complication that is present during the first 30 days post LTx or during the entire period of the patient's first hospital stay after LTx. RESULTS: We performed 384 LTx during the above-mentioned period. We carried out reconstruction of the biliary tree in the form of a choledochocholedochostomy (CDD) in 312 cases and in the form of a choledochojejunostomy (CDJ) in 72 cases. Sixty-eight patients had early BC (17.7%), 25 patients experienced biliary leak (6.5%), 40 patients had anastomotic stenosis (10.4%) and 3 patients (0.8%) experienced both complications (biliary leak and stenosis). Most complications were eliminated by ERCP with a papilosfincterotomy, a balloon dilatation of stenosis, and a biliary stent implant with repeated stent replacements (45 cases in total- all patients with biliary stenosis). Twenty-two patients were reoperated on (16x CDJ, 3x re-CDD, 2x suture of aberrant bile duct, 1x suture common bile duct) and 1 patient was treated by percutaneous transhepatic bilary drainage (PTD). The mortality rate was zero. CONCLUSION: BC after LTx continue to pose a serious surgical problem. The treatment of choice when dealing with BC is ERCP, which has more than a 70% success rate. If ERCP or PTD are not successful, or when biliary peritonitis is present, we perform a reanastomosis of the bile duct. The combined effort of the surgeon, gastroenterologist and radiologist is the most important factor for successful treatment. The incidence of BC after LTx at IKEM is similar to that of treatment centers all over the world.

[First Czech and Slovak domino liver transplantation]. / První Cesko-Slovenská domino transplantace jater.

INTRODUCTION: The study introduces the first international, Czech and Slovak Domino Transplantation performed based on a tight cooperation between the Czech and Slovak transplant centres. MATERIAL AND METHODS: The donor of the cadaveric graft was a young Slovak man with Familial amyloidotic polyneuropathy. The livers of these patients are the predominant source of circulating transthyretin, and liver transplantation is the only treatment available for the disease. The graft was obtained from heart beating deceased donor with brain death. The domino graft was then transplanted to Czech sixty-three years old man with hepatocellular carcinoma and liver cirrhosis based on HCV. RESULTS: Both recipients had an uneventful immediate postoperative course with early graft function. The Czech patient faced early HCV recurrence in a graft which necessitated the reduction of immunosuppressives. CONCLUSION: The domino liver transplantation represents a suitable way for addressing graft shortage and reducing waiting list time. A well-organized cooperation between the two international centres is required to complete successful domino transplantation.

[Autoimmune pancreatitis with biliary tree and liver involvement as a part of IgG4-related autoimmune sclerosing disease. Case report]. / Autoimunní pankreatitida s postizením zlucovodu a jater jako soucást IgG4 pozitivního onemocnení (IgG4-related autoimmune sclerosing disease). Kazuistika.

We report a rare case of autoimmune pancreatitis associated with sclerosing cholangitis, kidney, and salivary glands involvement. Abdominal ultrasound and CT scan showed enlarged pancreas, multiple nodular mass in the liver and kidney. ERCP showed features compatible with primary sclerosing cholangitis. The working clinical diagnosis considered malignant tumor with liver metastases. Histological examination of the liver biopsy sample revealed inflammatory process with numerous IgG4 positive plasma cells. The diagnostic conclusion of IgG4-related autoimmune sclerosing disease was drawn. The serum IgG level was elevated. Treatment with steroids improved the clinical course, all masses in the liver and kidneys disappeared, and laboratory tests were normalized. Now, 4 years after diagnosis the patient is free of all symptoms.

[Liver transplantations in children using reduced grafts]. / Transplantace jater u detí redukovaným stepem.

AIM: Liver transplantation is a life-saving procedure in patients with end stage liver disease. Five-year survival in patients indicated for transplantation based on standard indication criteria, has reached a rate over 80%. Shortage of suitable grafts remains the main problem in these procedures. While the situation in adult patients is relatively satisfactory, liver transplantations in children, mainly in the low-weight categories, remain a worldwide problem because of the absolute lack of suitable donors. In order to reduce mortality in the youngest patients on the waiting list, a concept of reduction of the adult graft for pediatric use was introduced in the early 1990s. Recent introduction of novel methods, such as split transplantations or transplantations between relatives, has resulted in lower mortality rates in the youngest recipients on the waiting lists. The author assesses a group of patients below 18 years of age, who underwent reduced liver graft transplantations in the Czech Republic. MATERIAL AND METHODS: From 1995 to 2009, a total of 43 patients below 18 years of age underwent transplantations, using 48 liver grafts. Further 17 children were sent abroad for transplantations, where a total of 23 liver grafts were used. Only patients who underwent transplantations using the liver grafts adjusted in IKEM were assessed in the patient group, i.e. 14 patients, resp. 16 liver grafts. Reduction was performed in 13 subjects. One subjects underwent transplantation between relatives and a liver split was used in two subjects. In the lowest weight category up to 10 kgs, 5 liver reductions were performed. OUTCOMES: Out of the total (n = 16), 4 grafts failed (2 were early postoperative failures, ie. within 2 postoperative days and 2 grafts failed in Month 5). The mean graft survival was 65 months. Within the youngest recipient age group (n = 5), no graft failure was recorded. The mean survival time is 26 months. CONCLUSION: Since 2007, the Czech Republic has been providing a program for all patients, including the lowest weight-category pediatric patients. To date data are satisfactory. No graft failure has been recorded in the category of the smallest (up to 10 kgs) pediatric patients.

Radical surgery for pancreatic malignancy in the elderly.

BACKGROUND: Improving life expectancy is associated with increasing incidence of pancreatic cancer. We reviewed morbidity and mortality in patients aged 65 years and older undergoing curative intent surgery in two centers in the Czech Republic. METHODS: Data were retrieved by retrospective analysis of the medical records over the period 2000-2007. In total, 60 patients were included. The mean age was 71 years (median 70 years; range 65-85 years). Most patients (43, 72%) underwent hemipancreatoduodenectomy, combined in 4 with portomesenterial vessel resection. Twelve patients (20%) had distal pancreatectomy and 5 patients (8%) total pancreatectomy. RESULTS: Overall morbidity was 28%. Only 10 patients (18%) developed serious surgical complications in terms of pancreatic leak (5, 8%), biliary leak (2, 3%), and intra-abdominal inflammatory collection (4, 7%). Four patients (6.6%) died within 30 days. The 1-year survival was 62.8%. CONCLUSION: We can conclude that age per se is not a contraindication to surgery. Patient's overall general condition, co-existing co-morbidities, and ability to get over with any potential complications are more important. and IAP.