Mitochondrial changes in adenocarcinoma of the pancreas.

The aim of our study was to analyse the mitochondrial ultrastructure in primary ductal adenocarcinomas of the pancreas and to compare it with normal pancreatic cells. 52 samples of adenocarcinoma of the pancreas obtained by surgical resection or by endosonographic biopsy were examined. Compared to normal mitochondrial ultrastructure in non-tumorous cells, the mitochondria in cancer cells had a dense matrix and condensed configuration or with lucent-swelling matrix associated with disarrangement and distortion of cristae and partial or total cristolysis. Functionally, these structural alterations presume the presence of hypoxia-tolerant and hypoxia-sensitive cancer cells.

Manometric perfusion test in biliary strictures treatment.

BACKGROUND/AIMS: To assess the biliary manometric perfusion test (BMPT) for evaluating success in treating benign biliary strictures. METHODOLOGY: During 2003 to 2010, 29 patients were subjected to BMPT after percutaneous balloon dilatation treatment. Intrabiliary pressure less than 20cm of water was considered the success threshold. Results of BMPT evaluation were retrospectively compared with a similar group where the standard clinical test was used for evaluating treatment success. The clinical test group included 21 patients treated for biliary strictures from 1994 to 2006. RESULTS: The two groups were statistically similar by age and gender. The BMPT group was tested without complications and pressure inside the biliary tree was less than 20cm of water in 27 of 29 patients. Subsequently, catheters were removed from all 27. Three patients required re-interventions 13 days, 11 months and 32 months later. Kaplan-Meier survival analysis showed that the probability of biliary patency at 3 year was 82.2%. There was no significant difference between groups by this measure (log rank test, p=0.624). CONCLUSIONS: The manometric test is an alternative for evaluating success in treating benign biliary strictures. It is simple, less time-consuming, economical, safe, effective and more comfortable for patients than the clinical test.

Routine SARS-CoV-2 RT-PCR testing before digestive endoscopy during the peak of the pandemic - a single tertiary center experience.

BACKGROUND AND AIMS: COVID-19 pandemic has impacted on all endoscopy centers in the Czech Republic, that belongs to the most affected countries in the world. The aim of our study was to analyze all procedures following routine RT-PCR testing in our tertiary center during the peak of the pandemic. METHODS: We retrospectively analyzed all procedures performed from October 2020 to January 2021 after a new RT-PCR center had been set up. Main outcomes were type of scheduled procedure, indication, rate of therapeutic interventions and rate of new relevant and malignant findings. Comparison to the same period before the pandemic and SARS-CoV-2 infection in endoscopy staff are also reported. RESULTS: A total of 1,953 procedures were performed. 624 patients were referred with a negative RT-PCR test and the remaining 1,346 patients were tested in the new center. 1,293 negative tests led to 1,329 procedures. A new relevant finding was reported in 589 (44.3%), including new malignancy in 56 (4.2%). 53 patients tested positive (3.9%). There was a reduction by 9% in the number of all procedures compared to the same period before the pandemic and an increase in the number of screening colonoscopies and ERCP procedures. In the study period, 9 of 54 staff members contracted SARS-CoV-2 infection. CONCLUSIONS: Routine RT-PCR testing of patients scheduled for elective endoscopy during the peak of COVID-19 pandemic enabled us to essentially maintain our unit productivity, including activities such as screening colonoscopy, endoscopic resection and pancreatobiliary endoscopy.

[Possibility of using the determination of minimal residual disease in pancreatic adenocarcinoma using real-time RT-PCR--a pilot study]. / Moznosti vyuzití stanovení minimální reziduální choroby u adenokarcinomu pankeatu pomocí metodiky real-tim RT-PCR--pilotní studie.

BACKGROUND: Minimal residual disease in patients with pancreatic cancer is defined as the presence of isolated tumor cells in the patient's body, in which the primary tumor was removed and is currently without clinical signs of disease. These isolated tumor cells may be described as precursors of micrometastases. Assessment of MRD in patients with this highly malignant disease could eliminate burdensome implementation of surgery in patients with systematic dissemination of molecular disease and provide a more precise prognosis. METHODS AND RESULTS; The study to date included 70 patients operated on with curative intent for carcinoma of the pancreas. Samples of peripheral and portal blood, bone marrow, peritoneal lavage and of the tumor itself were analyzed by real-time PCR which measured the expression of hTERT (telomerase), EGFR1 (receptor for epidermal growth factor) and CEA (carcinoembryonic antigen). The expression of these markers was correlated with clinicopathological characteristics and survival parameters. We found a statistically significant association between EGFR expression levels in the portal blood and clinical stage--patients with advanced disease have a higher expression of EGFR in the portal stream and peritoneal lavage in contrast to patients without the presence of metastases. CONCLUSIONS: The results of this pilot study demonstrated a high sensitivity and specificity of the RT-PCR method for detecting circulating tumor cells in patients with pancreatic cancer. By utilizing this methodology, we are able to provide prognostic value of minimal residual disease and its significance for the indication of radical surgery for pancreatic cancer.

Evaluation and management of toxicity of cytoreductive surgery/hyperthermic intraperitoneal chemotherapy: the initial experience of a single centre study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for peritoneal surface malignancies with efficacy reported in many trials. Discrepancies, however, in the indication criteria, the extent of the surgical procedure, HIPEC regimens and toxicity evaluation represent a problem when comparing this method with other therapeutic modalities. METHODS: We describe the initial experience with CRS/HIPEC using different chemotherapy regimens (oxaliplatin, cisplatin, mitomycin C and doxorubicin) at the Comprehensive Oncology Centre Olomouc. RESULTS: A perioperative mortality of 2% and perioperative morbidity of 11%, according to Clavien-Dindo were observed. Interestingly, all these patients underwent HIPEC with oxaliplatin 460 mg/m2. The median duration of admission to hospital was 6 days in the intensive care unit (range 2-28 days) and 7 days in the surgical ward (range 1-21 days). Hospital admission did not exceed 2 weeks in 75% of patients. These results are consistent with the published results of large centres performing this treatment modality mainly due to pre-operative preparation of patients and pre-treatment and post-treatment management of HIPEC/CRS toxicity. Evaluation of the efficacy in terms of time to progression and overall survival (OS) is limited by the short follow up period. CONCLUSION: CRS/HIPEC performed is a safe method with low perioperative mortality.

Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations.

BACKGROUND: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background. PATIENTS AND METHODS: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. RESULTS: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively. CONCLUSION: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.

JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes.

SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279-82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYP1A2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive element or with a plasmid containing 5'-flanking region of human CYP1A1 gene. SP600125 transactivated the reporter plasmids with EC(50) of 0.005 and 1.89 microM, respectively. On the other hand, TCDD-dependent transactivation of the reporter plasmids was inhibited by SP600125 with IC(50) values of 1.54 and 2.63 microM, respectively. We also tested, whether the effects of SP600125 are due to metabolism. Using liquid chromatography/mass spectrometry approach, we observed formation of two minor monohydroxylated metabolites of SP600125 in human hepatocytes, human liver microsomes but not in HepG2 cells. These data imply that biotransformation is not responsible for the effects of SP600125 on AhR signaling. In conclusion, we demonstrate that SP600125 is a partial agonist of human AhR, which induces CYP1A genes.

Percutaneous treatment of benign bile duct strictures.

PURPOSE: To evaluate long-term results of treatment of benign bile duct strictures. MATERIALS AND METHODS: From February 1994 to November 2005, 21 patients (9 men, 12 women) with median age of 50.6 years (range 27-77 years) were indicated to percutaneous treatment of benign bile duct stricture. Stricture of hepatic ducts junction resulting from thermic injury during laparoscopic cholecystectomy was indication for treatment in one patient, stricture of hepaticojejunostomy was indication for treatment in all other patients. Clinical symptoms (obstructive jaundice, anicteric cholestasis, cholangitis or biliary cirrhosis) have appeared from 3 months to 12 years after surgery. RESULTS: Initial internal/external biliary drainage was successful in 20 patients out of 21. These 20 patients after successful initial drainage were treated by balloon dilatation and long-term internal/external drainage. Sixteen patients were symptoms free during the follow-up. The relapse of clinical symptoms has appeared in four patients 9, 12, 14 and 24 months after treatment. One year primary clinical success rate of treatment for benign bile duct stricture was 94%. Additional two patients are symptoms free after redilatation (15 and 45 months). One patient is still in treatment, one patient died during secondary treatment period without interrelation with biliary intervention. The secondary clinical success rate is 100%. CONCLUSION: Benign bile duct strictures of hepatic ducts junction or biliary-enteric anastomosis are difficult to treat surgically and endoscopically inaccessible. Percutaneous treatment by balloon dilatation and long-term internal/external drainage is feasible in the majority of these patients. It is minimally invasive, safe and effective.

Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature.

AIM: To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. METHODS: One-hundred-fifty-nine consecutive pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical pancreatic surgery between 2006 and 2013 were included in this retrospective analysis. The clinical data including age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered, and follow-up were all obtained from medical records. Further analysis covered only patients with metachronous metastases. Clinical and histopathological data (age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered and follow-up) of patients with metachronous non-pulmonary metastases and patients with metachronous pulmonary metastases were statistically assessed. Disease-free survival (DFS) from pancreas resection until metastases onset and overall survival (OS) were calculated. Wilcoxon test, χ2 test and survival functions computed by the Kaplan-Meier method were used. Statistical significance was evaluated by the log-rank test using SPSS. A P-value of less than 0.05 was considered statistically significant. RESULTS: Metachronous pulmonary metastases were observed in 20 (16.9%) and were operable in 3 (2.5%) of PDAC patients after a prior curative-intent surgery. Patients with isolated pulmonary metastases (oligometastases and multiple metastases) had estimated prior DFS and OS of 35.4 and 81.4 mo, respectively, and those with metachronous pulmonary metastases accompanied by other metastases had prior DFS and OS of 17.3 and 23.4 mo, respectively. Patients with non-pulmonary metastases had prior DFS and OS of 9.4 and 15.8 mo, respectively. Different clinical scenarios according to the presentation of MPM were observed and patients could be divided to three subgroups with different prognosis which could be used for the selection of treatment strategy: isolated pulmonary oligometastases, isolated multiple pulmonary metastases and pulmonary metastases accompanied by other metastases. CONCLUSION: Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.

Dysregulation of KRAS signaling in pancreatic cancer is not associated with KRAS mutations and outcome.

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, and no targeted therapy is currently available. The aim of the present study was to investigate the prognostic significance of the expression of V-Ki-ras2 Κirsten rat sarcoma viral oncogene homolog (KRAS), downstream signaling pathway genes and the association with clinical characteristics in PDAC patients undergoing radical surgery. Tumors and adjacent non-neoplastic pancreatic tissues were examined in 45 patients with histologically verified PDAC. KRAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene mutation analysis was performed using the KRAS/BRAF/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α array. The transcript profile of 52 KRAS downstream signaling pathway genes was assessed using quantitative-polymerase chain reaction. KRAS mutation was detected in 80% of cases. The genes of four signaling pathways downstream of KRAS, including the phosphoinositide 3-kinase/3-phosphoinositide-dependent protein kinase 1/V-akt murine thymoma viral oncogene homolog 1, RAL guanine nucleotide exchange factor, Ras and Rab interactor 1/ABL proto-oncogene-1, non-receptor tyrosine kinase, and RAF proto-oncogene serine/threonine-protein kinase/mitogen-activated protein kinase pathways, exhibited differential expression in PDAC compared with that in the adjacent normal tissues. However, no significant differences in expression were evident between patients with KRAS-mutated and wild-type tumors. The expression of KRAS downstream signaling pathways genes did not correlate with angioinvasion, perineural invasion, grade or presence of lymph node metastasis. Additionally, the presence of KRAS mutations was not associated with overall survival. Among the KRAS downstream effective signaling pathways molecules investigated, only v-raf-1 murine leukemia viral oncogene homolog 1 expression was predictive of prognosis. Overall, KRAS mutation is present in the majority of cases of PDAC, but is not associated with changes in the expression of KRAS downstream signaling pathways and the clinical outcome. This may partly explain the failure of KRAS-targeted therapies in PDAC.

Neoadjuvant therapy for esophageal cancer--what can we accept?

BACKGROUND/AIMS: We evaluated neoadjuvant use in managing patients with esophageal carcinoma and its effects on the surgical resection and outcomes. METHODOLOGY: Patients prior to esophageal resection were offered the opportunity to receive a neoadjuvant cytostatic regimen (CDDP + FU, CDDP, or TAX + FU). Retrospective tumor chemoresistance analysis using the MTT test was also performed. RESULTS: Seventy patients were operated from 2001 until May 2004. A total of 55 resections were performed with preoperative neoadjuvant therapy and 15 elected to only undergo surgery without neoadjuvant therapy. No deaths occurred as a result of surgery or neoadjuvant therapy, but complications included fistulas and hemorrhages. CONCLUSIONS: There was no significant difference between the postoperative complications among the neoadjuvant and non-neoadjuvant groups. This therapy therefore does not have any influence on the course or results of surgical resection. MTT testing did not demonstrate any particular usefulness in tailoring neoadjuvant therapy. Chemoresistance could only be retrospectively evaluated and the results may be affected after cytostatic therapy. The long-term outcomes have not been evaluated yet due to the short follow-up time in our patient group.

Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review.

INTRODUCTION: Acute pancreatitis is a rare but frequently fatal complication in patients following kidney transplantation. The first case of acute pancreatitis in patients following a kidney transplant was described by Starzl in 1964. The incidence of acute pancreatitis is stated at between 1 and 5%. The mortality rate amongst these patients reaches as high as 50-100%. PRESENTATION OF CASE: Here we present a case of acute pancreatic abscess in a caucasian female - shortly following a kidney transplant complicated by the development of acute rejection, in which immunosuppressant therapy is a potential etiological agent. Emergency surgical treatment was indicated, which included drainage of the abscesses irrigation of the abdominal cavity. Immunosuppressive medication was considered a possible etiological factor, and as a result administration of tacrolimus and mycophenolate mofetil was discontinued. This was successful and three months later, diagnostic rebiopsy of the graft was performed without signs of rejection. DISCUSSION: The etiology of this illness is multifactorial. The clinical manifestation of acute pancreatitis in patients following kidney transplantation is the same as in the remainder of the population. However, in patients following transplantation with long-term immunosuppression, it usually manifests a more rapid development and a more severe, frequently fatal course. CONCLUSIONS: With regard to the patient's comorbidities, early surgical therapy was indicated - drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.

Long-term survival after resections for pancreatic ductal adenocarcinoma. Single centre study.

AIM: To analyse the 5-year survival rate of patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC) and to identify prognostic factors. METHODS: A prospectively maintained database of 90 consecutive patients who underwent radical resection for PDAC was analysed. Survival was evaluated using the Kaplan-Meier method. Log-rank test and Cox regression analysis were used for the evaluation of prognostic factors. P values less than 0.05 were considered significant. RESULTS: Mean age (± standard deviation) was 63.2±8.6 years (female 28.9% and male 71.1%). Tumour localisation was in the head in 76 (84.5%), multifocal in 3 (3.3%) and in the body/tail in 11 (12.2%). Pancreatic head resection was performed in 75 (83.3%), total pancreatectomy in 4 (4.4%) and distal pancreatectomy with splenectomy in 11 (12.2%), with standard lymphadenectomy. Venous resection was in 4 (4.4%). Thirty-day and in-hospital mortality occurred in 1 (1.1%), 90-day mortality was 3.3%. On univariate analysis absence of perineural and vascular invasion, stage, absence of lymph node infiltration and no need for transfusion were associated with improved overall survival. On multivariate analysis vascular invasion HR=3.137 (95%CI: 1.692-5.816; P = 0.0003) and postoperative complications HR=2.004 (95%CI: 1.198-3.354; P = 0.008) were identified as significant independent predictors of survival. The five-year survival rate was 18.9%, with five-year recurrence-free survival of 16.7%. CONCLUSION: Vascular invasion and postoperative complications were independent prognostic factors after curative resections of pancreatic cancer in studied cohort.

Radiofrequency assisted liver resection--a novel technique.

Surgical resection remains the curative procedure for liver tumors, but even with improvements in method it is still a major operation with significant morbidity and mortality in experts' hands, and a long learning curve for those surgeons who undertake it. Recently radiofrequency ablation has gained some credibility as an alternative method of dealing with liver tumors deemed unresectable. A novel technique of liver resection assisted by the application of radiofrequency is described here. A patient with colorectal liver metastases underwent a segment II/III liver resection with this technique. Following laparotomy, the tumor was identified with intraoperative ultrasound and a 'cooled-tipped' radiofrequency probe was used to ablate liver parenchyma 2cm away from the edge of the tumor. To achieve full thickness of radiofrequency ablation, several insertions were applied. The effect of radiofrequency on liver parenchyma was monitored with an intraoperative ultrasound by micro-bubbles generated by radiofrequency ablation. The length of the resection was 45 min with a blood loss of 30mL. The patient was discharged on the 6th postoperative day without complications. In this report we indicate how the use of radiofrequency ablation can be combined with standard surgical resection of liver cancers to provide a quick, and relatively bloodless operation that is likely to reduce morbidity and mortality and is easy for its practitioners to learn.

Peripheral portosystemic shunt and its selectivity changes measured on duplex ultrasound.

BACKGROUND/AIMS: Portosystemic shunts offer a symptomatic treatment for portal hypertension. Their main disadvantage is decreased perfusion of the liver with portal blood. Change of peripheral shunts into total shunts after a period of time is described. This study aims to evaluate long-term hemodynamic changes in peripheral portosystemic shunts. METHODOLOGY: The study was based on 12 patients in whom distal splenorenal shunts 8 patients) and mesocaval shunts (4 patients) were indicated respectively. Duplex sonography was used to measure the blood flow in the portal, splenic and mesenteric veins before shunt surgery and minimally 14 months postoperatively. RESULTS: It was found that the reduction of the portal blood flow was not critical and no centralization of the shunt was observed. CONCLUSIONS: Long-term blood flow in the portal vein was not severely reduced after peripheral portosystemic shunt creation, therefore the peripheral portosystemic shunt still has a role in the treatment of some patients with portal hypertension.

Assessment of growth inhibition and morphological changes in in vitro and in vivo hepatocellular carcinoma models post treatment with dl1520 adenovirus.

BACKGROUND AND AIMS: E1B-deleted virus dl1520 (ONYX-015) has been previously used in clinical trials mainly for treatment of head and neck tumors, and has been shown to have beneficial effects independent of p53 status. The main aim of this investigation was to carry out a preclinical study for assessment of the use of dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various p53 status (deleted, mutant, and wild type), and study the ultrastructural changes in the carcinoma cells during and following treatment with dl1520. METHODS: dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines in culture, then for treatment of developed xenografts in SCID mice. The effects of dl1520 on HCC cell growth and accompanied morphological changes were assessed by various techniques including transmission electron microscopy. dl1520 infection was confirmed using polymerase chain reaction and immunolabeling at transmission electron microscopy level. RESULTS: dl1520 was effective in killing cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing was at higher levels in cells possessing abnormal p53. Survival rates in SCID mice treated with dl1520 were statistically significantly higher in HCC tumors with deleted and mutant p53, than in tumors with wild-type p53. CONCLUSIONS: The findings in this study suggest that dl1520 could be safely and effectively used for treatment of HCC dependent on the p53 status of the cells in vivo. Characteristic morphological changes that took place in the dl1520-treated HCC cells/tumors were distinct at transmission electron microscopy level and are the first of their kind to be reported.

Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The prognosis of HCC is poor and current therapies are largely ineffective. Genetic abnormalities are commonly seen in HCC tumors particularly with inactivation of the p53 tumor suppressor. Gene therapy with E1B-deleted (dl1520) adenovirus could be of therapeutic value as it offers the potential of tumor growth control in patients with p53 mutation. Ten patients with posthepatitis cirrhosis and histologically proven HCC were enrolled into an open label, randomized prospective study. Randomization was to receive either percutaneous ethanol injection (control group) or dl1520. Toxicity and complications in the ethanol group were pain and fever, whereas in the gene therapy group complications were minimal. Grade I-II toxicity fever, stable performance status, and no significant rise in liver enzymes were observed in patients treated with dl1520. Analysis of patients' response to treatment in the gene therapy group showed one patient with a partial response and four patients with progressive disease. In the ethanol-treated group two patients had stable disease and three patients showed disease progression. In conclusion, this study showed that the adenovirus was well tolerated, but did not seem to offer significant tumor control. Although only a small number of patients were treated here it appears that more effective vectors are needed to achieve a useful clinical impact.

Gene therapy for liver metastases.

Although resection is currently the only curative approach for metastatic liver cancer, only a small number of cases are suitable for this procedure. In the past few years, gene therapy has emerged as an appealing treatment option for liver cancer. Phase I and II clinical trials have been conducted in patients with either primary or secondary liver cancer using a variety of genes including tumor-suppressor gene p53, suicide genes, immune genes, and replication-competent oncolytic adenoviruses. The results have shown that, although gene therapy has been well tolerated and toxicity has been low, the clinical benefit has so far been marginal. Gene therapy as a definitive treatment for liver metastases remains limited, at least for the time being, but it may be useful as an adjuvant treatment in combination with radiotherapy, chemotherapy, and/or surgery to achieve disease-free survival.

Esophagogastric devascularization as the last option in the management of variceal bleeding.

Variceal bleeding is a clinical emergency that may be difficult to treat in some patients, especially those with prehepatic portal hypertension, failed sclerotherapy, and with contraindications to transjugular intrahepatic portosystemic shunt. In such patients there are few remaining options. The authors refer to three patients for whom the modified Sugiura procedure was the only remaining option for the treatment of variceal bleeding. Two of them had pre-hepatic portal hypertension, and one had hepatic cirrhosis, and in all, other standard treatment options and failed. The modified Sugiura devascularization and esophageal transection was performed without operative or postoperative complications and in the follow-up, (mean: 4.2 years), there was no recurrence of variceal bleeding. The authors recommend the modified Sugiura procedure as safe and effective for patients in whom other treatment options for variceal bleeding have failed.

Pseudoaneurysm of the gastroduodenal artery following pancreatoduodenectomy. Stenting for hemorrhage.

Postpancreatectomy hemorrhage (PPH) and pancreatic fistula are main and serious complications following pancreaticoduodenectomy. Postpancreatectomy hemorrhage is considered life-threatening for its high rate of mortality. Postpancreatectomy hemorrhage is defined as early, occurring within 24 h after surgery, and late. The authors present a case of late PPH which developed in the third week following pylorus-preserving pancreaticoduodenectomy. A 58-year-old man was operated on for cancer of the pancreatic head. Hemorrhage occurred when the patient was in full health, convalescing at home. The cause was bleeding from a pseudoaneurysm of the stump of the gastroduodenal artery directly into the gastrointestinal tract. Diagnosis was established based on computed tomography angiography. Treatment was performed using minimally invasive technique during angiography. The implantation of a stent graft into the common hepatic artery for bridging the stump of the gastroduodenal artery was performed. This method thus enabled at once both diagnosis and successful minimally invasive treatment.