Effect of Locoregional Treatments in Hepatocellular Carcinoma: What Are the Pathologic/Radiologic Milan Criteria?

OBJECTIVES: Milan criteria is the most commonly used criteria for patients with hepatocellular carcinoma awaiting liver transplant. The effects of locoregional therapy on downstaging or bridging before liver transplant on survival remain controversial. Considering that the tumor size may change with locoregional therapy and formalin fixation after explantation, we aimed to evaluate the effects of locoregional therapy on radiological and pathological Milan criteria and survival. MATERIALS AND METHODS: Demographic data, etiology, preoperative alpha-fetoprotein value, Child-Pugh and Model for End-Stage Liver Disease-Na scores, status of being inside or outside of radiological Milan criteria, status of being inside or outside of Milan criteria in explant (pathological Milan criteria), and the locoregional therapy types and combinations were evaluated for their effects on inclusion in Milan criteria and survival. RESULTS: During the study period, 396 patients underwent liver transplant at our center, with 97 because of cirrhosis and hepatocellular carcinoma. When we viewed patients according to preoperative radiologic evaluations, 67.9% were within Milan criteria and 32.1% were outside. When we viewed according to explant (pathological) evaluations, 80.7% of patients were within Milan criteria. Among 97 patients, 71 (73.2%) had locoregional therapy (22 [30.9%] for downstaging, 49 [69.0%] for bridging to transplant), and 12 patients (12.3%) were within Milan criteria on explant examination while outside of Milan criteria before LT. One-year, 3-year, and 5-year survival rates were 80.7%, 76.1%, and 71.6%, respectively. CONCLUSIONS: As a result of radiological evaluations, in patients who were outside of Milan criteria and underwent locoregional therapy, explant pathology within Milan criteria had a positive effect on survival; however, after locoregional therapy, there was no significant effect on survival in patients who were still outside of Milan criteria.

Internal versus external biliary drainage in malignant biliary obstructions: is there a difference in the rate of infection?

BACKGROUND: Percutaneous biliary drainage is a frequently used method to provide biliary decompression in patients with biliary obstruction. PURPOSE: To investigate the between drainage type and infection risk in patients treated with internal-external and external biliary drainage catheterization for malignant biliary obstruction. MATERIAL AND METHODS: A total of 410 patients with malignant biliary obstruction who underwent internal-external or external biliary drainage catheterization between January 2012 and October 2016 were retrospectively evaluated. We investigated the correlation between percutaneous biliary drainage technique and infection frequency by evaluating patients with clinical findings, bile and blood cultures, complete blood counts, and blood biochemistry. RESULTS: There was no statistically significant difference between the selected patient groups (internal-external or external biliary drainage catheter placed) in terms of age, sex, primary diagnosis, receiving chemotherapy, catheter sizes, and outpatient-patient status. After catheterization, catheter-related infection was observed in 49 of 216 (22.7%) patients with internal-external and 18 of 127 (14.2%) patients with external biliary drainage catheters, according to the defined criteria. There was no difference in infection rate after the biliary drainage in the two groups (P > 0.05). There was also no difference concerning frequently proliferating microorganisms in bile cultures. CONCLUSION: Internal-external biliary drainage catheter placement does not bring an additional infection risk for uninfected cholestatic patients whose obstruction could be passed easily in the initial drainage.

Investigation of the Effectiveness of Oleuropein in a Three-Dimensional In Vitro Hepatocellular Tumor Sphere Model.

OBJECTIVES: This study was conducted to examine the dose-related effects over time of oleuropein on the proliferation and area of tumor spheroids in hepatocellular carcinoma cells. MATERIALS AND METHODS: We examined the possible effects of 100 to 500 µM dose concentrations of oleuropein on HepG2 cell proliferation using a real-time cell analyzer. A 3-dimensional hepatocellular carcinoma tumor spheroid model was established by seeding HepG2 cells at a density of 160 cells/well in custom 96-well microplates with low attachment surfaces and culturing for 3 days. Tumor spheres were treated with increasing oleuropein doses for 72 hours, and images were captured every 24 hours. The dose-dependent effects of oleuropein on tumor sphere size were analyzed by measuring the area of tumor spheres with ImageJ software. We conducted oleuropein viability and cytotoxicity analyses using calcein acetoxymethyl ester-based and propidium iodide-based staining in the tumor model. RESULTS: Oleuropein inhibited cell proliferation; as the dose concentration of oleuropein increased, so did its capacity to inhibit cell proliferation (P < .001). The size of untreated tumor spheres increased at 72 hours (P < .001). However, treatment with 100 to 500 µM oleuropein reduced tumor size by 63.56% to 88.06% compared with untreated cells at the end of 72 hours (P < .001). With increasing concentrations, oleuropein inhibited the viability of tumor spheres, eliminating necrotic death caused by tumor hypoxia. CONCLUSIONS: Overall, oleuropein reduced the size of tumors by inhibiting tumor proliferation and viability. In this context, oleuropein could be a candidate molecule for further extensive studies to reduce hepatocellular carcinoma tumors to meet Milan criteria for liver transplant.

Evaluation of the Trend of Biochemical Functions in the Early Period After Cadaveric Liver Transplantation.

BACKGROUND: Monitoring biochemical parameters to detect early complications after liver transplantation (LT) is important. Thus, we aimed to investigate parameter trends indicating liver function in patients who did not develop complications after cadaveric LT. METHODS: A total of 266 cadaveric LT operations performed by a single center between 2007-2022 were included in the study. Patients with any early complications were excluded from the study. During the first 15 days, the parameters reflecting the patients' liver integrity and synthesis functions were evaluated. All parameters studied were evaluated at the same time of day and by a single laboratory. RESULTS: Regarding synthesis functions, the coagulation parameters (prothrombin time and international normalized ratio) peaked on the first day and then decreased. Regarding tissue hypoxia, there was no significant change in lactate values. Total and direct bilirubin values also decreased after peaking on the first day. No significant change was observed in albumin, another liver synthesis value. CONCLUSIONS: Although an increase in aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, prothrombin time, and international normalized ratio, which was especially seen on the first day, is considered normal, values that do not decrease after the second day or lactate values that increase gradually should be a warning in terms of possible early complications.

Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Turkish HPB Surgery Association consensus report on hepatic cystic Echinococcosis (HCE).

Objectives: Cystic Echinococcosis (CE) is one of the important problems of the Eurasian region. We aimed to prepare a consensus report in order to update the treatment approaches of this disease. This study was conducted by Turkish HPB Surgery Association. Material and Methods: This study was conducted with the modified Delphi model. For this purpose, we conducted a three-stage consensus-building approach. Results: Six topics, including diagnosis, medical treatment, percutaneous treatment, surgical treatment, management of complications and posttreatment follow-up and recurrences in HCE were discussed. Conclusion: The expert panel made recommendations for every topic.

Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List.

BACKGROUND: As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. METHODS: Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. RESULTS: In our study, 46.7% (n = 28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P = 0.001). CONCLUSIONS: Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.

Comparison of the Effect of Anesthetic Agents on Blood Levels of Parathyroid Hormone and Ionized Calcium: A Prospective Randomized Controlled Trial.

The aim of this randomized control trial is to compare the effect of anesthetic agents on blood levels of parathyroid hormone and ionized calcium. 77 American Society of Anesthesiologists I-II patients who would undergo laparoscopic cholecystectomy were enrolled into this prospective study and randomized into 3 groups with sealed envelope technique as Group S: sevoflurane, Group D: desflurane, and Group TIVA: total intravenous anesthesia. The first blood sample was used to check the baseline blood levels of parathyroid hormone and ionized calcium. In Group S or D, maintenance of anesthesia was being performed with 1 MAC (minimum alveolar concentration) sevoflurane or desflurane, respectively, while in Group TIVA, it was performed with 150 mcg/kg/min propofol and 1 mcg/kg/min remifentanil IV infusions. At the 30th minute of anesthesia and at the 1st hour of end of anesthesia, 2nd and 3rd blood samples, respectively, were used to check the blood levels of PTH and Ca. During perioperative period, hemodynamic parameters were also noted. Blood levels of parathyroid hormone at the 30th min after anesthesia were found to be significantly different between groups (P=0,01). The PTH level at the 30th min after anesthesia was found significantly higher in Group S than that of Groups D and TIVA (P=0.005 and P=0.001, respectively). Blood levels of ionized calcium at 30th min after anesthesia were found significantly different between groups (P=0,048). It was found significantly higher in Group TIVA than that in Group S (P=0.024). Desflurane seems to be the best agent for parathyroidectomy procedures. Future research studies are needed to be conducted to reach out more correct and valuable outcomes.

Duration of operation and diagnosis of hepatitis B (HBV) is an independent risk factor for surgical site infections after liver transplantation.

Objectives: Surgical site infections (SSI) are the most common complications after liver transplantation (LT). Although there are some risk factors known in the literature after LT, the available data is insufficient for routine use. In the present study, it was aimed to define the parameters that may be used to clearly determine the risk of SSI after LT in our clinic. Material and Methods: In the present study, we evaluated 329 patients who underwent liver transplantation with regard to risk factors for surgical site infections. The relation between demographic data and SSI was evaluated using SPSS, Graphpad, and Medcalc statistical programs. Results: In a total of 329 patients, SSIs were determined in 37 (11.24%). Among the 37 patients, 24 were classified as organ space (64.9%) and 13 as deep SSI (35.1%). None of these patients developed superficial incisional infection. SSI showed statistically significant relation with operation time (p= 0.008), diabetes (p= 0.004), and cirrhosis due to hepatitis B (p <0.001). Conclusion: As a result, deep and organ space infections are much more observed in patients undergoing liver transplantation with hepatitis B, diabetes mellitus and prolonged surgery. This is thought to have developed because of chronic irritation and increased inflammation. Since data on hepatitis B and duration of surgery are limited in the literature, this study is considered to be a contribution to the literature.

Myelitis After Liver Transplant: A Case Report.

We report a case of neurotoxicity as a side effect of a calcineurin inhibitor (tacrolimus), which is used as an immunosuppressive drug after liver transplant. Our patient had chronic hepatic failure due to Budd-Chiari syndrome and underwent a liver transplant after an appropriate deceased donor organ was obtained. After organ transplant surgery, he was kept under the effect of an immunosuppressive drug (tacrolimus) with daily control of the level of drug in his blood to avoid drug toxicity. Despite the level of drug in his blood being within the ideal range, the patient developed neurotoxicity that presented as weakness of his extremities. Appropriate diagnostic tests were done, and all proved that these signs and symptoms were related to the use of tacrolimus. Therefore, the drug was changed to cyclosporine. After a few months, the patient regained normal neurological functions of his extremities. We should take precautions to monitor neurological symptoms and signs while we administer calcineurin inhibitors.

Clinical Features and Short-Term Outcomes of Bariatric Surgery in Morbidly Obese Patients: Institutional Experience at a Rural Hospital.

Objective: To prospectively evaluate the postoperative morbidity, mortality, and weight loss evolution of patients who underwent a bariatric procedure during 1 year of follow-up. Methods: Since July 2016, a total of 101 patients' data have been prospectively registered in a database. Comorbidities, operating time, hospital stay, early and late complications rate, and weight loss evolution after 1 year of follow-up were recorded. Results: The mean age was 38.41 ± 11.05 years with a mean body mass index (BMI) of 49.02 ± 5.89 kg/m2 (range 38-67). Laparoscopic sleeve gastrectomy (LSG) was performed in 93 patients (92.07%) and Roux-en-Y gastric bypass (RNYGB) in 8 patients (7.92%). Thirty-day morbidity rate was 7.92% (8/101). Within a mean 9.32 ± 2.25 (range 1-19) months follow-up time, mean percent of the excess of weight loss of 1st, 6th, and 12th months were 22.7 ± 6.1, 67.2 ± 11.2, and 81.4 ± 10.5, respectively. Diabetes (n = 38, 37.6%), hypertension (n = 13, 12.9%), and obstructive sleep apnea (n = 5, 4.9%) were resolved in 76%, 68.4%, and 100% of the patients, respectively (p < 0.001). Conclusions: LSG and RNYGB are safe and highly effective, particularly in patients with a BMI >50 kg/m2. Both techniques have been presented with better clinical outcomes regarding significant comorbidity resolution in the early evolution of weight loss.

Liver Transplantation in Alstrom Syndrome: A Case Report.

Alstrom syndrome is a genetic disorder with autosomal recessive inheritance and multiple organ failure. Hearing loss, childhood obesity, diabetes mellitus, and nonalcoholic fatty liver disease are common disorders in this disease. Degree of nonalcoholic fatty liver disease ranges from benign steatosis to cirrhosis. Since it first description in 1959, 89 cases have been reported, and none in the literature underwent liver transplant. In this report, we describe a 19-year-old male patient with a diagnosis of hearing loss, obesity, and diabetes mellitus started since childhood. He was evaluated for bloody vomiting, and grade 3 esophageal varices were detected, with liver cirrhosis findings made with abdominal tomography. The patient had a Model for End-Stage Liver Disease score of 23, and deceased donor liver transplant was planned. After an appropriate donor was identified, the patient underwent liver transplant with an operation lasting approximately 6 hours. Cold ischemia time was about 5 hours, and anastomosis time was about 30 minutes. The patient was extubated on posttransplant day 1. On posttransplant day 10, his vital parameters remained normal, but he had blurred consciousness and loss of orientation. Neurological examination and imaging revealed minimal subdural effusion and mild cerebral cortical dysfunction in electroencephalogram. The patient's symptoms improved after medical treatment, and the patient was discharged on day 13 posttransplant. At the month 24 outpatient follow-up, the patient had no problems. Alstrom syndrome is an autosomal recessive genetic disorder with multiple organ failure. Although various degrees of liver disease have been described in the literature that may progress to cirrhosis of the liver, our present case is considered original because of the absence of liver transplant descriptions in the literature.

Effect of High Fructose Corn Sirup on Pancreatic Ductal Adenocarcinoma Induced by Dimethyl Benzantracene (DMBA) in Rats.

Increased risk of pancreatic cancer may be associated with consumption of sugar containing foods. The aim of this study was to evaluate the effect of peach nectar containing high fructose corn sirup (HFCS) consumption in a pancreatic carcinogenesis rat model induced by 7,12-Dimethyl benzanthracene (DMBA). Fifty-day-old male Sprague Dawley rats were fed with peach nectar containing HFCS + chow, peach nectar containing sucrose + chow and only chow. After 8 mo, feeding period, each group was divided into two subgroups, in which the rats were implanted with DMBA and no DMBA (sham). Histologic specimens were evaluated according to the routine tissue processing protocol. The animals with ad libitum access to pn-HFCS, pn-sucrose and chow (only) showed significant differences in chow consumption and glucose level. Necropsy and histopathologic findings showed tumor formation in the entire group treated with DMBA. Excluding one rat in chow group, which was classified as poorly differentiated type, the others were classified as moderately differentiated pancreatic ductal adenocarcinoma (PDAC). This study demonstrated that daily intake of HFCS did not increase body weight and there was no effect of peach nectar consumption on the development of PDAC induced by DMBA in rats.

Anastomotic leaks at the pancreaticojejunostomy following pancreaticoduodenectomy in patients with pancreatic head adenocarcinoma increases the local recurrence rate.

INTRODUCTION: In contrast to colorectal cancer patients, the effect of anastomosis leakage following pancreatic adenocarcinoma surgery on survival and recurrence rate is not clear. The present study aimed to determine the effect of pancreaticojejunostomy (PJ) anastomosis leakage, especially on the local recurrence rate and time of recurrence, in patients that underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. MATERIALS AND METHODS: This retrospective study included 64 pancreatic adenocarcinoma patients that underwent PD between January 2007 and August 2015. PJ anastomosis leakage was evaluated based on International Study Group on Pancreatic Fistula criteria. The effects of PJ anastomosis leakage on local recurrence, disease-free survival, and overall survival were assessed. RESULTS: Among the patients, 44 were male and 20 were female, and median age was 61(39-84) years. In all, 11 patients developed PJ leakage. Local recurrence occurred in 5 (45,4%) of the patients that developed PJ leakage, versus in 4 (7,5%) of the patients without leakage (p=0.02). Local recurrence developed earlier in those with leakage than in those without (p= 0,013). In contrast, there weren't any significant differences in disease-free survival, or overall survival. CONCLUSION: PJ leakage seems to be associated with more frequent and earlier local recurrence while it did not influence survival. KEY WORDS: Leakage, Pancreatic cancer, Recurrence.

Overexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region Tumors.

OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of cancer-related deaths worldwide. Although recent studies have highlighted the prognostic value of the long noncoding RNA HomeoboxA transcript at the distal tip (HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this study was to clarify the prognostic significance of HOTTIP in patients with all PRTs related to KRAS mutational status. METHODS: HomeoboxA transcript at the distal tip expression was detected in 100 PRT samples using quantitative real-time polymerase chain reaction. The associations between HOTTIP levels, clinicopathological factors, and patient prognosis were also analyzed. RESULTS: The expression of HOTTIP was found to be significantly upregulated by 32-fold (P = 0.031) in tumor tissues compared with normal tissues. The over expression of HOTTIP was related with presence of invasion and metastasis (P = 0.0467, P = 0.0256). In addition, increased HOTTIP expression was associated with poor prognosis independent of KRAS mutation (P < 0.001; n = 72). Moreover, multivariate analysis showed that high HOTTIP expression was an unfavorable prognostic factor for overall survival. CONCLUSIONS: Our findings indicate that high levels of HOTTIP expression have the potential to be an independent, unfavorable prognostic factor for patients with PRT.

Routine Use of Prophylactic Antibiotics during Laparoscopic Cholecystectomy Does Not Reduce the Risk of Surgical Site Infections.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for the treatment of symptomatic gallbladder stones. As infections are rare in uncomplicated LC, it is widely accepted that prophylactic antibiotics need not be administered, and guidelines do not support routine antibiotic prophylaxis during elective LC. However, routine antibiotic prophylaxis for elective LC is still popular in many clinical settings. We investigated this situation in our department. METHOD: This randomized double-blind controlled study included 570 patients who underwent LC between March 2007 and February 2010. The exclusion criteria were antibiotic intake before surgery, steroid treatment, and the presence of pancreatitis, cholangitis, obstructive jaundice, cephalosporin allergy, or pregnancy. The patients were randomized into three groups. Group 1 (n = 193) received physiologic saline as placebo, Group 2 (n = 191) received a first-generation cephalosporin (cefazolin; 1 g), and Group 3 (n = 186) received a second-generation cephalosporin (cefuroksim aksetil; 750 mg). Bile and epigastric and umbilical port tissue samples were harvested for culture. All patients were observed until the end of the fourth week after surgery. Patient age, sex, weight, American Society of Anesthesiologists (ASA) score, diabetes mellitus, smoking history, history of biliary colic in the past month, length of the hospital stay before the operation, operational findings (acute or chronic cholecystitis), operation duration, use of drainage, type of prophylaxis administered if any, culture results, surgical site infection (SSI) development, and time to SSI development along with associated treatments were evaluated. RESULTS: There was no statistically significant difference between the groups with respect to any of the demographic and clinical features analyzed in this study. The SSI rate was 1.2% in total, and in Groups 1, 2, and 3, it was 1.5%, 1.04%, and 1.07%, respectively. There was no statistical difference regarding SSI among the groups (p = 1.00). Superficial SSI was observed in all groups, and in all patients, the site of infection was the entrance to the epigastric port through which the gallbladder had been removed. CONCLUSIONS: Surgical site infection is rare after LC, and antibiotic prophylaxis does not appear to affect the outcome significantly. Moreover, factors such as positive bile cultures, history of biliary attack, ASA score, diabetes, obesity, and smoking do not have any effect on SSI development. Thus, we conclude that antibiotic prophylaxis is not needed for elective LC.

Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.

OBJECTIVE: Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. METHODS: Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. RESULTS: We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.

miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation.

OBJECTIVES: The success of gemcitabine plus radiotherapy is dependent on the mutation status of pancreatic ductal adenocarcinoma (PDAC) tumors in the EGFR and KRAS genes; however, radiotherapy resistance may also be modulated epigenetically by microRNA (miRNA) regulation. In this study, we examined the potential effect of miRNAs on the resistance to radiotherapy in cases without EGFR or KRAS mutation. METHODS: The association of EGFR and KRAS mutation status and different expression patterns of 6 selected miRNAs related to the EGFR/KRAS signaling pathway were evaluated in the tumors of 42 patients with PDAC. RESULTS: Reduced miR-216b and miR-217 expression was associated with aggressive tumor characteristics and shortened disease-free survival. In addition, miR-216b expression was reduced 2.7-fold in the cases that did not benefit from therapy, although they did not demonstrate EGFR or KRAS expression (P = 0.0316). A negative correlation between FGFR1 and miR-216b expression (r = -0.355) was found in the tumors of these cases. CONCLUSIONS: Further studies and validations are required; in the tumors of patients with PDAC without activating mutations and induced expression of EGFR/KRAS genes, down-regulated miR-216b expression may be associated with a poor response to radiotherapy via deregulation of another signaling pathway related to FGFR1 signaling.

Two Cases With Developing Neurologic Complications After Liver Transplant.

The widespread use of immunosuppressive agents has significantly increased the rates of successful solid-organ and stem cell transplants, especially with liver and kidney. Cyclosporine and tacrolimus are most commonly used for this purpose. Although these agents have different mechanisms of action, both have various adverse effects, including nausea, vomiting, headache, hypertension, nephrotoxicity, and rarely epileptic seizures. In our first case, a patient presented with epileptic seizures and hemiparesis after a liver transplant, and posterior reversible encephalopathy syndrome related to cyclosporine toxicity was considered. Once cyclosporine levels in the blood decreased, the patient had both clinical and radiologic improvements. In our second case, a patient presented with delirium after a liver transplant. Again, when cyclosporine levels in the blood decreased, the patient showed improvement in clinical findings. Neurologic complications may develop after liver transplant, and these complications are encountered most frequently within the first postoperative month. Neurologic complications are multifactorial; insufficient graft function, intracranial bleeding, cerebral infarcts, infections, and immunosuppressive drug toxicity (tacrolimus and cyclosporine) may be considered among these factors. As shown in our presented cases, most neurologic complications can be successfully treated by correcting the underlying factor.

Factors Affecting Surgical Site Infection Rates in Hepatobiliary Surgery.

BACKGROUND: There are several studies regarding risk factors affecting surgical site infections (SSIs); nevertheless, there are an insufficient number of studies focusing on risk factors for SSI in hepatobiliary (HPB) surgery. In this study, we aimed to determine risk factors related to HPB surgery. METHODS: A total of 1,418 patients were included in this study, all of whom underwent hepatobiliary system surgery in a five-year period between January 2005 and December 2009. Demographic data, patient- and surgery-related risk factors, and laboratory parameters were analyzed retrospectively from a database maintained prospectively. RESULTS: The overall incidence of SSI was 3.94% for HPB surgery. In multivariable analysis, blood transfusion (OR: 20.9), the presence of surgical drains (OR: 10.7), a pre-operative hospital stay of more than eight days (OR: 8.1), diabetes mellitus (OR: 6.2), chronic obstructive pulmonary disease (OR: 6.127), inappropriate antimicrobial prophylaxis (OR: 6), obesity (OR: 3.2), the presence of an external-internal biliary drainage catheter (OR: 2), and a direct bilirubin concentrations more than 15 mg/dL (OR: 1.4) were determined as independent risk factors related to SSI. E.coli and Enterococcus spp. were the pathogens isolated most commonly in SSIs. CONCLUSIONS: Most of the independent risk factors for hepatobiliary system surgery are similar to those for other general abdominal surgical procedures. The presence of an external-internal biliary drainage catheter and direct bilirubin concentrations higher than 15 mg/dL were found to be specific risk factors for HPB surgery.