Postoperative liver dysfunction remains a major concern following hepatic resection. In order to identify patients who are at risk of developing liver dysfunction, indocyanine green (ICG) clearance ...has been proposed to predict postoperative liver function. All patients who underwent liver resection at the Medical University Vienna, Austria between 2006 and 2015 with preoperative ICG clearance testing (PDR, R15) were analyzed in this study. Postoperative liver dysfunction was analyzed as defined by the International Study Group of Liver Surgery. Overall, 698 patients (male: 394 (56.4%); female: 304 (43.6%)) with a mean age of 61.3 years (SD: 12.9) were included in this study, including 313 minor liver resections (44.8%) and 385 major liver resections (55.2%). One hundred and seven patients developed postoperative liver dysfunction after liver resection (15.3%). Factors associated with liver dysfunction were: male sex (p = 0.043), major liver resection (p < 0.0001), and preoperative ICG clearance (PDR (p = 0.002) and R15 (p < 0.0001)). Notably ICG clearance was significantly associated with liver dysfunction in minor and major liver resections respectively and remained a predictor upon multivariable analysis. An optimal cut-off for preoperative ICG clearance to accurately predict liver dysfunction was PDR < 19.5%/min and R15 > 5.6%. To the best of our knowledge, this is the largest study analyzing the predictive value of preoperative ICG clearance assessment in patients undergoing liver resection. ICG clearance is useful to identify patients at risk of postoperative liver dysfunction.
Summary Background Patients with biliary tract cancer have a poor prognosis, and, until recently, no standard palliative chemotherapy has been defined. We aimed to investigate the efficacy and safety ...of cetuximab in combination with gemcitabine and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer. Methods From Oct 1, 2006, to July 26, 2008, patients with unresectable locally advanced or metastatic biliary tract cancer were sequentially enrolled and treated at one centre in Austria. All patients received intravenous infusions of 500 mg/m2 cetuximab on day 1, 1000 mg/m2 gemcitabine on day 1, and 100 mg/m2 oxaliplatin on day 2, every 2 weeks for 12 cycles. The primary outcome was overall response rate. Analysis was by intention to treat. Adverse reactions were assessed according to National Cancer Institute Common Toxicity Criteria. The study is completed and registered with ClinicalTrials.gov , number NCT01216345. Findings 30 patients with median age of 68 years (IQR 62–73) were enrolled and included in the analysis. Objective response occurred in 19 patients (63%; 95% CI 56·2–69·8), of whom three (10%; 3·2–16·8) achieved complete response, and 16 (53%; 46·2–59·8) achieved partial response. Nine patients underwent potentially curative secondary resection after major response to therapy. Grade 3 adverse events were recorded in 13 patients: skin rash (n=4), peripheral neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhoea (n=1), and neutropenia (n=1); no grade 4 adverse events were recorded. Interpretation Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients. These findings warrant further study of cetuximab plus GEMOX in a large randomised trial. Funding Association of Research on the Biology of Liver Tumors, Vienna, Austria.
Postoperative complications are still a major concern after liver resection (LR). Systemic inflammation and deregulated reactive oxygen species during major abdominal surgery may impair outcome after ...hepatectomy.
Patients undergoing LR were included in this study (n = 40). Oxidative stress (OS) was measured peri- and post-operatively as static oxidation-reduction potential markers (sORP) and antioxidant capacity ORP (cORP) by using the RedoxSYS Diagnostic system. Furthermore, Th1- and Th2-specific cytokines were assessed.
Whereas there was no significant change in systemic sORP during LR and in the early postoperative course, there was a substantial decrease of cORP immediately post-surgery, and on postoperative days 1 and 3 (p<0.001). OS response was tightly regulated, as there was a significant correlation between sORP and cORP (p<0.0001; R2:0.457). An increase of OS (sORP) after LR of more than 3 mV was predictive for severe postoperative complications (53.8% vs. 12.5; p = 0.017). There was a significantly higher IL-2 (p = 0.006) and IL-5 (p = 0.001) increase during hepatectomy in patients who developed a severe morbidity.
Antioxidant capacity remained stable during LR but dropped during the post-surgical period, suggesting a consumption of antioxidants to maintain OS within healthy range. Severe postoperative complications were associated with a pronounced inflammatory response during surgery.
Background
Resection margin status is a known prognosticator in patients who undergo resection for hilar cholangiocarcinoma. However, the influence of an isolated positive circumferential margin on ...clinical outcome is unclear.
Methods
Patients with resected de novo hilar cholangiocarcinoma from two European hepatobiliary centres (Medical University of Vienna and Aintree University Hospital, 2006–2016) were classified according to resection margin status (negative, surgically positive, isolated circumferentially positive) and investigated with respect to overall survival (OS), recurrence-free survival (RFS) and recurrence pattern.
Results
Eighty-three (48 male/35 female) patients were enrolled. The median age was 64 years (range 33–80). The median follow-up was 21.7 months (range 0.3–92.4). Forty (48%) patients had negative resection margins, 25 (30%) had an isolated positive circumferential margin and 18 (22%) had a positive surgical margin. The 5-year OS rates in patients with negative, isolated positive circumferential and positive surgical resection margins were 47%, 33% and 0%, respectively. Median OS was 45.6, 32.7 and 14.5 months, respectively (log rank,
P
= 0.011). Upon multivariable Cox regression analysis, resection margin status and lymph node status remained statistically significant (
P
< 0.05). No difference with respect to RFS and recurrence pattern was found between the groups (
P
> 0.05).
Conclusion
Our data show that these three resection margin types were associated with different clinical outcomes. Circumferential margin status may therefore serve as a novel prognostic biomarker.
Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human ...echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria.
Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012-2014. These data were used in conjunction with epidemiological data from Austria's national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE.
In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ - 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th- 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th- 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th- 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th- 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs.
This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs.
Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. ...However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear.
This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality.
Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020).
Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time.
ClinicalTrials.gov NCT01785212.
FDG-PET/MRI in alveolar echinococcosis Lötsch, Felix; Waneck, Fredrik; Auer, Herbert ...
International journal of infectious diseases,
November 2017, 2017-11-00, 20171101, 2017-11-01, Letnik:
64
Journal Article
Background
Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%–40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin ...(FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.
Methods
Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.
Results
We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.
Conclusions
Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.
von Willebrand factor antigen (vWF-Ag) is a noninvasive predictor of portal hypertension that serves as a negative prognostic marker in various malignancies. Increased portal hypertension is ...associated with higher postoperative morbidity and decreased survival after hepatectomy. The purpose of this study was to determine the correlation between vWF-Ag, postoperative morbidity and oncological outcome.
This analysis includes 55 patients who underwent liver resection for hepatocellular carcinoma (HCC) between 2008 and 2015 with available preoperative vWF-Ag levels. The primary endpoints were postoperative complications and long-term outcome, including overall and disease-free survival.
The median plasma level of vWF-Ag was 191% (range, 162.5% to 277%). There was a significant correlation between vWF-Ag levels and tumor size in the resected specimens (p=0.010, r=0.350). Patients who developed any grade of postoperative complication had significantly higher preoperative vWF-Ag levels (216% range, 178% to 283.25% vs 176% range, 148% to 246%, p=0.041). Median overall survival was 39.8 months in patients with high vWF-Ag levels (≥191%) compared with 73.4 months in patients with low levels (<191%, p=0.007). Of note, there was a remarkable disparity in the number of patients who died of HCC with low versus high vWF-Ag levels (14.8% vs 28.6%, p=0.011).
vWF-Ag may serve as a prognostic marker for the outcome of patients undergoing liver resection for HCC that is closely connected to tumor size, postoperative complication rate and long-term outcome.
The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.
From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases ...at 10 collaborating international institutions with documented KRAS status were surveyed.
A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio HR: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.
While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
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