Interventional Radiology Options after Visceral Surgery.

Background: Postoperative management of patients undergoing visceral surgery can present challenging clinical situations with significant morbidity and mortality. Interventional radiological techniques offer quick, safe, and effective minimally invasive treatment options in the postoperative management of visceral surgery. Summary: Most commonly done procedures include - but are not limited to - fluid or abscess drainage, biliary diversion, bleeding embolization, and re-canalization of a thrombosed vessel. While bleeding from side branches after hepatobiliary and pancreatic surgeries can be managed by coil embolization, the hepatic arterial injury should be managed by stent-graft placement. Hepatic venous complications can require a transhepatic or transjugular approach, whereas the transjugular intrahepatic portosystemic shunt approach has a higher clinical success rate in patients with portal vein thrombosis. Biliary leakages require multidisciplinary management, and interventional radiology can offer an efficient treatment, especially in patients with biliodigestive anastomosis. Key Messages: Interventional radiology provides a broad spectrum of procedures in the management of patients with recent visceral surgery.

Liver transplantation versus watchful waiting in hepatocellular carcinoma patients with complete response to bridging therapy - a retrospective observational study.

Bridging therapy to prevent progression on the waiting list can result in a sustained complete response (sCR). In some patients, the liver transplantation (LT) risk might exceed those of tumor recurrence. We thus evaluated whether a watchful waiting (CR-WW) strategy could be a feasible alternative to transplantation (CR-LT). We performed a retrospective analysis of overall survival (OS) and recurrence-free survival (RFS) of patients with a sCR (CR > 6 months). Permitted bridging included thermoablation, resection, and combinations of either with transarterial chemoembolization. Patients were divided into the intended treatment strategies CR-WW and CR-LT. 39 (18.40%) sCR patients from 212 were investigated. 22 patients were treated with a CR-LT and 17 patients a CR-WW strategy. Five-year RFS was lower in the CR-WW than in the CR-LT group [53.3% (22.1%; 77.0%) and 84.0% (57.6%; 94.7%)]. 29.4% (5/17) CR-WW patients received salvage transplantation because of recurrence. OS (5-year) was 83.9% [56.8%; 94.7%] after LT and 75.4% [39.8%; 91.7%] after WW. Our analysis shows that the intuitive decision made by our patients in agreement with their treating physicians for a watchful waiting strategy in sCR can be justified. Applied on a larger scale, this strategy could help to reduce the pressure on the donor pool.

A novel machine learning algorithm to predict disease free survival after resection of hepatocellular carcinoma.

BACKGROUND: Due to organ shortage, liver transplantation (LT) in hepatocellular carcinoma (HCC) patients can only be offered subsidiary to other curative treatments, including liver resection (LR). We aimed at developing and validating a machine-learning algorithm (ML) to predict which patients are sufficiently treated by LR. METHODS: Twenty-six preoperatively available routine laboratory values along with standard clinical-pathological parameters [including the modified Glascow Prognostic Score (mGPS), the Kings Score (KS) and the Model of Endstage Liver Disease (MELD)] were retrieved from 181 patients who underwent partial LR due to HCC in non-cirrhosis or compensated cirrhosis from January 2007 through March 2018 at our institution. These data were processed using a Random Forest (RF)-based workflow, which included preprocessing, recursive feature elimination (RFE), resampling, training and cross-validation of the RF model. A subset of untouched patient data was used as a test cohort. Basing on the RF prediction, test data could be stratified according to high (HR) or low risk (LR) profile characteristics. RESULTS: RFE analysis provided 6 relevant outcome predictors: mGPS, aPTT, CRP, largest tumor size, number of lesions and age at time of operation. After down-sampling, the predictive value of our model was 0.788 (0.658-0.919) for early DFS. 16.7% of HR and 74.2% of LR patients survived 2 years of follow-up (P<0.001). CONCLUSIONS: Our RF model, based solely on clinical parameters, proved to be a powerful predictor of DFS. These results warrant a prospective study to improve the model for selection of suitable candidates for LR as alternative to transplantation. The predictive model is available online: tiny.cc/hcc_model.

Liver Transplantation for Extended Criteria Hepatocellular Carcinoma Using Stable Response to Locoregional Therapy and Alpha-Fetoprotein as Selection Criteria.

INTRODUCTION: Current practice to only prioritize hepatocellular carcinoma (HCC) that fulfill the Milan criteria (INMC) is changing, since it causes the exclusion of patients who could benefit from liver transplantation. To select patients outside MC (OUTMC) for transplantation, we implemented extended selection criteria without up-front morphometric restrictions containing surrogate parameters of tumor biology. METHODS: OUTMC patients were considered without restrictions of morphometrics and received locoregional treatment after interdisciplinary consultation. Our dynamic selection criteria for OUTMC patients required (INMUC): (1) treatment response over (2) at least 6 months and (3) alpha-fetoprotein ≤400 ng/mL over the entire evaluation period. Patients with INMC tumors served as control and internal validation cohort. RESULTS: 31 of 170 liver transplant candidates were OUTMC. Of these, 8 dropped out. The remaining 23 patients met the selection criteria and underwent transplantation. Recurrence-free survival was higher in patients transplanted INMC compared to those OUTMC INMUC (92.2% vs. 70.8%; p = 0.026) after 5 years of follow-up. Overall survival showed no significant difference (p = 0.552). With dynamic selection of transplant candidates, recurrence could also be predicted for the INMC patients as internal validation cohort (c-index: 0.896; CI 0.588-0.981, p = 0.005). CONCLUSION: Dynamic selection criteria for the stratification of patients with OUTMC HCCs is feasible and allows for excellent long-term results and acceptable tumor recurrence rates comparable to INMC patients.

Liver transplantation in patients with a history of migration-A German single center comparative analysis.

Liver transplant (LT) programs in Germany increasingly face a multiethnic patient population. To date no outcome data for LT in patients with a history of migration is available for Germany. This complicates decision-making before wait-listing such patients. We conducted a single-center cohort analysis of all primary LT between April 2007 and December 2015, stratified for the history of migration to investigate differences in the outcome. We found transplant rates resembling the proportion of persons with a history of migration in the general public in the region of our center. Differences were found concerning age at LT and prevalence of underlying diseases. Re-Transplant rates, Kaplan-Meier Estimates for overall survival, also after stratification for viral hepatitis, sex, ethnicity or presence of a language-barrier showed no statistical differences. The multivariate analysis showed no migration-related covariate associated with a negative outcome. These results stand in contrast to most of the previous evidence from North America and the UK and need to be taken into consideration during the wait-listing process of patients with a history of migration in need of a LT in centers in the Eurotransplant region.

Development of novel biological resection criteria for safe and oncologically satisfying resection of hepatocellular carcinoma.

OBJECTIVE: To develop criteria for safe and oncologically satisfying liver resection in case of early hepatocellular carcinoma with a 5-year overall survival (OS) similar to liver transplantation. SUMMARY BACKGROUND DATA: Liver resection (LR) and liver transplantation (LT) are potentially curative treatment options for hepatocellular carcinoma. Generally, LT achieves better OS. Due to organ shortage, however not all patients can receive a LT. METHODS: To decide which patients to resect and which to transplant we have developed biological resection criteria (BRC) as a compound out of mGPS (modified Glascow Prognostic Scale) and the Kings-Score (for HCV cirrhosis). These are based on routine clinical values that reflect both liver function and tumor biology/immunology. RESULTS: 276 patients were analyzed. Patients undergoing LR within BRC (inBRC) had a significantly better overall (73.6% vs. 35.4%, (p < 0.001)) and disease-free survival (54.7% vs. 17.2%, (p < 0.001)) as compared to patients outside the BRC (outBRC). The predictive value of BRC was independent of tumor burden. In a subgroup analysis outBRC patients had significantly worse outcome after major resection. In LT patients BRC had no predictive value. CONCLUSIONS: BRC may be a valuable tool to predict survival after LR for HCC. Patients resected inBRC may achieve comparable survival as LT. LR in outBRC patients are unlikely to be curative. All outBRC patients should be monitored closely for salvage LT.

Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer.

BACKGROUND: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. METHODS: Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. RESULTS: Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. CONCLUSIONS: This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential.

Neoadjuvant chemoradiation for esophageal cancer : Surgery improves locoregional control while response based on FDG-PET/CT predicts survival.

INTRODUCTION: To retrospectively analyze the outcome of patients with esophageal cancer treated with neoadjuvant chemoradiation. METHODS: A total of 41 patients received neoadjuvant intent chemoradiation for esophageal cancer. Most patients had a locally advanced disease (T3/4: 82%, N+: 83%, M0: 100%) and squamous cell carcinoma (83%). All patients received concurrent chemotherapy with cisplatin/5-fluorouracil or mitomycin/5-fluorouracil. Median radiation dose was 50.4 Gy in the 25 patients who proceeded to surgery and 57.4 Gy in 16 patients who did not undergo surgery. FDG-PET/CT was used for treatment planning in 24 patients. A second FDG-PET/CT was available for response evaluation in 18 patients. RESULTS: Median follow-up was 16 months in all patients and 30 months in survivors. Radiotherapy was completed without interruptions >3 days in 90% of patients, and chemotherapy was carried out to >80% in 85% of patients. The 2­year locoregional control rate was 60%, distant control rate 54% and overall survival rate 50%. Hematological toxicity grade 3/4 was observed in 34%/10% of patients and non-hematological toxicity grade 3/4 in 46%/2% of patients. Perioperative 30-day mortality was 4%. Subgroup analyses revealed that surgery significantly improved locoregional control (74% vs. 39%, p = 0.034), but not the 2­year survival rate (54% vs. 43%, p = 0.246). In contrast, response based on FDG-PET/CT prior and after chemoradiation significantly predicted improved overall survival (2-year overall survival 61% vs. 40%, p = 0.048). CONCLUSION: Outcomes of our cohort were comparable to other series using similar treatments. Surgery significantly improved locoregional control but not survival. Response based on FDG-PET/CT predicted survival and might be used for treatment stratification.

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

Autologous but not Fibrin Sealant Patches for Stump Coverage Reduce Clinically Relevant Pancreatic Fistula in Distal Pancreatectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) causes significant morbidity and mortality after distal pancreatectomy. Patch coverage of the pancreatic stump is often used with the intention to prevent POPF. Despite numerous investigations, the effects of patch coverage remain unclear. The present meta-analysis aims to clarify the effects of patch coverage in distal pancreatectomy on the incidence of POPF. METHODS: A systematic search of MEDLINE/PubMed and the Cochrane Database according to the PRISMA Statement was performed. Subsequently a meta-analysis on rates and overall incidence of POPF and length of hospital stay was carried out. By applying the inverse variance weighting method, the combined effect size and 95 % confidence interval were calculated. Heterogeneity was assessed using I 2 statistics. RESULTS: Five randomized controlled trials and six observational clinical studies were included for final analysis. A cumulative incidence of 43 % of POPF grades A-C was identified. Patch coverage in distal pancreatectomy is significantly associated with a decreased rate of POPF grade C (p = 0.006). Patches of autologous vascularized tissue significantly reduce the overall incidence of POPF (p = 0.04) and clinically relevant POPF grade B and C (p = 0.002). Fibrin sealant patches do not influence rates of POPF after distal pancreatectomy. None of the outcomes evaluated showed adverse results for the patch group. CONCLUSIONS: Patch coverage after distal pancreatectomy can reduce the rate of POPF. Patch coverage with autologous vascularized tissue but not fibrin sealant patches may be used to reduce clinically relevant POPF and postoperative morbidity in distal pancreatectomy.

Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer.

PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

Arterial blood flow predicts graft survival in liver transplant patients.

Proper liver perfusion is essential for sufficient organ function after liver transplantation. The aim of this study was to determine the effects of portal and arterial blood flow on liver function and organ survival after liver transplantation. The arterial and portal venous blood flow was measured intraoperatively by transit time flow measurement after reperfusion for 290 consecutive liver transplants. The graft survival, hepatic cell damage (alanine aminotransferase and aspartate aminotransferase), and liver function (prothrombin ratio and bilirubin) were determined. Grafts were stratified into groups according to arterial blood flow measurements [<100 mL/minute for arterial blood flow group I (ART I), 100-240 mL/minute for ART II, and ≥ 240 mL/minute for ART III] and portal venous blood flow measurements (<1300 mL/minute for portal venous blood flow group I and ≥ 1300 mL/minute for portal venous blood flow group II). With multivariate analysis, the impact of blood flow on graft survival was determined, and potential confounders were considered. Decreased portal venous blood flow was associated with significantly less organ survival in univariate analysis but not in multivariate analysis. In contrast, the arterial blood flow was significantly correlated with organ survival after liver transplantation in univariate and multivariate analyses [hazard rate ratio = 2.5, confidence interval = 1.6-4.1, P < 0.001, median survival = 56.6 (ART I), 82.7 (ART II), or 100.7 months (ART III)]. Moreover, low arterial blood flow resulted in impaired postoperative organ function and higher rates of primary nonfunction. Biliary complications were not affected by blood flow. Other risk factors for graft failure that were identified by multivariate analysis included retransplantation, histidine tryptophan ketoglutarate solution versus University of Wisconsin solution, and donor treatment with epinephrine. Impaired arterial blood flow after reperfusion represents a significant predictor of primary graft nonfunction and is associated with impaired graft survival. Whether the intraoperative measurement of hepatic arterial flow is predictive of graft survival should be evaluated in a prospective trial.

The role of L-arginine following trauma and blood loss.

PURPOSE OF REVIEW: Vascular endothelial cells control vascular smooth muscle tone via the release of nitric oxide. Following adverse circulatory conditions, namely trauma and hemorrhage, endothelial cell dysfunction occurs, leading to a decrease in the release of endothelium-derived nitric oxide, which contributes to further alterations in tissue perfusion and organ function. RECENT FINDINGS: Early administration of L-arginine (the precursor of nitric oxide) and the substrate for nitric oxide synthase in vascular endothelial cells has been found to restore the depressed organ blood flow and to reduce tissue injury following shock. This improvement in cardiovascular function was associated with restoration of the depressed cell-mediated immune responses and attenuation of the massive inflammatory response encountered under such conditions. Furthermore, the excessive infiltration of the liver with neutrophils following trauma-hemorrhage was decreased by L-arginine administration, thereby reducing hepatic injury. In addition, L-arginine treatment decreased the inflammatory response at the site of trauma and the improved wound-healing process following blood loss. SUMMARY: Despite those promising results in animal models at present, none of the published clinical trials has demonstrated efficacy of L-arginine at doses above standard dietary practices on the outcome in critically ill surgical patients, besides the reduction in infectious complications.