Bevacizumab in combination with octreotide rescues a patient with liver cirrhosis, GAVE syndrome and refractory hemorrhage - a case report.

Gastric antral vascular ectasia (GAVE) syndrome is a rare but often challenging etiology of upper gastrointestinal bleeding (UGIB).We report on a 60-year-old patient with liver cirrhosis, GAVE syndrome and recurrent and refractory GAVE-related UGIB. During a 5-month hospital stay, the patient required a total of 82 packed red blood cells (pRBCs) and 23 gastroscopies. All endoscopic approaches, including multiple argon plasma coagulation and band ligation sessions, remained unsuccessful. Antrectomy was waived because of the high perioperative mortality risk in Child-Pugh B liver cirrhosis. TIPS insertion also failed to control the bleeding. Only continuous intravenous octreotide infusion slowed the bleeding, but this forced the patient to be hospitalized. After 144 inpatient days, administration of subcutaneous octreotide allowed the patient to be discharged. However, the patient continued to require two pRBCs every 2-3 weeks. Based on recently published data, we treated the patient with bevacizumab (anti-VEGF antibody) off-label at a dose of 7.5 mg/kg body weight every three weeks in nine single doses over six months. Since the first administration, the patient has remained transfusion-free, has not required hospitalization, and leads an active life, working full-time. He remains on octreotide, which has been reduced but not yet discontinued. Additionally, no adverse events were observed.Thus, in patients with liver cirrhosis and refractory GAVE-related hemorrhage, bevacizumab combined with subcutaneous octreotide should be considered as an effective and durable pharmacological treatment option.

Multidisciplinary approach to the complex treatment for non-cirrhotic portal hypertension - case-report-based discussion.

Non-cirrhotic portal vein thrombosis (PVT) in patients with antiphospholipid syndrome (APS) is a rare complication, and the management has to be determined individually based on the extent and severity of the presentation. We report on a 37-year-old male patient with non-cirrhotic chronic PVT related to a severe thrombophilia, comprising APS, antithrombin-, factor V- and factor X-deficiency. Three years after the initial diagnosis of non-cirrhotic PVT, the patient presented with severe hemorrhagic shock related to acute bleeding from esophageal varices, requiring an emergency transjugular intrahepatic portosystemic stent shunt (TIPSS). TIPSS was revised after a recurrent bleeding episode due to insufficient reduction of the portal pressure. Additionally, embolization of the dilated V. coronaria ventriculi led to the regression of esophageal varices but resulted simultaneously in a left-sided portal hypertension (LSPH) with development of stomach wall and perisplenic varices. After a third episode of acute esophageal varices bleeding, a surgical distal splenorenal shunt (Warren shunt) was performed to reduce the LSPH. Despite anticoagulation with low molecular weight heparin and antithrombin substitution, endoluminal thrombosis led to a complete Warren shunt occlusion, aggravating the severe splenomegaly and pancytopenia. Finally, a partial spleen embolization (PSE) was performed. In the postinterventional course, leukocyte and platelet counts increased rapidly and the patient showed no further bleeding episodes. Overall, this complex course demonstrates the need for individual assessment of multimodal treatment options in non-cirrhotic portal hypertension. This young patient required triple modality porto-systemic pressure reduction (TIPSS, Warren shunt, PSE) and involved finely balanced anticoagulation and bleeding control.

Liver transplantation and BCLC classification: Limitations impede optimum treatment.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) system has been endorsed by international guidelines as a staging algorithm of hepatocellular carcinoma. This analysis was performed to assess the outcome of liver transplantation in patients treated against the BCLC recommendations. METHODS: The data of 198 patients who underwent liver transplantation for hepatocellular carcinoma were extracted from a prospectively maintained database to classify the patients according to the BCLC system. RESULTS: BCLC staging was as follows: 0, n = 5; A, n = 77; B, n = 41; C, n = 53; and D, n = 22. Accordingly, liver transplantation was performed in the majority of patients against BCLC recommendations. Surgery (n = 16), radiofrequency ablation (n = 15) and transarterial chemoembolization (n = 151) preceded liver transplantation in 182 patients. Sixteen patients were transplanted without pretreatment. The1-, 5- and 10-year survival rates were 83.8%, 62.4% and 45.9%, and 1-, 5-, and 10-year recurrence rates were 7.7%, 22.7% and 26.7%. The BCLC classification did neither impact survival (P = 0.796) nor recurrence (P = 0.693). In the Cox analysis, RECIST tumor progression and initial alpha fetoprotein were independent predictors of outcome. CONCLUSIONS: Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome. Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.

Endovascular simulation training: a tool to increase enthusiasm for interventional radiology among medical students.

OBJECTIVES: Interventional radiology (IR) is a growing field but is underrepresented in most medical school curricula. We tested whether endovascular simulator training improves medical students' attitudes towards IR. MATERIALS AND METHODS: We conducted this prospective study at two university medical centers; overall, 305 fourth-year medical students completed a 90-min IR course. The class consisted of theoretical and practical parts involving endovascular simulators. Students completed questionnaires before the course, after the theoretical and after the practical part. On a 7-point Likert scale, they rated their interest in IR, knowledge of IR, attractiveness of IR, and the likelihood to choose IR as subspecialty. We used a crossover design to prevent position-effect bias. RESULTS: The seminar/simulator parts led to the improvement for all items compared with baseline: interest in IR (pre-course 5.2 vs. post-seminar/post-simulator 5.5/5.7), knowledge of IR (pre-course 2.7 vs. post-seminar/post-simulator 5.1/5.4), attractiveness of IR (pre-course 4.6 vs. post-seminar/post-simulator 4.8/5.0), and the likelihood of choosing IR as a subspecialty (pre-course 3.3 vs. post-seminar/post-simulator 3.8/4.1). Effect was significantly stronger for simulator training compared with that for seminar for all items (p < 0.05). For simulator training, subgroup analysis of students with pre-existing positive attitude showed considerable improvement regarding "interest in IR" (× 1.4), "knowledge of IR" (× 23), "attractiveness of IR" (× 2), and "likelihood to choose IR" (× 3.2) compared with pretest. CONCLUSION: Endovascular simulator training significantly improves students' attitude towards IR regarding all items. Implementing such courses at a very early stage in the curriculum should be the first step to expose medical students to IR and push for IR. KEY POINTS: • Dedicated IR-courses have a significant positive effect on students' attitudes towards IR. • Simulator training is superior to a theoretical seminar in positively influencing students' attitudes towards IR. • Implementing dedicated IR courses in medical school might ease recruitment problems in the field.

Validation of the SNACOR clinical scoring system after transarterial chemoembolisation in patients with hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation is the standard of care for intermediate stage (BCLC B) hepatocellular carcinoma, but it is challenging to decide when to repeat or stop treatment. Here we performed the first external validation of the SNACOR (tumour Size and Number, baseline Alpha-fetoprotein, Child-Pugh and Objective radiological Response) risk prediction model. METHODS: A total of 1030 patients with hepatocellular carcinoma underwent transarterial chemoembolisation at our tertiary referral centre from January 2000 to December 2016. We determined the following variables that were needed to calculate the SNACOR at baseline: tumour size and number, alpha-fetoprotein level, Child-Pugh class, and objective radiological response after the first transarterial chemoembolisation. Overall survival, time-dependent area under receiver-operating characteristic curves, Harrell's C-index, and the integrated Brier score were calculated to assess predictive ability. Finally, multivariate analysis was performed to identify independent predictors of survival. RESULTS: The study included 268 patients. Low, intermediate, and high SNACOR scores predicted a median survival of 31.5, 19.9, and 9.2 months, respectively. The areas under the receiver-operating characteristic curve for overall survival were 0.641, 0.633, and 0.609 at 1, 3, and 6 years, respectively. Harrell's C-index was 0.59, and the integrated Brier Score was 0.175. Independent predictors of survival included tumour size (P < 0.001), baseline alpha-fetoprotein level (P < 0.001) and Child-Pugh class (P < 0.004). Objective radiological response (P = 0.821) and tumour number (P = 0.127) were not additional independent predictors of survival. CONCLUSIONS: The SNACOR risk prediction model can be used to identify patients with a dismal prognosis after the first transarterial chemoembolisation who are unlikely to benefit from further transarterial chemoembolisation. However, Harrell's C-index showed only moderate performance. Accordingly, this risk prediction model can only serve as one of several components used to make the decision about whether to repeat treatment.

Validation of Clinical Scoring Systems ART and ABCR after Transarterial Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To perform an external validation of the Assessment for Retreatment with Transarterial Chemoembolization (ART) and α-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), Child-Pugh, and response (ABCR) scores and to compare them in terms of prognostic power. MATERIALS AND METHODS: From 2000 to 2015, 871 patients with hepatocellular carcinoma underwent transarterial chemoembolization at a tertiary referral hospital, and 176 met all inclusion and exclusion criteria for both scores and were analyzed. Nineteen percent (n = 34) had BCLC stage A disease and 81% had stage B disease. Thirty-nine patients (22%) presented with elevated AFP levels. Overall survival was calculated. Scores were validated and compared with a Harrell C-index, integrated Brier score (IBS), and prediction error curves. RESULTS: Before the second chemoembolization procedure, 22 patients (12%) showed an increase of 1 point in Child-Pugh score and 51 patients (22%) had an increase of ≥ 2 points. Thirty-one patients (23%) showed a > 25% increase in aspartate aminotransferase level, and 114 (65%) showed a response to treatment. Consequently, 127 patients (72%) had a low ART score and 49 (28%) had a high ART score. One hundred fifty-eight patients (90%) had a low ABCR score, whereas 18 (10%) had a high ABCR score. Low and high ART score groups had median survival durations of 20.8 and 15.3 mo, respectively. Harrell C-indexes were 0.572 and 0.608, and IBSs were 0.135 and 0.128, for ART and ABCR, respectively. For both scores, an increase in Child-Pugh score ≥ 2 points and a radiologic response were significantly associated with survival. CONCLUSIONS: Both scores were of limited predictive value, and neither was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for making valid clinical predictions.

Conventional transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for the treatment of hepatocellular carcinoma.

BACKGROUND: To compare the overall survival of patients with hepatocellular carcinoma (HCC) who were treated with lipiodol-based conventional transarterial chemoembolization (cTACE) with that of patients treated with drug-eluting bead transarterial chemoembolization (DEB-TACE). METHODS: By an electronic search of our radiology information system, we identified 674 patients that received TACE between November 2002 and July 2013. A total of 520 patients received cTACE, and 154 received DEB-TACE. In total, 424 patients were excluded for the following reasons: tumor type other than HCC (n=91), liver transplantation after TACE (n=119), lack of histological grading (n=58), incomplete laboratory values (n=15), other reasons (e.g., previous systemic chemotherapy) (n=114), or were lost to follow-up (n=27). Therefore, 250 patients were finally included for comparative analysis (n=174 cTACE; n=76 DEB-TACE). RESULTS: There were no significant differences between the two groups regarding sex, overall status (Barcelona Clinic Liver Cancer classification), liver function (Child-Pugh), portal invasion, tumor load, or tumor grading (all p>0.05). The mean number of treatment sessions was 4±3.1 in the cTACE group versus 2.9±1.8 in the DEB-TACE group (p=0.01). Median survival was 409 days (95% CI: 321-488 days) in the cTACE group, compared with 369 days (95% CI: 310-589 days) in the DEB-TACE group (p=0.76). In the subgroup of Child A patients, the survival was 602 days (484-792 days) for cTACE versus 627 days (364-788 days) for DEB-TACE (p=0.39). In Child B/C patients, the survival was considerably lower: 223 days (165-315 days) for cTACE versus 226 days (114-335 days) for DEB-TACE (p=0.53). CONCLUSION: The present study showed no significant difference in overall survival between cTACE and DEB-TACE in patients with HCC. However, the significantly lower number of treatments needed in the DEB-TACE group makes it a more appealing treatment option than cTACE for appropriately selected patients with unresectable HCC.

Visceral artery aneurysms: Incidence, management, and outcome analysis in a tertiary care center over one decade.

OBJECTIVES: To evaluate the incidence, management, and outcome of visceral artery aneurysms (VAA) over one decade. METHODS: 233 patients with 253 VAA were analyzed according to location, diameter, aneurysm type, aetiology, rupture, management, and outcome. RESULTS: VAA were localized at the splenic artery, coeliac trunk, renal artery, hepatic artery, superior mesenteric artery, and other locations. The aetiology was degenerative, iatrogenic after medical procedures, connective tissue disease, and others. The rate of rupture was much higher in pseudoaneurysms than true aneurysms (76.3% vs.3.1%). Fifty-nine VAA were treated by intervention (n = 45) or surgery (n = 14). Interventions included embolization with coils or glue, covered stents, or combinations of these. Thirty-five cases with ruptured VAA were treated on an emergency basis. There was no difference in size between ruptured and non-ruptured VAA. After interventional treatment, the 30-day mortality was 6.7% in ruptured VAA compared to no mortality in non-ruptured cases. Follow-up included CT and/or MRI after a mean period of 18.0 ± 26.8 months. The current status of the patient was obtained by a structured telephone survey. CONCLUSIONS: Pseudoaneurysms of visceral arteries have a high risk for rupture. Aneurysm size seems to be no reliable predictor for rupture. Interventional treatment is safe and effective for management of VAA. KEY POINTS: • Diagnosis of visceral artery aneurysms is increasing due to CT and MRI. • Diameter of visceral arterial aneurysms is no reliable predictor for rupture. • False aneurysms/pseudoaneurysms and symptomatic cases need emergency treatment. • Interventional treatment is safe and effective.

Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention-to-treat principle.

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre-treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention-to-treat principle resulted in a better five-yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five-yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five-yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.

Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1066 cases of a German HCC Registry.

GOALS: The aim of this study was to analyze clinical presentation, course of disease, and management of patients with hepatocellular carcinoma (HCC) in a German referral center between 1998 and 2009. BACKGROUND: HCC is a rare tumor in Germany, but its incidence has increased over the last 30 years. New therapies such as chemoembolization with drug-eluting beads, selective internal radiotherapy, and sorafenib were introduced recently; however, the impact on clinical management and overall survival (OS) is unclear. STUDY: In this retrospective analysis, 1066 patients with HCC, separated into two 6-year periods (n=385; 1998 to 2003 and n=681; 2004 to 2009) were evaluated. RESULTS: The number of patients presenting each year (64 vs. 114 per year), with an age over 80 years or with nonalcoholic steatohepatitis increased significantly between periods. The main risk factors were alcoholic liver disease in 51.7%, chronic hepatitis C virus in 28.2%, and chronic hepatitis B virus in 13.4% of patients with liver cirrhosis and HCC. Patients presented with more advanced tumor stages and with worse liver function in period 2. The majority (61.6%) of patients received local treatment over a spectrum of Barcelona Clinic Liver-Cancer (BCLC) stages, whereas systemic therapy was offered to a minority (8.8%) and limited to BCLC stage C patients only. OS decreased in BCLC stage A and D and improved in BCLC stage B and C and decreased for all patients from 16.5 to 15.3 months between periods. CONCLUSIONS: No improvement of OS was observed when comparing time periods, partly because of the more advanced stage of HCC and because of the increasing age in the second time period. Improved and new therapeutic options and the intensification of surveillance programs are likely to increase survival of HCC patients in the future.

How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?

BACKGROUND & AIMS: Liver transplantation is a curative treatment option for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. To date, patient selection for transplantation is based on size and number of nodules as assessed by imaging before listing. We hypothesized that changes in tumour features resulting from pre-transplant transarterial chemoembolisation (TACE) is a superior criterion to predict tumour recurrence. METHODS: 136 patients with HCC in cirrhosis with two or more cycles of pre-transplant TACE were included in this study. According to the surgical specimens, 46 patients exceeded the Milan criteria. RESULTS: Tumour recurrence occurred in 21 patients (15%). Classification of Milan criteria according to the imaging at referral was not predictive for recurrence (p=0.58), whereas the Milan criteria in the imaging immediately before transplantation reflected changes after pre-transplant TACE and were highly predictive (p<0.0001). Of the 99 patients constantly within Milan or downstaged to within Milan, 88% were recurrence-free after 5 years, compared to 55% of the patients exceeding the Milan criteria despite pre-transplant TACE. Five-year absence of recurrence was better predicted by the criterion "Progressive Disease" according to RECIST (p<0.0001). If progression was defined as any progression (including less than 20% of the sum of target lesions or new measurable lesions), predictability of recurrence in the receiver operating characteristic was 0.86. CONCLUSIONS: Imprecise assessment of size and number of tumour lesions limits prognostic importance of initial imaging. Characteristics of tumour response to TACE are reliably recognized and allow identification of suitable patients for transplantation. Future selection criteria for LT in HCC should consider this aspect.

Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.

Strategies for endovascular aortic repair in aortobronchial and aortoesophageal fistulas.

OBJECTIVE: To report our experience of thoracic endovascular aortic repair (TEVAR) for acute bleeding originating from the thoracic aorta in patients with aortobronchial fistula (ABF) or aortoesophageal fistula (AEF). PATIENTS AND METHODS: A total of nine patients (three woman) were treated from September 1995 to March 2012 by TEVAR for ABF (n = 5) and AEF (n = 4). The implants (N = 14) were introduced with fluoroscopic guidance via the aorta (n = 1), the iliac (n = 2), or femoral (n = 11) artery, respectively. RESULTS: All aortic lesions could be sealed successfully. Perioperative morbidity was 0% in the ABF group and 50% (2 of 4) in the AEF group and no procedure-related morbidity was noted except one patient who received aortofemoral reconstruction because of iliac occlusive disease. After an overall mean follow-up of 56 months, three patients of the ABF group are alive and well and two patients died of nonrelated cause. Of the AEF group, one patient is alive after 22 months, and one died from metastasized esophageal cancer after 7 months. CONCLUSION: TEVAR is a safe and reliable procedure in the management of ABF. For AEF, TEVAR provides a successful first-line treatment to seal the fistula and control bleeding. However, prognosis is limited by the esophageal lesion and by ongoing mediastinitis/sepsis.

Minimal invasive aortic arch repair with suture-mediated closure system.

Port implantation can be associated with an array of serious vascular complications, typically involving the subclavian artery. We report a case in which implantation of a port resulted in iatrogenic perforation of the aortic arch at the level of the left subclavian artery, which was sealed off using a percutaneous vascular closure device.

Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

OBJECTIVES: To determine the most comprehensive imaging technique for the assessment of pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: 24 patients with CTEPH were examined by ECG-gated multi-detector CT angiography (MD-CTA), contrast-enhanced MR angiography (ce-MRA) and selective digital subtraction angiography (DSA) within 3 days. Two readers in consensus separately evaluated each imaging technique (48 main, 144 lobar and 449 segmental arteries) for typical changes like complete obstructions, vessel cut-offs, intimal irregularities, incorporated thrombus formations, and bands and webs. A joint interpretation of all three techniques served as a reference standard. RESULTS: Based on image quality, there was no non-diagnostic examination by either imaging technique. DSA did not sufficiently display 1 main, 3 lobar and 4 segmental arteries. The pulmonary trunk was not assessable by DSA. One patient showed thrombotic material at this level only by MD-CTA and MRA. Sensitivity and specificity of MD-CTA regarding CTEPH-related changes at the main/lobar and at the segmental levels were 100%/100% and 100%/99%, of ce-MRA 83.1%/98.6% and 87.7%/98.1%, and of DSA 65.7%/100% and 75.8%/100%, respectively. CONCLUSION: ECG-gated MD-CTA proved the most adequate technique for assessment of the pulmonary arteries in the diagnostic work-up of CTEPH patients. KEY POINTS: • A prospective single-centre study evaluated ECG-gated MDCTA, ce-MRA and DSA in CTEPH patients. • ECG-gated MD-CT angiography outperformed DSA and ce-MRA. • Right heart catheterisation should be reserved only for assessment of pulmonary haemodynamics.

Radiation exposure in vascular angiographic procedures.

PURPOSE: To evaluate dose reduction in vascular angiographic procedures by using fluoroscopy capture instead of digital subtraction angiography frames for documentation. MATERIALS AND METHODS: A total of 764 consecutive vascular interventional procedures performed over a period of 1 year were retrospectively analyzed with respect to the fluoroscopy time and the resulting dose-area product (DAP), the DAP of the radiographic frames, and the overall DAP. RESULTS: A total of 70% of the total DAP was a result of the acquisition of radiographic frames, leaving only 30% being applied by fluoroscopy. CONCLUSIONS: Fluoroscopy capture should be used for documentation whenever possible. A registry of radiation exposure should not only comprise a sufficiently large number of interventions but also different intervention types to allow the development of interventional reference levels.

Prognostic factors and outcomes of patients with hepatocellular carcinoma in non-cirrhotic liver.

OBJECTIVES: To report the outcome of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver depending on the mode of primary treatment and to define clinicopathological factors influencing patients' prognosis. METHODS: A retrospective analysis of an unselected cohort of 105 patients was performed. Overall survival (OS) was estimated by the Kaplan-Meier method and potentially prognostic factors were analyzed in Cox regression models. RESULTS: OS of the whole cohort at 1, 3, and 5 years was 66%, 47%, and 29%, respectively. Tobacco consumption, ECOG >0, macroscopic vascular invasion, continuous tumor diameter, and treatment other than resection were predictors of decreased OS in the whole cohort. Resection was performed in 64% of patients with 1-, 3-, and 5-year OS rates of 84%, 69%, and 42%, respectively. Siderosis and BCLC stage were associated with decreased OS after resection. Recurrence occurred in 57% of patients with 1-, 3-, and 5-year disease-free survival (DFS) rates of 63%, 39%, and 31%, respectively. Viral hepatitis and macroscopic vascular invasion were associated with decreased DFS. One-, 3-, and 5-year OS rates in patients with non-surgical approaches (transarterial chemoembolization, systemic therapy, best supportive care) were 38%, 11%, and 7%, respectively. Tobacco consumption and Okuda stage were associated with decreased OS in these patients. CONCLUSIONS: OS and DFS of patients with HCC in non-cirrhotic liver depend most notably on tumor-related, demographic, and etiological factors. Features of the non-neoplastic liver tissue play only a minor role. Liver resection leads to a significantly better prognosis than non-surgical treatment approaches.

Transjugular Portosystemic Stent Shunt: Impact of Right Atrial Pressure on Portal Venous Hemodynamics Within the First Week.

PURPOSE: Porto-systemic pressure gradient is used to prognosticate rebleeding and resolution of ascites after TIPS. This study investigates the reliability of portal pressure characteristics as quantified immediately after TIPS placement and at short-term control. PATIENTS AND METHODS: Portal venous pressure (PVP) and right atrial pressure (RAP) were prospectively obtained before and after TIPS as well as ≥ 48 h after TIPS procedure. Porto-systemic pressure gradients (PSG) and pressure changes were calculated. A multivariate regression analysis was performed to predict portal hemodynamics at short-term control. RESULTS: The study included 124 consecutive patients. Indications for TIPS were refractory ascites, variceal bleeding or combinations of both. Pre- and post-interventional PSG yielded 16.4 ± 5.3 mmHg and 5.9 ± 2.7 mmHg, respectively. At that time, 105/124 patients (84.7%) met the target (PSG ≤ 8 mmHg). After 4 days (median), PSG was 8.5 ± 3.5 mmHg and only 66 patients (53%) met that target. In patients exceeding the target PSG at follow-up, PVP was significantly higher and RAP was lower resulting in the increased PSG. The highly variable changes of RAP were the main contributor to different pressure gradients. In the multivariate regression analysis, PVP and RAP immediately after TIPS were predictors for PSG at short-term control with moderately predictive capacity (AUC = 0.75). CONCLUSION: Besides the reduction of portal vein pressure, the highly variable right atrial pressure was the main contributor to different pressure gradients. Thus, immediate post-TIPS measurements do not reliably predict portal hemodynamics during follow-up. These findings need to be further investigated with respect to the corresponding clinical course of the patients.

Prevalence and clinical significance of clinically evident portal hypertension in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND: Clinically evident portal hypertension (CEPH) was previously identified as a prognostic factor for patients with hepatocellular carcinoma (HCC). However, little is known about the prognostic influence of CEPH on the long-term outcome of patients with HCC undergoing transarterial chemoembolization (TACE), particularly in Western populations. OBJECTIVES: This study investigated the prevalence and prognostic influence of CEPH in a Western population of patients with HCC undergoing TACE. METHODS: This retrospective study included 349 treatment-naïve patients that received initial TACE treatment at our tertiary care center between January 2010 and November 2020. CEPH was defined as a combination of ascites, esophageal/gastric varices, splenomegaly and a low platelet count. We assessed the influence of CEPH and its defining factors on median overall survival (OS) in HCC patients. We compared the effects of CEPH to those of well-known prognostic factors. RESULTS: Of the 349 patients included, 304 (87.1%) patients had liver cirrhosis. CEPH was present in 241 (69.1%) patients. The median OS times were 10.6 months for patients with CEPH and 17.1 months for patients without CEPH (log rank p = 0.036). Median OS without a present surrogate was 17.1 months, while patients with one respectively more than two present CEPH surrogates had a median OS of 10.8 and 9.4 months (log rank p = 0.053). In multivariate analysis, CEPH was no significant risk factor for OS (p = 0.190). Of the CEPH-defining factors, only ascites reached significance in a univariate analysis. CONCLUSION: CEPH was present in more than two thirds of the patients with HCC undergoing TACE in our cohort of Western patients. Patients with CEPH had a significantly impaired survival in univariate analysis. However, no significance was reached in multivariate analysis. Thus, when TACE treatment is deemed oncologically reasonable, patients should not be excluded from TACE treatment due to the presence of surrogates of portal hypertension alone.

13 C-Methacetin Breath Test Predicts Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

INTRODUCTION: The 13 C-methacetin breath test ( 13 C-MBT) is a dynamic method for assessing liver function. This proof-of-concept study aimed to investigate the association between 13 C-MBT values and outcomes in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: A total of 30 patients with HCC were prospectively recruited. Of these, 25 were included in baseline and 20 in longitudinal analysis. 13 C-MBTs were performed before the first and second TACE session. Patients were followed for at least 1 year. RESULTS: At baseline, the median 13 C-MBT value was 261 µg/kg/hr (interquartile range 159-387). 13 C-MBT, albumin-bilirubin, Child-Pugh, and Model for End-Stage Liver Disease scores were associated with overall survival in extended univariable Cox regression ( 13 C-MBT: standardized hazard ratio [sHR] 0.297, 95% confidence interval [CI] 0.111-0.796; albumin-bilirubin score: sHR 4.051, 95% CI 1.813-9.052; Child-Pugh score: sHR 2.616, 95% CI 1.450-4.719; Model for End-Stage Liver Disease score: sHR 2.781, 95% CI 1.356-5.703). Using a cutoff of 140 µg/kg/hr at baseline, 13 C-MBT was associated with prognosis (median overall survival 28.5 months [95% CI 0.0-57.1] vs 3.5 months [95% CI 0.0-8.1], log-rank P < 0.001). Regarding prediction of 90-day mortality after second 13 C-MBT, the relative change in 13 C-MBT values yielded an area under the receiver-operating characteristic curve of 1.000 ( P = 0.007). DISCUSSION: Baseline and longitudinal 13 C-MBT values predict survival of patients with HCC undergoing TACE. The relative change in 13 C-MBT values predicts short-term mortality and may assist in identifying patients who will not benefit from further TACE treatment.