Michael Bernhard Pitton

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety‐six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5‐year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P < 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n = 39) with progress‐free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n = 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P = 0.0017). Progress‐free course of TACE during the waiting time (P = 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P = 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number. Liver Transpl 12:1260‐1267, 2006.

Mid-term results of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension

BACKGROUND In patients with chronic thromboembolic pulmonary hypertension, acute and striking decreases of pulmonary artery pressures and vascular resistance can be achieved by pulmonary thromboendarterectomy. In this study, the long-term effects of pulmonary thromboendarterectomy on hemodynamic indices and right ventricular function were investigated. METHODS Sixty-five patients (31 women and 34 men; mean age, 47 +/- 17 years; range, 19 to 69 years; New York Heart Association [NYHA] functional class II, n = 3; class III, n = 38; class IV, n = 24) were reassessed 13 to 48 months (mean, 27 months) after pulmonary thromboendarterectomy. Measurements are reported as mean +/- standard deviation. RESULTS All patients reported a significant improvement of symptoms: 46 patients were in NYHA functional class I, 16 patients in class II, and 3 patients in class III. Mean pulmonary vascular resistance was significantly reduced compared with preoperative and postoperative values (preoperative: 1,015 +/- 454 dynes.s.cm-5; postoperative: 322 +/- 154 dynes.s.cm-5; follow-up: 198 +/- 72 dynes.s.cm-5; p < 0.001 versus preoperative; p < 0.025 versus postoperative). Concomitantly, cardiac index was significantly increased compared with preoperative values (preoperative: 2.0 +/- 0.7 L.min-1.m-2; follow-up: 2.9 +/- 0.5 L.min-1.m-2; p < 0.001). Significant reductions of right ventricular dimensions and recovery of right ventricular function could be demonstrated radiologically and echocardiographically. In 3 patients (preoperative NYHA class IV, NYHA class III at follow-up) with proven coagulation abnormalities, pulmonary vascular resistance was moderately increased at follow-up compared with postoperative measurements. CONCLUSIONS In patients with chronic thromboembolic pulmonary hypertension, a persistent decrease of pulmonary vascular resistance and improvement of right ventricular function and NYHA functional status can be achieved by pulmonary thromboendarterectomy.

Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery.

Objective:Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery. Summary Background Data:Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment. Methods:According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n = 28). Resection (n = 82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible. Results:Local recurrence at the site of ablation or resection occurred in 32% and 4% (P < 0.001), new metastases apart from the site of previous treatment in 50% and 34% (P = 0.179), and systemic recurrence in 32% and 37% (P = 0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P = 0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P = 0.93. Conclusions:Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.

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. Liver Transpl 19:1108‐1118, 2013.

MRI Versus Helical CT for Endoleak Detection After Endovascular Aneurysm Repair

OBJECTIVE The objective of our study was to investigate the diagnostic accuracy of MRI and helical CT for endoleak detection. SUBJECTS AND METHODS Fifty-two patients underwent endovascular aneurysm repair with nitinol stent-grafts. Follow-up data sets included contrast-enhanced biphasic CT and MRI within 48 hr after the intervention; at 3, 6, and 12 months; and yearly thereafter. The endoleak size was categorized as < or = 3%, > 3% < or = 10%, > 10% < or = 30%, or > 30% of the maximum cross-sectional aneurysm area. A consensus interpretation of CT and MRI was defined as the standard of reference. RESULTS Of 252 data sets, 141 showed evidence for endoleaks. The incidence of types I, II, and III endoleaks and complex endoleaks was 3.2%, 40.1%, 8.7%, and 4.0%, respectively. The sensitivity for endoleak detection was 92.9%, 44.0%, 34.8%, and 38.3% for MRI, biphasic CT, uniphasic arterial CT, and uniphasic late CT, respectively. The corresponding negative predictive values were 91.7%, 58.4%, 54.7%, and 56.1%, respectively. The overall accuracy of endoleak detection and correct sizing was 95.2%, 58.3%, 55.6%, and 57.1% for MRI, biphasic CT, uniphasic arterial CT, and uniphasic late CT, respectively. CONCLUSION MRI is significantly superior to biphasic CT for endoleak detection and rating of endoleak size, followed by uniphasic late and uniphasic arterial CT scans. MRI shows a significant number of endoleaks in cases with negative CT findings and may help illuminate the phenomenon of endotension. Endoleak rates reported after endovascular aneurysm repair substantially depend on the imaging techniques used.

Hemodynamic Effects of Nonionic Contrast Bolus Injection and Oxygen Inhalation During Pulmonary Angiography in Patients With Chronic Major-Vessel Thromboembolic Pulmonary Hypertension

BACKGROUND Pulmonary angiography is the gold standard for the diagnosis of chronic thromboembolic pulmonary hypertension; however, major complications have been reported. This study evaluates the hemodynamic effects of direct pulmonary nonionic contrast bolus injection and oxygen inhalation in patients with chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS In 33 patients, hemodynamic parameters were measured after oxygen inhalation and during bolus injection of nonionic contrast medium in a control group (group 1. n = 11), in a group of patients with moderately severe pulmonary hypertension (group 2, n = 9), and in a group with severe pulmonary hypertension (group 3, n = 13). Oxygen inhalation significantly improved oxygen supply. Pulmonary artery pressure and heart rate were reduced, but pulmonary vascular resistance and total pulmonary resistance were not significantly affected. One hundred ninety-eight angiograms were performed selectively on both pulmonary arteries in the posterior-anterior, oblique, and lateral views. Before contrast bolus injection, RAP and PAP significantly increased because of initial inspiration. Contrast bolus injection caused only a minor pressure increase (delta PA systolic, 2.3 +/- 1.4, 2.5 +/- 1.8, and 5.0 +/- 5.2 mm Hg, groups 1, 2, and 3, respectively) without significance between the groups. After the angiography, pulmonary artery pressure was moderately increased, predominantly in group 3, but pulmonary vascular resistance was not significantly changed. Systemic vascular resistance was decreased. Cardiac index increased in groups 1 and 2 but was unchanged in group 3. Systemic pressure therefore decreased in group 3. CONCLUSIONS We concluded that bolus injection of nonionic contrast medium causes no major hemodynamic effects even in patients with severe chronic thromboembolic pulmonary hypertension. Oxygen contributes to safety during the procedure.

Long-term results after thromboendarterectomy for chronic pulmonary embolism

OBJECTIVE In patients with chronic thromboembolic pulmonary hypertension, pulmonary vascular resistance (PVR) can be reduced by pulmonary thromboendarterectomy (PTE). In this study, long-term symptomatic and hemodynamic effects were investigated. METHODS Twenty-two patients (12 female, 10 male, mean age 40 years, preoperative NYHA functional class II/III/IV: n = 1/12/9) were re-evaluated 48-72 months (mean 60 months) after surgery. In addition to clinical assessment, radiologic, hemodynamic and echocardiographic investigations were performed. RESULTS All patients reported a marked improvement of their clinical condition. At follow-up, 11 patients were identified as NYHA class I, 10 as NYHA class II and one patient was in class III. PVR and mean pulmonary artery pressure (mPAP) were significantly reduced (preoperative PVR 800+/-274 dynes/s per cm(-5), follow-up PVR 180+/-28.3 dynes/s per cm(-5); P < 0.001; preoperative mPAP 48.5+/-7.4 mmHg, follow-up mPAP 27.5+/-4.9 mmHg; P < 0.001). There was also a significant increase in arterial blood oxygen tension (preoperative PaO2 59+/-10 mmHg; follow-up PaO2 84+/-12 mmHg; P < 0.001). Chest roentgenograms and echocardiographic examinations revealed significantly decreased right heart dimensions and a recovery of right heart function. CONCLUSION In patients with severe chronic thromboembolic pulmonary hypertension, persistent symptomatic and hemodynamic improvements can be achieved by PTE.

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.

Long-Term Follow-Up After Endovascular Treatment of Acute Aortic Emergencies

PurposeTo investigate the long-term outcome and efficacy of emergency treatment of acute aortic diseases with endovascular stent-grafts.MethodsFrom September 1995 to April 2007, 37 patients (21 men, 16 women; age 53.9 ± 19.2 years, range 18–85 years) with acute complications of diseases of the descending thoracic aorta were treated by endovascular stent-grafts: traumatic aortic ruptures (n = 9), aortobronchial fistulas due to penetrating ulcer or hematothorax (n = 6), acute type B dissections with aortic wall hematoma, penetration, or ischemia (n = 13), and symptomatic aneurysm of the thoracic aorta (n = 9) with pain, penetration, or rupture. Diagnosis was confirmed by contrast-enhanced CT. Multiplanar reformations were used for measurement of the landing zones of the stent-grafts. Stent-grafts were inserted via femoral or iliac cut-down. Two procedures required aortofemoral bypass grafting prior to stent-grafting due to extensive arteriosclerotic stenosis of the iliac arteries. In this case the bypass graft was used for introduction of the stent-graft.ResultsA total of 46 stent-grafts were implanted: Vanguard/Stentor (n = 4), Talent (n = 31), and Valiant (n = 11). Stent-graft extension was necessary in 7 cases. In 3 cases primary graft extension was done during the initial procedure (in 1 case due to distal migration of the graft during stent release, in 2 cases due to the total length of the aortic aneurysm). In 4 cases secondary graft extensions were performed—for new aortic ulcers at the proximal stent struts (after 5 days) and distal to the graft (after 8 months) and recurrent aortobronchial fistulas 5 months and 9 years after the initial procedure—resulting in a total of 41 endovascular procedures. The 30-day mortality rate was 8% (3 of 37) and the overall follow-up was 29.9 ± 36.6 months (range 0–139 months). All patients with traumatic ruptures demonstrated an immediate sealing of bleeding. Patients with aortobronchial fistulas also demonstrated a satisfactory follow-up despite the necessity for reintervention and graft extension in 3 of 6 cases (50%). Two patients with type B dissection died due to mesenteric ischemia despite sufficient mesenteric blood flow being restored (but too late). Two suffered from neurologic complications, 1 from paraplegia and 1 from cerebral ischemia (probably embolic), 1 from penetrating ulcer, and 1 from persistent ischemia of the kidney. Five of 9 (56%) patients with symptomatic thoracic aneurysm demonstrated endoleaks during follow-up and there was an increase in the aneurysm in 1.ConclusionEndovascular treatment is safe and effective for emergency treatment of life-threatening acute thoracic aortic syndromes. Results are encouraging, particularly for traumatic aortic ruptures. However, regular follow-up is mandatory, particularly in the other pathologies, to identify late complications of the stent-graft and to perform appropriate additional corrections as required.

Endovascular treatment of acute bleeding complications in traumatic aortic rupture and aortobronchial fistula.

OBJECTIVE Herein we report our experience in placement of endovascular stentgrafts in the descending aorta in patients with acute bleeding complications due to traumatic rupture or aortobronchial fistula. METHODS Six patients (one woman, five men, mean age 47+/-19 years) were treated from September 1995 to February 2000 by implantation of endovascular stentgrafts in the descending aorta. Indications included traumatic ruptures of the aortic isthmus (n=3) and aortobronchial fistulas (n=3). All procedures were performed under general anaesthesia. The implants were introduced under fluoroscopic guidance via the aorta (n=1), the iliac (n=4) or femoral (n=2) artery, respectively. RESULTS All aortobronchial fistulas and ruptures were sealed up successfully. There was no perioperative morbidity and no procedure-related morbidity except one patient who received aortofemoral reconstruction because of iliac occlusive disease. All patients are alive and well after a mean follow-up of 31 months (range 6-60). Two patients had recurrent hemoptysis, in one case, the patient received a second implant (distal extension), the other patient was managed conservatively. CONCLUSION Endovascular treatment by a stentgraft is a safe and reliable procedure in the management of acute bleeding complications in patients with aortic rupture or aortobronchial fistulas.