ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Surgical complications after kidney transplantation: different impacts of immunosuppression, graft function, patient variables, and surgical performance.

The population of kidney transplant (KTx) recipients often has complex medical and immunological conditions. Surgical complications (SCs) contribute to the increasing morbidity and costs in these patients. We analyzed the risk factors for SC in 405 KTx patients treated using defined immunosuppressive regimens according to their clinical and immunological risk profile: (1) standard immunosuppression (SIS) with IL-2 receptor mAb, CNI, and (a) mycophenolic acid (MPA) or (b) mTOR inhibitor; and (2) more intense immunosuppression (IIS) with (a) ATG or (b) the additional use of plasma exchange and B- and T-cell-depleting agents. In a mixed effects logistic regression model, we identified the following risk factors for SC: male gender, diabetes, and post-operative dialysis. No difference was found between the patients who received SIS with MPA and those who received mTOR inhibitors. The risk of suffering complications with IIS increases with age. In addition to IIS, diabetes was a risk for wound healing disorders. Therapeutic anticoagulation and a third or subsequent retransplantation increased the rate of bleeding. We did not identify immunosuppression or patient demographics as risk factors for lymphoceles or ureter complications; however, we demonstrated that the surgeon had a significant impact on severe complications, especially those of the ureter.

[Diagnostic and prognostic significance of α-fetoprotein in hepatocellular carcinoma]. / Diagnostische und prognostische Bedeutung des α-Feto-Proteins beim hepatozellulären Karzinom.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive tumor with a growing socioeconomic burden. International guidelines do not predominantly recommend the pretherapeutic determination of the alpha-fetoprotein (AFP) concentration. Regarding the prognostic value of AFP, the European study data are not sufficiently meaningful. OBJECTIVE: This study aimed to demonstrate possible aspects of the AFP level and to investigate the prognostic value of AFP levels as well as to provide impetus for future prospective studies. MATERIAL AND METHODS: At the time of data retrieval the prospective liver databank showed 1382 entries. All patients with a histologically confirmed HCC were included resulting in 92 final entries. For these patients, information on T, N, M and G stages, R status as well as sex, age and etiology of the HCC were available. For data analysis the patient population was divided into six groups based on three cut-off values. Furthermore, a survival analysis was performed using Kaplan-Meier and a multifactorial analysis of the influencing factors regarding outcome. RESULTS: The AFP serum level showed a statistically significant correlation with the tumor diameter (T1/T2 vs. T3/T4) and grading (G1/G2 vs. G3/G4). The survival prognosis was significantly lower in patients with higher AFP values (p < 0.05). The median survival time for patients with AFP levels >8 µg/l was 35 months, with AFP levels >200 µg/l or >400 µg/l showed a reduced median survival of 15 months and 11 months, respectively. High AFP levels were a significant influencing factor for the outcome independent of the T stage, age and R status of patients in comparison to low AFP levels. CONCLUSION: Taking the present results into consideration, the AFP level can have a therapeutic usefulness. Therapeutic consequences could be derived from the height of the measured AFP concentration, with respect to the treatment strategy. Therefore, preoperative and postoperative determination of the AFP serum level is recommended in all HCC patients.

Renal Impairment Is Associated with Reduced Outcome After Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown. METHODS: An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1. RESULTS: A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1. CONCLUSION: This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications.

[Intraoperative fluorescence angiography and cholangiography with indocyanine green in hepatobiliary surgery]. / Intraoperative Fluoreszenzangio- und cholangiographie mit Indocyaningrün bei hepatobiliären Eingriffen.

Intraoperative fluorescence angiography and cholangiography with indocyanine green (ICG) are increasingly used in routine hepatobiliary surgery. Its usage is manifold. It improves and facilitates navigation especially in minimal invasive and robotic surgery and therefore increases the safety of the surgical intervention. In laparoscopic cholecystectomy for example, the bileduct anatomy can be easily visualized, even in complicated cholecystitis or anatomical variants without being too time consuming. ICG fluorescence also enables the visualization of vascular structures and perfusion. Anatomical liver resections, for example in hepatocellular carcinoma (HCC), can be performed easily as liver segments and territories can be identified. Anatomical resection is becoming more important, e.g. in the treatment of HCC. Another useful application is the intraoperative detection of bile leakages after liver resection. In particular, the intraoperative control of a biliodigestive anastomosis is possible with ICG fluorescence cholangiography and therefore reduces morbidity. Even primary and secondary liver tumors can be detected with ICG fluorescence. Whereas well-differentiated HCCs homogeneously take up ICG, poorly differentiated HCCs and metastases do not: however, in these cases the adjacent liver parenchyma stores ICG more intensively than healthy liver tissue, which creates a ring-like fluorescence pattern. To conclude, the use of ICG fluorescence in hepatobiliary surgery is diverse but in Germany it is still at the beginning compared to other countries.

Usefulness of the Hardman index in predicting outcome after endovascular repair of ruptured abdominal aortic aneurysms.

OBJECTIVES: The Hardman index, which has five variables, has been recommended as a predictor of outcome after open repair of ruptured abdominal aortic aneurysms (RAAAs). It has been reported that the presence of three or more variables is uniformly fatal. The aim of this study was to test the same model in an independent series of RAAA patients undergoing endovascular repair. METHODS: A consecutive series of 41 patients undergoing endovascular repair for RAAA during an 8-year period was analyzed retrospectively. Thirty-day mortality and patient variables, including the five Hardman risk factors of age >76 years, serum creatinine >190 micromol/L, hemoglobin <9 g/dL, loss of consciousness, and electrocardiographic (ECG) evidence of ischemia, were recorded. The Hardman index and a revised version of the index with four variables (without ECG ischemia) were calculated and related to clinical outcome. RESULTS: Operative mortality was 41% (17 of 41). On univariate analysis, only age >76 years (P = .01) and the use of local anesthesia (P < .0001) were statistically significant. Loss of consciousness (P = .05) showed a trend toward a higher mortality, albeit not statistically significant. On multivariate analysis, the use of local anesthesia was the only significant predictor of survival (odds ratio [OR], 0.03; 95% confidence interval [CI], 0.003-0.25, P = .001). Again, loss of consciousness showed an association with a higher chance of dying but did not achieve statistical significance (OR, 6.30; 95% CI, 0.93-42.51, P = .059). The original and revised versions of the Hardman index were both significantly associated with death (P = .02 and P = .001, chi(2) test for trend). The cumulative effect of 0, 1, 2, and >/=3 risk factors on mortality was 0%, 27%, 36%, and 71% for the original index, and 12.5%, 21%, 60%, and 78% for the revised version, respectively. Four and two patients with a score of >/=3 in each version of the index survived endovascular repair. CONCLUSIONS: The Hardman index, with or without incorporating ECG ischemia, seems to be a simple and useful predictive tool in patients undergoing endovascular repair of RAAA, with the mortality rate increasing along with the Hardman score. However, the index cannot be used to accurately identify patients with no chance of survival after endovascular repair.