Resection of Colorectal Liver Metastases with Major Vessel Involvement.

BACKGROUND: Treatment of CRLM with major vessel involvement is still challenging and valid data on outcomes are still rare. We analyzed our experience of hepatectomies with resection and reconstruction of major hepatic vessels with regard to operative and perioperative details, histopathological findings and oncological outcome. METHODS: Data of 32 hepatectomies with major hepatic vessel resections and reconstructions were included. Results were correlated with perioperative and oncological outcome. RESULTS: Out of 1236 surgical resections due to CRLM, we performed 35 major hepatic vessel resections and reconstructions in 32 cases (2.6%) during the study period from January 2008 to March 2023. The vena cava inferior (VCI) was resected and reconstructed in 19, the portal vein (PV) in 6 and a hepatic vein (HV) in 10 cases. Histopathological examination confirmed a vascular infiltration in 6/32 patients (VCI 3/17, HV 2/10 and PV 1/6). There were 27 R0 and 5 R1 resections. All R1 situations affected the parenchymal margin. Vascular wall margins were R0. Ninety-day mortality was 0. The median overall survival (OS) for the patient group with vascular infiltration (V1) was 21 months and for the V0 group 33.3 months. CONCLUSION: Liver resections with vascular resection and reconstruction are rare and histological vessel infiltration occurs seldom. In cases with presumed vascular wall infiltration, liver resection combined with major vessel resection and reconstruction can be performed with low morbidity and mortality. We prefer a parenchymal sparing liver resection with vascular resection and reconstruction to achieve negative resection margins, but in technically difficult cases with higher risk for postoperative complications, tumor detachment from vessels without resection is a most reasonable surgical alternative.

Computer-assisted intraoperative 3D-navigation for liver surgery: a prospective randomized-controlled pilot study.

Background: Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. Methods: This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. Results: The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. Conclusions: Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility.

Mixed Hepatocellular Cholangiocarcinoma: A Comparison of Survival between Mixed Tumors, Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma from a Single Center.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, followed by intrahepatic cholangiocarcinoma (ICC). In addition, there is a mixed form for which only limited data are available. The aim of this study was to compare recurrence and survival of the mixed form within the cohorts of patients with HCC and ICC from a single center. METHODS: Between January 2008 and December 2020, all patients who underwent surgical exploration for ICC, HCC, or mixed hepatocellular cholangiocarcinoma (mHC-CC) were included in this retrospective analysis. The data were analyzed, focusing on preoperative and operative details, histological outcome, and tumor recurrence, as well as overall and recurrence-free survival. RESULTS: A total of 673 surgical explorations were performed, resulting in 202 resections for ICC, 344 for HCC (225 non-cirrhotic HCC, ncHCC; 119 cirrhotic HCC, cHCC), and 14 for mHC-CC. In addition, six patients underwent orthotopic liver transplant (OLT) in the belief of dealing with HCC. In 107 patients, tumors were irresectable (resection rate of 84%). Except for the cHCC group, major or even extended liver resections were required. Vascular or visceral extensions were performed regularly. Overall survival (OS) was highly variable, with a median OS of 17.6 months for ICC, 26 months for mHC-CC, 31.8 months for cHCC, and 37.2 months for ncHCC. Tumor recurrence was common, with a rate of 45% for mHC-CC, 48.9% for ncHCC, 60.4% for ICC, and 67.2% for cHCC. The median recurrence-free survival was 7.3 months for ICC, 14.4 months for cHCC, 16 months for mHC-CC, and 17 months for ncHCC. The patients who underwent OLT for mHC-CC showed a median OS of 57.5 and RFS of 56.5 months. CONCLUSIONS: mHC-CC has a comparable course and outcome to ICC. The cholangiocarcinoma component seems to be the dominant one and, therefore, may be responsible for the prognosis. 'Accidental' liver transplant for mHC-CC within the Milan criteria offers a good long-term outcome. This might be an option in countries with no or minor organ shortage.

Role of associating liver partition and portal vein ligation for staged hepatectomy for advanced colorectal liver disease: indispensable or overstressed?

BACKGROUND: The aim of this study was to analyse the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced colorectal liver disease. Surgery offers the best long-term survival in patients with colorectal liver metastases (CRLM). To increase the rates of resectability, two-stage procedures (TSH) and ALPPS are established methods in cases of advanced colorectal liver disease to avoid post hepatectomy liver failure (PHLF). There is still a debate of the oncological utility and the surgical ranking of ALPPS in this clinical scenario. The aim of this analysis was to share our ALPPS data of the perioperative and oncological outcome in patients with CRLM and to compare them with regard to recommendations of published data. METHODS: Ten patients (1.1%) out of 881 received a classical ALPPS procedure between January 2008 and November 2021 at our institution. The median volume increase was 76% (range 55-125%) in a median time interval of 7 days. RESULTS: The completion rate was 100% and all resections were R0-situations (100%). No patient developed PHLF. The median overall survival (OS) was 36.7 months and the median recurrence-free survival (RFS) 6.1 months. CONCLUSIONS: The ALPPS procedure is a surgical approach to achieve a R0 situation in patients with an extensive intrahepatic tumor burden. Nevertheless, the use of ALPPS should be allocated for patients who have no other surgical options.

Patient-individualized resection planning in liver surgery using 3D print and virtual reality (i-LiVR)-a study protocol for a prospective randomized controlled trial.

BACKGROUND: A multitude of different diseases-benign and malign-can require surgery of the liver. The liver is an especially challenging organ for resection planning due to its unique and interindividually variable anatomy. This demands a high amount of mental imagination from the surgeon in order to plan accordingly - a skill, which takes years of training to acquire and which is difficult to teach. Since the volume of the functional remnant liver is of great importance, parenchyma sparing resections are favoured. 3D reconstructions of computed tomography imaging enable a more precise understanding of anatomy and facilitate resection planning. The modality of presentation of these 3D models ranges from 2D monitors to 3D prints and virtual reality applications. METHODS: The presented trial compares three different modes of demonstration of a 3D reconstruction of CT scans of the liver, which are 3D print, a demonstration on a regular computer screen or using a head-mounted virtual reality headset, with the current gold standard of viewing the CT scan on a computer screen. The group size was calculated with n=25 each. Patients with major liver resections in a laparoscopic or open fashion are eligible for inclusion. Main endpoint is the comparison of the quotient between planned resection volume and actual resection volume between these groups. Secondary endpoints include usability for the surgical team as well as patient specifics and perioperative outcome measures and teaching issues. DISCUSSION: The described study will give insight in systematic planning of liver resections and the comparison of different demonstration modalities of 3D reconstruction of preoperative CT scans and the preference of technology. Especially teaching of these demanding operations is underrepresented in prior investigations. TRIAL REGISTRATION: Prospective trials registration at the German Clinical Trials register with the registration number DRKS00027865 . Registration Date: January 24, 2022.

[Extended Liver Resection with Complex Vascular Reconstruction in Locally Advanced Alveolar Echinococcosis]. / Erweiterte Leberresektion mit komplexer Gefäßrekonstruktion bei fortgeschrittener alveolärer Echinokokkose der Leber.

BACKGROUND: Hepatic echinococcosis is rare in Germany. Liver resection is a potentially curative treatment, if a complete resection according to oncological standards can be achieved. Due to the infiltrating growth of E. multilocularis, liver resections can be challenging. CASE: We present a case of hepatic echinococcosis with complete infiltration of left and middle hepatic vein and a partial infiltration of the right hepatic vein (RHV) and the vena cava (VCI). To better evaluate resectability, we performed a three-dimensional reconstruction based on the preoperative CT scan. Complete resection was achieved with an extended left hemihepatectomy (removal of segment 1-5 and partially segment 8) and tangential resection of the VCI and partial resection of the RHV. VCI was reconstructed with a bovine pericardial patch and the RHV was reconstructed end-to-end. CONCLUSION: Liver resection may require complex vascular resections and reconstructions to achieve an R0 situation in the therapy of E. multilocularis. Three dimensional planning of the resection facilitated curative resection in the current case.

Cancer gene related characterization of patterns and point of recurrence after resection of colorectal liver metastases.

BACKGROUND: Outcome after resection of CRLM is hampered by a high rate of recurrence. There are little data about the role of cancer related genes and their mutations in this scenario. The aim of our analysis was to assess the predictive power of cancer-related genes and their mutations on risk for and distribution of recurrence and the time of occurrence after resection of colorectal liver metastases (CRLM). METHODS: We included 130 patients with 167 liver resections. The work-up consisted of the analysis of a total of 720 cancer-related genes by next-generation sequencing (NGS). Results were correlated with the patterns and time of recurrence and survival. RESULTS: At the time of analysis, 89/130 patients (68%) had developed recurrence. This included liver only recurrence in 52%, lung only recurrence in 11% and disseminated disease in 37% of cases. In univariate analysis, alterations in the RAS/RAF pathway and in the SMAD family had significant predictive power for the time of recurrence (P<0.0001) whereas single mutations did not reach statistical significance in multivariate analysis. Mutations of PIK3CA were associated with a better prognosis and a later occurrence of relapse. A recurrence risk score (r-RS) based on mutations in these cancer related genes is predictive of the time of recurrence. CONCLUSIONS: In conclusion, mutations in the RAS/RAF pathway and the SMAD family are risk factors for early recurrence. Mutations of PIK3CA are associated with a lower risk for recurrence after resection of CRLM. Cancer related genes and their mutations do not correlate with patterns of recurrence but are predictive for the timely onset of recurrence.

Liver Resection for Intrahepatic Cholangiocarcinoma-Single-Center Experience with 286 Patients Undergoing Surgical Exploration over a Thirteen Year Period.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) accounts for about 10% of primary liver cancer. Surgery is the only potentially curative treatment. We report on our current series of 229 consecutive hepatic resections for iCCA, which is one of the largest Western single-center series published so far. METHODS: Between January 2008 to December 2020, a total of 286 patients underwent 307 surgical explorations for intended liver resection of iCCA at our department. Data were analyzed with regard to (1) preoperative treatment of tumor, (2) operative details, (3) perioperative morbidity and mortality, (4) histopathology, (5) outcome measured by tumor recurrence, treatment of recurrence and survival and (6) prognostic factors for overall and disease-free survival. RESULTS: the resectability rate was 74.6% (229/307). In total, 202 primary liver resections, 21 repeated, 5 re-repeated, and 1 re-re-repeated liver resections were performed. In primary liver resections there were 77% (155/202) major hepatectomies. In 39/202 (20%) of patients additional hepatic wedge resections and in 87/202 (43%) patients additional 119 other surgical procedures were performed next to hepatectomy. Surgical radicality in first liver resections was 166 R0-, 33 R1- and 1 R2-resection. Following the first liver resection, the calculated 1-, 3- and 5-year-survival is 80%, 39%, and 22% with a median survival of 25.8 months. Until the completion of data acquisition, tumors recurred in 123/202 (60.9%) patients after a median of 7.5 months (range 1-87.2 months) after resection. A multivariate cox regression revealed tumor size (p < 0.001), T stage (p < 0.001) and N stage (p = 0.003) as independent predictors for overall survival. N stage (p = 0.040), preoperative therapy (p = 0.005), T stage (p = 0.004), tumor size (p = 0.002) and M stage (p = 0.001) were independent predictors for recurrence-free survival. CONCLUSIONS: For complete surgical removal, often extended liver resection in combination with complex vascular or biliary reconstruction is required. However, despite aggressive surgery, tumor recurrence is frequent and long-term oncological results are poor. This indicated that surgery alone is unlikely to make great strides in improving prognosis of patients with iCCA, instead clearly suggesting that liver resection should be incorporated in multimodal treatment concepts.

Survival Prediction in Intrahepatic Cholangiocarcinoma: A Proof of Concept Study Using Artificial Intelligence for Risk Assessment.

Several scoring systems have been devised to objectively predict survival for patients with intrahepatic cholangiocellular carcinoma (ICC) and support treatment stratification, but they have failed external validation. The aim of the present study was to improve prognostication using an artificial intelligence-based approach. We retrospectively identified 417 patients with ICC who were referred to our tertiary care center between 1997 and 2018. Of these, 293 met the inclusion criteria. Established risk factors served as input nodes for an artificial neural network (ANN). We compared the performance of the trained model to the most widely used conventional scoring system, the Fudan score. Predicting 1-year survival, the ANN reached an area under the ROC curve (AUC) of 0.89 for the training set and 0.80 for the validation set. The AUC of the Fudan score was significantly lower in the validation set (0.77, p < 0.001). In the training set, the Fudan score yielded a lower AUC (0.74) without reaching significance (p = 0.24). Thus, ANNs incorporating a multitude of known risk factors can outperform conventional risk scores, which typically consist of a limited number of parameters. In the future, such artificial intelligence-based approaches have the potential to improve treatment stratification when models trained on large multicenter data are openly available.

Influence of Lymphangio (L), Vascular (V), and Perineural (Pn) Invasion on Recurrence and Survival of Resected Intrahepatic Cholangiocarcinoma.

(1) Background: Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy. Besides tumor, nodal, and metastatic status, the UICC TNM classification describes further parameters such as lymphangio- (L0/L1), vascular (V0/V1/V2), and perineural invasion (Pn0/Pn1). The aim of this study was to analyze the influence of these parameters on recurrence and survival. (2) Methods: All surgical explorations for patients with ICC between January 2008 and June 2018 were collected and further analyzed in our institutional database. Statistical analyses focused on perineural, lymphangio-, and vascular invasion examined histologically and their influence on tumor recurrence and survival. (3) Results: Of 210 patients who underwent surgical exploration, 150 underwent curative-intended resection. Perineural invasion was present in 41, lymphangioinvasion in 21, and vascular invasion in 37 patients (V1 n = 34, V2 n = 3). Presence of P1, V+ and L1 was significantly associated with positivity of each other of these factors (p < 0.001, each). None of the three parameters showed direct influence on tumor recurrence in general, but perineural invasion influenced extrahepatic recurrence significantly (p = 0.019). Whereas lymphangio and vascular invasion was neither associated with overall nor recurrence-free survival, perineural invasion was significantly associated with a poor 1-, 3- and 5-year overall survival (OS) of 80%, 35%, and 23% for Pn0 versus 75%, 23%, and 0% for Pn1 (p = 0.027). Concerning recurrence-free survival (RFS), Pn0 showed a 1-, 3- and 5-year RFS of 42%, 18%, and 16% versus 28%, 11%, and 0% for Pn1, but no significance was reached (p = 0.091). (4) Conclusions: Whereas lymphangio- and vascular invasion showed no significant influence in several analyses, the presence of perineural invasion was associated with a significantly higher risk of extrahepatic tumor recurrence and worse overall survival.

Using virtual 3D-models in surgical planning: workflow of an immersive virtual reality application in liver surgery.

PURPOSE: Three-dimensional (3D) surgical planning is widely accepted in liver surgery. Currently, the 3D reconstructions are usually presented as 3D PDF data on regular monitors. 3D-printed liver models are sometimes used for education and planning. METHODS: We developed an immersive virtual reality (VR) application that enables the presentation of preoperative 3D models. The 3D reconstructions are exported as STL files and easily imported into the application, which creates the virtual model automatically. The presentation is possible in "OpenVR"-ready VR headsets. To interact with the 3D liver model, VR controllers are used. Scaling is possible, as well as changing the opacity from invisible over transparent to fully opaque. In addition, the surgeon can draw potential resection lines on the surface of the liver. All these functions can be used in a single or multi-user mode. RESULTS: Five highly experienced HPB surgeons of our department evaluated the VR application after using it for the very first time and considered it helpful according to the "System Usability Scale" (SUS) with a score of 76.6%. Especially with the subitem "necessary learning effort," it was shown that the application is easy to use. CONCLUSION: We introduce an immersive, interactive presentation of medical volume data for preoperative 3D liver surgery planning. The application is easy to use and may have advantages over 3D PDF and 3D print in preoperative liver surgery planning. Prospective trials are needed to evaluate the optimal presentation mode of 3D liver models.

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. METHODS: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. RESULTS: Out of 184 patients, 135 (73.4%) underwent curative intended resection. Median overall survival (OS) was 22.2 months with a consecutive 1-, 3- and 5-year OS of 73%, 29%, and 17%. Median recurrence-free survival (RFS) was 9.3 months with a consecutive 1-, 3- and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction (POP) score was created showing significance for OS and RFS (all P < 0.001). In multivariate analysis, POP score (HR = 1.779; 95% CI: 1.268-2.495; P = 0.001), T stage (HR = 1.255; 95% CI: 1.040-1.514; P = 0.018) and N stage (HR = 1.334; 95% CI: 1.081-1.645; P = 0.007) were the independent predictors for OS. For RFS, POP score (HR = 1.733; 95% CI: 1.300-2.311; P < 0.001) and M stage (HR = 3.036; 95% CI: 1.376-6.697; P = 0.006) were the independent predictors. CONCLUSIONS: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

Experiences With Three-dimensional Printing in Complex Liver Surgery.

OBJECTIVE: We present a series of cases where we used 3D printing in planning of complex liver surgery. BACKGROUND: In liver surgery, three-dimensional reconstruction of the liver anatomy, in particular of vascular structures, has shown to be helpful in operation planning. So far, 3D printing has been used for medical applications only rarely. METHODS AND PATIENTS: From December 2017 to December 2019, in 10 cases where surgery was assumed to be challenging operation planning was performed using full size 3D prints in addition to standard 3 phase CT scans. Models included transparent parenchyma, hepatic veins, vena cava, portal vein, hepatic artery, (biliary tree if requested), and tumors. In 7/10 cases vascular reconstructions were needed during the procedure. Nonstructured feedback of the surgical team revealed that the major benefit was visualization of the critical areas of vascular reconstruction, the expected dimensions of tangential vascular infiltration and the planning of reconstruction. In the multifocal tumors, 3D prints were considered to be helpful for intraoperative orientation to detect metastases and to improve planning of the resection. CONCLUSIONS: In complex liver surgery with potential need for vascular reconstructions operation planning may be optimized using a 3D printed liver model. Prospective studies are needed to evaluate the clinical impact of 3D printing in liver surgery compared to other 3D visualizations.

Relevance of suspicious lymph nodes in preoperative imaging for resectability, recurrence and survival of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at an advanced stage resulting in a low resectability rate. Even after potentially curative resection the risk for tumor recurrence is high. Although the extent and value of lymphadenectomy is part of ongoing discussion, the role of preoperative imaging for assessment of suspicious lymph nodes (suspLN) has only been studied modestly. Aim of this study is to demonstrate the influence of suspicious lymph nodes in preoperative imaging on resectability, recurrence, and long-term outcome. METHODS: All patients who underwent exploration for ICC between January 2008 and June 2018 were included. Preoperative imaging (CT or MRI) was analysed with focus on suspLN at the hepatoduodenal ligament, lesser curvature, interaortocaval, and superior to the diaphragm; suspLN were classified according to the universally accepted RECIST 1.1 criteria; histopathology served as gold standard. RESULTS: Out of 187 patients resection was performed in 137 (73.3%), in 50 patients the procedure was terminated after exploration. Overall, suspLN were found preoperatively in 73/187 patients (39%). Comparing patients who underwent resection and exploration only, suspLN were significantly more common in the exploration group (p = 0.011). Regarding lymph node stations, significant differences could be shown regarding resectability: All tumors with suspLN superior to the diaphragm were irresectable. Preoperative imaging assessment showed a strong correlation with final histopathology, especially of suspLN of the hepatoduodenal ligament and the lesser curvature. Sensitivity of suspLN was 71.1%, specificity 90.8%. Appearance of tumor recurrence was not affected by suspLN (p = 0.289). Using a short-axis cut-off of <> 1 cm, suspLN had significant influence on recurrence-free survival (RFS, p = 0.009) with consecutive 1-, 3-, and 5-year RFS of 41, 21, and 15% versus 29, 0, and 0%, respectively. Similarly, 1-, 3- and 5-year overall survival (OS) was 75, 30, and 18% versus 59, 18, and 6%, respectively (p = 0.040). CONCLUSION: Suspicious lymph nodes in preoperative imaging are predictor for unresectability and worse survival. Explorative laparoscopy should be considered, if distant suspicious lymph nodes are detected in preoperative imaging. Nevertheless, given a sensitivity of only 71.1%, detection of suspicious lymph nodes in the preoperative imaging alone is not sufficient to allow for a clear-cut decision against a surgical approach.

Intrahepatic cholangiocarcinoma - influence of resection margin and tumor distance to the liver capsule on survival.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed in advanced stage. Aim of this study was to analyse the influence of resection margins and tumor distance to the liver capsule on survival and recurrence in a single center with a high number of extended resections. METHODS: From January 2008 to June 2018 data of all patients with ICC were collected and further analysed with Kaplan Meier Model, Cox regression or Chi2 test for categorical data. RESULTS: Out of 210 included patients 150 underwent curative intended resection (71.4%). Most patients required extended resections (n = 77; 51.3%). R0-resection was achieved in 131 patients (87.3%) with minimal distances to the resection margin > 1 cm in 22, 0.5-1 cm in 11, 0.1-0.5 cm in 49 patients, and <  0.1 cm in 49 patients. Overall survival (OS) for margins > 0.5 cm compared to 0.5-0.1 cm or R1 was better, but without reaching significance. All three groups had significantly better OS compared to the irresectable group. Recurrence-free survival (RFS) was also better in patients with a margin > 0.5 cm than in the < 0.5-0.1 cm or the R1-group, but even without reaching significance. Different distance to the liver capsule significantly affected OS, but not RFS. CONCLUSIONS: Wide resection margins (> 0.5 cm) should be targeted but did not show significantly better OS or RFS in a cohort with a high percentage of extended resections (> 50%). Wide margins, narrow margins and even R1 resections showed a significant benefit over the irresectable group. Therefore, extended resections should be performed, even if only narrow margins can be achieved.

Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Registry: What Have We Learned?

In 2007, the first associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure was performed in Regensburg, Germany. ALPPS is a variation of twostage hepatectomy to induce rapid liver hypertrophy allowing the removal of large tumors otherwise considered irresectable due to a too small future liver remnant. In 2012, the international ALPPS registry was created, and it now contains more than 1,000 cases. During the past years, improved patient selection and refinements in operative techniques, in particular, less invasive approaches such as Partial ALPPS, Tourniquet ALPPS, Ablation-assisted ALPPS, Hybrid ALPPS or Laparoscopic or Robotic approaches, have resulted in significant improvements in safety. The most frequent indication for ALPPS is colorectal liver metastases. In the first randomized controlled study, ALPPS provided a higher resectability rate than conventional two-stage hepatectomy, with similar complication rates. Long-term outcome data are still missing. The initial results of ALPPS for hepatocellular carcinoma and for perihilar cholangiocarcinoma were devastating, but with progress in surgical technic and better patient selection, ALPPS could serve as a treatment alternative in carefully selected cases, even for these tumors. ALPPS has enlarged the armamentarium of hepato-pancreato-biliary surgeons, but there is still discussion regarding how to use this novel technique, which may allow resection of tumors that are otherwise deemed irresectable.

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.

Resection of intrahepatic cholangiocarcinoma in elderly patients - is it reasonable?

BACKGROUND: Intrahepatic cholangiocarinoma (ICC) has a rising incidence in western countries. Often major or extended resections are necessary for complete tumor removal. Due to demographical trends the number of elderly patients diagnosed with ICC is rising accordingly. Aim of this study is to show whether resection of ICC in elderly patients is reasonable or not. METHODS: Between January 2008 and June 2018 all consecutive patients with ICC were collected. Analyses were focussed on the performed resection, its extent, postoperative morbidity and mortality as well as survival. Statistics were performed with Chi2 test for categorical data and for survival analyses the Kaplan Meier model with log rank test was used. RESULTS: In total 210 patients underwent surgical exploration with 150 resections (71.4%). Patients were divided in 70-years cut-off groups (> 70 vs < 70 years of age) as well as a young (age 30-50, n = 23), middle-age (50-70, n = 76) and old (> 70, n = 51) group, whose results are presented here. Resectability (p = 0.709), extent of surgery (p = 0.765), morbidity (p = 0.420) and mortality (p = 0.965) was comparable between the different age groups. Neither visceral (p = 0.991) nor vascular (p = 0.614) extension differed significantly, likewise tumor recurrence (p = 0.300) or the localisation of recurrence (p = 0.722). In comparison of patients > or < 70 years of age, recurrence-free survival (RFS) was significantly better for the younger group (p = 0.047). For overall survival (OS) a benefit could be shown, but without reaching significance (p = 0.072). In subgroup analysis the middle-age group had significant better OS (p = 0.020) and RFS (p = 0.038) compared to the old group. Additionally, a better OS (p = 0.076) and RFS (p = 0.179) was shown in comparison with the young group as well, but without reaching significance. The young compared to the old group had analogous OS (p = 0.931) and RFS (p = 0.845). CONCLUSION: Resection of ICC in elderly patients is not associated with an increased perioperative risk. Even extended resections can be performed in elderly patients without obvious disadvantages. Middle-age patients have a clear benefit for OS and RFS, while young and old patients have a comparable and worse long-term outcome.