Health Economic Evaluation of Patients With Colorectal Liver Metastases Randomized to ALPPS or TSH: Analysis From the LIGRO Trial.

Objective: This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH). Summary Background Data: TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; P = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; P = 0.314) and 0.1285 (95% CI: -0.11-0.36; P = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively. Conclusions: Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. METHODS: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. RESULTS: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. CONCLUSIONS: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

Enhanced recovery after surgery is feasible and safe in liver transplantation: a cohort study.

BACKGROUND: The principles of enhanced recovery after surgery (ERAS) are being applied to still more advanced procedures. Liver transplantation offers a unique opportunity for a multimodal approach including donor care as well. Our objective was to determine if ERAS was applicable and safe in orthotopic liver transplantation (OLT). METHODS: A national single centre retrospective study showing the implementation of ERAS from 2013 to 2019 with the proceeding 2 years serving as baseline. The primary endpoints were mortality, length of stay (LOS) in the ward and intensive care unit stay. Secondary endpoints were complications estimated by Dindo-Clavien classification, comprehensive complication index (CCI®) and re-admissions. RESULTS: A total of 334 patients were included. LOS was significantly reduced from a median of 22.5 days at introduction to 14 days at 2019. Cold ischaemia time was reduced from a mean of 10.7 to 6.0 h and the use of blood products (erythrocytes, plasma and thrombocytes) from a median of 28 to 6 units. Complications were reduced in severity. Mortality and readmission rates were not affected. CONCLUSION: ERAS principles are safe and recommended in patients undergoing OLT resulting in reduced severity of complications and LOS without affecting re-admissions or mortality.

Robotic liver resection in Denmark: Report of the first 50 cases at Rigshospitalet Copenhagen.

While most centers around the globe still consider open hepatic resection as the standard, innovative centers step in light of future developments of the robotic platform forward and introduce a robotic liver program while skipping the laparoscopic approach for its technological flaws. This applies also for our Department of Surgery and Transplantation at Rigshospitalet, Copenhagen University Hospital in Denmark. We herewith present as-to our best knowledge-the first center in Scandinavia our experience with the initial 50 robotic liver resections.

Liver transplantation in patients with post-hepatectomy liver failure - A Northern European multicenter cohort study.

BACKGROUND: Liver transplantation (LTX) has been described as a rescue treatment option in severe, intractable post-hepatectomy liver failure (PHLF), but is not considered to be indicated for this condition by many hepatobiliary and transplant surgeons. In this article we describe the clinical experience of five northern European tertiary centers in using LTX to treat selected patients with severe PHLF. METHODS: All patients subjected to LTX due to PHLF at the participating centers were identified from prospective clinical databases. Preoperative variables, surgical outcome (both resection surgery and LTX) and follow-up data were assessed. RESULTS: A total of 10 patients treated with LTX due to severe PHLF from September 2008 to May 2020 were identified and included in the study. All patients but one were male and the median age was 70 years (range 49-72). In all patients the indication for liver resection was suspected malignancy, but in six patients post-resection pathology revealed benign or pre-malignant disease. There was no 90-day mortality after LTX. Patients were followed for a median of 49 months (13-153) and eight patients were alive without recurrence at last follow-up. DISCUSSION: In selected patients with PHLF LTX can be a life-saving procedure with low short-term risk.

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

Spontaneous intestinal bleeding due to pseudoaneurism of the gastroduodenal artery: case report of a rare complication to median arcuate ligament syndrome.

Median arcuate ligament syndrome (MALS) is the compression of the celiac artery (CA) by the median arcuate ligament. MALS can cause pseudoaneurysm of the gastroduodenal artery, which can lead to fatal bleeding. A 40-year-old male with no prior medical history presented with symptoms of upper gastrointestinal hemorrhage (UGIH). Severe duodenal bleeding was confirmed although endoscopic hemostasis was impossible and final hemostasis was achieved following a subsequent open duodenotomy. A postoperative computed tomographic angiography (CTA) visualized a significant CA stenosis, post-stenotic dilatation and an aneurysm on a jejunal branch artery. The patient underwent coiling of the gastroduodenal artery, gastroepiploic artery and two pancreaticoduodenal arterial branches. The patient was diagnosed with MALS and 6 months later underwent open resection of the median arcuate ligament. MALS should be considered as a rare cause of upper gastrointestinal bleeding. The literature and proposed treatments are discussed.

Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer.

BACKGROUND: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. METHODS: Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. RESULTS: The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0-44.3) and 12.9 months (95% CI 10.2-15.6), respectively. CONCLUSIONS: Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained.

Second Generation of a Fast-track Liver Resection Programme.

BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and decrease morbidity and hospital stay in several major surgical procedures. The aim of this study was to investigate the effect over time of a modified previously published fast-track programme in unselected patients undergoing open or laparoscopic liver resection. METHODS: A prospective study includes the first 121 consecutive patients following an updated fast-track programme for liver resection. High-dose methylprednisolone was given to all patients before surgery, catheters and drains were systematically removed early, and patients were mobilized and started eating and drinking from the day of surgery. An opioid-sparing multimodal pain treatment was given for the first week. The discharge criteria were (1) pain sufficiently controlled by oral analgesics only; (2) patient comfortable with discharge; (3) no untreated complications. RESULTS: The median length of stay (LOS) for all patients was 4 days, with 2 days after laparoscopic vs. 4 days for open resections. The median LOS after major hepatectomies (≥3 segments) was 5 days. The readmission rate was 6% and the 30-day mortality zero. The LOS decreased compared to our first-generation fast-track programme with LOS 5 days. CONCLUSIONS: Fast-track principles for perioperative care and early discharge are safe even after major liver resection. The introduction of high-dose steroids preoperatively might have facilitated a shorter LOS. Routine discharge on POD 1 or 2 after laparoscopic resection and on POD 4 after open liver resection has proven to be feasible.

ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis: Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial).

OBJECTIVE: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). BACKGROUND: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. METHODS: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. RESULTS: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. CONCLUSION: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

Cystic echinococcosis of the liver: experience from a Danish tertiary reference center (2002-2010).

BACKGROUND: Cystic echinococcosis (CE) of the liver can be treated with ultrasound-guided puncture, aspiration, injection, and re-aspiration (PAIR), with surgery and with benzimidazole derivatives. The aim of this study was to review available data concerning treatment modality and outcome for patients treated for CE of the liver in a Danish tertiary reference center. METHODS: A search was made for patients treated for CE infection between January 1, 2002 and January 1, 2010. All relevant patient records and radiology exams were scrutinized and all cysts were re-classified according to the WHO-IWGE, blinded as to which treatment the patient had received. PAIR was performed as a first choice treatment and surgery was reserved for cases where PAIR was impossible. Inactive cyst stages received medical treatment only. RESULTS: The search revealed 26 cases with confirmed CE of the liver. Nine patients underwent PAIR and nine patients surgery as a first choice treatment. Three patients were treated with PAIR secondary to surgery and one patient was treated with surgery secondary to PAIR. For all PAIR treatments, the success rate was 58% regardless of cyst stage and for surgery the success rate was 70%. The difference between the rates was not statistically significant (p = 0.67). CONCLUSION: CE is a rare disease in Denmark and our study is the first describing clinical management of CE in our institution.

Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: an open, randomized, prospective, multicenter, parallel-group trial.

BACKGROUND: The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation (ABC) treatment in liver resection. METHODS: This trial was designed as an international, multicenter, randomized, controlled surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥ 1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondary hemostasis. Secondary end points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). RESULTS: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC was 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did not differ between the 2 groups. Mortality (2 vs 4 patients) and adverse reactions (24 vs 28 patients) for TachoSil versus ABC did not differ. CONCLUSION: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality remained unchanged between both groups.

Resection of hilar cholangiocarcinoma with left hepatectomy after pre-operative embolization of the proper hepatic artery.

BACKGROUND: Right or right-extended hepatectomy including the caudate lobe is the most common treatment for hilar cholangiocarcinoma (HC). A 5-year survival of up to 60% can be achieved using this procedure if R0-resection is obtained. However, for some patients a left-sided liver resection is necessary to obtain radical resection. The close relationship between the right hepatic artery and the HC in these patients frequently limits the ability to achieve a radial R0-resection without difficult vascular reconstruction. The aim of the present study was to describe the outcome of patients who underwent pre-operative embolization of the proper hepatic artery in an effort to induce development of arterial collaterals thus allowing the resection of the proper and right hepatic artery without vascular reconstruction. METHODS: In patients presenting with HC who were considered to require a left hepatic lobectomy and in whom pre-operative work up revealed possible tumour invasion of the right hepatic artery, transcatheter arterial embolization (TAE) of the proper hepatic artery or the left and right hepatic arteries was performed. Three weeks later, a left-sided hepatectomy with resection of all portal structures except the portal vein was performed. RESULTS: In six patients, pre-operative embolization of the proper hepatic artery was performed. Almost instantaneously in all six patients arterial flow signals could be detected in the liver using Doppler ultrasonography. No patient died peri-operatively. In all six patients an R0 radial resection was achieved and in three an R0 proximal transection margin was obtained. All post-operative complications were managed successfully using percutaneous drainage procedures. No patient developed local recurrence and two patients remain disease free more than 7 years after surgery. SUMMARY: After pre-operative embolization of the proper hepatic artery, resection of the HC with left hepatectomy is a promising new approach for these technically demanding patients, giving them the chance of a cure.

[Liver resection over the last decade]. / Leverresektioner gennem ti år.

AIMS: The results after liver resection have improved over the last decade with an operative mortality rate of less than 5% in high-volume centres. The aim of the present study was to assess the perioperative outcome after hepatic resection and to assess the long-term survival after liver resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma in our institution. MATERIALS AND METHODS: The patients who underwent their primary liver resection from 1.1.1995-31.12.2004 in our institution were included. The surgical outcome was reviewed retrospectively and the five-year survival after resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma was estimated. RESULTS: 141 patients (71M/70F), median age 58 years (1-78), underwent a liver resection in the ten-year period. The number of resections increased from two in 1995 to 32 in 2004. Median hospital stay was 9 days (3-38). The most frequent complication was biliary leakage (7.8%), haemorrhage (2.8%) and hepatic insufficiency (2.8%). 30-days mortality was 1.4%. The actuarial 5-survival after hepatic resection for colorectal liver metastases and hepatocellular carcinoma was 39% and 42%, respectively. CONCLUSION: The morbidity and mortality rate after hepatic resection and the long-term survival for patients undergoing resection for hepatic metastases from colorectal cancer and hepatocellular carcinoma in our institution are comparable with the best high-volume centres.

Long-term graft outcome of pediatric liver transplantation in Copenhagen: analysis of the first 51 cases.

BACKGROUND: Graft loss after liver transplantation remains a significant problem, especially in pediatric patients. The aim of this study was to assess our initial series of pediatric liver transplantation and to identify the risk factors that influence graft outcome. METHODS: The first 51 transplantations were analyzed retrospectively. All transplantations were stratified into three groups according to graft type (full-size, reduced-size, and living-related-donor graft). Survival data of the grafts were stratified and multivariate analysis conducted with respect to preoperative and surgical factors. RESULTS: Seventeen of all the transplants were full-size grafts and 34 technical-variant grafts (27 reduced-size grafts from cadavers and 7 living-related-donor grafts). The overall graft survival rates were 65, 62 and 53% at 1, 3 and 5 years, respectively. Twenty-three of 51 grafts (45%) were lost. Poor status of the recipients (hospitalization or intensive care unit care before surgery), a retransplanted graft, and a reduced-size graft were independent risk factors for graft failure. With experience, overall graft survival has improved significantly and the differences in graft survival between graft types have disappeared. CONCLUSIONS: To improve graft survival after pediatric liver transplantation, the timely referral of potential recipients to the transplant team and employing a meticulous technique during the operation, particularly for the technical-variant graft, are required.