Search

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The number of laparoscopic liver resections is increasing worldwide, including in Switzerland. However, laparoscopy is mostly used for minor resections. Little is known about indications for and outcomes of major liver resections performed laparoscopically. The aim of this study was to compare the clinical outcome of open and laparoscopic major liver resection cohorts in two Swiss centres., Methods: Patients undergoing open or laparoscopic major hepatectomy (>3 segments) in two cantonal hospitals from January 2015 to December 2019 were analysed. All disease types except perihilar cholangiocarcinomas, rare malignancies and resections with biliary reconstruction were included. The primary outcome was the number of complications incurred. Operation time, blood loss, hospital stay and 90-day mortality were secondary outcomes investigated. A separate analysis was performed for colorectal liver metastases, the most common indication. Potential risk factors for major complications were evaluated in a multivariate analysis., Results: A total of 88 patients were identified. Among those, 34 patients underwent laparoscopic major hepatectomy (LAPH) and 54 patients open major hepatectomy (OH). The two groups did not differ in demographics. The most common indication was malignancy (LAPH 94% vs OH 98%), mainly colorectal liver metastases (LAPH 53% vs OH 59%). There was no significant difference in major complications (21% vs 15%, p = 0.565). Median operation time (LAPH 433 minutes, interquartile range [IQR 351-482 vs OH 397 minutes, IQR 296-446; p = 0.222), blood loss (325 ml, IQR 200-575 vs 475 ml, IQR 300-800; p = 0.150) and hospital stay (9 days, IQR 8-14 vs 11 days, IQR 9-14; p = 0.441) were comparable between the two cohorts. There was no significant difference in 90-day mortality (3% vs 7%, p = 0.881). The laparoscopic technique was not identified as a risk factor for major complications in a multivariate analysis., Conclusion: This first report from Switzerland evaluating outcomes of laparoscopic major hepatectomies showed no difference in complications and clinical non-inferiority compared with open major hepatectomy.

Aim: Defining sensitivity, specificity, diagnostic accuracy for detection of colorectal liver metastases in imaging compared to intraoperative assessment. Defining a cutoff, where accuracy of detection is impaired., Methods: Prospective single-institution clinical trial (clinicaltrials.gov: NCT01522209). Patients underwent CEUS, MDCT, and 3 Tesla EOB-MRI within 2 weeks preoperatively. Intraoperative palpation, IOUS, and CEIOUS were performed. A patient and lesion-based database was analyzed for accuracy of detection of CEUS, CT, MRI, and Palp/IOUS/CEIOUS combined read. Histology was standard of reference., Results: Forty-seven high tumor load (mean 5, 4 lesions) patients were analyzed. Histopathology confirmed 264 lesions (245 malignant: 19 benign). Accuracy for detection of all lesions: CEUS 63%, CT 71%, MRI 92%, and PALP/IOUS/CEIOUS 98%. ROC analysis for lesion size showed severe impairment of accuracy in lesion detection smaller than 5mm. Intraoperative imaging was not impaired by lesion size. Patient-based analysis revealed a change of resection plan after IOUS/CEIOUS in 35% of patients., Conclusion: At 5-mm lesion size, preoperative imaging shows a drop in accuracy of detection. In patients with multiple lesions, addition of MRI to MDCT seems useful. Accuracy of intraoperative ultrasound is not impacted by lesion size and should be mandatory. CEIOUS can improve intraoperative decision-making., Trial Registration: Study registered with clinicaltrials.gov : NCT01522209., (© 2021. The Society for Surgery of the Alimentary Tract.)

To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable. SIGNIFICANCE: Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor. This article is highlighted in the In This Issue feature, p. 2355 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Regenerative liver surgery expands the limitations of technical resectability by increasing the future liver remnant (FLR) volume before extended resections in order to avoid posthepatectomy liver failure (PHLF). Portal vein rerouting with ligation of one branch of the portal vein bifurcation (PVL) or embolization (PVE) leads to a moderate liver volume increase over several weeks with a clinical dropout rate of 20-40%, mostly due to tumor progression during the waiting period. Accelerated liver regeneration by the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) was poised to overcome this limitation by reduction of the waiting time, but failed due increased perioperative complications. Simultaneous portal and hepatic vein embolization (PVE/HVE) is a novel minimal invasive way to induce rapid liver growth without the need of two surgeries., Purpose: This article summarizes published results of PVE/HVE and analyzes what is known about its efficacy to achieve resection, safety, and the volume changes induced., Conclusions: PVE/HVE holds promise to induce accelerated liver regeneration in a similar safety profile to PVE. The demonstrated accelerated hypertrophy may increase resectability. Randomized trials will have to compare PVE/HVE and PVE to determine if PVE/HVE is superior to PVE., (© 2020. The Author(s).)

Background: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes., Methods: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network., Results: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116)., Conclusions: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Colorectal liver metastases (CRLM) affect over 50 % of all patients with colorectal cancer, which is the second leading cause of cancer in the western world. Resection of CRLM may provide cure and improves survival over chemotherapy alone. However, resectability of CLRM has to be decided in multidisciplinary tumor boards and is based on oncological factors, technical factors and patient factors. The advances of chemotherapy lead to the abolition of contraindications to resection in favor of technical resectability, but somatic mutations and molecular subtyping may improve selection of patients for resection in the future. Technical factors center around anatomy of the lesions, volume of the remnant liver and quality of the liver parenchymal. Multiple strategies have been developed to overcome volume limitations and they are reviewed here. The least investigated topic is how to select the right patients among an elderly and frail patient population for the large variety of technical options specifically for bi-lobar CRLM to keep 90-day mortality as low as possible. The review is an overview over the current state-of-the art and a systematic guide to the topic of resectability of CRLM for both clinicians and patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Simultaneous portal vein embolization (PVE) and hepatic vein embolization (HVE) has been shown to be feasible, safe and lead to a faster growth of future liver remnant (FLR) than PVE alone. The objective of this study is to highlight different technical aspects as well as importance of embolization order., Materials and Methods: Seven patients were treated with simultaneous PVE and HVE. In three cases, HVE was performed first followed by PVE and in four cases the other way around. Portal vein branches were embolized using Glubran-Lipiodol mixture in all cases. Hepatic veins were embolized using Amplatzer II plugs sized 8-20 mm. Specific consideration was given to depth of glue penetration in the portal vein defined by visible branch order on the treated side., Results: Six of seven patients were discharged home the same day. One patient with infected tumor necrosis died of liver failure 40 days later, otherwise there were no periprocedural clinical complications. Median glue penetration was to the 5th order (4th - 5th) when PVE was performed first and 3rd order (2nd - 4th) when PVE was performed after HVE. In one PVE first case, glue spillage was seen due to marked reduced flow in the right portal vein. There was sufficient FLR growth for subsequent surgical resection in the remaining six patients., Conclusion: PVE should be performed prior to HVE because the reduced flow in the portal vein after HVE leads to less deep glue penetration with presumably increased risk of contralateral spillage.

Purpose of Review: For three decades, portal vein embolization (PVE) has been the "gold-standard" strategy to hypertrophy the anticipated future liver remnant (FLR) in advance of major hepatectomy. During this time, CT volumetry was the most common method to preoperatively assess FLR quality and function and used to determine which patients are appropriate surgical candidates. This review provides the most up-to-date methods for preoperatively assessing the anticipated FLR and summarizes data from the currently available strategies used to induce FLR hypertrophy before surgery for hepatobiliary malignancy., Recent Findings: Functional and physiological imaging is increasingly replacing standard CT volumetry as the method of choice for preoperative FLR assessment. PVE, associating liver partition and portal vein ligation, radiation lobectomy, and liver venous deprivation are all currently available techniques to hypertrophy the FLR. Each strategy has pros and cons based on tumor type, extent of resection, presence or absence of underlying liver disease, age, performance status, complication rates, and other factors. Numerous strategies can lead to FLR hypertrophy and improve the safety of major hepatectomy. Which is best has yet to be determined.

Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hypoxic HSC. Hypoxia signaling in HSC induces VEGF-dependent angiogenesis. HSC play a crucial role in the cellular crosstalk of rapid liver regeneration.

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials., Methods: The National Cancer Database was used to examine treatment patterns and survival in patients diagnosed with ACC from 2006 to 2015. Treatment modalities were compared within that group and with a historical cohort (1985 to 2005). χ2 tests were performed, and Cox proportional hazards models were created., Results: From 2006 to 2015, 2752 patients were included; 38% of patients (1042) underwent surgery alone, and 31% (859) underwent surgery with adjuvant therapy. Overall 5-year survival rates for all stages after resection were 43% (median, 41 months) in the contemporary cohort and 39% (median, 32 months) in the historical cohort. After 2007, patients who underwent surgery were more likely to receive adjuvant chemotherapy (P = 0.005), and 5-year survival with adjuvant chemotherapy improved (41% vs 25%; P = 0.02). However, survival did not improve in patients with unresectable tumors after 2011 compared with 2006 to 2011 (P = 0.79). Older age, tumor size ≥10 cm, distant metastases, and positive margins were associated with lower survival after resection (hazard ratio range: 1.39 to 3.09; P < 0.03)., Conclusions: Since 2007, adjuvant therapy has been used more frequently in patients with resected ACC, and survival for these patients has improved but remains low. More effective systemic therapies for patients with ACC, especially those in advanced stages, are desperately needed., (Copyright © 2019 Endocrine Society.)

Background: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery., Methods: All patients with complete liver volume data in the associating liver partition and portal vein ligation for staged hepatectomy registry were included in this study. Estimate total liver volume and estimated future remnant liver volume were calculated for 16 published formulas. The median over- or underestimation compared with actual measured volumes were determined for estimate total liver volume and future remnant liver volume. The proportion of patients with an under- or overestimated future remnant liver volume for each formula were compared with each other using a 25% cut-off for each formula., Results: Among 529 studied patients, the formulas ranged from a 19% underestimation to a 63% overestimation of estimate total liver volume. Estimation of future remnant liver volume lead to a 10% underestimation to a 5% overestimation among the formulas. Of all studied formulas, the Vauthey1 formula was the most accurate, generating underestimation of future remnant liver volume in 20% and overestimation of future remnant liver volume in 6% of patients., Conclusion: Validation of 16 published total liver volume formulas in a multicenter international cohort of 529 patients that underwent staged hepatectomy revealed that the Vauthey formula (estimate total liver volume = 18.51 × body weight + 191.8) provides the most accurate prediction of the actual future remnant liver volume., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: ALPPS is a two-stage hepatectomy that induces more rapid liver growth compared to conventional strategies. This report aims to establish a risk-score to avoid adverse outcomes of ALPPS only for patients with colorectal liver metastases (CRLM) as primary indication for ALPPS., Methods: All patients with CRLM included in the ALPPS registry were included. Risk score analysis was performed for 90-day mortality after ALPPS, defined as death within 90 days after either stage. Two risk scores were generated i.e. one for application before stage-1, and one for application before stage-2. Logistic regression analysis was performed to establish the risk-score., Results: In total, 486 patients were included, of which 35 (7%) died 90 days after stage-1 or 2. In the stage-1 risk score, age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.9) and total center-volume (OR 2.4) were included. For the stage-2 score age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.8), bilirubin 5 days after stage-1 >50 μmol/L (OR 2.4), and stage-1 morbidity grade IIIA or higher (OR 6.3) were included., Conclusions: The CRLM risk-score to predict mortality after ALPPS demonstrates that older patients with small remnant livers in inexperienced centers, especially after experiencing morbidity after stage-1 have adverse outcomes. The risk score may be used to restrict ALPPS to low-risk patient populations., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) occurs at high incidence in abdominal cancer surgery; therefore, a 4-week postoperative VTE prophylaxis is advocated. However, most patients with neuroendocrine tumors (NETs) have more favorable prognoses. This study aimed to determine the incidence of VTE in patients with abdominal NETs, compare these rates to other abdominal malignancies, and identify VTE risk factors., Methods: The ACS-NSQIP database was queried to identify patients with abdominal NETs and other abdominal malignancies who underwent surgery from 2008 to 2015. A 30-day postoperative VTE incidence for each group was compared. Univariable and multivariable analyses were used to identify VTE risk factors., Results: Of the 7226 operations for patients with benign (2154) and malignant (5072) abdominal NETs, 144 patients experienced a VTE without significant differences between groups. Subgroup analysis revealed a spectrum of VTE rates. Compared to VTE rates of other abdominal malignancies, patients with benign (1.1% vs. 2.4%, p < 0.001) or malignant (1.7% vs. 2.4%, p < 0.001) non-pancreatic abdominal NETs had significantly lower rates, malignant pancreatic NETs (PNETs) (3.4% vs. 2.4%, p = 0.03) had significantly higher rates, and benign PNETs (3.2% vs. 2.4%, p = 0.21) had comparable rates. Multivariable analysis identified pre-operative albumin (p < 0.001), bleeding disorders (p < 0.001), operative time (p < 0.001), and having a PNET (p = 0.04) as risk factors for VTE in abdominal NET patients., Conclusion: Routine extended VTE prophylaxis after surgery may be necessary in PNETs, but probably unnecessary in other abdominal NETs. However, clinicians should use risk factors identified in this study when considering to forego extended VTE prophylaxis in NET patients.

Background: Parenchymal-sparing hepatectomies (PSH) are liver resections with preservation of as much liver parenchyma as possible. PSH can be performed laparoscopically (LPSH), but access to the posterosuperior segments is difficult and they are challenging when there are multiple bilobar lesions; the procedure may require repositioning and may be long and cumbersome. The objective of this systematic review is to analyze the feasibility and limitations of laparoscopic PSH in the literature., Methods: A systematic review of the literature was performed by searching Medline/PubMed, Scopus, and Cochrane databases. Resections were categorized by segment(s), and data regarding operative time, blood loss, length of hospital stay, complications, and R0 resection were analyzed., Results: Of 351 studies screened for relevance, 48 studies were reviewed. Ten publications fulfilled inclusion criteria, reporting data from 579 patients undergoing LPSH. The most common indication was CRLM (58%) followed by hepatocellular carcinoma (16%). Only 92 patients were reported to have resections of more than one tumor; the maximum number of lesions resected was seven. Of resected lesions, 21.5% were located in the cranial segments. Mean operating time was 335.2 min, estimated blood loss was 462 cc, and hospital stay was 7.6 days. Conversion rate was 9.7%, and complications occurred in 19.4% of cases. No perioperative mortality was reported. R0 resections were achieved in 87.7% of cases., Conclusion: Laparoscopic PSH is performed and reported, but the data quality is low so far. The main limitation of LPSH is the low number of lesions resected, especially for bilobar, metastatic disease. Prospective reports with tumor-specific oncological data are desirable.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly present with metastatic disease, and the liver is the most frequent metastatic site. Herein, we studied whether primary tumor site affects survival in patients with GEP-NETs and liver metastases (NELM). As a secondary endpoint, we studied whether extrahepatic disease and surgical resection impact survival in this patient population., Methods: Patients with NELM diagnosed from 2006 to 2014 were identified from the National Cancer Database. Kaplan-Meier curves and nested Cox proportional hazards were used to assess variables associated with survival., Results: 2947 patients with well- or moderately differentiated GEP-NETs and NELM met the inclusion criteria for this study. Patients with small bowel NETs survived the longest of all GEP-NETs with NELM (median not reached). Rectal and gastric NETs with NELM had the shortest survival (median 31 months). Patients with extrahepatic metastases who underwent any operation survived longer than those managed nonoperatively (median survival 38.7 months vs. 18.6 months, p = 0.01). On multivariable analysis, operations on the primary tumor and distant metastatic site (HR 0.23-0.43 vs. no surgery), treatment at an academic/research hospital, Charlson comorbidity index of 0, no extrahepatic metastases, and younger age were associated with prolonged survival ( p < 0.01)., Conclusions: Primary tumor site affects survival in patients with GEP-NETs and NELM. Surgical resection seems beneficial for all GEP-NETs with NELM, even in the presence of extrahepatic metastases.

Background: Liver hypertrophy induced by partial portal vein occlusion (PVL) is accelerated by adding simultaneous parenchymal transection ("ALPPS procedure"). This preclinical experimental study in pigs tests the hypothesis that simultaneous ligation of portal and hepatic veins of the liver also accelerates regeneration by abrogation of porto-portal collaterals without need for operative transection., Methods: A pig model of portal vein occlusion was compared with the novel model of simultaneous portal and hepatic vein occlusion, where major hepatic veins draining the portal vein-deprived lobe were identified with intraoperative ultrasonography and ligated using pledgeted transparenchymal sutures. Kinetic growth was compared, and the portal vein system was then studied after 7 days using epoxy casts of the portal circulation. Portal vein flow and portal pressure were measured, and Ki-67 staining was used to evaluate the proliferative response., Results: Pigs were randomly assigned to portal vein occlusion (n = 8) or simultaneous portal and hepatic vein occlusion (n = 6). Simultaneous portal and hepatic vein occlusion was well tolerated and led to mild cytolysis, with no necrosis in the outflow vein-deprived liver sectors. The portal vein-supplied sector increased by 90 ± 22% (mean ± standard deviation) after simultaneous portal and hepatic vein occlusion compared with 29 ± 18% after PVL (P < .001). Collaterals to the deportalized liver developed after 7 days in both procedures but were markedly reduced in simultaneous portal and hepatic vein occlusion. Ki-67 staining at 7 days was comparable., Conclusion: This study in pigs found that simultaneous portal and hepatic vein occlusion led to rapid hypertrophy without necrosis of the deportalized liver. The findings suggest that the use of simultaneous portal and hepatic vein occlusion accelerates liver hypertrophy for extended liver resections and should be evaluated further., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with gastroenteropancreatic neuroendocrine tumors often present with stage IV disease. Primary tumor resection in these patients remains controversial. Herein, we studied the impact of primary tumor removal, identified variables associated with prolonged survival for each neuroendocrine tumor subtype, and determined factors that influence surgeons to perform primary tumor resection., Methods: Patients with metastatic gastroenteropancreatic neuroendocrine tumors diagnosed from 2004 to 2014 were identified from the National Cancer Database. Nested Cox proportional hazards and logistic regression models were used to assess variables associated with survival and primary resection., Results: A total of 14,510 patients met inclusion criteria. On multivariable analysis, resection of the primary tumor and grade 1 or 2 tumors was associated with prolonged survival in all subtypes (P < .001). Organ-specific variables associated with prolonged survival in patients undergoing primary tumor resection included the following: low grade for all organs; young age for pancreatic, small intestinal, colonic, and rectal neuroendocrine tumor; tumor size for colonic and rectal neuroendocrine tumor; and tumor location for colonic neuroendocrine tumor. Low tumor grade was found to be significantly associated with removal of the primary tumor across all organs., Conclusion: This study is the first suggesting that primary tumor resection is associated with prolonged survival for all gastro-entero-pancreatic NETs. Additional variables related to survival for each NET subtype were identified and might help select patients who benefit from primary tumor removal., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: 68 Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68 Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors., Methods: Records of patients who underwent 68 Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68 Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted., Results: A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68 Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006)., Conclusion: Performing 68 Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Conservative obesity treatment often leads to limited results. Bariatric surgery is highly efficient, but the candidates are at risk of developing perioperative complications. Bariatric outcomes have been well described in the past, but there are only few reports of perioperative outcomes. The aim of this study was to evaluate the incidence of anaesthetic and surgical complications of Roux-en-Y bypass., Methods: Data of all adult patients, who underwent primary Roux-en-Y gastric bypass surgery between 1/2006 and 12/2013 at the University Hospital Zurich were analysed. Using our clinical database, anaesthetic and surgical complications during the first 30 days after surgery were analysed and risk factors determined by multivariate analysis., Results: Seven hundred eleven patients (72% female, median age 40 years) were analysed. Overall, surgical complications occurred in 34% patient, while complications attributable to anaesthesia occurred in 37%. Post-operative nausea and vomiting (PONV) were observed in 34%, intubation-related complications in 4%, and delayed extubation in 2% of our patients. Within the first 30 days after surgery, 22% of the patients presented with an infection. Gastrointestinal complications were found in 8%, and bleeding complications in 3%. Anaesthesia complications were less common in older patients and in patients anaesthetized with a volatile anaesthetic. Severe complications were more common in patients with a lower body mass index (BMI) and with longer surgery. The risk to develop a postoperative infection was higher in diabetic patients., Conclusion: Roux-en-Y bariatric surgery has few anaesthetic complications, the most common is PONV. PONV is more common in younger patients and not more common with volatile anaesthetics. Major complications are overall rare and occur in patients with lower BMI and longer surgery, likely reflecting more difficult procedures.

Background: Randomized controlled trials (RCTs) data demonstrate that sevoflurane postconditioning improves clinical outcomes of liver resection with inflow occlusion, presumably due to hepatocyte protection from ischemic injury. However, mechanisms remain unclear. This study examines liver biopsy samples obtained in an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane attenuates hepatocyte apoptosis., Methods: Messenger ribonucleic acid (mRNA) of pro- and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined in hepatic biopsies obtained during the RCT. Hepatic stellate cells (HSCs) and hepatocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to evaluate the effect of sevoflurane postconditioning on apoptosis. The role of HSC as a potential apoptosis trigger in hepatocytes through the production of reactive oxygen species induced by H/R was explored by transferring supernatants from H/R-exposed HSC to hepatocytes as target cells., Results: In patients of the RCT, the Bax/Bcl2 mRNA ratio in liver tissue was markedly decreased in the sevoflurane arm (25% ± 21% reduction; P = .001). In vitro, H/R increased reactive oxygen species production in HSC by 33% ± 16% (P = .025), while it was abolished in the presence of sevoflurane (P < .001). In hepatocytes, caspase was minimally activated by H/R. However, incubation of hepatocytes with supernatants of HSC, previously exposed to H/R, increased caspase activity by 28% ± 13% (P < .001). When exposed to supernatants from HSC undergoing sevoflurane postconditioning, caspase activation in hepatocytes was reduced by 20% ± 9% (P < .001), similarly to the sevoflurane effect on the BAX/Bcl2 mRNA ratio in the liver samples., Conclusions: The study shows that sevoflurane postconditioning affects apoptosis of hepatocytes after ischemia-reperfusion injury in patients. It also demonstrates that HSC may be the effector cells of sevoflurane protection.

Ten years ago the first patient underwent Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). This report aimed to critically review literature on ALPPS in terms of methods, outcomes, and bias. In total, 237 English papers on ALPPS were identified, 75 (32%) were letters and 43 (18%) case-reports. Forty-nine single-center series reported a median 10 patients, with 0-69% morbidity and 0-50% mortality. The indications for ALPPS were reported in 35% and 47% reported on modifications. Twenty-three multicenter series included a median 45 patients. Some reports excluded up to 399 cases. 26% reported on the indications and 35% on ALPPS modifications. Across journals, variation in positive and negative conclusions on ALPPS was observed. Ten years of ALPPS have resulted in diverse publications with a high concern of bias. Although one randomized study has been published, a more critical approach towards retrospective methodology is needed to allow pragmatic conclusions for HPB-surgeons., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: In the international associating liver partition and portal vein ligation for staged hepatectomy registry, more than 50% of patients underwent associating liver partition and portal vein ligation for staged hepatectomy with a right hepatectomy. This study evaluated the necessity of two-stage hepatectomies being performed as right hepatectomy associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases versus right trisectionectomy associating liver partition and portal vein ligation for staged hepatectomy., Patients and Methods: All patients registered between 2012 and 2017 undergoing associating liver partition and portal vein ligation for staged hepatectomy for colorectal liver metastases were included. A liver to body weight index of 0.5 or less prior to stage I in the presence of liver damage was used as an internationally accepted standard to justify a two-stage hepatectomy., Results: Four-hundred and three patients with colorectal liver metastases with right hepatectomy associating liver partition and portal vein ligation for staged hepatectomy (n = 183) or right trisectionectomy associating liver partition and portal vein ligation for staged hepatectomy (n = 220) were analyzed. Presence of metastases in segments II/III, liver damage, number of patients on chemotherapy, and cycles were comparable, and there was a comparable response to chemotherapy. Liver to body weight index was different prior to stage 1 (right trisectionectomy associating liver partition and portal vein ligation for staged hepatectomy: 0.33 ± 0.12 versus right hepatectomy associating liver partition and portal vein ligation for staged hepatectomy: 0.40 ± 0,14; P < .001) and prior to stage 2 (right trisectionectomy associating liver partition and portal vein ligation for staged hepatectomy: 0.58 ± 0.17 versus right hepatectomy associating liver partition and portal vein ligation for staged hepatectomy: 0.66 ± 0,18; P < .001). Hypertrophy rates were similar between groups. As much as 16.9% and 7.2% of patients in right hepatectomy associating liver partition and portal vein ligation for staged hepatectomy and right trisectionectomy associating liver partition and portal vein ligation for staged hepatectomy had no apparent justification for a two-stage hepatectomy based on LBWI prior to stage 1 and absence of chemotherapy (<12 cycles)., Conclusion: More than 15% of associating liver partition and portal vein ligation for staged hepatectomy procedures were performed in patients who may have had no indication for a two-stage hepatectomy, especially in the group of patients with right hepatectomy. Thus, it appears that there is a risk of the overuse of associating liver partition and portal vein ligation for staged hepatectomy because of its great potential to induce volume growth. Due to the high perioperative risk of associating liver partition and portal vein ligation for staged hepatectomy, indications should be carefully reconsidered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Over 50% of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have stage IV disease at presentation and the most likely organ to be affected by metastases is the liver. Hepatic involvement and hepatic tumor burden is a key prognostic factor affecting survival of these patients and 80% eventually die of liver failure due to tumor dissemination within the liver. This commentary explores the efficacy and limitations of systemic treatments in patients with GEP-NETs and liver metastases. Landmark randomized trials using systemic therapies including sandostatin (PROMID), lanreotide (CLARINET), everolimus (RADIANT 3 and 4), sunitinib and Peptide Receptor Radionuclide Therapy (NETTER-1) have not shown efficacy in reducing liver tumor burden in patients with stage IV GEP-NETs with liver metastases as outlined in this review. Although often overlooked, surgical debulking has been associated with a significant survival advantage in large retrospective studies and in our opinion should remain an important therapeutic option for patients with stage IV GEP-NETs and liver metastases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver growth than portal vein ligation (PVL). Transection of parenchyma in ALPPS may prevent the formation of collaterals between lobes. The aim of this study was to determine if abrogating the formation of collaterals through parenchymal transection impacted growth rate., Methods: Twelve Yorkshire Landrace pigs were randomized to undergo ALPPS, PVL, or "partial ALPPS" by varying degrees of parenchymal transection. Hepatic volume was measured after 7 days. Portal blood flow and pressure were measured. Portal vein collaterals were examined from epoxy casts., Results: PVL, ALPPS, and partial ALPPS led to volume increases of the RLL by 15.5% (range 3-22), 64% (range 45-76), and 32% (range 18-77), respectively, with significant differences between PVL and ALPPS/partial ALPPS (p < 0.05). In PVL and partial ALPPS, substantial new portal vein collaterals were found. The number of collaterals correlated inversely with the growth rate (p = 0.039). Portal vein pressure was elevated in all models after ligation suggesting hyperflow to the portal vein-supplied lobe (p < 0.05)., Conclusions: These data suggest that liver hypertrophy following PVL is inversely proportional to the development of collaterals. Hypertrophy after ALPPS is likely more rapid due to reduction of collaterals through transection.

Background: Liver resection is a well-established treatment for colorectal, neuroendocrine and sarcomatous metastases but remains ill-defined for metastases from other primary sites. This study aimed to analyze the outcomes of hepatic resection for metastases not of colorectal, neuroendocrine, sarcomatous, or ovarian (NCNSO) origin and to identify predictors of outcome., Methods: Retrospective analysis of patients undergoing resection for NCNSO metastases in three western centers. Patients were analyzed according to the primary cancer. Outcomes were recurrence and survival., Results: We analyzed 188 patients, divided in: gastrointestinal (59), breast (59) and "others" (70). Median time to recurrence was 15.3 months, while median survival was 52 months. Survival at 1, 3, and 5 years was 78%, 60.4% and 47.8%, respectively. In term of prognostic factors, metastases >35 mm from gastrointestinal tumors were associated with lower survival (p = 0.029) and age>60 years was associated with better survival in breast metastases (p = 0.018)., Conclusions: Liver resection for NCNSO metastases is feasible and results in long-term survival are similar to colorectal metastases. In gastrointestinal metastases, size (<35 mm) could be used to select patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Colorectal metastases - Current treatment strategies Abstract. In the course of their disease, more than 50 % of patients with colorectal cancer develop metastases. They are most frequently localized in the liver, followed by the peritoneum and the lungs. The therapeutic options and prognosis of colorectal metastases have improved markedly in recent years. Modern treatment concepts are multimodal and are customized for the individual patient by interdisciplinary tumour boards that follow widely recognised guidelines and norms. The recommendation of an appropriate treatment option in metastasized patients by an interdisciplinary panel of experts is of paramount importance. Besides technical possibilities, factors such as comorbidities, medical outcomes, quality of processes as well as patient-related outcome are all crucial in the decision-making process. In most patients diagnosed with distant metastases, the prognosis is determined by the extent of the liver burden. Hereby, the resection of the liver metastases is of utmost importance to improve the prognosis of a patient, since only those individuals who have successfully undergone resection have a chance for long-term disease free-survival. Whether liver metastases are resectable depends on sufficient volume and function of the future liver remnant (FLR). Manipulation of the FLR as well as upfront oncological treatment of metastases improves the resectability rates in patients with an advanced tumor load in the liver. Laparoscopic liver resection improves patient outcomes by reducing pain and results in a shortened hospital stay. Lung resection for pulmonary metastases as well as cytoreductive surgery for peritoneal metastases are important mainstays of modern personalized treatment concepts. However, results of ongoing trials are eagerly awaited to help quantify the prognostic effects of those therapies and assess their true therapeutic value.

Background: A minimum future liver remnant (FLR) of 30% is required to avoid post hepatectomy liver failure (PHLF). Portal vein occlusion (PVO) is the main strategy to induce hypertrophy of the FLR, but some patients will not reach sufficient FLR hypertrophy to enable resection. Recently ALPPS has emerged as a "Salvage Procedure" for PVO failure. The aim of this study was to report the short term outcomes of ALPPS following PVO failure., Methods: A retrospective analysis of patients enrolled within the international ALPPS Registry between October 2012 and November 2015 (NCT01924741) was performed. Patients with documented PVO failure were included. The outcomes reported included feasibility, FLR growth rate and safety of ALPPS. Complications were recorded as per Clavien-Dindo classification., Results: From 510 patients enrolled in the Registry there were 22 patients with previous PVO failure. Two patients were excluded due to missing data and twenty patients were analysed. All of them completed the proposed ALPPS with a medium FLR increase of 88% (23-115%) between two stages and no 90-day mortality., Conclusion: In experienced centers, ALPPS following PVO failure is feasible and safe. The FLR hypertrophy was similar to other ALPPS series. ALPPS is a potential rescue strategy after PVO failure., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was introduced with the promise to reduce posthepatectomy liver failure (PHLF) in extended hepatectomies but has higher morbidity and mortality rates compared to conventional methods of volume enhancement. There are few studies of the incidence of PHLF after ALPPS and little information on how to avoid PHLF by functional testing. It remains unclear what causes the compromise in liver function despite rapid volume gain and if any of the modifications proposed reduce the incidence of PHLF. This review summarizes published data on this topic., Methods: This is a systematic review that studies literature on the incidence of liver failure and assessment of liver function following ALPPS as well as modifications of the existing technique. Articles were searched in PubMed, evaluated, selected, and tabulated., Results: The literature search revealed 326 articles that met the selection criteria. PHLF criteria as defined by the International Study Group of Liver Surgery (ISGLS) were the most commonly used criteria, but PHLF was frequently not defined. PHLF occurred most frequently after stage 2 of ALPPS at around 30% in most larger studies. Hepatobiliary scintigraphy showed a discrepancy between volume and functional growth of the liver. Function increase was only 50% compared to volume increase. Mechanistic explanations using histologic analyses have been given to explain the immaturity of the liver after rapid hypertrophy. Modifications of ALPPS showed a comparable volumetric gain when compared to classic ALPPS, but data were lacking to assess PHLF., Conclusion: ALPPS has relatively high rates of PHLF, morbidity, and mortality. This may be explained by data demonstrating functional growth when compared to volume growth. ALPPS should not be performed without functional assessment and with caution.

Background: Associating liver partition with portal vein ligation for staged hepatectomy induces more extensive liver hypertrophy than ligation alone; however, the mechanisms underlying the accelerated liver regrowth and the functional quality of the hypertrophic liver are presently elusive. This study, therefore, investigated the effect of parenchymal transection on liver volume and function after portal vein embolization in a standardized rabbit model., Methods: Twelve rabbits were subjected to portal vein embolization of the cranial liver lobes and randomized between parenchymal transection of the left lateral liver lobe versus no transection (portal vein embolization only). Liver volume of the nonembolized liver lobe was assessed using computed tomography-volumetry, and liver uptake function was determined by 99m Tc-mebrofenin hepatobiliary scintigraphy before and 3 and 7 days after portal vein embolization., Results: The increase in nonembolized liver volume 3 days after portal vein embolization was 2.7-fold greater in the transected group compared with the portal vein embolization only group (56 ± 16% vs 21 ± 12%, respectively, P < .01) and 1.7-fold greater 7 days after portal vein embolization (113 ± 34% vs 68 ± 24%, P < .01). Liver uptake function did not differ between groups before portal vein embolization (8.4 ± 3.7%/min in the transection group vs 8.9 ± 1.6%/min) on day 3 (33.2 ± 4.7% after transection vs 30.3 ± 4.6%/min, respectively) and day 7 after portal vein embolization (42.6 ± 8.4% vs 39.1 ± 5.3%/min, respectively)., Conclusion: Parenchymal transection after portal vein embolization increases liver growth in terms of volume but not function. These results indicate that the rapid volume increase observed after associating liver partition with portal vein ligation for staged hepatectomy does not coincide with the clinically more relevant functional increase. Quantitative liver function tests might be essential in associating liver partition with portal vein ligation for staged hepatectomy to better assess the hypertrophy response and improve clinical decision-making., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces a rapid and extensive increase in liver volume. The functional quality of this hypertrophic response has been called into question because ALPPS is associated with a substantial incidence of liver failure and high perioperative mortality. This multicenter study aimed to evaluate functional liver regeneration in contrast to volumetric liver regeneration in ALPPS, using technetium-99m hepatobiliary scintigraphy and computed tomography volumetry, respectively., Methods: Patients who underwent ALPPS and hepatobiliary scintigraphy in 6 centers were included. Hepatobiliary scintigraphy data were analyzed centrally at the Academic Medical Center in Amsterdam according to established protocols. Increase in liver function as measured by hepatobiliary scintigraphy after stage 1 of ALPPS was compared with the increase in liver volume. In addition, we analyzed the impact of liver function and volume on postoperative outcomes including liver failure, morbidity, and mortality., Results: In 60 patients, future liver remnant volume increased by a median 78% (interquartile range 48-110) during a median 8 (interquartile range 6-14) days after stage 1, while function as measured by hepatobiliary scintigraphy increased by a median 29% (interquartile range 1-55) throughout 7 days (interquartile range 6-10) in the 27 patients with paired measurements. After stage 2 of ALPPS, liver failure occurred in 5/60 (8%) patients, severe complications in 24/60 (40%), and mortality occurred in 4/60 (7%)., Conclusion: In ALPPS, volumetry overestimates liver function as measured by hepatobiliary scintigraphy and may be responsible for the high rate of liver failure. Quantitative liver function tests are highly recommended to avoid post hepatectomy liver failure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

Background: After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal transection. We found that in patients undergoing portal vein ligation and parenchymal transection, portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response. We postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growth., Methods: A rat model of rapid (portal vein ligation and parenchymal transection) and slow regeneration (portal vein ligation) was established. Portal vein flow and pressure data were collected. Liver regeneration was assessed in rats using computed tomography, proliferation with Ki-67, and hypoxia with pimonidazole and HIF-1α staining., Results: The rat model confirmed acceleration of regeneration in portal vein ligation and parenchymal transection as well as the portal vein hyperflow seen in patients. Additionally, tissue hypoxia was observed after portal vein ligation and parenchymal transection, while little hypoxia staining was detected after portal vein ligation. To determine if hypoxia is a consequence or an inciting stimulus of rapid liver regeneration, we used a prolyl-hydroxylase blocker to activate hypoxia signaling pathways in the slow model. This clearly accelerated slow to rapid liver regeneration. Inversely, abrogation of hypoxia led to a blunting of rapid growth to slow growth. The topical application of prolyl-hydroxylase inhibitors on livers in rats induced spontaneous areas of regeneration., Conclusion: This study shows that pharmacologically induced hypoxic signaling accelerates liver regeneration similar to portal vein ligation and parenchymal transection. Hypoxia is likely an accelerator of liver regeneration. Also, prolyl-hydroxylase inhibitors may be used to enhance liver regeneration pharmaceutically., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Laparoscopic ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) has previously been reported but has been the authors' default option since 2015 in patients with small future liver remnant., Methods: A retrospective analysis of all consecutive patients undergoing ALPPS at a single referral center was performed using a prospective database from July 2011 to June 2016. Feasibility was studied by assessing conversions. The 90-day mortality and complications were analyzed using a Dindo-Clavien score and the comprehensive complication index. Operative time, blood loss, volumetric growth, and hospital stay were examined. The CUSUM analysis was performed., Results: ALPPS was performed in 30 patients, 10 of whom underwent a laparoscopic approach. There was no mortality and no complication grade ≥3A observed in laparoscopic ALPPS. In open ALPPS, 10 of 20 patients experienced complications grade ≥3A (p = 0.006) and one patient died. Liver failure was not observed after laparoscopic ALPPS, but two patients in the open ALPPS group developed complications that precluded the second stage. The total hospital stay was shorter in the laparoscopic ALPPS group., Conclusion: Laparoscopic ALPPS is feasible as the default procedure for patients with very small FLR, and it is not inferior to the open approach. Surgeons experienced with complex laparoscopy should be encouraged to use a laparoscopic approach to ALPPS., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study compares the Glissonian approach with the standard approach to laparoscopic liver resection for safety and efficacy., Background: The standard laparoscopic approach to anatomic liver resection is the dissection of the elements of the Glissonian pedicle below the hilar plate. In contrast, the Glissonian approach identifies the intrahepatic pedicles by tentative clamping. Concerns have been raised about the safety of the Glissonian approach in laparoscopic liver surgery. The study was performed to examine the initial 7 years of experience in a single center with regard to safety and efficacy., Methods: All consecutive patients undergoing laparoscopic liver resections from April 2007 to April 2014 at a single referral center for liver tumors were included. An observational comparison was performed between Glissonian and standard laparoscopic liver resections performed by the same team but during different eras. The primary endpoint was safety of the procedures as assessed by the recently published comprehensive complication index. Secondary endpoints were parameters of surgical efficacy, such as operating time, blood loss, blood transfusion, conversion rate, duration of hospitalization, and pathologic margin of the specimen., Results: Between 2007 and 2014, 234 resections were performed laparoscopically at our institution, 120 using the conventional approach and 114 using the Glissonian approach. There was no difference in age, sex, tumor types, or comorbidities between the groups. The number of major liver resections was greater in the Glissonian group, yet there were fewer complications in the Glissonian group compared with the standard group (P < .05). Operative time was greater and more transfusions were given in the standard group; in addition, more patients had positive margins (P < .01). Overall hospital stay was less in the Glissonian group., Conclusions: In the 7-year experience of a single center, the Glissonian approach is not less safe and may seems to offer advantages when compared with the standard laparoscopic approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) is a new surgical approach for the treatment of liver tumors. It is indicated in cases where the future liver remnant is not sufficient to maintain postoperative liver function. We report a totally laparoscopic ALPPS with selective hepatic artery clamping. Pneumoperitoneum itself results in up to 53% of portal vein flow and selective hepatic artery clamping can reduce blood loss while maintaining hepatocellular function. Therefore, the combination of both techniques may result in effective control of bleeding with no damage in the liver function that may have direct impact in the result of ALPPS procedure., Methods: A 65-year-old man with colorectal liver metastases in all liver segments, except liver segment 1 (S1), were evaluated as unresectable. He underwent chemotherapy with objective response and multidisciplinary board decided for ALPPS procedure. First stage was performed entirely by laparoscopy and consisted of enucleation of metastases from segments 2 and 3, ligation of the right portal vein and liver splitting under selective common hepatic artery clamping. The second stage was done 3 weeks later and consisted of laparoscopic right trisectionectomy by laparoscopy., Results: Operative time was 250 and 200 minutes, respectively. Estimated blood loss was 150 and 100 mL. There was no need for transfusion or hospitalization in intensive care. He was discharged on the 3rd and 5th postoperative day, respectively. Recovery was uneventful after both stages and patient did not present any sign of liver failure. Elevation of liver enzymes was minimal. Computerized tomography (CT) scan before second stage showed a liver hypertrophy of 53%, sFLR was 0.37 before second stage, or 33% of the total liver volume. CT scan shows no residual liver disease and optimum liver regeneration. Patient is well with no evidence of the disease 11 months after the procedure., Conclusions: Totally laparoscopic ALPPS is a feasible and safe approach for selected patients with liver tumors. The hypertrophy of the remaining liver was adequate and sequential procedures were performed without morbidity and no mortality. Selective hepatic artery clamping seems to be an interesting solution to decrease intraoperative blood loss without the harsh effect of Pringle maneuver., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates., Method: A national audit was performed to gather information about the safety of the procedure and to better understand the complications. The audit was offered to all high-volume hepatobiliary centers in Italy., Results: Of all Italian centers approached in January 2012, 12 centers with experience in ALPPS enrolled and participated in collection of data. Fifty patients underwent ALPPS between 2012 and 2014. In 48/50 patients completion of hepatectomy was performed successfully. Major morbidity occurred in 54% with a 20% 90-day mortality. Uni- and multivariate analysis showed that ALPPS for cholangiocarcinoma and a peak of bilirubin over 5 mg/dl between stages was associated with increase of 90-day mortality and worse survival., Discussion: It is proposed that a moratorium be introduced for classic ALPPS in cholangiocarcinoma and to abort ALPPS in patients who develop an interstage increase in bilirubin, due to the high risk of liver failure and mortality., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: ALPPS was developed to induce accelerated future liver remnant (FLR) hypertrophy in order to increase hepatic tumour resectability and reduce the risk of post-operative liver failure. While early studies demonstrated concerning complication rates, others reported favourable results. This inconsistency may be due to variability in surgical indications and technique., Methods: A web-based survey was sent to surgeons participating in the International ALPPS Registry in September of 2014. Questions addressed surgeon demographics and training, surgical indications and technique, and clinical management approaches., Results: Fifty six out of 85 surgeons from 78 centers responded (66%) and half (n = 30) had training in liver transplantation. Forty seven (84%) did not reserve ALPPS solely for colorectal liver metastases (CRLM) and 30 (54%) would perform ALPPS for an FLR over 30%. Neoadjuvant chemotherapy for CRLM was recommended by 37 (66%) respondents. Surgical approaches varied considerably, with 30% not preserving outflow to the middle hepatic vein and 39% believing it necessary to skeletonize the hepatoduodenal ligament. Twenty five (45%) surgeons have observed segment 4 necrosis., Conclusion: There is considerable variability in how ALPPS is performed internationally. This heterogeneity in practice patterns may explain the current incongruity in published outcomes, and highlights the need for standardization., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2., Background Data: ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown., Methods: Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality., Results: Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive., Conclusions: This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel strategy to resect liver tumors despite the small size of the liver remnant. It is an hepatectomy in two stages, with PVL and parenchymal transection during the first stage, which induces rapid growth of the remnant liver exceeding any other technique. Despite high postoperative morbidity and mortality in most reports, the technique was adopted by a number of surgeons., Materials and Methods: This systematic review explores current data regarding the feasibility, safety, and oncologic efficacy of ALPPS; the search strategy has been published online. A meta-analysis of hypertrophy, feasibility (ALPPS stage 2 performed), mortality, complications, and R0 (complete) resection was performed., Results: A literature search revealed a total of 13 publications that met the search criteria, reporting data from 295 patients. Evidence levels were low, with the highest Oxford evidence level being 2c. The most common indication was colorectal liver metastasis in 203 patients. Hypertrophy in the meta-analysis was 84 %, feasibility (ALPPS stage 2 performed) 97 % (CI 94-99 %), 90-day mortality 11 % (CI 8-16 %), and complications grade IIIa or higher occured in 44 % (CI 38-50 %) of patients. A standardized reporting format for complications is lacking despite the widespread use of the Clavien-Dindo classification. Oncological outcome is not well-documented. The most common topics in the selected studies published were technical feasibility and indications for the procedures. Publication bias due to case-series and single-center reports is common., Conclusion: A systematic exploration of this novel operation with a rigid methodology, such as registry analyses and a randomized controlled trial, is highly advised.

Background: During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation., Methods: Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay., Results: Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance., Conclusions: This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.