Fernando A. Alvarez

Nuevo Metodo de Regeneracion hepatica

Postoperative liver failure (PLF) is the most feared and serious complication after extensive liver resections. We present an innovative surgical technique for the treatment of a patient with colorectal cancer and initially unresectable liver metastases. After completing neoadjuvant chemotherapy, it was decided to perform simultaneous surgery. A left hemicolectomy and cleaning of the metastases in the left liver was performed. As the future liver remnant (FLR) was insufficient, it was decided to perform an in situ liver split and a right portal vein ligation. On the 6(th) day after the surgery a volumetric CT showed an increase greater than 40% of the FLR. The right hepatectomy was completed and the patient was discharged on the 11(th) day after surgery. The technique induced a rapid growth of the FLR, exceeding that reported using portal occlusion. If these findings are corroborated in future studies, this revolutionary technique could enable surgery to be performed in two stages on patients with initially unresectable liver disease during the same hospital admission and without PLF.

Citrate utilization by homo- and heterofermentative lactobacilli

Citrate utilization by several homo- and heterofermentative lactobacilli was determined in Kempler and McKay and in calcium citrate media. The last medium with glucose permitted best to distinguish citrate-fermenting lactobacilli. Lactobacillus rhamnosus ATCC 11443, Lactobacillus zeae ATCC 15820 and Lactobacillus plantarum ATCC 8014 used citrate as sole energy source, whereas in the other strains, glucose and citrate were cometabolized. Some lactobacilli strains produced aroma compounds from citrate. Citrate transport experiments suggested that all strains studied presented a citrate transport system inducible by citrate. The levels of induction were variable between several strains. Dot blot experiment showed that lactobacilli do not present an equivalent plasmid coding for citrate permease.

The Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Approach Using Only Segments I and IV as Future Liver Remnant

Liver resection, with or without chemotherapy, remains the only treatment with the potential for curingmalignant liver tumors. Frequently, major liver resections are mandatory to achieve tumor-free surgical margins. One of the most severe complications associated with extended resections is posthepatectomy liver failure (PHLF). The best candidates for liver resection with curative intention are those who have enough parenchymal reserve, which should be at least 20% of the total liver volume in the case of a healthy future liver remnant (FLR), and between 30% and 40% in patients with chemotherapy-related liver injury, fibrosis orsteatosis. Portal vein occlusion has become the gold standard strategy to regenerate the FLR with a low morbidity, allowing up to 20% to 35% hypertrophy in 45 days. However, up to 40% of patients treated with this approach are finally not candidates for resection, either because of tumor progression during the interval period or insufficient FLR hypertrophy. Recently, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been introduced as a strategy for preventing PHLF by inducing a rapid (1 week) and large FLR volume increase (21% to 200%). Briefly, during the first surgical stage, the complete removal of any tumor in the FLR must be completed whenever bilateral disease is present. Then the liver parenchyma is transected and portal vein ligation of the tumor-bearing side is applied. The second stage is performed when sufficient hypertrophy of the FLR is demonstrated, usually as a right hepatectomy or trisectionectomy, leaving the left lateral segments of the liver (segments II and III) as part of the FLR. Here we describe a new surgical strategy using the principles of the ALPPS technique, preserving only segments I and IV as the FLR.

Hepatic artery reconstruction first for the treatment of hilar cholangiocarcinoma bismuth type IIIB with contralateral arterial invasion: a novel technical strategy

BACKGROUND En-bloc liver resection with the extrahepatic bile duct is mandatory to obtain tumour-free surgical margins and better long-term outcomes in hilar cholangiocarcinoma (CC). One of the most important criteria for irresectability is local extensive invasion to major vessels. As hilar CC Bismuth type IIIB often requires a major left hepatic resection, the invasion of the right hepatic artery (RHA) usually contraindicates this procedure. METHODS The authors describe a novel technique that allowed an oncological resection in two patients with hilar CC Bismuth type IIIB and contralateral arterial invasion. Arterial reconstruction between the posterior branch of the RHA and the left hepatic artery (LHA) was performed as the first surgical step. Once arterial vascular flow was restored, a left trisectionectomy with caudate lobe resection and portal vein reconstruction was performed. RESULTS In both patients an R0 resection was achieved. Both patients made a full recovery and were discharged within 14 days of surgery. Both patients remain free of disease at 18 months. CONCLUSIONS This new technique allows a R0 resection to be achieved in patients with Bismuth type IIIB hilar CC with contralateral arterial involvement.

Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity

Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome. Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome. Methods: ALPPS centers of the International ALPPS Registry having performed ≥10 cases over a period of ≥3 years were assessed for 90-day mortality and major interstage complications (≥3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies. Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P < 0.001; OR: 1.62; 95% CI: 1.36–1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18–0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers. Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.

The ALPPS Approach for the Management of Colorectal Carcinoma Liver Metastases

Liver resection is the treatment of choice for patients with colorectal liver metastases (CRLM). The possibility of achieving curative resection is limited by the future liver remnant (FLR), with posthepatectomy liver failure (PHLF) the most severe possible complication after major liver resection. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been introduced as a strategy for prevention of PHLF by inducing a rapid and large FLR hypertrophy not achieved by other methods. To date, most of the evidence regarding ALPPS is based on retrospective analysis of small series of patients or of case reports. The promising short-term results obtained are difficult to interpret oncologically, because of the heterogeneous groups of patients with different underlying pathology, variable chemotherapy use, and technical variations applied. Only increased experience and long-term outcomes will better define the utility of this novel method.

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy A Better Approach to Treat Patients With Extensive Liver Disease

Liver resection is the treatment of choice and a hope for cure for patients with malignant liver tumors. Resection is many times limited by the amount of future liver remnant, with liver failure being the most severe complication after major resections. To minimize this risk and expand resectability, portal vein occlusion of the tumorbearing lobe is used to redistribute portal flow and induce hypertrophy of contralateral healthy parenchyma. Right portal vein embolization (PVE) is best used before surgery when the future liver remnant is tumor free, while portal vein ligation (PVL) is usually applied as part of 2-stage procedures for patients with bilobar disease who initially require tumor removal in the liver remnant. Around 20% to 40% hypertrophy can be achieved in 8 to 12 weeks with these strategies. However, up to 40% of patients never arrive to tumor resection either because of disease progression or insufficient hypertrophy during these long interval periods. The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach has emerged as an innovative 2-stage hepatectomy developed in Germany and characterized by a short interval between both surgical procedures. 1 Briefly, during the first stage, the liver parenchyma is divided in 2 hemilivers and PVL of the diseasedhemiliverisperformed.Oncesufficienthypertrophy

Intermediate-term survival and quality of life outcomes in patients with advanced colorectal liver metastases undergoing associating liver partition and portal vein ligation for staged hepatectomy

Background. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative, 2‐staged hepatectomy which has elicited controversy within the international hepatobiliary community. Uptake of ALPPS has been limited due to concerns related to evidence of high morbidity and mortality, and scant oncologic and outcome data on quality of life (Qol). Demonstrating reasonable long‐term benefits with a short‐term risk is necessary to support more widespread endorsement of ALPPS. Our aim was to describe the intermediate‐term survival and patient‐reported quality of life outcomes after an ALPPS. Methods. Prospectively collected data from 2 high‐volume ALPPS centers, who were pioneers with the technique, were combined and analyzed for disease‐free and overall survival from date of the ALLPS. Only patients treated for colorectal liver metastases with >6 month postoperative follow‐up were included. All patients had bilateral colorectal liver metastases with an initially unresectable tumor load, and received preoperative chemotherapy. Information concerning the demographics of the patients, characteristics of the tumor, and treatment were analyzed. The well‐validated European Organization for Research and Treatment for Cancer Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess patient quality of life. Results. A total of 58 patients underwent ALPPS for colorectal liver metastases, and 47 patients met our inclusion criteria. There were no perioperative mortalities, and the rate of severe complications was 21%. At 3 years post‐ALPPS, the overall survival was 50%, while the disease‐free survival was 13%. The commonest site of first recurrence was the liver alone (38%). Patient‐reported quality of life after ALPPS was similar to reference values for general population. Conclusion. In select patients operated at experienced centers, ALPPS results in low perioperative risk, satisfactory overall survival, and excellent quality of life. Hepatic recurrence and not systemic recurrence is the most common site of relapse after ALPPS.

The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation Status in Survival

Background/Aims: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations influence survival after hepatectomy for colorectal liver metastases (CRLM). However, their prognostic significance has never been evaluated in patients who undergo Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS). Methods: Between June 2011 and March 2016, 26 patients underwent ALPPS for CRLM. Complications were classified according to the Clavien-Dindo classification. Bi- and multivariate cox analyses were performed to evaluate variables potentially associated with survival. Results: Overall, morbidity grade ≥3a and 90-day mortality were 38.5 and 0%, respectively. The median follow-up from the time of discharge was 21.5 months (interquartile range 9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%, respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3 months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p = 0.023). KRAS mutation was found to be an independent risk factor for OS (hazard ratio 7.15, 95% CI 1.50-34.11; p = 0.014). Conclusion: KRAS mutation is an independent predictor of poor survival after ALPPS. This finding will help to optimize patient selection, both avoiding futile surgical indication and maximizing the benefit for patients with extensive disease who are otherwise subjected to high-risk aggressive surgery.

Surgical strategies for restoring liver arterial perfusion in pancreatic resections

BackgroundHepatic perfusion failure represents an important risk factor for severe complications and death after pancreatic resections. Arterial reconstruction could be required during pancreatic surgery because of tumor infiltration, benign strictures, or as a consequence of accidental arterial injury during dissection. All these situations can be faced with a certain frequency in high-volume pancreatic centers, where surgeons must be aware of the different alternatives to deal with these intricate scenarios.PurposeWe herein describe the preoperative surgical planning as well as different surgical strategies for the restoration of arterial perfusion of the liver in pancreatic resections.ConclusionA thorough preoperative evaluation is essential for planning pancreatic surgery and preparing the surgeon and patient for potentially high complex procedures. The various therapeutic alternatives presented in this technical report might represent a good solution for selected patients with no other potentially curative option than surgery.